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  1. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases

    International Nuclear Information System (INIS)

    Gaspar, Laurie E.; Scott, Charles; Murray, Kevin; Curran, Walter

    2000-01-01

    Purpose: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. Methods and Materials: A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. Results: For RPA Class I, the median survival time was 6.2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22). Conclusion: This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials

  2. Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases

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    Videtic, Gregory M.M.; Adelstein, David J.; Mekhail, Tarek M.; Rice, Thomas W.; Stevens, Glen H.J.; Lee, S.-Y.; Suh, John H.

    2007-01-01

    Purpose: Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. Methods and Materials: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Results: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Conclusions: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons

  3. Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

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    Berk, Lawrence; Berkey, Brian; Rich, Tyvin; Hrushesky, William; Blask, David; Gallagher, Michael; Kudrimoti, Mahesh; McGarry, Ronald C.; Suh, John; Mehta, Minesh

    2007-01-01

    Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients

  4. Prognostic factors derived from recursive partition analysis (RPA) of radiation therapy oncology group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases

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    Agboola, Olusegun; Benoit, Brien; Cross, Peter; Silva, Vasco da; Esche, Bernd; Lesiuk, Howard; Gonsalves, Carol

    1998-01-01

    Purpose: (a) To identify the prognostic factors that determine survival after surgical resection and irradiation of tumors metastatic to brain. (b) To determine if the prognostic factors used in the recursive partition analysis (RPA) of brain metastases cases from Radiation Therapy Oncology Group (RTOG) studies into three distinct survival classes is applicable to surgically resected and irradiated patients. Method: The medical records of 125 patients who had surgical resection and radiotherapy for brain metastases from 1985 to 1997 were reviewed. The patients' disease and treatment related factors were analyzed to identify factors that independently determine survival after diagnosis of brain metastasis. The patients were also grouped into three classes using the RPA-derived prognostic parameters which are: age, performance status, state of the primary disease, and presence or absence of extracranial metastases. Class 1: patients ≤ 65 years of age, Karnofsky performance status (KPS) of ≥70, with controlled primary disease and no extracranial metastases; Class 3: patients with KPS < 70. Patients who do not qualify for Class 1 or 3 are grouped as Class 2. The survival of these patients was determined from the time of diagnosis of brain metastases to the time of death. Results: The median survival of the entire group was 9.5 months. The three classes of patients as grouped had median survivals of 14.8, 9.9, and 6.0 months respectively (p = 0.0002). Age of < 65 years, KPS of ≥ 70, controlled primary disease, absence of extracranial metastases, complete surgical resection of the brain lesion(s) were found to be independent prognostic factors for survival; the total dose of radiation was not. Conclusion: Based on the results of this study, the patients and disease characteristics have significant impact on the survival of patients with brain metastases treated with a combination of surgical resection and radiotherapy. These parameters could be used in selecting

  5. Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

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    Gondi, Vinai; Tome, Wolfgang A.; Marsh, James; Struck, Aaron; Ghia, Amol; Turian, Julius V.; Bentzen, Soren M.; Kuo, John S.; Khuntia, Deepak; Mehta, Minesh P.

    2010-01-01

    Background and purpose: RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin). Materials/methods: Patients with ≤10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p 3 increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p = 0.003) for the presence of perihippocampal metastasis. Conclusion: With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.

  6. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    International Nuclear Information System (INIS)

    Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-01-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects

  7. Defining treatment for brain metastases patients: nihilism versus optimism.

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    Craighead, Peter S; Chan, Alexander

    2012-02-01

    Treatment of brain metastases patients has included whole brain radiotherapy (WBRT) for over 50 years, and there is much data showing this to be associated with short-term gains. The integration of resection and radiosurgery to these patients allows some better prognostic groups to experience long-term local control and improvement in quality of life. The recursive partitioning analysis of the Radiation Therapy Oncology Group (RTOG) has been used as a predictive model for over a decade to identify three classes of patients. Number of lesions has been used to define treatment for a good prognostic subgroup that is eligible for surgery or radiosurgery, but there are few prospective studies of poorer prognosis brain metastases patients to evaluate the influence of number of lesions on the prediction of outcome. We examined patient, treatment and outcome parameters of all brain metastases patients in a 5-year period so that we could measure outcome and evaluate various factors on survival. This was a population-based study of all brain metastases patients in Southern Alberta between 2000 and 2005. It used an Excel spreadsheet database and STATA 8 software to analyze outcomes. The study included 568 patients representing 4.4% of our radiotherapy population. Median age, performance status and distribution of primary disease sites were comparable with other large series. Overall survival for the whole group was 3.05 months. Independent factors predicting for improved overall survival included younger age, KPS <70, less than four lesions and the use of stereotactic radiosurgery. Presence of extracranial disease or persistence of primary disease did not adversely impact survival outcome. This series shows that the number of lesions is a strong predictor of outcome. Integration of this factor into a decision-making model allows for identification of not only good prognosis patients who will benefit from aggressive treatment but it also facilitates decision making for poorer

  8. Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

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    Krayenbuehl, J; Di Martino, M; Guckenberger, M; Andratschke, N

    2017-10-02

    Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective

  9. Dosimetric comparison of volumetric modulated arc therapy and linear accelerator-based radiosurgery for the treatment of one to four brain metastases.

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    Salkeld, Alison L; Unicomb, Kylie; Hayden, Amy J; Van Tilburg, Kevin; Yau, Shan; Tiver, Kenneth

    2014-12-01

    The purpose of this study is to compare and evaluate volumetric modulated arc therapy (VMAT) and linear accelerator-based radiosurgery (Linac RS) for the treatment of one to four brain metastases. Radiotherapy plans for 10 patients with 1 to 4 brain metastases that were planned and treated using conventional Linac RS were replanned using a mono-isocentric VMAT technique using two to four arcs. The same doses, target volumes and organs at risk (OAR) were used in both plans. The plans were evaluated for target volume coverage, dose conformity, homogeneity and dose to OAR. For VMAT plans, 18/19 brain metastases met acceptable Radiation Therapy Oncology Group (RTOG) radiosurgery dose coverage, homogeneity and conformity criteria. There was no observed difference between the mean homogeneity indices for VMAT and Linac RS plans. VMAT plans had a lower mean RTOG conformity index compared with the Linac RS plans (1.10 ± 0.06 versus 2.06 ± 1.02). For the OAR, there was no difference in maximal doses to the brain stem, optic chiasm or optic nerves. The volume of normal brain receiving 12 Gy was lower in the VMAT plans (13.3 cm(3) versus 23.1 cm(3) ) compared with the Linac RS plans. The mean total number of monitor units (MUs) was 31.3% less in the VMAT plans (5231.2 MU versus 3593.5 MU). Mono-isocentric VMAT plans using two to four arcs meet RTOG radiosurgery quality criteria in patients with one to four brain metastases, with an improvement in conformity and 12-Gy normal brain volume when compared with patients treated with Linac RS at our institution. © 2014 The Royal Australian and New Zealand College of Radiologists.

  10. Analysis of outcome in patients reirradiated for brain metastases

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    Wong, William W.; Schild, Steven E.; Sawyer, Timothy E.; Shaw, Edward G.

    1996-01-01

    Purpose: Patients with newly diagnosed brain metastases generally benefit from whole brain radiation therapy (WBRT). However, the role of reirradiation for patients who develop progressive brain metastases has been controversial. This retrospective study examines our experience with reirradiation of patients for progressive brain metastases after an initial course of WBRT. Methods and Materials: From 1975-1993, 2658 patients received WBRT for brain metastases at our institution. Eighty-six patients were subsequently reirradiated for progressive brain metastases. The median age of these patients was 58 (range: 31-81). The most common primary sites were breast and lung. Fifty patients had metastatic disease at other sites. Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (40 patients) or 3 (38 patients). The median dose of the first course of irradiation was 30 Gy (range: 1.5-50.6 Gy). The median dose of the second course of irradiation was 20 Gy (range: 8.0-30.6 Gy). Results: Twenty-three patients (27%) had resolution of neurologic symptoms, 37 patients (43%) had partial improvement of neurologic symptoms, and 25 patients (29%) had either no change or worsened after reirradiation. The median survival following reirradiation was 4 months (range: 0.25-72 months). The majority of patients had no significant toxicity secondary to reirradiation. Five patients had radiographic abnormalities of their brain consistent with radiation-related changes. One patient had symptoms of dementia that was thought to be caused by radiotherapy. Various potential prognostic factors were evaluated for possible associations with survival, including age, sex, primary site, ECOG performance status, RTOG neurologic functional class, absence of extracranial metastases, number of brain metastases, and dose of reirradiation. Absence of extracranial metastasis, solitary brain metastasis, and a retreatment dose > 20 Gy were associated with improved survival in

  11. A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the radiation therapy oncology group (RTOG) 9104

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    Murray, Kevin J.; Scott, Charles; Greenberg, Harvey M.; Emami, Bahman; Seider, Michael; Vora, Nayana L.; Olson, Craig; Whitton, Anthony; Movsas, Benjamin; Curran, Walter

    1997-01-01

    Purpose: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. Methods and Materials: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. Results: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary

  12. Radiosurgery for brain metastases: a score index for predicting prognosis

    International Nuclear Information System (INIS)

    Weltman, Eduardo; Salvajoli, Joao Victor; Brandt, Reynaldo Andre; Morais Hanriot, Rodrigo de; Prisco, Flavio Eduardo; Cruz, Jose Carlos; Oliveira Borges, Sandra Regina de; Wajsbrot, Dalia Ballas

    2000-01-01

    Purpose: To analyze a prognostic score index for patients with brain metastases submitted to stereotactic radiosurgery (the Score Index for Radiosurgery in Brain Metastases [SIR]). Methods and Materials: Actuarial survival of 65 brain metastases patients treated with radiosurgery between July 1993 and December 1997 was retrospectively analyzed. Prognostic factors included age, Karnofsky performance status (KPS), extracranial disease status, number of brain lesions, largest brain lesion volume, lesions site, and receiving or not whole brain irradiation. The SIR was obtained through summation of the previously noted first five prognostic factors. Kaplan-Meier actuarial survival curves for all prognostic factors, SIR, and recursive partitioning analysis (RPA) (RTOG prognostic score) were calculated. Survival curves of subsets were compared by log-rank test. Application of the Cox model was utilized to identify any correlation between prognostic factors, prognostic scores, and survival. Results: Median overall survival from radiosurgery was 6.8 months. Utilizing univariate analysis, extracranial disease status, KPS, number of brain lesions, largest brain lesion volume, RPA, and SIR were significantly correlated with prognosis. Median survival for the RPA classes 1, 2, and 3 was 20.19 months, 7.75 months, and 3.38 months respectively (p = 0.0131). Median survival for patients, grouped under SIR from 1 to 3, 4 to 7, and 8 to 10, was 2.91 months, 7.00 months, and 31.38 months respectively (p = 0.0001). Using the Cox model, extracranial disease status and KPS demonstrated significant correlation with prognosis (p 0.0001 and 0.0004 respectively). Multivariate analysis also demonstrated significance for SIR and RPA when tested individually (p = 0.0001 and 0.0040 respectively). Applying the Cox Model to both SIR and RPA, only SIR reached independent significance (p = 0.0004). Conclusions: Systemic disease status, KPS, SIR, and RPA are reliable prognostic factors for patients

  13. Prospective Evaluation of Quality of Life and Neurocognitive Effects in Patients With Multiple Brain Metastases Receiving Whole-Brain Radiotherapy With or Without Thalidomide on Radiation Therapy Oncology Group (RTOG) Trial 0118

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    Corn, Benjamin W.; Moughan, Jennifer M.S.; Knisely, Jonathan P.S.; Fox, Sherry W.; Chakravarti, Arnab; Yung, W.K. Alfred; Curran, Walter J.; Robins, H. Ian; Brachman, David G.; Henderson, Randal H.; Mehta, Minesh P.; Movsas, Benjamin

    2008-01-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) ± thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. Methods and Materials: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. Results: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. Conclusions: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population

  14. Analysis of outcome in patients reirradiated for brain metastases

    International Nuclear Information System (INIS)

    Wong, William W.; Schild, Steven E.; Sawyer, Timothy E.; Shaw, Edward G.

    1995-01-01

    Purpose: Patients with brain metastases generally benefit from whole brain irradiation (WBRT). However, the role of reirradiation for patients who develop progressive brain metastases after a course of WBRT has been controversial. This retrospective study examines our experience with reirradiation of patients for progressive brain metastases after an initial course of WBRT. Materials and Methods: From 1975 to 1993, 2658 patients received WBRT for brain metastases at our institutions. Eighty-six patients were subsequently reirradiated for progressive brain metastases. The median age of these patients was 58 (range: 31-81). The primary sites included breast (31 patients), lung (31 patients), colon (6 patients), melanoma (5 patients), and others (13 patients). Fifty patients had metastatic disease at other sites. Most patients had ECOG performance status of 2 (39 patients) or 3 (36 patients). The median dose of the first course of irradiation was 30 Gy (range: 20-50.4 Gy). The median time interval between the first and second courses of irradiation was 7.6 months (range: 1.5-50.6 months). The median dose of the second course of irradiation was 20 Gy (range: 8.0 to 30.6 Gy). All except one patients were given steroids. Patients were followed until death, except for one patient who was lost to follow-up and one long-term surviver who was followed for 72 months. Results: Twenty-three patients (27%) had complete resolution of neurologic symptoms, 37 patients (43%) had partial improvement of neurologic symptoms, and 24 patients (28%) had either no subjective response or worsened after reirradiation. The RTOG neurological function class improved in 32 patients, remained unchanged in 40 patients, and deteriorated in 8 patients. Survival following reirradiation ranged from 0.25 to 72 months with a median survival of 4 months. The majority of patients had no toxicity secondary to reirradiation. Five patients had radiographic abnormalities of their brains consistent with

  15. Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

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    Daniel eGorovets

    2015-05-01

    Full Text Available Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT in patients with brain metastases treated with stereotactic radiosurgery (SRS as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104, and those who died or required salvage WBRT within 3 mo of SRS (N=56. Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p<0.05 included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.Conclusions: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

  16. Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes?

    International Nuclear Information System (INIS)

    Nieder, Carsten; Nestle, Ursula; Motaref, Babak; Walter, Karin; Niewald, Marcus; Schnabel, Klaus

    2000-01-01

    Purpose: To determine whether or not Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) derived prognostic classes for patients with brain metastases are generally applicable and can be recommended as rational strategy for patient selection for future clinical trials. Inclusion of time to non-CNS death as additional endpoint besides death from any cause might result in further valuable information, as survival limitation due to uncontrolled extracranial disease can be explored. Methods: We performed a retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases. For this purpose, patients were divided into groups with Karnofsky performance status (KPS) 0.05 for RPA class II versus III). However, it was 8.5 months in RPA class II patients with controlled primary tumor, which was found to be the only prognostic factor for time to non-CNS death in patients with KPS ≥70%. In patients with KPS <70%, no statistically significant prognostic factors were identified for this endpoint. Conclusions: Despite some differences, this analysis essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG, when survival was chosen as endpoint. RPA class I patients seem to be most likely to profit from aggressive treatment strategies and should be included in appropriate clinical trials. However, their number appears to be very limited. Considering time to non-CNS death, our results suggest that certain patients in RPA class II also might benefit from increased local control of brain metastases

  17. Radiosurgery without whole brain radiotherapy in melanoma brain metastases

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    Grob, J.J.; Regis, J.; Laurans, R.; Delaunay, M.; Wolkenstein, P.; Paul, K.; Souteyrand, P.; Koeppel, M.C.; Murraciole, X.; Perragut, J.C.; Bonerandi, J.J.

    1998-01-01

    To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. Metabolic Profiles of Brain Metastases

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    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  19. The role of chemotherapy in brain metastases

    International Nuclear Information System (INIS)

    Ohori, Hisatsugu; Takahashi, Shin; Ishioka, Chikashi

    2007-01-01

    Brain metastases are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases have a very poor prognosis with a median survival of 1-2 months. Despite the use of surgery and radiotherapy including whole-brain radiation and stereotactic radiosurgery to locally control brain metastases, survival times for those patients has not improved. Although chemotherapy plays a limited role in the treatment of brain metastases, metastases from lung or breast cancer are often well-controlled by chemotherapy. Accumulating evidence suggest that brain metastases are equally sensitive to chemotherapy as are metastases elsewhere in the body in particular chemotherapy-naive cases. Finally, since nearly a half of patients with brain metastases die from progression of systemic disease, control of systemic disease as well as intracranial disease are both important. (author)

  20. The Effect of Contouring Variability on Dosimetric Parameters for Brain Metastases Treated With Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Stanley, Julia; Dunscombe, Peter; Lau, Harold; Burns, Paul; Lim, Gerald; Liu, Hong-Wei; Nordal, Robert; Starreveld, Yves; Valev, Boris; Voroney, Jon-Paul; Spencer, David P.

    2013-01-01

    Purpose: To quantify the effect of contouring variation on stereotactic radiosurgery plan quality metrics for brain metastases. Methods and Materials: Fourteen metastases, each contoured by 8 physicians, formed the basis of this study. A template-based dynamic conformal 5-arc dose distribution was developed for each of the 112 contours, and each dose distribution was applied to the 7 other contours in each patient set. Radiation Therapy Oncology Group (RTOG) plan quality metrics and the Paddick conformity index were calculated for each of the 896 combinations of dose distributions and contours. Results: The ratio of largest to smallest contour volume for each metastasis varied from 1.25 to 4.47, with a median value of 1.68 (n=8). The median absolute difference in RTOG conformity index between the value for the reference contour and the values for the alternative contours was 0.35. The variation of the range of conformity index for all contours for a given tumor varied with the tumor size. Conclusions: The high degree of interobserver contouring variation strongly suggests that peer review or consultation should be adopted to standardize tumor volume prescription. Observer confidence was not reflected in contouring consistency. The impact of contouring variability on plan quality metrics, used as criteria for clinical trial protocol compliance, was such that the category of compliance was robust to interobserver effects only 70% of the time

  1. Management of Brain Metastases.

    Science.gov (United States)

    Jeyapalan, Suriya A.; Batchelor, Tracy

    2004-07-01

    Advances in neurosurgery and the development of stereotactic radiosurgery have expanded treatment options available for patients with brain metastases. However, despite several randomized clinical trials and multiple uncontrolled studies, there is not a uniform consensus on the best treatment strategy for all patients with brain metastases. The heterogeneity of this patient population in terms of functional status, types of underlying cancers, status of systemic disease control, and number and location of brain metastases make such consensus difficult. Nevertheless, in certain situations, there is Class I evidence that supports one approach or another. The primary objectives in the management of this patient population include improved duration and quality of survival. Very few patients achieve long-term survival after the diagnosis of a brain metastasis.

  2. Hemorrhagic brain metastases

    International Nuclear Information System (INIS)

    Takahashi, Motoichiro; Takekawa, S.D.; Suzuki, Kenzo

    1986-01-01

    Tumor hemorrhage on computed tomography (CT) was found in 14 patients with brain metastases (7 % of two hundred patients with brain metastases), from April 1979 to July 1983. Primary foci of these lesions were the lung (6 patients), breast (2), kidney (2), uterus (2), colon (1) and adrenal gland (1). ''Stroke'' syndrome was the initial presenting symptom in 3 patients; neurological focal sign or symptoms of increased intracranial pressure in the remaining patients. CT demonstrated peritumoral hemorrhage in all patients with solid mass, intratumoral hemorrhage in a few patients and also cerebral or ventricular hemorrhage, which was fatal complication, in 2 patients (colon and breast cancers). A cystic mass with fluid-blood level was noted in a patient with breast cancer. Several predisposing factors including chemotherapy, thrombocytopenia, radiotherapy or combination of these were recognized in 8 patients. Of these, chemotherapy was the most causative factor of tumor hemorrhage. Brain irradiation for hemorrhagic brain metastases was effective for prolongation of mean survival time of these patients as follows; 10 months in irradiated group, whereas 1.5 months in non-irradiated group. (author)

  3. Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04

    International Nuclear Information System (INIS)

    Regine, W.F.; Scott, C.; Murray, K.; Curran, W.

    2001-01-01

    Purpose: To evaluate neurocognitive outcome as measured by the Mini-Mental Status Examination (MMSE) among patients with unresectable brain metastases randomly assigned to accelerated fractionation (AF) vs. accelerated hyperfractionated (AH) whole-brain radiation therapy (WBRT). Methods and Materials: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients with unresectable brain metastases to a Phase III comparison of AH (1.6 Gy b.i.d. to 54.4 Gy) vs. AF (3 Gy q.d. to 30 Gy). All had a KPS of ≥ 70 and a neurologic function status of 0-2. Three hundred fifty-nine patients had MMSEs performed and were eligible for this analysis. Changes in the MMSE were analyzed according to criteria previously defined in the literature. Results: The median survival was 4.5 months for both arms. The average change in MMSE at 2 and 3 months was a drop of 1.4 and 1.1, respectively, in the AF arm as compared to a drop of 0.7 and 1.3, respectively, in the AH arm (p=NS). Overall, 91 patients at 2 months and 23 patients at 3 months had both follow-up MMSE and computed tomography/magnetic resonance imaging documentation of the status of their brain metastases. When an analysis was performed taking into account control of brain metastases, a significant effect on MMSE was observed with time and associated proportional increase in uncontrolled brain metastases. At 2 months, the average change in MMSE score was a drop of 0.6 for those whose brain metastases were radiologically controlled as compared to a drop of 1.9 for those with uncontrolled brain metastases (p=0.47). At 3 months, the average change in MMSE score was a drop of 0.5 for those whose brain metastases were radiologically controlled as compared to a drop of 6.3 for those with uncontrolled brain metastases (p=0.02). Conclusion: Use of AH as compared to AF-WBRT was not associated with a significant difference in neurocognitive function as measured by MMSE in this patient population with unresectable brain metastases and

  4. Role of surgery in brain metastases.

    Science.gov (United States)

    Laghari, Altaf Ali; Ahmed, Syed Ijlal; Shamim, Muhammad Shahzad

    2017-08-01

    Brain metastases remain the commonest type of brain tumour, being four times more common than primary brain tumours. Although surgical intervention may be recommended for one of various reasons in the management of these tumours, including but not limited to conformation of diagnosis, relief of mass effect, improvement of neurological status and prolongation of survival, the guidelines for management of brain metastases remain largely subjective and therefore controversial. Herein the authors have attempted to review some of the existing evidence on role of surgery in the management of brain metastases and have presented their selected guidelines for the readers.

  5. Stereotactic radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Obedian, E.; Lotbiniere, A.C.J. de; Haffty, B.G.; Piepmeier, J.M.; Fischer, D.B.; Knisely, J.P.S.

    1997-01-01

    Purpose: This study evaluates the influence of several prognostic factors on overall survival and progression free survival in patients undergoing stereotactic radiosurgery (SRS) for brain metastases. Materials and Methods: Records of 61 coecutive patients with pathologically confirmed extra-cranial malignancies undergoing SRS at Yale University School of Medicine between 12/18/91 and 7/2/96 were reviewed. All patients underwent head frame localization and CT and/or MRI based treatment planning. Outcome was analyzed with respect to age, number of lesions, size of lesions, location of lesions, site and stage of primary tumor, status of primary tumor at time of SRS, history of whole brain radiation therapy (WBRT), surgery, and/or chemotherapy prior to or after SRS, delay in SRS from diagnosis of brain metastases, dose of radiation delivered, and brain metastasis free interval. Both overall survival and progression free survival were analyzed by the Kaplan-Meier method. Tests for statistical significance were performed using the Cox proportional hazards model. Results: Median follow-up was 29 months. 3% ((8(61))) of patients displayed evidence of progressive disease at the site of SRS, and 87% ((53(61))) of patients have died. Overall and progression free survival rates for the entire cohort of patients were 43.8% and 89.5% at 1 year and 11.1% and 71.4% at 2 years, respectively. Patients undergoing SRS for a solitary brain metastasis had a significant improvement in overall survival with 1 year survival rates of 52.6% vs. 32.7% for patients undergoing SRS for more than 1 brain metastasis (p=0.002). Patients who presented with progressive systemic disease at the time of SRS had an inferior overall survival with a 1 year survival rate of 15.4% compared to patients with presumed/known stable disease who had a 1 year survival rate of 51.5%/54.2% (p<0.001). Patients treated for cerebral metastases had a higher progression free survival compared to patients undergoing SRS

  6. Whole-brain radiation therapy for brain metastases: detrimental or beneficial?

    International Nuclear Information System (INIS)

    Gemici, Cengiz; Yaprak, Gokhan

    2015-01-01

    Stereotactic radiosurgery is frequently used, either alone or together with whole-brain radiation therapy to treat brain metastases from solid tumors. Certain experts and radiation oncology groups have proposed replacing whole-brain radiation therapy with stereotactic radiosurgery alone for the management of brain metastases. Although randomized trials have favored adding whole-brain radiation therapy to stereotactic radiosurgery for most end points, a recent meta-analysis demonstrated a survival disadvantage for patients treated with whole-brain radiation therapy and stereotactic radiosurgery compared with patients treated with stereotactic radiosurgery alone. However the apparent detrimental effect of adding whole-brain radiation therapy to stereotactic radiosurgery reported in this meta-analysis may be the result of inhomogeneous distribution of the patients with respect to tumor histologies, molecular histologic subtypes, and extracranial tumor stages between the groups rather than a real effect. Unfortunately, soon after this meta-analysis was published, even as an abstract, use of whole-brain radiation therapy in managing brain metastases has become controversial among radiation oncologists. The American Society of Radiation Oncology recently recommended, in their “Choose Wisely” campaign, against routinely adding whole-brain radiation therapy to stereotactic radiosurgery to treat brain metastases. However, this situation creates conflict for radiation oncologists who believe that there are enough high level of evidence for the effectiveness of whole-brain radiation therapy in the treatment of brain metastases

  7. Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

    International Nuclear Information System (INIS)

    Sneed, Penny K.; Lamborn, Kathleen R.; Forstner, Julie M.; McDermott, Michael W.; Chang, Susan; Park, Elaine; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1999-01-01

    Purpose: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS ± WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. Methods and Materials: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. Results: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjusted p = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). Conclusions: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases

  8. Functional Interference Clusters in Cancer Patients With Bone Metastases: A Secondary Analysis of RTOG 9714

    International Nuclear Information System (INIS)

    Chow, Edward; James, Jennifer; Barsevick, Andrea; Hartsell, William; Ratcliffe, Sarah; Scarantino, Charles; Ivker, Robert; Roach, Mack; Suh, John; Petersen, Ivy; Konski, Andre; Demas, William; Bruner, Deborah

    2010-01-01

    Purpose: To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases. Methods: Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Principal component analysis with varimax rotation was used to determine the clusters between the functional items at baseline and the follow-up. Cronbach's alpha was used to determine the consistency and reliability of each cluster at baseline and follow-up. Results: There were 448 male and 461 female patients, with a median age of 67 years. There were two functional interference clusters at baseline, which accounted for 71% of the total variance. The first cluster (physical interference) included normal work and walking ability, which accounted for 58% of the total variance. The second cluster (psychosocial interference) included relations with others and sleep, which accounted for 13% of the total variance. The Cronbach's alpha statistics were 0.83 and 0.80, respectively. The functional clusters changed at week 12 in responders but persisted through week 12 in nonresponders. Conclusion: Palliative radiotherapy is effective in reducing bone pain. Functional interference component clusters exist in patients treated for bone metastases. These clusters changed over time in this study, possibly attributable to treatment. Further research is needed to examine these effects.

  9. Radiosurgery for brain metastases: is whole brain radiation therapy necessary?

    International Nuclear Information System (INIS)

    Forstner, Julie M.; Sneed, Penny K.; Lamborn, Kathleen R.; Shu, H.-K.G.; McDermott, Michael W.; Park, Elaine; Ho, Maria; Chang, Susan; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1996-01-01

    Purpose: Because whole brain radiotherapy (WBRT) carries a significant risk of dementia in long-term survivors, it is desirable to determine if some patients with brain metastases may be managed with radiosurgery (RS) alone, reserving WBRT for salvage therapy as needed. To begin to approach this problem, we retrospectively reviewed freedom from brain failure/progression (Brain FFP) and survival of patients with newly-diagnosed solitary or multiple brain metastases treated with Gamma Knife RS ± WBRT. Materials and Methods: All patients treated at our institution with Gamma Knife RS for newly-diagnosed solitary or multiple (2-8) brain metastases from September 1991 through December 1995 were reviewed. Whether or not WBRT was given depended on physician preference and referral patterns. Brain FFP was measured from the date of RS until development of a new brain metastasis or progression of a treated metastasis, with censoring at the time of the last imaging study. Survival was measured from the date of RS until death or last clinical follow-up. Actuarial curves were estimated using the Kaplan-Meier method and compared with the log rank test. Multivariate analyses to adjust for known prognostic variables (age, KPS, history of extracranial metastases, and total target volume) were performed using the Cox proportional hazards model. Results: From September 1991-December 1995, 90 patients with newly-diagnosed brain metastases underwent RS. Three patients treated palliatively to a small component of their intracranial disease were excluded, leaving 54 treated with RS alone and 33 treated with RS + WBRT. Age ranged from 31-83 years (median, 59 years), KPS from 60-100 (median, 90), and total target volume from 0.15-26.1 cm 3 (median, 5.5 cm 3 ). Fifty patients had a history of extracranial metastases. Results are shown below. In the RS alone group, (22(54)) patients (41%) had a brain failure and (20(54)) (37%) died without evidence of brain failure. In the RS + WBRT group

  10. Whole brain radiotherapy with radiosensitizer for brain metastases

    Directory of Open Access Journals (Sweden)

    Viani Gustavo

    2009-01-01

    Full Text Available Abstract Purpose To study the efficacy of whole brain radiotherapy (WBRT with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. Methods A meta-analysis of randomized controlled trials (RCT was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently. Results A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77. Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03 and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3 when the two arms were compared. Conclusion Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide, have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast to have positive action in lung and breast carcinoma brain metastases in association with WBRT.

  11. SU-E-T-536: LINAC-Based Single Isocenter Frameless SRT for Brain Metastases

    International Nuclear Information System (INIS)

    Liu, B; Zhang, L; Rigor, N; Kim, J

    2015-01-01

    Purpose: Single-isocenter Stereotactic Radiotherapy of multiple brain metastases with Varian 21 IX LINAC, using Aktina Pinpoint system for patient setup. Methods: In 2014, five single-isocenter RapidArc SRT plans were delivered to five patients with 2 to 8 brain metastases using Varian 21 IX. Aktina Pinpoint system was used for setup and 2mm PTV margin were used. CBCT was acquired before and after the beam delivery. The prescription is 2100 cGy in 3 fractions. Eclipse planning system was used for treatment planning. Depending on the number of metastases and their locations, 1 to 5 coplanar or non coplanar arcs were used. Typically, 2 or 3 arcs are used. IMRT QAs were performed by comparing an A1SL ion chamber point dose measurement in solid water phantom to point dose of the plan; also, based on EPID measurement, 3D spatial dose was calculated using DosimetryCheck software package from MathResolutions Inc. The EPID system has an active area of 40cm by 30cm with 1024 by 768 photodiodes, which corresponds to a resolution of 0.4mm by 0.4mm pixel dimension. Results: for all the plans, at least 95% PTV coverage was achieved for full prescription dose, with plan normalization > 75%. RTOG conformity indices are less than 1.1 and Paddick gradient indices are less than 4.5. The distance from prescription IDL to 50% IDL increases as the number of metastases increases, and it ranges from 0.6mm to 0.8mm. Treatment time varies from 10mins to 30mins, depending on the number of arcs and if the arcs are coplanar. IMRT QA shows that the ion chamber measurement agree with the eclipse calculation within 3%, and 95% of the points passed Gamma, using 3% dose difference and 3mm DTA Conclusion: High quality single isocenter RapidArc SRT plan can be optimized and accurately delivered using Eclipse and Varian 21IX

  12. Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

    International Nuclear Information System (INIS)

    Viani, Gustavo A; Castilho, Marcus S; Salvajoli, João V; Pellizzon, Antonio Cassio A; Novaes, Paulo E; Guimarães, Flavio S; Conte, Maria A; Fogaroli, Ricardo C

    2007-01-01

    Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). Our

  13. Radiation therapy of brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, R; Huenig, R [Kantonsspital Basel (Switzerland). Universitaetsinstitut fuer Medizinische Radiologie

    1975-08-01

    Experiences are reported obtained with radiation therapy of brain metastases in 121 patients during the last 15 years. The treatment to a lesser extent aimed at prolongation of survival but much more at the attempt to alleviate troubles and to spare pain. The indication thus involved medical points of view as well as ethical ones. The radiotherapy of cerebral metastases comprises the whole cranial volume and requires a focal dose of minimally 4,000 R within four weeks. In 53% of the patients, the regression of neurological symptoms was considerable, in 18% even complete, partly beginning already after a few days of treatment. The number of recurrences was small. Under conditions of rigorous indication, the radiation therapy of brain metastases offers a rewarding palliative measure.

  14. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon T

    2013-01-01

    -enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2......The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P...

  15. Role of palliative radiotherapy in brain metastases

    Directory of Open Access Journals (Sweden)

    Ramesh S Bilimagga

    2009-01-01

    Full Text Available Background: Brain metastases are a common manifestation of systemic cancer and exceed primary brain tumors in number and are a significant cause of neurologic problems. They affect 20-40% of all cancer patients. Aggressive management of brain metastases is effective in both symptom palliation and prolonging the life. Radiotherapy has a major role to play in the management of brain metastases. AIM: The aim of the study was to know the outcome of palliative radiotherapy in symptomatic brain metastases in terms of improvement in their performance status. Materials and Methods: This is a retrospective study of 63 patients diagnosed to have brain metastases and treated with palliative whole brain radiotherapy to a dose of 30 Gy in 10 fractions over two weeks between June 1998 and June 2007. Diagnosis was done in most of the cases with computed tomography scan and in a few with magnetic resonance imaging. Improvement in presenting symptoms has been assessed in terms of improvement in their performance status by using the ECOG scale. Results: Fifty-four patients completed the planned treatment. Eight patients received concurrent Temozolamide; 88% of patients had symptom relief at one month follow-up; 39/54 patients had a follow-up of just one to three months. Hence survival could not be assessed in this study. Conclusion: External beam radiotherapy in the dose of 30 Gy over two weeks achieved good palliation in terms improvement in their performance status in 88% of patients. Addition of concurrent and adjuvant Timozolamide may improve the results.

  16. Results of radiotherapy for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

    1987-01-01

    Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation. (author)

  17. Results of radiotherapy for brain metastases from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

    1987-02-01

    Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation.

  18. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC Registry

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

    Full Text Available Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT and magnetic resonance imaging (MRI scans of 300 breast cancer patients with brain metastases (BMs were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC in Germany. Patients with positive estrogen (ER, progesterone (PR, or human epidermal growth factor receptor 2 (HER2 statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001. Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021, whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038. The localization of Brain metastases (BMs was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025. A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012. Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  19. [Guideline on brain metastases: not a cookbook].

    Science.gov (United States)

    Reijneveld, Jaap C

    2011-01-01

    The guideline 'Brain Metastases', which was revised on behalf of the Dutch Society for Neuro-Oncology (LWNO), provides an excellent overview of levels of scientific evidence on diagnosis and treatment of patients with parenchymal brain metastases of solid tumours. I would like to emphasize, however, that this guideline is not a cookbook for facilitating individual physicians to treat patients on their own. It is important that every patient suffering from brain metastases is discussed by a multidisciplinary tumour board consisting of at least a neurologist, a neurosurgeon, a medical oncologist, a radiation oncologist, a pathologist and a radiologist, and that several crucial questions need to be explicitly asked and answered about every single patient.

  20. Neuropsychological testing and biomarkers in the management of brain metastases

    International Nuclear Information System (INIS)

    Baschnagel, Andrew; Wolters, Pamela L; Camphausen, Kevin

    2008-01-01

    Prognosis for patients with brain metastasis remains poor. Whole brain radiation therapy is the conventional treatment option; it can improve neurological symptoms, prevent and improve tumor associated neurocognitive decline, and prevents death from neurologic causes. In addition to whole brain radiation therapy, stereotactic radiosurgery, neurosurgery and chemotherapy also are used in the management of brain metastases. Radiosensitizers are now currently being investigated as potential treatment options. All of these treatment modalities carry a risk of central nervous system (CNS) toxicity that can lead to neurocognitive impairment in long term survivors. Neuropsychological testing and biomarkers are potential ways of measuring and better understanding CNS toxicity. These tools may help optimize current therapies and develop new treatments for these patients. This article will review the current management of brain metastases, summarize the data on the CNS effects associated with brain metastases and whole brain radiation therapy in these patients, discuss the use of neuropsychological tests as outcome measures in clinical trials evaluating treatments for brain metastases, and give an overview of the potential of biomarker development in brain metastases research

  1. Use of cerebral CT as prognosticator of treatment response of brain metastases

    International Nuclear Information System (INIS)

    Asbell, S.O.; Hitchon, H.D.; Sklaroff, D.M.

    1986-01-01

    The authors analyzed data on 43 patients at the Albert Einstein Medical Center in Philadelphia who participated in RTOG phase III protocol 79-16 (evaluation of misonidazole combined with varying dose schedules of radiation therapy in the treatment of brain metastases). Karnofsky status and brain CT findings were correlated as prognosticators of response to radiation therapy. CT was performed at specific intervals before treatment and at 6 and 12 weeks after completion of therapy. Based on CT appearance, the maximum response to radiation therapy occurred 1.5 months after the initiation of treatment. Average survival, defined from the first day of treatment, was 5.9 months. Patients with total resolution on CT at 6 weeks had an average survival of 9.5 months, while those who showed improvement only on 6-week CT scans had an average survival of 7.2 months, and those who showed no change had an average survival of 5.2 months. Patients whose Karnofsky score improved with radiation therapy or remained the same had an average survival of 8.5 months; those whose score decreased had an average survival of 5.8 months. CT is a valuable indicator of response to radiation therapy, and CT findings closely correlate with the Karnofsky score

  2. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  3. Immunotherapy targeting immune check-point(s) in brain metastases.

    Science.gov (United States)

    Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

    2017-08-01

    Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Multiple brain metastases - current management and perspectives for treatment with electrochemotherapy

    DEFF Research Database (Denmark)

    Linnert, Mette; Iversen, Helle Klingenberg; Gehl, Julie

    2012-01-01

    BACKGROUND: Due to the advanced oncological treatments of cancer, an overall increase in cancer incidence, and better diagnostic tools, the incidence of brain metastases is on the rise. This review addresses the current treatment options for patients with multiple brain metastases, presenting...... of the chemotherapeutic drug bleomycin by 300 times. Preclinical data are promising and the first patient has been treated in an ongoing clinical trial for patients with brain metastases. Perspectives for ECT in the brain include treatment of primary and secondary brain tumors as well as soft tissue metastases elsewhere....

  5. Consensus for the brain metastases treatment

    International Nuclear Information System (INIS)

    Rabadan, Alejandra; Diez, Blanca; Martinez, Ana M.; Antico, Julio; Saidon, Patricia; Christiansen, Silvia; Rojas, Galeno

    2006-01-01

    The advancement in oncology therapies has made brain metastases treatment a major factor influencing the survival time and quality of life of patients with cancer. Although there are numerous publications on the issue, there is not yet to be consensus regarding the best strategy for treatment, which is probably due to population heterogeneity in terms of functional status, type of neoplasia, control of the systemic disease, and the number and localization of the lesions in the central nervous system. Our objective is to present general recommendations based on rational analysis in order to guide the practical management of brain metastases. With this purpose, a multidisciplinary team composed by neurosurgeons, neuro-oncologists, neuro-pathologist, radio therapist and neurologists was brought together, conducting a thorough search, in english and spanish, for publications in Pub- Med from 1980 to July 2006 (the starting period was set at the beginning of use of RM in medical practice). Review and original articles with n= or >20 were selected. Also, book chapters of renowned authors in the different consulted areas were included. The assessment of the literature, in addition to the experience of the authors allowed for the development of the 'Consensus for the brain metastases treatment'. Finally, the authors expect the present work will contribute to the multidisciplinary approach for the management of brain metastases with simple and practical recommendations, and probably stimulating future developments in this field. (author)

  6. A case of lung adenocarcinoma with multiple intracranial hemorrhages of brain metastases after whole-brain radiation therapy

    International Nuclear Information System (INIS)

    Nakamichi, Shinji; Hirano, Satoshi; Asao, Tetsuhiko; Takeda, Yuichiro; Sugiyama, Haruhito; Kobayashi, Nobuyuki

    2011-01-01

    Whole-brain radiation therapy (WBRT) is widely applied in cases of brain metastases of non-small cell lung cancer (NSCLC). However, there are few case reports on hemorrhages of brain metastases occurring after WBRT. A 63-year-old woman was given a diagnosis of stage IV (T4N0M1b) lung adenocarcinoma about 4 years previously, and received chemotherapy regimens and gamma knife radiosurgery. However, her brain metastases exacerbated and she received WBRT in November 2010 and docetaxel monotherapy in December 2010. Two weeks after completing WBRT, she experienced dysarthria and an MRI showed multiple hemorrhages within brain metastases. Over a period of careful observation, these hemorrhages repeatedly alternated between improvement and exacerbation. Radiotherapy for metastatic brain tumors is considered to suppress hemorrhagic events of brain metastases. However, multiple intracranial hemorrhages of brain metastases occurred after WBRT in the present case. The accumulation of further studies of similar cases is necessary to identify the exact mechanism of these hemorrhages. (author)

  7. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  8. Management of melanoma brain metastases in the era of targeted therapy.

    Science.gov (United States)

    Shapiro, Daniela Gonsalves; Samlowski, Wolfram E

    2011-01-01

    Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy." These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

  9. Management of Melanoma Brain Metastases in the Era of Targeted Therapy

    International Nuclear Information System (INIS)

    Shapiro, D. G.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.

    2011-01-01

    Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy."These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

  10. Brain metastases in lung cancer. Impact of prognostic factors on patient survival

    International Nuclear Information System (INIS)

    Smrdel, U.; Zwitter, M.; Kovac, V.

    2003-01-01

    Background. Brain metastases are common patterns of dissemination in lung cancer patients. In this paper we would like to assess the pattern of brain metastases in lung cancer patients and the impact of prognostic factors on the survival of lung cancer patients with brain metastases. Patients and methods. In the year 1998 there were 974 registered patients with lung cancer in Slovenia, six hundred and fifteen of them were treated at the Institute of Oncology Ljubljana and we analyzed them. Among 615 patients 137 (22.3 %) of them have had brain metastases during a natural course of disease. Results. For 12 patients presenting with solitary brain metastases (most of them were undertaken metastasectomy) median survival was 7.6 months, while in patients with multiple brain metastases the median survival was 2.8 months (p 0.0018). Of the 137 patients 45 (32.8 %) were small cell lung cancer patients, 43 (31.4 %) were adenocarcinoma patients and 19 (13.9 %) were squamous cell carcinoma patients. Patients with performance status (WHO scale) less than 2 had the median survival time 3.7 months while patients with performance status 2 or more had median survival time 2.7 moths (p=0.0448). Conclusions. Patients with solitary brain metastases had better survival comparing with those who had multiple metastases. It is surprisingly that the portion of brain metastases patients with adenocarcinoma is almost equal to those with small-call lung cancer therefore, the prophylactic cranial radiation becomes actual for both groups of patients. The performance status of patients with brain metastases remains very important prognostic factor. (author)

  11. Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

    International Nuclear Information System (INIS)

    Levegrün, Sabine; Pöttgen, Christoph; Wittig, Andrea; Lübcke, Wolfgang; Abu Jawad, Jehad; Stuschke, Martin

    2013-01-01

    Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N mets ) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV mets ) and of the individual metastasis planning target volume (PTV ind met ) were 8.7 ± 8.9 cm 3 (range, 1.3-35.5 cm 3 ) and 2.5 ± 4.5 cm 3 (range, 0.19-24.7 cm 3 ), respectively. Dose distributions in PTV mets and PTV ind met were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N mets was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV mets amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV ind met were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV mets (CN = 0.737 for PTV mets ≤4.32 cm 3 vs CN = 0.848 for PTV mets >4.32 cm 3 , P=.006), in contrast to N mets . The achieved dose conformity to PTV mets , assessed by both CN and PITV, was in all investigated volume strata

  12. Whole brain helical Tomotherapy with integrated boost for brain metastases in patients with malignant melanoma–a randomized trial

    International Nuclear Information System (INIS)

    Hauswald, Henrik; Habl, Gregor; Krug, David; Kehle, Denise; Combs, Stephanie E; Bermejo, Justo Lorenzo; Debus, Jürgen; Sterzing, Florian

    2013-01-01

    Patients with malignant melanoma may develop brain metastases during the course of the disease, requiring radiotherapeutic treatment. In patients with 1–3 brain metastases, radiosurgery has been established as a treatment option besides surgery. For patients with 4 or more brain metastases, whole brain radiotherapy is considered the standard treatment. In certain patients with brain metastases, radiation treatment using whole brain helical Tomotherapy with integrated boost and hippocampal-sparing may improve prognosis of these patients. The present prospective, randomized two-armed trial aims to exploratory investigate the treatment response to conventional whole brain radiotherapy applying 30 Gy in 10 fractions versus whole brain helical Tomotherapy applying 30 Gy in 10 fractions with an integrated boost of 50 Gy to the brain metastases as well as hippocampal-sparing in patients with brain metastases from malignant melanoma. The main inclusion criteria include magnetic resonance imaging confirmed brain metastases from a histopathologically confirmed malignant melanoma in patients with a minimum age of 18 years. The main exclusion criteria include a previous radiotherapy of the brain and not having recovered from acute high-grade toxicities of prior therapies. The primary endpoint is treatment-related toxicity. Secondary endpoints include imaging response, local and loco-regional progression-free survival, overall survival and quality of life

  13. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, Dirk; Huttenlocher, Stefan; Hornung, Dagmar; Blanck, Oliver; Schild, Steven E; Fischer, Dorothea

    2014-01-01

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant. In breast cancer patients with few brain metastases, radiosurgery plus whole-brain

  14. BRAIN METASTASES OF GERM CELL TUMORS. THE RUSSIAN CANCER RESEARCH CENTER'S EXPERIENCE

    Directory of Open Access Journals (Sweden)

    A. A. Tryakin

    2014-07-01

    Full Text Available This paper analyzes the experience in treating 20 patients with nonseminomatous germ cell tumors metastasizing to the brain. It presents brain metastasis-associated factors: multiple lung metastases; IGCCCG poor prognosis; and a baseline human chorionic gonadotropin level of > 50000 mIU/ml. The authors have identified a group to be screened for brain metastasis, which includes patients with intermediate/poor prognosis and multiple lung metastases. Long-term survival was achieved in 45 % of patients with baseline brain damage and in 22 % of those with metastases revealed after first-line chemotherapy. The positive prognostic factors associated with long-term survival were a single brain lesion, no neurological symptoms, and achievement of clinical complete personse in the brain.

  15. Therapeutic challenge in brain metastases: chemotherapy, surgery or radiotherapy

    International Nuclear Information System (INIS)

    Mena, Ivan; Contreras, Manuel; Ceballos Francisco

    1998-01-01

    Metastases to the brain occur in 25 to 35% of patients with systemic cancer. Cerebral metastatic is the most common intracranial tumor in adults and occur up to 10 times more frequently than primary tumors in the central nervous system. Significant advances have occurred in the diagnosis and treatment of metastases to the brain, and the therapeutic nihilism of the past is now no longer warranted for most patients. With the currently available treatments, most patients do not die of their brain metastases and usually experience effective palliation of neurologic symptoms and meaning full extension of life. As a trial to limit the cerebral metastatic disease, many and diverse therapy options have been developed such as: chemotherapy, surgery plus whole-brain radiotherapy, only radiation therapy, therapy with neutron, intersticial brachytherapy and stereotactic radiosurgery. In selected cases, surgery plus whole-brain radiotherapy is the conventional treatment for single metastases. However, recurrence usually limits the quality of life and greatly decrease the patients time life, and the therapy options are scarce. This piece of writing also includes a review of the available therapy forms to manage this kind of lesions. (The author)

  16. Is a diagnostic CT of the brain indicated in patients with choroidal metastases before radiotherapy?

    International Nuclear Information System (INIS)

    Bottke, D.; Wiegel, T.; Hoecht, S.; Hinkelbein, W.; Kreusel, K.M.

    2005-01-01

    Background and purpose: there is no evidence in the literature about the incidence of synchronous brain metastases in patients with choroidal metastases. This is of major importance, because the radiation fields of choroidal metastases and, later on, brain metastases, if treated consecutively, are partly overlapping, thus potentially increasing the rate of late side effects such as brain necrosis. The goal of this study was to determine the frequency of synchronous brain metastases. Patients and methods: 50 patients with choroidal metastases were enrolled into a study of the ''Arbeitsgemeinschaft Radiologische Onkologie'' of the German Cancer Society (ARO 95-08) with standardized 40 Gy radiotherapy, 2 Gy single dose. All patients were staged before treatment with a computed tomography of the brain (CCT). No patient showed clinical signs of brain metastases. Results: 13 out of 50 patients (26%) had brain metastases in the CCT leading to radiotherapy of the brain and choroidal metastases in one volume. Conclusion: a CCT is indicated at the diagnosis of choroidal metastases for screening of synchronous brain metastases. The incidence is about 25%, and the diagnosis of brain metastases results in a different target volume: the whole brain including the posterior parts of the eyes compared to the posterior parts of the eyes alone. Therefore, the risk of late side effects could be reduced compared with an additional later radiotherapy of the whole brain with partly overlapping fields. (orig.)

  17. Treatment strategies for lung cancer brain metastases

    International Nuclear Information System (INIS)

    Nakade, Masaharu; Kohno, Keijirou; Watanabe, Hiroyoshi

    1997-01-01

    Forty-one patients suffered initial relapses with brain metastasis after surgery for non-small lung cancer at our hospital between 1978 and 1995. These patients were a total of 8.4% of all cases of surgical removal, and had an average relapse period of 8.6 months ± 8.0 months after surgery on the primary lesions. Of these, surgical removal of metastasized lesions was performed on 18 patients (43%), in which the 5-year post-operative survival rate was 35.7%, and the median survival time was good at 28 months. It was found that the survival period was significantly extended in the group whose relapse period was less than one year after surgery on the primary lesions, and in the group who received cranial irradiation post-operatively on the metastasized brain lesion. Following surgery on the metastasized lesion, second relapses occurred in nine patients, and six patients suffered from second relapses in the brain, of which four did not receive cranial irradiation post-operatively. Cases of radiotherapy in patients of 70 years of age or more frequently manifested post-radiotherapy subacute neuropathy. From the above, it is thought that the following procedures should be adopted: Periodic examination for brain metastasis during the 24 months following surgery for non-small cell lung carcinoma for purposes of early detection; in cases where brain metastasis is detected, if no metastasis is identified in other organs, a policy of surgical removal should be adopted where possible; and, in cases of 70 years of age or less following surgery on the metastasized lesion, cranial irradiation should be considered. (author)

  18. Brain abscess mimicking lung cancer metastases; a case report.

    Science.gov (United States)

    Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

    2013-01-01

    A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

    Science.gov (United States)

    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  20. Treatment of brain metastases from primary lung cancer

    International Nuclear Information System (INIS)

    Ryan, Gail F.; Ball, David L.; Smith, Jennifer G.

