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Sample records for brain metastases clinical

  1. In-vivo longitudinal MRI study: an assessment of melanoma brain metastases in a clinically relevant mouse model.

    Science.gov (United States)

    Henry, Mariama N; Chen, Yuhua; McFadden, Catherine D; Simedrea, Felicia C; Foster, Paula J

    2015-04-01

    Brain metastases are an important clinical problem. Few animal models exist for melanoma brain metastases; many of which are not clinically relevant. Longitudinal MRI was implemented to examine the development of tumors in a clinically relevant mouse model of melanoma brain metastases. Fifty thousand human metastatic melanoma (A2058) cells were injected intracardially into nude mice. Three Tesla MRI was performed using a custom-built gradient insert coil and a mouse solenoid head coil. Imaging was performed on consecutive days at four time points. Tumor burden and volumes of metastases were measured from balanced steady-state free precession image data. Metastases with a disrupted blood-tumor barrier were identified from T1-weighted spin echo images acquired after administration of gadopentetic acid (Gd-DTPA). Metastases permeable to Gd-DTPA showed signal enhancement. The number of enhancing metastases was determined by comparing balanced steady-state free precession images with T1-weighted spin echo images. After the final imaging session, ex-vivo permeability and histological analyses were carried out. Imaging showed that both enhancing and nonenhancing brain metastases coexist in the brain, and that most metastases switched from the nonenhancing to the enhancing phenotype. Small numbers of brain metastases were enhancing when first detected by MRI and remained enhancing, whereas other metastases remained nonenhancing to Gd-DTPA throughout the experiment. No clear relationship existed between the permeability of brain metastases and size, brain location and age. Longitudinal in-vivo MRI is key to studying the complex and dynamic processes of metastasis and changes in the blood-tumor barrier permeability, which may lead to a better understanding of the variable responses of brain metastases to treatments. PMID:25513779

  2. Clinical practice guideline on the optimal radiotherapeutic management of brain metastases

    Directory of Open Access Journals (Sweden)

    Wong Rebecca KS

    2005-04-01

    Full Text Available Abstract Background An evidence-based clinical practice guideline on the optimal radiotherapeutic management of single and multiple brain metastases was developed. Methods A systematic review and meta-analysis was performed. The Supportive Care Guidelines Group formulated clinical recommendations based on their interpretation of the evidence. External review of the report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from Cancer Care Ontario's Practice Guidelines Coordinating Committee (PGCC. Results One hundred and nine Ontario practitioners responded to the survey (return rate 44%. Ninety-six percent of respondents agreed with the interpretation of the evidence, and 92% agreed that the report should be approved. Minor revisions were made based on feedback from external reviewers and the PGCC. The PGCC approved the final practice guideline report. Conclusions For adult patients with a clinical and radiographic diagnosis of brain metastases (single or multiple we conclude that, • Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis. • Postoperative whole brain radiotherapy (WBRT should be considered to reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis. • Radiosurgery boost with WBRT may improve survival in select patients with unresectable single brain metastases. • The whole brain should be irradiated for multiple brain metastases. Standard dose-fractionation schedules are 3000 cGy in 10 fractions or 2000 cGy in 5 fractions. • Radiosensitizers are not recommended outside research studies. • In select patients, radiosurgery may be considered as boost therapy with WBRT to improve local tumour control. Radiosurgery boost may improve survival in select patients. • Chemotherapy as primary therapy or

  3. Optically-guided frameless linac-based radiosurgery for brain metastases: clinical experience

    OpenAIRE

    Nath, Sameer K; Lawson, Joshua D.; Wang, Jia-Zhu; Simpson, Daniel R.; Newman, C. Benjamin; Alksne, John F.; Mundt, Arno J.; Murphy, Kevin T.

    2009-01-01

    The purpose of this study was to describe our clinical experience using optically-guided linear accelerator (linac)-based frameless stereotactic radiosurgery (SRS) for the treatment of brain metastases. Sixty-five patients (204 lesions) were treated between 2005 and 2008 with frameless SRS using an optically-guided bite-block system. Patients had a median of 2 lesions (range, 1–13). Prescription dose ranged from 14 to 22 Gy (median, 18 Gy) and was given in a single fraction. Clinical and radi...

  4. Comparing Postoperative Radiation Therapies for Brain Metastases

    Science.gov (United States)

    In this clinical trial, patients with one to four brain metastases who have had at least one of the metastatic tumors removed surgically will be randomly assigned to undergo whole-brain radiation therapy or stereotactic radiosurgery.

  5. Hemorrhagic brain metastases

    International Nuclear Information System (INIS)

    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)

  6. Intracranial arterial infusion chemotherapy for lung cancer complicated by brain metastases: a clinical observation

    International Nuclear Information System (INIS)

    Objective: T evaluate the efficacy of intracranial arterial infusion chemotherapy in treating advanced lung cancer with brain metastases and to discuss the factors influencing prognosis. Methods: From September 2007 to August 2008, a total of 27 patients of lung cancer with brain metastases received intracranial arterial infusion chemotherapy. This procedure was performed every 4 weeks for three times in succession. Follow-up brain MRI was regularly performed at intervals of eight weeks after the treatment in order to evaluate the therapeutic efficacy, which was conducted until the disease became worse or the patient could tolerate the drug toxicity no longer. Results: All 27 cases were treated 3 times at least, and one case received 7 times. Of the 27 cases, partial response was obtained in 15 (55.6%), stable condition in 8 (29.6%) and deterioration in 4 (14.8%), although no one showed complete alleviation. The effective rate for intracranial lesions was 55.6% (15/27) and the 85.2% of lesions (23/27) were brought under control. Overall median survival time was 7 months. The 6-month survival rate and 1-year survival rate were 81.5% and 14.8%, respectively. Conclusion: Intracranial arterial infusion chemotherapy is one of the most effective methods for the treatment of lung cancer associated with brain metastases. Karnofsky performance status ≥ 60 and absent of extra cranial metastases are good prognostic factors for lung cancer patients with brain metastases. (authors)

  7. BRAIN METASTASES FROM CARCINOMA OF UTERINE CERVIX

    Institute of Scientific and Technical Information of China (English)