    1995-01-01

    Purpose: A retrospective study of patients treated at the Peter MacCallum Cancer Institute for brain metastases from primary carcinoma of the lung is presented. Methods and Materials: The medical records of 416 patients with the diagnosis of primary carcinoma of the lung who presented with, or subsequently developed, brain metastases during the period January 1984 to December 1987 were reviewed. Information on a number of factors of potential prognostic significance (sex, age, histology, performance status and interval between diagnosis of the primary and brain metastases) was collected. Details of surgery, radiation and steroid usage were recorded, and any steroid side effects documented. Survival was calculated from the date of diagnosis of brain metastases. Stepwise regression based on Cox's proportional hazards model was used to determine significant prognostic factors affecting survival. Patients with and without steroid side effects were compared using Yate's corrected chi-square test. Results: The overall estimated median survival was only 3.3 months (95% confidence interval 2.9-3.7 months). Only two factors were found to be associated with a significantly improved survival--surgical intervention and good performance status. After taking these two factors into account, the dose of radiation used (< 30 Gy or ≥ 30 Gy) did not influence survival. There was a 3% incidence of gastric bleeding or perforation in patients taking steroids, with a 40% fatality rate. Predisposing factors to gastric side effects were a prior history of peptic ulcer and/or aspirin or nonsteroidal anti-inflammatory drug consumption. Conclusion: Radiation of brain metastases from primary lung cancer results in modest survival benefit. Radiation dose (< 30 Gy or ≥ 30 Gy) is not a significant determinant of survival. Other treatment modifications, such as concurrent radiation and chemotherapy, should be explored. Steroids should be used with caution as fatal side effects can occur

  1. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

    Institute of Scientific and Technical Information of China (English)

    Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

    2004-01-01

    AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS <70 (P<0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

  2. Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. A comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Romagna, Alexander; Schwartz, Christoph; Tonn, Joerg-Christian; Kreth, Friedrich-Wilhelm [Ludwig-Maximilians-University, Department of Neurosurgery, Munich (Germany); Egensperger, Rupert [Ludwig-Maximilians-University, Center for Neuropathology and Prion Research, Munich (Germany); Watson, Juliana; Belka, Claus; Nachbichler, Silke Birgit [Ludwig-Maximilians-University, Department of Radiation-Oncology, Munich (Germany)

    2016-11-15

    Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy{sub 3} and 249.6 Gy{sub 3}). No toxicity-related risk factors were identified. SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment. (orig.) [German] Daten zu Risiko und Effizienz ablativer

  3. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

    International Nuclear Information System (INIS)

    Tallet, Agnes V; Azria, David; Barlesi, Fabrice; Spano, Jean-Philippe; Carpentier, Antoine F; Gonçalves, Antony; Metellus, Philippe

    2012-01-01

    Whole brain radiation therapy (WBRT) is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests) with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more), insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation

  4. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

    Directory of Open Access Journals (Sweden)

    Tallet Agnes V

    2012-05-01

    Full Text Available Abstract Whole brain radiation therapy (WBRT is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more, insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation.

  5. Role of the Blood-Brain Barrier in the Formation of Brain Metastases

    Directory of Open Access Journals (Sweden)

    István A. Krizbai

    2013-01-01

    Full Text Available The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB. The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.

  6. Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

    International Nuclear Information System (INIS)

    Ono, Makiko; Ando, Masashi; Yunokawa, Mayu

    2009-01-01

    Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Among the patients who received a trastuzumab-containing regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2-14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0-45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases. (author)

  7. Response assessment criteria for brain metastases : proposal from the RANO group

    NARCIS (Netherlands)

    Lin, Nancy U.; Lee, Eudocia Q.; Aoyama, Hidefumi; Barani, Igor J.; Barboriak, Daniel P.; Baumert, Brigitta G.; Bendszus, Martin; Brown, Paul D.; Camidge, D. Ross; Chang, Susan M.; Dancey, Janet; de Vries, Elisabeth G. E.; Gaspar, Laurie E.; Harris, Gordon J.; Hodi, F. Stephen; Kalkanis, Steven N.; Linskey, Mark E.; Macdonald, David R.; Margolin, Kim; Mehta, Minesh P.; Schiff, David; Soffietti, Riccardo; Suh, John H.; van den Bent, Martin J.; Vogelbaum, Michael A.; Wen, Patrick Y.

    CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation

  8. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer.

    Science.gov (United States)

    Duchnowska, Renata; Loibl, Sibylle; Jassem, Jacek

    2018-06-01

    Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy. The small-molecule tyrosine kinase inhibitors of epidermal growth factor receptors family have established activity in HER2-positive breast cancer in both advanced disease and neoadjuvant setting. Favorable physico-chemical properties of these compounds allow them for a more efficient penetration through the blood-brain barrier, and hold the promise for more effective prevention and treatment of brain metastases. In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Radiosurgery for brain metastases: the Tuebingen experience

    International Nuclear Information System (INIS)

    Becker, Gerd; Jeremic, Branislav; Engel, Corinna; Buchgeister, Markus; Paulsen, Frank; Duffner, Frank; Meisner, Christoph; Bamberg, Michael

    2002-01-01

    Purpose: To retrospectively investigate the effectiveness of linear accelerator based radiosurgery (RS) in the treatment of brain metastases (BM). Material and methods: Of 55 patients with a total of 72 BM, 41 patients had a single brain metastasis and 14 patients had two or three metastases. Median tumour dose of 15 Gy (range 8-20 Gy) was prescribed to a median isodose surface of 90% (range 70-100%) encompassing the target volume. Results: The median survival time (MST) for all 55 patients was 7 months [95% confidence interval (CI), 5-10 months] and 2-year survival is 18%. There was no significant difference between patients who had one brain metastasis and those with either two or three metastases (log rank P=0.7565). Multivariate analysis in patients with a single BM showed that interval between primary diagnosis (PD) to BM, maximum size of metastasis, and histology (renal cell carcinoma and melanoma versus others) were independent prognostic factors influencing survival. Local control was obtained in 66/72 (92%) metastases. Actuarial local control at 24 months was 52%. Only age (≤50 years vs >50 years) and histology (renal cell versus others) influenced local control in the univariate analysis in patients with a single BM. In multivariate analysis, size, histology (renal cell and melanoma versus others), activity of extracranial metastatic disease, age, interval from PD to BM and location (midline versus other) independently influenced local control, while the dose was not significant for our patient group. Only one patient developed radiographically suspected RS-induced necrosis after previous whole brain RT. Conclusion: RS was effective and little toxic in BM. Identification of prognostic factors must be performed to gain knowledge on patients most likely to benefit from this procedure

  10. Do patients with a limited number of brain metastases need whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, D.; Schild, S.E.

    2012-01-01

    Background: About 40% of patients with brain metastases have a very limited number of lesions and may be candidates for radiosurgery. Radiosurgery alone is superior to whole-brain radiotherapy (WBRT) alone for control of treated and new brain metastases. In patients with a good performance status, radiosurgery also resulted in better survival. However, the question is whether the results of radiosurgery alone can be further improved with additional WBRT. Methods: Information for this review was compiled by searching the PubMed and MEDLINE databases. Very important published meeting abstracts were also considered. Results: Based on both retrospective and prospective studies, the addition of WBRT to radiosurgery improved control of treated and new brain metastases but not survival. However, because a recurrence within the brain has a negative impact on neurocognitive function, it is important to achieve long-term control of brain metastases. Conclusion: The addition of WBRT provides significant benefits. Further randomized studies including adequate assessment of neurocognitive function and a follow-up period of at least 2 years are needed to help customize the treatment for individual patients. (orig.)

  11. Mr imaging and mr spectroscopy of brain metastases by mr perfusion

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Lichy, M.P.; Thilmann, C.; Guenther, M.; Bachert, P.; Delorme, S.; Schad, L.R.; Debus, J.; Schlemmer, H.P.; Maudsley, A.A.

    2003-01-01

    In follow-up examinations of irradiated brain metastases conventional contrast-enhanced morphological MR imaging is often unable to distinguish between transient radiation effects, radionecrosis, and tumor recurrence. To evaluate changes of relative cerebral blood flow (rCBF) in irradiated brain metastases arterial spin-labeling techniques (ASL) were applied and compared to the outcome of 1 H MR spectroscopy and spectroscopic imaging ( 1 H MRS, SI). Patients and methods In 2 patients follow-up examinations of irradiated brain metastases were performed on a 1.5-T tomograph (average single dose: 20 Gy/80% isodose). Relative CBF values of gray matter (GM), white matter (WM), and metastases (Met) were measured by means of the ASL techniques ITS-FAIR and Q2TIPS. 1 H MRS was performed with PRESS 1500/135. In both patients with initially hyperperfused metastases (Met/GM >1) the reduction of rCBF after stereotactic radiosurgery indicated response to treatment - even if the contrast-enhancing region increased - while increasing rCBF values indicated tumor progression. The findings were confirmed by 1 H MRS, SI and subsequent follow-up. The ASL techniques ITS-FAIR and Q2TIPS are able to monitor changes of rCBF in irradiated brain metastases. The two cases imply a possible role for ASL-MR perfusion imaging and 1 H MR spectroscopy in differentiating radiation effects from tumor progression. (orig.) [de

  12. Radiosurgery for Large Brain Metastases

    International Nuclear Information System (INIS)

    Han, Jung Ho; Kim, Dong Gyu; Chung, Hyun-Tai; Paek, Sun Ha; Park, Chul-Kee; Jung, Hee-Won

    2012-01-01

    Purpose: To determine the efficacy and safety of radiosurgery in patients with large brain metastases treated with radiosurgery. Patients and Methods: Eighty patients with large brain metastases (>14 cm 3 ) were treated with radiosurgery between 1998 and 2009. The mean age was 59 ± 11 years, and 49 (61.3%) were men. Neurologic symptoms were identified in 77 patients (96.3%), and 30 (37.5%) exhibited a dependent functional status. The primary disease was under control in 36 patients (45.0%), and 44 (55.0%) had a single lesion. The mean tumor volume was 22.4 ± 8.8 cm 3 , and the mean marginal dose prescribed was 13.8 ± 2.2 Gy. Results: The median survival time from radiosurgery was 7.9 months (95% confidence interval [CI], 5.343–10.46), and the 1-year survival rate was 39.2%. Functional improvement within 1–4 months or the maintenance of the initial independent status was observed in 48 (60.0%) and 20 (25.0%) patients after radiosurgery, respectively. Control of the primary disease, a marginal dose of ≥11 Gy, and a tumor volume ≥26 cm 3 were significantly associated with overall survival (hazard ratio, 0.479; p = .018; 95% CI, 0.261–0.880; hazard ratio, 0.350; p = .004; 95% CI, 0.171–0.718; hazard ratio, 2.307; p = .006; 95% CI, 1.274–4.180, respectively). Unacceptable radiation-related toxicities (Radiation Toxicity Oncology Group central nervous system toxicity Grade 3, 4, and 5 in 7, 6, and 2 patients, respectively) developed in 15 patients (18.8%). Conclusion: Radiosurgery seems to have a comparable efficacy with surgery for large brain metastases. However, the rate of radiation-related toxicities after radiosurgery should be considered when deciding on a treatment modality.

  13. Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone

    International Nuclear Information System (INIS)

    Rowe, John D. del; Bello, Jacqueline; Mitnick, Robin; Sood, Brij; Filippi, Christopher; Moran, Justin Ph.D.; Freeman, Katherine; Mendez, Frances; Bases, Robert

    1999-01-01

    Purpose: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. Methods and Materials: The organ distribution of 3 H lucanthone in mice and 125 I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. Results: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. Conclusion: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536

  14. Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

    International Nuclear Information System (INIS)

    Welzel, Grit; Fleckenstein, Katharina; Schaefer, Joerg; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Mai, Sabine K.; Wenz, Frederik

    2008-01-01

    Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects

  15. Results of radiotherapy for brain metastases in old-aged patients

    International Nuclear Information System (INIS)

    Nieder, C.; Niewald, M.; Schnabel, K.

    1995-01-01

    To evaluate which patients older tahn 70 years will benefit by radiotherapy for their brain metastases the data of 35 patients in this age-group who were treated between 1983 and 1994 were retrospectivley analyzed. All patients were previously untreated and received a whole-brain irradiation and concomitantly corticosteroids. The median total dose was 30 Gy (fractionation: 10 times 3 Gy in 2 weeks). Six patients each received lower or higher total doses with 50.4 Gy at maximum. Six patients failed to complete their prescribed treatment (17%). The median survival of all patients who completed their radiotherapy course was 67 days only. Patients with extracerebral metastases had a median survival of 31 days. Survival was not dependent on total dose of radiotherapy. In 56% of all cases the general condition of the patients improved or remained stable at a high level. Karnofsky-performance status was the most important prognostic factor. Advanced age is an unfavourable prognostic factor. Only patients in good general condition without extracerebral metastases had survival times which justify radiotherapy for their brain metastases. (orig./MG) [de

  16. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    International Nuclear Information System (INIS)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 ± 0.62 Gy and 6.29 ± 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 ± 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 ± 0.7 Gy and 32.7 ± 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 ± 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  17. Radiological Patterns of Brain Metastases in Breast Cancer Patients : A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    NARCIS (Netherlands)

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Wuerschmidt, Florian; Fehm, Tanja; Moebus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain

  18. Combining stereotactic radiosurgery and systemic therapy for brain metastases: a potential role for temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Hardee, Matthew E. [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Department of Medical Oncology, New York University Langone Medical Center, New York, NY (United States)

    2012-08-09

    Brain metastases are unfortunately very common in the natural history of many solid tumors and remain a life-threatening condition, associated with a dismal prognosis, despite many clinical trials aimed at improving outcomes. Radiation therapy options for brain metastases include whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). SRS avoids the potential toxicities of WBRT and is associated with excellent local control (LC) rates. However, distant intracranial failure following SRS remains a problem, suggesting that untreated intracranial micrometastatic disease is responsible for failure of treatment. The oral alkylating agent temozolomide (TMZ), which has demonstrated efficacy in primary malignant central nervous system tumors such as glioblastoma, has been used in early phase trials in the treatment of established brain metastases. Although results of these studies in established, macroscopic metastatic disease have been modest at best, there is clinical and preclinical data to suggest that TMZ is more efficacious at treating and controlling clinically undetectable intracranial micrometastatic disease. We review the available data for the primary management of brain metastases with SRS, as well as the use of TMZ in treating established brain metastases and undetectable micrometastatic disease, and suggest the role for a clinical trial with the aims of treating macroscopically visible brain metastases with SRS combined with TMZ to address microscopic, undetectable disease.

  19. Radiotherapy for brain metastases: defining palliative response

    International Nuclear Information System (INIS)

    Bezjak, Andrea; Adam, Janice; Panzarella, Tony; Levin, Wilfred; Barton, Rachael; Kirkbride, Peter; McLean, Michael; Mason, Warren; Wong, Chong Shun; Laperriere, Normand

    2001-01-01

    Background and purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. Materials and methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT

  20. The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Walbert, T.; Gilbert, M.R.

    2009-01-01

    Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints. (author)

  1. Stereotactic radiosurgery for newly diagnosed brain metastases. Comparison of three dose levels

    International Nuclear Information System (INIS)

    Rades, Dirk; Hornung, Dagmar; Blanck, Oliver; Martens, Kristina; Khoa, Mai Trong; Trang, Ngo Thuy; Hueppe, Michael; Terheyden, Patrick; Gliemroth, Jan; Schild, Steven E.

    2014-01-01

    Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size ( 24 months). For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79 %, respectively (p [de

  2. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Schild Steven E

    2010-10-01

    Full Text Available Abstract Background This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. Methods Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA class. Results Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038, KPS ≥70 (p Conclusions Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

  3. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  4. Isolated brain metastases of osteosarcoma in a patient presenting with a patent foramen ovale

    International Nuclear Information System (INIS)

    Menassa, L.; Haddad, S.; Aoun, N.; Slaba, S.; Atallah, N.

    1997-01-01

    We report the case of a patient in whom brain MR imaging was requested for initial symptoms of intracranial hypertension. The presence of multiple intracranial hemorrhagic lesions suggested brain metastases. Body screening showed periosteal osteosarcoma of the left fibula with no lung metastases, but with a patent foramen ovale which probably allowed neoplastic cells to reach the brain without being filtered through the lungs. The conclusion of this study was that a left-right cardiac communication is to be considered in cases of isolated brain metastases from osteosarcoma. (orig.). With 3 figs

  5. Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

    International Nuclear Information System (INIS)

    Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

    2013-01-01

    Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients

  6. Predictors of Distant Brain Recurrence for Patients With Newly Diagnosed Brain Metastases Treated With Stereotactic Radiosurgery Alone

    International Nuclear Information System (INIS)

    Sawrie, Stephen M.; Guthrie, Barton L.; Spencer, Sharon A.; Nordal, Robert A.; Meredith, Ruby F.; Markert, James M.; Cloud, Gretchen A.; Fiveash, John B.

    2008-01-01

    Purpose: To ascertain predictors of distant brain failure (DBF) in patients treated initially with stereotactic radiosurgery alone for newly diagnosed brain metastases. We hypothesize that these factors may be used to group patients according to risk of DBF. Methods and Materials: We retrospectively analyzed 100 patients with newly diagnosed brain metastases treated from 2003 to 2005 at our Gamma Knife radiosurgery facility. The primary endpoint was DBF. Potential predictors included number of metastases, tumor volume, histologic characteristics, extracranial disease, and use of temozolomide. Results: One-year actuarial risk of DBF was 61% for all patients. Significant predictors of DBF included more than three metastases (hazard ratio, 3.30; p = 0.004), stable or poorly controlled extracranial disease (hazard ratio, 2.16; p = 0.04), and melanoma histologic characteristics (hazard ratio, 2.14; p = 0.02). These were confirmed in multivariate analysis. Those with three or fewer metastases, no extracranial disease, and nonmelanoma histologic characteristics (N = 18) had a median time to DBF of 89 weeks vs. 33 weeks for all others. One-year actuarial freedom from DBF for this group was 83% vs. 26% for all others. Conclusions: Independent significant predictors of DBF in our series included number of metastases (more than three), present or uncontrolled extracranial disease, and melanoma histologic characteristics. These factors were combined to identify a lower risk subgroup with significantly longer time to DBF. These patients may be candidates for initial localized treatment, reserving whole-brain radiation therapy for salvage. Patients in the higher risk group may be candidates for initial whole-brain radiation therapy or should be considered for clinical trials

  7. Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases

    Science.gov (United States)

    Lee, Chul-Kyu; Lee, Sang Ryul; Cho, Jin Mo; Yang, Kyung Ah

    2011-01-01

    Objective The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results The overall median survival after GKRS was 9.1±1.7 months. Among various factors, primary tumor control was a significant prognostic factor (11.1±1.3 months vs. 3.3±2.4 months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase. PMID:22102945

  8. Analysis of fractional anisotropy facilitates differentiation of glioblastoma and brain metastases in a clinical setting

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    Bette, Stefanie, E-mail: stefanie.bette@tum.de [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Huber, Thomas; Wiestler, Benedikt; Boeckh-Behrens, Tobias [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Zimmer, Claus; Kirschke, Jan S. [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany)

    2016-12-15

    Purpose: Differentiating glioblastoma from brain metastases is important for therapy planning. Diffusion tensor imaging (DTI) was described as a promising tool, however with conflicting results. Aim: of this study was to analyze the clinical utility of DTI for the differentiation of brain metastases and glioblastoma. Methods: 294 patients (165 glioblastoma, 129 brain metastases) with preoperative DTI were included in this retrospective study. Fractional anisotropy (FA) was measured via regions of interest (ROIs) in the contrast-enhancing tumor, the necrosis and the FLAIR-hyperintense non-enhancing peritumoral region (NEPTR). Two neuroradiologists classified patient cases as glioblastoma or brain metastases without and with knowledge of FA values. Results: Glioblastoma showed significantly higher FA{sub contrast} (median glioblastoma = 0.33, metastases = 0.23; P < 0.001) whereas no significant difference was observed for FA{sub NEPTR} (0.21 vs. 0.22; P = 0.28) and for FA{sub necrosis} (0.17 vs. 0.18, P = 0.37). FA improved diagnostic accuracy of the neuroradiologists significantly from an AUC of 0.84/0.85 (Reader1/Reader2) to 0.89/0.92. Conclusions: Glioblastoma show significantly higher FA values in the contrast enhancing tumor part than brain metastases. Implementation of a ROI-based measurement of FA values and FA color maps in clinical routine helps to differentiate between glioblastoma and brain metastases.

  9. Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

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    Yi LIU

    2013-07-01

    Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

  10. Radiosurgery alone for 5 or more brain metastases: expert opinion survey.

    Science.gov (United States)

    Knisely, Jonathan P S; Yamamoto, Masaaki; Gross, Cary P; Castrucci, William A; Jokura, Hidefumi; Chiang, Veronica L S

    2010-12-01

    Oligometastatic brain metastases may be treated with stereotactic radiosurgery (SRS) alone, but no consensus exists as to when SRS alone would be appropriate. A survey was conducted at 2 radiosurgery meetings to determine which factors SRS practitioners emphasize in recommending SRS alone, and what physician characteristics are associated with recommending SRS alone for ≥ 5 metastases. All physicians attending the 8th Biennial Congress and Exhibition of the International Stereotactic Radiosurgery Society in June 2007 and the 18th Annual Meeting of the Japanese Society of Stereotactic Radiosurgery in July 2009 were asked to complete a questionnaire ranking 14 clinical factors on a 5-point Likert-type scale (ranging from 1 = not important to 5 = very important) to determine how much each factor might influence a decision to recommend SRS alone for brain metastases. Results were condensed into a single dichotomous outcome variable of "influential" (4-5) versus "not influential" (1-3). Respondents were also asked to complete the statement: "In general, a reasonable number of brain metastases treatable by SRS alone would be, at most, ___." The characteristics of physicians willing to recommend SRS alone for ≥ 5 metastases were assessed. Chi-square was used for univariate analysis, and logistic regression for multivariate analysis. The final study sample included 95 Gamma Knife and LINAC-using respondents (54% Gamma Knife users) in San Francisco and 54 in Sendai (48% Gamma Knife users). More than 70% at each meeting had ≥ 5 years experience with SRS. Sixty-five percent in San Francisco and 83% in Sendai treated ≥ 30 cases annually with SRS. The highest number of metastases considered reasonable to treat with SRS alone in both surveys was 50. In San Francisco, the mean and median numbers of metastases considered reasonable to treat with SRS alone were 6.7 and 5, while in Sendai they were 11 and 10. In the San Francisco sample, the clinical factors identified to be

  11. Radiotherapy management of brain metastases using conventional linear accelerator.

    Science.gov (United States)

    Matzenauer, Marcel; Vrana, David; Vlachova, Zuzana; Cwiertka, Karel; Kalita, Ondrej; Melichar, Bohuslav

    2016-09-01

    As treatments for primary cancers continue to improve life expectancy, unfortunately, brain metastases also appear to be constantly increasing and life expectancy for patients with brain metastases is low. Longer survival and improved quality of life may be achieved using localised radiological and surgical approaches in addition to low dose corticosteroids. Stereotactic brain radiotherapy is one rapidly evolving localized radiation treatment. This article describes our experience with stereotactic radiotherapy using a linear accelerator. We reviewed patients treated with stereotactic radiotherapy, from the time of its introduction into daily practice in our Department of Oncology in 2014. We collected the data on patient treatment and predicted survival based on prognostic indices and actual patient outcome. A total of 10 patients were treated by stereotactic radiotherapy, in one case in combination with whole brain radiotherapy and hippocampal sparing. There was no significant treatment related toxicity during the treatment or follow-up and due to the small number of fractions, the overall tolerance of the treatment was excellent. The patient intrafractional movement in all cases was under 1 mm suggesting that 1 mm margin around the CTV to create the PTV is sufficient and also that patient immobilization using the thermoplastic mask compared with invasive techniques, is feasible. We also found that prognostic indices such as the Graded Prognostic Assessment provide accurate predictions of patient survival. Based on our current evidence, patients with brain metastases fit enough, should be considered for stereotactic radiotherapy treatment.

  12. Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP)

    International Nuclear Information System (INIS)

    Rades, D.; Bohlen, G.; Dunst, J.; Lohynska, R.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.

    2007-01-01

    Background: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. Patients and Methods: Data regarding 101 CUP patients who received either short course WBRT (n = 34) with 5 x 4 Gy or long-course WBRT (n = 67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. Results: On univariate analysis, the radiation program was not associated with survival (p = 0.88) nor intracerebral control (p = 0.36). Improved survival was associated with KPS ≥ 70 (p < 0.001), absence of extracranial metastases (p < 0.001), and RPA-class 1 (p < 0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p < 0.001), extracranial metastases (RR: 1.70; p = 0.018), and RPA-class (RR: 2.86; p < 0.001) maintained significance. On univariate analysis, KPS (p < 0.001) and RPA-class (p < 0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p < 0.001) and RPA-class (RR: 2.09; p < 0.001) remained significant. Conclusion: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients. (orig.)

  13. Melanoma brain metastases presenting as delirium: a case report

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    Sofia Morais

    Full Text Available Abstract Background Metastatic tumours sometimes present with neuropsychiatric symptoms, however psychiatric symptoms as rarely the first clinical manifestation. Cutaneous melanoma is the third most common cause of brain metastasis, with known risk factors increasing the chance of such central nervous system metastization. Objectives We present a clinical report of delirium as the first clinical manifestation of melanoma brain metastases, illustrating the relevance of an adequate and early differential diagnosis. Methods In addition to describing the clinical case, searches were undertaken in PubMed and other databases using keywords such as “brain metastasis”, “melanoma”, “agitation”, “psychiatric” and “delirium”. Results We here report the case of a 52-year-old female patient evaluated by Liaison Psychiatry after sudden onset of delirium while admitted at the Gastroenterology Department to study a hypothesis of pancreatitis. A head CT scan identified brain metastases, and after further examination, including brain biopsy, melanoma brain metastization was confirmed. Discussion Some of the diagnostic challenges of psychiatric symptoms associated with secondary brain tumours are discussed, underlining the importance of an adequate differential diagnosis when working in Psychiatry Liaison.

  14. Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

    International Nuclear Information System (INIS)

    Fogarty, Gerald; Shivalingam, Brindha; Dhillon, Haryana; Thompson, John F; Morton, Rachael L; Vardy, Janette; Nowak, Anna K; Mandel, Catherine; Forder, Peta M; Hong, Angela; Hruby, George; Burmeister, Bryan

    2011-01-01

    Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete. This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function. Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain

  15. Radiation therapy of brain metastases

    International Nuclear Information System (INIS)

    Obata, Yasunori; Morita, Kozo; Watanabe, Michiko; Niwa, Kokichi

    1982-01-01

    From January 1974 to December 1980, 104 patients with brain metastases were treated by irradiation to the whole brain. The results of treatment and the relation between CT images and effectiveness of irradiation were analized. The lung was the most common site of the primary tumor (67/104, 64.4%). The breast was a distant second in frequency (13/104, 12.5%) and fewer cases had other primary tumors (24/104, 23.1%). There were 63 males and 41 females. Their mean age was 56.0 years old. The interval between onset of symptoms from primary disease and of those from the brain metastases were 26.5 months for the breast cancer, 7.6 months for undifferentiated carcinoma of the lung and 13.2 months for all patients. Significant neurologic improvement was obtained in 85.7% of the patients (86 cases) irradiated as previous plans. The survival for the entire group of patients (86 cases) was 60.5% at 3 months, 31.4% at 6 months, 11.6% at 12 months an 3.5% at 18 months. Multiplicity of the metastatic brain tumror did not affect the prognosis but the control of the primary lesion affected the prognosis. The CT images of 41 cases before treatment revealed the enhanced mass was mainly homogeneous for the case with the breast cancer and mainly ring like for the case with squamous cell carcinoma of the lung. But the characters of the enhanced mass did not affect the prognosis. On the other hand, the analysis of the CT images of 37 cases before and after the treatment revealed the relation between the tumor regression and the improvement in neurologic symptoms. (J.P.N.)

  16. Longitudinal MRI evaluation of intracranial development and vascular characteristics of breast cancer brain metastases in a mouse model.

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    Heling Zhou

    Full Text Available Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34% of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03 than that of contralateral normal brain (mean= 1.00±0.03; p<0.005. Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05. The rCBV data were concordant with histological analysis of microvascular density (MVD. Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

  17. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients

    International Nuclear Information System (INIS)

    Lagerwaard, Frank J.; Levendag, Peter C.; Nowak, Peter J.C.M.; Eijkenboom, Wilhelmina M.H.; Hanssens, Patrick E.J.; Schmitz, Paul I.M.

    1999-01-01

    Purpose: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials. Materials and Methods: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports. Results: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic

  18. Diffusion-weighted imaging of brain metastases: their potential to be misinterpreted as focal ischaemic lesions

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    Geijer, B. [Department of Radiology, University Hospital, Lund (Sweden); Holtaas, S. [Department of Diagnostic Imaging, King Fahd Hospital, Riyadh (Saudi Arabia)

    2002-07-01

    Small focal ischaemic brain lesions are said to be easy to identify in the acute stage and to differentiate from older lesions using diffusion-weighted imaging (DWI). Brain metastases are common and the aim of this study was to evaluate the risk of misinterpretation as ischaemic lesions in a standard MRI protocol for clinical stroke. Of 26 patients investigated with MRI for possible metastases, 12 did have metastatic brain lesions, including most of the common tumours. On a 1.5 tesla imager, we obtained DWI, plus T2- and T1-weighted images, the latter before and after triple-dose contrast medium. Well-circumscribed brain lesions with a decreased apparent diffusion coefficient and a slightly or moderately increased signal on T2-weighted images were found in patients with metastases from a small-cell bronchial carcinoma and a pulmonary adenocarcinoma. The same features were also found in metastases from a breast carcinoma but the lesions were surrounded by oedema. With a standard DWI protocol, the features of common brain metastases may overlap with those of small acute and subacute ischaemic lesions. (orig.)

  19. Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

    International Nuclear Information System (INIS)

    Lekic, Mirko; Kovac, Viljem; Triller, Nadja; Knez, Lea; Sadikov, Aleksander; Cufer, Tanja

    2012-01-01

    Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis. All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of

  20. Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nagla Abdel Karim

    2015-01-01

    Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

  1. Diazepam prophylaxis of contrast media-induced seizures during computed tomography of patients with brain metastases

    International Nuclear Information System (INIS)

    Pagani, J.J.; Hayman, L.A.; Bigelow, R.H.; Libshitz, H.I.; Lepke, R.A.; Wallace, S.

    1983-01-01

    The effect of 5 mg of intravenous diazepam (Valium) on contrast media-associated seizer incidence was studied in a randomized controlled trial involving 284 patients with known or suspected brain metastases undergoing cerebral computed tomography. Of these patients, 188 were found to have brain metastases, and it is estimated that for this subgroup prophylactic diazepam reduces the risk of contrast-assocated seizure by a factor of 0.26. Seizures occurred in three of 96 patients with metastases on diazepam and in 14 of 92 patients with metastases but without diazepam. Factors related to increased risk of contrast media-associated seizures are: (1) prior seizure history due to brain metatases and/or prior contrast, (2) progressive cerebral metastases, and (3) prior or concurrent brain antineoplastic therapy. Factors not related to an increased risk of these seizures are: (1) contrast media dosage, chemical composition, or osmolarity, (2) computed tomographic appearance of metastases, and (3) type of primary malignancy. Concomitant therapeutic levels of diphenylhydantoin (Dilantin) do not protect completely against contrast media-associated seizures. Pathophysiology of contrast media-associated seizures is discussed in view of the risk factors determined by this study

  2. Unsanctifying the sanctuary: challenges and opportunities with brain metastases.

    Science.gov (United States)

    Puhalla, Shannon; Elmquist, William; Freyer, David; Kleinberg, Lawrence; Adkins, Chris; Lockman, Paul; McGregor, John; Muldoon, Leslie; Nesbit, Gary; Peereboom, David; Smith, Quentin; Walker, Sara; Neuwelt, Edward

    2015-05-01

    While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Innovative Therapeutic Strategies in the Treatment of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Francesco Tomasello

    2013-01-01

    Full Text Available Brain metastases (BM are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood into tissue elsewhere in the body, and formation of a secondary tumor. In the recent past, important results have been obtained in the management of patients affected by BM, using surgery, radiation therapy, or both. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood–brain barrier. The advent of new technologies has led to the discovery of novel molecules and pathways that have better depicted the metastatic process. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review, we will report current data on targeted therapies. A brief review about brain metastatic process will be also presented.

  4. Radiosurgery for brain metastases at the Royal Adelaide Hospital: are we treating the right patients?

    International Nuclear Information System (INIS)

    Roos, D.E.; Brophy, B.P.; Zavgorodni, S.F.; Katsilis, E.S.

    2002-01-01

    Although non-randomized data strongly suggest improved outcome from radiosurgery (RS) for brain metastases relative to whole brain radiotherapy (WBRT) alone, selection factors account for much of the observed differences. This retrospective review of the 16 brain metastases patients treated so far with RS at the Royal Adelaide Hospital confirms a median survival of 10.1 months, consistent with recent multi-institutional pooled results and significantly longer than the median survival of 3-6 months typically reported for WBRT alone. The emerging randomized trials comparing surgery, RS and WBRT for brain metastases are reviewed in the context of the Radiation Therapy Oncology Group Recursive Partitioning Analysis prognostic Class concept in order to assess whether we are using this resource intensive technique to treat the 'right' patients. We conclude that it is reasonable to continue our current policy of considering RS primarily for patients of good performance status with solitary brain metastases. VVe have a flexible approach to adjuvant WBRT which appears to decrease brain relapse, but not improve survival. Copyright (2002) Blackwell Science Pty Ltd

  5. The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    Goyal, Lav K.; Suh, John H.; Reddy, Chandana A.; Barnett, Gene H.

    2000-01-01

    Purpose: We reviewed our experience with patients who have undergone stereotactic radiosurgery (SRS) for brain metastases secondary to renal cell carcinoma (RCC). Analysis was performed to determine the survival, local control, distant brain failure (DBF), and then to define which tumors may not require upfront whole-brain radiotherapy (WBRT). Methods and Materials: Twenty-nine patients with 66 tumors underwent SRS from 1991 to 1998. Median follow-up from time of brain metastases diagnoses relative to each tumor was 12.5 months and 6.8 months from the time of SRS. Median SRS dose was 1,800 cGy to the 60% isodose line. Three patients had undergone SRS for previously treated tumors. Results: Median survival time from diagnosis was 10.0 months. Overall survival was not affected by age, addition of WBRT, number of lesions, tumor volume, or the presence of systemic disease. Of the 23 patients with follow-up neuroimaging, 4 of 47 (9%) tumors recurred. The addition of WBRT did not improve local control. Of the 13 patients who presented with a single lesion, 3 went on to develop DBF (23%), while 6 of the 10 patients who presented with multiple metastases developed DBF (60%). Conclusion: Patients with brain metastases secondary to RCC treated by SRS alone have excellent local control. The decision of whether or not to add WBRT to SRS should depend on whether the patient has a high likelihood of developing DBF. Our study suggests that patients who present with multiple brain lesions may be more likely to benefit from the addition of WBRT because they appear to be more than twice as likely to develop DBF as compared to patients with a single lesion

  6. Post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma

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    Kim, Kyung Su; Kim, Kyu Bo; Chie, Eui Kyu; Kim, Yoon Jun; Yoon, Jung Hwan; Lee, Hyo Suk; Ha, Sung W. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-03-15

    To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.

  7. Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

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    Patrick N Harter

    Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

  8. Survival and prognostic factors in patients treated with stereotactic radiotherapy for brain metastases

    DEFF Research Database (Denmark)

    Leth, Thomas; Oettingen, Gorm von; Lassen-Ramshad, Yasmin A.

    2015-01-01

    Abstract Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors...... will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven...... months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related...

  9. [Timing of Brain Radiation Therapy Impacts Outcomes in Patients with 
Non-small Cell Lung Cancer Who Develop Brain Metastases].

    Science.gov (United States)

    Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran

    2016-08-20

    Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; Pbrain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; Pbrain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.

  10. Adverse radiation effect after stereotactic radiosurgery for brain metastases : incidence, time course, and risk factors

    NARCIS (Netherlands)

    Sneed, Penny K.; Mendez, Joe; Vemer-van den Hoek, Johanna; Seymour, Zachary A.; Ma, Lijun; Molinaro, Annette M.; Fogh, Shannon E.; Nakamura, Jean L.; McDermott, Michael W.

    OBJECT The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases. METHODS All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at

  11. Automatic detection and segmentation of brain metastases on multimodal MR images with a deep convolutional neural network.

    Science.gov (United States)

    Charron, Odelin; Lallement, Alex; Jarnet, Delphine; Noblet, Vincent; Clavier, Jean-Baptiste; Meyer, Philippe

    2018-04-01

    Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  13. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Nieder, Carsten; Grosu, Anca L; Astner, Sabrina; Thamm, Reinhard; Molls, Michael

    2006-01-01

    Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy

  14. Whole Brain Radiotherapy With Hippocampal Avoidance and Simultaneous Integrated Boost for 1-3 Brain Metastases: A Feasibility Study Using Volumetric Modulated Arc Therapy

    International Nuclear Information System (INIS)

    Hsu, Fred; Carolan, Hannah; Nichol, Alan; Cao, Fred; Nuraney, Nimet; Lee, Richard; Gete, Ermias; Wong, Frances; Schmuland, Moira; Heran, Manraj; Otto, Karl

    2010-01-01

    Purpose: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT) to deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) for one to three brain metastases. Methods and Materials: Ten patients previously treated with stereotactic radiosurgery for one to three brain metastases underwent repeat planning using VMAT. The whole brain prescription dose was 32.25 Gy in 15 fractions, and SIB doses to brain metastases were 63 Gy to lesions ≥2.0 cm and 70.8 Gy to lesions 2 . Plans were optimized for conformity and target coverage while minimizing hippocampal and ocular doses. Plans were evaluated on target coverage, prescription isodose to target volume ratio, conformity number, homogeneity index, and maximum dose to prescription dose ratio. Results: Ten patients had 18 metastases. Mean values for the brain metastases were as follows: conformity number = 0.73 ± 0.10, target coverage = 0.98 ± 0.01, prescription isodose to target volume = 1.34 ± 0.19, maximum dose to prescription dose ratio = 1.09 ± 0.02, and homogeneity index = 0.07 ± 0.02. For the whole brain, the mean target coverage and homogeneity index were 0.960 ± 0.002 and 0.39 ± 0.06, respectively. The mean hippocampal dose was 5.23 ± 0.39 Gy 2 . The mean treatment delivery time was 3.6 min (range, 3.3-4.1 min). Conclusions: VMAT was able to achieve adequate whole brain coverage with conformal hippocampal avoidance and radiosurgical quality dose distributions for one to three brain metastases. The mean delivery time was under 4 min.

  15. A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    Full Text Available Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS treatment planning. In this work, we developed a deep learning convolutional neural network (CNN algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.

  16. Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Nichol, Alan, E-mail: anichol@bccancer.bc.ca [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Ma, Roy [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Hsu, Fred [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Abbotsford Centre, Abbotsford, British Columbia (Canada); Gondara, Lovedeep [Department of Surveillance and Outcomes, BC Cancer Agency, Vancouver, British Columbia (Canada); Carolan, Hannah [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Olson, Robert [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Centre for the North, Prince George, British Columbia (Canada); Schellenberg, Devin [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Fraser Valley Centre, Surrey, British Columbia (Canada); Germain, François [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Sindi Ahluwalia Centre for the Southern Interior, Kelowna, British Columbia (Canada); Cheung, Arthur [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Fraser Valley Centre, Surrey, British Columbia (Canada); Peacock, Michael [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); and others

    2016-02-01

    Purpose: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). Methods and Materials: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with (ClinicalTrials.gov) ( (clinicaltrials.gov) identifier (NCT01046123)). Results: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60

  17. Risks of postoperative paresis in motor eloquently and non-eloquently located brain metastases

    International Nuclear Information System (INIS)

    Obermueller, Thomas; Schaeffner, Michael; Gerhardt, Julia; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2014-01-01

    When treating cerebral metastases all involved multidisciplinary oncological specialists have to cooperate closely to provide the best care for these patients. For the resection of brain metastasis several studies reported a considerable risk of new postoperative paresis. Pre- and perioperative chemotherapy (Ctx) or radiotherapy (Rtx) alter vasculature and adjacent fiber tracts on the one hand, and many patients already present with paresis prior to surgery on the other hand. As such factors were repeatedly considered risk factors for perioperative complications, we designed this study to also identify risk factors for brain metastases resection. Between 2006 and 2011, we resected 206 brain metastases consecutively, 56 in eloquent motor areas and 150 in non-eloquent ones. We evaluated the influences of preoperative paresis, previous Rtx or Ctx as well as recursive partitioning analysis (RPA) class on postoperative outcome. In general, 8.7% of all patients postoperatively developed a new permanent paresis. In contrast to preoperative Ctx, previous Rtx as a single or combined treatment strategy was a significant risk factor for postoperative motor weakness. This risk was even increased in perirolandic and rolandic lesions. Our data show significantly increased risk of new deficits for patients assigned to RPA class 3. Even in non-eloquently located brain metastases the risk of new postoperative paresis has not to be underestimated. Despite the microsurgical approach, our cohort shows a high rate of unexpected residual tumors in postoperative MRI, which supports recent data on brain metastases’ infiltrative nature but might also be the result of our strict study protocol. Surgical resection is a safe treatment of brain metastases. However, preoperative Rtx and RPA score 3 have to be taken into account when surgical resection is considered

  18. Risk factors for local failure requiring salvage neurosurgery after radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Weltman, Eduardo; Hanriot, Rodrigo de Morais; Prisco, Flavio Eduardo; Nadalin, Wladimir; Brandt, Reynaldo Andre; Moreira, Frederico Rafael

    2004-01-01

    Objective: the aim of this study is to select the risk factors for local failure requiring salvage neurosurgery in patients with brain metastases treated with stereotactic radiosurgery in a single institution. Methods: the follow-up of 123 patients, with 255 brain metastases treated with radiosurgery at the Radiation Oncology Department of the Hospital Israelita Albert Einstein from July 1993 to August 2001, was retrospectively analyzed. The criteria for salvage neurosurgery were tumor volume enlargement, or tumor persistence leading to severe neurological symptoms, life threatening situation or critical steroid dependence. We considered the case as local failure when the histopathologic evaluation showed morphologically preserved cancer cells (tumor recurrence, persistence or progression). We applied the Fisher's exact test to evaluate the statistical correlation between local failure and primary tumor histology, volume of the brain metastases, prescribed radiosurgery dose, and whole brain radiotherapy. Results: fourteen of 123 patients (11%) underwent salvage neurosurgery. Histology showed preserved cancer cells with necrosis and/or bleeding in 11 cases (9% of the total accrual), and only necrosis with or without bleeding (without preserved cancer cells) in three cases. The primary tumor histology among the 11 patients considered with active neoplasia was malignant melanoma in five cases (21% of the patients with melanoma), breast adenocarcinoma in three (16% of the patients with breast cancer), and other histology in the remaining three. Breast cancer diagnosis, non-elective whole brain irradiation, volume of the brain metastases, and the prescribed radiosurgery dose did not correlate with the risk of local failure. Patients treated with elective whole brain radiotherapy showed fewer local failures, when compared to all patients receiving whole brain radiotherapy, and to the patients not receiving this treatment, with incidence of failure in 4%,7% and 14

  19. Intensity-modulated Radiosurgery for patients with brain metastases: a mature outcomes analysis.

    Science.gov (United States)

    Wang, Samuel J; Choi, Mehee; Fuller, Clifton D; Salter, Bill J; Fuss, Martin

    2007-06-01

    The purpose of this study was to evaluate the outcomes of patients with brain metastases treated by tomotherapeutic Intensity-modulated Radiosurgery (IMRS). Using retrospective chart review, we analyzed the outcomes of 78 patients (age 33-83 years, median 57 years) who underwent 111 sessions of IMRS (1 to 7 sessions per patient, median 1) for brain metastases (1 to 4 targets per IMRS session, median 1) treated between 2000 and 2005 using a serial tomotherapeutic intensity-modulated radiotherapy treatment (IMRT) planning and delivery system (Peacock, Nomos Corp., Cranberry Township, PA). Treatment planning was performed using an inverse treatment planning optimization algorithm that was optimized for IMRS. A median prescription dose of 15 Gy in combination with WBI, and median 20 Gy for IMRS alone was delivered using 2-4 couch angles over 4-24 rotational arcs. Overall survival was calculated using Kaplan-Meier analysis. To determine the effects of prognostic variables on survival, univariate and multivariate analyses using proportional hazards were performed to assess the effects of age, tumor size, the combination with whole brain irradiation, presence of multiple brain metastases, and presence of extracranial disease. The median overall survival was 6.5 months (95% CI, 5.5-7.9). One- and two-year survival rates were 24% and 10%. In multivariate analyses, age greater than 60 years was the only statistically significant variable that affected survival (hazard rate 1.29, p=0.049). We conclude that tomotherapeutic IMRS is safe and effective to treat patients with brain metastases.

  20. Homogeneous MGMT immunoreactivity correlates with an unmethylated MGMT promoter status in brain metastases of various solid tumors.

    Directory of Open Access Journals (Sweden)

    Barbara Ingold

    Full Text Available The O(6-methylguanine-methyltransferase (MGMT promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical reports on treating brain metastases with temozolomide describe varying effects. This may be due to the fact that MGMT promoter methylation of brain metastases has not yet been explored in depth. Therefore, we assessed MGMT promoter methylation of various brain metastases including those derived from lung (n = 91, breast (n = 72 kidney (n = 49 and from malignant melanomas (n = 113 by methylation-specific polymerase chain reaction (MS-PCR and MGMT immunoreactivity. Fifty-nine of 199 brain metastases (29.6% revealed a methylated MGMT promoter. The methylation rate was the highest in brain metastases derived from lung carcinomas (46.5% followed by those from breast carcinoma (28.8%, malignant melanoma (24.7% and from renal carcinoma (20%. A significant correlation of homogeneous MGMT-immunoreactivity (>95% MGMT positive tumor cells and an unmethylated MGMT promoter was found. Promoter methylation was detected in 26 of 61 (43% tumors lacking MGMT immunoreactivity, in 17 of 63 (27% metastases with heterogeneous MGMT expression, but only in 5 of 54 brain metastases (9% showing a homogeneous MGMT immunoreactivity. Our results demonstrate that a significant number of brain metastases reveal a methylated MGMT-promoter. Based on an obvious correlation between homogeneous MGMT immunoreactivity and unmethylated MGMT promoter, we hypothesize that immunohistochemistry for MGMT may be a helpful diagnostic tool to identify those tumors that probably will not benefit from the use of alkylating agents. The discrepancy between promoter methylation and a lack of MGMT immunoreactivity argues for assessing MGMT promoter methylation both by immunohistochemical as well as by molecular approaches for diagnostic purposes.

  1. Multiple brain metastases irradiation with Eleka Axesse stereotactic system

    Science.gov (United States)

    Filatov, P. V.; Polovnikov, E. S.; Orlov, K. Yu.; Krutko, A. V.; Kirilova, I. A.; Moskalev, A. V.; Filatova, E. V.; Zheravin, A. A.

    2017-09-01

    Brain metastases are one of the factors complicating the treatment of a malignant tumor. Radiation therapy, especially radiosurgery, plays an important role in the modern treatment practice. During 2011-2016, 32 patients (from 29 to 67 years old) with multiple brain metastases underwent the treatment with SRS or SRT in our center. The number of secondary lesions varied from 2 to 11. Eight patients underwent microsurgery resection. Seven patients had recurrence after whole brain radiotherapy. Thirty patient underwent single fraction SRS and two patients with large metastases (bigger than 3 cm) underwent fractionated SRT. The treatment was done with dedicated linear accelerator stereotactic system Elekta Axesse (Elekta AB, Stockholm, Sweden). Different stereotactic fixation devices were used, namely, Leksell G frame, non-invasive HeadFIX frame, and reinforced thermoplastic mask (IMRT perforation). All treatments included a volumetric modulated arc therapy (VMAT) technique and of Inage Guided Radiation Therapy (IGRT) technique. All lesions were treated from a single isocenter, which allowed reducing the treatment time and overall dose to the patient's body. All patients suffered the treatment satisfactorily. No adverse reactions or complications were met in any case during or right after the treatment. Different stereotactic fixation devices and modern treatment techniques allowed creating an optimal, safe and comfortable way for patient treatment. The treatment time was from 15 to 50 minutes. Patient position verification after or during the treatment demonstrated good accuracy for all fixation types and low level of intrafraction motion.

  2. The role of stereotactic radiation therapy and whole-brain radiotherapy in the treatment of multiple brain metastases

    International Nuclear Information System (INIS)

    Chen Xiujun; Xiao Jianping; Li Xiangpan; Jiang Xuesong; Zhang Ye; Xu Yingjie; Dai Jianrong; Li Yexiong

    2012-01-01

    Objective: To summarize the results of stereotactic radiation therapy (SRT) with or without whole-brain radiotherapy (WBRT) in the treatment of multiple brain metastasis. Methods: From May 1995 to April 2010, totally 98 newly diagnosed multiple (2 - 13 lesions) brain metastases patients were treated in our centre. Forty-four patients were treated with SRT alone and 54 with SRT + WBRT. Dose fractionation schemes were 15 -26 Gy in 1 fraction or 24.0 -52.5 Gy in 2 - 15 fractions with 3.5 - 12.0 Gy per fraction, depending on the tumor volume, location, and history of prior irradiation. Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis. The median age of the whole group was 55 years. The survival time was calculated from the date of radiation treatment to the day of death by any cause. Results: The median follow-up time for the whole group was 12 months, and the follow-up rate was 100%. The median overall survival time was 13.5 months for the whole group, there was no difference between SRT alone group and SRT + WBRT group (13.0 months vs. 13.5 months, χ 2 =0.31, P =0.578). The Karnofsky Performance Score (KPS) at the time of treatment (χ 2 =6.25, P =0.012), the interval between the diagnosis of the primary tumor and brain metastases (χ 2 =7.34, P =0.025) and the status of extracranial metastases (χ 2 =4.20, P =0.040) were independent prognosis factors for survival in multivariate analyses. Conclusions: Stereotactic radiation therapy is an effective and alternative treatment choice for multiple brain metastases. (authors)

  3. Assessment of brain metastases by means of dynamic susceptibility contrast enhanced MRI

    International Nuclear Information System (INIS)

    Knopp, M.; Wenz, F.; Debus, J.; Hentrich, H.R.

    2002-01-01

    Full text: To assess if pre therapeutic measurements of regional cerebral blood flow (rCBF) and volume (rCVB) are able to predict the response of brain metastases to radiation therapy and to assess the influence of radiosurgery on rCBF and rCBV on brain metastases and normal surrounding tissue. We examined 25 patients with brain metastases prior to high dose radiosurgery with conventional T1 and T2 weighted MRI and dynamic susceptibility contrast enhanced MRI (DSC MRI). For DSC MRI 55 T2*w GE images of two sections were acquired after bolus administration of 0.1 mmol/kg gadoteridol (ProHance) for the simultaneous measurement of brain feeding arteries and brain tissue. This allowed an absolute quantification of rCBF and rCBV. Follow-up examinations were performed 6 weeks and 3 months after radiotherapy and the acquired perfusion data were related to a 3 point scale of treatment outcome. Radiosurgery was performed by a linear accelerator with a 80% isodose of 18-20 Gv. For treatment planning the heads of the patients were immobilized by a cask mask to avoid head movement. DSC MRI was able to assess perfusion data in all patients. Higher pre therapeutic rCBV seems to predict a poor treatment outcome. After radiosurgery patients with tumor remission and stable disease presented a decrease of rCBV over time regardless of temporary tumor volume increase. Patients with tumor progression at the 3 month followup presented an increase of rCBV. Effects on normal surrounding tissue could not be observed. DSC MRI using Gadoteridol allows the non-invasive assessment of rCBV and rCBF of brain metastases and its changes due to radiosurgery. The method may also be able to predict treatment outcome. Furthermore radiofrequency effects on surrounding unaffected tissue can be monitored. Copyright (2002) Blackwell Science Pty Ltd

  4. Clinical outcomes of brain metastases treated with gamma knife radiosurgery with 3.0 T versus 1.5 T MRI-based treatment planning: have we finally optimised detection of occult brain metastases?

    International Nuclear Information System (INIS)

    Loganathan, Amritraj G.; Alphonse, Natalie; Chan, Michael D.

    2012-01-01

    The goal of this study was to determine if clinically relevant endpoints were changed by improved MRI resolution during radiosurgical treatment planning. Between 2003 and 2008, 200 consecutive patients with brain metastases treated with Gamma Knife radiosurgery (GKRS) using either 1.5 T or 3.0 T MRI for radiosurgical treatment planning were retrospectively analysed. The number of previously undetected metastases at time of radiosurgery, distant brain failures, time delay to whole brain radiotherapy (WBRT), overall survival and likelihood of neurological death were determined. Additional metastases were detected in 31.3% and 24.5% of patients at time of radiosurgery with 3.0 T and 1.5 T MRI, respectively (P = 0.27). Patients with multiple metastases at diagnostic scan were more likely to have additional metastases detected by 3.0 T MRI (P < 0.1). Median time to distant brain failure was 4.87 months and 5.43 months for the 3.0 T and 1.5 T cohorts, respectively (P = 0.44). Median time to WBRT was 5.8 months and 5.3 months for the 3.0 T and 1.5 T cohorts, respectively (P = 0.87). Median survival was 6.4 months for the 3.0 T cohort, and 6.1 months for the 1.5 T cohort (P = 0.71). Likelihood of neurological death was 25.3% and 16.7% for the 3.0 and 1.5 T populations, respectively (P = 0.26). The 3.0 T MRI-based treatment planning for GKRS did not appear to affect the likelihood of distant brain failure, the need for WBRT or the likelihood of neurological death in this series.

  5. Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases

    International Nuclear Information System (INIS)

    Ohguri, Takayuki; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori

    2007-01-01

    Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit

  6. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

    International Nuclear Information System (INIS)

    Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

    2010-01-01

    Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

  8. Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

    Full Text Available INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.

  9. Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery

    2016-12-15

    Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

  10. Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study

    Energy Technology Data Exchange (ETDEWEB)

    Wiggenraad, R.; Verbeek-de Kanter, A.; Mast, M. [Radiotherapy Centre West, The Hague (Netherlands); Molenaar, R. [Diaconessenhuis, Leiden (Netherlands). Dept. of Neurology; Lycklama a Nijeholt, G. [Medical Centre Haagladen, The Hague (Netherlands). Dept. of Radiology; Vecht, C. [Medical Centre Haagladen, The Hague (Netherlands). Dept. of Neurology; Struikmans, H. [Radiotherapy Centre West, The Hague (Netherlands); Leiden Univ. Medical Centre (Netherlands). Dept. of Radiotherapy; Kal, H.B.

    2012-08-15

    Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. Materials and methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm{sup 3} or metastases in the brainstem. Results: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. Conclusion: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. (orig.)

  11. Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study

    International Nuclear Information System (INIS)

    Wiggenraad, R.; Verbeek-de Kanter, A.; Mast, M.; Molenaar, R.; Lycklama a Nijeholt, G.; Vecht, C.; Struikmans, H.; Leiden Univ. Medical Centre; Kal, H.B.

    2012-01-01

    Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. Materials and methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm 3 or metastases in the brainstem. Results: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. Conclusion: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. (orig.)

  12. Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases

    International Nuclear Information System (INIS)

    Steinmann, Diana; Gerstein, Johanna; Gharbi, Nadine; Hagg, Juliane; Hipp, Matthias; Kleff, Irmgard; Müller, Axel; Schäfer, Christof; Schleicher, Ursula; Sehlen, Susanne; Theodorou, Marilena; Paelecke-Habermann, Yvonne; Wypior, Hans-Joachim; Zehentmayr, Franz; Oorschot, Birgitt van; Vordermark, Dirk; Geinitz, Hans; Aschoff, Raimund; Bayerl, Anja; Bölling, Tobias; Bosch, Elisabeth; Bruns, Frank; Eichenseder-Seiss, Ute

    2012-01-01

    Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information

  13. Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chee, R. J.; Bydder, S.; Cameron, F.

    2007-01-01

    Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

  14. Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

    Directory of Open Access Journals (Sweden)

    Wu S

    2016-12-01

    Full Text Available San-Gang Wu,1,* Jia-Yuan Sun,2,* Qin Tong,3 Feng-Yan Li,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China *These authors contributed equally to this work Objective: The objectives of this study were to describe the distribution of brain metastases (BM in breast cancer patients and investigate the risk factors for perihippocampal metastases (PHM. Patients and methods: Retrospective analysis of the clinicopathological characteristics and patterns of BM was performed. Associations between clinicopathological characteristics and PHM (the hippocampus plus 5 mm margin were evaluated using logistic regression analyses. Results: A total of 1,356 brain metastatic lesions were identified in 192 patients. Patients with 1–3 BM, 4–9 BM, and ≥10 BM accounted for 63.0%, 18.8%, and 18.2%, respectively. There were only 7 (3.6% patients with hippocampal metastases (HM and 14 (7.3% patients with PHM. On logistic regression, the number of BM was an independent risk factor for PHM. Patients with ≥10 BM had a significantly higher risk of PHM compared with those with <10 BM. Breast cancer subtype (BCS was not associated with PHM. The number of BM was significantly correlated with various BCSs. Patients with hormone receptor (HR+/human epidermal growth factor receptor 2 (HER2+, HR-/HER2+, and HR-/HER2- subtypes had a higher probability of ≥10 BM, relative to patients with an HR+/HER2- subtype. Conclusion: Our study suggests that a low incidence of PHM may be acceptable to perform hippocampal-sparing whole-brain radiation therapy for breast cancer patients

  15. Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

    Energy Technology Data Exchange (ETDEWEB)

    Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya; Von Eyben, Rie; Gibbs, Iris C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Choi, Clara Y.H. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Department of Radiation Oncology, Santa Clara Valley Medical Center, San Jose, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Adler, John R. [Department of Neurosurgery, Stanford University School of Medicine, Stanford, California (United States); Hancock, Steven L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-08-01

    Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  16. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg

    International Nuclear Information System (INIS)

    Hintz, Mandy

    2017-01-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  17. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

    2010-01-01

    Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

  18. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

  19. Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.

    Science.gov (United States)

    Piccirilli, Manolo; Sassun, Tanya Enny; Brogna, Christian; Giangaspero, Felice; Salvati, Maurizio

    2007-01-01

    Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor. Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30). Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years). Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.

  20. Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases. Plan comparison and early clinical evaluation

    International Nuclear Information System (INIS)

    Rieber, J.; Tonndorf-Martini, E.; Schramm, O.; Rhein, B.; Stefanowicz, S.; Lindel, K.; Debus, J.; Rieken, S.; Kappes, J.; Hoffmann, H.

    2016-01-01

    Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 x 20 Gy or 1 x 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 x 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. FFF mode resulted in significant reductions in beam-on time (p [de

  1. NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer

    International Nuclear Information System (INIS)

    Adkins, Chris E.; Nounou, Mohamed I.; Hye, Tanvirul; Mohammad, Afroz S.; Terrell-Hall, Tori; Mohan, Neel K.; Eldon, Michael A.; Hoch, Ute; Lockman, Paul R.

    2015-01-01

    Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (>20 ng/g for 168 h) versus conventional irinotecan (>1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m 2 NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results. The online version of this article (doi:10.1186/s12885-015-1672-4) contains supplementary material, which is available to authorized users

  2. Chemotherapy in the management of brain metastases: the emerging role of fotemustine for patients with melanoma and NSCLC.

    Science.gov (United States)

    Addeo, Raffaele; Zappavigna, Silvia; Luce, Amalia; Facchini, Sergio; Caraglia, Michele

    2013-09-01

    An estimated 20 - 40% of cancer patients will develop brain metastases that are the most common intracranial tumors in adults. Patients with cerebral metastases represent a variegate group where selection of the most appropriate treatment depends on many patient- and disease-related factors. The impact of therapeutic option on overall survival is lacking and it is important to consider quality of life (QOL) when treating patients with brain metastases. A considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. The role of chemotherapy was limited in the past. Recently, several chemotherapeutic agents have been identified as potentially useful. This article examines the pharmacokinetics, efficacy and safety and tolerability of fotemustine (FTM) for the management of patients with cerebral metastasis from melanoma and non-small cell lung cancer (NSCLC). FTM is a third-generation nitrosourea that has proved its efficacy on brain metastases of melanoma and showed promising results for the treatment of brain metastasis of NSCLC because of its ability to pass the blood-brain barrier.

  3. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...

  4. Emerging role of brain metastases in the prognosis of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Hambrecht A

    2011-08-01

    Full Text Available Amanda Hambrecht1,2, Rahul Jandial2, Josh Neman21Department of Biology, University of Southern California; 2Department of Neurosurgery, Beckman Research Institute, City of Hope National Cancer Center, CA, USAAbstract: Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. Keywords: metastasis, breast cancer, blood-brain barrier, epithelial-mesenchymal transition, mesenchymal-epithelial transition

  5. Proxy assessment of patients before and after radiotherapy for brain metastases. Results of a prospective study using the DEGRO brain module

    International Nuclear Information System (INIS)

    Steinmann, D.; Vordermark, D.; Geinitz, H.; Aschoff, R.; Bayerl, A.; Gerstein, J.; Hipp, M.; Schaefer, C.; Oorschot, B. van; Wypior, H.J.

    2013-01-01

    Purpose: Proxies of patients with poor performance status could give useful information about the patients' quality of life (QoL). We applied a newly developed questionnaire in a prospective QoL study of patients undergoing radiotherapy for brain metastases in order to make the first move to validate this instrument, and we compared the results with scores obtained using validated patient-completed instruments. Materials and methods: From January 2007 to June 2010, 166 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module BN20 were used to assess QoL in patients at the start of treatment and 3 months later. At the same time points, 141 of their proxies estimated the QoL with the new DEGRO brain module (DBM), a ten-item questionnaire rating the general condition as well as functions and impairment by symptoms in areas relevant to patients with brain metastases. Results: At 3 months, 85 of 141 patients (60%) with initial response by a proxy were alive. Sixty-seven of these patients (79% of 3-month survivors) and 65 proxies completed the second set of questionnaires. After 3 months, QoL significantly deteriorated in all items of proxy-assessed QoL except headache. Correlations between self-assessed and proxy-assessed QoL were high in single items such as nausea, headache, and fatigue. Conclusions: The high correlation between self-assessment and proxy ratings as well as a similar change over time for both approaches suggest that in patients with brain metastases, proxy assessment using the DBM questionnaire can be an alternative approach to obtaining QoL data when patients are unable to complete questionnaires themselves. Our self-constructed and first applied DBM is the only highly specific instrument for patients with brain metastases, but further tests are needed for its final validation. (orig.)

  6. Metastatic disease of the brain: extra-axial metastases (skull, dura, leptomeningeal) and tumour spread

    Energy Technology Data Exchange (ETDEWEB)

    Maroldi, Roberto; Ambrosi, Claudia; Farina, Davide [University of Brescia, Department of Radiology, Brescia, BS (Italy)

    2005-03-01

    Extra-axial intracranial metastases may arise through several situations. Hematogenous spread to the meninges is the most frequent cause. Direct extension from contiguous extra-cranial neoplasms, secondary invasion of the meninges by calvarium and skull base metastases, and migration along perineural or perivascular structures are less common. Leptomeningeal invasion gives rise to tumour cell dissemination by the cerebrospinal fluid (CSF), eventually leading to neoplastic coating of brain surfaces. Contrast-enhanced magnetic resonance (MR) imaging is complementary to CSF examinations and can be invaluable, detecting up to 50% of false-negative lumbar punctures. MR findings range from diffuse linear leptomeningeal enhancement to multiple enhancing extra-axial nodules, obstructive communicating and non-communicating hydrocephalus. Both calvarial and epidural metastases infrequently transgress the dura, which acts as a barrier against tumour spread. Radionuclide bone studies are still a valuable screening test to detect bone metastases. With computed tomography (CT) and MR, bone metastases extending intracranially and primary dural metastases show the characteristic biconvex shape, usually associated with brain displacement away from the inner table. Although CT is better in detecting skull base erosion, MR is more sensitive and provides more detailed information about dural involvement. Perineural and perivascular spread from head and neck neoplasms require thin-section contrast-enhanced MR. (orig.)

  7. Outcome After Radiosurgery for Brain Metastases in Patients With Low Karnofsky Performance Scale (KPS) Scores

    International Nuclear Information System (INIS)

    Chernov, Mikhail F.; Nakaya, Kotaro; Izawa, Masahiro; Hayashi, Motohiro; Usuba, Yuki; Kato, Koichi; Muragaki, Yoshihiro; Iseki, Hiroshi; Hori, Tomokatsu; Takakura, Kintomo

    2007-01-01

    Purpose: The objective of this retrospective study was evaluation of the outcome after stereotactic radiosurgery (SRS) in patients with intracranial metastases and poor performance status. Methods and Materials: Forty consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores ≤50 (mean, 43 ± 8; median, 40) treated with SRS were analyzed. Poor performance status was caused by presence of intracranial metastases in 28 cases (70%) and resulted from uncontrolled extracerebral disease in 12 (30%). Results: Survival after SRS varied from 3 days to 11.5 months (mean, 3.8 ± 2.9 months; median, 3.3 months). Survival probability constituted 0.50 ± 0.07 at 3 months and 0.20 ± 0.05 at 6 months posttreatment. Cause of low KPS score (p = 0.0173) and presence of distant metastases beside the brain (p = 0.0308) showed statistically significant associations with overall survival in multivariate Cox proportional hazards regression analysis. Median survival was 6.0 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were absent, 3.3 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were present, and 1.0 month if poor performance status resulted from extracerebral disease. Conclusions: Identification of the cause of low KPS score (cerebral vs. extracerebral) in patients with metastatic brain tumor(s) may be important for prediction of the outcome after radiosurgical treatment. If poor patient performance status without surgical indications is caused by intracranial tumor(s), SRS may be a reasonable treatment option

  8. Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

    Science.gov (United States)

    Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

    2017-01-01

    Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

  9. Development of a Modelling to Correlate Site and Diameter of Brain Metastases with Hippocampal Sparing Using Volumetric Modulated Arc Therapy

    Directory of Open Access Journals (Sweden)

    Silvia Chiesa

    2013-01-01

    Full Text Available Purpose. To correlate site and diameter of brain metastases with hippocampal sparing in patients treated by RapidArc (RA technique on whole brain with simultaneously integrated boost (SIB. Methods and Materials. An RA plan was calculated for brain metastases of 1-2-3 cm of diameter. The whole brain dose was 32.25 Gy (15 fractions, and SIB doses to brain metastases were 63 Gy (2 and 3 cm or 70.8 Gy (1 cm. Plans were optimized and evaluated for conformity, target coverage, prescription isodose to target volume, homogeneity index, and hippocampal sparing. Results. Fifteen brain lesions and RA plan were generated. Hippocampal volume was 4.09 cm3, and hippocampal avoidance volume was 17.50 cm3. Related to site of metastases, the mean hippocampal dose was 9.68 Gy2 for occipital lobe, 10.56 Gy2 for frontal lobe, 10.56 Gy2 for parietal lobe, 10.94 Gy2 for deep brain structures, and 40.44 Gy2 for temporal lobe. The mean hippocampal dose was 9.45 Gy2, 10.15 Gy2, and 11.70 Gy2 for diameter’s metastases of 1.2 and 3 cm, respectively, excluding results relative to temporal brain lesions. Conclusions. Location more than size of metastases can adversely influence the hippocampus sparing. Further investigation is necessary to meet definitive considerations.

  10. Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience.

    Science.gov (United States)

    Kelly, Paul J; Lin, Yijie Brittany; Yu, Alvin Y C; Ropper, Alexander E; Nguyen, Paul L; Marcus, Karen J; Hacker, Fred L; Weiss, Stephanie E

    2011-09-01

    To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.

  11. Cerebral control and survival after stereotactic radiotherapy of brain metastases

    International Nuclear Information System (INIS)

    Arnold, Elmar Till

    2014-01-01

    This retrospective study, including 275 patients who underwent stereotactic radiotherapy due to brain metastases between 2003 and 2008, investigates influencing factors regarding cerebral control and survival, symptomatic effects and a potential benefit for patients older than 70 years. We were able to identify risk factors for remote brain failure which leads to a therapeutic recommendation. Furthermore we confirm a positive symptomatic effect and a benefit of stereotactic readiotherapy for patients over 70 years.

  12. Stereotactic radiosurgery for the treatment of brain metastases; results from a single institution experience.

    LENUS (Irish Health Repository)

    Burke, D

    2013-09-01

    Stereotactic radiosurgery is frequently used for the treatment of brain metastases. This study provides a retrospective evaluation of patients with secondary lesions of the brain treated with stereotactic radiosurgery (SRS) at our institution.

  13. Plan Quality and Treatment Efficiency for Radiosurgery to Multiple Brain Metastases: Non-Coplanar RapidArc vs Gamma Knife

    Directory of Open Access Journals (Sweden)

    Haisong eLiu

    2016-02-01

    Full Text Available Objectives: This study compares the dosimetry and efficiency of two modern radiosurgery (SRS modalities for multiple brain metastases (Gamma Knife and LINAC-based RapidArc/volumetric modulated arc therapy, with a special focus on the comparison of low dose spread.Methods: Six patients with three or four small brain metastases were used in this study. The size of targets varied from 0.1 ~ 10.5 cc. SRS doses were prescribed according to size of lesions. SRS plans were made using both Gamma Knife® Perfexion and a single-isocenter, multiple non-coplanar RapidArc®. Dosimetric parameters analyzed included RTOG conformity index (CI, gradient index (GI, 12 Gy isodose volume (V12Gy for each target, and the dose spread (Dspread for each plan. Dspread reflects SRS plan’s capability of confining radiation to within the local vicinity of the lesion and to not spread out to the surrounding normal brain tissues. Each plan has a dose (Dspread, such that once dose decreases below Dspread (on total tissue DVH, isodose volume starts increasing dramatically. Dspread is defined as that dose when volume increase first exceeds 20 cc per 0.1 Gy dose decrease. Results: RapidArc SRS has smaller CI (1.19 ±0.14 vs. 1.50 ± 0.16, p<0.001 and larger GI (4.77 ± 1.49 vs. 3.65 ± 0.98, p <0.01. V12Gy results were comparable (2.73 ± 1.38 cc vs. 3.06 ± 2.20 cc, p = 0.58. Moderate to lower dose spread, V6, V4.5, and V3, were also equivalent. Gamma Knife plans achieved better very low dose spread (≤3 Gy and also had slightly smaller Dspread, 1.9 Gy vs 2.5 Gy. Total treatment time for Gamma Knife is estimated between 60~100 min. Gamma Knife treatments are between 3~5 times longer compared to RapidArc treatment techniques.Conclusion: Dosimetric parameters reflecting prescription dose conformality (CI, dose fall off (GI, radiation necrosis indicator (V12Gy, and dose spread (Dspread were compared between Gamma Knife SRS and RapidArc SRS for multi-mets. RapidArc plans have

  14. Stereotactic Radiosurgical Treatment of Brain Metastases to the Choroid Plexus

    International Nuclear Information System (INIS)

    Siomin, Vitaly; Lin, Jennifer L.; Marko, Nicholas F.; Barnett, Gene H.; Toms, Steven A.; Chao, Samuel T.; Angelov, Lilyana; Vogelbaum, Michael A.; Navaratne, Kapila; Suh, John H.; Weil, Robert J.

    2011-01-01

    Purpose: Choroid plexus metastases (CPM) are uncommon lesions. Consequently, optimal management of CPM is uncertain. We summarize our experience with stereotactic radiosurgery (SRS) of CPM. Methods and Materials: Sixteen consecutive patients with presumed CPM treated with SRS between 1997 and 2007 were examined. Twelve were men with a median age at diagnosis of CPM of 61.9 ± 9.9 years; 14 had metastases from renal cell carcinoma (RCC). All patients had controlled primary disease at the time of treatment for CPM. Four patients with RCC and 1 with non-small-cell lung cancer had undergone whole-brain radiotherapy (WBRT) previously and 2 had received SRS to other brain metastases. The disease-free interval from the primary diagnosis to CPM diagnosis averaged 39.3 ± 46.2 months (range, 1.0-156.3). Five patients were asymptomatic; of the remaining 11, none had symptoms related to CPM. All presented with a single CPM. Results: Average maximum diameter of the CPMs was 2.0 ± 1.0 cm (range, 0.9-4.1 cm); mean volume was 2.4 ± 2.6 cm 3 (range, 0.2-9.3). Median SRS dose was 24 Gy to the 53% isodose line (range, 14-24 Gy). Survival after SRS to the CPM was 25.3 ± 23.4 months (range, 3.2-101.6). Patients in Recursive Partitioning Analysis (RPA) class I (n = 10) had improved survival compared to those in class II (n = 6), as did those with better GPA scores. There were no local failures. After SRS, 1 patient underwent WBRT, 3 patients had one, and another had two subsequent SRS treatments to other brain lesions. Of the 14 patients who have died, 11 succumbed to systemic disease progression, 2 to progressive, multifocal central nervous system disease, and 1 to systemic disease with concurrent, stable central nervous system disease. There were no complications related to SRS. Conclusions: Most CPMs are associated with RCC. SRS represents a safe and viable treatment option as primary modality for these metastases, with excellent outcomes.

  15. Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Ansa Maer [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Scherwath, Angela [Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg (Germany); Ernst, Gundula [Department of Medical Psychology, Medical School Hannover, Hannover (Germany); Lanfermann, Heinrich [Institute for Neuroradiology, Medical School Hannover, Hannover (Germany); Bremer, Michael [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Steinmann, Diana, E-mail: steinmann.diana@mh-hannover.de [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany)

    2013-11-15

    Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

  16. Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

    International Nuclear Information System (INIS)

    Cole, Ansa Maer; Scherwath, Angela; Ernst, Gundula; Lanfermann, Heinrich; Bremer, Michael; Steinmann, Diana

    2013-01-01

    Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

  17. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  18. Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram.

    Science.gov (United States)

    Ayala-Peacock, Diandra N; Attia, Albert; Braunstein, Steve E; Ahluwalia, Manmeet S; Hepel, Jaroslaw; Chung, Caroline; Contessa, Joseph; McTyre, Emory; Peiffer, Ann M; Lucas, John T; Isom, Scott; Pajewski, Nicholas M; Kotecha, Rupesh; Stavas, Mark J; Page, Brandi R; Kleinberg, Lawrence; Shen, Colette; Taylor, Robert B; Onyeuku, Nasarachi E; Hyde, Andrew T; Gorovets, Daniel; Chao, Samuel T; Corso, Christopher; Ruiz, Jimmy; Watabe, Kounosuke; Tatter, Stephen B; Zadeh, Gelareh; Chiang, Veronica L S; Fiveash, John B; Chan, Michael D

    2017-11-01

    Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

  19. Computed tomography in brain metastases of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuratsu, Jun-ichi; Matsukado, Yasuhiko; Sueyoshi, Nobuyuki [Kumamoto Univ. (Japan). School of Medicine; Nonaka, Nobuhito; Sano, Yoshinori; Itoyama, Yoichi; Miura, Giichi

    1984-10-01

    Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery.

  20. A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases

    Directory of Open Access Journals (Sweden)

    Hanson Peter W

    2012-08-01

    Full Text Available Abstract Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.

  1. RTOG: Updated results of randomized trials

    International Nuclear Information System (INIS)

    Curran, Walter J.

    1997-01-01

    Objective: To review the background, rationale and available results for recently completed randomized comparative clinical trials of the Radiation Therapy Oncology Group (RTOG), including inter group trials in which the RTOG has been the managing group or a major participant. When available, laboratory studies will be correlated with clinical results

  2. External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

    Science.gov (United States)

    Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

    2017-07-01

    A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  4. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    Science.gov (United States)

    Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

    2014-01-01

    Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed. PMID:24897023

  5. Retrospective study on therapy options of brain metastases: surgery versus stereotactic radiotherapy with the linear accelerator

    International Nuclear Information System (INIS)

    Fortunati, M.K.S.

    2001-04-01

    Background: in the therapy of brain metastases there has been a great progress in the last years. It was shown, that more aggressive therapies can not only extend the survival of the patients, but also improve quality of life. The major question of this study was, whether surgery or stereotactic radiotherapy with the linear accelerator show better results in behalf of the survival. Beside this major question many parameters regarding the patient or his primary cancer were examined. Methods: from the 1st of January 1995 until the 30th of June 2000 233 patients with one or more brain metastases have been treated in the Wagner Jauregg Landesnervenkrankenhaus Oberoesterreich (WJ LNKH OeO). The LINAC has been established on the 1st of July 1997. The patients have been distributed in three groups: 1. LINAC-group: 81 patients have been treated from the 1st of July 1997 until the 30th of June 2000 with the LINAC. 2. Surgery-group: 81 patients have been operated from the 1st of July 1997 until the 30th June 2000. 3 Control-group: 71 patients have been operated from the 1st of January 1995 until the 30th of June 1997, before the LINAC has been established on the 1st of July 1997. Results: There are shown the mean survival times. Therapy options (0,05): LINAC-group: 377 days. Surgery-group: 195 days. Control-group: 285 days. Primary cancer (0,05): unknown primary: 203 days. Cancer of the colon tract: 218 days. Breast cancer: 314 days. Melanoma: 162 days. Kidney: 466 days. Lung 261 days. Others: 439 days. Metastases in one/in both hemispheres (0,05): in one hemisphere 310 days, in both 184 days. All the other parameters (age, sex, Karnofsky-Index, period between diagnose of the primary and the brain metastases, primary cancer therapy, extra cerebral metastases, number of metastases, localization of metastases supra- or infratentoriell, dose/effect relationship in the LINAC-group, whole brain radiotherapy) showed interesting differences, but the results were not statistically

  6. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  7. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    Directory of Open Access Journals (Sweden)

    Barbara Palumbo

    2014-06-01

    Full Text Available Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI is discussed.

  8. Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Kocher, Martin; Wittig, Andrea; Piroth, Marc Dieter; Treuer, Harald; Ruge, Maximilian; Seegenschmiedt, Heinrich; Grosu, Anca-Ligia; Guckenberger, Matthias

    2014-01-01

    This report from the Working Group on Stereotaktische Radiotherapie of the German Society of Radiation Oncology (Deutsche Gesellschaft fuer Radioonkologie, DEGRO) provides recommendations for the use of stereotactic radiosurgery (SRS) on patients with brain metastases. It considers existing international guidelines and details them where appropriate. The main recommendations are: Patients with solid tumors except germ cell tumors and small-cell lung cancer with a life expectancy of more than 3 months suffering from a single brain metastasis of less than 3 cm in diameter should be considered for SRS. Especially when metastases are not amenable to surgery, are located in the brain stem, and have no mass effect, SRS should be offered to the patient. For multiple (two to four) metastases - all less than 2.5 cm in diameter - in patients with a life expectancy of more than 3 months, SRS should be used rather than whole-brain radiotherapy (WBRT). Adjuvant WBRT after SRS for both single and multiple (two to four) metastases increases local control and reduces the frequency of distant brain metastases, but does not prolong survival when compared with SRS and salvage treatment. As WBRT carries the risk of inducing neurocognitive damage, it seems reasonable to withhold WBRT for as long as possible. A single (marginal) dose of 20 Gy is a reasonable choice that balances the effect on the treated lesion (local control, partial remission) against the risk of late side effects (radionecrosis). Higher doses (22-25 Gy) may be used for smaller ( [de

  9. Surgical treatment of brain metastases - a review. Part 2. Results of treatment

    International Nuclear Information System (INIS)

    Wronski, M.; Czernicki, Z.

    1994-01-01

    Results of treatment of most frequent brain metastases from nonsmall cell lung cancer, breast cancer, malignant melanoma and kidney tumors are discussed. Also efficacy of surgical treatment, chemotherapy, radiotherapy and radiosurgery is analyzed

  10. Stereotactic Radiosurgery in the Management of Brain Metastases: An Institutional Retrospective Analysis of Survival

    International Nuclear Information System (INIS)

    Frazier, James L.; Batra, Sachin; Kapor, Sumit; Vellimana, Ananth; Gandhi, Rahul; Carson, Kathryn A.; Shokek, Ori; Lim, Michael; Kleinberg, Lawrence; Rigamonti, Daniele

    2010-01-01

    Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy. Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment. Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy. Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

  11. CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

    Science.gov (United States)

    Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

    2015-04-01

    Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

  12. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT + SRS) for one to three brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk [University Hospital Schleswig-Holstein, Luebeck (Germany). Department of Radiation Oncology]|[University Medical Center, Hamburg (Germany). Department of Radiation Oncology; Kueter, Jan-Dirk; Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany). Department of Radiation Oncology; Hornung, Dagmar [University Medical Center, Hamburg (Germany). Department of Radiation Oncology; Veninga, Theo; Hanssens, Patrick [Dr. Bernard Verbeeten Institute, Tilburg (Netherlands). Department of Radiation Oncology; Schild, Steven E. [Mayo Clinic Scottsdale, AZ (United States). Department of Radiation Oncology

    2008-12-15

    The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT + SRS). Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n = 93) or WBRT + SRS (n = 51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients. 1-year-OS was 53% after SRS and 56% after WBRT + SRS (p = 0.24). 1-year-IC rates were 51% and 66% (p = 0.015), respectively. 1-year-LC rates were 66% and 87% (p = 0.003), respectively. On multivariate analyses, OS was associated with age (p = 0.004), ECOG-PS (p = 0.005), extracerebral metastases (p < 0.001), RPA class (p < 0.001), and interval from tumor diagnosis to irradiation (p < 0.001). IC was associated with interval from tumor diagnosis to irradiation (p = 0.004) and almost with treatment (p = 0.09), and LC with treatment (p = 0.026) and almost with interval (p = 0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients. WBRT + SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients. (orig.)

  13. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT + SRS) for one to three brain metastases

    International Nuclear Information System (INIS)

    Rades, Dirk; University Medical Center, Hamburg; Kueter, Jan-Dirk; Dunst, Juergen; Hornung, Dagmar; Veninga, Theo; Hanssens, Patrick; Schild, Steven E.

    2008-01-01

    The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT + SRS). Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n = 93) or WBRT + SRS (n = 51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients. 1-year-OS was 53% after SRS and 56% after WBRT + SRS (p = 0.24). 1-year-IC rates were 51% and 66% (p = 0.015), respectively. 1-year-LC rates were 66% and 87% (p = 0.003), respectively. On multivariate analyses, OS was associated with age (p = 0.004), ECOG-PS (p = 0.005), extracerebral metastases (p < 0.001), RPA class (p < 0.001), and interval from tumor diagnosis to irradiation (p < 0.001). IC was associated with interval from tumor diagnosis to irradiation (p = 0.004) and almost with treatment (p = 0.09), and LC with treatment (p = 0.026) and almost with interval (p = 0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients. WBRT + SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients. (orig.)

  14. Use of 3.0-T MRI for Stereotactic Radiosurgery Planning for Treatment of Brain Metastases: A Single-Institution Retrospective Review

    International Nuclear Information System (INIS)

    Saconn, Paul A.; Shaw, Edward G.; Chan, Michael D.; Squire, Sarah E.; Johnson, Annette J.; McMullen, Kevin P.; Tatter, Stephen B.; Ellis, Thomas L.; Lovato, James; Bourland, J. Daniel; Ekstrand, Kenneth E.; DeGuzman, Allan F.; Munley, Michael T.

    2010-01-01

    Purpose: To investigate the efficacy of 3.0-T magnetic resonance imaging (MRI) for detecting brain metastases for stereotactic radiosurgery (SRS) planning. Methods and Materials: All adult patients scheduled for SRS treatment for brain metastases at our institution between October 2005 and January 2008 were eligible for analysis. All patients underwent radiosurgery treatment planning 3.0-T MRI on the day of scheduled radiosurgery and a diagnostic 1.5-T MRI in the days or weeks prior to radiosurgery for comparison. Both scans were interpreted by neuroradiologists who reported their findings in the radiology reports. We performed a retrospective review of the radiology reports to determine the number of brain metastases identified using each MRI system. Results: Of 254 patients scheduled for treatment from October 2005 to January 2008, 138 patients had radiology reports that explicitly described the number of metastases identified on both scans. With a median interval of 17 days (range, 1-82) between scans, the number of metastases detected using 1.5-T MRI system ranged from 1 to 5 and from 1 to 8 using the 3.0 T-MRI system. Twenty-two percent of patients were found to have a greater number of metastases with the 3.0 T-MRI system. The difference in number of metastases detected between the two scans for the entire cohort ranged from 0 to 6. Neither histology (p = 0.52 by chi-sq test) nor time between scans (p = 0.62 by linear regression) were significantly associated with the difference in number of metastases between scans. Conclusions: The 3.0-T MRI system appears to be superior to a 1.5-T MRI system for detecting brain metastases, which may have significant implications in determining the appropriate treatment modality. Our findings suggest the need for a prospectively designed study to further evaluate the use of a 3.0 T-MRI system for stereotactic radiosurgery planning in the treatment of brain metastases.

  15. Survival in patients with brain metastases treated with radiotherapy holoencefalica at the National Institute of Cancerology

    International Nuclear Information System (INIS)

    Ospino, Rosalba; Cendales, Ricardo; Tria, Jaime

    2009-01-01

    Objective: To describe the overall survival among patients with brain metastases treated with whole brain radiation therapy at the Instituto Nacional de Cancerologia (INC) during 2004-2006. Methods: A survival study was conducted. All patients with brain metastases treated with whole brain radiotherapy were included. Frequencies, central tendency, and dispersion measures were used to describe discrete and continuous variables. Survival analysis was performed by the Kaplan-Meyer method. Results: 109 patients were included and the vital status was updated in 85 patients (80%). The median follow-up time was 2.76 months. 78 deaths were observed; the median survival time was 5.2 months and the cumulated one-year overall survival 25.5%. Karnofsky index, extra-cranial metastases, type of lesion, and recursive partitioning analysis (RPA) were significant prognostic factors. The overall median survival for recursive partitioning analysis class I was 7.2 months; class II 6.9 months; class III 1.8 months. Conclusion: Overall survival INC are similar than previous international series for RPA class I and III, while it was better in RPA class II.

  16. Efficacy of EGFR-TKI therapy in patients with brain metastases from ...

    African Journals Online (AJOL)

    Purpose: This meta-analysis aimed to systematically evaluate the efficacy of tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from nonsmall- cell lung cancer (NSCLC), and to compare this treatment modality to chemotherapy or radiotherapy. Methods: ...

  17. Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

    Directory of Open Access Journals (Sweden)

    Yamamoto D

    2012-09-01

    Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

  18. Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

    Directory of Open Access Journals (Sweden)

    He YY

    2016-04-01

    Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

  19. Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.

    Science.gov (United States)

    Xu, Jian-Ping; Liu, Xiao-Yan; Yang, Sheng; Zhang, Chang-Gong; Wang, Lin; Shi, Yuan-Kai

    2016-07-01

    To evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. Twenty-one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute-Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg. The median overall and progression-free survival rates were 15.2 (1.2-31.5 months, 95% confidence interval [CI] 6.6-23.7 months) and 8.9 months (0.6-30.5 months, 95% CI 3.4-14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%). Icotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases.

  20. Selection of optimal treatment scheme for brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dong Mingxin; Zhao Tong; Huang Jingzi; Yu Shukun; Ma Yan; Tian Zhongcheng; Jin Xiangshun; Quan Jizhong; Liu Jin; Wang Dongxu

    2006-01-01

    Objective: To select the optimal treatment scheme for brain metastases of non-small cell lung cancers (NSCLCs). Methods: Seventy-two NSCLC cases diagnosesd by pathology with brain metastases were randomly classified into three groups, Group I, 24 cases with whole brain conventional external fractioned irradiation of D T 36-41 Gy/4-5 w, Group II, 22 eases with y-knife treatment plus whole brain conventional external fractioned irradiation, and Group III, 26 cases with γ-knife plus whole brain conventional external fractioned irradiation in combination with chemotherapy of Vm-26. The surrounding area of tumor was strictly covered with 50% para-central-dosal curve in γ-knife treatment (D T 16-25 Gy with a mean of 16 Gy). The muirleaf collimator was selected according to the volume of tumors. Chemotherapy of Vm-26 (60 mg/m 2 d1-3) was applied during the treatment with whole brain conventional external fractioned irradiation (D T 19-29 Gy/2-3 w), 21 days in a period, 2 periods in total. Results: The median survival time was estimated to be 6.0 months (ranged from 1.2 to 19.0 months) in the Group I, 9.2 months (4.4-30 months) in the Group II, and 10.8 months (5.2-42.2 months) in the Group III. The 1-year and 2-year survival rates were 34.6% and 12.6% , 62.2% and 30.2%, and 70.8% and 35.6% respectively in Group I, Group II, and Group III, respectively. Conclusion: For brain metastases of NSCLC, γ-knife plus whole brain conventional external fractioned irradiation combined with treatment of Vm-26 had a significantly beneficial influence on improvement of the local control and 1-year and 2-year survival. There was no complaint about the side-effects of the treatment. (authors)

  1. Efficacy of EGFR-TKI therapy in patients with brain metastases from ...

    African Journals Online (AJOL)

    Purpose: This meta-analysis aimed to systematically evaluate the efficacy of tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from non- small-cell lung cancer (NSCLC), and to compare this treatment modality to chemotherapy or radiotherapy. Methods: ...

  2. The value of diffusion tensor imaging in differentiating high-grade gliomas from brain metastases: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rui Jiang

    Full Text Available Differentiation of high-grade gliomas and solitary brain metastases is an important clinical issue because the treatment strategies differ greatly. Our study aimed to investigate the potential value of diffusion tensor imaging (DTI in differentiating high-grade gliomas from brain metastases using a meta-analytic approach.We searched Pubmed, Embase and the Cochrane Library for relevant articles published in English. Studies that both investigated high-grade gliomas and brain metastases using DTI were included. Random effect model was used to compare fractional anisotropy (FA and mean diffusivity (MD values in the two tumor entities.Nine studies were included into the meta-analysis. In the peritumoral region, compared with brain metastases, high-grade gliomas had a significant increase of FA (SMD  = 0.47; 95% CI, 0.22-0.71; P<0.01 and a significant decrease of MD (SMD  = -1.49; 95% CI, -1.91 to -1.06; P<0.01. However, in the intratumoral area, no significant change in FA (SMD  = 0.16; 95% CI, -0.49 to 0.82; P = 0.73 or MD (SMD  = 0.34; 95% CI, -0.91 to 1.60; P = 0.59 was detected between gliomas and metastases.High-grade gliomas may be distinguished from brain metastases by comparing the peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing solitary intracranial lesions.

  3. Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.

    Science.gov (United States)

    Li, Yingmei; Liu, Boxiang; Connolly, Ian David; Kakusa, Bina Wasunga; Pan, Wenying; Nagpal, Seema; Montgomery, Stephen B; Hayden Gephart, Melanie

    2018-03-29

    When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  4. Stereotactic radiosurgery for newly diagnosed brain metastases. Comparison of three dose levels

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Hornung, Dagmar [University Medical Center Hamburg-Eppendorf, Department of Radiation Oncology, Hamburg (Germany); Blanck, Oliver [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Martens, Kristina [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Center for Integrative Psychiatry, Luebeck (Germany); Khoa, Mai Trong [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, Ngo Thuy [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hueppe, Michael [University of Luebeck, Department of Anesthesiology, Luebeck (Germany); Terheyden, Patrick [University of Luebeck, Department of Dermatology, Luebeck (Germany); Gliemroth, Jan [University of Luebeck, Department of Neurosurgery, Luebeck (Germany); Schild, Steven E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale (United States)

    2014-09-15

    Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15 vs. ≥ 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and interval of cancer diagnosis to SRS (≤ 24 vs. > 24 months). For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79 %, respectively (p < 0.001). The SRS dose maintained significance on multivariate analysis (risk ratio: 2.25; 95 % confidence interval: 1.56-3.29; p < 0.001). On intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p < 0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose in the univariate analysis. SRS doses of 18 Gy and 20 Gy resulted in better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose. (orig.) [German] Drei Dosislevel bei der alleinigen stereotaktischen Radiochirurgie (SRS) von 1 bis 3 neu diagnostizierten Hirnmetastasen wurden hinsichtlich lokaler Kontrolle der bestrahlten Metastasen, Nichtauftreten neuer Hirnmetastasen und Gesamtueberleben verglichen. Nach der am Rand der Metastasen applizierten SRS-Dosis wurden 134 Patienten den Gruppen 13

  5. Value of stereotactic radiosurgery in patients with multiple brain metastases

    International Nuclear Information System (INIS)

    Chen Jie; Lin Zhiguo; Li Qingguo; Shen Hong

    2002-01-01

    Objective: To analyze the prognostic factors and evaluate the effect of stereotactic radiosurgery for patients with multiple brain metastases. Methods: Comparison was made in 53 such patients treated by stereotactic radiosurgery plus radiotherapy and 53 treated by radiotherapy alone. Patients were matched-paired according to the following criteria: age, Karnofsky performance scale (KPS) before treatment, extent of systemic cancer and number of brain metastasis. Forty patients had stereotactic radiosurgery, 13 patients stereotactic fractionated radiosurgery. In the stereotactic radiosurgery group, the patients were given a mean marginal dose of 20 Gy. Methods of stereotactic fractionated radiosurgery was 4-12 Gy per fraction , twice a week to a total dose of 15-30 Gy. Whole brain radiotherapy was given immediately after stereotactic radiosurgery. For patients treated by radiotherapy alone, the entire brain was treated by 30-40 Gy in 3-4 weeks. Results: The median survival was 11.6 months in stereotactic radiosurgery plus radiotherapy and 6.7 months in radiotherapy alone. The one year survival rate and one year local control rate were 44.3%, 17.1% and 50.9%, 13. 2%. Those with KPS increased after treatment gave 1-year survivals of 69.8% and 30.2%, respectively. The validity rates in CT or MRI three months after treatment were 82.0% and 55.0%. The difference in the two groups was found to be statistically significant (P < 0.01). 23.3% of death in the stereotactic radiosurgery plus radiotherapy group was due to brain metastasis vs 51.0% in the radiotherapy alone group (P < 0.05). Complication of the two groups was similar. Conclusion: Stereotactic radiosurgery plus radiotherapy is superior to radiotherapy alone for multiple brain metastases in improving the local control and ultimate outcome

  6. Imaging of rare radiation injuries after radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Yamanaka, Kazuhiro; Yoshimura, Masaki; Iwai, Yoshiyasu

    2011-01-01

    Gamma knife radiosurgery (GKS) is generally an effective and safe treatment for brain metastases. We report 3 rare complicated cases after GKS due to radiation injury including image findings. Case 1: A 58-year-old man received whole brain radiation therapy for right occipital brain metastasis from lung cancer. However, local recurrence was noted and GKS was carried out 5 months later (size 28 mm, marginal dose 23 Gy (50% isodose)). Four years later, a cyst appeared and the patient developed apraxia and visual disturbance. Surgery was performed and the histopathology showed necrosis. Case 2: A 51-year-old woman received GKS for 4 brain metastases from breast cancer. The right occipital lobe lesion was treated with marginal dose of 18 Gy (size 24 mm, 50% isodose). Thirty-one months later, she developed left homonymous hemianopsia and MR imaging and CT scan showed intracerebral hemorrhage with cyst formation. An operation was performed and the histology revealed necrosis. Case 3: A 37-year-old man received GKS for left temporal brain metastasis from lung cancer (size 14 mm, marginal dose 23 Gy (50% isodose)). Twelve months later, the lesion increased in size again, so we carried out a second GKS on the same lesion (size 15 mm, marginal dose 23 Gy (50% isodose)). Thirty-five months later, massive peritumoral edema appeared and the patient developed left oculomotor palsy. An emergency operation was performed and the histopathological diagnosis was cavernous malformation that was thought to be induced by radiosurgery. Although the incidence is low, rare complications associated with radiation therapy can also occur by radiosurgery. (author)

  7. Accelerated split course regimen in the treatment of brain metastases

    International Nuclear Information System (INIS)

    Franchin, G.; Minatel, E.; Roncadin, M.; Trovo, M.G.; De Paoli, A.; Bortolus, R.; Arcicasa, M.; Boz, G.; Gobitti, C.; Grigoletto, E.; Bassignano, G.

    1988-01-01

    63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1. Median age was 58 years. The most frequent site of primary tumor was lung (41 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. Complete remission was obtained in 4 patients and partial remission in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results obtained are similar to those reported by others; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required. 36 refs.; 2 figs.; 3 tabs

  8. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.; Morris, David E.; Hayman, James A.; Flickinger, John C.; Mills, Michael; Rogers, C. Leland; Souhami, Luis

    2005-01-01

    Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated

  9. Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it [Radiation Oncology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Esposito, Vincenzo [Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Clarke, Enrico; Scaringi, Claudia [Radiation Oncology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Lanzetta, Gaetano [Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Salvati, Maurizio [Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Neurosurgery Unit, Umberto I Hospital, University “Sapienza,” Rome (Italy); Raco, Antonino [Neurosurgery Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Bozzao, Alessandro [Neuroradiology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Maurizi Enrici, Riccardo [Radiation Oncology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy)

    2013-07-15

    Purpose: To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases. Methods and Materials: Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm{sup 3} (range, 12.6-35.7 cm{sup 3}). The primary endpoint was local control. Secondary endpoints were survival and distant failure rates, cause of death, performance measurements, and toxicity of treatment. Results: With a median follow-up of 16 months (range, 6-44 months), the 1-year and 2-year actuarial survival rates were 69% and 34%, respectively. The 1-year and 2-year local control rates were 93% and 84%, with respective incidences of new distant brain metastases of 50% and 66%. Local control was similar for radiosensitive (non-small cell lung cancer and breast cancer) and radioresistant (melanoma and renal cell cancer) brain metastases. On multivariate Cox analysis stable extracranial disease, breast cancer histology, and Karnofsky performance status >70 were associated with significant survival benefit. Brain radionecrosis occurred in 9 patients (9%), being symptomatic in 5 patients (5%). Conclusions: Adjuvant multidose SRS to resection cavity represents an effective treatment option that achieves excellent local control and defers the use of whole-brain radiation therapy in selected patients with large brain metastases.

  10. Neurological Change after Gamma Knife Radiosurgery for Brain Metastases Involving the Motor Cortex

    Science.gov (United States)

    Park, Chang-Yong; Choi, Hyun-Yong; Lee, Sang-Ryul; Roh, Tae Hoon; Seo, Mi-Ra

    2016-01-01

    Background Although Gamma Knife radiosurgery (GKRS) can provide beneficial therapeutic effects for patients with brain metastases, lesions involving the eloquent areas carry a higher risk of neurologic deterioration after treatment, compared to those located in the non-eloquent areas. We aimed to investigate neurological change of the patients with brain metastases involving the motor cortex (MC) and the relevant factors related to neurological deterioration after GKRS. Methods We retrospectively reviewed clinical, radiological and dosimetry data of 51 patients who underwent GKRS for 60 brain metastases involving the MC. Prior to GKRS, motor deficits existed in 26 patients (50.9%). The mean target volume was 3.2 cc (range 0.001–14.1) at the time of GKRS, and the mean prescription dose was 18.6 Gy (range 12–24 Gy). Results The actuarial median survival time from GKRS was 19.2±5.0 months. The calculated local tumor control rates at 6 and 12 months after GKRS were 89.7% and 77.4%, respectively. During the median clinical follow-up duration of 12.3±2.6 months (range 1–54 months), 18 patients (35.3%) experienced new or worsened neurologic deficits with a median onset time of 2.5±0.5 months (range 0.3–9.7 months) after GKRS. Among various factors, prescription dose (>20 Gy) was a significant factor for the new or worsened neurologic deficits in univariate (p=0.027) and multivariate (p=0.034) analysis. The managements of 18 patients were steroid medication (n=10), boost radiation therapy (n=5), and surgery (n=3), and neurological improvement was achieved in 9 (50.0%). Conclusion In our series, prescription dose (>20 Gy) was significantly related to neurological deterioration after GKRS for brain metastases involving the MC. Therefore, we suggest that careful dose adjustment would be required for lesions involving the MC to avoid neurological deterioration requiring additional treatment in the patients with limited life expectancy. PMID:27867921

  11. CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2–neu-positive breast cancer

    Science.gov (United States)

    Sengupta, S.; Rojas, R.; Mahadevan, A.; Kasper, E.; Jeyapalan, S.

    2015-01-01

    Nervous system relapse of patients with advanced HER2–neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood–brain barrier, as combination therapy to treat HER2–neu-positive breast cancer with brain metastases. PMID:26634139

  12. Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer

    NARCIS (Netherlands)

    Rades, Dirk; Fischer, Dorothea; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.

    2009-01-01

    The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate

  13. Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience.

    Science.gov (United States)

    Bates, James E; Youn, Paul; Peterson, Carl R; Usuki, Kenneth Y; Walter, Kevin A; Okunieff, Paul; Milano, Michael T

    2017-10-01

    Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

  14. Efficacy of EGFR-TKI therapy in patients with brain metastases from ...

    African Journals Online (AJOL)

    of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from non- small-cell lung ... [9,10]. Many studies have shown the responses of. NSCLC patients with BM to EGFR-TKIs [11-14], but most of ... The ORR was defined as the percentage of ..... d), which permit unrestricted use, distribution,.

  15. Automatic planning on hippocampal avoidance whole-brain radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuo, E-mail: shuo0220@gmail.com; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R.; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A.; Zhou, Sumin

    2017-04-01

    Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle{sup 3} Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle{sup 3} Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle{sup 3} Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D{sub 2%} and D{sub 98%} of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D{sub 100%} and D{sub max} of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle{sup 3} Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The

  16. Automatic planning on hippocampal avoidance whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Wang, Shuo; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R.; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A.; Zhou, Sumin

    2017-01-01

    Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle 3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle 3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle 3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D 2% and D 98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D 100% and D max of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle 3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by

  17. Recurrent spinal primitive neuroectodermal tumor with brain and bone metastases: A case report.

    Science.gov (United States)

    Chen, Frank; Chiou, Shyh-Shin; Lin, Sheng-Fung; Lieu, Ann-Shung; Chen, Yi-Ting; Huang, Chih-Jen

    2017-11-01

    Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brain MRI showed extensive bilateral calvarial metastases and leptomeningeal metastases in the right frontoparietal regions. Bone scan showed multiple bone metastases. T-spine tumor removal and adjuvant radiotherapy (RT) to T-spine tumor bed were performed in the initial treatment. After clinical tumor recurrence, tumor removal was done again. She then received chemotherapy followed by whole brain irradiation with hippocampal sparing with 35 gray in 20 fractions. After treatment, follow-up images showed that the disease was under control. There was no neurological sequela. She has survived more than 7 years from diagnosis and more than 4 years from recurrence to date. Multimodality treatments including operation, RT, and chemotherapy should be considered in the initial treatment planning, and salvage chemotherapy was useful in this case.