    张国楠; 徐世强; 石宇; 樊英; 吴艳丽; 殷红; 余健; 陈毅男

    2002-01-01

    Objective: To study the mechanism, clinical characteristics, therapy regimens, and survival of cervical carcinoma metastases to the brain. Methods: We retrospectively analyzed 11 patients with brain metastases from cervical carcinoma. Results: Two cases were at stage lb, two at IIa, and seven at IIIb, respectively. Histologically, they were squamous cell carcinoma (6 cases), adeno-squamous carcinoma (2 cases), small cell carcinoma (2 cases), or adenocarcinoma (1 cases), poorly differentiated. Eight were accompanied with lung, liver, and bone metastases disease and three had no any other systemic metastases at the time of the brain metastases diagnosis. Two had controlled, and other nine were uncontrolled or progressive primary disease. The median interval from the diagnosis of the primary carcinoma to the detection of brain lesion was 14.6 months. Headache was the most common symptom of brain metastases. Eight of 11 patients developed multiple lesions and other 3 cases had a solitary lesion in brain. The patients were treated by combination of surgery and whole brain radiation therapy (WBRT) (3 cases), stereotactic radiosurgery (SRS) (3 cases), or WBRT (5 cases). The patients had a median survival of 6.6 months. Conclusion: Brain metastases are not always a late complication of cervical carcinoma. The development of the metastases is related to pathological type, poorly differentiation, and advanced stage. Surgery and SRS arc the appropriate therapy regimen for these patients.

  8. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial12

    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.

    2016-01-01

    BACKGROUND: 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. SIGNIFICANCE: 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. PMID:27084426

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

    Directory of Open Access Journals (Sweden)

    Michelle M. Kim

    2016-04-01

    Full Text Available BACKGROUND: 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. SIGNIFICANCE: 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.

  10. Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group.

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    Lin, Nancy U; Lee, Eudocia Q; Aoyama, Hidefumi; Barani, Igor J; Baumert, Brigitta G; Brown, Paul D; Camidge, D Ross; Chang, Susan M; Dancey, Janet; Gaspar, Laurie E; Harris, Gordon J; Hodi, F Stephen; Kalkanis, Steven N; Lamborn, Kathleen R; 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; Wefel, Jeffrey S; Wen, Patrick Y

    2013-09-01

    Therapeutic outcomes for patients with brain metastases need to improve. A critical review of trials specifically addressing brain metastases shows key issues that could prevent acceptance of results by regulatory agencies, including enrolment of heterogeneous groups of patients and varying definitions of clinical endpoints. Considerations specific to disease, modality, and treatment are not consistently addressed. Additionally, the schedule of CNS imaging and consequences of detection of new or progressive brain metastases in trials mainly exploring the extra-CNS activity of systemic drugs are highly variable. The Response Assessment in Neuro-Oncology (RANO) working group is an independent, international, collaborative effort to improve the design of trials in patients with brain tumours. In this two-part series, we review the state of clinical trials of brain metastases and suggest a consensus recommendation for the development of criteria for future clinical trials.

  11. Brain metastases: A single institute experience

    Directory of Open Access Journals (Sweden)

    Asifa Andleeb

    2016-01-01

    Full Text Available Background: Brain metastases represent an important cause of morbidity for cancer patients. Its incidence has increased overall overtime as a consequence of improved detection by magnetic resonance imaging (MRI. However, in Indian literature, scant data are available. At this moment, we have analyzed our data from a single tertiary care center in North India. The purpose of the study was to analyze the clinical profile of patients with brain metastases. A retrospective study from a single tertiary care center. Patients and Methods: A retrospective review of records of all patients who were registered in hospital-based cancer registry and developed brain metastases from June 2011 to June 2013 yielded 95 patients for analyses. Results: Majority of cases were seen in the 6th decade of life. Lung cancer was the most common primary followed by breast. On imaging (computed tomography or MRI, multiple lesions were more common than single. Most of the patients presented with a headache (37.9%. Supratentorial involvement was seen in 87.3% against 12.6% infratentorial involvement. Median time interval from diagnosis of primary and development of brain metastases was 13.8 months. A median survival of only 3 months was seen after development of brain metastases. Conclusion: The present study highlights that brain metastases occur mainly in elderly people with lung being the most common primary malignancy. It is a deadly event with a median survival of only 3 months.

  12. Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers.

    Directory of Open Access Journals (Sweden)

    Bob T Li

    Full Text Available Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown.Serum NSE, CYFRA 21-1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pre-treatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray's test.A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19-0.35 had brain metastases at baseline and a further 26 (22%; 95% CI 0.15-0.30 developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22-7.34, P = 0.02 by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2, but this was not statistically significant possibly due to small sample size.Serum NSE, CYFRA 21-1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time may be applied to independent datasets

  13. Prediction of Clinical Outcomes by Chemokine and Cytokine Profiling In CSF from Radiation Treated Breast Cancer Primary with Brain Metastases

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    Lok, Edwin

    Whole brain radiation is the standard treatment for patients with brain metastasis but unfortunately tumors can recover from radiation-induced damage with the help of the immune system. The hypothesis that differences in immunokines in the cerebrospinal fluid (CSF) pre- and post-irradiation could reveal tumor biology and correlate with outcome of patients with metastatic breast cancer to the brain is tested. Collected CSF samples were analyzed using Luminex's multiplexing assays to survey global immunokine levels while Enzyme-Linked Immunosorbent Assays were used to quantify each individual immunokines. Cluster analysis was performed to segregate patients based on their common immunokine profile and each cluster was correlated with survival and other clinical parameters. Breast cancer brain metastasis was found to have altered immunokine profiles in the CSF, and that Interleukin-1α expression was elevated after irradiation. Therefore, immunokine profiling in the CSF could enable cancer physicians to monitor the status of brain metastases.

  14. Stereotactic radiosurgery of brain metastases.

    Science.gov (United States)

    Specht, Hanno M; Combs, Stephanie E

    2016-09-01

    Brain metastases are a common problem in solid malignancies and still represent a major cause of morbidity and mortality. With the ongoing improvement in systemic therapies, the expectations on the efficacy of brain metastases directed treatment options are growing. As local therapies against brain metastases continue to evolve, treatment patterns have shifted from a palliative "one-treatment-fits-all" towards an individualized, patient adapted approach. In this article we review the evidence for stereotactic radiation treatment based on the current literature. Stereotactic radiosurgery (SRS) as a local high precision approach for the primary treatment of asymptomatic brain metastases has gained wide acceptance. It leads to lasting tumor control with only minor side effects compared to whole brain radiotherapy, since there is only little dose delivered to the healthy brain. The same holds true for hypofractionated stereotactic radiotherapy (HFSRT) for large metastases or for lesions close to organs at risk (e.g. the brainstem). New treatment indications such as neoadjuvant SRS followed by surgical resection or postoperative local therapy to the resection cavity show promising data and are also highlighted in this manuscript. With the evolution of local treatment options, optimal patient selection becomes more and more crucial. This article aims to aid decision making by outlining prognostic factors, treatment techniques and indications and common dose prescriptions. PMID:27071010

  15. 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....