  18. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    International Nuclear Information System (INIS)

    Halasz, Lia M.; Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan; Punglia, Rinaa S.

    2013-01-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  19. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M., E-mail: lhalasz@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan [Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  20. Prognostic indices for brain metastases – usefulness and challenges

    Directory of Open Access Journals (Sweden)

    Nieder Carsten

    2009-03-01

    Full Text Available Abstract Background This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed. Methods Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA. Results So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA, all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool. Conclusion This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.

  1. Reliability of the Bony Anatomy in Image-Guided Stereotactic Radiotherapy of Brain Metastases

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Baier, Kurt; Guenther, Iris; Richter, Anne; Wilbert, Juergen; Sauer, Otto; Vordermark, Dirk; Flentje, Michael

    2007-01-01

    Purpose: To evaluate whether the position of brain metastases remains stable between planning and treatment in cranial stereotactic radiotherapy (SRT). Methods and Materials: Eighteen patients with 20 brain metastases were treated with single-fraction (17 lesions) or hypofractionated (3 lesions) image-guided SRT. Median time interval between planning and treatment was 8 days. Before treatment a cone-beam CT (CBCT) and a conventional CT after application of i.v. contrast were acquired. Setup errors using automatic bone registration (CBCT) and manual soft-tissue registration of the brain metastases (conventional CT) were compared. Results: Tumor size was not significantly different between planning and treatment. The three-dimensional setup error (mean ± SD) was 4.0 ± 2.1 mm and 3.5 ± 2.2 mm according to the bony anatomy and the lesion itself, respectively. A highly significant correlation between automatic bone match and soft-tissue registration was seen in all three directions (r ≥ 0.88). The three-dimensional distance between the isocenter according to bone match and soft-tissue registration was 1.7 ± 0.7 mm, maximum 2.8 mm. Treatment of intracranial pressure with steroids did not influence the position of the lesion relative to the bony anatomy. Conclusion: With a time interval of approximately 1 week between planning and treatment, the bony anatomy of the skull proved to be an excellent surrogate for the target position in image-guided SRT

  2. Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

    International Nuclear Information System (INIS)

    Gorovets, Daniel; Ayala-Peacock, Diandra; Tybor, David J.; Rava, Paul; Ebner, Daniel; Cielo, Deus; Norén, Georg; Wazer, David E.; Chan, Michael; Hepel, Jaroslaw T.

    2017-01-01

    Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

  3. Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Gorovets, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York (United States); Ayala-Peacock, Diandra [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Tybor, David J. [Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts (United States); Rava, Paul [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, Massachusetts (United States); Ebner, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Cielo, Deus; Norén, Georg [Department of Neurosurgery, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Wazer, David E. [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Chan, Michael [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States)

    2017-02-01

    Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

  4. External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center

    International Nuclear Information System (INIS)

    Wronski, Marek; Maor, Moshe H.; Davis, Brian J.; Sawaya, Raymond; Levin, Victor A.

    1997-01-01

    Purpose: Approximately 10% of patients with metastatic renal cell carcinoma are diagnosed with brain metastases. Most of these patients receive palliative radiotherapy and die of progressive brain metastatic disease. This retrospective study examines the M. D. Anderson Cancer Center experience with such patients who received only whole brain radiation therapy (WBRT). Methods and Materials: Records of 200 patients with brain metastases from renal carcinoma who were treated at M. D. Anderson Cancer Center between 1976 and 1993 were reviewed. Of these patients, 119 received WBRT only and constitute the basis of this study. Different prognostic factors were analyzed. Results: Overall median survival time from diagnosis of the brain metastases was 4.4 months. Multiple brain tumors were treated in 70 patients (58.8%) who had a survival of 3.0 months compared with 4.4 months for patients having a single brain metastasis (p = 0.043). Among 117 patients the causes of death were neurologic in 90 (76%), systemic cancer in 19 (16%), and unknown in 9 (8%). Survival rates at 6 months, 1 year, and 2 years, were 33.6, 16.8, and 5.9%, respectively. Patients in whom brain metastases were diagnosed synchronously with a renal primary (n = 24) had a median survival time of 3.4 months compared with 3.2 months for those 95 who were diagnosed metachronously (p < 0.79, NS). In the Cox multivariate analysis of 13 possible prognostic factors, only a single brain metastasis (p = 0.0329), lack of distant metastases at the time of diagnosis (p = 0.0056), and tumor diameter ≤ 2 cm (p < 0.0016) were statistically significant. Conclusion: These unsatisfactory results with WBRT suggest that more aggressive approaches, such as surgery or radiosurgery should be applied whenever possible

  5. Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Sundaresan, P.; Yeghiaian, R.; Gebski, V.

    2010-01-01

    Full text: Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

  6. Real-Time Pretreatment Review Limits Unacceptable Deviations on a Cooperative Group Radiation Therapy Technique Trial: Quality Assurance Results of RTOG 0933

    International Nuclear Information System (INIS)

    Gondi, Vinai; Cui, Yunfeng; Mehta, Minesh P.; Manfredi, Denise; Xiao, Ying; Galvin, James M.; Rowley, Howard; Tome, Wolfgang A.

    2015-01-01

    Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a “dry-run” credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging–computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. Conclusions: Although >95% of the

  7. Real-Time Pretreatment Review Limits Unacceptable Deviations on a Cooperative Group Radiation Therapy Technique Trial: Quality Assurance Results of RTOG 0933

    Energy Technology Data Exchange (ETDEWEB)

    Gondi, Vinai, E-mail: vgondi@chicagocancer.org [Cadence Brain Tumor Center and CDH Proton Center, Warrenville, Illinois (United States); University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin (United States); Cui, Yunfeng [Duke University School of Medicine, Durham, North Carolina (United States); Mehta, Minesh P. [University of Maryland School of Medicine, Baltimore, Maryland (United States); Manfredi, Denise [Radiation Therapy Oncology Group—RTQA, Philadelphia, Pennsylvania (United States); Xiao, Ying; Galvin, James M. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Rowley, Howard [University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin (United States); Tome, Wolfgang A. [Montefiore Medical Center and Institute for Onco-Physics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States)

    2015-03-01

    Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a “dry-run” credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging–computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. Conclusions: Although >95% of the

  8. RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.

    Science.gov (United States)

    Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

    2016-11-08

    Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.

  9. Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Aoyama, Hidefumi [Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan); Kocher, Martin [Department of Radiation Oncology, University of Cologne, Cologne (Germany); Neupane, Binod [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Collette, Sandra [Statistics Department, European Organisation for Research and Treatment of Cancer, Brussels (Belgium); Tago, Masao [Department of Radiology, Teikyo University Mizonokuchi Hospital, Kanagawa (Japan); Shaw, Prakesh [Department of Pediatrics, Mount Sinai Hospital, Institute of Health Policy Management and Evaluation, University of Toronto, Ontario (Canada); Beyene, Joseph [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Chang, Eric L. [Department of Radiation Oncology, University of Southern California, Los Angeles, California (United States); Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States)

    2015-03-15

    Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.

  10. Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

    International Nuclear Information System (INIS)

    Sahgal, Arjun; Aoyama, Hidefumi; Kocher, Martin; Neupane, Binod; Collette, Sandra; Tago, Masao; Shaw, Prakesh; Beyene, Joseph; Chang, Eric L.

    2015-01-01

    Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group

  11. A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases: research protocol CAR-study B.

    Science.gov (United States)

    Schimmel, Wietske C M; Verhaak, Eline; Hanssens, Patrick E J; Gehring, Karin; Sitskoorn, Margriet M

    2018-02-21

    Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing. CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11-20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment. Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups. The Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717

  12. Cognitive dysfunction in patients with brain metastases: influences on caregiver resilience and coping.

    Science.gov (United States)

    Saria, Marlon Garzo; Courchesne, Natasia; Evangelista, Lorraine; Carter, Joshua; MacManus, Daniel A; Gorman, Mary Kay; Nyamathi, Adeline M; Phillips, Linda R; Piccioni, David; Kesari, Santosh; Maliski, Sally

    2017-04-01

    Neurologic deficits that may be manifested as cognitive impairment contribute to the challenges faced by caregivers of patients with brain metastases. To better address their needs, we examined how caregivers respond to these challenges and explore the relationship between the patient's cognitive impairment and caregiver resilience and coping. We conducted a descriptive, cross-sectional study using self-reported data from 56 caregivers of patients with brain metastases. Study participants from a comprehensive cancer center were asked to complete a series of instruments that measured their perception of the patient's cognitive dysfunction (revised memory and behavior problems checklist, RMBC), their own personal resilience (Resilience Scale, RS), and their utilization of a broad range of coping responses (COPE inventory and Emotional-Approach Coping scale). Caregivers reported that memory-related problems occurred more frequently in the patients they cared for compared to depression and disruptive behavior (mean scores 3.52 vs 2.34 vs. 1.32, respectively). Coping strategies most frequently used by caregivers were acceptance (3.28), planning (3.08), and positive reinterpretation and growth (2.95). Most caregivers scored moderate to high on the RS (77%). The coping strategy acceptance correlated significantly with the memory and disruptive behavior subscales of the RMBC. Given the protective effect of problem-focused coping and the high rate of caregivers utilizing less effective coping strategies in instances of worsening cognitive dysfunction, healthcare professionals need to systematically assess the coping strategies of caregivers and deliver a more personalized approach to enhance effective coping among caregivers of patients with brain metastases.

  13. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-01-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery

  14. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    International Nuclear Information System (INIS)

    Stea, Baldassarre; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-01-01

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm

  15. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2012-07-15

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  16. Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: A report using RTOG 90-06

    International Nuclear Information System (INIS)

    Scott, Charles B.; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher U.; Simpson, Joseph R.; Fischbach, A. Jennifer; Curran, Walter J.

    1998-01-01

    Purpose: The recursive partitioning analysis (RPA) classes for malignant glioma patients were previously established using data on over 1500 patients entered on Radiation Therapy Oncology Group (RTOG) clinical trials. The purpose of the current analysis was to validate the RPA classes with a new dataset (RTOG 90-06), determine the predictive power of the RPA classes, and establish the usefulness of the database norms for the RPA classes. Patients and Methods: There are six RPA classes for malignant glioma patients that comprise distinct groups of patients with significantly different survival outcome. RTOG 90-06 is a randomized Phase III study of 712 patients accrued from 1990 to 1994. The minimum potential follow-up is 18 months. The treatment arms were combined for the purpose of this analysis. There were 84, 13, 105, 240, 150, and 23 patients in the RPA Classes I-VI from RTOG 90-06, respectively. Results: The median survival times (MST) and 2-year survival rates for the six RPA classes in RTOG 90-06 are compared to those previously published. The MST and 2-year survival rates for the RTOG RPA classes were within 95% confidence intervals of the 90-06 estimates for Classes I, III, IV, and V. The RPA classes explained 43% of the variation (squared error loss). By comparison, a Cox model explains 30% of the variation. The RPA classes within RTOG 90-06 are statistically distinct with all comparisons exceeding 0.0001, except those involving Class II. A survival analysis from a prior RTOG study indicated that 72.0 Gy had superior outcome to literature controls; analysis of this data by RPA classes indicates the survival results were not superior to the RTOG database norms. Conclusion: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival. Further evidence is given by prediction of MST and 2-year survival for all classes except Class II. The RPA classes explained a good portion of the variation in

  17. Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

    Science.gov (United States)

    Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

    2012-01-01

    Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

  18. [Global brain metastases management strategy: a multidisciplinary-based approach].

    Science.gov (United States)

    Métellus, P; Tallet, A; Dhermain, F; Reyns, N; Carpentier, A; Spano, J-P; Azria, D; Noël, G; Barlési, F; Taillibert, S; Le Rhun, É

    2015-02-01

    Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources. Copyright © 2015. Published by Elsevier SAS.

  19. The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

    International Nuclear Information System (INIS)

    Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

    2010-01-01

    Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score ≥70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p 2; p = 0.006) and age (≥70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

  20. Hemorrhagic brain metastases with high signal intensity on diffusion-weighted MR images. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mori, H.; Abe, O.; Aoki, S.; Masumoto, T.; Yoshikawa, T.; Kunimatsu, A; Hayashi, N.; Ohtomo, K. [Graduate School of Medicine, Univ. of Tokyo (Japan). Dept. of Radiology

    2002-11-01

    Diffusion-weighted MR imaging has been applicable to the differential diagnosis of abscesses and necrotic or cystic brain tumors. However, restricted water diffusion is not necessarily specific for brain abscess. We describe ring-enhancing metastases of lung carcinoma characterized by high signal intensity on diffusion-weighted MR images. The signal pattern probably reflected intralesional hemorrhage. The present report adds to the growing literature regarding the differential diagnosis of ring-enhancing brain lesions.

  1. The Palliative Radiotherapy in Bone Metastases

    International Nuclear Information System (INIS)

    Choi, Young Min; Lee, Hyung Sik; Hur, Won Joo

    1994-01-01

    To objectively compare the response of the palliative radiotherapy in bone metastatic patients which decreases pain and prevents pathologic fractures, we introduced and applied the RTOG pain and narcotic measure system. From Oct in 1991 to July in 1993, thirty-two patients with painful bone metastases, 17 of them were solitary lesions and others were multiple lesions, were treated with mainly 6 MV photon otherwise 15 MV photon. Radiation doses to bone metastatic sites ranged about from 2000 to 4600cGy. Responses of radiation therapy were compared with days of pre-RT, RT finish, 3, 6, 9 months after the start of RT and solitary versus multiple lesions and follow up scores according to the RTOG measure system. Survival analysis was done. Pain and narcotic score of the entire patients were 7.3, 7.8 at the pre-RT period and 2.6, 3.9 at the immediate or 2 weeks after RT, which was 64%, 50% decrement compared with the pre-RT score. Pain scores of 3, 6 and 9 months after the beginning of irradiation were 3.6, 3.7 and 3.3. The best response found in the breast and prostate primaries was 84%, 78% decrement of pain score as compared with pre-RT score (statistically insignificant). Median survival was 5.5 months and mean survival was 5 months. We conclude that the RTOG pain and narcotic measure system in relatively effective scale in the comparison of before and after palliative irradiation to the painful bone metastatic sites but more detailed parameters will be required in the narcotic scoring system. More aggressive but less or similar toxic radiotherapy is needed in the patients having relatively long life expected time

  2. RTOG's first quality of life study--RTOG 90-20: a phase II trial of external beam radiation with etanidazole for locally advanced prostate cancer

    International Nuclear Information System (INIS)

    Watkins-Bruner, Deborah; Scott, Charles; Lawton, Colleen; Del Rowe, John; Rotman, Marvin; Buswell, Lori; Beard, Clair; Cella, David

    1995-01-01

    Purpose: To assess institutional and patient compliance with quality of life (QL) instruments in RTOG clinical trials. To assess feasibility of using the Functional Assessment Cancer Therapy (FACT), Sexual Adjustment Questionnaire (SAQ), and Changes in Urinary Function (CUF) QL instruments in a prostate clinical trial and to compare patient self-report of symptoms to medical professional ratings of the same symptoms using the RTOG acute toxicity rating scales. Methods and Materials: Three self-assessment QL instruments, the FACT, the SAQ, and CUF, were to be administered to patients on a Phase II locally advanced prostate trial at specified time points. Specific instructions for both data managers and for patients on when, how, and why to fill out the questionnaires were included. Results: Sixty-seven percent (24 out of 36) of patients accrued to RTOG 90-20 completed both the initial FACT and SAQ. Eighty-five percent completed FACT at end of RT and 73% at 3 months. Eighty-one percent completed SAQ at end of treatment, while 69% completed this form at 3 months. Compliance drops off thereafter. Seventy-five percent of patients who had their symptom of dysuria rated by a medical professional as 0 on the RTOG toxicity rating scale self-reported the same. Only 56% of patient self-reports on FACT regarding diarrhea were in agreement with the medical professional's RTOG rating of 0 toxicity. The measures were determined to be in moderate agreement when the patient evaluated a symptom as a 1 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG toxicity rating scale. There was moderate agreement in 13% of patients with dysuria and 31% of patients with diarrhea. Low agreement occurred when the patient evaluated a symptom as a 2 or 3 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG scale. Low agreement occurred in 13% of both patients reporting dysuria and diarrhea. Differences between how medical professionals

  3. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  4. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases

    International Nuclear Information System (INIS)

    Rojas-Puentes, Luis L; Gonzalez-Pinedo, Marcelino; Crismatt, Alejando; Ortega-Gomez, Alette; Gamboa-Vignolle, Carlos; Nuñez-Gomez, Rodrigo; Dorantes-Gallareta, Yusmiren; Arce-Salinas, Claudia; Arrieta, Oscar

    2013-01-01

    Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings

  5. Psychometric validation of the functional assessment of cancer therapy--brain (FACT-Br) for assessing quality of life in patients with brain metastases.

    Science.gov (United States)

    Thavarajah, Nemica; Bedard, Gillian; Zhang, Liying; Cella, David; Beaumont, Jennifer L; Tsao, May; Barnes, Elizabeth; Danjoux, Cyril; Sahgal, Arjun; Soliman, Hany; Chow, Edward

    2014-04-01

    This study aimed to test the reliability, psychometric, and clinical validity of the use of the Functional Assessment of Cancer Therapy--Brain (FACT-Br) in patients with brain metastases. Patients with brain metastases were interviewed using the FACT-Br (including the FACT-general) 1 week prior to treatment. All patients completed a follow-up assessment 1 month post-treatment. Patients with a good performance status and receiving stereotactic radiosurgery completed an additional 1 week follow-up assessment after the initial baseline interview to assess test-retest reliability. Forty patients had complete 1 month follow-up data. Ten of these patients also completed the 1 week follow-up assessment from baseline. The median Karnofsky performance status of patients was 80 and the median age was 64 years. All subscales of the FACT-Br were found to be conceptually related (except for two correlations) using the following subscales: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), FACT-G total score, brain cancer subscale (BrC), and the FACT-Br total score. All FACT-Br scores demonstrated excellent reliability, except for the SWB scale which revealed good reliability. The FACT-Br scores showed no significant change in the quality of life (QoL) of patients from baseline to 1 month follow-up. The use of the combined FACT-G and FACT-Br Subscale to assess QoL specifically in patients with brain metastases has successfully undergone psychometric validation. Future clinical trials should use the FACT-G and FACT-Br Subscale to assess QoL in this patient population.

  6. RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases – results and lessons learnt

    Science.gov (United States)

    Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

    2016-01-01

    Background: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. Methods: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Results: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6–5.6) in the vandetanib group and 2.5 months (90% CI: 0.2–4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6–6.3) and 2.5 months (90% CI: 0.2–7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. Conclusions: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area. PMID:27711083

  7. A Single-Institution Analysis of 126 Patients Treated with Stereotactic Radiosurgery for Brain Metastases

    Directory of Open Access Journals (Sweden)

    Kevin B. Harris

    2017-05-01

    Full Text Available BackgroundThe objective of this study was to report our institutional experience with Gamma Knife® Radiosurgery (GKRS in the treatment of patients with brain metastases.MethodsRetrospectively collected demographic and clinical data on 126 patients with intracranial metastases were reviewed. The patients in our study underwent GKRS at Vidant Medical Center between 2009 and 2014. Kaplan–Meier curves were used to compare survival based on clinical characteristics for univariate analysis, and a Cox proportional hazards model was used for multivariate analysis.ResultsThe median age of the patient population was 62 years. Medicare patients constituted 51% of our patient cohort and Medicaid patients 15%. The most common tumor histologies were non-small cell lung cancer (50%, breast cancer (12.7%, and melanoma (11.9%. The median overall survival time for all patients was 5.8 months. Patients with breast cancer had the longest median survival time of 9.15 months, while patients with melanoma had the shortest median survival time of 2.86 months. On univariate analysis, the following factors were predictors for improved overall survival, ECOG score 0 or 1 vs. 2 or greater (17.0 vs. 1.8 months, p < 0.001, controlled extracranial disease vs. progressive extracranial disease (17.4 vs. 4.6 months, p = 0.0001, recursive partitioning analysis Stage I vs. II–III (18.2 vs. 6.2 months, p < 0.007, multiple GKRS treatments (p = 0.002, prior brain metastasectomy (p = 0.012, and prior chemotherapy (p = 0.021. Age, ethnicity, gender, previous external beam radiation therapy, number of brain metastases, and hemorrhagic vs. non-hemorrhagic tumors were not predictors of longer median survival time. Number of metastatic brain lesions of 1–3 vs. ≥4 (p = 0.051 and insurance status of Medicare/Medicaid vs. commercial insurance approached significance (13.7 vs. 6.8 months, p = 0.08. On multivariate analysis, ECOG

  8. 18F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    International Nuclear Information System (INIS)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing; Pan, Donghui; Xu, Yuping; Yang, Min; Lang, Lixin; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    We report the biodistribution and radiation dosimetry of an integrin α v β 3 specific PET tracer 18 F-AlF-NOTA-E[PEG 4 -c(RGDfk)] 2 (denoted as 18 F-Alfatide II). We also assessed the value of 18 F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of 18 F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with 18 F-FDG (5.55 MBq/kg) and 18 F-Alfatide II. Injection of 18 F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18 F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by 18 F-Alfatide II PET, while only ten lesions were visualized by 18 F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18 F-Alfatide II is feasible for human studies. 18 F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  9. Comparison of Tc-99m HM-PAO SPECT brain scan and x-ray CT in the detection of brain metastases

    International Nuclear Information System (INIS)

    Abdel-Dayem, H.M.; Sadek, S.; Sahwell, A.; Kubasek, H.; El-Sayed, M.; Ziada, G.; Mobarak, L.; Al-Huda, F.; Omar, Y.T.

    1986-01-01

    Tc-99m HM-PAO imaging was compared with x-ray CT in 14 patients with known or suspected brain metastases. Both studies were done within 3 days of each other. Static and single photon emission CT (SPECT) images were acquired after intravenous injection of 13 mCi of Tc-99m HM-PAO. All 14 patients underwent static and SPECT Tc-99m HM-PAO imaging and x-ray CT. Studies were positive in 7, 12, and 10 patients, respectively, by static, SPECT, and x-ray CT imaging, and negative in 7, 2, and 2. The number of lesions identified was 0 (static imaging), 32 (SPECT), and 26(x-ray CT). There were no ''suspicious'' studies by any modality. This study indicates that Tc-99m HM-PAO SPECT cerebral blood flow imaging is more sensitive than x-ray CT for detecting brain metastases, that biplane imaging is not sensitive and SPECT is essential, and that for Tc-99m HM-PAO SPECT brain imaging to regain its importance with respect to x-ray CT, acquisition time must be 10 minutes or less and determination of percentage brain uptake of the injected dose, and of regional distribution, is necessary

  10. Brain Metastases from Breast Cancer and Response to Treatment with Eribulin: A Case Series

    Directory of Open Access Journals (Sweden)

    Alex Y. Chang

    2015-01-01

    Full Text Available Brain metastases are common in patients with advanced breast cancer (BC, causing considerable morbidity and mortality. Eribulin is a microtubule dynamics inhibitor approved for treating certain patients with metastatic BC, previously treated with an anthracycline and a taxane. In the 301 phase 3 study in 1102 women with advanced BC, eribulin and capecitabine treatments did not differ for co-primary endpoints (overall survival [OS]: 15.9 vs 14.5 months, P = 0.056; progression-free survival [PFS]: 4.1 vs 4.2 months, P = 0.30. Here, we report outcomes for six patients (eribulin, n = 3; capecitabine, n = 3 who had received treatment for brain metastases from BC (BCBM at baseline. All eribulin-treated patients experienced brain lesion shrinkage at some point during treatment, compared with one capecitabine-treated patient. Fewer patients in study 301 developed new BCBM with eribulin (13/544, 2.4% compared with capecitabine (25/546, 4.6%. Eribulin does not cross the healthy blood–brain barrier (BBB, but could have the potential to do so after cranial radiation therapy. Capecitabine may cross the BBB and has demonstrated activity in BCBM. Data from these patients and previous cases suggest that further investigation of eribulin for BCBM may be warranted.

  11. CSF-ctDNA SMSEQ Analysis to Tailor the Treatment of a Patient with Brain Metastases: A Case Report

    Directory of Open Access Journals (Sweden)

    Wen-Tsung  Huang

    2018-02-01

    Full Text Available Brain metastases are the most common neurological complications of adult cancers, accounting for more than half of brain tumors. The incidence of brain metastases may be increasing due to improved detection of small lesions by advanced imaging technologies. Given the fast evolution of targeted and immunotherapy regimens, it is essential to serially assess brain malignancies during the disease course for disease monitoring and tailoring of the therapeutic management. For such serial and repetitive assessment, cerebrospinal fluid (CSF could be the biological fluid of choice to supplement cytology examination for the presence or absence of CNS malignancy, as well as provide extensive information on tumor mutational profile for personalization of treatment. The case described here emphasizes the importance of CSF-ctDNA analysis with the CellMax SMSEQ technology that led to treatment adjustment resulting in clinical remission of the patient.

  12. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

    Science.gov (United States)

    Patil, Chirag G; Pricola, Katie; Sarmiento, J Manuel; Garg, Sachin K; Bryant, Andrew; Black, Keith L

    2017-09-25

    Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012. To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases. For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review. We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis. We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in

  13. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Larsen, Pia Bükmann; Kümler, Iben; Nielsen, Dorte Lisbet

    2013-01-01

    Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatm......, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed....

  14. Selected Arterial Infusion Chemotherapy Combined with Target Drugs 
for Non-small Cell Lung Cancer with Multiple Brain Metastase

    Directory of Open Access Journals (Sweden)

    Jinduo LI

    2012-05-01

    Full Text Available Background and objective The aim of this study is to evaluate the efficacy of selected arterial infusion chemotherapy in treating non-small cell lung cancer (NSCLC with multiple brain metastases and corresponding factors to influencing prognosis. Methods From September 2008 to October 2011, a total of 31 patients of NSCLC with multiple brain metastases (≥3 received selected incranial, bronchial and corresponding target arterial infusion chemotherapy combined with EGFR-TKIs. Interventional treatment was performed every four weeks, two-six cycles with synchronized or sequential targeted drugs (erlotinib, gefitinib or icotinib. Follow-up CT and MRI were regularly finished at interval of four weeks after two cycles of interventional treatment were finished or during taking targeted drugs in order to evaluate efficacy of the therapy. The procedure was stopped for the tumor disease was worse or the patient could not tolerate the toxity of drugs any longer. Results 31 patients was performed two to six cycles of interventional therapy, 3cycles at average. Response assessment showed that 5 (16.1% patients got a complete response (CR, 7 (22.6% had a partial response (PR, 11 (35.5% had a stable disease (SD and 8 (25.8% had a progressive disease (PD. The objective response rate (ORR was 38.7%, and the disease control rate was 74.2%. The median progression free survival (PFS and overall survival (OS were 13.1 months and 15.1 months. The 6-month survival rate, one-year survival rate and two-year survival rate were 79%, 61.1%, and 31.1%, respectively. The patients’ OS and PFS were influenced by smoking state, tumor pathology, extracranial metastases, period of targeted drug taking and performance status, not by sex, age, before therapy and the total of brain metastases. Conclusion Selected arterial infusion chemotherapy with targeted drugs is one of the most effective and safe treatment to NSCLC with multiple brain metastases. Smoking status, tumor

  15. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Science.gov (United States)

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  16. Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the radiation therapy oncology group protocol 91-04

    International Nuclear Information System (INIS)

    Murray, Kevin J.; Scott, Charles; Zachariah, Babu; Michalski, Jeff M.; Demas, William; Vora, Nayana L.; Whitton, Anthony; Movsas, Benjamin

    2000-01-01

    Purpose: Little information is available on the importance of pretreatment Mini-Mental Status Exam (MMSE) on long-term survival and neurologic function following treatment for unresectable brain metastases. This study examines the importance of the MMSE in predicting outcome in a group of patients treated with an accelerated fractionation regimen of 30 Gy in 10 daily fractions in 2 weeks. Materials and Methods: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastases were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. Two hundred twenty-four patients were entered on the accelerated fractionated arm, and 182 were eligible for analysis (7 patients were judged ineligible, no MMSE information in 29, no survival data in 1, no forms submitted in 1). Results: Average age was 60 years; 58% were male and 25% had a single intracranial lesion on their pretherapy evaluation. KPS was 70 in 32%, 80 in 31%, 90 in 29%, and 100 in 14%. The average MMSE was 26.5, which is the lower quartile for normal in the U.S. population. The range of the MMSE scores was 11-30 with 30 being the maximum. A score of less than 23 indicates possible dementia, which occurred in 16% of the patients prior to treatment. The median time from diagnosis to treatment was 5 days (range, 0-158 days). The median survival was 4.2 months with a 95% confidence interval of 3.7-5.1 months. Thirty-seven percent of the patients were alive at 6 months, and 17% were alive at 1 year. The following variables were examined in a Cox proportional-hazards model to determine their prognostic value for overall survival

  17. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    International Nuclear Information System (INIS)

    Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V_1_0_0. All of the other measured dosimetric parameters including the V_9_5, V_9_9, and D_1_0_0 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  18. Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

    Science.gov (United States)

    Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of

  19. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  20. What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach

    International Nuclear Information System (INIS)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Atalar, Banu; Lieberson, Robert E.; Soltys, Scott G.

    2012-01-01

    Purpose: Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity. Patients and Methods: We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method. Results: The median imaging follow-up duration for all patients was 10 months (range, 1–80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%–16.1%), and the median time to LF was 6 months (range, 3–17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%–63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (≥80 vs. <80; hazard ratio 0.54; 95% CI 0.31–0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08–1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity. Conclusion: Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  1. Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Xu J

    2016-05-01

    Full Text Available Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China Objective: The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs from lung adenocarcinoma.Patients and methods: Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125 mg icotinib orally three times a day. Progression of disease, intolerable adverse reactions, and number of deaths were recorded.Results: For all the patients, the remission rate of icotinib was 67.8% and the disease control rate was 96.4%. The median overall survival time of patients was 21.2 months, and the median progression-free survival time of patients was 10.9 months. Only mild adverse events of grade 1/2 were observed during the treatment.Conclusion: Icotinib was an effective and safe strategy to treat patients with BMs from lung adenocarcinoma.Keywords: icotinib, lung adenocarcinoma, brain metastases 

  2. Whole brain radiotherapy for brain metastases: The technique of irradiation influences the dose to parotid glands

    International Nuclear Information System (INIS)

    Loos, G.; Paulon, R.; Verrelle, P.; Lapeyre, M.

    2012-01-01

    In the treatment of brain metastases, whole brain radiotherapy can be carried out according two distinct methods: one using multi-leaf collimator for field shaping and protection of organs at risk, and a second one is to make a rotation of the field to avoid the eyes. The aim of the study was to compare for 10 patients the dose distributions at organs at risk for each method. Patients received 30 Gy in 10 fractions. Except for parotid glands, the dose received by organs at risk and the planning target volume was the same with each method. For whole brain radiotherapy, excluding the cisterna cerebellomedullaris, the mean parotid dose was 9.63 Gy using the multi-leaf collimator versus 12.32 Gy using the field rotation (P = 0.04). For whole brain radiotherapy including the cisterna cerebellomedullaris, the mean parotid dose was 11.12 Gy using the multi-leaf collimator versus 20.06 Gy using field rotation (P < 0.001). Using the multi-leaf collimator seems recommended for whole brain radiotherapy, to reduce the dose to the parotids. (authors)

  3. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2012-06-15

    To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

  4. Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.

    Science.gov (United States)

    Stokes, William A; Binder, David C; Jones, Bernard L; Oweida, Ayman J; Liu, Arthur K; Rusthoven, Chad G; Karam, Sana D

    2017-12-15

    Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Adding immunotherapy to radiotherapy for MBM is associated with improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Is whole brain radiation therapy needed for all patients with newly diagnosed brain metastases undergoing stereotactic radiosurgery?

    International Nuclear Information System (INIS)

    Suh, John H.; Barnett, Gene H.; Miller, David W.; Kupelian, Patrick A.; Cohen, Bruce H.

    1997-01-01

    PURPOSE: Since whole brain radiation therapy (WBRT) carries risks for long term survivors of brain metastases, some have advocated the use of stereotactic radiosurgery (SRS) alone for patients with brain metastases. We retrospectively reviewed our results of stereotactic radiosurgery (SRS) with immediate or delayed WBRT. MATERIALS/METHODS: From March 1990 to December 1996, linear accelerator-based SRS was performed on patients with Karnofsky score ≥ 70 and asymptomatic or mildly symptomatic brain metastases < 4 cm diameter. After excluding those patients with recurrent disease, 87 patients with 106 metastatic lesions (72 pts- single or solitary lesion, 13 pts- 2 lesions, 1 pt- 3 lesions, and 1 pt- 5 lesions) remained for analysis. The use of WBRT was dependent on physician preference but was given to all patients who developed local or regional failure after SRS. Survival was measured from the date of SRS until death or last follow-up using Kaplan-Meier method. Freedom from progression (FFP) was defined as no local or regional brain failure on follow-up radiographs and was measured from the date of SRS. RESULTS: Prognostic variables (age, sex, initial KPS, systemic disease, and extent of surgical resection) were similar for the 40 patients in the immediate WBRT group (iWBRT) and for the 47 patients in the delayed WBRT group (dWBRT). With a median follow-up of 5.8 months, no significant difference in median survival (6.9 months for both groups) was noted. On multivariate analysis, absence of systemic disease (p=0.008) and KPS 90-100 (p=0.001) were the only significant predictors for survival. For the 29 patients with a minimum KPS of 90 and no systemic disease, the median survival was 17.8 months. For those patients with a solitary lesion (no systemic disease), there was a trend for better median survival for the iWBRT group (22.8 months) versus the dWBRT group (9.3 months), p=0.06. FFP data was available on 78 patients (97 lesions). A significant difference was

  6. A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases : Research protocol CAR-study B

    NARCIS (Netherlands)

    Schimmel, W.C.M.; Verhaak, E.; Hanssens, Patrick E. J.; Gehring, K.; Sitskoorn, M.M.

    2018-01-01

    Background Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is

  7. Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

    OpenAIRE

    Stark, Andreas M.

    2010-01-01

    Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present...

  8. Correlates of objectively measured sedentary behavior in cancer patients with brain metastases: an application of the theory of planned behavior.

    Science.gov (United States)

    Lowe, Sonya S; Danielson, Brita; Beaumont, Crystal; Watanabe, Sharon M; Baracos, Vickie E; Courneya, Kerry S

    2015-07-01

    The aim of this study is to examine the demographic, medical, and social-cognitive correlates of objectively measured sedentary behavior in advanced cancer patients with brain metastases. Advanced cancer patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with palliative performance scale greater than 30%, were recruited from a Rapid Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed the theory of planned behavior variables and medical and demographic information. Participants wore activPAL™ (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time spent supine, sitting, standing, and stepping during 7 days encompassing palliative whole brain radiotherapy treatments. Thirty-one patients were recruited. Correlates of median time spent supine or sitting in hours per day were instrumental attitude (i.e., perceived benefits) of physical activity (r = -0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine for greater than 20.7 h per day reported significantly lower instrumental attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years of age spent more time sitting or being supine. Instrumental attitude and affective attitude were the strongest correlates of objectively measured sedentary behavior. This information could inform intervention studies to increase physical activity in advanced cancer patients with brain metastases. Copyright © 2014 John Wiley & Sons, Ltd.

  9. A comparison of radiotherapy with radiotherapy plus surgery for brain metastases from urinary bladder cancer. Analysis of 62 patients

    Energy Technology Data Exchange (ETDEWEB)

    Engenhart-Cabillic, Rita [Dept. of Radiotherapy and Radiation Oncology, Philipps Univ. Marburg (Germany); Fokas, Emmanouil; Henzel, Martin

    2010-10-15

    Purpose: To evaluate the role of radiotherapy (RT) and prognostic factors in 62 patients with brain metastases from transitional cell carcinoma (TCC) of the urinary bladder. Patients and Methods: 62 patients received either RT (n = 49), including whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS), or surgery (OP) combined with WBRT (n = 13). Overall survival (OS), intracerebral control (ICC) and local control (LC) were retrospectively analyzed. Six potential prognostic factors were assessed: age, gender, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to RT. Results: Median OS and ICC for the entire cohort were 9 and 7 months. No significant difference between RT and OP + RT was found for OS (p = 0.696) and ICC (p = 0.996). On multivariate analysis, improved OS was associated with lack of extracerebral metastases (p < 0.001) and RPA class (p < 0.001), and ICC with the latter (p < 0.001). SRS-incorporating RT resulted in 1-, 2-, and 3-year LC probability of 78%, 66%, and 51%. No association between LC and any of the potential prognostic factors was observed. The results of the subgroup RPA class analyses were similar to the entire cohort. Conclusion: Patient outcome for the RT-alone arm was not significantly different from OP + RT. SRS-incorporating treatment offers excellent LC rates. RPA class and the presence of extracerebral metastases demonstrated a significant prognostic role for survival. The latter should be used as stratification factors in randomized trials and can help define the cohort of patients that may benefit from more aggressive therapies. (orig.)

  10. The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Varlotto, John M.; Flickinger, John C.; Niranjan, Ajay; Bhatnagar, Ajay; Kondziolka, Douglas; Lunsford, L. Dade

    2005-01-01

    Purpose: To better analyze how whole-brain radiotherapy (WBXRT) affects long-term tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for brain metastases, we studied these outcomes in patients who had survived at least 1 year from SRS. Methods and Materials: We evaluated the results of gamma knife radiosurgery for 160 brain metastases in 110 patients who were followed for a median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a solitary brain metastasis and 28 patients had multiple metastases. Seventy patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas 40 patients (44 lesions) initially received radiosurgery alone. Median treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy). Results: At 1, 3, and 5 years, local tumor control was 84.1% ± 5.5%, 68.6% ± 8.7%, and 68.6% ± 8.7% with SRS alone compared with 93.1% ± 2.4%, 87.7% ± 4.9%, and 65.7% ± 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found that WBXRT improved local control in patient subsets tumor volume ≥2 cc, peripheral dose ≤16 Gy, single metastases, nonradioresistant tumors, and lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure developed at 1, 3, and 5 years in 26.0% ± 7.1%, 74.5% ± 9.4%, and 74.5% ± 9.4% with SRS alone compared with 20.7% ± 4.9%, 49.0% ± 8.7%, and 61.8% ± 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend for improved distal intracranial control with WBXRT for only nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in 2.8% ± 1.2% and 10.7% ± 3.5% at 1 and 3-5 years and was unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or in any subsets. Conclusions: In this retrospective study of 1-year survivors of SRS for brain metastases, the

  11. Brain metastases of solid tumour. Treatment distribution and analysis of survival in the period 1/01/2004 to 31/12/2008

    International Nuclear Information System (INIS)

    Xavier, F.; Rodriguez, R.; Lima, R.; Rios, A.; Mara, C.

    2010-01-01

    Objective: To retrospectively analyze the characteristics, treatments and survival analysis in patients with solid tumors with brain metastases (E IV) assisted in Unit Neuro-Oncology over a period of five years. Patients and methods: The records of patients (pts) with diagnosis of brain metastases from solid tumors assisted in Neuro-Oncology Unit, from 1/01/2004 and 31/12/2008. Results: 51 new patients carriers of brain metastases were treated with solid tumors. The median age at diagnosis was 57 years, ranging from 30 to 75. They corresponded to the male 37 and female 14 ratio 2.5 / 1. The majority was presented as metastases 31/51. The location was in the supratentorial region in 27 cases, posterior fossa in 11 and 13 were supra and infratentorial. In only 5 patients cranial MRI was performed in only one case and it changed the therapeutical strategy. In 35 patients he corresponded to the lung primary tumor (CBP), following cancer renal (5/51). Within the CBP, the most common histologic subtypes were to large cells and adenocarcinomas, 11 and 10, respectively. In 32 patients were not found dissemination elsewhere. Surgery + RT was performed in 30 cases, in 11 exclusive RT, exclusive surgery in 4 and 3 patients symptomatic treatment. In 39 cases did not Systemic treatment diagnosis. When a progression was only diagnosed It could make systemic treatment 5 pts. The median survival was 15.4 weeks (1-301 weeks). Conclusions: Lung cancer is the most common source of metastases brain, with a poor survival. The results of other characteristics patients, systemic treatments performed and survival according to the treatments performed will be presented during the congresss

  12. Recursive partitioning analysis (RPA) classification predicts survival in patients with brain metastases from sarcoma.

    Science.gov (United States)

    Grossman, Rachel; Ram, Zvi

    2014-12-01

    Sarcoma rarely metastasizes to the brain, and there are no specific treatment guidelines for these tumors. The recursive partitioning analysis (RPA) classification is a well-established prognostic scale used in many malignancies. In this study we assessed the clinical characteristics of metastatic sarcoma to the brain and the validity of the RPA classification system in a subset of 21 patients who underwent surgical resection of metastatic sarcoma to the brain We retrospectively analyzed the medical, radiological, surgical, pathological, and follow-up clinical records of 21 patients who were operated for metastatic sarcoma to the brain between 1996 and 2012. Gliosarcomas, sarcomas of the head and neck with local extension into the brain, and metastatic sarcomas to the spine were excluded from this reported series. The patients' mean age was 49.6 ± 14.2 years (range, 25-75 years) at the time of diagnosis. Sixteen patients had a known history of systemic sarcoma, mostly in the extremities, and had previously received systemic chemotherapy and radiation therapy for their primary tumor. The mean maximal tumor diameter in the brain was 4.9 ± 1.7 cm (range 1.7-7.2 cm). The group's median preoperative Karnofsky Performance Scale was 80, with 14 patients presenting with Karnofsky Performance Scale of 70 or greater. The median overall survival was 7 months (range 0.2-204 months). The median survival time stratified by the Radiation Therapy Oncology Group RPA classes were 31, 7, and 2 months for RPA class I, II, and III, respectively (P = 0.0001). This analysis is the first to support the prognostic utility of the Radiation Therapy Oncology Group RPA classification for sarcoma brain metastases and may be used as a treatment guideline tool in this rare disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    International Nuclear Information System (INIS)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-01-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective

  14. Radiotherapy of brain metastases and glioblastomas in elderly patients; Radiotherapie des metastases cerebrales et des glioblastomes chez le sujet age

    Energy Technology Data Exchange (ETDEWEB)

    Lauche, O.; Kerr, C.; Riou, O.; Dhermain, F. [Institut Gustave-Roussy, Villejuif (France)

    2011-10-15

    As the occurrence of malignant gliomas and brain metastases is increasing in elderly people, the authors report the definition of an optimal therapeutic strategy for these patients. For patients in good health condition, a prospective randomized showed a modest benefit of radiotherapy alone with respect to support cares in terms of survival. The radiotherapy scheme is discussed in terms of dose and number of fractions. It seems that the physiological age is a strong prognosis factor. Short communication

  15. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

    Science.gov (United States)

    Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

    2014-07-01

    To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

  16. Population-based outcomes after brain radiotherapy in patients with brain metastases from breast cancer in the Pre-Trastuzumab and Trastuzumab eras

    International Nuclear Information System (INIS)

    Karam, Irene; Hamilton, Sarah; Nichol, Alan; Woods, Ryan; Speers, Caroline; Kennecke, Hagen; Tyldesley, Scott

    2013-01-01

    To evaluate the survival of patients with human epidermal growth factor receptor 2 (HER2) positive and negative metastatic breast cancer irradiated for brain metastases before and after the availability of trastuzumab (T). Women diagnosed with brain metastasis from breast cancer in two eras between 2000 and 2007 (T-era, n = 441) and 1986 to 1992 (PreT-era, n = 307), treated with whole brain radiotherapy (RT) were identified. In the T-era, HER2 testing was part of routine clinical practice, and in the preT-era 128/307 (42%) cases had HER2 testing performed retrospectively on tissue microarrays. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons between eras used log-rank tests. In the preT- and T-era cohorts, the rate of HER2 positivity was 40% (176/441) and 26% (33/128) (p < 0.001). The median time from diagnosis to brain RT was longer in the preT-era (3.3 years versus 2.3 years, p < 0.001). Survival after brain RT was improved in the T-era compared to the preT-era (1-year OS 26% versus 12%, p < 0.001). The 1-year OS rate for HER2 negative patients was 20% in both eras (p = 0.97). Among HER2 positive patients, the 1-year OS in the preT-era was 5% compared to 40% in the T-era (p < 0.001). Distinct from patients with HER2 negative disease in whom no difference in survival after brain RT was observed over time, patients with HER2 positive brain metastases experienced significantly improved survival subsequent to the availability of trastuzumab

  17. The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy.

    Science.gov (United States)

    Kaidar-Person, Orit; Zagar, Timothy M; Deal, Allison; Moschos, Stergios J; Ewend, Matthew G; Sasaki-Adams, Deanna; Lee, Carrie B; Collichio, Frances A; Fried, David; Marks, Lawrence B; Chera, Bhishamjit S

    2017-07-01

    Stereotactic radiotherapy (SRT) is the standard treatment for patients with limited number of brain metastases. In the past few years, newer immunotherapies (immune checkpoint inhibitors) have been proven to prolong survival in patients with metastatic melanoma. The safety of the combination of SRT and immunotherapy for brain metastases is unknown. We retrospectively identified patients with melanoma brain metastases treated with SRT between 2007 and 2015. Patients who did not have at least 3 months of follow-up with imaging after SRT were excluded from the analysis. Outcomes were compared between patients who were treated with or without immunotherapy. A total of 58 patients were included; of these, 29 were treated with SRT and immunotherapy. MAPK inhibitors (BRAF, MEK inhibitors) were used more often in the immunotherapy group (nine vs. two patients). There was a higher incidence of intracranial complications in patients treated with immunotherapy and SRT. Eight patients had radiation necrosis; all occurred in patients who were treated with immunotherapy. Nine patients had hemorrhage, of which seven occurred in patients who were treated with immunotherapy (P=0.08). However, patients treated with immunotherapy and SRT had a significant overall survival advantage compared with SRT without immunotherapy (15 vs. 6 months, P=0.0013). Patients treated with SRT and immunotherapy have a higher incidence/risk of intracranial complications, but a longer overall survival.

  18. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  19. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S

    2014-01-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment

  20. Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Cicone, Francesco; Papa, Annalisa; Scopinaro, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; ' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Minniti, Giuseppe; Scaringi, Claudia; Maurizi Enrici, Riccardo [' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Sant' Andrea Hospital, Rome (Italy). Unit of Radiotherapy; Romano, Andrea; Tavanti, Francesca; Bozzao, Alessandro [Sant' Andrea Hospital, Rome (Italy). Unit of Neuroradiology; Rome Univ. (Italy). Dept. of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.)

    2015-01-15

    We assessed the performance of 6-[{sup 18}F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR). In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis. Several semiquantitative PET parameters were recorded, and their diagnostic accuracy was compared by receiver operating characteristic curve analyses. The diagnosis was established by either surgery or follow-up. A comparison was made between F-DOPA PET and perfusion-MR sequences acquired no more than 3 weeks apart. Definitive outcome was available in 46 of the 50 lesions (20 PD, 26 RN). Of the 46 lesions, 11 were surgically excised while in the remaining 35 lesions the diagnosis was established by radiological and clinical criteria. The best diagnostic performance was obtained using the semiquantitative PET parameter maximum lesion to maximum background uptake ratio (SUVL{sub max}/Bkgr{sub max}). With a cut-off value of 1.59, a sensitivity of 90 % and a specificity of 92.3 % were achieved in differentiating RN from PD lesions (accuracy 91.3 %). Relative cerebral blood volume (rCBV) derived from perfusion-MR was available for comparison in 37 of the 46 metastases. Overall accuracy of rCBV was lower than that of all semiquantitative PET parameters under study. The best differentiating rCBV cut-off value was 2.14; this yielded a sensitivity of 86.7 % and a specificity of 68.2 % (accuracy 75.6 %). F-DOPA PET is a highly accurate tool for differentiating RN from PD brain metastases after stereotactic radiosurgery. In this specific setting, F-DOPA PET seems to perform better than perfusion-MR. (orig.)

  1. An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-06-01

    Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

  2. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Ge, Xiao-hui; Liu, Miao-ling; Lin, Qiang; Ren, Xiao-cang; Liu, Yue-e; Chen, Xue-ji; Wang, Dong-ying; Wang, Yong-qiang; Cao, Bin; Li, Zhi-gang

    2013-01-01

    Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ 2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ 2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ 2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

  3. Ultrasound imaging-guided intracardiac injection to develop a mouse model of breast cancer brain metastases followed by longitudinal MRI.

    Science.gov (United States)

    Zhou, Heling; Zhao, Dawen

    2014-03-06

    Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T2-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.

  4. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg; Ganzhirnbestrahlung bei Hirnmetastasen von 2005 bis 2011 in der Klinik fuer Strahlenheilkunde des Universitaetsklinikums Freiburg

    Energy Technology Data Exchange (ETDEWEB)

    Hintz, Mandy

    2017-10-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  5. A 3D T1-weighted gradient-echo sequence for routine use in 3D radiosurgical treatment planning of brain metastases: first clinical results

    International Nuclear Information System (INIS)

    Hawighorst, H.; Schad, L.R.; Gademann, G.; Knopp, M.V.; Wenz, F.; Kaick, G. van

    1995-01-01

    The authors report on a 3D sequence for MRI of the brain and its application in radiosurgical treatment planning of 35 brain metastases. The measuring sequence, called magnetization - prepared rapid gradient echo (MPRAGE), was compared with 2D T1-weighted spin-echo (SE) sequences following intravenous contrast-medium application in 19 patients with brain metastases. The average diameter of all lesions was similar in both sequences, with 16.8 and 17.0 mm for SE and MPRAGE, respectively. Target point definition was equal in 29 metastases, and in 6 cases superior on MPRAGE, due to better gray-white matter contrast and increased contrast enhancement. In cases of bleeding metastases there was improved depiction of internal structures in 3D MRI. Postprocessing of 3D MPRAGE data created multiplanar reconstruction along any chosen plane with isotropic spatial resolution, which helped to improve radiosurgical isodose distribution in 4 cases when compared to 2D SE. However, sensitivity of 3D MPRAGE to detect small lesions (< 3 mm) was decreased in one patient with more than 50 metastases. We conclude that 3D gradient-echo (GE) imaging might be of great value for radiosurgical treatment planning, but does not replace 2D SE with its current parameters. (orig.)

  6. {sup 18}F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing [Affiliated Hospital of Jiangnan University (Wuxi No. 4 People' s Hospital), Department of Nuclear Medicine, Wuxi (China); Pan, Donghui; Xu, Yuping; Yang, Min [Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi (China); Lang, Lixin; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2015-12-15

    We report the biodistribution and radiation dosimetry of an integrin α{sub v}β{sub 3} specific PET tracer {sup 18}F-AlF-NOTA-E[PEG{sub 4}-c(RGDfk)]{sub 2} (denoted as {sup 18}F-Alfatide II). We also assessed the value of {sup 18}F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of {sup 18}F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with {sup 18}F-FDG (5.55 MBq/kg) and {sup 18}F-Alfatide II. Injection of {sup 18}F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. {sup 18}F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by {sup 18}F-Alfatide II PET, while only ten lesions were visualized by {sup 18}F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that {sup 18}F-Alfatide II is feasible for human studies. {sup 18}F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  7. Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

    International Nuclear Information System (INIS)

    Brown, Lindsay C.; Diehn, Felix E.; Boughey, Judy C.; Childs, Stephanie K.; Park, Sean S.; Yan, Elizabeth S.; Petersen, Ivy A.; Mutter, Robert W.