  16. Brain metastases of breast cancer.

    Science.gov (United States)

    Palmieri, Diane; Smith, Quentin R; Lockman, Paul R; Bronder, Julie; Gril, Brunilde; Chambers, Ann F; Weil, Robert J; Steeg, Patricia S

    Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells. PMID:17473372

  17. A clinical nomogram and recursive partitioning analysis to determine the risk of regional failure after radiosurgery alone for brain metastases

    International Nuclear Information System (INIS)

    Purpose: This investigation defined patient populations at high-, intermediate-, and low-risk of regional failure (RF) after stereotactic radiosurgery (SRS) lesion treatment using clinical nomograms and recursive partitioning analysis (RPA). Methods and materials: We created a retrospective database compiling 361 oligometastatic brain metastases patients treated with single-modality Linac-based SRS. Logistic analysis was performed to identify factors to be included in a RPA to predict for cumulative RF at 1-year. A 1-year cumulative RF clinical nomogram was constructed and validated (c-index statistic). Results: Age, number of brain metastases, World Health Organization (WHO) performance status (PS), and maximum gross tumor volume (GTV) size were found to be statistically significant predictors of the primary outcome. RPA classifications were defined as follows: low-risk (<25% 1-year RF): solitary lesion AND age >55Y; intermediate-risk (25–40% 1-year RF): age ⩽55Y AND solitary lesion OR WHO ⩾ 1 AND 2–3 lesions; and high-risk (>40% 1-year RF): WHO PS = 0 AND 2–3 lesions. These classifications were highly statistically significant (p < 0.01) for RF. A clinical nomogram (containing patient age, lesion number, largest GTV volume, and WHO PS) for the prediction of 1-year cumulative RF was created (c-index 0.69). Conclusion: A risk-adapted treatment approach can be applied for BM radiosurgery either using RPA categories and/or nomogram-based risk estimates

  18. Whole brain reirradiation for brain metastases

    International Nuclear Information System (INIS)

    A retrospective analysis was done for 31 patients with brain metastases who had undergone reirradiation. Initial whole brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole brain reirradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). The median interval between the initial irradiation and reirradiation was 10 months (range: 2-69 months). The median survival time after reirradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after reirradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed grade 1 acute reactions. Whole brain reirradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. (author)

  19. Physician self-reported treatment of brain metastases according to patients’ clinical and demographic factors and physician practice setting

    International Nuclear Information System (INIS)

    Limited data guide radiotherapy choices for patients with brain metastases. This survey aimed to identify patient, physician, and practice setting variables associated with reported preferences for different treatment techniques. 277 members of the American Society for Radiation Oncology (6% of surveyed physicians) completed a survey regarding treatment preferences for 21 hypothetical patients with brain metastases. Treatment choices included combinations of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. Vignettes varied histology, extracranial disease status, Karnofsky Performance Status (KPS), presence of neurologic deficits, lesion size and number. Multivariate generalized estimating equation regression models were used to estimate odds ratios. For a hypothetical patient with 3 lesions or 8 lesions, 21% and 91% of physicians, respectively, chose WBRT alone, compared with 1% selecting WBRT alone for a patient with 1 lesion. 51% chose WBRT alone for a patient with active extracranial disease or KPS=50%. 40% chose SRS alone for an 80 year-old patient with 1 lesion, compared to 29% for a 55 year-old patient. Multivariate modeling detailed factors associated with SRS use, including availability of SRS within one’s practice (OR 2.22, 95% CI 1.46-3.37). Poor prognostic factors, such as advanced age, poor performance status, or active extracranial disease, correspond with an increase in physicians’ reported preference for using WBRT. When controlling for clinical factors, equipment access was independently associated with choice of SRS. The large variability in preferences suggests that more information about the relative harms and benefits of these options is needed to guide decision-making

  20. 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)

    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.

  1. 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)

    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% (χ2 = 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% (χ2 = 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% (χ2 = 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

  2. Radiosurgery for Large Brain Metastases

    International Nuclear Information System (INIS)

    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 cm3) 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 cm3, 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 cm3 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.

  3. Bone and brain metastases from ampullary adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ioannis A Voutsadakis; Stergios Doumas; Konstantinos Tsapakidis; Maria Papagianni; Christos N Papandreou

    2009-01-01

    Ampullary carcinoma is the second most common cancer of the peri-ampullary area after pancreatic carcinoma and metastasizes mostly intra-abdominally and to the liver. Extra-abdominal metastases are less frequent. In this report we describe the case of a patient with resected adenocarcinoma of the ampulla of Vater who developed skeletal metastases in the lower extremity and brain metastases. We briefly discuss aspects of this comparatively rare gastrointestinal malignancy.

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

    International Nuclear Information System (INIS)

    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

  5. Radiosurgery without whole brain radiotherapy in melanoma brain metastases

    International Nuclear Information System (INIS)

    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.)

  6. 131I treatment for brain metastases from differentiated thyroid carcinoma

    Institute of Scientific and Technical Information of China (English)

    YU Yong-Li; LU Han-Kui; ZHU Rei-Sen; MA Ji-Xiao

    2004-01-01

    To assess the clinical value of treatment with 131I for brain metastases from differentiated thyroid cancer (DTC), we have observed 8 cases of brain metastases from DTC who received follow-up after 131I therapy (2male, 6 female, aged 12~65 years). The results of 131I therapy were evaluated with clinical presentation, imaging scan and survival analysis. The main results are as follows. (1) All cases had been survival for 2~35 years in follow-up. (2)A space-occupying lesion in right cerebellum was reduced after taking 20.65 GBq and disappeared after 23.61 GBq,demonstrated by computed tomography. (3) The sequences and doses of 131I therapy were clearly decreased for the cases with total thyroidectomy in comparison with those with semithyroidectomy (p<0.01). (4) The brain metastases with lung and/or bone metastasis from DTC were 75% (6/8) and it was difficult to cure these metastases at the same time. It is concluded that the postoperative treatment of 131I for brain metastases from DTC after undergoing thyroidectomy may improve clinical symptoms and life quality, reduce lesions, and prolong survival.

  7. 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.

  8. [Systemic treatment of melanoma brain metastases].