    2015-01-01

    Purpose: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. Methods and Materials: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Results: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastases were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. Conclusions: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted

  8. Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Lindsay C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Diehn, Felix E. [Department of Radiology, Mayo Clinic, Rochester, Minnesota (United States); Boughey, Judy C. [Department of Surgery, Mayo Clinic, Rochester, Minnesota (United States); Childs, Stephanie K.; Park, Sean S.; Yan, Elizabeth S.; Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Mutter, Robert W., E-mail: mutter.robert@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2015-07-01

    Purpose: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. Methods and Materials: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Results: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastases were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. Conclusions: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted.

  9. Radiotherapy of brain metastases of a breast cancer: present strategies, technological innovations and biological perspectives

    International Nuclear Information System (INIS)

    Chargari, C.; Vedrine, L.; Bauduceau, O.; Jacob, J.; Fayolle, M.; Chargari, C.; Campana, F.; Pierga, J.Y.; Idrissi, H.R.; Fourquet, A.; Kirova, Y.

    2010-01-01

    The authors propose an overview of strategies which are presently used for the treatment of brain metastases related to a breast cancer. They outline the perspectives and recent developments of encephalic irradiation with new technologies allowing an increased conformation to be obtained, and also in terms of radiosensitization and radioprotection experiences. Short communication

  10. Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases.

    Science.gov (United States)

    Wilhelm, Imola; Fazakas, Csilla; Molnár, Kinga; Végh, Attila G; Haskó, János; Krizbai, István A

    2018-04-01

    Despite the potential obstacle represented by the blood-brain barrier for extravasating malignant cells, metastases are more frequent than primary tumors in the central nervous system. Not only tightly interconnected endothelial cells can hinder metastasis formation, other cells of the brain microenvironment (like astrocytes and microglia) can also be very hostile, destroying the large majority of metastatic cells. However, malignant cells that are able to overcome these harmful mechanisms may benefit from the shielding and even support provided by cerebral endothelial cells, astrocytes and microglia, rendering the brain a sanctuary site against anti-tumor strategies. Thus, cells of the neurovascular unit have a Janus-faced attitude towards brain metastatic cells, being both destructive and protective. In this review, we present the main mechanisms of brain metastasis formation, including those involved in extravasation through the brain vasculature and survival in the cerebral environment.

  11. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

    Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

  12. Skull metastases detecting on arterial spin labeling perfusion: Three case reports and review of literature.

    Science.gov (United States)

    Ryu, Kyeong H; Baek, Hye J; Cho, Soo B; Moon, Jin I; Choi, Bo H; Park, Sung E; An, Hyo J

    2017-11-01

    Detection of skull metastases is as important as detection of brain metastases because early diagnosis of skull metastases is a crucial determinant of treatment. However, the skull can be a blind spot for assessing metastases on routine brain magnetic resonance imaging (MRI). To the best of our knowledge, the finding of skull metastases on arterial spin labeling (ASL) has not been reported. ASL is a specific MRI sequence for evaluating cerebral blood flow using magnetized endogenous inflow blood. This study uses ASL as a routine sequence of brain MRI protocol and describes 3 clinical cases of skull metastases identified by ASL. The study also highlights the clinical usefulness of ASL in detecting skull metastases. Three patients with known malignancy underwent brain MRI to evaluate for brain metastases. All of the skull metastases were conspicuously depicted on routine ASL images, and the lesions correlated well with other MRI sequences. Three patients received palliative chemotherapy. Three patients are being followed up regularly at the outpatient department. The routine use of ASL may help to detect lesions in blind spots, such as skull metastases, and to facilitate the evaluation of intracranial pathologies without the use of contrast materials in exceptional situations.

  13. Validation and predictive power of radiation therapy oncology group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06

    International Nuclear Information System (INIS)

    Scott, Charles B.; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher U.; Simpson, Joseph R.; Fischbach, A. Jennifer; Curran, Walter J.

    1996-01-01

    Background/Purpose: The recursive partitioning analysis (RPA) classes for malignant glioma patients were previously established by Curran et al. (JNCI 85:704-10, 1993) using data on over 1500 patients from the Radiation Therapy Oncology Group (RTOG). The current analysis was to validate the RPA classes on a new dataset (RTOG 90-06) and determine the predictive power of the RPA classes. Patients and Methods: There are six RPA classes for malignant glioma patients that comprise distinct groups of patients with significantly different survival outcome. RTOG 90-06 is a randomized phase III study of 712 patients accrued from 1990 to 1994. The minimum potential follow-up is 18 months. The treatment arms were combined for the purpose of this analysis. There were 84, 13, 105, 240, 150, and 23 patients in the six RPA classes from RTOG 90-06. Results: The median survival times (MST) and two-year survivals for the six RPA classes in RTOG 90-06 are compared to those published by Curran et al. (JNCI 1993). The RPA classes appear in descending order in the following table. The MST and 2-year survivals for the RTOG RPA classes were within 95% confidence intervals of the 90-06 estimates for classes I, III, IV, and V. The RPA classes explained 43% of the variation (squared error loss). By comparison, a model containing only histology explains only 13% of the variation. The RPA classes are statistically distinct with all comparisons exceeding 0.0001, except those involving class II. Conclusion: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival. Further evidence is given by prediction of MST and 2-year survival for all classes except class II. The RPA classes explained a good portion of the variation in the data. RPA class II did not perform well which may be an artifact of the small sample size or an indication that this class is not distinct. The validation of the RPA classes attests to their usefulness as

  14. Relative significance of surgery and radiotherapy in treatment of brain metastases of lung cancer

    International Nuclear Information System (INIS)

    Yamashita, Junkoh; Ohtsuka, Sinichi; Yamasaki, Toshiki; Gi, Hidefuku; Ha, Young-Soo; Handa, Hajime

    1983-01-01

    One hundred and sixteen cases of brain metastases of lung cancer were retrospectively analysed with special reference to the relative significance of surgery and radiotherapy. The median survival time from diagnosis of brain metastases was 1.2 months in 27 cases without treatment, 2.5 months in 51 cases treated by surgery alone, 4.2 months in 31 cases treated by radiotherapy alone and 6.5 months in 7 cases treated by surgery and radiotherapy. The survival rate in patients treated by radiotherapy was significantly better than in those not treated by radiotherapy. However, the effect of surgery was not significant in prolongation of survival time. On the other hand, the rate of improvement in neurological symptoms assessed at one month after the initiation of treatment was 80.9% in 47 cases treated by surgery and 19.4 % in 31 cases treated by radiotherapy. The result suggested that surgery is superior to radiotherapy in alleviating neurological symptoms. It is important to understand the nature of effect of each treatment. A better result will be anticipated by proper selection or combination of these treatments. (author)

  15. Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcsDosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs.

    Science.gov (United States)

    Liu, Haisong; Li, Jun; Pappas, Evangelos; Andrews, David; Evans, James; Werner-Wasik, Maria; Yu, Yan; Dicker, Adam; Shi, Wenyin

    2016-09-08

    An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 ± 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the

  16. Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma

    OpenAIRE

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2016-01-01

    Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China Objective: The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs) from lung adenocarcinoma.Patients and methods: Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125&am...

  17. Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

    International Nuclear Information System (INIS)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Lieberson, Robert E.; Soltys, Scott G.

    2012-01-01

    Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  18. Two unusual cases of brain metastases from lung primary malignant melanoma

    International Nuclear Information System (INIS)

    Rodríguez, A.; Mañana, G.; Panuncio, A.; Rodríguez, R.; Roldán, G.; Sosa, A.

    2004-01-01

    Start with two cases of brain metastases from lung melanoma are presented who were diagnosed in the Neuropathology Laboratory of the Department of Anatomy Pathology, Institute of Neurology, Hospital de Clinicas, Montevideo, emphasizing the pathological diagnostic criteria and their evolution clinic. Both patients presented at the time of the initial consultation injuries amelánica respectively pigmented single brain. In both cases ruled by the morphology and the use of complementary techniques metastasis carcinoma. The main differential diagnosis of these lesions is whether is a primitive brain tumor, pigmented or not, or of a secondary tumor melanin: metastatic malignant melanoma. In both cases the patients had been studied one being in an unresectable lung injury, and in the other showed a single pulmonary nodule was resected in its entirety. the pulmonary lesions were for malignant melanoma, one with ample pigment and the other for the most part amelánico, with few areas retained pigment. He studied dermatologist, discarded the presence of a cutaneous malignant melanoma primitive. Other locations were also excluded

  19. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    International Nuclear Information System (INIS)

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Rhodes, C. Harker; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    2013-01-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

  20. Stereotactic radiosurgery for brain metastasis: Pitie-Salpetriere Hospital experience

    International Nuclear Information System (INIS)

    Feuvret, L.; Germain, I.; Cornu, P.; Boisserie, G.; Dormont, D.; Hardiman, C.; Tep, B.; Faillot, T.; Duffau, H.; Simon, J.M.; Dendale, R.; Delattre, J.Y.; Poisson, M.; Marsault, C.; Philippon, J.; Fohanno, D.; Baillet, F.; Mazeron, J.J.

    1998-01-01

    Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. From january 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm 3 . The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Sixty-five metastasis were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm. (authors)

  1. Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors.

    Science.gov (United States)

    Sneed, Penny K; Mendez, Joe; Vemer-van den Hoek, Johanna G M; Seymour, Zachary A; Ma, Lijun; Molinaro, Annette M; Fogh, Shannon E; Nakamura, Jean L; McDermott, Michael W

    2015-08-01

    The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases. All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded. Brain scans and pathology reports were reviewed to ensure consistent scoring of dates of ARE, treatment failure, or both; in case of uncertainty, the cause of lesion worsening was scored as indeterminate. Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier method with censoring at last imaging. Univariate and multivariate Cox proportional hazards analyses were performed. Among 435 patients and 2200 brain metastases evaluable, the median patient survival time was 17.4 months and the median lesion imaging follow-up was 9.9 months. Calculated on the basis of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%, 1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were symptomatic and 85% occurred 3-18 months after SRS (median 7.2 months). For 99 ARE cases managed without surgery or bevacizumab, the probabilities of improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months after onset of ARE. The most important risk factors for ARE included prior SRS to the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of ARE were 2.1 cm, target volume > 1.2 cm(3), prescription isodose volume > 1.8 cm(3

  2. Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire – RTOG Modification

    Science.gov (United States)

    Pugh, Stephanie L.; Wyatt, Gwen; Wong, Raimond K. W.; Sagar, Stephen M.; Yueh, Bevan; Singh, Anurag K.; Yao, Min; Nguyen-Tan, Phuc Felix; Yom, Sue S.; Cardinale, Francis S.; Sultanem, Khalil; Hodson, D. Ian; Krempl, Greg A.; Chavez, Ariel; Yeh, Alexander M.; Bruner, Deborah W.

    2016-01-01

    Context The 15-item University of Washington Quality of Life questionnaire – Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537. Objectives This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales. Methods EFA on the UW-QOL - RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach's α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS) was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability. Results The 15-item EFA of the modified tool resulted in 11 items split into 4 factors: mucus, eating, pain, and activities. Cronbach's α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ≥0.60) between consecutive time points and between total score and the XeQOLS total score (ρ>0.65). Conclusion The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items. PMID:27899312

  3. A Phase 2 Trial of Stereotactic Radiosurgery Boost After Surgical Resection for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, Cameron [Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yang, T. Jonathan [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hilden, Patrick; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Kelvin; Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lymberis, Stella C. [Department of Radiation Oncology, New York University Langone Medical Center, New York, New York (United States); Narayana, Ashwatha [Department of Radiation Oncology, Greenwich Hospital, Greenwich, Connecticut (United States); Tabar, Viviane; Gutin, Philip H. [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ballangrud, Åse [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn, E-mail: BealK@MSKCC.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-01-01

    Purpose: To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age ≥18 years, and Karnofsky performance status (KPS) ≥70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). Results: The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF (P=.008). Other factors associated with improved local control include non-small cell lung cancer histology (P=.048), tumor diameter <3 cm (P=.010), and deep parenchymal tumors (P=.036). Large tumors (≥3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions (P<.001). Conclusions: Postoperative SRS is associated with high rates of local control, especially for deep brain metastases <3 cm. Tumors ≥3 cm with superficial dural

  4. Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control

    International Nuclear Information System (INIS)

    Shiau, C.-Y.; Sneed, Penny K.; Shu, H.-K.G.; Lamborn, Kathleen R.; McDermott, Michael W.; Chang, Susan; Nowak, Peter; Petti, Paula L.; Smith, Vernon; Verhey, Lynn J.; Ho, Maria; Park, Elaine; Wara, William M.; Gutin, Philip H.; Larson, David A.

    1997-01-01

    Purpose: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). Methods and Materials: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. Results: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving ≥ 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). Conclusion: A minimum prescribed radiosurgical dose ≥ 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a

  5. Gamma knife radiosurgery for ten or more brain metastases. Analysis of the whole brain irradiation doses

    International Nuclear Information System (INIS)

    Nakaya, Kotaro; Hori, Tomokatsu; Izawa, Masahiro; Yamamoto, Masaaki

    2002-01-01

    Gamma knife (GK) radiosurgery has recently been recognized as the most powerful treatment modality in managing patients with brain metastasis, be they radioresistant or not, solitary or multiple. Very recently, this treatment has been employed in patients with numerous brain metastases, even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain, with such treatment, remain unknown. Since the Gamma Plan ver. 5.10 (ver. 5.30 is presently available, Leksell Gamma Plan) became available in November, 1998, 105 GK procedures have been performed at our two facilities, Tokyo Women's Medical University and Katsuta Hospital Mito Gamma House. The median lesion number was 17, ranging 10-43, and the median cumulative volume of all tumors was 8.72 cm 3 , ranging 0.41-81.41 cm 3 . The selected doses at the lesion periphery ranged 12-25 Gy, the median being 20 Gy. Based on these treatment protocols, the cumulative irradiation dose was computed. The median cumulative irradiation dose to the whole brain was 4.83, ranging 2.16-8.51 Gy: the median integrated dose to the whole brain was 6.2 J, ranging 2.16-11.9 J. The median brain volumes receiving ≥2, ≥5, ≥10, ≥15 and ≥20 Gy were 1105 (range: 410-1501), 309 (46-1247), 64 (13-282), 24 (2-77), and 8 (0-40) cm 3 , respectively. The cumulative whole brain irradiation doses for patients with numerous radiosurgical targets were considered not to exceed the threshold level of normal brain necrosis. (author)

  6. (64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients.

    Science.gov (United States)

    Kurihara, Hiroaki; Hamada, Akinobu; Yoshida, Masayuki; Shimma, Schuichi; Hashimoto, Jun; Yonemori, Kan; Tani, Hitomi; Miyakita, Yasuji; Kanayama, Yousuke; Wada, Yasuhiro; Kodaira, Makoto; Yunokawa, Mayu; Yamamoto, Harukaze; Shimizu, Chikako; Takahashi, Kazuhiro; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro; Tamura, Kenji

    2015-01-01

    The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. PET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity in metastatic brain tumors was evaluated based on PET images in five patients. Autoradiography, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab. Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in all of five cases, which might indicated that trastuzumab passes through the blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was demonstrated in one patient by autoradiography, immunohistochemistry, and LC-MS/MS. Cu-DOTA-trastuzumab PET could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer. UMIN000004170.

  7. Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study.

    Science.gov (United States)

    Ortiz-Ramón, Rafael; Larroza, Andrés; Ruiz-España, Silvia; Arana, Estanislao; Moratal, David

    2018-05-14

    To examine the capability of MRI texture analysis to differentiate the primary site of origin of brain metastases following a radiomics approach. Sixty-seven untreated brain metastases (BM) were found in 3D T1-weighted MRI of 38 patients with cancer: 27 from lung cancer, 23 from melanoma and 17 from breast cancer. These lesions were segmented in 2D and 3D to compare the discriminative power of 2D and 3D texture features. The images were quantized using different number of gray-levels to test the influence of quantization. Forty-three rotation-invariant texture features were examined. Feature selection and random forest classification were implemented within a nested cross-validation structure. Classification was evaluated with the area under receiver operating characteristic curve (AUC) considering two strategies: multiclass and one-versus-one. In the multiclass approach, 3D texture features were more discriminative than 2D features. The best results were achieved for images quantized with 32 gray-levels (AUC = 0.873 ± 0.064) using the top four features provided by the feature selection method based on the p-value. In the one-versus-one approach, high accuracy was obtained when differentiating lung cancer BM from breast cancer BM (four features, AUC = 0.963 ± 0.054) and melanoma BM (eight features, AUC = 0.936 ± 0.070) using the optimal dataset (3D features, 32 gray-levels). Classification of breast cancer and melanoma BM was unsatisfactory (AUC = 0.607 ± 0.180). Volumetric MRI texture features can be useful to differentiate brain metastases from different primary cancers after quantizing the images with the proper number of gray-levels. • Texture analysis is a promising source of biomarkers for classifying brain neoplasms. • MRI texture features of brain metastases could help identifying the primary cancer. • Volumetric texture features are more discriminative than traditional 2D texture features.

  8. Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

    Science.gov (United States)

    Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

    2015-07-10

    Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

  9. Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lind, Joline S.W.; Lagerwaard, Frank J.; Smit, Egbert F.; Senan, Suresh

    2009-01-01

    Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

  10. A phase I/II study to evaluate the effect of fractionated hemibody irradiation in the treatment of osseous metastases--RTOG 88-22

    International Nuclear Information System (INIS)

    Scarantino, C.W.; Caplan, R.; Rotman, M.; Coughlin, C.; Demas, W.; Delrowe, J.

    1996-01-01

    Purpose: The present study was initiated to determine the maximum tolerated total dose that can be delivered by fractionated hemibody irradiation (HBI), as defined by the acute hematological and non hematological toxicity. Although it was designed as a dose searching trial, the influence of higher doses on occult and overt disease were considered equally important. The study was not designed to evaluate pain relief. The results were compared to Radiation Therapy Oncology Group (RTOG) 82-06, which employed single high-dose HBI, to determine if either single or fractionated HBI is more effective in controlling occult or overt disease. Methods and Materials: A total of 144 patients were entered from September 1989 to April 1993. Only patients with a single symptomatic bone metastases from either prostate or breast cancer primaries and a KPS ≥ 60 were eligible. All patients initially received 30.0 Gy in 10 fractions to the symptomatic area followed by HBI in 2.50 Gy fractions to one of five arms: I--10.0 Gy (37 patients); II--12.5 Gy (23 patients); III--15.0 Gy (18 patients); IV--17.5 Gy (40 patients), and V--20.0 Gy (26 patients). A dose limiting toxicity was defined as an observed toxicity of ≥ Grade 3 lasting more than 30 days post completion of HBI. If three or more dose-limiting toxicities occurred at any dose level, the previous dose was considered as the maximum tolerable dose. Results: Thirty-six of 142 patients experienced ≥ Grade 3 hematological toxicity at some time following HBI. The distribution of dose-limiting hematological toxicity in each arm was: I--two patients; II--one patient; III--zero patients; IV--one patient; and V--three patients. The major non hematological toxicity was gastrointestinal and occurred in 10 patients. None were dose limiting. At 12 months from the initiation of treatment, the percent of patients with new disease were: Arms I--19%; II-9%; III-17%; IV--19%; V--13%; the percent of patients requiring additional treatment in

  11. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data

    Directory of Open Access Journals (Sweden)

    Fan Y

    2014-11-01

    Full Text Available Yun Fan,1,2 Xiaoling Xu,3 Conghua Xie4 1Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People's Republic of China; 2Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 3Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 4Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People’s Republic of China Introduction: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC. The use of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods: Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR, disease control rate (DCR, progression-free survival (PFS, overall survival (OS, and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results: Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group, and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8% and 75.7% (95% CI: 70.3%–80.5%, respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%; a similar trend was observed for the DCR (94.6% vs 71.3%. The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9 and 11.9 months (95% CI, 7.7–16.2, respectively, with longer PFS (12.3 months vs 5.9 months and OS (16.2 months vs

  12. Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2015-06-01

    Full Text Available OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB, which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2 were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105 across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05; interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001. Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05 in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

  13. Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

    Directory of Open Access Journals (Sweden)

    Andreas M. Stark

    2011-01-01

    Full Text Available Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

  14. Neurosurgical treatment of breast cancer metastases to the neurocranium.

    Science.gov (United States)

    Stark, Andreas M

    2010-12-16

    Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4-11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

  15. A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

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    Caravatta, Luciana; Deodato, Francesco; Ferro, Marica [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Massaccesi, Mariangela [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Cilla, Savino [Medical Physics Unit, Fondazione di Ricerca e Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Padula, Gilbert D.A. [Department of Radiation Oncology, The Lacks Cancer Center Saint Mary' s Health Care, Grand Rapids, Michigan (United States); Mignogna, Samantha; Tambaro, Rosa [Department of Palliative Therapies, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Carrozza, Francesco [Department of Oncology, A. Cardarelli Hospital, Campobasso (Italy); Flocco, Mariano [Madre Teresa di Calcutta Hospice, Larino (Italy); Cantore, Giampaolo [Department of Neurological Sciences, Istituto Neurologico Mediterraneo Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, Pozzilli (Italy); Scapati, Andrea [Department of Radiation Oncology, ' San Francesco' Hospital, Nuoro (Italy); Buwenge, Milly [Department of Radiotherapy, Mulago Hospital, Kampala (Uganda); and others

    2012-11-15

    Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

  16. Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

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    Yamamoto, Masaaki, E-mail: BCD06275@nifty.com [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Tokyo Women' s Medical University Medical Center East, Tokyo (Japan); Kawabe, Takuya [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto (Japan); Higuchi, Yoshinori [Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba (Japan); Sato, Yasunori [Clinical Research Center, Chiba University Graduate School of Medicine, Chiba (Japan); Nariai, Tadashi [Department of Neurosurgery, Graduate School, Tokyo Medical and Dental University School of Medicine, Tokyo (Japan); Barfod, Bierta E. [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Kasuya, Hidetoshi [Department of Neurosurgery, Tokyo Women' s Medical University Medical Center East, Tokyo (Japan); Urakawa, Yoichi [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan)

    2013-01-01

    Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume {<=}10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases

  17. Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases. Plan comparison and early clinical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Rieber, J.; Tonndorf-Martini, E.; Schramm, O.; Rhein, B.; Stefanowicz, S.; Lindel, K.; Debus, J.; Rieken, S. [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology, Heidelberg (Germany); Kappes, J. [Heidelberg University, Translational Research Unit, Thoraxklinik, Heidelberg (Germany); Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); Member of the German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Hoffmann, H. [Heidelberg University, Translational Research Unit, Thoraxklinik, Heidelberg (Germany); Heidelberg University, Department of Thoracic Surgery, Thoraxklinik, Heidelberg (Germany); Member of the German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany)

    2016-11-15

    Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 x 20 Gy or 1 x 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 x 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6-month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity. (orig.) [German] Die radiochirurgische Behandlung (SRS) von Hirnmetastasen wird vielfach in der klinischen Routine durchgefuehrt. Die zusaetzliche Anwendung von ausgleichsfilterfreien Bestrahlungstechniken (FFF) kann die Bestrahlungszeit

  18. A Simple and Efficient Methodology To Improve Geometric Accuracy in Gamma Knife Radiation Surgery: Implementation in Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Karaiskos, Pantelis, E-mail: pkaraisk@med.uoa.gr [Medical Physics Laboratory, Medical School, University of Athens (Greece); Gamma Knife Department, Hygeia Hospital, Athens (Greece); Moutsatsos, Argyris; Pappas, Eleftherios; Georgiou, Evangelos [Medical Physics Laboratory, Medical School, University of Athens (Greece); Roussakis, Arkadios [CT and MRI Department, Hygeia Hospital, Athens (Greece); Torrens, Michael [Gamma Knife Department, Hygeia Hospital, Athens (Greece); Seimenis, Ioannis [Medical Physics Laboratory, Medical School, Democritus University of Thrace, Alexandroupolis (Greece)

    2014-12-01

    Purpose: To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. Methods and Materials: The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, “average” image data are compounded from data acquired from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (<2 cm) metastases treated with GK radiation surgery. Results: Phantom study results showed that use of average MR images eliminates the effect of sequence-dependent distortions, leading to a total spatial uncertainty of less than 0.3 mm, attributed mainly to gradient nonlinearities. In brain metastases patients, non-eliminated sequence-dependent distortions lead to target localization uncertainties of up to 1.3 mm (mean: 0.51 ± 0.37 mm) with respect to the corresponding target locations in the “average” MRI series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. Conclusions: The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets.

  19. Lymphopenia: A new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma

    International Nuclear Information System (INIS)

    Claude, Line; Perol, David; Ray-Coquard, Isabelle; Petit, Thierry; Blay, Jean-Yves; Carrie, Christian; Bachelot, Thomas

    2005-01-01

    Background and purpose: To determine overall survival (OS) and independent prognostic factors in patients with brain metastases (BM) from breast cancer treated by whole brain radiotherapy (WBR). Patients and methods: One hundred and twenty (120) women with BM, treated in a single French cancer center between 02/91 and 06/01, were reviewed. BM were confirmed by computed tomography or magnetic resonance imaging. Survival time was defined as the time interval from the date of BM to the date of death or last follow-up. A Cox proportional hazards regression model was used to determine significant prognostic factors in a multivariate analysis. Results: Surgery was followed by WBR in 5 patients. One hundred and four (104) patients received exclusive WBR, eight received concomitant chemo-radiation, and one received chemo-radiation after surgery. The median survival time was 5 months (95% CI: 3-7 months). In the multivariate analysis, performance status over 1 and lymphopenia (<0.7 G/L) were found to be independent prognostic factors for poor survival. Based on the number of these independent prognostic factors, we propose a predictive model for survival in brain metastatic cancer patients. Median survival was 7 months for patients presenting none or one poor prognosis factor at diagnosis versus 2 months for patients with 2 poor prognosis factors (p<0.0001) Conclusion: Brain metastases from breast cancer remain associated with very poor prognosis and there is a need for better treatment procedures. If confirmed in predictive models, the identification of prognostic subgroups, based on KPS and lymphopenia, among patients with BM from breast cancer would help physicians select patients for future clinical trials

  20. Intracranial metastases: spectrum of MR imaging findings

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    Lee, Eun Kyoung; Lee, Eun Ja; Lee, Yong Seok [Department of Radiology, Dongguk University Ilsan Hospital, Goyang-shi (Korea, Republic of)], E-mail: ejl1048@hanmail.net; Kim, Mi Sung; Park, No Hyuck [Department of Radiology, Kwandong University, College of Medicine, Myongji Hospital, Goyang-shi (Korea, Republic of); Park, Hee-Jin [Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); II, Sung Park [Department of Diagnostic Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2012-12-15

    Intracranial metastatic lesions arise through a number of routes. Therefore, they can involve any part of the central nervous system and their imaging appearances vary. Magnetic resonance imaging (MRI) plays a key role in lesion detection, lesion delineation, and differentiation of metastases from other intracranial disease processes. This article is a reasoned pictorial review illustrating the many faces of intracranial metastatic lesions based on the location - intra-axial metastases, calvarial metastases, dural metastases, leptomeningeal metastases, secondary invasion of the meninges by metastatic disease involving the calvarium and skull base, direct or perineural intracranial extension of head and neck neoplasm, and other unusual manifestations of intracranial metastases. We also review the role of advanced MRI to distinguish metastases from high-grade gliomas, tumor-mimicking lesions such as brain abscesses, and delayed post-radiation changes in radiosurgically treated patients.

  1. Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy.

    Science.gov (United States)

    Naddaf, Sleiman Y; Syed, Ghulam Mustafa Shah; Hadb, Abdulrahman; Al-Thaqfi, Saif

    2016-09-01

    We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs.

  2. OS03.4 Gammaknife versus Linac based (EDGE) radiosurgery (SRS) for patients with limited brain metastases (BMS) from different solid tumor: a phase III randomized trial.

    Science.gov (United States)

    Scorsetti, M.; Navarria, P.; Ascolese, A.; Clerici, E.; Mancosu, P.; Picozzi, P.; Pecchioli, G.; Franzese, C.; Reggiori, G.; Tomatis, S.

    2017-01-01

    Abstract Introduction: Radiosurgery is an emerging terapeutich approach for the treatment of brain metastases (BMs), considering the effective local control obtained without neurological impairment. Different technological modalities have been used: Gammaknife, Cybernife, or Linac with comparable results and different incidence of symptomatic radionecrosis. To date no comparative randomized studies have been published on this matter. We draw this randomized phase III trial with the aim to evaluate incidence of symptomatic radionecrosis using gamma knife radiosurgery versus linac based (EDGE) radiosurgery. Local control (LC) rate and patients overall survival (OS) were assessed as well. Materials: Patients with limited BMs (up to 4) from different solid tumors, except SCLC or hematologic malignancies, were enrolled. Inclusion criteria were a histopatological diagnosis of malignant primary tumor, a KPS ≥70, RPA class I-II, and BMs with maximum diameter ≤3 cm and/or with a total tumor volume <30 cm3. The total dose prescribed was 24 Gy for BMs ≤ 20 mm or 4.2 cm3, and 20 Gy for BMs 21–30 mm or volume <14.1 cm3 as suggested by RTOG guidelines. Clinical outcome was evaluated by neurological examination and MRI at 2 months after SRS and then every 3 months. The radionecrosis was considered the presence of central hypodensity and peripheral enhancement on T1-weighted post-contrast imaging, with edema on T2-weighted sequences and a clear lack of perfusion without any nodular highly vascularized area within the contrast enhanced lesion on perfusion MRI. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume on serial MR imaging, and distant failure by the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Results: From October 2014 to December 2015, 101 consecutives patients of the expected 250, for 167 BMs treated, were evaluated. The most common primary

  3. Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence.

    Science.gov (United States)

    Zakaria, Rasheed; Pomschar, Andreas; Jenkinson, Michael D; Tonn, Jörg-Christian; Belka, Claus; Ertl-Wagner, Birgit; Niyazi, Maximilian

    2017-02-01

    Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = -0.45, p = 0.653) but showed differing conformations (CI 0.53, p recurrence than the standard plan (median 3.53 cm 3 vs. 3.84 cm 3 , p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning.

  4. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases.

    Science.gov (United States)

    Magnuson, William J; Yeung, Jacky T; Guillod, Paul D; Gettinger, Scott N; Yu, James B; Chiang, Veronica L

    2016-06-01

    To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases (BM) to evaluate our hypothesis that the use of upfront EGFR-tyrosine kinase inhibitors (TKIs), and deferral of radiation therapy (RT), would result in inferior intracranial progression-free survival but similar overall survival (OS). Of 202 patients diagnosed with EGFR-mutant NSCLC between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS) or develop brain metastases. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI with RT at intracranial progression versus upfront RT followed by EGFR-TKI is urgently needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. "Term delivery following successful treatment of choriocarcinoma with brain metastases, (a case report"

    Directory of Open Access Journals (Sweden)

    F. Behnamfar

    2006-08-01

    Full Text Available Background: Cerebral metastases from choriocarcinoma are poor prognostic indicator of outcome in both the World Health Organization and FIGO classification systems. Although gestational trophoblastic neoplasia has become the most curable gynecological malignancy, failure rate among “high-risk” patients is still high despite the use of aggressive multidrug regimens. case: A 27 year old woman (G4P2Ab1 presented with hemiplegia due to brain metastases of choriocarcinoma one year after spontaneous abortion. She underwent craniotomy and was treated with nine courses of multiple agent etoposide, methotrexate, actinomycin-etoposide and cisplatinum (EMA-EP regimen combined with whole brain irradiation. She delivered a term healthy child two years after termination of treatment. Conclusion: Multiagent EMA-EP chemotherapy and whole brain irradiation with craniotomy in selected patients preserves fertility and may improve a patient overall prognosis. Methods: In a descriptive study from February to April 2005, two hundred sixty six consecutive pregnant women referring to a university hospital were asked to answer a questionnaire containing questions their sexual status and some demographic data. In 122 cases the answers of the spouses was collected also. The answers were compared in divided groups according to age range, duration of marriage, parity and educational status. Results: Fifty five percent of men and fifty eight percent of women had a negative attitude about sexual relations during pregnancy, and 60% of men and 75% of women presented incorrect knowledge about sexuality during pregnancy. Main reasons for decreased sexual relations in pregnancy were mentioned to be dysparaunia, and the fear of trauma to the baby, abortion, membrane rapture, preterm labor and infection. Conclusion: As couples’ knowledge and attitudes about sexuality affect their general sexual behavior during pregnancy it is crucial to provide proper consultation regarding

  6. Managing brain metastases patients with and without radiotherapy: initial lessonsfrom a team-based consult service through a multidisciplinary integrated palliative oncology clinic.

    Science.gov (United States)

    Jung, Hellen; Sinnarajah, Aynharan; Enns, Bert; Voroney, Jon-Paul; Murray, Alison; Pelletier, Guy; Wu, Jackson Sai-Yiu

    2013-12-01

    A new ambulatory consultative clinic with integrated assessments by palliative care, radiation oncology, and allied health professionals was introduced to (1) assess patients with brain metastases at a regional comprehensive cancer center and (2) inform and guide patients on management strategies, including palliative radiotherapy, symptom control, and end-of-life care issues. We conducted a quality assurance study to inform clinical program development. Between January 2011 and May 2012, 100 consecutive brain metastases patients referred and assessed through a multidisciplinary clinic were evaluated for baseline characteristics, radiotherapy use, and supportive care decisions. Overall survival was examined by known prognostic groups. Proportion of patients receiving end-of-life radiotherapy (death within 30 and 14 days of brain radiotherapy) was used as a quality metric. The median age was 65 years, with non-small cell lung cancer (n = 38) and breast cancer (n = 23) being the most common primary cancers. At least 57 patients were engaged in advance care planning discussions at first consult visit. In total, 75 patients eventually underwent brain radiotherapy, whereas 25 did not. The most common reasons for nonradiotherapy management were patient preference and rapid clinical deterioration. Overall survival for prognostic subgroups was consistent with literature reports. End-of-life brain radiotherapy was observed in 9 % (death within 30 days) and 1 % (within 14 days) of treated patients. By integrating palliative care expertise to address the complex needs of patients with newly diagnosed brain metastases, end-of-life radiotherapy use appears acceptable and improved over historical rates at our institution. An appreciable proportion of patients are not suitable for palliative brain radiotherapy or opt against this treatment option, but the team approach involving nurses, palliative care experts, allied health, and clinical oncologists facilitates

  7. Radiation-induced dementia in patients cured of brain metastases

    International Nuclear Information System (INIS)

    DeAngelis, L.M.; Delattre, J.Y.; Posner, J.B.

    1989-01-01

    When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review

  8. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

    2011-01-01

    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

  9. A cost-effectiveness and cost-utility analysis of radiosurgery vs. resection for single-brain metastases

    International Nuclear Information System (INIS)

    Mehta, Minesh; Noyes, William; Craig, Bruce; Lamond, John; Auchter, Richard; French, Molly; Johnson, Mark; Levin, Allan; Badie, Behnam; Robbins, Ian; Kinsella, Timothy

    1997-01-01

    Purpose: The median survival of well-selected patients with single-brain metastases treated with whole-brain irradiation and resection or radiosurgery is comparable, although a randomized trial of these two modalities has not been performed. In this era of cost containment, it is imperative that health-care professionals make fiscally prudent decisions. The present environment necessitates a critical appraisal of apparently equi-efficacious therapeutic modalities, and it is within this context that we present a comparison of the actual costs of resection and radiosurgery for brain metastases. Methods and Materials: Survival and quality of life outcome data for radiation alone or with surgery were obtained from two randomized trials, and radiosurgical results were obtained from a multiinstitutional analysis that specifically evaluated patients meeting surgical criteria. Only linear accelerator radiosurgery data were considered. Cost analysis was performed from a societal view point, and the following parameters were evaluated: actual cost, cost ratios, cost effectiveness, incremental cost effectiveness, cost utility, incremental cost utility, and national cost burden. The computerized billing records for all patients undergoing resection or radiosurgery for single-brain metastases from January 1989 to July 1994 were reviewed. A total of 46 resections and 135 radiosurgery procedures were performed. During the same time period, 454 patients underwent whole-brain radiation alone. An analysis of the entire bill was performed for each procedure, and each itemized cost was assigned a proportionate figure. The relative cost ratios of resection and radiosurgery were compared using the Wilcoxon rank sum test. Cost effectiveness of each modality, defined as the cost per year of median survival, was evaluated. Incremental cost effectiveness, defined as the additional cost per year of incremental gain in median survival, compared to the next least expensive modality, was also

  10. Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

    International Nuclear Information System (INIS)

    Mehta, Minesh P.; Shapiro, William R.; Phan, See C.; Gervais, Radj; Carrie, Christian; Chabot, Pierre; Patchell, Roy A.; Glantz, Michael J.; Recht, Lawrence; Langer, Corey; Sur, Ranjan K.; Roa, Wilson H.; Mahe, Marc A.; Fortin, Andre; Nieder, Carsten; Meyers, Christina A.; Smith, Jennifer A.; Miller, Richard A.; Renschler, Markus F.

    2009-01-01

    Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable

  11. Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

    Directory of Open Access Journals (Sweden)

    Wen-Chih Liu

    2012-05-01

    Full Text Available A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

  12. SU-F-T-616: Comparison of Different Techniques Using RTOG0631 Guidelines in Spine SBRT

    International Nuclear Information System (INIS)

    Acar, H; Cebe, M; Mabhouti, H; Codel, G; Pacaci, P; Serin, E; Sanli, E; Kucuk, N; Kucukmorkoc, E; Doyuran, M; Canoglu, D; Altinok, A; Caglar, H

    2016-01-01

    Purpose: Stereotactic body radiosurgery (SBRT) for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to investigate a Hybrid VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for spine SBRT in terms of its dosimetric quality and treatment efficiency using Radiation Therapy Oncology Group (RTOG) 0631 guidelines. Methods: 7 fields IMRT, 2 full arcs VMAT and Hybrid VMAT/IMRT were created for ten previously treated patients. The Hybrid VMAT/IMRT technique consisted of 1 full VMAT arc and 5 IMRT fields. Hybrid VMAT/IMRT plans were compared with IMRT and VMAT plans in terms of the dose distribution, spinal cord sparing, homogeneity, conformity and gradient indexies, monitor unit (MU) and beam on time (BOT). RTOG 0631 recommendations were applied for treatment planning. All plans were normalized and prescribed to deliver 18.0 Gy in a single fraction to 90% of the target volume. Results: The Hybrid VMAT/IMRT technique significantly improved target dose homogeneity and conformity compared with IMRT and VMAT techniques. Providing sharp dose gradient Hybrid VMAT/IMRT plans spare the spinal cord and healthy tissue more effectively. Although, both MU and BOT slightly increased in Hybrid VMAT/IMRT plans there is no statistically meaningful difference between VMAT and Hybrid VMAT/IMRT plans. Conclusion: In IMRT, a smaller volume of healthy tissue can be irradiated in the low dose region, VMAT plans provide better target volume coverage, favorable dose gradient, conformity and better OAR sparing and also they require a much smaller number of MUs and thus a shorter treatment time than IMRT plans. Hybrid plan offers a sinergy through combination of these two techniques with slightly increased number of MU and thus more treatment time.

  13. SU-F-T-616: Comparison of Different Techniques Using RTOG0631 Guidelines in Spine SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Acar, H; Cebe, M; Mabhouti, H; Codel, G; Pacaci, P; Serin, E; Sanli, E; Kucuk, N; Kucukmorkoc, E; Doyuran, M; Canoglu, D; Altinok, A; Caglar, H [Ozkok Medipol University, Istanbul, Istanbul (Turkey)

    2016-06-15

    Purpose: Stereotactic body radiosurgery (SBRT) for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to investigate a Hybrid VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for spine SBRT in terms of its dosimetric quality and treatment efficiency using Radiation Therapy Oncology Group (RTOG) 0631 guidelines. Methods: 7 fields IMRT, 2 full arcs VMAT and Hybrid VMAT/IMRT were created for ten previously treated patients. The Hybrid VMAT/IMRT technique consisted of 1 full VMAT arc and 5 IMRT fields. Hybrid VMAT/IMRT plans were compared with IMRT and VMAT plans in terms of the dose distribution, spinal cord sparing, homogeneity, conformity and gradient indexies, monitor unit (MU) and beam on time (BOT). RTOG 0631 recommendations were applied for treatment planning. All plans were normalized and prescribed to deliver 18.0 Gy in a single fraction to 90% of the target volume. Results: The Hybrid VMAT/IMRT technique significantly improved target dose homogeneity and conformity compared with IMRT and VMAT techniques. Providing sharp dose gradient Hybrid VMAT/IMRT plans spare the spinal cord and healthy tissue more effectively. Although, both MU and BOT slightly increased in Hybrid VMAT/IMRT plans there is no statistically meaningful difference between VMAT and Hybrid VMAT/IMRT plans. Conclusion: In IMRT, a smaller volume of healthy tissue can be irradiated in the low dose region, VMAT plans provide better target volume coverage, favorable dose gradient, conformity and better OAR sparing and also they require a much smaller number of MUs and thus a shorter treatment time than IMRT plans. Hybrid plan offers a sinergy through combination of these two techniques with slightly increased number of MU and thus more treatment time.

  14. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases

    Science.gov (United States)

    Brown, Paul D.; Jaeckle, Kurt; Ballman, Karla V.; Farace, Elana; Cerhan, Jane H.; Anderson, S. Keith; Carrero, Xiomara W.; Barker, Fred G.; Deming, Richard; Burri, Stuart H.; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W.; Pollock, Bruce E.; Galanis, Evanthia; Buckner, Jan C.; Asher, Anthony L.

    2017-01-01

    IMPORTANCE Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, −28.2%; 90% CI, −41.9% to −14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, −0.1 vs −12.0 points; mean difference, 11.9; 95% CI, 4.8–19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2–5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, −1.5 points for SRS alone vs −4

  15. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Rades, Dirk; Nadrowitz, Roger; Buchmann, Inga; Meller, Birgit; Hunold, Peter; Noack, Frank; Schild, Steven E.

    2010-01-01

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m 2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m 2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m 2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ( 123 I-Erbi) on scintigraphy; 123 I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  16. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk; Nadrowitz, Roger [Dept. of Radiation Oncology, Univ. of Luebeck (Germany); Buchmann, Inga; Meller, Birgit [Section of Nuclear Medicine, Univ. of Luebeck (Germany); Hunold, Peter [Dept. of Radiology, Univ. of Luebeck (Germany); Noack, Frank [Inst. of Pathology, Univ. of Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2010-08-15

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m{sup 2} cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m{sup 2} cetuximab (cold antibody) were given. Weekly doses of 250 mg/m{sup 2} cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ({sup 123}I-Erbi) on scintigraphy; {sup 123}I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  17. Efficacy and adverse effects of icotinib in treatment of 30 NSCLC patients with brain metastases

    Directory of Open Access Journals (Sweden)

    Yu-hong DAI

    2016-06-01

    Full Text Available Objective  To evaluate the efficacy and adverse effects of icotinib in the treatment for non-small cell lung cancer (NSCLC patients with brain metastases. Methods  This study was performed at Tongji Hospital Cancer Center over the period between September 2011 and November 2015. Thirty cases of advanced NSCLC patients with icotinib monotherapy were enrolled, all with brain metastases, the median follow-up time being 24 months (5.5-49.0 months, with no case censored. The follow-up rate was 100%, and the data of efficacy and adverse effects were collected. Results  The intracranial progression-free survival (iPFS was 9.6 months, while no patient exhibited complete remission (CR, 8 patients showed partial remission (PR and 14 showed stable disease (SD in the intracranial foci. The intracranial disease control rate (DCR was 73.3%, and the objective remission rate (ORR was 26.7%. The extracranial progression-free survival (ePFS was 10.1 months, while no patient exhibited CR, 11 patients showed PR and 11 patients showed SD in the extracranial foci. The extracranial DCR was 73.3%, and the ORR was 36.7%. The one-year survival rate was 63.8% in all the 30 patients. Twelve (40.0% of the total 30 patients developed rash, five (16.7% developed grade 1 diarrhea, one (3.3% developed grade 2 transaminase elevation. None of the patients experienced headache, nausea, vomiting, fatigue, etc. Conclusion  Icotinib hydrochloride is effective and safe for NSCLC patients with brain metastasis. DOI: 10.11855/j.issn.0577-7402.2016.06.11

  18. Effects of radiotherapy for brain metastases on quality of life (QoL). Prospective pilot study of the DEGRO QoL working party

    Energy Technology Data Exchange (ETDEWEB)

    Steinmann, Diana; Bruns, Frank [Medical School, Hannover (Germany). Radiation Oncology; Schaefer, Christof; Hipp, Matthias [Regensburg Univ. (Germany). Radiation Oncology; Oorschot, Birgitt van [Wuerzburg Univ. (Germany). Radiation Oncology; Wypior, Hans-Joachim [Hospital Landshut (Germany). Radiation Oncology; Boelling, Tobias [Muenster Univ. (Germany). Radiation Oncology; Sehlen, Susanne [Ludwig Maximilians Univ., Muenchen (Germany). Radiation Oncology; Hagg, Juliane [Ulm Univ. (Germany). Radiation Oncology; Bayerl, Anja [Hospital Krems (Austria). Radiation Oncology; Geinitz, Hans [Technical Univ. Muenchen (Germany). Radiation Oncology; Vordermark, Dirk [Halle-Wittenberg Univ., Halle (Germany). Radiation Oncology

    2009-03-15

    Background: Prospective data on quality-of-life (QoL) effects of radiotherapy for brain metastases are currently lacking, but would be of great interest to guide therapeutic decisions. Patients and Methods: From 01/2007 to 08/2007, 46 patients with previously untreated brain metastases were recruited at eight centers. QoL was measured at start of treatment (T{sub 0}) and at 3 months ({sub T3mo}). In the pilot study, two combinations of QoL instruments could be used at the discretion of the centers (A: EORTC QLQ-C30 and B: EORTC QLQ-C15-PAL both with brain module BN20, assessment by proxies with A: Palliative Care Outcome Scale, B: self-constructed brain-specific instrument). Results: All patients received whole-brain radiotherapy, four with an additional boost irradiation. At T{sub 3mo}, 26/46 patients (56.5%) had died. 17/20 survivors (85%) completed the questionnaires. In 3-month survivors, QoL deteriorated in most domains, significant in drowsiness, hair loss and weakness of legs. The scores for headaches and seizures were slightly better after 3 months. Assessment by proxies also suggested worsening of QoL. Initial QoL at T{sub 0} was better in those alive than in those deceased at T{sub 3mo}, significant for physical function and for the symptom scales of fatigue and pain, motor dysfunction, communication deficit and weakness of legs. Conclusion: Practicability and compliance appeared better with the (shorter) version B. This version is now used in the ongoing main phase of the study with additional centers. First results indicate a moderate worsening of QoL during the first 3 months after start of palliative radiotherapy for brain metastases. QoL at initiation of radiotherapy may be prognostic for survival. (orig.)

  19. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

    Directory of Open Access Journals (Sweden)

    Anja Kafka

    2014-06-01

    Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  20. Metastases cerebrales d'un cancer de l'endometre: a propos d'une ...

    African Journals Online (AJOL)

    Mots clés: cancer, endomètre, métastases, cerveau, Lomé, Togo. English Title: Brain metastases of endometrial cancer: an observation at Lome and literature review. English Abstract. Introduction: document the clinical, paraclinical, therapeutic and prognostic of brain metastases of endometrial cancer in hospital in Togo.

  1. Skin metastases from lung cancer: a case report.

    Science.gov (United States)

    Pajaziti, Laura; Hapçiu, Syzana Rexhepi; Dobruna, Shkendije; Hoxha, Naim; Kurshumliu, Fisnik; Pajaziti, Artina

    2015-04-11

    Lung cancer is one of the most frequent malignancies, with high mortality rates. It can metastasize in almost all organs, but more often invades hilar nodes, liver, adrenal glands, bones and brain. There are various data on the incidence of lung cancer metastases in the skin. In 1-12% of patients with lung cancer are developed skin metastases. Metastases in the skin may be the first sign of lung cancer. Forty-five years old Albanian male, smoker, was admitted to our department with multiple nodules localized in the skin of the head, neck, back and chest. The nodules measuring 5-15 millimeters in greatest dimension were round and skin-colored, with telangiectasias, firm and tender. They appeared in an eruptive form about two weeks before being admitted at our hospital. In addition, the patient exhibited signs of weight loss, anorexia and fatigue. Excisional biopsy was performed to one of the lesions. Histopathology confirmed metastatic nature of the lesion namely, malignant tumor of neuroendocrine phenotype consistent with small-cell carcinoma. Chest X-ray and computed tomography revealed an expansive process in the 7(th) segment of the left lung, left hilar and mediastinal lymphadenopathy and a suspicious initial secondary deposit in the left adrenal gland. The patient was referred to the department of oncology for further treatment. After the third cycle of chemotherapy, the magnetic resonance imaging revealed brain metastases. The patient passed away four months after the diagnosis of lung cancer first presented with skin metastases. Metastases in skin may be the first sign of lung cancer. Although rare appearing, we should raise suspicion in cases of atypical lesions in the skin not only of the smokers, but also of the non-smokers. Skin metastases from small-cell lung carcinoma are a poor prognostic indicator. The appearance of multiple skin metastases with other internal metastases shorten the survival time.

  2. [Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

    Science.gov (United States)

    Schmid, K W

    2015-11-01

    The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

  3. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer.

    Science.gov (United States)

    Kaul, David; Angelidis, Alexander; Budach, Volker; Ghadjar, Pirus; Kufeld, Markus; Badakhshi, Harun

    2015-11-26

    Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic

  4. BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

    Science.gov (United States)

    Zavitsanos, Peter J; Wazer, David E; Hepel, Jaroslaw T; Wang, Yihong; Singh, Kamaljeet; Leonard, Kara L

    2018-05-18

    Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls. We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype. Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.

  5. Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients

    International Nuclear Information System (INIS)

    Herfarth, K.K.; Pirzkall, A.; Izwekowa, O.; Wannenmacher, M.; Thilmann, C.; Debus, J.; Delorme, S.; Hofmann, U.; Schadendorf, D.; Zierhut, D.

    2003-01-01

    Purpose: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors. Patients and Methods: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at that time. The median dose to the 80% isodose line, prescribed to encompass the tumor margin, was 20 Gy (range, 15-22 Gy). Results: Neurologic symptoms improved in five of twelve symptomatic patients. 41 patients remained asymptomatic or unchanged in their neurologic symptoms. Only five patients (8%) temporarily worsened neurologically after therapy despite no signs of tumor progression. With a mean follow-up time of 9.4 months, actuarial local control was 81% after 1 year. There was a statistically significant dose and size dependency of local tumor control. Median actuarial survival after treatment was 10.6 months. Patients without extracerebral tumor manifestation showed a superior survival (p = 0.04). Conclusions: Despite high local tumor control rates, the prognosis of patients with cerebral metastases of malignant melanoma remains poor. Stereotactic radiosurgery has the potential of stabilizing or improving neurologic symptoms in these patients in a palliative setting. (orig.)