    Science.gov (United States)

    Le Rhun, É; Mateus, C; Mortier, L; Dhermain, F; Guillot, B; Grob, J-J; Lebbe, C; Thomas, M; Jouary, T; Leccia, M-T; Robert, C

    2015-02-01

    Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) - ipilimumab - or BRAF (serine/threonine-protein kinase B-raf) inhibitors - vemurafenib, dabrafenib - has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase).

  9. Radiosurgery for brain metastases and cerebral edema.

    Science.gov (United States)

    Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

    2015-03-01

    The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79±4.12 cc to 2.8±4.48 cc (p=0.001), and the mean edema volume decreased from 16.91±30.15 cc to 12.85±24.47 cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change 10%, 2-14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27±37.21 cc to 24.84±35.6 cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

  10. Updates in the management of brain metastases.

    Science.gov (United States)

    Arvold, Nils D; Lee, Eudocia Q; Mehta, Minesh P; Margolin, Kim; Alexander, Brian M; Lin, Nancy U; Anders, Carey K; Soffietti, Riccardo; Camidge, D Ross; Vogelbaum, Michael A; Dunn, Ian F; Wen, Patrick Y

    2016-08-01

    The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers. PMID:27382120

  11. Targeted Therapies for Brain Metastases from Breast Cancer

    Science.gov (United States)

    Venur, Vyshak Alva; Leone, José Pablo

    2016-01-01

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways. PMID:27649142

  12. Targeted Therapies for Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vyshak Alva Venur

    2016-09-01

    Full Text Available The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2 and epidermal growth factor receptor (EGFR, vascular endothelial growth factor (VEGF receptor, mechanistic target of rapamycin (mTOR pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6 pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  13. Platinum Sensitivity as an Independent Prognostic Factor in Patients with Brain Metastases from Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    John Windara Green

    2011-10-01

    Full Text Available Background: The brain is a rare site of metastases from ovarian cancer. Limited data are available on prognostic factors, standard treatment, and survival. Knowledge of clinical prognostic factors would help the management of patients with brain metastases. The aim of this study is to evaluate the impact of clinical factors and treatment modalities on survival in patients with brain metastases from ovarian cancer. Methods: We performed a retrospective analysis of an electronic database of patients with brain metastases from ovarian primary treated at Clatterbridge Centre for Oncology. Results: A total of 20 patients with brain metastases from an ovarian primary were treated from April 2001-February 2011. Median age at occurrence of brain metastases was 55 years. The median time from primary diagnosis to occurrence of brain metastases was 23 months. Median overall survival from diagnosis of brain metastases was 9 months. Poor ECOG performance status, platinum resistance, andadvanced FIGO staging were the most significant adverse variables identified. Median survival was 13 months for platinum sensitive patients and 6 months for platinum resistant patients. Conclusion: Platinum sensitivity is an important prognostic factor in patients with brain metastases from an ovarian primary tumor. Multimodal therapy that consists of surgery, radiotherapy, and chemotherapy should be considered where feasible.

  14. 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.

    2015-01-01

    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

  15. Two cases of liver alveolar echinococcosis associated with simultaneous lung and brain metastases

    Institute of Scientific and Technical Information of China (English)

    蒋次鹏

    2002-01-01

    @@ Alveolar echinococcosis (AE) of liver associated with simultaneous lung and brain metastases is rare clinically. During a period of 15 years (1985-2000), 2 (1.9%) of 103 cases with liver AE diagnosed at our laboratory were associated with simultaneous lung or brain metastases.1 They were confirmed pathologically through surgical biopsy or autopsy respectively, and reported as follows.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. High risk factors of brain metastases in 295 patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Min; L(U) Hui-min; LIU Zhen-zhen; LIU Hui; ZHANG Meng-wei; SUN Xi-bin; CUI Shu-de

    2013-01-01

    Background The incidence of brain metastases in patients with breast cancer is approximately 10%-16%,and survival after diagnosis of brain metastases is usually short.This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients,with a view to help predict patient groups with high risk of brain metastases.Methods In total,295 patients with advanced breast cancer were evaluated.All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging.All patients were examined at least once every 6 months with head CT or MRI.Patients showing symptoms underwent immediate inspection,and brain metastatic lesions were confirmed by head CT and/or MRI.Results At a median follow-up of 12 months from the occurrence of metastases,brain metastases had occurred in 49 patients (16.6%).In our univariate analysis,variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors,epidermal growth factor receptor 2 (HER2)-positive tumors,and multiple distant metastases.Patients with dominant tumor sites in soft tissue,or defined as Luminal A subtype,tended to have a lower risk of brain metastases than patients with visceral metastases,Luminal B subtype,triple-negative subtype or HER2-enriched subtype tumors.Conclusions Our results strongly suggest that factors such as Luminal B,triple-negative,and HER2-enriched subtypes are high risk factors for brain metastases.These data,therefore,provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.

  18. Brain metastases from breast cancer during pregnancy

    Directory of Open Access Journals (Sweden)

    Ashish Sharma

    2016-01-01

    Conclusion: There is a lack of guidelines and clinical consensus on medical and surgical treatment for breast cancer metastases in pregnant patients. Treatment usually varies based upon underlying tumor burden, location, gestational age of the fetus, and patient′s preference and symptomatology.

  19. Outcomes After Whole Brain Reirradiation in Patients With Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: Patients with brain metastases are often treated with whole brain radiation therapy (WBRT) for purposes of palliation. The treatment of those who experience subsequent intracranial disease progression can include a second course of WBRT, although there is controversy surrounding its safety and efficacy. This study examines the outcomes in patients at Massachusetts General Hospital who underwent reirradiation. Patients and Methods: We examined the medical records of 17 patients at Massachusetts General Hospital with brain metastases who were initially treated with WBRT between 2002 and 2008 and were subsequently retreated with a second course of WBRT. The median dose for the first course of WBRT was 35 Gy (range, 28–40 Gy), with a fraction size of 2 to 3 Gy (median, 2.5 Gy). The median dose at reirradiation was 21.6 Gy (range, 14–30 Gy), with a fraction size of 1.5 to 2 Gy (median, 1.8 Gy). Results: The second course of WBRT was administered upon radiographic disease progression in all patients. Of 10 patients with complete follow-up data, 8 patients experienced complete or partial symptom resolution, and 2 did not show clinical improvement. The time to radiographic progression was 5.2 months. The median overall survival for all patients after diagnosis of metastases was 24.7 months. The median survival time after initiation of reirradiation was 5.2 months (95% CI, 1.3–8.7). In 6 patients with stable extracranial disease, the median survival time after retreatment was 19.8 months (95% CI, 2.7–∞), compared with 2.5 months (95% CI, 0.8–5.5) for those with extracranial disease progression (p = 0.05). Acute adverse reactions occurred in 70.5% of patients but were mild to moderate in severity. Conclusion: In select patients and especially those with stable extracranial disease, reirradiation may be an appropriate and effective intervention to provide symptomatic relief and slow intracranial disease progression. Side effects were minimal and did not

  20. Linear accelerator based stereotactic radiosurgery for melanoma brain metastases

    OpenAIRE

    Bernard, Mark E.; Wegner, Rodney E; Katharine Reineman; Dwight E Heron; John Kirkwood; Burton, Steven A; Mintz, Arlan H.