  6. Gamma Knife Treatment of Brainstem Metastases

    Science.gov (United States)

    Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; MacKay, Alexander R.; Lamoreaux, Wayne T.; Call, Jason A.; Carlson, Jonathan D.; Ling, Benjamin C.; Demakas, John J.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

    2014-01-01

    The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control. PMID:24886816

  7. Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuchcinski, Gregory; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine [University of Lille, CHU Lille, Department of Neuroradiology, Lille (France); Le Rhun, Emilie [University of Lille, CHU Lille, Department of Neurosurgery, Lille (France); Oscar Lambret Center, Department of Medical Oncology, Lille (France); Inserm U1192-PRISM-Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse, Lille (France); Cortot, Alexis B. [University of Lille, CHU Lille, Department of Thoracic Oncology, Lille (France); Drumez, Elodie [University of Lille, CHU Lille, Department of Biostatistics, Lille (France)

    2017-09-15

    To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K{sup trans}, k{sub ep}, v{sub e}, v{sub p}) and their early variation (∇K{sup trans}, ∇k{sub ep}, ∇v{sub e}, ∇v{sub p}). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∇K{sup trans}, ∇v{sub e} and ∇v{sub p} were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∇v{sub e} with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∇v{sub e} may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. (orig.)

  8. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

    Directory of Open Access Journals (Sweden)

    Chowdhary M

    2016-12-01

    Full Text Available Mudit Chowdhary,1,2 Kirtesh R Patel,1 Hasan H Danish,1 David H Lawson,3 Mohammad K Khan1 1Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA Abstract: Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM. Keywords: brain metastases, melanoma, radiation, BRAF inhibitors, vemurafenib, dabrafenib

  9. Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Johnson, Matthew D.; Avkshtol, Vladimir; Baschnagel, Andrew M.; Meyer, Kurt; Ye, Hong; Grills, Inga S.; Chen, Peter Y.; Maitz, Ann; Olson, Rick E.; Pieper, Daniel R.; Krauss, Daniel J.

    2016-01-01

    Purpose: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. Methods and Materials: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. Results: With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06). Conclusions: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an

  10. Intraoperative ultrasonography for presumed brain metastases: a case series study

    Directory of Open Access Journals (Sweden)

    Helder Picarelli

    2012-10-01

    Full Text Available Brain metastases (BM are one of the most common intracranial tumors and surgical treatment can improve both the functional outcomes and patient survival, particularly when systemic disease is controlled. Image-guided BM resection using intraoperative exams, such as intraoperative ultrasound (IOUS, can lead to better surgical results. METHODS: To evaluate the use of IOUS for BM resection, 20 consecutives patients were operated using IOUS to locate tumors, identify their anatomical relationships and surgical cavity after resection. Technical difficulties, complications, recurrence and survival rates were noted. RESULTS: IOUS proved effective for locating, determining borders and defining the anatomical relationships of BM, as well as to identify incomplete tumor resection. No complications related to IOUS were seen. CONCLUSION: IOUS is a practical supporting method for the resection of BM, but further studies comparing this method with other intraoperative exams are needed to evaluate its actual contribution and reliability.

  11. Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study

    International Nuclear Information System (INIS)

    Inoue, Hiroshi K; Sato, Hiro; Suzuki, Yoshiyuki; Saitoh, Jun-ichi; Noda, Shin-ei; Seto, Ken-ichi; Torikai, Kota; Sakurai, Hideyuki; Nakano, Takashi

    2014-01-01

    A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications. Eighty-eight patients with large brain metastases ≥10 cm 3 in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm 3 for individual lesions. Univariate and multivariate analyses were conducted. As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm 3 (median, 16.2 cm 3 ) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10–19.9 cm 3 , 2) 20–29.9 cm 3 and 3) ≥30 cm 3 . The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm 3 were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection. Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction

  12. Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients With Breast Cancer and Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Sperduto, Paul W., E-mail: psperduto@mropa.com [University of Minnesota Gamma Knife, Minneapolis Radiation Oncology, Minneapolis, MN (United States); Kased, Norbert [Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA (United States); Roberge, David [Radiation Oncology, McGill University Health Center, Montreal, QC (Canada); Xu Zhiyuan [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Shanley, Ryan [Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Luo, Xianghua [Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN (United States); Sneed, Penny K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA (United States); Chao, Samuel T. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Weil, Robert J. [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Suh, John [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Bhatt, Amit [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Jensen, Ashley W.; Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Shih, Helen A. [Massachusetts General Hospital, Department of Radiation Oncology, Harvard Medical School, Boston, MA (United States); Kirkpatrick, John [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Gaspar, Laurie E. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO (United States); Fiveash, John B. [Radiation Oncology, University of Alabama Medical Center at Birmingham, Birmingham, AL (United States); and others

    2012-04-01

    Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

  13. Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

    International Nuclear Information System (INIS)

    Videtic, Gregory M.M.; Reddy, Chandana A.; Chao, Samuel T.; Rice, Thomas W.; Adelstein, David J.; Barnett, Gene H.; Mekhail, Tarek M.; Vogelbaum, Michael A.; Suh, John H.

    2009-01-01

    Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

  14. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

    Science.gov (United States)

    Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

    2017-09-01

    For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

  15. Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus ≥ 4 Brain Metastases.

    Science.gov (United States)

    Murovic, Judith; Ding, Victoria; Han, Summer S; Adler, John R; Chang, Steven D

    2017-10-24

    Introduction This study's objective is to compare the overall survivals (OSs) and various parameters of patients with 1-3 versus ≥ 4 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for overall survival (OS) and patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). Patients and their data were divided into those with 1-3 (group 1) versus ≥ 4 brain metastases (group 2). For each CR and LF patient, absolute neutrophil count (ANC), absolute lymphocyte count (ALC)), and ANC/ALC ratio (NLR) were obtained, when available, at the time of CKRS. Results Both group 1 and group 2 had a median OS of 13 months. The patient median age for the 115 group 1 patients versus the 35 group 2 patients was 62 versus 56 years. Group 1 had slightly more males and group 2, females. The predominant ECOG score for each group was 1 and the number of ECD sites was one and two, respectively. Uncontrolled ECD occurred in the majority of both group 1 and group 2 patients. The main COD was ECD in both groups. The prevalent tumor histology for groups 1 and 2 was non-small cell lung carcinoma. Median TVs were 1.08 cc versus 1.42 cc for groups 1 and 2, respectively. The majority of patients in both groups did not undergo post-CKRS WBRT. Imaging outcomes were LC (CR, PR, or stable imaging) in 93 (80.9%) and 26 (74.3%) group 1 and 2 patients, of whom 32 (27.8%) and six (17.1%) had CR; 38 (33.0%) and 18 (51.4%), PR and 23

  16. Sensitivity of different MRI sequences in the early detection of melanoma brain metastases

    Science.gov (United States)

    Breckwoldt, Michael O.; Schwarz, Daniel; Radbruch, Alexander; Enk, Alexander; Bendszus, Martin; Hassel, Jessica; Schlemmer, Heinz-Peter

    2018-01-01

    Background After the emergence of new MRI techniques such as susceptibility- and diffusion-weighted imaging (SWI and DWI) and because of specific imaging characteristics of melanoma brain metastases (MBM), it is unclear which MRI sequences are most beneficial for detection of MBM. This study was performed to investigate the sensitivity of six clinical MRI sequences in the early detection of MBM. Methods Medical records of all melanoma patients referred to our center between November 2005 and December 2016 were reviewed for presence of MBM. Analysis encompassed six MRI sequences at the time of initial diagnosis of first or new MBM, including non-enhanced T1-weighted (T1w), contrast-enhanced T1w (ceT1w), T2-weighted (T2w), T2w-FLAIR, susceptibility-weighted (SWI) and diffusion-weighted (DWI) MRI. Each lesion was rated with respect to its conspicuity (score from 0—not detectable to 3—clearly visible). Results Of 1210 patients, 217 with MBM were included in the analysis and up to 5 lesions per patient were evaluated. A total of 720 metastases were assessed and all six sequences were available for 425 MBM. Sensitivity (conspicuity ≥2) was 99.7% for ceT1w, 77.0% for FLAIR, 64.7% for SWI, 61.0% for T2w, 56.7% for T1w, and 48.4% for DWI. Thirty-one (7.3%) of 425 lesions were only detectable by ceT1w but no other sequence. Conclusions Contrast-enhanced T1-weighting is more sensitive than all other sequences for detection of MBM. Disruption of the blood-brain-barrier is consistently an earlier sign in MBM than perifocal edema, signal loss on SWI or diffusion restriction. PMID:29596475

  17. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.

    Science.gov (United States)

    Brown, Paul D; Jaeckle, Kurt; Ballman, Karla V; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Barker, Fred G; Deming, Richard; Burri, Stuart H; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L

    2016-07-26

    Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median

  18. Correlation of Tumor and Peritumoral Edema Volumes with Survival in Patients with Cerebral Metastases.

    Science.gov (United States)

    Kerschbaumer, Johannes; Bauer, Marlies; Popovscaia, Marina; Grams, Astrid E; Thomé, Claudius; Freyschlag, Christian F

    2017-02-01

    Surgical resection in combination with radiotherapy in selected cases remains the best option for patients with cerebral metastases. Postoperative relapse of brain metastases occurs frequently and can be reduced by postoperative whole-brain radiotherapy (WBRT). Continuous spread of tumor cells from the primary lesions is debated as a cause of recurrence. It is well known that in gliomas, infiltration takes place within the surrounding edema. Obviously, most brain metastases are usually associated with peritumoral edema, which may act as an indicator of infiltration and more aggressive tumor biology. Therefore, we aimed to investigate the correlation of tumor and edema volumes with overall survival in patients with cerebral metastases. A total of 143 patients diagnosed with brain metastasis (male:female=1.1:1) who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient files. The volumes of tumor and edema calculated by manual delineation. The ratio of edema to tumor volume was calculated, leading to dichotomization of the patients. The median tumor volume was 20.1 cc (range=0.8-90.8 cc) and the median volume of edema 49.5 cc (range=0-179.9 cc). The volume of metastases did not significantly correlate with overall survival. The ratio of edema to tumor volume was also not a prognostic factor in terms of overall survival. Only surgical resection, preoperative recursive partitioning analysis class, and postoperative addition of WBRT, as well as female sex, demonstrated beneficial effects. The extent of edema surrounding cerebral metastases does not appear to influence overall survival in patients suffering from brain metastases, although it seems to be responsible for most of the patients' symptoms. The hypothesis that the extent of edema was disadvantageous concerning survival was supported by our data. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios

  19. Incidence of Brain Atrophy and Decline in Mini-Mental State Examination Score After Whole-Brain Radiotherapy in Patients With Brain Metastases: A Prospective Study

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Baba, Fumiya; Oda, Kyota; Hayashi, Shinya; Kokubo, Masaki; Ishihara, Shun-Ichi; Itoh, Yoshiyuki; Ogino, Hiroyuki; Koizumi, Masahiko

    2008-01-01

    Purpose: To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. Methods and Materials: Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. Results: Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 ± 0.39 (SD) at 6 months and 1.32 ± 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. Conclusions: Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent

  20. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  1. Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases

    OpenAIRE

    Yun Fan; Yanjun Xu; Lei Gong; luo Fang; Hongyang Lu; Jing Qin; Na Han; Fajun Xie; Guoqin Qiu; Zhiyu Huang

    2017-01-01

    EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole ...

  2. Prognostic factors for survival and radiation necrosis after stereotactic radiosurgery alone or in combination with whole brain radiation therapy for 1–3 cerebral metastases

    International Nuclear Information System (INIS)

    Schüttrumpf, Lars Hendrik; Niyazi, Maximilian; Nachbichler, Silke Birgit; Manapov, Farkhad; Jansen, Nathalie; Siefert, Axel; Belka, Claus

    2014-01-01

    In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. 340 patients with 1–3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS ≤ 70: 122 days; KPS > 70: 342 days), for RPA (recursive partitioning analysis) class (RPA class I: 1800 days; RPA class II: 281 days; RPA class III: 130 days), irradiated volume (≤2.5 ml: 354 days; > 2.5 ml: 234 days), prescribed dose (≤18 Gy: 235 days; > 18 Gy: 351 days), gender (male: 235 days; female: 327 days) and whole brain radiotherapy (+WBRT: 341 days/-WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA class and gender. MRI and clinical symptoms suggested radiation necrosis in 21 patients after SRS +/− whole brain radiotherapy (WBRT). In five patients clinically relevant radiation necrosis was confirmed by PET imaging. SRS alone or in combination with WBRT represents a feasible option as initial treatment for patients with brain metastases; however a significant subset of patients may develop neurological complications. Performance status, RPA class and gender were identified to predict improved survival in cerebral metastasized patients

  3. Treatment planning for MLC based robotic radiosurgery for brain metastases: plan comparison with circular fields and suggestions for planning strategies

    OpenAIRE

    Schmitt Daniela; El Shafie Rami; Klüter Sebastian; Arians Nathalie; Schubert Kai; Rieken Stefan; Debus Jürgen; Paul Angela

    2017-01-01

    To evaluate the possible range of application of the new InCise2 MLC for the CyberKnife M6 system in brain radiosurgery, a plan comparison was made for 10 brain metastases sized between 1.5 and 9cm3 in 10 patients treated in a single fraction each. The target volumes consist of a PTV derived by expanding the GTV by 1mm and were chosen to have diversity in the cohort regarding regularity of shape, location and the structures needed to be blocked for beam transmission in the vicinity. For each ...

  4. Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

    Science.gov (United States)

    Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

    2018-01-01

    Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

  5. SU-E-T-395: Evaluation of Multiple Brain Metastases Stereotactic Treatment Planning in Cyberknife Versus Linac

    International Nuclear Information System (INIS)

    Vikraman, S; Rajesh, Thiyagarajan; Karrthick, Kp; Sambasivaselli, R; Senniandavar, V; Ramu, M; Maragathaveni, S; Dhivya, N; Tejinder, K; Manigandan, D; Muthukumaran, M

    2015-01-01

    Purpose: The purpose of this study was to evaluate multiple brain metastases stereotactic treatment planning of Cyberknife versus linac using dose volume based indices. Methods: Fifteen multiple brain metastases patients were taken for this study from Cyberknife Multiplan TPSv4.6.0. All these patients underwent stereotactic treatment in Cyberknife. For each patient VMAT stereotactic treatment plan was generated in MONACO TPSv5.0 using Elekta beam modulator MLC and matched the delivered plan. A median dose of 8.5Gy(range 7–12Gy) per fraction was prescribed. Tumor volume was in the range of 0.06–4.33cc. Treatment plan quality was critically evaluated by comparing DVH indices such as D98, D95, CI, and HI for target volumes. Maximum point doses and volume doses were evaluated for critical organs. Results: For each case, target coverage of D98 was achieved with 100% prescription dose with SD of 0.29% and 0.41% in Linac and Cyberknife respectively. The average conformity index(CI) of 1.26±0.0796 SD for Cyberknife and 1.92±0.60SD for linac were observed. Better homogeneity Index (HI) of 1.17±0.09SD was observed in linac as compared to Cyberknife HI of 1.24±0.05SD.All the critical organ doses were well within tolerance limit in both linac and Cyberknife plans. There is no significant difference of maximum point doses for brainstem and optic chiasm. Treatment time and number of monitor units are more in Cyberknife compared to linac. The average volume receiving 12Gy in whole brain was 6% and 12% for Cyberknife and linac respectively. 1000cc of whole brain received 60% lesser dose in Linac compared to Cyberknife in all cases. Conclusion: The study shows that dosimetrically comparable plans are achievable Cyberknife and Linac. However, a better conformity, target coverage, lesser OAR dose is achieved with Cyberknife due to greater degrees of freedom with robotic gantry and smaller collimator for multiple targets

  6. Heuristic knowledge-based planning for single-isocenter stereotactic radiosurgery to multiple brain metastases.

    Science.gov (United States)

    Ziemer, Benjamin P; Sanghvi, Parag; Hattangadi-Gluth, Jona; Moore, Kevin L

    2017-10-01

    Single-isocenter, volumetric-modulated arc therapy (VMAT) stereotactic radiosurgery (SRS) for multiple brain metastases (multimets) can deliver highly conformal dose distributions and reduce overall patient treatment time compared to other techniques. However, treatment planning for multimet cases is highly complex due to variability in numbers and sizes of brain metastases, as well as their relative proximity to organs-at-risk (OARs). The purpose of this study was to automate the VMAT planning of multimet cases through a knowledge-based planning (KBP) approach that adapts single-target SRS dose predictions to multiple target predictions. Using a previously published artificial neural network (ANN) KBP system trained on single-target, linac-based SRS plans, 3D dose distribution predictions for multimet patients were obtained by treating each brain lesion as a solitary target and subsequently combining individual dose predictions into a single distribution. Spatial dose distributions di(r→) for each of the i = 1…N lesions were merged using the combination function d(r→)=∑iNdin(r→)1/n. The optimal value of n was determined by minimizing root-mean squared (RMS) difference between clinical multimet plans and predicted dose per unit length along the line profile joining each lesion in the clinical cohort. The gradient measure GM=[3/4π]1/3V50%1/3-V100%1/3 is the primary quality metric for SRS plan evaluation at our institution and served as the main comparative metric between clinical plans and the KBP results. A total of 41 previously treated multimet plans, with target numbers ranging from N = 2-10, were used to validate the ANN predictions and subsequent KBP auto-planning routine. Fully deliverable KBP plans were developed by converting predicted dose distribution into patient-specific optimization objectives for the clinical treatment planning system (TPS). Plan parity was maintained through identical arc configuration and target normalization. Overall

  7. Edema is not a reliable diagnostic sign to exclude small brain metastases.

    Directory of Open Access Journals (Sweden)

    Tanja Schneider

    Full Text Available No prior systematic study on the extent of vasogenic edema (VE in patients with brain metastases (BM exists. Here, we aim to determine 1 the general volumetric relationship between BM and VE, 2 a threshold diameter above which a BM shows VE, and 3 the influence of the primary tumor and location of the BM in order to improve diagnostic processes and understanding of edema formation. This single center, retrospective study includes 173 untreated patients with histologically proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images was conducted. Statistical analyses were performed using a paired-samples t-test, linear regression/generalized mixed-effects model, and receiver-operating characteristic (ROC curve controlling for the possible effect of non-uniformly distributed metastases among patients. For BM with non-confluent edema (n = 545, there was a statistically significant positive correlation between the volumes of the BM and the VE (P < 0.001. The optimal threshold for edema formation was a diameter of 9.4 mm for all BM. The primary tumors as interaction term in multivariate analysis had a significant influence on VE formation whereas location had not. Hence VE development is dependent on the volume of the underlying BM and the site of the primary neoplasm, but not from the location of the BM.

  8. Feasibility of Single-Isocenter Volumetric Modulated Arc Radiosurgery for Treatment of Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Clark, Grant M.; Popple, Richard A.; Young, P. Edward; Fiveash, John B.

    2010-01-01

    Purpose: To evaluate the relative plan quality of single-isocenter vs. multi-isocenter volumetric modulated arc therapy (VMAT) for radiosurgical treatment of multiple central nervous system metastases. Methods and Materials: VMAT plans were created using RapidArc technology for treatment of simulated patients with three brain metastases. The plans consisted of single-arc/single-isocenter, triple-arc (noncoplanar)/single-isocenter, and triple-arc (coplanar)/triple-isocenter configurations. All VMAT plans were normalized to deliver 100% of the 20-Gy prescription dose to all lesions. The plans were evaluated by calculation of Paddick and Radiation Therapy Oncology Group conformity index scores, Paddick gradient index scores, and 12-Gy isodose volumes. Results: All plans were judged clinically acceptable, but differences were observed in the dosimetric parameters, with the use of multiple noncoplanar arcs showing small improvements in the conformity indexes compared with the single-arc/single-isocenter and triple-arc (coplanar)/triple-isocenter plans. Multiple arc plans (triple-arc [noncoplanar]/single-isocenter and triple-arc [coplanar]/triple-isocenter) showed smaller 12-Gy isodose volumes in scenarios involving three metastases spaced closely together, with only small differences noted among all plans involving lesions spaced further apart. Conclusion: Our initial results suggest that single-isocenter VMAT plans can be used to deliver conformity equivalent to that of multiple isocenter VMAT techniques. For targets that are closely spaced, multiple noncoplanar single-isocenter arcs might be required. VMAT radiosurgery for multiple targets using a single isocenter can be efficiently delivered, requiring less than one-half the beam time required for multiple isocenter set ups. VMAT radiosurgery will likely replace multi-isocenter techniques for linear accelerator-based treatment of multiple targets.

  9. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  10. Cerebral metastases from lung carcinoma: neurological and CT correlation: work in progress

    International Nuclear Information System (INIS)

    Tarver, R.D.; Richmond, B.D.; Klatte, E.C.

    1984-01-01

    To determine the role of brain CT in neurologically asymptomatic lung cancer patients a review was made of the CT and clinical findings in 279 patients. Brain metastases were found in 94.5% of patients with specific abnormal neurological findings, 26.6% of patients with vague neurological signs and symptoms, 11% of patients with oat cell carcinoma and a normal neurological examination, and 40% of patients with adenocarcinoma and a normal neurological examination. Brain metastasis was not seen on CT in the 29 patients with squamous cell carcinoma and a normal neurological examination. It is concluded that brain CT is useful for the detection of occult brain metastases, particularly oat cell carcinoma and adenocarcinoma, in neurologically asymptomatic lung cancer patients

  11. Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

    International Nuclear Information System (INIS)

    Roos, Daniel E.; Wirth, Andrew; Burmeister, Bryan H.; Spry, Nigel A.; Drummond, Katharine J.; Beresford, Jennifer A.; McClure, Beverley E.

    2006-01-01

    We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting

  12. Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial.

    Science.gov (United States)

    Choi, Clara Y H; Wakelee, Heather A; Neal, Joel W; Pinder-Schenck, Mary C; Yu, Hsiang-Hsuan Michael; Chang, Steven D; Adler, John R; Modlin, Leslie A; Harsh, Griffith R; Soltys, Scott G

    2017-09-01

    To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days. From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS. The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. MO-G-201-04: Knowledge-Based Planning for Single-Isocenter Stereotactic Radiosurgery to Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Ziemer, B; Shiraishi, S; Hattangadi-Gluth, J; Sanghvi, P; Moore, K

    2016-01-01

    Purpose: Single-isocenter, linac-based SRS for multiple brain metastases (multi-mets) can deliver highly conformal radiation doses and reduce overall patient treatment time compared to other therapy techniques. This study aims to quantify the dosimetric benefits of knowledge-based planning (KBP) for multi-met treatments. Methods: Using a previously-published KBP methodology (an artificial neural network (ANN) trained on single-target linac-based SRS plans), 3D dose distribution predictions for multi-met patients were obtained by treating each brain lesion as a solitary target and subsequently combining individual predictions into a single distribution using a dose-weighted geometric averaging to obtain the best results in the inter-target space. 17 previously-treated multi-met plans, with target numbers ranging from N=2–5, were used to validate the ANN predictions and subsequent KBP auto-planning routine. The fully-deliverable KBP plans were developed by converting dose distribution predictions into patient-specific optimization objectives while maintaining identical target normalizations (typically PTV V100%=D98%). Plan quality improvements were quantified by the difference between SRS quality metrics (QMs): δdQM=QM(clinical)-QM(KBP). QMs of interest were: gradient measure (GM), conformity index (CI), brain V10 and V5, brainstem D0.1cc and heterogeneity index (HI). Finally, overall plan quality was judged via blinded plan comparison by SRS-specializing physicians. Results: Two clinical plans were found to be significant outliers wherein plan quality was dramatically worse than KBP. Despite indicating KBP superiority, these were removed from the QM analysis to prevent skewing the results. In the remaining cases, clinical and KBP QMs were nearly identical with modest improvements in the KBP sample: δGM=0.12±0.56mm, δCI=−0.01±0.04, Brain δV10=0.8±2.6cc, brain δV5=6.3 ±10.7cc, brainstem δD0.1cc=0.06±1.19Gy and δHI= −0.04±0.05. Ultimately, 13/17 KBP

  14. MO-G-201-04: Knowledge-Based Planning for Single-Isocenter Stereotactic Radiosurgery to Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ziemer, B [University of California, San Diego, La Jolla, CA (United States); Shiraishi, S [Mayo Clinic, Rochester, MN (United States); Hattangadi-Gluth, J; Sanghvi, P; Moore, K

    2016-06-15

    Purpose: Single-isocenter, linac-based SRS for multiple brain metastases (multi-mets) can deliver highly conformal radiation doses and reduce overall patient treatment time compared to other therapy techniques. This study aims to quantify the dosimetric benefits of knowledge-based planning (KBP) for multi-met treatments. Methods: Using a previously-published KBP methodology (an artificial neural network (ANN) trained on single-target linac-based SRS plans), 3D dose distribution predictions for multi-met patients were obtained by treating each brain lesion as a solitary target and subsequently combining individual predictions into a single distribution using a dose-weighted geometric averaging to obtain the best results in the inter-target space. 17 previously-treated multi-met plans, with target numbers ranging from N=2–5, were used to validate the ANN predictions and subsequent KBP auto-planning routine. The fully-deliverable KBP plans were developed by converting dose distribution predictions into patient-specific optimization objectives while maintaining identical target normalizations (typically PTV V100%=D98%). Plan quality improvements were quantified by the difference between SRS quality metrics (QMs): δdQM=QM(clinical)-QM(KBP). QMs of interest were: gradient measure (GM), conformity index (CI), brain V10 and V5, brainstem D0.1cc and heterogeneity index (HI). Finally, overall plan quality was judged via blinded plan comparison by SRS-specializing physicians. Results: Two clinical plans were found to be significant outliers wherein plan quality was dramatically worse than KBP. Despite indicating KBP superiority, these were removed from the QM analysis to prevent skewing the results. In the remaining cases, clinical and KBP QMs were nearly identical with modest improvements in the KBP sample: δGM=0.12±0.56mm, δCI=−0.01±0.04, Brain δV10=0.8±2.6cc, brain δV5=6.3 ±10.7cc, brainstem δD0.1cc=0.06±1.19Gy and δHI= −0.04±0.05. Ultimately, 13/17 KBP

  15. Stereotactic radiosurgery for brainstem metastases: Survival, tumor control, and patient outcomes

    International Nuclear Information System (INIS)

    Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.; Pollock, Bruce E.

    2007-01-01

    Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival time after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS

  16. Value of radiotherapy in the treatment of metastases of the hypernephroma

    International Nuclear Information System (INIS)

    Bostel, F.; Kuhne-Velte, H.J.; Woellgens, P.

    1983-01-01

    52 own cases are retrospectively evaluated in order to investigate the importance of radiotherapy for the treatment of the metastazing hypernephroma. The treatment is above all indicated in case of painful osseous metastases, but the success is retarded and often appears only after a focal dose of more than 30 Gy. Furthermore, radiotherapy of brain metastases and lymph node metastases within the mediastinum is often successful, whereas the irradiation of pulmonary metastases has to be judged less favorably. In most of all cases, surgical interventions are not an alternative, but a complementary treatment to radiotherapy. In default of promising systemic therapy methods, radiotherapy of metastases of the hypernephroma are a possibility to achieve a real palliative effect. (orig.) [de

  17. Rectal Metastases from Squamous Cell Carcinoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    S. Cedrés

    2012-01-01

    Full Text Available Non-small-cell lung cancer (NSCLC represents 85% of lung cancer. The most frequent sites of distant metastasis are the liver, adrenal glands, bones and brain. Gastrointestinal metastases are uncommon and rectal metastases are extremely rare. Here we report a case of squamous cell carcinoma of the lung with rectal metastases.

  18. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

    Science.gov (United States)

    Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

    2017-09-01

    Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

  19. Rare aggressive behavior of MDM2-amplified retroperitoneal dedifferentiated liposarcoma, with brain, lung and subcutaneous metastases

    Directory of Open Access Journals (Sweden)

    Imen Ben Salha

    2016-10-01

    Full Text Available Dedifferentiated liposarcoma (DDL is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, nonlipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma.

  20. Distant Metastases of Nasopharyngeal Carcinoma after Definite Irradiation

    International Nuclear Information System (INIS)

    Chung, Eun Ji; Lee, Hyung Sik; Moon, Sun Rock; Kim, Gwi Eon; Loh, John Juhn-Kyu

    1991-01-01

    One hundred and thirty five patients with carcinoma of the nasopharynx were treated by radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University between August 1977 and July 1987. Of the 30 patients omitted: 8 had distant metastases at initial diagnosis or during radiotherapy; 18 patients refused or did not received a full course of radiation therapy, and four had not been confirmed histologically. The remaining 105 patients were analyzed to determine the incidence and patter of distant metastases. Diagnosis of distant metastases was made based on clinical signs and radiography, even though histologic confirmation was not made. Twenty-six patients developed distant metastases after definite irradiation of nasopharynx and neck, an incidence rate of 24.8%. The common sites of distant metastases were, in descending order, bone, lung, liver, and brain. There was a strong correlation between Ho's N stage and distant metastases rate. But sex, age, histologic subtype (squamous cell and undifferentiated cell), AJC T and N stage, treatment modalities (radiotherapy alone and radiotherapy combined with chemotherapy) were not significant. Of those patients who developed distant metastases, 80.8% were discovered within 2 years of their radical radiotherapy. The prognosis for nasopharyngeal carcinoma patients developing distant metastases was poor: median survival was nine months and 80% of those patients died within two years of the initial diagnosis of distant metastasis

  1. Plan quality comparison between 4-arc and 6-arc noncoplanar volumetric modulated arc stereotactic radiotherapy for the treatment of multiple brain metastases.

    Science.gov (United States)

    Yoshio, Kotaro; Mitsuhashi, Toshiharu; Wakita, Akihisa; Kitayama, Takahiro; Hisazumi, Kento; Inoue, Daisaku; Shiode, Tsuyoki; Akaki, Shiro; Kanazawa, Susumu

    2018-01-04

    To compare the plans of 4-arc and 6-arc noncoplanar volumetric modulated arc stereotactic radiotherapy (VMA-SRT) for multiple brain metastases and to investigate the cutoff value for the tumor number and volume for 6-arc rather than 4-arc VMA-SRT. We identified 24 consecutive multiple-target cases (3 to 19 targets in each case) with 189 total targets. We constructed plans using both 4- and 6-arc noncoplanar VMA-SRT. The prescribed dose was 36 Gy/6 fr, and it was delivered to 95% of the planning target volume (PTV). The plans were evaluated for the dose conformity using the Radiation Therapy Oncology Group and Paddick conformity indices (RCI and PCI), fall-off (Paddick gradient index [PGI]), and the normal brain dose. The median (range) RCI, PCI, and PGI was 0.94 (0.92 to 0.99), 0.89 (0.77 to 0.94), and 3.75 (2.24 to 6.54) for the 4-arc plan and 0.94 (0.91 to 0.98), 0.89 (0.76 to 0.94), and 3.65 (2.24 to 6.5) for the 6-arc plan, respectively. The median (range) of the normal brain dose was 910.3 cGy (381.4 to 1268.9) for the 4-arc plan and 898.8 cGy (377 to 1252.9) for the 6-arc plan. The PGI of the 6-arc plan was significantly superior to that of the 4-arc plan (p = 0.0076), and the optimal cutoff values for the tumor number and volume indicative of 6-arc (and not 4-arc) VMA-SRT were cases with ≥ 5 metastases and a PTV of ≥ 12.9 mL, respectively. The PCI values, however, showed no significant difference between the 2 plans. We believe these results will help in considering the use of 6-arc VMA-SRT for multiple brain metastases. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  2. Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

    Science.gov (United States)

    Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

    2016-06-01

    Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, Picotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. A simple and efficient methodology to improve geometric accuracy in gamma knife radiation surgery: implementation in multiple brain metastases.

    Science.gov (United States)

    Karaiskos, Pantelis; Moutsatsos, Argyris; Pappas, Eleftherios; Georgiou, Evangelos; Roussakis, Arkadios; Torrens, Michael; Seimenis, Ioannis

    2014-12-01

    To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, "average" image data are compounded from data acquired from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

    Directory of Open Access Journals (Sweden)

    Hauswald Henrik

    2012-08-01

    Full Text Available Abstract Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT in patients with multiple brain metastases (BM from malignant melanoma (MM. Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56 or 40 Gy in 20 fractions (n = 31. All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months, the 6- and 12-months overall-(OS survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11 patients showed a complete (partial remission, while 11 (17 patients had stable disease (intra-cerebral tumor progression. In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months. Furthermore, DS-GPA score (p  Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

  5. Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma.

    Science.gov (United States)

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2016-01-01

    The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs) from lung adenocarcinoma. Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125 mg icotinib orally three times a day. Progression of disease, intolerable adverse reactions, and number of deaths were recorded. For all the patients, the remission rate of icotinib was 67.8% and the disease control rate was 96.4%. The median overall survival time of patients was 21.2 months, and the median progression-free survival time of patients was 10.9 months. Only mild adverse events of grade 1/2 were observed during the treatment. Icotinib was an effective and safe strategy to treat patients with BMs from lung adenocarcinoma.

  6. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

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    Beauchesne, Patrick [Neuro-Oncology, CHU de NANCY, Hôpital Central, CO n°34, 54035 Nancy Cedex (France)

    2011-01-27

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases.

  7. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

    International Nuclear Information System (INIS)

    Beauchesne, Patrick

    2011-01-01

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases

  8. Impact of target volume coverage with Radiation Therapy Oncology Group (RTOG) 98-05 guidelines for transrectal ultrasound guided permanent Iodine-125 prostate implants

    International Nuclear Information System (INIS)

    Horwitz, Eric M.; Mitra, Raj K.; Uzzo, Robert G.; Das, Indra J.; Pinover, Wayne H.; Hanlon, Alexandra L.; McNeeley, Shawn W.; Hanks, Gerald E.

    2003-01-01

    Purpose: Despite the wide use of permanent prostate implants for the treatment of early stage prostate cancer, there is no consensus for optimal pre-implant planning guidelines that results in maximal post-implant target coverage. The purpose of this study was to compare post-implant target volume coverage and dosimetry between patients treated before and after Radiation Therapy Oncology Group (RTOG) 98-05 guidelines were adopted using several dosimetric endpoints. Materials and methods: Ten consecutively treated patients before the adoption of the RTOG 98-05 planning guidelines were compared with ten consecutively treated patients after implementation of the guidelines. Pre-implant planning for patients treated pre-RTOG was based on the clinical target volume (CTV) defined by the pre-implant TRUS definition of the prostate. The CTV was expanded in each dimension according to RTOG 98-05 and defined as the planning target volume. The evaluation target volume was defined as the post-implant computed tomography definition of the prostate based on RTOG 98-05 protocol recommendations. Implant quality indicators included V 100 , V 90 , V 100 , and Coverage Index (CI). Results: The pre-RTOG median V 100 , V 90 , D 90 , and CI values were 82.8, 88.9%, 126.5 Gy, and 17.1, respectively. The median post-RTOG V 100 , V 90 , D 90 , and CI values were 96.0, 97.8%, 169.2 Gy, and 4.0, respectively. These differences were all statistically significant. Conclusions: Implementation of the RTOG 98-05 implant planning guidelines has increased coverage of the prostate by the prescription isodose lines compared with our previous technique, as indicated by post-implant dosimetry indices such as V 100 , V 90 , D 90 . The CI was also improved significantly with the protocol guidelines. Our data confirms the validity of the RTOG 98-05 implant guidelines for pre-implant planning as it relates to enlargement of the CTV to ensure adequate margin between the CTV and the prescription isodose

  9. Seven cases of brain metastasis from papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Ikekubo, Katsuji; Hino, Megumu; Ito, Hidetomi; Hirao, Kazuyuki; Ueshima, Miho; Tanaka, Tomohiro; Kobayashi, Hiromasa; Ishihara, Takashi; Kurahachi, Hiroyuki

    2000-01-01

    Brain metastases from differentiated thyroid carcinoma are extremely rare and carry a poor prognosis. We describe here clinical details of 7 cases of brain metastases from papillary thyroid carcinoma. Of 153 patients with metastases from differentiated thyroid carcinoma (papillary in 123, follicular in 30) treated at our institution between 1981 and 1999, 7 patients (4.6%) had brain metastases. Histologically, the primary tumor was papillary carcinoma in all 7 cases. Four were males and 3 were females. The median age at first diagnosis of distant metastases was 63 yr (range, 47-76 yr). Of these patients, one had brain metastases only and six and metastases to the lungs as well. Five of these patients were treated with 131 I. Three of these 5 patients had marked uptake in the metastases ( 131 I positive) on post-therapy 131 I scans and another 2 patients had no significant activity ( 131 I negative) in both pulmonary and brain metastatic lesions. One of 3 patients with 131 I positive lesions had intense activity in the brain tumor, but no uptake in multiple pulmonary metastatic tumors. In a patient with 131 I positive brain metastases, the tumors progressed rapidly after 131 I therapy. In another one patient, acute hemorrhage of the tumor occurred four days after 131 I therapy, requiring surgical removal. Loner case of 131 I negative 2 patients was treated with radiosurgery (γ-knife) and complete reduction in tumor volume was observed. On the other hand, one of 2 patients receiving no 131 I therapy had radiosurgery (x-knife) and remaining one received conventional external radiation and chemotherapy for small solitary brain and pulmonary metastatic tumors. These therapeutic interventions were useful in both cases. The mean length of survival after the development of brain metastases in the five patients who died of the disease was 30 months. One patient treated with x-knife has been alive at 21 months and another one who has 131 I uptake in the brain tumor without

  10. Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

    Science.gov (United States)

    Harputluoglu, Hakan; Dizdar, Omer; Aksoy, Sercan; Kilickap, Saadettin; Dede, Didem S; Ozisik, Yavuz; Guler, Nilufer; Barista, Ibrahim; Gullu, Ibrahim; Hayran, Mutlu; Selek, Ugur; Cengiz, Mustafa; Zorlu, Faruk; Tekuzman, Gulten; Altundag, Kadri

    2008-05-01

    The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

  11. [The prognostic factors for the radiation treatment of the cerebral metastases from breast carcinoma].

    Science.gov (United States)

    Busetto, M; Polico, R; Antonello, M; Conte, G; Masato, M; Ravenna, C; Bruscagnin, A

    1991-11-01

    Complex mechanisms of various nature, not only physical, can influence the patterns of metastases. We compared the patients with recurrences to the brain as the only metastatic site from breast cancer with the patients relapsing in the brain and other organs. All cases were staged and treated following professional protocols. When brain metastases were diagnosed, the patients were accurately restaged before being submitted to radiation therapy; the whole brain was irradiated with various total doses and the same fractionation. The patients underwent clinical examination before and after irradiation. Survival analysis was carried out using the product-limit method considering the following periods: total survival, relapse-free survival, elapsed time till the appearance of brain metastases, and survival after radiation therapy. The cases were grouped and compared using Mantel-Cox and Breslow methods according to the following prognostic factors: brain as the first site of recurrence, pausal state, total radiation dose, stage (TNM), T and N. No significant difference in survival was observed between the cases with brain as the first metastasized organ and the others. The patients were grouped according to the extant prognostic factors: longer total and postirradiation survival rates were observed in patients in premenopausal state (Breslow: p = 0.025 and 0.005) and in the cases treated with total radiation doses greater than 40 Gy (Breslow: p = 0.023 and 0.005). T levels seemed to significantly affect all the examined periods--which influences the stage effect. Conversely, N levels seemed to be of no significant value. The menopausal factor may reflect the effects of age, from which it cannot be separated. These results can be useful for treatment planning.

  12. Proposal of a post-prostatectomy clinical target volume based on pre-operative MRI: volumetric and dosimetric comparison to the RTOG guidelines

    International Nuclear Information System (INIS)

    Croke, Jennifer; Maclean, Jillian; Nyiri, Balazs; Li, Yan; Malone, Kyle; Avruch, Leonard; Kayser, Cathleen; Malone, Shawn

    2014-01-01

    Recurrence rates following radiotherapy for prostate cancer in the post-operative adjuvant or salvage setting remain substantial. Previous work from our institution demonstrated that published prostate bed CTV guidelines frequently do not cover the pre-operative MRI defined prostate. Inadequate target delineation may contribute to the high recurrence rates, but increasing target volumes may increase dose to organs at risk. We propose guidelines for delineating post-prostatectomy target volumes based upon an individual’s co-registered pre-operative MRI. MRI-based CTVs and PTVs were compared to those created using the RTOG guidelines in 30 patients. Contours were analysed in terms of absolute volume, intersection volume (Jaccard Index) and the ability to meet the RADICALS and QUANTEC rectal and bladder constraints (tomotherapy IMRT plans with PTV coverage of V98% ≥98%). CTV MRI was a mean of 18.6% larger than CTV RTOG: CTV MRI mean 138 cc (range 72.3 - 222.2 cc), CTV RTOG mean 116.3 cc (range 62.1 - 176.6 cc), (p < 0.0001). The difference in mean PTV was only 4.6%: PTV MRI mean 386.9 cc (range 254.4 – 551.2), PTV RTOG mean 370 cc (range 232.3 - 501.6) (p = 0.05). The mean Jaccard Index representing intersection volume between CTVs was 0.72 and 0.84 for PTVs. Both criteria had a similar ability to meet rectal and bladder constraints. Rectal DVH: 77% of CTV RTOG cases passed all RADICALS criteria and 37% all QUANTEC criteria; versus 73% and 40% for CTV MRI (p = 1.0 for both). Bladder DVH; 47% of CTV RTOG cases passed all RADICALS criteria and 67% all QUANTEC criteria, versus 57% and 60% for CTV MRI (p = 0.61for RADICALS, p = 0.79 for QUANTEC). CTV MRI spares more of the lower anterior bladder wall than CTV RTOG but increases coverage of the superior lateral bladder walls. CTV contours based upon the patient’s co-registered pre-operative MRI in the post-prostatectomy setting may improve coverage of the individual’s prostate bed without substantially increasing

  13. Can vascular risk factors influence number and size of cerebral metastases? A 3D-MRI study in patients with different tumor entities.

    Science.gov (United States)

    Nagel, Sandra; Berk, Benjamin-Andreas; Kortmann, Rolf-Dieter; Hoffmann, Karl-Titus; Seidel, Clemens

    2018-02-01

    There is increasing evidence that cerebral microangiopathy reduces number of brain metastases. Aim of this study was to analyse if vascular risk factors (arterial hypertension, diabetes mellitus, smoking, and hypercholesterolemia) or the presence of peripheral arterial occlusive disease (PAOD) can have an impact on number or size of brain metastases. 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Mean number of metastases (NoM) and mean diameter of metastases (mDM) were compared between patients with/without vascular risk factors (vasRF). No general correlation of vascular risk factors with brain metastases was found in this monocentric analysis of a patient cohort with several tumor types. Arterial hypertension, diabetes mellitus, hypercholesterolemia and smoking did not show an effect in uni- and multivariate analysis. In patients with PAOD the number of BM was lower than without PAOD. This was the case independent from cerebral microangiopathy but did not persist in multivariate analysis. From this first screening approach vascular risk factors do not appear to strongly influence brain metastasation. However, larger prospective multi-centric studies with better characterized severity of vascular risk are needed to more accurately detect effects of individual factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: Results of the RTOG dose escalating protocol

    International Nuclear Information System (INIS)

    Russell, A.H.; Clyde, C.; Wasserman, T.H.; Turner, S.S.; Rotman, M.

    1993-01-01

    This study was prepared to address two objectives: (a) to determine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases and (b) to refine existing concepts of liver tolerance for fractionated external radiation. One hundred seventy-three analyzable patients with computed tomography measurable liver metastases from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial risk of severe (Grade 3) radiation hepatitis of 10.0% at 6 months, resulting in closure of the study to patient entry. The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question

  15. A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

    Science.gov (United States)

    Ayala-Peacock, Diandra N.; Peiffer, Ann M.; Lucas, John T.; Isom, Scott; Kuremsky, J. Griff; Urbanic, James J.; Bourland, J. Daniel; Laxton, Adrian W.; Tatter, Stephen B.; Shaw, Edward G.; Chan, Michael D.

    2014-01-01

    Background We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases. Materials and methods Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression. Results Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ2= 16.748, P < .001), number of metastases at SRS (χ2 = 27.216, P < .001), discovery of new metastases at time of SRS (χ2 = 9.197, P < .01), and histology (χ2 = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ2 = 11.020, P < .001) and low risk subtypes (her2 + breast, χ2 = 11.343, P < .001) were identified. Progressive systemic disease (χ2 = 9.549, P < .01), number of brain metastases (χ2 = 16.953, P < .001), minimum SRS dose (χ2 = 21.609, P < .001), and widespread metastatic disease (χ2 = 29.396, P < .001) were predictive of shorter time to WBRT. Conclusion Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases. PMID:24558022

  16. A Nomogram to Predict Radiation Pneumonitis, Derived From a Combined Analysis of RTOG 9311 and Institutional Data

    International Nuclear Information System (INIS)

    Bradley, Jeffrey D.; Hope, Andrew; El Naqa, Issam; Apte, Aditya M.S.; Lindsay, Patricia E.; Bosch, Walter D.Sc.; Matthews, John D.Sc.; Sause, William; Graham, Mary V.; Deasy, Joseph O.

    2007-01-01

    Purpose: To test the Washington University (WU) patient dataset, analysis of which suggested that superior-to-inferior tumor position, maximum dose, and D35 (minimum dose to the hottest 35% of the lung volume) were valuable to predict radiation pneumonitis (RP), against the patient database from Radiation Therapy Oncology Group (RTOG) trial 9311. Methods and Materials: The entire dataset consisted of 324 patients receiving definitive conformal radiotherapy for non-small-cell lung cancer (WU = 219, RTOG 9311 = 129). Clinical, dosimetric, and tumor location parameters were modeled to predict RP in the individual datasets and in a combined dataset. Association quality with RP was assessed using Spearman's rank correlation (r) for univariate analysis and multivariate analysis; comparison between subgroups was tested using the Wilcoxon rank sum test. Results: The WU model to predict RP performed poorly for the RTOG 9311 data. The most predictive model in the RTOG 9311 dataset was a single-parameter model, D15 (r = 0.28). Combining the datasets, the best derived model was a two-parameter model consisting of mean lung dose and superior-to-inferior gross tumor volume position (r = 0.303). An equation and nomogram to predict the probability of RP was derived using the combined patient population. Conclusions: Statistical models derived from a large pool of candidate models resulted in well-tuned models for each subset (WU or RTOG 9311), which did not perform well when applied to the other dataset. However, when the data were combined, a model was generated that performed well on each data subset. The final model incorporates two effects: greater risk due to inferior lung irradiation, and greater risk for increasing normal lung mean dose. This formula and nomogram may aid clinicians during radiation treatment planning for lung cancer

  17. How to treat brain metastasis in 2012?

    International Nuclear Information System (INIS)

    Braccini, A.L.; Azria, D.; Mazeron, J.J.; Mornex, F.; Jacot, W.; Metellus, P.; Tallet, A.

    2012-01-01

    During the last French radiation oncology society annual congress, the therapeutic options for the management of brain metastases were presented. The indications and limits of surgery, stereotactic radiotherapy and whole brain radiotherapy, as well as their benefit in terms of overall survival, local control and improvement of the functional and neuro-cognitive status were discussed. The prognosis significance of the different phenotypes of breast cancer on the risk for BM as well as their roles in the treatment of brain metastases were also described. Surgery improves overall survival for patients with a single brain metastase and should be considered in the case of symptomatic lesions. The overall survival of patients treated with stereotactic radiotherapy do not differ from that of patients treated with surgery. These treatments should be mainly considered for patients with good performance status, one to three small brain metastases (< 3 cm) and limited extracranial disease. Whole brain radiotherapy is more and more discussed in adjuvant setting due to potential late neuro-cognitive toxicity. This toxicity could be improved with the development of techniques sparing the hippocampus. HER2+ and triple-negative breast cancer patients are at increased risk for brain metastases. Prognosis of these patients differs as the overall survival of HER2+ patients has improved with anti-HER2 therapies. The optimal combination of local and systemic therapies remain to be determined. (authors)

  18. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed M Ragab Shalaby

    2016-01-01

    Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

  19. Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

    Science.gov (United States)

    Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

    2018-04-01

    This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

  20. Inclusion of brain in FDG PET/CT scanning techniques in cancer patients: Does it obviate the need for dedicated brain imaging?

    International Nuclear Information System (INIS)

    Purandare, Nilendu C.

    2011-01-01

    Metastases to the brain can affect about 10-20% cancer patients. Rising incidence of brain metastases in recent years is related to improved survival rates as a result of advances in cancer therapy and development of more sensitive diagnostic imaging techniques. In patients with extracranial malignancies detection of brain metastases is very important in deciding further diagnostic procedures, planning therapeutic strategies and also to ascertain prognosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) are the modalities which have been traditionally used to assess metastatic disease to the central nervous system. It is generally accepted that MRI (contrast enhanced) is superior to CT scan (contrast enhanced) in the diagnosis of brain metastases. An inherently better soft tissue contrast resolution, stronger contrast enhancement, lack of bone artifacts and partial volume effects and direct multiplanar imaging enables MRI to pick up smaller sized as well as more number of metastases than a CT scan

  1. Cerebellar metastases in patients with uterine cervical cancer. Two cases reports and review of the literature

    International Nuclear Information System (INIS)

    El Omari-Alaoui, H.; Gaye, P.M.; Kebdani, T.; El Ghazi, E.; Benjaafar, N.; Mansouri, A.; Errihani, H.; Kettani, F.; El Ouahabi, A.; El Gueddari, B.K.

    2003-01-01

    Brain metastases from cervical cancer are extremely rare. We report on two patients who developed cerebellar metastases following uterine cervical cancer. The interval between diagnosis of the primary cancer and diagnosis of brain metastasis was 8 months. The main complaint was symptoms of increased intracranial pressure and cerebellar syndrome. Surgical excision of the brain lesion followed by radiation therapy was performed in the first case. The second patient received palliative radiation therapy. The first patient died 8 months after diagnosis. The second patient is alive 2 months after diagnosis. (authors)

  2. Subclassification of Recursive Partitioning Analysis Class II Patients With Brain Metastases Treated Radiosurgically

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Masaaki, E-mail: BCD06275@nifty.com [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Tokyo Women' s Medical University Medical Center East, Tokyo (Japan); Sato, Yasunori [Clinical Research Center, Chiba University Graduate School of Medicine, Chiba (Japan); Serizawa, Toru [Tokyo Gamma Unit Center, Tsukiji Neurologic Clinic, Tokyo (Japan); Kawabe, Takuya [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto (Japan); Higuchi, Yoshinori [Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba (Japan); Nagano, Osamu [Gamma Knife House, Chiba Cardiovascular Center, Ichihara (Japan); Barfod, Bierta E. [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Ono, Junichi [Gamma Knife House, Chiba Cardiovascular Center, Ichihara (Japan); Kasuya, Hidetoshi [Department of Neurosurgery, Tokyo Women' s Medical University Medical Center East, Tokyo (Japan); Urakawa, Yoichi [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan)

    2012-08-01

    Purpose: Although the recursive partitioning analysis (RPA) class is generally used for predicting survival periods of patients with brain metastases (METs), the majority of such patients are Class II and clinical factors vary quite widely within this category. This prompted us to divide RPA Class II patients into three subclasses. Methods and Materials: This was a two-institution, institutional review board-approved, retrospective cohort study using two databases: the Mito series (2,000 consecutive patients, comprising 787 women and 1,213 men; mean age, 65 years [range, 19-96 years]) and the Chiba series (1,753 patients, comprising 673 female and 1,080 male patients; mean age, 65 years [range, 7-94 years]). Both patient series underwent Gamma Knife radiosurgery alone, without whole-brain radiotherapy, for brain METs during the same 10-year period, July 1998 through June 2008. The Cox proportional hazard model with a step-wise selection procedure was used for multivariate analysis. Results: In the Mito series, four factors were identified as favoring longer survival: Karnofsky Performance Status (90% to 100% vs. 70% to 80%), tumor numbers (solitary vs. multiple), primary tumor status (controlled vs. not controlled), and non-brain METs (no vs. yes). This new index is the sum of scores (0 and 1) of these four factors: RPA Class II-a, score of 0 or 1; RPA Class II-b, score of 2; and RPA Class II-c, score of 3 or 4. Next, using the Chiba series, we tested whether our index is valid for a different patient group. This new system showed highly statistically significant differences among subclasses in both the Mito series and the Chiba series (p < 0.001 for all subclasses). In addition, this new index was confirmed to be applicable to Class II patients with four major primary tumor sites, that is, lung, breast, alimentary tract, and urogenital organs. Conclusions: Our new grading system should be considered when designing future clinical trials involving brain MET

  3. Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Johannesen, Helle H; Geertsen, Poul

    2017-01-01

    An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospect......An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later....... In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point...