    2012-01-01

    Purpose: Melanoma is one of the most common malignancies to metastasize to the brain. Many patients with this disease will succumb to central nervous system (CNS) disease, highlighting the importance of effective local treatment of brain metastases for both palliation and survival of the disease. Our objective was to evaluate the outcomes associated with stereotactic radiosurgery (SRS) in the treatment of melanoma brain metastases. Materials and Methods: We retrospectively reviewed 54 pa...

  1. Radiation Therapy for the Management of Brain Metastases.

    Science.gov (United States)

    Garrett, Matthew D; Wu, Cheng-Chia; Yanagihara, Ted K; Jani, Ashish; Wang, Tony J C

    2016-08-01

    Brain metastases are the most common malignant intracranial tumors and carry a poor prognosis. The management of brain metastases may include a variety of treatment modalities including surgical resection, radiation therapy, and/or systemic therapy. The traditional treatment for brain metastasis involved whole brain irradiation. However, improved systemic control of primary cancers has led to longer survival for some groups of patients and there is increasing need to consider the late effects of radiation to the entire brain. With advances in imaging and radiation treatment planning and delivery stereotactic radiosurgery has become more frequently utilized and may be delivered through Gamma Knife Stereotactic Radiosurgery or linear accelerator-based systems. Furthermore, experience in treating thousands of patients on clinical trials has led to diagnosis-specific prognostic assessment systems that help guide our approach to the management of this common clinical scenario. This review provides an overview of the literature supporting radiotherapy for brain metastasis and an update on current radiotherapeutic options that is tailored for the nonradiation oncologist. PMID:27213494

  2. 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.

  3. Metabolic profiling of human brain metastases using in vivo proton MR spectroscopy at 3T

    International Nuclear Information System (INIS)

    Metastases to the central nervous system from different primary cancers are an oncologic challenge as the overall prognosis for these patients is generally poor. The incidence of brain metastases varies with type of primary cancer and is probably increasing due to improved therapies of extracranial metastases prolonging patient's overall survival and thereby time for brain metastases to develop. In addition, the greater access to improved neuroimaging techniques can provide earlier diagnosis. The aim of this study was to investigate the feasibility of using proton magnetic resonance spectroscopy (MRS) and multivariate analyses to characterize brain metastases originating from different primary cancers, to assess changes in spectra during radiation treatment and to correlate the spectra to clinical outcome after treatment. Patients (n = 26) with brain metastases were examined using single voxel MRS at a 3T clinical MR system. Five patients were excluded due to poor spectral quality. The spectra were obtained before start (n = 21 patients), immediately after (n = 6 patients) and two months after end of treatment (n = 4 patients). Principal component analysis (PCA) and partial least square regression analysis (PLS) were applied in order to identify clustering of spectra due to origin of metastases and to relate clinical outcome (survival) of the patients to spectral data from the first MR examination. The PCA results indicated that brain metastases from primary lung and breast cancer were separated into two clusters, while the metastases from malignant melanomas showed no uniformity. The PLS analysis showed a significant correlation between MR spectral data and survival five months after MRS before start of treatment. MRS determined metabolic profiles analysed by PCA and PLS might give valuable clinical information when planning and evaluating the treatment of brain metastases, and also when deciding to terminate further therapies

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

    Directory of Open Access Journals (Sweden)

    Matthew E Hardee

    2012-08-01

    Full Text Available 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 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.

  5. MR imaging of brain metastases. Pt. 1

    International Nuclear Information System (INIS)

    Sensitifity and specificity of plain T2-WI and Gd-DTPA enhanced T1-WI were compared by evaluating MR exams of 30 patients with brain metastases. Large lesions with high signal on T2-WI always enhanced (43/43) when a structure (perifocal edema, tumor tissue, centralnecrosis) was found. Large lesions nearly always enhanced (53/55) even if no such structure was found. 65% of small unstructured white matter lesions with high signal on T2-WI, which are generally considered vascular, did not enhance. Surprisingly, 35% did enhance. Demonstration of blood brain barrier disturbance in these lesions suggested a metastatic origin. In 3 patients with multiple metastases, Gd-DTPA enhanced T1-WI disclosed more than 140 lesions not seen on T2-WI. All of them were located in or adjacent to grey matter. Our results indicate that enhanced T1-WI should be obtained even if T1-WI are normal or show only small white matter lesions. (orig.)

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

    OpenAIRE

    Barbara Ingold; Peter Schraml; Heppner, Frank L.; Holger Moch

    2009-01-01

    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 fr...

  7. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases

    OpenAIRE

    Kohutek, Zachary A.; Yamada, Yoshiya; Chan, Timothy A.; Brennan, Cameron W.; Tabar, Viviane; Gutin, Philip H.; Yang, T. Jonathan; Rosenblum, Marc K.; Ballangrud, Åse; Young, Robert J; Zhang, Zhigang; Beal, Kathryn

    2015-01-01

    Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed eithe...