  4. Quality of life and neuropsychological evaluation for patients with malignant astrocytomas: RTOG 91-14

    International Nuclear Information System (INIS)

    Choucair, Ali K.; Scott, Charles; Urtasun, Raul; Nelson, Diana; Mousas, Benjamin; Curran, Walter

    1997-01-01

    Abstract: With increasingly aggressive neurosurgical and radiation therapy modalities (gamma knife, external beam stereotactic radiation and interstitial brachytherapy with or without hyperthermia) offered to patients with malignant astrocytomas (MA), increasing national demand for medical outcome studies and rising health care costs amidst public, business, and governmental debate to cut spending, we as physicians are obligated to continue our research to find effective treatments for malignant astrocytoma (MA) and a cost-effective means to study their impact upon the patient's quality of life (QOL). Purpose: We report data that was collected within the Radiation Therapy Oncology Group (RTOG) on 126 patients with MA who were enrolled in RTOG 91-14. This study was undertaken to prospectively test the feasibility of performing quality of life (QOL) and neuropsychological evaluation (NPE) and collecting this data within the RTOG. Results: The NPE and QOL parameters that were used in this study are cost effective. They are not only much cheaper than formal cognitive and memory testing, but also provide additional information regarding the patients' day to day functional abilities that are not provided by the current routinely used means, such as KPS. The Mini-Mental Status Exam (MMSE) provides greater sensitivity to patients' differences in neurological status and may be preferable to NFS as an eligibility criteria

  5. Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients

    International Nuclear Information System (INIS)

    Gu, Xiao-Dong; Cai, Yan-Tao; Zhou, Yi-Ming; Li, Zhen-Yang; Xiang, Jian-Bin; Chen, Zong-You

    2015-01-01

    The purpose of this study was to review patient characteristics and evaluate the potential factors affecting prognosis in cases of brain metastasis (BM) from colorectal cancer (CRC). We retrospectively reviewed 93 cases of BM from CRC in our hospital. Patient demographics, neurologic symptoms, and location and number of BMs were recorded. Factors analyzed included: age; sex; Karnofsky performance score; number of BMs; presence of extracranial metastases; dimensions; location of tumors; treatment modalities. The overall 1- and 2-year survival rates were 27.7 and 9.9 %. On multivariate analysis, the number of BMs, extracranial metastases and the initial treatment modalities were found to be independent prognostic factors for overall survival. Patients treated with surgical resection followed by WBRT or SRS had an improved prognosis relative to those treated with surgery alone (P = 0.02 and P = 0.02, respectively). No significance difference in survival rate was found between patients treated with SRS alone or SRS plus WBRT (P = 0.11). Surgical resection of BMs from CRC in selected patients may help prolong survival. Additional radiotherapy following surgery is valuable in improving prognosis. Extracranial metastasis, multiple BM lesions and initial non operation can be considered as independent factors associated with poor prognosis

  6. Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases.

    Science.gov (United States)

    Kim, H; Rajagopalan, M S; Beriwal, S; Smith, K J

    2017-10-01

    Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. A Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. In the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. Based on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  7. Significance of Co-expression of Epidermal Growth Factor Receptor and Ki67 on Clinical Outcome in Patients With Anal Cancer Treated With Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811.

    Science.gov (United States)

    Doll, Corinne M; Moughan, Jennifer; Klimowicz, Alexander; Ho, Clement K; Kornaga, Elizabeth N; Lees-Miller, Susan P; Ajani, Jaffer A; Crane, Christopher H; Kachnic, Lisa A; Okawara, Gordon S; Berk, Lawrence B; Roof, Kevin S; Becker, Mark J; Grisell, David L; Ellis, Robert J; Sperduto, Paul W; Marsa, Gerald W; Guha, Chandan; Magliocco, Anthony M

    2017-03-01

    To measure co-expression of EGFR and Ki67 proteins in pretreatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5-fluorouracil/mitomycin-C/radiation therapy (Arm A) versus 5-fluorouracil/cisplatin/radiation therapy (Arm B), and to correlate expression with clinical outcome. EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis. The Ki67 score within EGFR high versus low areas (Ki67ratio in EGFR high:low ) in each tumor core was analyzed at the median, quartiles, and as a continuous variable. Associations between the tumor markers and clinical endpoints (overall and disease-free survival, locoregional and colostomy failure, and distant metastases) were explored. A total of 282 pretreatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFR high:low  ≥median had worse overall survival (hazard ratio 2.41, 95% confidence interval 1.38-4.19, P=.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFR high:low  ≥ median had a higher risk of a disease-free failure (hazard ratio 1.85, 95% confidence interval 1.18-2.92, P=.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. High Ki67ratio in EGFR high:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor

  8. Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy

    International Nuclear Information System (INIS)

    Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R.; Wong, Eric T.; Uhlmann, Erik J.; Sengupta, Soma; Kasper, Ekkehard M.

    2015-01-01

    Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V 24 (9 cc vs. 44 cc, p < 0.0000) and V 30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia

  9. Concurrent radiotherapy and fotemustine for brain metastases of non small cell cancer of the lung

    International Nuclear Information System (INIS)

    Pignon, T.; Ruggieri, S.; Orabona, P.; Muracciole, X.; Juin, P.; Astoul, P.; Vialette, J.P.; Boutin, C.

    1994-01-01

    The radiotherapy is the most employed in the treatment of cerebral metastases, even if results are deceptive. The tests with chemotherapy are not better and the nitrosoureas remain the most employed drugs. The fotemustin is a new one which can give good results for bearing cerebral metastases patients's response. The associations radiotherapy and chemotherapy are developing to potentiate radiotherapy action but are still a little studied in the cases of cerebral metastases; that is why we choose to treat in an open study the patients bearers of cerebral metastases in lungs cancers with no little cells. 18 refs

  10. Over-all accuracy of sup(99m)Tc-pertechnetate brain scanning for brain tumours

    International Nuclear Information System (INIS)

    Bjoernsson, O.G.; Petursson, E.; Sigurbjoernsson, B.; Davidsson, D.

    1978-01-01

    A 3-year follow-up and re-evaluation of all scans on all patients referred for brain scanning in Iceland during 1 year was performed in order to assess the diagnostic reliability of radioisotope scanning for brain tumours. The study included 471 patients. Of these 25 had primary brain tumours and 7 brain metastases. Scans were positive and correctly interpreted in 68% of the patients with primary brain tumours and in 3 of the 7 patients with metastases. The over-all accuracy of brain scanning for brain tumours defined as the total number of correct positive scans and correct negative scans versus total number of scans examined was 96%, this figure being mainly influenced by the high number of true negative scans. (orig.) [de

  11. Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

    NARCIS (Netherlands)

    Dziadziuszko, R; Ardizzoni, A.; Postmus, P.E.; Smit, E.F.; Price, A; Debruyne, C.; Legrand, C; Giaccone, G.

    2003-01-01

    This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naive non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day,

  12. Surgical Resection Followed by Whole Brain Radiotherapy Versus Whole Brain Radiotherapy Alone for Single Brain Metastasis

    International Nuclear Information System (INIS)

    Rades, Dirk; Kieckebusch, Susanne; Haatanen, Tiina; Lohynska, Radka; Dunst, Juergen; Schild, Steven E.

    2008-01-01

    Purpose: To compare the outcome of surgical resection followed by whole brain radiotherapy (WBRT) with WBRT alone in patients treated for single brain metastasis. Methods and Materials: The data from 195 patients with single brain metastases were retrospectively evaluated. Of the 195 patients, 99 underwent resection of the metastasis followed by WBRT and 96 underwent WBRT alone. Seven additional potential prognostic factors were investigated: age, gender, Eastern Cooperative Oncology Group performance score, tumor type, interval between initial tumor diagnosis and WBRT, extracranial metastases, and recursive partitioning analysis class. Both treatment groups were well balanced for these factors. Results: On multivariate analysis, improved survival was associated with resection (relative risk [RR], 1.20; 95% confidence interval [CI], 1.11-1.31; p < 0.001), lower recursive partitioning analysis class (RR, 1.58; 95% CI, 1.22-2.06; p < 0.001), age ≤61 years (RR, 1.79; 95% CI, 1.23-2.61; p = 0.002), Eastern Cooperative Oncology Group performance score of 0-1 (RR, 2.47; 95% CI, 1.70-3.59; p < 0.001), and the absence of extracranial metastases (RR, 1.99; 95% CI, 1.41-2.79; p < 0.001). Improved local control was associated with resection (RR, 1.25; 95% CI, 1.11-1.41; p < 0.001) and age ≤61 years (RR, 1.77; 95% CI, 1.09-2.88; p = 0.020). Improved brain control distant from the original site was associated with lower recursive partitioning analysis class (RR, 1.65; 95% CI, 1.03-2.69; p < 0.035), age ≤61 years (RR, 1.81; 95% CI, 1.12-2.96; p = 0.016), and the absence of extracranial metastases (RR, 2.42; 95% CI, 1.52-3.88; p < 0.001). Improved control within the entire brain was associated with surgery (RR, 1.24; 95% CI, 1.12-1.38; p < 0.001) and age ≤61 years (RR, 1.83; 95% CI, 1.21-2.77; p = 0.004). Conclusion: In patients with a single brain metastasis, the addition of resection to WBRT improved survival, local control at the original metastatic site, and control

  13. MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

    International Nuclear Information System (INIS)

    Wu, Q; Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N

    2015-01-01

    Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API

  14. MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Q [Wayne State University, Detroit, MI (United States); Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.

  15. Cyberknife fractionated radiotherapy for adrenal metastases: Preliminary report from a multispecialty Indian cancer care center

    Directory of Open Access Journals (Sweden)

    Trinanjan Basu

    2015-03-01

    Full Text Available Purpose: Metastasis to adrenal gland from lung, breast, and kidney malignancies are quite common. Historically radiotherapy was intended for pain palliation. Recent studies with stereotactic body radiotherapy (SBRT including Cyberknife robotic radiosurgery aiming at disease control brings about encouraging results. Here we represent the early clinical experience with Cyberknife stereotactic system from an Indian cancer care center. The main purpose of this retrospective review is to serve as a stepping stone for future prospective studies with non- invasive yet effective technique compared to surgery. Methods: We retrospectively reviewed four cases of adrenal metastases (three: lung and one: renal cell carcinoma treated with Cyberknife SBRT. X sight spine tracking was employed for planning and treatment delivery. Patients were evaluated for local response clinically as well as with PETCT based response criteria.Results: With a median gross tumor volume of 20.5 cc and median dose per fraction of 10 Gy, two patients had complete response (CR and two had partial response (PR when assessed 8-12 weeks post treatment as per RECIST. There was no RTOG grade 2 or more acute adverse events and organs at risk dosage were acceptable. Till last follow up all the patients were locally controlled and alive. Conclusion: Cyberknife SBRT with its unique advantages like non- invasive, short duration outpatient treatment technique culminating in similar local control rates in comparison to surgery is an attractive option. World literature of linear accelerator based SBRT and our data with Cyberknife SBRT with small sample size and early follow up are similar in terms of local control in adrenal metastases. Future prospective data would reveal more information on the management of adrenal metastases.

  16. Management of lung cancer brain metastasis: An overview

    Directory of Open Access Journals (Sweden)

    Himanshu Srivastava

    2017-01-01

    Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

  17. Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ebinu, Julius O.; Lwu, Shelly; Monsalves, Eric; Arayee, Mandana [Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, Toronto, Ontario (Canada); Chung, Caroline; Laperriere, Normand J. [Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario (Canada); Kulkarni, Abhaya V.; Goetz, Pablo [Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario (Canada); Zadeh, Gelareh, E-mail: gelareh.zadeh@uhn.on.ca [Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, Toronto, Ontario (Canada)

    2013-03-01

    Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results: A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.

  18. Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

    International Nuclear Information System (INIS)

    Ebinu, Julius O.; Lwu, Shelly; Monsalves, Eric; Arayee, Mandana; Chung, Caroline; Laperriere, Normand J.; Kulkarni, Abhaya V.; Goetz, Pablo; Zadeh, Gelareh

    2013-01-01

    Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results: A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates

  19. Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

    International Nuclear Information System (INIS)

    Siraj, Ahsan; Gonin, Julie; Radu, Aurelian; Ghinea, Nicolae; Desestret, Virginie; Antoine, Martine; Fromont, Gaëlle; Huerre, Michel; Sanson, Marc; Camparo, Philippe; Pichon, Christophe; Planeix, François

    2013-01-01

    The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors

  20. Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

    Directory of Open Access Journals (Sweden)

    Poujol Sylvain

    2010-06-01

    Full Text Available Abstract Background Since 1999, patients presenting with brain metastases (BM from breast cancer (BC are treated in our institution with a carmustine (BCNU - methotrexate (MTX combination. We report here our clinical experience regarding this combination. Patients and Methods Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity. Results 50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5. Median number of cycles was 3 (1-20. There were 11 objective responses (23% [95%CI 12-37] among 48 evaluable patients. Median progression-free survival and overall survival (OS were 4.2 (95%CI: 2.8-5.3 and 6.9 (4.2-10.7 months respectively, with a one-year OS rate of 32% (20-46. Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1 and 0.96 (0.57-1.66 respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis. Conclusions This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.

  1. A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

    International Nuclear Information System (INIS)

    Khalid, Usman; McGough, Camilla; Hackett, Claire; Blake, Peter; Harrington, Kevin J.; Khoo, Vincent S.; Tait, Diana; Norman, Andrew R.; Andreyev, H. Jervoise N.

    2006-01-01

    Purpose: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Methods and Materials: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. Results: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. Conclusion: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading

  2. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

  3. Miliary pattern of brain metastases – a case report of a hyperacute onset in a patient with malignant melanoma documented by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Reiter, Florian P.; Giessen-Jung, Clemens; Dorostkar, Mario M.; Ertl-Wagner, Birgit; Denk, Gerald U.; Heck, Suzette; Rieger, Christina T.; Pfister, Hans W.; Winkel, Mark op den

    2015-01-01

    Miliary brain metastases are a rare condition but associated with an exceedingly poor prognosis. We present the case of a patient suffering from malignant melanoma with an acute progressively worsening of neurological symptoms up to the loss of consciousness. The magnetic resonance imaging (MRI) demonstrated a new onset of disseminated, miliary spread of central nervous system metastases from a malignant melanoma within 4 days. We report on a 57-year-old woman suffering from metastatic malignant melanoma positive for BRAF-V600E mutation who developed an acute onset of neurological symptoms. The patient received vemurafenib and dacarbacin as chemotherapeutic regime for treatment of malignant melanoma. After admission to our hospital due to progressive disturbance of memory and speech difficulty a magnetic resonance tomography (MRI) was performed. This showed no evidence of cerebral tumour manifestation. The symptoms progressed until a loss of consciousness occurred on day five after admission and the patient was admitted to our intensive care unit for orotracheal intubation. No evidence for infectious, metabolic or autoimmune cerebral disorders was found. Due to the inexplicable acute worsening of the neurological symptoms a second MRI was performed on day five. This revealed a new onset of innumerable contrast-enhancing miliary lesions, especially in the grey matter which was proven as metastases from malignant melanoma on histopathology. This case describes an unique hyperacute onset of tumour progression correlating with an acute deterioration of neurological symptoms in a patient suffering from miliary brain metastasis from BRAF positive malignant melanoma

  4. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial

    OpenAIRE

    Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl

    2016-01-01

    Summary Background Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. Methods The Quality of Life a...

  5. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Riely, Gregory J. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yu, Helena A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  6. An Interindividual Comparison of O-(2- [18F]Fluoroethyl)-L-Tyrosine (FET)– and L-[Methyl-11C]Methionine (MET)–PET in Patients With Brain Gliomas and Metastases

    International Nuclear Information System (INIS)

    Grosu, Anca-Ligia; Astner, Sabrina T.; Riedel, Eva; Nieder, Carsten; Wiedenmann, Nicole; Heinemann, Felix; Schwaiger, Markus

    2011-01-01

    Purpose: L-[methyl- 11 C]methionine (MET)–positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of 11 C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2- [ 18 F]fluoroethyl)-L-tyrosine (FET) is labeled with 18 F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI). Methods and Materials: We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion–to–gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up. Results: There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p 18 F]fluoroethyl)-L-tyrosine–PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.

  7. Elective brain irradiation in patients with small-cell carcinoma of the lung: preliminary report

    International Nuclear Information System (INIS)

    Katsenis, A.T.; Karpasitis, N.; Giannakakis, D.; Maragoudakis, N.; Kiparissiadis, P.

    1982-01-01

    The brain is a common site of metastases in small-cell carcinoma of the lung. Prophylactic brain irradiation with doses of 4000-4500 rads in 3-4 weeks appears to decrease the occurrence of brain metastases although it does not prevent this completely. In a group of patients with small-cell carcinoma of the lung and without evidence of brain metastases, the authors review the site and extent of the primary, the methods of treatment, the techniques of brain irradiation, and the relapses rate in relation to the status of the primary and the rate of brain metastases in another group without prophylactic brain irradiation. They further attempt to investigate combined modalities of treatment which would prolong life and prevent neurological complications in the small number of long survivors with small-cell carcinoma of the lung. (Auth.)

  8. Predictors of Survival in Contemporary Practice After Initial Radiosurgery for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Likhacheva, Anna; Pinnix, Chelsea C. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Parikh, Neil R. [Baylor College of Medicine, Houston, Texas (United States); Allen, Pamela K.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chiu, Max S. [University of Nebraska-Lincoln, Lincoln, Nebraska (United States); Sulman, Erik P.; Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guha-Thakurta, Nandita [Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Prabhu, Sujit S. [Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cahill, Daniel P. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Luo, Dershan; Shiu, Almon S. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L., E-mail: eric.chang@med.usc.edu [Department of Radiation Oncology, University of Southern California, Los Angeles, Los Angeles, California (United States)

    2013-03-01

    Purpose: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone. Methods and Materials: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS). Results: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm{sup 3} (HR, 1.98; P<.001), age ≥60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm{sup 3}). The number of BM was not predictive of DBF, LC, or OS. Conclusions: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT.

  9. Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Compliance to the Dosimetry Requirements of RTOG-0413

    Energy Technology Data Exchange (ETDEWEB)

    Wen Bixiu [Department of Radiation Oncology, New York University Medical Center, New York, New York (United States); Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Hsu, Howard; Formenti-Ujlaki, George F.; Lymberis, Stella; Magnolfi, Chiara; Zhao Xuan; Chang Jenghwa; DeWyngaert, J. Keith; Jozsef, Gabor [Department of Radiation Oncology, New York University Medical Center, New York, New York (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University Medical Center, New York, New York (United States)

    2012-11-15

    Purpose: The dosimetric results from our institution's trials of prone accelerated partial breast irradiation are compared with the dosimetric requirements of RTOG-0413. Methods and Materials: Trial 1 and Trial 2 are 2 consecutive trials of prone-accelerated partial breast irradiation. Eligible for both trials were stage I breast cancer patients with negative margins after breast-conserving surgery. The planning target tumor volume (PTV) was created by extending the surgical cavity 2.0 cm for Trial 1 and 1.5 cm for Trial 2, respectively. Contralateral breast, heart, lungs, and thyroid were contoured. Thirty Gray was delivered in five daily fractions of 6 Gy by a three-dimensional conformal radiation therapy technique in Trial 1 and were by image-guided radiation therapy/intensity-modulated radiation therapy in Trial 2. Dosimetric results from the trials are reported and compared with RTOG 0413 requirements. Results: One hundred forty-six consecutive plans were analyzed: 67 left and 79 right breast cancers. The plans from the trials complied with the required >90% of prescribed dose covering 90% of PTV{sub E}VAL (=generated from the PTV by cropping 0.5 cm from the skin edge and excluding the chest wall): V90% was 98.1 {+-} 3.0% (with V100% and V95%, 89.4 {+-} 12.8%, 96.4 {+-} 5.1%, respectively). No significant difference between laterality was found (Student's t test). The dose constraints criteria of the RTOG-0413 protocol for ipsilateral and contralateral lung (V30 <15% and Dmax <3%), heart (V5 <40%), and thyroid (Dmax <3%) were satisfied because the plans showed an average V5% of 0.6% (range, 0-13.4) for heart, an average V30% of 0.6% (range, 0-9.1%) for ipsilateral lung, and <2% maximum dose to the thyroid. However, our partial breast irradiation plans demonstrated a higher dose to contralateral breast than that defined by RTOG constraints, with a median value of maximum doses of 4.1% (1.2 Gy), possibly as a result of contouring differences

  10. Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Lee, Cheng-Chia [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Kano, Hideyuki; Cohen, Jonathan [Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Janopaul-Naylor, James; Alonso-Basanta, Michelle; Lee, John Y.K. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Simonova, Gabriela; Liscak, Roman [Department of Radiation and Stereotactic Neurosurgery, Na Homolce Hospital, Prague (Czech Republic); Wolf, Amparo; Kvint, Svetlana [Department of Neurosurgery, New York University Lagone Medical Center, New York, New York (United States); Grills, Inga S.; Johnson, Matthew [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Liu, Kang-Du; Lin, Chung-Jung [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Mathieu, David; Héroux, France [Division of Neurosurgery, Université de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Québec (Canada); Silva, Danilo; Sharma, Mayur [Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (United States); Cifarelli, Christopher P. [Departments of Neurosurgery and Radiation Oncology, West Virginia University, Morgantown, West Virginia (United States); and others

    2016-10-01

    Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.

  11. Gadolinium-Enhanced Three-Dimensional Magnetization - Prepared Rapid Gradient-Echo (3D MP-RAGE) Imaging is Superior to Spin-Echo Imaging in Delineating Brain Metastases

    International Nuclear Information System (INIS)

    Takeda, T.; Takeda, A.; Nagaoka, T.; Kunieda, E.; Takemasa, K.; Watanabe, M.; Hatou, T.; Oguro, S.; Katayama, M.

    2008-01-01

    Background: Precisely defining the number and location of brain metastases is very important for establishing a treatment strategy for malignancies. Although magnetic resonance imaging (MRI) is now considered the best modality, various improvements in sequences are still being made. Purpose: To prospectively compare the diagnostic ability of three-dimensional, magnetization-prepared rapid gradient-echo (3D MP-RAGE) imaging in detecting metastatic brain tumors, with that of two-dimensional spin-echo (2D SE) T1-weighted imaging. Material and Methods: A total of 123 examinations were included in this study, and 119 examinations from 88 patients with known malignancies were analyzed. All patients underwent T1- and T2-weighted 2D SE transverse imaging, followed by gadolinium-enhanced T1-weighted transverse and coronal 2D SE imaging and 3D MP-RAGE transverse imaging. Four radiologists interpreted the images to compare the accuracy and the time required for interpretation for each imaging. Results: 3D MP-RAGE imaging was significantly better than 2D SE imaging for detecting metastatic brain lesions, regardless of the readers' experience. The sensitivities of the 3D MP-RAGE and 2D SE imaging for all observers were 0.81 vs. 0.80 (P>0.05), specificities were 0.93 vs. 0.87 (P 0.05), and accuracies were 0.84 vs. 0.78 (P<0.05), respectively. There was no significant difference in the time required for image interpretation between the two modalities (15.6±4.0 vs. 15.4±4.1 min). Conclusion: 3D MP-RAGE imaging proved superior to 2D SE imaging in the detection of brain metastases

  12. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Local recurrence of metastatic brain tumor after surgery

    International Nuclear Information System (INIS)

    Shinoura, Nobusada; Yamada, Ryoji; Okamoto, Koichiro; Nakamura, Osamu; Shitara, Nobuyuki; Karasawa, Katsuyuki

    2006-01-01

    We analyzed factors associated with the local recurrence of brain metastases after surgery. Forty-seven patients with 67 metastatic brain tumors underwent surgery between 1994 and 2001. The survival time in the ''no recurrence'' group (34.7 months) was significantly longer than that in the recurrence group (21.9 months) (p=0.0008; log rank test). The factors affecting the local recurrence of brain metastases after surgery were as follows: cyst (p=0.0156), dural invasion (p=0.0029) of tumors, failure to totally remove tumors (p=0.0040), and lack of post-surgical irradiation (p<0.0001). Sex, age, tumor histology, tumor size, pre-surgical radiation, dose (≥45 vs <45, ≥50 vs <50 Gy) and the method (local vs whole brain) of post-surgical radiation did not affect the local recurrence rate of brain metastases after surgery. To avoid early recurrences of metastatic brain tumors, the factors associated with local recurrence should be considered in providing optimal treatment of tumors by surgery. (author)

  14. Prognosis of patients treated with whole brain radiation therapy for metastatic gestational trophoblastic disease

    International Nuclear Information System (INIS)

    Schechter, Naomi R.; Mychalczak, Borys; Jones, Walter; Spriggs, David

    1996-01-01

    Purpose/Objective: To evaluate the effect of multiple treatment and disease related variables on the local control and survival of patients receiving whole brain radiation therapy for metastatic gestational trophoblastic disease. Materials and Methods: Between November 1967 and December 1994, 21 patients were treated at our institution for gestational trophoblastic disease metastatic to the brain. 29% ((6(21))) were diagnosed with their brain metastases before the onset of chemotherapy (early group). 79% ((15(21))) developed their brain metastases during or after the administration of first-line chemotherapy (late group). All patients were treated with whole brain radiation therapy. The total dose ranged from 200 cGy to 3600 cGy (median 2200 cGy). Sixteen patients (76%) received concurrent systemic chemotherapy. None of the patients received intrathecal chemotherapy as a component of their initial treatment. Survival and local control were calculated from the date of diagnosis of brain metastases. Follow-up ranged from 11 months to 170 months with a median of 77 months. Results: The median overall survival was 21 months, with 2- and 5-year actuarial survivals of 46% and 31%, respectively. Neither survival nor local control was significantly affected by age at diagnosis of brain metastases (<35 vs. ≥35 years), time of presentation of brain metastases (early vs. late), or use of concurrent chemotherapy. The total dose of radiation (<2200 cGy vs. ≥2200 cGy) significantly affected initial local control, but not survival. The 5-year actuarial local control of the initial brain metastases with ≥2200 cGy was 91%, as compared to 24% with <2200 cGy (p=0.05). Survival was significantly affected by control of disease at extracranial sites. The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100% and 83%, respectively, as compared to 8% and 0% for the 12 whose extracranial disease was not controlled (p=0

  15. Brain Metastases Treatment Worsens Cognitive Decline

    Science.gov (United States)

    In some patients with cancer that has spread to the brain, whole brain radiation following radiosurgery causes more severe cognitive decline and does not improve survival compared with radiosurgery alone, a new study has found.

  16. [Concentration of glutathione (GSH), ascorbic acid (vitamin C) and substances reacting with thiobarbituric acid (TBA-rs) in single human brain metastases].

    Science.gov (United States)

    Dudek, Henryk; Farbiszewski, Ryszard; Rydzewska, Maria; Michno, Tadeusz; Kozłowski, Andrzej

    2005-01-01

    The aim of the study was to estimate the concentration of glutathione (GSH), ascorbic acid (vitamin C) and thiobarbituric acid (TBA-rs) in single human brain metastases and histologically unchanged nerve tissue. The research was conducted on fragments of neoplasmatic tissue collected from 45 patients undergoing surgery in the Department of Neurosurgery, Medical University of Białystok in years 1996-2002. Concentration of GSH was evaluated using the GSH-400 method, vitamin C using the method of Kyaw and TBA-rs using the method of Salaris and Babs. It has been found that there is a decrease of concentration of GSH and vitamin C and a considerable increase (p TBA-rs in investigated single brain human metastasis in correlation to the concentration of the mentioned above substances in unchanged nerve tissue.

  17. Medulloblastoma in an Adult With Late Extraneural Metastases to the Mediastinum

    Directory of Open Access Journals (Sweden)

    Abhimanyu Ghose MD

    2014-04-01

    Full Text Available Background. Medulloblastoma, although the most common brain tumor of childhood, is exceedingly rare in adults. These tumors have a propensity for local recurrence and to metastasize along the leptomeninges; however, extraneural metastases are very rare and typically occur in the bone or bone marrow. We have not come across any case in literature of medulloblastoma with mediastinal metastases in an adult. Case Presentation. We report a case of medulloblastoma in a 38-year-old lady who was treated with surgery followed by craniospinal radiation. Ten years later she presented with hoarseness from true vocal cord paralysis. She was diagnosed to have infiltrating metastases of her medulloblastoma to the mediastinum, which was confirmed by biopsy. There was no local recurrence. This was treated with chemotherapy followed by stem cell rescue, and she remained progression free for 2 years. Conclusion. Medulloblastomas are rare in adults and can present with late extraneural metastases following treatment. Although most common reported sites are bone and bone marrow, late metastases to other unexpected areas like the mediastinum are possible too and warrant awareness. This can be treated with chemotherapy followed by high-dose chemotherapy and stem cell rescue in a young patient with good performance status.

  18. Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: A Cochrane Review

    International Nuclear Information System (INIS)

    Lester, Jason Francis; MacBeth, Fergus R.; Coles, Bernadette

    2005-01-01

    Purpose: To investigate whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small-cell lung cancer (NSCLC) treated with curative intent. Methods and Materials: A search strategy was designed to identify randomized controlled trials (RCTs) comparing PCI with no PCI in NSCLC patients treated with curative intent. The electronic databases MEDLINE, EMBASE, LILACS, and Cancerlit were searched, along with relevant journals, books, and review articles to identify potentially eligible trials. Four RCTs were identified and reviewed. A total of 951 patients were randomized in these RCTs, of whom 833 were evaluable and reported. Forty-two patients with small-cell lung cancer were excluded, leaving 791 patients in total. Because of the small patient numbers and trial heterogeneity, no meta-analysis was attempted. Results: Prophylactic cranial irradiation did significantly reduce the incidence of brain metastases in three trials. No trial reported a survival advantage with PCI over observation. Toxicity data were poorly collected and no quality of life assessments were carried out in any trial. Conclusion: Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit. It was not possible to evaluate whether any radiotherapy regimen is superior, and the effect of PCI on quality of life is not known. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial

  19. Current Standards in the Management of Cerebral Metastases

    Directory of Open Access Journals (Sweden)

    Pablo Goetz

    2012-01-01

    Full Text Available The last 30 years have seen major changes in attitude toward patients with cerebral metastases. This paper aims to outline the major landmarks in this transition and the therapeutic strategies currently used. The controversies surrounding control of brain disease are discussed, and two emerging management trends are reviewed: tumor bed radiosurgery and salvage radiation.

  20. Primary brain tumours, meningiomas and brain metastases in pregnancy

    DEFF Research Database (Denmark)

    Verheecke, Magali; Halaska, Michael J; Lok, Christianne A

    2014-01-01

    to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973......, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed...... were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery....

  1. Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients.

    Science.gov (United States)

    Srivastava, Geetika; Rana, Vishal; Wallace, Suzy; Taylor, Sarah; Debnam, Matthew; Feng, Lei; Suki, Dima; Karp, Daniel; Stewart, David; Oh, Yun

    2009-03-01

    Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). The underlying risk of ICH from NSCLC brain metastases is low, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. Two thousand one hundred forty-three patients with metastatic NSCLC registering from January 1998 to September 2005 were followed till March 2006. Seven hundred seventy-six patients with and 1,367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. The incidence of ICH seemed to be higher in those with brain metastasis compared with those without brain metastases, in whom they occurred as result of cerebrovascular accidents. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and had been free of anticoagulation. Most of the brain metastasis-associated ICH's were asymptomatic, detected during increased radiologic surveillance. The rates of symptomatic ICH, or other cerebrovascular accidents in general were similar and not significantly different between the two groups. In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared with those without, but was very low in both groups without a statistically significant difference. These data suggest a minimal risk of clinically significant ICH for NSCLC

  2. Prognostic factors of HER2-positive breast cancer patients who develop brain metastasis: a multicenter retrospective analysis.

    Science.gov (United States)

    Hayashi, Naoki; Niikura, Naoki; Masuda, Norikazu; Takashima, Seiki; Nakamura, Rikiya; Watanabe, Ken-ichi; Kanbayashi, Chizuko; Ishida, Mayumi; Hozumi, Yasuo; Tsuneizumi, Michiko; Kondo, Naoto; Naito, Yoichi; Honda, Yayoi; Matsui, Akira; Fujisawa, Tomomi; Oshitanai, Risa; Yasojima, Hiroyuki; Yamauchi, Hideko; Saji, Shigehira; Iwata, Hiroji

    2015-01-01

    The clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine prognostic factors associated with HER2-positive patients who develop brain metastases. This retrospective study assessed the largest dataset to date of 432 HER2-positive patients who were diagnosed with brain metastases from 24 institutions of the Japan Clinical Oncology Group, Breast Cancer Study Group. The median age of the 432 patients was 54 years (range, 20-86 years). Of the patients, 162 patients (37.5 %) had ER-positive/HER2-positive (ER+HER2+) breast cancer, and 270 (62.5 %) had ER-negative/HER2-positive (ER-HER2+) breast cancer. The median brain metastasis-free survival period from primary breast cancer was 33.5 months in both groups. The median survival after developing brain metastasis was 16.5 and 11.5 months in the ER+HER2+ and ER-HER2+ groups, respectively, (p = 0.117). Patients with >3 brain metastases had significantly shorter overall survival in both ER+HER2+ (p developing brain metastases was not associated with survival duration after developing brain metastases (p = 0.571). However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p brain metastases, regardless of the use of trastuzumab before developing brain metastasis, treatment with both trastuzumab and lapatinib might improve survival.

  3. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Magnuson, William J., E-mail: william.magnuson@yale.edu [Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Yeung, Jacky T. [Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut (United States); Guillod, Paul D. [Yale School of Medicine, New Haven, Connecticut (United States); Gettinger, Scott N. [Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Yu, James B. [Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Chiang, Veronica L. [Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut (United States)

    2016-06-01

    Purpose: To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases (BM) to evaluate our hypothesis that the use of upfront EGFR–tyrosine kinase inhibitors (TKIs), and deferral of radiation therapy (RT), would result in inferior intracranial progression-free survival but similar overall survival (OS). Methods and Materials: Of 202 patients diagnosed with EGFR-mutant NSCLC between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS) or <6 months' follow-up. Of the remaining 50 patients, 17 received upfront EGFR-TKI followed by SRS or WBRT, 17 WBRT then EGFR-TKI, and 16 SRS followed by EGFR-TKI. Disease-specific-graded prognostic assessment was similar among all 3 groups. Results: The median OS was longer in the upfront RT group compared with the upfront EGFR-TKI group (34.1 vs 19.4 months; P=.01). On subgroup analysis, the SRS group had longer OS than the upfront EGFR-TKI group (58.4 vs 19.4 months; P=.01), but the WBRT group did not (29.9 vs 19.4 months; P=.09). Intracranial progression-free survival was improved in patients receiving upfront RT compared with those receiving upfront EGFR-TKI (37.9 vs 10.6 months; P<.001). Conclusions: The present study suggests that the use of upfront EGFR-TKI, and the deferral of SRS or WBRT, may result in inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI with RT at intracranial progression versus upfront RT followed by EGFR-TKI is urgently needed.

  4. Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hao; Zou, Tianyu; Wang, Xianlong; Du, Yongxing; Jiang, Chunxiu; Ma, Ling; Zhu, Jianbin; He, Wen; Rui, Qihong; Wen, Zhibo [Zhujiang Hospital, Southern Medical University, Department of Radiology, Guangzhou, Guangdong (China); Lou, Huiling [The First People' Hospital of Guangzhou, Department of Geriatrics, Guangzhou, Guangdong (China); Jiang, Shanshan [Zhujiang Hospital, Southern Medical University, Department of Radiology, Guangzhou, Guangdong (China); Johns Hopkins University School of Medicine, Division of MR Research, Department of Radiology, Baltimore, MD (United States); Huang, Zhongqing [Shantou University Medical College, Department of Medical Image Center, Yuebei People' s Hospital, Shantou, Guangdong (China); Zhou, Jianyuan [Johns Hopkins University School of Medicine, Division of MR Research, Department of Radiology, Baltimore, MD (United States)

    2017-11-15

    To determine the utility of amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs). Forty-five patients with SBMs and 43 patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumour core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver-operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups. The APTw{sub max}, APTw{sub min}, APTw{sub mean}, rAPTw{sub max}, rAPTw{sub min} or rAPTw{sub mean} values in the tumour core were not significantly different between the SBM and GBM groups (P = 0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTw{sub max}, APTw{sub min}, APTw{sub mean}, rAPTw{sub max}, rAPTw{sub min} or rAPTw{sub mean} values in the PBZ were significantly lower in the SBM group than in the GBM group (P < 0.001). The APTw{sub min} values had the highest area under the ROC curve 0.905 and accuracy 85.2% in discriminating between the two neoplasms. As a noninvasive imaging method, APT-weighted MR imaging can be used to distinguish SBMs from GBMs. (orig.)

  5. Brain imaging before primary lung cancer resection: a controversial topic.

    Science.gov (United States)

    Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

    2017-01-01

    International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

  6. Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

    Science.gov (United States)

    Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

    2006-11-07

    We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

  7. Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Fumio Kanda; Hiroshi Kobessho; Koji Sugimoto; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2006-01-01

    We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-yearold woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI)disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement.The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

  8. Abnormal P-53 suppressor gene expression predicts for a poorer outcome in patients with locally advanced adenocarcinoma of the prostate treated by external beam radiation therapy with or without pre-radiation androgen ablation: results based on RTOG study 86-10

    International Nuclear Information System (INIS)

    Lawton, Colleen A.; Grignon, David; Caplan, Richard; Sarkar, Fazlul; Forman, Jeffrey; Mesic, John; Fu, Karen K.; Abrams, Ross

    1995-01-01

    Purpose/Objective: The purpose of this study is to establish the effect of the abnormal expression of the P-53 suppressor gene on the results of locally advanced adenocarcinoma of the prostate treated with radiation therapy with or without pre-radiation therapy androgen ablation. Materials and Methods: Patients evaluated were part of a RTOG phase III multi-institutional trial. This trial assessed the value of pre-radiation therapy androgen ablation on patients with locally advanced disease (bulky stage B and stage C). Of the 471 patients registered, pre-treatment pathological material was available for 129 patients. P-53 status was determined immunohistochemically utilizing a commercially available antibody (D07). Clinical endpoints evaluated were overall survival and development of metastases. Results: Twenty-three of the 129 patients had abnormal expression of the P-53 suppressor gene. Presence of this abnormal expression significantly correlated with lower overall survival (p=0.03) and the development of distant metastases (p=0.03). Abnormal expression of the P-53 gene was an independent prognostic indicator when evaluated against clinical stage and Gleason score. Conclusion: This data from patients entered on a phase III multi-institutional, randomized clinical trial shows that abnormal P-53 suppressor gene expression as determined immunohistochemically is an independent predictor of poorer survival and the development of distant metastases in patients with locally advanced adenocarcinoma of the prostate treated with radiation therapy with or without pre-radiation therapy androgen ablation

  9. Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the radiation therapy oncology group

    International Nuclear Information System (INIS)

    Borgelt, B.; Gelber, R.; Larson, M.; Hendrickson, F.; Griffin, T.; Rother, R.

    1981-01-01

    Between January, 1971, and February, 1976, the Radiation Therapy Oncology Group entered 1902 evaluable patients into two sequential Phase III national cooperative trials to study the effectiveness of different time dose radiotherapy schemes on the palliation of patients with brain metastases. Each trial included an optional arm into which patients were randomized to receive 1000 rad/1 fraction (26 patients, First study) or 1200 rad/2 fractions (33 patients, Second study). Comparisons were made with 143 control patients randomized by the same participating institutions to receive a more protracted course of irradiation (2000, 3000 or 4000 rad/1-4wks). Response of patients receiving ultra-rapid treatment, as assessed by the percent who had improvement in neurologic function, was comparable to that of patients receiving the more protracted schedules. Promptness of neurologic function improvement, treatment morbidity and median survival were also comparable to those of patients receiving 2000 to 4000 rad. However, the duration of improvement, time to progression of neurologic status and rate of complete disappearance of neurologic symptoms were generally less for those patients who received 1000 or 1200 rad. These results suggest that ultra-rapid, high dose irradiation schedules may not be so effective as higher dose schedules in the palliation of patients with brain metastases

  10. Combined-modality therapy for patients with regional nodal metastases from melanoma

    International Nuclear Information System (INIS)

    Ballo, Matthew T.; Ross, Merrick I.; Cormier, Janice N.; Myers, Jeffrey N.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Hwu, Patrick; Zagars, Gunar K.

    2006-01-01

    Purpose: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Methods and Materials: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. Results: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed

  11. Sentinel lymph node imaging guided IMRT for prostate cancer: Individualized pelvic radiation therapy versus RTOG guidelines

    Directory of Open Access Journals (Sweden)

    Chien P. Chen, MD, PhD

    2016-01-01

    Conclusions: SLN-guided pelvic radiation therapy can be used to either treat the most critical nodes only or as an addition to RTOG guided pelvic radiation therapy to ensure that the most important nodes are included.

  12. A rare metastasis from a rare brain tumour

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior........ Oligodendroglioma are rare primary brain tumours of which extraneural metastasis is even more rare. The incidence of cases like this may be increasing because of better treatment and thus longer survival of patients with oligodendroglioma....

  13. Xerostomia health-related quality of life: NRG oncology RTOG 0537.

    Science.gov (United States)

    Wyatt, Gwen; Pugh, Stephanie L; Wong, Raimond K W; Sagar, Stephen; Singh, Anurag K; Koyfman, Shlomo A; Nguyen-Tân, Phuc F; Yom, Sue S; Cardinale, Francis S; Sultanem, Khalil; Hodson, Ian; Krempl, Greg A; Lukaszczyk, Barbara; Yeh, Alexander M; Berk, Lawrence

    2016-09-01

    The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

  14. Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Medicine; Tromsoe Univ. (Norway). Inst. of Clinical Medicine; Andratschke, N.H. [University Hospital Rostock (Germany). Dept. of Radiation Oncology; Geinitz, H. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Grosu, A.L. [University Hospital Freiburg (Germany). Dept. of Radiation Oncology

    2012-08-15

    Background and purpose: Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours. Patients and methods: This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests. Results: The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival. Conclusion: Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable. (orig.)

  15. Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies

    International Nuclear Information System (INIS)

    Nieder, C.; Tromsoe Univ.; Andratschke, N.H.; Geinitz, H.; Grosu, A.L.

    2012-01-01

    Background and purpose: Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours. Patients and methods: This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests. Results: The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival. Conclusion: Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable. (orig.)

  16. Computed tomographic brain scanning in the diagnosis of metastatic neoplasms

    International Nuclear Information System (INIS)

    Ringelstein, E.B.; Zeumer, H.; Hacke, W.; Keulers, P.

    1981-01-01

    Clinical investigations and computed brain scanning were done in 305 patients with primary extracerebral malignant tumours. One third of the patients had cerebral metastases. In most patients with brain metastases extracerebral secondary tumours were known already. Silent brain metastases were present in only 0.6% of all investigated tumour patients. All other patients had either objective neurologic-psychiatric defects or at least symptoms (headache, vomiting). Use of cranial computed tomography in all tumour patients as a pure screening method is thus not justified. The indication for the investigation is dependent on the clinical symptomatology. However, not only objective neurologic-psychiatric defects must be taken into account, but also occurrence of new symptoms. (orig.) [de

  17. SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

    Energy Technology Data Exchange (ETDEWEB)

    Honig, N; Alani, S; Schlocker, A; Shtraus, N; Kanner, A [B Corn Tel Aviv Medical Center, Tel Aviv (Israel)

    2016-06-15

    Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam delivery efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer monitor units

  18. SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

    International Nuclear Information System (INIS)

    Honig, N; Alani, S; Schlocker, A; Shtraus, N; Kanner, A

    2016-01-01

    Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam delivery efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer monitor units

  19. A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases

    International Nuclear Information System (INIS)

    Rodrigues, George; Yartsev, Slav; Tay, Keng Yeow; Pond, Gregory R; Lagerwaard, Frank; Bauman, Glenn

    2012-01-01

    Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT) to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS) boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT) was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. A phase I trial has been now completed at our institution with a total of 60 enrolled patients and 48 evaluable patients. The phase II dose has been determined to be the final phase I cohort dose of 60 Gy/10 fractions. The objective of this clinical trial is to subject the final phase I cohort dose to a phase II assessment of the endpoints of overall survival, intracranial control (ICC) and intralesional control (ILC). We hypothesize HT would be considered unsuitable for further study if the median OS for patients treated with the HT SIB technique is degraded by 2 months, or the intracranial progression-free rates (ICC and ILC) are inferior by 10% or greater compared to the expected results with treatment by whole brain plus SRS as defined by the RTOG randomized trial. A sample size of 93 patients was calculated based on these parameters as well as the statistical assumptions of alpha = 0.025 and beta = 0.1 due to multiple statistical testing. Secondary assessments of toxicity, health-related quality-of-life, cognitive changes, and tumor response are also integrated into this research protocol. To summarize, the purpose of this phase II trial is to assess this non-invasive alternative to SRS in terms of central nervous system (CNS) control when compared to SRS historical controls. A follow-up phase III trial may be required depending on the results of this trial in order to definitively assess non-inferiority/superiority of this approach. Ultimately, the purpose of this line of research is to

  20. Why avoid the hippocampus? A comprehensive review

    International Nuclear Information System (INIS)

    Gondi, Vinai; Tome, Wolfgang A.; Mehta, Minesh P.

    2010-01-01

    In this review article, we provide a detailed and comprehensive discussion of the rationale for using modern IMRT techniques to spare the subgranular zone of the hippocampus during cranial irradiation. We review the literature on neurocognitive effects of cranial irradiation; discuss clinical and preclinical data associating damage to neural progrenitor cells located in subgranular zone of the hippocampus with radiation-induced neurocognitive decline, specifically in terms of short-term memory formation and recall; and present a review of our pilot investigations into the feasibility and risks of sparing the subgranular zone of the hippocampus during whole-brain radiotherapy for brain metastases. We also introduce our phase II cooperative group clinical trial (RTOG 0933) designed to prospectively evaluate the postulated neurocognitive benefit of hippocampal subgranular zone sparing and scheduled to open in 2010.

  1. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  2. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets

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    Nitesh Rohatgi

    2018-01-01

    Full Text Available Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10–16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

  3. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  4. Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment

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    Donna H. Murrell

    2016-06-01

    Full Text Available INTRODUCTION: The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood-brain barrier (BBB limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT plan to investigate the impact of radiation on brain metastasis development and BBB permeability in a murine model. We hypothesize that radiotherapy will decrease tumor burden and increase tumor permeability, which could offer a mechanism to increase drug uptake in brain metastases. METHODS: Contrast-enhanced magnetic resonance imaging (MRI and high-resolution anatomical MRI were used to evaluate BBB integrity associated with brain metastases due to breast cancer in the MDA-MB-231-BR-HER2 model during their natural development. Novel image-guided microirradiation technology was employed to develop WBRT treatment plans and to investigate if this altered brain metastatic growth or permeability. Histology and immunohistochemistry were performed on whole brain slices corresponding with MRI to validate and further investigate radiological findings. RESULTS: Herein, we show successful implementation of microirradiation technology that can deliver WBRT to small animals. We further report that WBRT following diagnosis of brain metastasis can mitigate, but not eliminate, tumor growth in the MDA-MB-231-BR-HER2 model. Moreover, radiotherapy did not impact BBB permeability associated with metastases. CONCLUSIONS: Clinically relevant WBRT is not curative when delivered after MRI-detectable tumors have developed in this model. A dose of 20 Gy in 2 fractions was not sufficient to increase tumor permeability such that it could be used as a method to increase systemic drug uptake in brain metastasis.

  5. On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

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    Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher; Shen, Xinglei; Badkul, Rajeev; Jiang, Hongyu; Mallory, Matthew; Mitchell, Mellissa; Wang, Fen; Lominska, Christopher

    2017-04-01

    To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planning target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and

  6. Bone metastases from gastric cancer

    International Nuclear Information System (INIS)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

    1983-01-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

  7. An Institutional Retrospective Analysis of 93 Patients with Brain Metastases from Breast Cancer: Treatment Outcomes, Diagnosis-Specific Prognostic Factors

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    Delphine Antoni

    2012-12-01

    Full Text Available To evaluate the prognostic factors and indexes of a series of 93 patients with breast cancer and brain metastases (BM in a single institution. Treatment outcomes were evaluated according to the major prognostic indexes (RPA, BSBM, GPA scores and breast cancer subtypes. Independent prognostic factors for overall survival (OS were identified. The median OS values according to GPA 0–1, 1.5–2, 2.5–3 and 3.5–4, were 4.5, 9.5, 14.2 and 19.1 months, respectively (p < 0.0001 and according to genetic subtypes, they were 5, 14.2, 16.5 and 17.1 months for basal-like, luminal A and B and HER, respectively (p = 0.04. Using multivariate analysis, we established a new grading system using the six factors that were identified as indicators of longer survival: age under 60 (p = 0.001, high KPS (p = 0.007, primary tumor control (p = 0.05, low number of extracranial metastases and BM (p = 0.01 and 0.0002, respectively and triple negative subtype (p = 0.002. Three groups with significantly different median survival times were identified: 4.1, 9.5 and 26.3 months, respectively (p < 0.0001. Our new grading system shows that prognostic indexes could be improved by using more levels of classification and confirms the strength of biological prognostic factors.

  8. Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain metastases using intensity-modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pokhrel, Damodar, E-mail: dpokhrel@kumc.edu; Sood, Sumit; McClinton, Christopher; Shen, Xinglei; Lominska, Christopher; Saleh, Habeeb; Badkul, Rajeev; Jiang, Hongyu; Mitchell, Melissa; Wang, Fen

    2016-01-01

    Purpose: To retrospectively evaluate the accuracy, plan quality and efficiency of intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with multiple brain metastases (m-BM). Materials and methods: A total of 5 patients with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT treatment planning. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been fused with the planning CT image set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were contoured on T1/T2-weighted MRI registered with the 3D planning computed tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30 Gy for WB-PTV and 45 Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit avoidance sectors were used. Treatment plans were evaluated using homogeneity (HI) and conformity indices (CI) for target coverage and dose to organs at risk (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded and a gamma index was used to compare dose agreement between the planned and measured doses. Results: All 5 HS-WBRT with SIB plans met WB-PTV D{sub 2%}, D{sub 98%}, and V{sub 30} {sub Gy} NRG-CC001 requirements. The plans demonstrated highly conformal and homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 ± 0.04 (range: 0.27 to 0.36), and 0.96 ± 0.01 (range: 0.95 to 0.97), respectively. All 5

  9. Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain metastases using intensity-modulated arc therapy

    International Nuclear Information System (INIS)

    Pokhrel, Damodar; Sood, Sumit; McClinton, Christopher; Shen, Xinglei; Lominska, Christopher; Saleh, Habeeb; Badkul, Rajeev; Jiang, Hongyu; Mitchell, Melissa; Wang, Fen

    2016-01-01

    Purpose: To retrospectively evaluate the accuracy, plan quality and efficiency of intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with multiple brain metastases (m-BM). Materials and methods: A total of 5 patients with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT treatment planning. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been fused with the planning CT image set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were contoured on T1/T2-weighted MRI registered with the 3D planning computed tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30 Gy for WB-PTV and 45 Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit avoidance sectors were used. Treatment plans were evaluated using homogeneity (HI) and conformity indices (CI) for target coverage and dose to organs at risk (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded and a gamma index was used to compare dose agreement between the planned and measured doses. Results: All 5 HS-WBRT with SIB plans met WB-PTV D 2% , D 98% , and V 30 Gy NRG-CC001 requirements. The plans demonstrated highly conformal and homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 ± 0.04 (range: 0.27 to 0.36), and 0.96 ± 0.01 (range: 0.95 to 0.97), respectively. All 5 hippocampal sparing

  10. SU-F-T-43: Prediction of Dose Increments by Brain Metastases Resection Cavity Shrinkage Model with I-125 and Cs-131 LDR Seed Implantations

    Energy Technology Data Exchange (ETDEWEB)

    Han, D; Braunstein, S; Sneed, P; McDermott, M; Ma, L [University of California San Francisco, San Francisco, CA (United States)

    2016-06-15

    Purpose: This work aims to determine dose variability via a brain metastases resection cavity shrinkage model (RC-SM) with I-125 or Cs-131 LDR seed implantations. Methods: The RC-SM was developed to represent sequential volume changes of 95 consecutive brain metastases patients. All patients underwent serial surveillance MR and change in cavity volume was recorded for each patient. For the initial resection cavity, a prolate-ellipsoid cavity model was suggested and applied volume shrinkage rates to correspond to 1.7, 3.6, 5.9, 11.7, and 20.5 months after craniotomy. Extra-ring structure (6mm) was added on a surface of the resection volume and the same shrinkage rates were applied. Total 31 LDR seeds were evenly distributed on the surface of the resection cavity. The Amersham 6711 I-125 seed model (Oncura, Arlington Heights, IL) and the Model Cs-1 Rev2 Cs-131 seed model (IsoRay, Richland, WA) were used for TG-43U1 dose calculation and in-house-programed 3D-volumetric dose calculation system was used for resection cavity rigid model (RC-RM) and the RC-SM dose calculation. Results: The initial resection cavity volume shrunk to 25±6%, 35±6.8%, 42±7.7%, 47±9.5%, and 60±11.6%, with respect to sequential MR images post craniotomy, and the shrinkage rate (SR) was calculated as SR=56.41Xexp(−0.2024Xt)+33.99 and R-square value was 0.98. The normal brain dose as assessed via the dose to the ring structure with the RC-SM showed 29.34% and 27.95% higher than the RC-RM, I-125 and Cs-131, respectively. The dose differences between I-125 and Cs-131 seeds within the same models, I-125 cases were 9.17% and 10.35% higher than Cs-131 cases, the RC-RM and the RC-SM, respectively. Conclusion: A realistic RC-SM should be considered during LDR brain seed implementation and post-implement planning to prevent potential overdose. The RC-SM calculation shows that Cs-131 is more advantageous in sparing normal brain as the resection cavity volume changes with the LDR seeds implementation.

  11. Microenvironment Determinants of Brain Metastasis

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    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  12. Rare clinical experiences for surgical treatment of melanoma with osseous metastases in Taiwan

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    Yang Rong-Sen

    2007-07-01

    Full Text Available Abstract Background Malignant melanoma occurs infrequently in Taiwan. Once it has progressed into osseous metastases, the prognosis is poor. There are no reported clinical experiences of surgical management in this area. Methods To improve our understanding of the rare clinical experiences, we retrospectively investigated clinical characteristics, radiological findings, treatment modalities, survival outcomes and prognoses of 11 Taiwanese patients with osseous metastasis of melanoma treated surgically at two national medical centers, National Taiwan University Hospital and National Cheng Kung University Hospital from January 1983 to December 2006. Results Six patients suffered from acral-lentiginous melanoma. Nine patients sustained multiple osseous metastases and most lesions were osteolytic. Nine patients also had sustained metastases to other organs including liver, lungs, lymph nodes, brain and spleen. Second malignancies including lung cancer, thyroid papillary carcinoma, renal cell carcinoma and cervical cancer co-existed in four patients. The interval from the initial diagnosis of melanoma to the clinical detection of osseous metastases varied from 0–37.8 months (mean 9.75 months. Metastatic melanoma was invariably fatal; the mean survival time from bone metastases to death was 5.67 months. Conclusion Due to the high morbidity and poor survival of Taiwanese patients with osseous metastases of melanoma, surgical treatment should be directed towards pain relief and the prevention of skeletal debilitation in order to maintain their quality of life.

  13. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  14. Evaluation of Biomarkers Predictive of Benefit from the PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases

    Science.gov (United States)

    2017-07-01

    Small Cell Lung Cancer and Brain Metastases PRINCIPAL INVESTIGATOR: Sarah B. Goldberg, MD CONTRACTING ORGANIZATION: Yale University New Haven, CT...benefit in patients with non- small cell lung cancer (NSCLC). However, the overall response rate is only 20-30% and there is no clearly-defined...9. Appendices……………………………………………………………14 4 1. INTRODUCTION: Lung cancer is the leading cause of cancer death in the United States, resulting in more

  15. Gamma Knife Radiosurgery for Treatment of Cerebral Metastases From Non–Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Motta, Micaela; Vecchio, Antonella del; Attuati, Luca; Picozzi, Piero; Perna, Lucia; Franzin, Alberto; Bolognesi, Angelo; Cozzarini, Cesare; Calandrino, Riccardo; Mortini, Pietro; Muzio, Nadia di

    2011-01-01

    Purpose: To evaluate clinical and physico-dosimetric variables affecting clinical outcome of patients treated with Gamma Knife radiosurgery (GKRS) for brain metastases from non–small cell lung cancer (NSCLC). Methods and Materials: Between 2001 and 2006, 373 patients (298 men and 75 women, median age 65 years) with brain metastases from NSCLC underwent GKRS. All of them had KPS ≥ 60%, eight or fewer brain metastases, confirmed histopathological diagnosis and recent work-up ( 3 . Median marginal dose was 22.5 Gy at 50% isodose.; median 10 Gy and 12 Gy isodose volumes were 30.8 cm 3 and 15.8 cm 3 , respectively. Follow-up with MRI was performed every 3 months. Overall survival data were collected from internal database, telephone interviews, and identifying registries. Results: Mean follow-up after GKRS was 51 months (range, 6 to 96 months); mean overall survival was 14.2 months. Of 373 patients, 29 were alive at time of writing, 104 had died of cerebral progression, and 176 had died of systemic progression. In 64 cases it was not possible to ascertain the cause. Univariate and multivariate analysis were adjusted for the following: RPA class, surgery, WBRT, age, gender, number of lesions, median tumor volume, median peripheral dose, and 10 Gy and 12 Gy volumes. Identified RPA class and overall tumor volume >5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression. Conclusions: Global volume of brain disease should be the main parameter to consider for performing GKRS, which is a first-line therapy for patient in good general condition and controlled systemic disease.

  16. Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

    International Nuclear Information System (INIS)

    Lawton, Colleen A.F.; Lin, Xiaolei; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Brereton, Harmar D.; Bedi, Meena; Rosenthal, Seth A.; Zeitzer, Kenneth L.; Venkatesan, Varagur M.; Horwitz, Eric M.; Pisansky, Thomas M.; Kim, Harold; Parliament, Matthew B.; Rabinovitch, Rachel; Roach, Mack; Kwok, Young; Dignam, James J.; Sandler, Howard M.

    2017-01-01

    Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

  17. Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Colleen A.F., E-mail: clawton@mcw.edu [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lin, Xiaolei [University of Chicago, Chicago, Illinois (United States); Hanks, Gerald E. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Lepor, Herbert [New York University, New York, New York (United States); Grignon, David J. [Indiana University, Indianapolis, Indiana (United States); Brereton, Harmar D. [Northeast Radiation Oncology Center, Dunmore, Pennsylvania (United States); Bedi, Meena [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Rosenthal, Seth A. [Sutter General Hospital, Sacramento, California (United States); Zeitzer, Kenneth L. [Albert Einstein Medical Center, Philadelphia, Pennsylvania (United States); Venkatesan, Varagur M. [London Regional Cancer Program, London, Ontario (Canada); Horwitz, Eric M. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Pisansky, Thomas M. [Mayo Clinic, Rochester, Minnesota (United States); Kim, Harold [Wayne State University-Karmanos Cancer Institute, Detroit, Michigan (United States); Parliament, Matthew B. [Cross Cancer Institute, Edmonton, Alberta (Canada); Rabinovitch, Rachel [University of Colorado Denver, Denver, Colorado (United States); Roach, Mack [University of California, San Francisco, California (United States); Kwok, Young [University of Maryland Medical System, Baltimore, Maryland (United States); Dignam, James J. [University of Chicago, Chicago, Illinois (United States); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sandler, Howard M. [Cedars-Sinai Medical Center, Los Angeles, California (United States)

    2017-06-01

    Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

  18. Assessment of irradiated brain metastases using dynamic contrast-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Almeida-Freitas, Daniela B.; Pinho, Marco C.; Otaduy, Maria C.G.; Costa Leite, Claudia da; Braga, Henrique F.; Meira-Freitas, Daniel

    2014-01-01

    The purpose of this study was to evaluate the effect of stereotactic radiosurgery (SRS) on cerebral metastases using the transfer constant (K trans ) assessed by dynamic contrast-enhanced (DCE) MRI. Furthermore, we aimed to evaluate the ability of K trans measurements to predict midterm tumor outcomes after SRS. The study received institutional review board approval, and informed consent was obtained from all subjects. Twenty-six adult patients with a total of 34 cerebral metastases underwent T1-weighted DCE MRI in a 1.5-T magnet at baseline (prior to SRS) and 4-8 weeks after treatment. Quantitative analysis of DCE MRI was performed by generating K trans parametric maps, and region-of-interest-based measurements were acquired for each metastasis. Conventional MRI was performed at least 16 weeks after SRS to assess midterm tumor outcome using volume variation. The mean (±SD) K trans value was 0.13 ± 0.11 min -1 at baseline and 0.08 ± 0.07 min -1 after 4-8 weeks post-treatment (p trans after SRS was predictive of tumor progression (hazard ratio = 1.50; 95 % CI = 1.16-1.70, p trans showed a sensitivity of 78 % and a specificity of 85 % for the prediction of progression at midterm follow-up. SRS was associated with a reduction of K trans values of the cerebral metastases in the early post-treatment period. Furthermore, K trans variation as assessed using DCE MRI may be helpful to predict midterm outcomes after SRS. (orig.)

  19. Quality of Life in Patients With Brain Metastases Using the EORTC QLQ-BN20+2 and QLQ-C15-PAL

    International Nuclear Information System (INIS)

    Caissie, Amanda; Nguyen, Janet; Chen, Emily; Zhang Liying; Sahgal, Arjun; Clemons, Mark; Kerba, Marc; Arnalot, Palmira Foro; Danjoux, Cyril; Tsao, May; Barnes, Elizabeth; Holden, Lori; Danielson, Brita; Chow, Edward

    2012-01-01

    Purpose: The 20-item European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Neoplasm (QLQ-BN20) is a validated quality-of-life (QOL) questionnaire for patients with primary brain tumors. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 15 Palliative (QLQ-C15-PAL) core palliative questionnaire is a 15-item version of the core 30-item QLQ-C30 and was developed to decrease the burden on patients with advanced cancer. The combination of the QLQ-BN20 and QLQ-C30 to assess QOL may be too burdensome for patients. The primary aim of this study was to assess QOL in patients before and after treatment for brain metastases using the QLQ-BN20+2 and QLQ-C15-PAL, a version of the QLQ-BN20 questionnaire with 2 additional questions assessing cognitive functioning that were not addressed in the QLQ-C15-PAL. Methods and Materials: Patients with brain metastases completed the QLQ-C15-PAL and QLQ-BN20+2 questionnaires to assess QOL before and 1 month after radiation. Linear regression analysis was used to assess changes in QOL scores over time, as well as to explore associations between the QLQ-BN20+2 and QLQ-C15-PAL scales, patient demographics, and clinical variables. Spearman correlation assessed associations between the QLQ-BN20+2 and QLQ-C15-PAL scales. Results: Among 108 patients, the majority (55%) received whole-brain radiotherapy only, with 65% of patients completing follow-up at 1 month after treatment. The most prominent symptoms at baseline were future uncertainty (QLQ-BN20+2) and fatigue (QLQ-C15-PAL). After treatment, significant improvement was seen for the QLQ-C15-PAL insomnia scale, as well as the QLQ-BN20+2 scales of future uncertainty, visual disorder, and concentration difficulty. Baseline Karnofsky Performance Status was negatively correlated to QLQ-BN20+2 motor dysfunction but positively related to QLQ-C15-PAL physical functioning and QLQ-BN20+2 cognitive functioning at

  20. Quality of Life in Patients With Brain Metastases Using the EORTC QLQ-BN20+2 and QLQ-C15-PAL

    Energy Technology Data Exchange (ETDEWEB)

    Caissie, Amanda; Nguyen, Janet; Chen, Emily; Zhang Liying [Rapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Sahgal, Arjun [Rapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Clemons, Mark [Department of Medical Oncology, Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada); Kerba, Marc [Department of Radiation Oncology, Tom Baker Cancer Centre, Calgary, Alberta (Canada); Arnalot, Palmira Foro [Parc de Salut Mar Hospital de l' Esperanca, Barcelona (Spain); Danjoux, Cyril; Tsao, May; Barnes, Elizabeth; Holden, Lori [Rapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Danielson, Brita [Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta (Canada); Chow, Edward, E-mail: edward.chow@sunnybrook.ca [Rapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2012-07-15

    Purpose: The 20-item European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm (QLQ-BN20) is a validated quality-of-life (QOL) questionnaire for patients with primary brain tumors. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15 Palliative (QLQ-C15-PAL) core palliative questionnaire is a 15-item version of the core 30-item QLQ-C30 and was developed to decrease the burden on patients with advanced cancer. The combination of the QLQ-BN20 and QLQ-C30 to assess QOL may be too burdensome for patients. The primary aim of this study was to assess QOL in patients before and after treatment for brain metastases using the QLQ-BN20+2 and QLQ-C15-PAL, a version of the QLQ-BN20 questionnaire with 2 additional questions assessing cognitive functioning that were not addressed in the QLQ-C15-PAL. Methods and Materials: Patients with brain metastases completed the QLQ-C15-PAL and QLQ-BN20+2 questionnaires to assess QOL before and 1 month after radiation. Linear regression analysis was used to assess changes in QOL scores over time, as well as to explore associations between the QLQ-BN20+2 and QLQ-C15-PAL scales, patient demographics, and clinical variables. Spearman correlation assessed associations between the QLQ-BN20+2 and QLQ-C15-PAL scales. Results: Among 108 patients, the majority (55%) received whole-brain radiotherapy only, with 65% of patients completing follow-up at 1 month after treatment. The most prominent symptoms at baseline were future uncertainty (QLQ-BN20+2) and fatigue (QLQ-C15-PAL). After treatment, significant improvement was seen for the QLQ-C15-PAL insomnia scale, as well as the QLQ-BN20+2 scales of future uncertainty, visual disorder, and concentration difficulty. Baseline Karnofsky Performance Status was negatively correlated to QLQ-BN20+2 motor dysfunction but positively related to QLQ-C15-PAL physical functioning and QLQ-BN20+2 cognitive functioning at

  1. Sanctuary site leptomeningeal metastases in HER-2 positive breast cancer: A review in the era of trastuzumab.

    Science.gov (United States)

    Kordbacheh, T; Law, W Y; Smith, I E

    2016-04-01

    The development of trastuzumab and other targeted systemic therapies has transformed the management of HER-2 positive breast cancers. However, as patients live longer and systemic therapies may not cross the blood brain barrier a rising number of patients are developing leptomeningeal metastases and brain metastases as a sanctuary site of disease. Intrathecal trastuzumab has been reported to treat these. We describe a breast cancer patient with HER-2 positive leptomeningeal disease in the spinal cord successfully treated with intrathecal trastuzumab and methotrexate, alongside systemic anti-HER-2 therapy and radiotherapy. We also review the literature to date on the efficacy and safety of intrathecal trastuzumab, and recent evidence suggesting that intrathecal trastuzumab passes via the blood brain barrier into the serum to achieve intravenous concentrations similar to that seen with systemic therapy alone. Overall, intrathecal trastuzumab appears to be a safe and often effective treatment for leptomeningeal metastases in HER-2 positive breast cancer. Ongoing phase I and II studies are required to determine optimum dosing schedules, validate CSF and CSF-to-serum pharmacokinetics, determine efficacy, and to assess the added benefits or disadvantages of prior radiotherapy and concomitant systemic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients.

    Science.gov (United States)

    Harries, M; Taylor, A; Holmberg, L; Agbaje, O; Garmo, H; Kabilan, S; Purushotham, A

    2014-08-01

    Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with early, and proportionately fewer patients in this group. Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

    Science.gov (United States)

    Churilla, Thomas M; Ballman, Karla V; Brown, Paul D; Twohy, Erin L; Jaeckle, Kurt; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Garces, Yolanda I; Barker, Fred G; Deming, Richard; Dixon, Jesse G; Burri, Stuart H; Chung, Caroline; Ménard, Cynthia; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L

    2017-12-01

    To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5). A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Pulmonary Benign Metastasizing Leiomyoma from the Uterine Leiomyoma: A Case Report

    International Nuclear Information System (INIS)

    Kołaczyk, Katarzyna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Chosia, Maria; Szydłowska, Iwona; Starczewski, Andrzej; Grodzki, Tomasz; Smereczyński, Andrzej; Sawicki, Marcin

    2015-01-01

    Benign metastasizing leiomyoma (BML) is a rare condition described as multiple well-differentiated leiomyomas at sites distant from the uterus. Apart from lungs it has also been reported in lymph nodes, heart, brain, bone, skin, eye and spinal cord. We present a case of pulmonary benign metastasizing leiomyoma in a female patient admitted to our hospital with suspicion of left adnexal tumor. A 45-year-old woman was referred to our hospital with suspicion of left adnexal tumor. The control transvaginal ultrasound examination performed at admission to the Gynecological Department excluded adnexal neoplasm. However, a large amount of fluid within the Douglas pouch raised the oncological concern. The patient underwent myomectomy in 2005. In the same year she was diagnosed with multiple lung nodules and underwent pulmonary wedge resection with the diagnosis of pulmonary benign metastasizing leiomyoma being stated. The decision of reevaluation of the specimen, control CT and puncture of the Douglas pouch fluid was made. Computed tomography performed at the Department of Diagnostic Imaging and Interventional Radiology of the Pomeranian Medical University Hospital revealed multiple, bilateral nodules. The microscopic examination of the samples confirmed the initial diagnosis of benign metastasizing leiomyoma with no evidence of neoplastic cells within the fluid. Pulmonary benign metastasizing leiomyoma is a rare entity. However, it should be always taken into consideration in women with a previous or coincident history of uterine leiomyoma, especially when no evidence of other malignancy is present

  5. Pain palliation therapy of bone metastases: palliative or curative?

    International Nuclear Information System (INIS)

    Fischer, M.

    2007-01-01

    In Germany the incidence of breast cancer is about 85 and of prostate cancer about 50 new patients per 100.000 inhabitants/year. In about 80% of prostate cancer patients and 75% of breast cancer patients bone metastases are observed in autopsy. Most of these patients develop severe pain syndrome from bone metastases reducing quality of life during life time. Therapy of these patients should aim at adding life to the years not years to their life. The knowledge of metastatic cell biology, of cell-cell interaction and of tumor-cell, tumor cell-skeleton interaction may modify the therapeutic procedure. Already in 1940/41, Pecher treated a patient suffering from painful prostate cancer bone metastases administering 296 MBq 89 Strontium chloride. About 10 years later, Friedell introduced 32 Phosphorus for treatment of bone metastases from breast cancer. Today in Europe 3 radionuclides are approved for pain palliation therapy as shown in Table.1. Indication: - pain palliation therapy of bone metastases from prostate cancer ( 89 Sr and 186 Re); - pain palliation of all osteoblastic metastases independent from primary tumors ( 153 Sm). Contraindications: - pregnant and lactating females - myelosuppression ( 3 granulocytes; 3 platelets); - impaired renal function (urea >12 mmol/l; creatinine > 150 mmol/l) - incontinence; - acute or chronic spinal cord compression and/or brain metastases causing neurological symptoms; - disseminated intravascular coagulopathy. The recommended activities per treatment are: 89 Sr 150 MBq, 186 Re 1.295 MBq, and 153 Sm 37 MBq/kg BW. Shortly (6-8 weeks) prior to radionuclide therapy for pain palliation no high dose chemotherapy or large field radiation therapy should be performed. Stopping unlabelled bisphosphonate therapy prior to pain palliation therapy is not necessary. This radionuclide therapy may be repeated several time, the interval between tracer administration depends on blood cell count rate. The recommended intervals are for 89 Sr

  6. High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

    Science.gov (United States)

    Wu, Yingjen Jeffrey; Pagel, Michael A; Muldoon, Leslie L; Fu, Rongwei; Neuwelt, Edward A

    2017-08-01

    Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.

    Science.gov (United States)

    Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl; Sydes, Benjamin; Stephens, Richard; Parmar, Mahesh K; Langley, Ruth E

    2016-10-22

    Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061. Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to

  8. Importance of the spinal venous system in the formation of metastases

    International Nuclear Information System (INIS)

    Gowin, W.

    1983-01-01

    The vertebral veins and their anastomoses to the other venous vascular regions are presented in their anatomy, physiological and pathophysiological function, with a special reference to the spreading of tumor cells through the veins of the vertebral column. The causes of the accumulation of metastases in the trunk skeleton and brain is pointed out by malignant tumors of the prostata, of the ren, of the lung, of the mamma, of the genital organs and the thyroid gland. The signification of the vertebral venous system as a spread of metastases is emphasized under consideration of the tumor cell kinetics in the blood-flow and the different forms of the metastatic formations, and is verifying by experienced clinical cases and reviews of the literature. (orig.) [de

  9. Stereotactic radiotherapy for brain metastasis

    International Nuclear Information System (INIS)

    Noel, G.; Daisne, J.F.; Thillays, F.

    2012-01-01

    Stereotactic radiosurgery is now well implanted in the radiotherapy treatment tools of brain metastasis. The dose can be delivered in one or multiple sessions. Results seem equivalent. CT scan and MRI imaging are required to delineate and calculate dosimetry. Doses are variable according to the size of the metastases, localization, pathology or equipment. Stabilization or reduction of tumour size is the rules after stereotactic treatment. Impact in terms of overall survival is more difficult to apprehend because of the general context of the disease. Many questions remain unresolved, such as the usefulness of whole brain irradiation, adaptation of the treatment schedule to tumour pathophysiology, role of stereotactic treatment after surgery of metastases, etc. (authors)

  10. Analysis of 2000 cases treated with gamma knife surgery: validating eligibility criteria for a prospective multi-institutional study of stereotactic radiosurgery alone for treatment of patients with 1-10 brain metastases (JLGK0901) in Japan

    Science.gov (United States)

    Higuchi, Yoshinori; Nagano, Osamu; Sato, Yasunori; Yamamoto, Masaaki; Ono, Junichi; Saeki, Naokatsu; Miyakawa, Akifumi; Hirai, Tatsuo

    2012-01-01

    Objective The Japan Leksell Gamma Knife (JLGK) Society has conducted a prospective multi-institute study (JLGK0901, UNIN000001812) for selected patients in order to prove the effectiveness of stereotactic radiosurgery (SRS) alone using the gamma knife (GK) for 1-10 brain lesions. Herein, we verify the validity of 5 major patient selection criteria for the JLGK0901 trial. Materials and Methods Between 1998 and 2010, 2246 consecutive cases with 10352 brain metastases treated with GK were analyzed to determine the validity of the following 5 major JLGK0901 criteria; 1) 1-10 brain lesions, 2) less than 10 cm3 volume of the largest tumor, 3) no more than 15 cm3 total tumor volume, 4) no cerebrospinal fluid (CSF) dissemination, 5) Karnofsky performance status (KPS) score ≥70. Results For cases with >10 brain metastases, salvage treatments for new lesions were needed more frequently. The tumor control rate for lesions larger than 10 cm3 was significantly lower than that of tumors 15 cm3 total tumor volume or positive magnetic resonance imaging findings of CSF were significantly poorer. Outcomes in cases with KPS <70 were significantly poorer in terms of OS. Conclusion Our retrospective results of 2246 GK-treated cases verified the validity of the 5 major JLGK0901 criteria. The inclusion criteria for the JLGK0901 study are appearently good indications for SRS. PMID:29296339

  11. Fluid–fluid level in hepatic metastases: A characteristic sign of metastases of neuroendocrine origin

    International Nuclear Information System (INIS)

    Sommer, Wieland H.; Zech, Christoph J.; Bamberg, Fabian; Auernhammer, Christoph J.; Helck, Andreas; Paprottka, Philipp M.; Notohamiprodjo, Mike; Reiser, Maximilian F.; Herrmann, Karin A.

    2012-01-01

    Objectives: The aim of this study is to determine MRI characteristics which indicate liver metastases of neuroendocrine tumors (NET) rather than metastases of other origin (non-NET). Methods: Sixty-nine patients with histopathologically proven liver metastases from NET and 69 patients with known liver metastases of other origin underwent MRI of the liver using a 1.5 T MR-scanner. Two board certified radiologists assessed presence of fluid–fluid-levels, number and distribution pattern, signal intensity (SI) characteristics, lesion homogeneity, presence of central necrosis and intratumoral hemorrhage in T2w and T1w non-contrast imaging. A multivariate logistic regression analysis was performed to determine the independent association of image findings and occurrence of NET. Results: Fluid–fluid-levels were identified in 19/69 of patients with NET-metastases, and in none of the patients in the control group (p < 0.0001). Hyperintense SI in T1w imaging, markedly hyperintense SI in T2w imaging, a disseminated distribution pattern and intratumoral hemorrhage were indicative of NET metastases (p < 0.05). After statistical adjustment for all significant MRI findings, fluid–fluid-levels (OR: 17.6, 95% CI: 1.9–166.5), strongly hyperintense SI in T2w (OR: 4.7, 95% CI: 1.8–12.7) and a disseminated distribution pattern (OR: 2.9, 95% CI: 1.1–7.4) were independent predictors for NET metastases. Conclusions: The presence of fluid–fluid-levels is highly indicative of NET liver metastases and can be used as an independent predictor to distinguish them from metastases of other origin

  12. Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

    Science.gov (United States)

    Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

    2018-01-22

    Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  13. P13.10 Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases

    Science.gov (United States)

    Yust-Katz, S.; Dudnik, E.; Perlov, E.; Zer, A.; Flex, D.; Peled, N.; Siegal, T.

    2016-01-01

    Abstract Background: Central nervous system (CNS) metastases occur in about 30% of patients (pts) with advanced non-small cell lung cancer (NSCLC). Local treatment strategies (e.g., radiotherapy or surgery) result in delays in systemic therapy administration and are frequently associated with neurocognitive impairment. Nivolumab is an anti-PD1 immune check-point inhibitor which has been recently approved by the FDA as a second line treatment of NSCLC. Data regarding its intracranial activity is lacking. Methods: We retrospectively reviewed efficacy and safety of nivolumab administered intravenously at a dose of 3mg/kg q2 weeks in five pts with advanced NSCLC and new or progressing intracranial metastases which were diagnosed before or within 1 month after starting the treatment. Results: Pt baseline characteristics were as follows: median age 78y (range, 52–84); 2 males; 4 smokers; ECOG PS 0/1/2 - 2 pts/1 pt/2 pts; histological subtype: adenocarcinoma/ squamous-cell carcinoma/NSCLC NOS 3 pts /1 pt/1 pt; EGFR WT/ALK neg/KRAS M all/all/2 pts. Four pts had parenchymal brain metastases, three pts had leptomeningeal disease. All pts were asymptomatic and did not require corticosteroids or immediate brain irradiation. Dramatic response in the brain was observed in two pts (including 1 pt with leptomeningeal spread demonstrating a complete response in the CNS); time-to-response comprised 5 weeks and 9 weeks; all responses are still ongoing at the time of the report (18+ weeks, 19+ weeks). In one pt stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved. Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS-metastases related grade ≥ 3 adverse events were observed. Conclusions: Nivolumab has a promising intracranial activity and favorable safety profile in pts with NSCLC and untreated/progressing CNS metastases. Nivolumab CNS activity warrants further evaluation.

  14. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  15. SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

    International Nuclear Information System (INIS)

    Kraus, J; Thomas, E; Wu, X; Fiveash, J; Popple, R

    2016-01-01

    Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC. Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.

  16. SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, J; Thomas, E; Wu, X; Fiveash, J; Popple, R [University Alabama Birmingham, Birmingham, AL (United States)

    2016-06-15

    Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC. Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.

  17. Efficacy on maximum intensity projection of contrast-enhanced 3D spin echo imaging with improved motion-sensitized driven-equilibrium preparation in the detection of brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Yun Jung; Choi, Byung Se; Yoon, Yeon Hong; Woo, Leonard Sun; Jung, Cheol Kyu; Kim, Jae Hyoung [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Lee, Kyung Mi [Dept. of Radiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2017-08-01

    To evaluate the diagnostic benefits of 5-mm maximum intensity projection of improved motion-sensitized driven-equilibrium prepared contrast-enhanced 3D T1-weighted turbo-spin echo imaging (MIP iMSDE-TSE) in the detection of brain metastases. The imaging technique was compared with 1-mm images of iMSDE-TSE (non-MIP iMSDE-TSE), 1-mm contrast-enhanced 3D T1-weighted gradient-echo imaging (non-MIP 3D-GRE), and 5-mm MIP 3D-GRE. From October 2014 to July 2015, 30 patients with 460 enhancing brain metastases (size > 3 mm, n = 150; size ≤ 3 mm, n = 310) were scanned with non-MIP iMSDE-TSE and non-MIP 3D-GRE. We then performed 5-mm MIP reconstruction of these images. Two independent neuroradiologists reviewed these four sequences. Their diagnostic performance was compared using the following parameters: sensitivity, reading time, and figure of merit (FOM) derived by jackknife alternative free-response receiver operating characteristic analysis. Interobserver agreement was also tested. The mean FOM (all lesions, 0.984; lesions ≤ 3 mm, 0.980) and sensitivity ([reader 1: all lesions, 97.3%; lesions ≤ 3 mm, 96.2%], [reader 2: all lesions, 97.0%; lesions ≤ 3 mm, 95.8%]) of MIP iMSDE-TSE was comparable to the mean FOM (0.985, 0.977) and sensitivity ([reader 1: 96.7, 99.0%], [reader 2: 97, 95.3%]) of non-MIP iMSDE-TSE, but they were superior to those of non-MIP and MIP 3D-GREs (all, p < 0.001). The reading time of MIP iMSDE-TSE (reader 1: 47.7 ± 35.9 seconds; reader 2: 44.7 ± 23.6 seconds) was significantly shorter than that of non-MIP iMSDE-TSE (reader 1: 78.8 ± 43.7 seconds, p = 0.01; reader 2: 82.9 ± 39.9 seconds, p < 0.001). Interobserver agreement was excellent (κ > 0.75) for all lesions in both sequences. MIP iMSDE-TSE showed high detectability of brain metastases. Its detectability was comparable to that of non-MIP iMSDE-TSE, but it was superior to the detectability of non-MIP/MIP 3D-GREs. With a shorter reading time, the false-positive results of MIP i

  18. Validity of Three Recently Proposed Prognostic Grading Indexes for Breast Cancer Patients With Radiosurgically Treated Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Masaaki, E-mail: BCD06275@nifty.com [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Tokyo Women' s Medical University Medical Center E, Tokyo (Japan); Kawabe, Takuya [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto (Japan); Higuchi, Yoshinori [Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba (Japan); Sato, Yasunori [Clinical Research Center, Chiba University Graduate School of Medicine, Chiba (Japan); Barfod, Bierta E. [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Kasuya, Hidetoshi [Department of Neurosurgery, Tokyo Women' s Medical University Medical Center E, Tokyo (Japan); Urakawa, Yoichi [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan)

    2012-12-01

    Purpose: We tested the validity of 3 recently proposed prognostic indexes for breast cancer patients with brain metastases (METs) treated radiosurgically. The 3 indexes are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), New Breast Cancer (NBC)-Recursive Partitioning Analysis (RPA), and our index, sub-classification of RPA class II patients into 3 sub-classes (RPA class II-a, II-b and II-c) based on Karnofsky performance status, tumor number, original tumor status, and non-brain METs. Methods and Materials: This was an institutional review board-approved, retrospective cohort study using our database of 269 consecutive female breast cancer patients (mean age, 55 years; range, 26-86 years) who underwent Gamma Knife radiosurgery (GKRS) alone, without whole-brain radiation therapy, for brain METs during the 15-year period between 1996 and 2011. The Kaplan-Meier method was used to estimate the absolute risk of each event. Results: Kaplan-Meier plots of our patient series showed statistically significant survival differences among patients stratified into 3, 4, or 5 groups based on the 3 systems (P<.001). However, the mean survival time (MST) differences between some pairs of groups failed to reach statistical significance with all 3 systems. Thus, we attempted to regrade our 269 breast cancer patients into 3 groups by modifying our aforementioned index along with the original RPA class I and III, (ie, RPA I+II-a, II-b, and II-c+III). There were statistically significant MST differences among these 3 groups without overlap of 95% confidence intervals (CIs) between any 2 pairs of groups: 18.4 (95% CI = 14.0-29.5) months in I+II-a, 9.2 in II-b (95% CI = 6.8-12.9, P<.001 vs I+II-a) and 5.0 in II-c+III (95% CI = 4.2-6.8, P<.001 vs II-b). Conclusions: As none of the new grading systems, DS-GPS, BC-RPA and our system, was applicable to our set of radiosurgically treated patients for comparing survivals after GKRS, we slightly modified our system for breast cancer

  19. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  20. Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

    2012-01-01

    The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

  1. Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery.

    Science.gov (United States)

    Chowdhary, Mudit; Switchenko, Jeffrey M; Press, Robert H; Jhaveri, Jaymin; Buchwald, Zachary S; Blumenfeld, Philip A; Marwaha, Gaurav; Diaz, Aidnag; Wang, Dian; Abrams, Ross A; Olson, Jeffrey J; Shu, Hui-Kuo G; Curran, Walter J; Patel, Kirtesh R

    2018-05-30

    Neutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM). BM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. 188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03-2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30-2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes. Post-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

  2. Are metastases from metastases clinical relevant? Computer modelling of cancer spread in a case of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Anja Bethge

    Full Text Available BACKGROUND: Metastasis formation remains an enigmatic process and one of the main questions recently asked is whether metastases are able to generate further metastases. Different models have been proposed to answer this question; however, their clinical significance remains unclear. Therefore a computer model was developed that permits comparison of the different models quantitatively with clinical data and that additionally predicts the outcome of treatment interventions. METHODS: The computer model is based on discrete events simulation approach. On the basis of a case from an untreated patient with hepatocellular carcinoma and its multiple metastases in the liver, it was evaluated whether metastases are able to metastasise and in particular if late disseminated tumour cells are still capable to form metastases. Additionally, the resection of the primary tumour was simulated. The simulation results were compared with clinical data. RESULTS: The simulation results reveal that the number of metastases varies significantly between scenarios where metastases metastasise and scenarios where they do not. In contrast, the total tumour mass is nearly unaffected by the two different modes of metastasis formation. Furthermore, the results provide evidence that metastasis formation is an early event and that late disseminated tumour cells are still capable of forming metastases. Simulations also allow estimating how the resection of the primary tumour delays the patient's death. CONCLUSION: The simulation results indicate that for this particular case of a hepatocellular carcinoma late metastases, i.e., metastases from metastases, are irrelevant in terms of total tumour mass. Hence metastases seeded from metastases are clinically irrelevant in our model system. Only the first metastases seeded from the primary tumour contribute significantly to the tumour burden and thus cause the patient's death.

  3. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg -/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg -/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  4. Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

    Energy Technology Data Exchange (ETDEWEB)

    Farris, Michael, E-mail: mfarris@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); McTyre, Emory R.; Cramer, Christina K.; Hughes, Ryan; Randolph, David M.; Ayala-Peacock, Diandra N.; Bourland, J. Daniel [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Ruiz, Jimmy [Department of Medicine - Hematology & Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Watabe, Kounosuke [Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Laxton, Adrian W.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Zhou, Xiaobo [Center for Bioinformatics & Systems Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States)

    2017-05-01

    Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.

  5. Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

    International Nuclear Information System (INIS)

    Farris, Michael; McTyre, Emory R.; Cramer, Christina K.; Hughes, Ryan; Randolph, David M.; Ayala-Peacock, Diandra N.; Bourland, J. Daniel; Ruiz, Jimmy; Watabe, Kounosuke; Laxton, Adrian W.; Tatter, Stephen B.; Zhou, Xiaobo; Chan, Michael D.

    2017-01-01

    Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.

  6. Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

    International Nuclear Information System (INIS)

    Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam; Hope, Andrew J.; Lindsay, Patricia E.; Bosch, Walter R.; Matthews, John W.; Sause, William T.; Graham, Mary V.; Deasy, Joseph O.

    2012-01-01

    Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non–small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose–volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior–inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 ∗ MED+1.50 ∗ ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis

  7. Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Hope, Andrew J.; Lindsay, Patricia E. [Princess Margaret Hospital, Toronto, ON (Canada); Bosch, Walter R.; Matthews, John W. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Sause, William T. [Department of Radiation Oncology, LDS Hospital, Salt Lake City, UT (United States); Graham, Mary V. [Department of Radiation Oncology, Phelps County Regional Hospital, Rolla, MO (United States); Deasy, Joseph O., E-mail: deasyj@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts

  8. Modeling the risk of radiation-induced acute esophagitis for combined Washington University and RTOG trial 93-11 lung cancer patients.

    Science.gov (United States)

    Huang, Ellen X; Bradley, Jeffrey D; El Naqa, Issam; Hope, Andrew J; Lindsay, Patricia E; Bosch, Walter R; Matthews, John W; Sause, William T; Graham, Mary V; Deasy, Joseph O

    2012-04-01

    To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 MED+1.50 ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets. Copyright

  9. CSF protein profiling using Multiplex Immuno-assay : A potential new diagnostic tool for leptomeningeal metastases.

    NARCIS (Netherlands)

    Brandsma, D.; Voest, E.E.; Jager, W. de; Bonfrer, H.; Algra, A.; Boogerd, W.; Korse, T.; Reijneveld, J.C.; Verbeek, M.M.; Rijkers, G.; Taphoorn, M.J.B.

    2006-01-01

    OBJECTIVE: The diagnosis of leptomeningeal metastases (LM) is based on clinical symptoms, magnetic resonance imaging (MRI) of brain and spine and cytological analysis of cerebrospinal fluid (CSF). The clinical picture of LM is highly variable and both cytological CSF analysis and contrast-enhanced

  10. Spinal metastases of malignant gliomas

    International Nuclear Information System (INIS)

    Materlik, B.; Steidle-Katic, U.; Feyerabend, T.; Richter, E.; Wauschkuhn, B.

    1998-01-01

    Purpose: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. Patients and Method: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. Results: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. Conclusions: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms. (orig.) [de

  11. Characterization of the melanoma brain metastatic niche in mice and humans

    International Nuclear Information System (INIS)

    Amit, Moran; Laider-Trejo, Leonor; Shalom, Vardit; Shabtay-Orbach, Ayelet; Krelin, Yakov; Gil, Ziv

    2013-01-01

    Brain metastases occur in 15% of patients with melanoma and are associated with a dismal prognosis. Here, we investigate the architectural phenotype and stromal reaction of melanoma brain metastasis in mice and humans. A syngeneic, green fluorescence protein (GFP)-expressing murine B16-F1 melanoma clone was introduced via intracardiac injection, and was examined in vivo in comparison with human specimens. Immunofluorescence analyses of the brain metastases revealed that F4/80 + macrophages/microglia were most abundant at the tumor front, but rare in its core, where they were found only around blood vessels (P = 0.01). Similar pattern of infiltration was found in CD3 + T cells (P < 0.01). Infiltrating T cells were prominently CD4 + compared with CD8 + T cells (P < 0.001). Blood vessels (CD31 + ) were less abundant at the tumor front than in its center (12 ± 1 vs. 4 ± 0.6 vessels per high-power field [HPF], P < 0.001). In contrast, there were few vessels at the tumor front, but their diameter was significantly larger at the front (8236 μm 2 vs. 4617 μm 2 average cross-sectional area, P < 0.005). This is the first comparative analysis of melanoma brain metastases showing similar stromal reaction in murine models and human specimens. Our results validate the utility of this murine model of melanoma brain metastases for investigating the mechanism of the human disease

  12. Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases.

    Science.gov (United States)

    Fan, Yun; Xu, Yanjun; Gong, Lei; Fang, Luo; Lu, Hongyang; Qin, Jing; Han, Na; Xie, Fajun; Qiu, Guoqin; Huang, Zhiyu

    2017-03-23

    EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole cohort (95% CI, 23.9-30.1 months). There was no difference in OS between the RT followed by icotinib group and the icotinib alone group (31.9 vs. 27.9 months, P = 0.237), and similar results were found in the SRS subgroup (35.5 vs. 27.9 months, P = 0.12). Patients with the EGFR Del19 mutation had a longer OS than patients with the exon 21 L858R mutation (32.7 vs. 27.4, P = 0.037). Intracranial progression-free survival (PFS) was improved in the patients who received RT followed by icotinib compared to those receiving icotinib alone (22.4 vs. 13.9 months, P = 0.043). Patients with EGFR-mutant adenocarcinoma and BM treated with icotinib exhibited prolonged survival. A longer duration of intracranial control was observed with brain RT.

  13. A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer.

    Science.gov (United States)

    Fan, Yun; Huang, Zhiyu; Fang, Luo; Miao, Lulu; Gong, Lei; Yu, Haifeng; Yang, Haiyan; Lei, Tao; Mao, Weimin

    2015-09-01

    Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated. Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry. Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0%. The median progression-free survival time was 7.0 months (95% CI 1.2-13.2 months), and the median survival time (MST) was 14.6 months (95% CI 12.5-16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 ± 9.1 ng/mL and 1.4 ± 1.1%, respectively. No patient experienced ≥grade 4 toxicity. Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.

  14. Cortical bone metastases

    International Nuclear Information System (INIS)

    Davis, T.M. Jr.; Rogers, L.F.; Hendrix, R.W.

    1986-01-01

    Twenty-five cases of bone metastases involving the cortex alone are reviewed. Seven patients had primary lung carcinoma, while 18 had primary tumors not previously reported to produce cortical bone metastases (tumors of the breast, kidney, pancreas, adenocarcinoma of unknown origin, multiple myeloma). Radiographically, these cortical lesions were well circumscribed, osteolytic, and produced soft-tissue swelling and occasional periosteal reaction. A recurrent pattern of metadiaphyseal involvement of the long bones of the lower extremity (particularly the femur) was noted, and is discussed. Findings reported in the literature, review, pathophysiology, and the role of skeletal radiographs, bone scans, and CT scans in evaluating cortical bone metastases are addressed

  15. Changing practice patterns of Gamma Knife versus linear accelerator-based stereotactic radiosurgery for brain metastases in the US.

    Science.gov (United States)

    Park, Henry S; Wang, Elyn H; Rutter, Charles E; Corso, Christopher D; Chiang, Veronica L; Yu, James B

    2016-04-01

    Single-fraction stereotactic radiosurgery (SRS) is a crucial component in the management of limited brain metastases from non-small cell lung cancer (NSCLC). Intracranial SRS has traditionally been delivered using a frame-based Gamma Knife (GK) platform, but stereotactic modifications to the linear accelerator (LINAC) have made an alternative approach possible. In the absence of definitive prospective trials comparing the efficacy and toxicities of treatment between the 2 techniques, nonclinical factors (such as technology accessibility, costs, and efficiency) may play a larger role in determining which radiosurgery system a facility may choose to install. To the authors' knowledge, this study is the first to investigate national patterns of GK SRS versus LINAC SRS use and to determine which factors may be associated with the adoption of these radiosurgery systems. The National Cancer Data Base was used to identify patients > 18 years old with NSCLC who were treated with single-fraction SRS to the brain between 2003 and 2011. Patients who received "SRS not otherwise specified" or who did not receive a radiotherapy dose within the range of 12-24 Gy were excluded to reduce the potential for misclassification. The chi-square test, t-test, and multivariable logistic regression analysis were used to compare potential demographic, clinicopathologic, and health care system predictors of GK versus LINAC SRS use, when appropriate. This study included 1780 patients, among whom 1371 (77.0%) received GK SRS and 409 (23.0%) underwent LINAC SRS. Over time, the proportion of patients undergoing LINAC SRS steadily increased, from 3.2% in 2003 to 30.8% in 2011 (p < 0.001). LINAC SRS was adopted more rapidly by community versus academic facilities (overall 29.2% vs 17.2%, p < 0.001). On multivariable analysis, 4 independent predictors of increased LINAC SRS use emerged, including year of diagnosis in 2008-2011 versus 2003-2007 (adjusted OR [AOR] 2.04, 95% CI 1.52-2.73, p < 0

  16. Multivoxel proton MRS for differentiation of radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Chernov, M.F.; Hayashi, Motohiro; Izawa, Masahiro

    2006-01-01

    Multivoxel proton magnetic resonance spectroscopy (MRS) was used for differentiation of radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for intracranial metastases in 33 consecutive cases. All patients presented with enlargement of the treated lesion, increase of perilesional brain edema, and aggravation or appearance of neurological signs and symptoms on average 9.3±4.9 months after primary treatment. Metabolic imaging defined four types of lesions: pure tumor recurrence (11 cases), partial tumor recurrence (11 cases), radiation-induced tumor necrosis (10 cases), and radiation-induced necrosis of the peritumoral brain (1 case). In 1 patient, radiation-induced tumor necrosis was diagnosed 9 months after radiosurgery; however, partial tumor recurrence was identified 6 months later. With the exception of midline shift, which was found to be more typical for radiation-induced necrosis (P<0.01), no one clinical, radiologic, or radiosurgical parameter either at the time of primary treatment or at the time of deterioration showed a statistically significant association with the type of the lesion. Proton MRS-based diagnosis was confirmed histologically in all surgically treated patients (7 cases) and corresponded well to the clinical course in others. In conclusion, multivoxel proton MRS is an effective diagnostic modality for identification of radiation-induced necrosis and tumor recurrence that can be used for monitoring of metabolic changes in intracranial neoplasms after radiosurgical treatment. It can be also helpful for differentiation of radiation-induced necrosis of the tumor and that of the peritumoral brain, which may have important clinical and medicolegal implications. (author)

  17. Analysis of outcome in patients irradiated for brain metastases of lung (no oatcell) cancer

    International Nuclear Information System (INIS)

    Lione, Marcelo; Tissera, Norberto

    2004-01-01

    Purpose: To correlate our findings with those of the international literature and identify the factors related to survival. Material and methods: Fifty patients with central nervous system metastases of non-small cell lung cancer were evaluated. Holocranial radiotherapy was performed with a daily dose of 1.8 Gy and a total dose of 50.4 Gy. Results: Overall survival of all patients at 6 months, 1 year and 2 years was 37%, 27% and 5% respectively. Mean survival was 5 months; 9 months for the group with a favorable outcome and 4 months for the group with an unfavorable outcome. Conclusion: The results are similar to those published in the international literature. Factors that relate to survival are: age, performance status, and the presence or absence of metastases in other sites. (author)

  18. Use of bone and brain scans as screening procedures in patients with malignant lesions

    International Nuclear Information System (INIS)

    Felix, E.L.; Sindelar, W.F.; Bagley, D.H.; Johnston, G.S.; Ketcham, A.S.

    1975-01-01

    A retrospective study to determine the value of bone and brain scans was performed in preoperative patients with melanoma, sarcoma, cancer of the head and neck and carcinoma of the pelvis. No occult metastases were identified in 170 patients in whom brain scan was performed. On late follow-up data, eight patients had neurologic symptoms develop and had brain metastases identified on scan. Of 223 bone scans performed, only one distant metastatic lesion was identified. It is, therefore, suggested that, in these types of patients, bone and brain scans be reserved for those with symptoms referable to the neurologic or skeletal systems

  19. RTOG 0211: A Phase 1/2 Study of Radiation Therapy With Concurrent Gefitinib for Newly Diagnosed Glioblastoma Patients

    International Nuclear Information System (INIS)

    Chakravarti, Arnab; Wang, Meihua; Robins, H. Ian; Lautenschlaeger, Tim; Curran, Walter J.; Brachman, David G.; Schultz, Christopher J.; Choucair, Ali; Dolled-Filhart, Marisa; Christiansen, Jason; Gustavson, Mark; Molinaro, Annette; Mischel, Paul; Dicker, Adam P.

    2013-01-01

    Purpose: To determine the safety and efficacy of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with radiation for newly diagnosed glioblastoma (GBM) patients. Methods and Materials: Between March 21, 2002, and May 3, 2004, Radiation Therapy Oncology Group (RTOG) 0211 enrolled 31 and 147 GBM patients in the phase 1 and 2 arms, respectively. Treatment consisted of daily oral gefinitnib started at the time of conventional cranial radiation therapy (RT) and continued post RT for 18 months or until progression. Tissue microarrays from 68 cases were analyzed for EGFR expression. Results: The maximum tolerated dose (MTD) of gefitinib was determined to be 500 mg in patients on non-enzyme-inducing anticonvulsant drugs (non-EIAEDs). All patients in the phase 2 component were treated at a gefitinib dose of 500 mg; patients receiving EIADSs could be escalated to 750 mg. The most common side effects of gefitinib in combination with radiation were dermatologic and gastrointestinal. Median survival was 11.5 months for patients treated per protocol. There was no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone, matched by RTOG recursive partitioning analysis (RPA) class distribution. Younger age was significantly associated with better outcome. Per protocol stratification, EGFR expression was not found to be of prognostic value for gefitinib + RT-treated patients. Conclusions: The addition of gefitinib to RT is well tolerated. Median survival of RTOG 0211 patients treated with RT with concurrent and adjuvant gefitinib was similar to that in a historical control cohort treated with radiation alone

  20. Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery.

    Science.gov (United States)

    Nikolaoul, Marinos; Stamenković, Srdjan; Stergiou, Christos; Skarleas, Christos; Torrens, Michael

    2015-01-01

    Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance.The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.