  8. Treatment options in patients with small-cell lung cancer and brain metastases

    International Nuclear Information System (INIS)

    Small cell lung cancer (SCLC) accounts for some 20-25% of all lung cancers, with some 60-70% of patients presenting with the extensive stage (ES) of SCLC at the time of the diagnosis. Brain metastases are observed in 10-35% patients with ES SCLC, and 33% of them are asymptomatic. The main method of treatment in case of ES SCLC patients is cisplatin-containing systemic therapy. Radiotherapy is used as palliative treatment (primary tumour in chest, metastases localized in bones, brain or spinal cord) or as a prophylactic procedure (prophylactic cranial irradiation).The purpose of paper is to present the treatment possibilities in case of ES SCLC patients with brain metastases. Between 1995 and 2005 at the Oncology Centre in Krakow we evaluated 170 patients with SCLC in order to establish the stage of the disease recognising 39 cases (22.9%) with the extensive stage of the disease. The most frequent localizations of distant metastases were: the brain (11 patients, of whom 3 developed brain metastases without clinical symptoms), liver (10 patients), and bones (10 patients). Further analysis has been performed in the group of patients with brain metastases. In these patients treatment based on palliative irradiation of the whole brain and on chemotherapy according to the EP (etoposide and cisplatine) regimen. For cranial irradiation the dose of 20 Gy was given in 5 fractions. In 3 patients with brain metastases without clinical symptoms radiotherapy of brain was repeated after a 4-week interruption. These patients received 5-6 cycles of EP chemotherapy, followed by consolidation radiotherapy of the primary tumour region in the chest. Overall survival was estimated at 2 to 19 months (median: 8.9 months). In the subgroup of 3 patients with brain metastases without clinical symptoms we observed complete regression within the primary tumour region and of the brain metastases. These results were confirmed radiologically. In these patients disease-free survival of 5-9 months

  9. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    Science.gov (United States)

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

  10. Management of solitary and multiple brain metastases from breast cancer

    Directory of Open Access Journals (Sweden)

    Addison Willett

    2015-01-01

    Full Text Available As local and systemic control of breast cancer improves, metastasis to the brain remains a common event requiring a specialized management approach. Women diagnosed with breast cancer who develop brain metastases have superior overall survival compared to patients with other forms of metastatic carcinoma. This article summarizes some of the unique aspects of care for patients with breast cancer metastases to the brain.

  11. Brain metastases free survival differs between breast cancer subtypes

    Science.gov (United States)

    Berghoff, A; Bago-Horvath, Z; De Vries, C; Dubsky, P; Pluschnig, U; Rudas, M; Rottenfusser, A; Knauer, M; Eiter, H; Fitzal, F; Dieckmann, K; Mader, R M; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2012-01-01

    Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. PMID:22233926

  12. Small Vessel Ischemic Disease of the Brain and Brain Metastases in Lung Cancer Patients

    OpenAIRE

    Mazzone, Peter J.; Marchi, Nicola; Fazio, Vince; Taylor, J. Michael; Masaryk, Thomas; Bury, Luke; Mekhail, Tarek; Janigro, Damir

    2009-01-01

    Background Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID) of the brain is protective against the development of brain metastases in lung cancer patients. Methodology/Principal Findings A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the ...

  13. Hypofractionated stereotactic radiotherapy for brain metastases larger than three centimeters

    International Nuclear Information System (INIS)

    To evaluate the efficacy and outcomes of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases > 3 cm. From March 2003 to October 2009, 40 patients with brain metastases larger than 3 cm were treated by HSRT. HSRT was applied in 29 patients for primary treatment and in 11 patients for rescue. Single brain metastasis was detected in 21 patients. Whole brain radiotherapy was incorporated into HSRT in 10 patients for primary treatment. HSRT boosts were applied in 23 patients. The diameters of the brain metastases ranged from 3.1 to 5.5 cm (median, 4.1 cm). The median prescribed dose (not including HSRT boosts) was 40 Gy (range, 20-53 Gy) with a median of 10 fractions (range, 4-15 fractions) to the 90% isodose line. The median dose of the boost was 20 Gy (range, 10-35 Gy) in 4 fractions (range, 2-10 fractions). The median overall survival time was 15 months. The overall survival and local control rate at 12 months was 55.3% and 94.2%, respectively. Four patients experienced local progression of large brain metastases. Nine patients died of intracranial disease progression. One patient died of radiation necrosis with brain edema. HSRT was a safe and effective treatment for patients with brain metastases ranged from 3.1 to 5.5 cm. Dose escalation of HSRT boost may improve local control with an acceptable toxicity

  14. DIAGNOSTIC PITFALLS OF BRAIN METASTASES AFTER BRAIN IRRADIATION

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    Nikolay A. Peev

    2010-11-01

    Full Text Available Although brain metastases are one of the most frequently diagnosed sequelae of systemic malignancy, their optimal management still is not well defined. In that respect the different diagnostic and therapeutic approaches of BMs patients is an issue for serious discussions. Among the most commonly used diagnostic tools are computed tomography (CT scans, magnetic resonance imaging (MRI scans, single photon emission computed tomography (SPECT and positron emission tomography (PET scans etc. Nowadays the aforementioned diagnostic modalities are usually combined in order to obtain complete diagnostic information important for establishing the optimal treatment. With the present report we try to elaborate on the value of the modern diagnostic tools in differentiating between tumor progressions versus radiation necrosis in irradiated patients with resected brain metastases. Although the present advancement of the modern imaging modalities differentiating between tumor progression versus radiation necrosis is often difficult. Application of the metabolic imaging modalities like SPECT, PET and proton magnetic resonance spectroscopy (1H-MRS contributes for the diagnose but still pathological specimens remain a gold standard for distinguishing tumor from necrosis, because none of the imaging modalities is possible to reliably differentiate necrosis from progression in 100% of the cases.

  15. LDA-SVM-Based EGFR Mutation Model for NSCLC Brain Metastases

    Science.gov (United States)

    Hu, Nan; Wang, Ge; Wu, Yu-Hao; Chen, Shi-Feng; Liu, Guo-Dong; Chen, Chuan; Wang, Dong; He, Zhong-Shi; Yang, Xue-Qin; He, Yong; Xiao, Hua-Liang; Huang, Ding-De; Xiong, Kun-Lin; Wu, Yan; Huang, Ming; Yang, Zhen-Zhou

    2015-01-01

    Abstract Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non–small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this

  16. LDA-SVM-based EGFR mutation model for NSCLC brain metastases: an observational study.

    Science.gov (United States)

    Hu, Nan; Wang, Ge; Wu, Yu-Hao; Chen, Shi-Feng; Liu, Guo-Dong; Chen, Chuan; Wang, Dong; He, Zhong-Shi; Yang, Xue-Qin; He, Yong; Xiao, Hua-Liang; Huang, Ding-De; Xiong, Kun-Lin; Wu, Yan; Huang, Ming; Yang, Zhen-Zhou

    2015-02-01

    Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non-small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this small cohort of

  17. It is time to reevaluate the management of patients with brain metastases.

    Science.gov (United States)

    Kondziolka, Douglas; Kalkanis, Steven N; Mehta, Minesh P; Ahluwalia, Manmeet; Loeffler, Jay S

    2014-07-01

    There are many elements to the science that drives the clinical care of patients with brain metastases. Although part of an understanding that continues to evolve, a number of key historical misconceptions remain that commonly drive physicians' and researchers' attitudes and approaches. By understanding how these relate to current practice, we can better comprehend our available science to provide both better research and care. These past misconceptions include: Misconception 1: Once a primary cancer spreads to the brain, the histology of that primary tumor does not have much impact on response to chemotherapy, sensitivity to radiation, risk of further brain relapse, development of additional metastatic lesions, or survival. All tumor primary histologies are the same once they spread to the brain. They are the same in terms of the number of tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and survival. Misconception 2: The number of brain metastases matters. This number matters in terms of subsequent brain relapse, survival, and cognitive dysfunction; the precise number of metastases can also be used as a limit in determining which patients might be eligible for a particular treatment option. Misconception 3: Cancer in the brain is always a diffuse problem due to the presence of micrometastases. Misconception 4: Whole-brain radiation therapy invariably causes disabling cognitive dysfunction if a patient lives long enough. Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth screening patients for brain metastases, especially because the impact on survival is minimal. The conduct and findings of past clinical research have led to conceptions that affect clinical care yet appear limiting. PMID:24662510

  18. Stereotactic radiosurgery (SRS) for brain metastases: a systematic review

    International Nuclear Information System (INIS)

    In many patients with brain metastases, the primary therapeutic aim is symptom palliation and maintenance of neurologic function, but in a subgroup, long-term survival is possible. Local control in the brain, and absent or controlled extracranial sites of disease are prerequisites for favorable survival. Stereotactic radiosurgery (SRS) is a focal, highly precise treatment option with a long track record. Its clinical development and implementation by several pioneering institutions eventually rendered possible cooperative group randomized trials. A systematic review of those studies and other landmark studies was undertaken. Most clinicians are aware of the potential benefits of SRS such as a short treatment time, a high probability of treated-lesion control and, when adhering to typical dose/volume recommendations, a low normal tissue complication probability. However, SRS as sole first-line treatment carries a risk of failure in non-treated brain regions, which has resulted in controversy around when to add whole-brain radiotherapy (WBRT). SRS might also be prescribed as salvage treatment in patients relapsing despite previous SRS and/or WBRT. An optimal balance between intracranial control and side effects requires continued research efforts

  19. 脑转移癌全脑放疗相关认知功能损害的临床研究%Clinical research of cognitive impairment of brain metastases paitents treated by radiation therapy

    Institute of Scientific and Technical Information of China (English)

    胡晓菲; 唐菲

    2015-01-01

    目的::探讨脑转移癌全脑放疗相关认知功能损害情况,以期提高临床诊治水平。方法:选取2010年5月-2013年5月65例脑转移癌患者为研究对象,以简易精神状态量表作为认知评估工具,对其放疗1-6个月进行总体认知评估,根据有无神经系统症状对患者放疗前后进行总体认知功能改变分析。结果:有无症状在性别、年龄、影响认知基础疾病、颅内转移数目、肿瘤最大直径、其他部位转移、既往化疗史中比较差异无统计学意义(P>0.05);而在放疗前认知评分、既往靶向治疗、原发灶癌上比较差异有统计学意义(P0.05)。结论:脑转移癌全脑放疗对认知功能有损害,放疗后认知功能损害最明显,其后有所恢复。%Objective:To explore cognitive impairment of the whole brain radiotherapy of brain metastases-relat-ed,in order to improve the clinical diagnosis and treatment. Methods:All 65 paitents of brain metastases from May 2010 to May 2013 were selected,and they were checked with mini-Mental State Examination after radiotherapy. Over-all cognitive assessment were analysised according to neurological symptoms before and after radiotherapy. Results:There were asymptomatic in gender,age,underlying diseases affecting cognition,the number of brain metastases,tumor diameter,the other parts of the transfer,the history of previous chemotherapy,the difference was not statistically signif-icant(P>0. 05). Radiotherapy before cognitive score,previous targeted therapy,difference was statistically significant (P0. 05). Conclusion:Brain metastases whole brain radiotherapy on cognitive function impairment,cognitive dysfunc-tion after radiotherapy most obvious subsequently was restored.

  20. 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.

  1. Small vessel ischemic disease of the brain and brain metastases in lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Peter J Mazzone

    Full Text Available BACKGROUND: Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID of the brain is protective against the development of brain metastases in lung cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the brain as part of their standard initial staging evaluation was reviewed. Information collected included demographics, comorbidities, details of the lung cancer, and the presence of SVID of the brain. A portion of the cohort had the degree of SVID graded. The primary outcome measure was the portion of study subjects with and without SVID of the brain who had evidence of brain metastases at the time of initial staging of their lung cancer.109 patients (20.8% had evidence of brain metastases at presentation and 345 (66.0% had evidence of SVID. 13.9% of those with SVID and 34.3% of those without SVID presented with brain metastases (p<0.0001. In a model including age, diabetes mellitus, hypertension, hyperlipidemia, and tobacco use, SVID of the brain was found to be the only protective factor against the development of brain metastases, with an OR of 0.31 (0.20, 0.48; p<0.001. The grade of SVID was higher in those without brain metastases. CONCLUSIONS/SIGNIFICANCE: These findings suggest that vascular changes in the brain are protective against the development of brain metastases in lung cancer patients.

  2. Radiotherapy for multiple brain metastases from hepatocellular carcinomas

    Institute of Scientific and Technical Information of China (English)

    Nobuyuki Toshikuni; Kazuhiko Morii; Michinori Yamamoto

    2007-01-01

    A 78-year-old man with liver cirrhosis was found to have multiple hepatocellular carcinomas (HCCs)and underwent 3 sessions of transcatheter arterial chemoembolization. Fourteen months after diagnosis,the patient presented with left hemiparesis. Contrastenhanced magnetic resonance imaging showed multiple metastases with ring-shaped enhancement in the cerebrum and cerebellum. There were no metastases to other organs. The metastatic lesions almost completely disappeared after whole-brain radiotherapy with a total dose of 50 Gy. Neurologic symptoms decreased,and the patient's quality of life improved. The patient underwent 2 more sessions of transcatheter arterial chemoembolization. Twelve months after the diagnosis of brain metastasis, the patient remains alive. The present case indicates that radiotherapy can improve quality of life and prolong survival in some patients with brain metastases from HCCs.

  3. MicroRNAs in Brain Metastases: Potential Role as Diagnostics and Therapeutics

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    Samer Alsidawi

    2014-06-01

    Full Text Available Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs, regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unresolved problem. Understanding these events will reveal disease-based targets and offer effective strategies to treat brain metastases. Effective therapeutic strategies based upon the biology of brain metastases represent an urgent, unmet need with immediate potential for clinical impact. Studies have demonstrated the ability of miRNAs to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on miRNA profiles. Interestingly, manipulation of miRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy and individually directed personalized anti-cancer therapy, using miRNA in the treatment of metastatic brain tumors may prove very useful and improve patient outcome. In this review, we focus on the potential of miRNAs as diagnostic and therapeutic targets for the treatment of metastatic brain lesions.

  4. Clinical Value of Whole-body Magnetic Resonance Diffusion Weighted Imaging on Detection of Malignant Metastases

    Institute of Scientific and Technical Information of China (English)

    Cheng Li; Zhen-sheng Liu; Xian-mao Du; Ling He; Jian Chen; Wei Wang; Fei Sun; Fang Du; Zhi-gang Luo; Zhen-long Xue; Yi Zhao; Chang-wu Zhou

    2009-01-01

    To evaluate the value of whole-body diffusion weighted imaging (WB-DWI) on detection of malignant metastasis.Methods Forty-six patients with malignant tumors underwent WB-DWI examinations between April 2007 and August 2007 in our hospital. Before WB-DWI examination, the primary cancers of all the patients were confirmed by pathology, and the TNM-stage was assessed with conventional magnetic resonance imaging (MRI) or computed tomography (CT). WB-DWl was performed using short TI inversion recovery echo-planar imaging (STIR-EPI) sequence. Abnormal high signal intensities on WB-DWI were considered as metastases. The results of WB-DWI were compared with other imaging modalities. For the assessment of the diagnostic capability of WB-DWl, WB-DWI were compared with CT for demonstrating mediastinal lymph node metastases and lung metastases, and with conventional MRI for demonstrating metastases in other locations.Results WB-DWI demonstrated 143 focuses, 14 of which were diagnosed to he benign lesions in routine imaging. The number of bone metastases depicted on WB-DWI and routine imaging was 85 and 86; lymph node metastases was 17 and 18; liver metastases was 14 and 14; lung metastases was 4 and 8; and brain metastases was 6 and 8, respectively. WB-DWI failed to detect 12 metastatic lesions including 3 osteoplastic bone metastases, 4 lung metastases, 3 mediastinal lymph node metastases, and 2 brain metastases. Four metastatic lesions including 2 deltopectoral lymph nodes and 2 rib metastases were detected with WB-DWI alone, all of which evolved greatly during clinical follow-up for more than 6 months. WB-DWI had higher detection rates for metastatic lesions in liver, bone, and lymph nodes than those in lung and brain (X2=30, P<0.001).Conclusions WB-DWI could detect most of metastatic lesions that were diagnosed with conventional MRI and CT. The limitations of WB-DWI might be had high false-positive rate and low efficiency in detecting mediastinal lymph node, brain, and

  5. 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.

  6. New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of ≤60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.

  7. HFSRT of the resection cavity in patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Specht, Hanno M.; Oechsner, Markus [Technische Universitaet Muenchen, Klinik fuer RadioOnkologie und Strahlentherapie, Klinikum rechts der Isar, Munich (Germany); Kessel, Kerstin A. [Technische Universitaet Muenchen, Klinik fuer RadioOnkologie und Strahlentherapie, Klinikum rechts der Isar, Munich (Germany); Helmholtz Zentrum Muenchen, Institut fuer Innovative Radiotherapie, Oberschleissheim (Germany); Meyer, Bernhard [Technische Universitaet Muenchen, Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Munich (Germany); Zimmer, Claus [Technische Universitaet Muenchen, Abteilung Neuroradiologie, Klinikum rechts der Isar, Munich (Germany); Technische Universitaet Muenchen, Deutsches Konsortium fuer Translationale Krebsforschung, Munich (Germany); Combs, Stephanie E. [Technische Universitaet Muenchen, Klinik fuer RadioOnkologie und Strahlentherapie, Klinikum rechts der Isar, Munich (Germany); Helmholtz Zentrum Muenchen, Institut fuer Innovative Radiotherapie, Oberschleissheim (Germany); Technische Universitaet Muenchen, Deutsches Konsortium fuer Translationale Krebsforschung, Munich (Germany)

    2016-06-15

    Aim of this single center, retrospective study was to assess the efficacy and safety of linear accelerator-based hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity of brain metastases after surgical resection. Local control (LC), locoregional control (LRC = new brain metastases outside of the treatment volume), overall survival (OS) as well as acute and late toxicity were evaluated. 46 patients with large (> 3 cm) or symptomatic brain metastases were treated with HFSRT. Median resection cavity volume was 14.16 cm{sup 3} (range 1.44-38.68 cm{sup 3}) and median planning target volume (PTV) was 26.19 cm{sup 3} (range 3.45-63.97 cm{sup 3}). Patients were treated with 35 Gy in 7 fractions prescribed to the 95-100 % isodose line in a stereotactic treatment setup. LC and LRC were assessed by follow-up magnetic resonance imaging. The 1-year LC rate was 88 % and LRC was 48 %; 57% of all patients showed cranial progression after HFSRT (4% local, 44% locoregional, 9% local and locoregional). The median follow-up was 19 months; median OS for the whole cohort was 25 months. Tumor histology and recursive partitioning analysis score were significant predictors for OS. HFSRT was tolerated well without any severe acute side effects > grade 2 according to CTCAE criteria. HFSRT after surgical resection of brain metastases was tolerated well without any severe acute side effects and led to excellent LC and a favorable OS. Since more than half of the patients showed cranial progression after local irradiation of the resection cavity, close patient follow-up is warranted. A prospective evaluation in clinical trials is currently being performed. (orig.) [German] Ziel dieser monozentrischen, retrospektiven Studie war es, die Effektivitaet und Sicherheit einer hypofraktionierter stereotaktischer Radiotherapie (HFSRT) nach chirurgischer Resektion von Hirnmetastasen zu untersuchen. Neben der lokalen Kontrolle (LC), der lokoregionaeren Kontrolle (LRC = neue

  8. Hair-sparing whole brain radiotherapy with volumetric arc therapy in patients treated for brain metastases: dosimetric and clinical results of a phase II trial

    International Nuclear Information System (INIS)

    To report the dosimetric results and impact of volumetric arc therapy (VMAT) on temporary alopecia and hair-loss related quality of life (QOL) in whole brain radiotherapy (WBRT). The potential of VMAT-WBRT to reduce the dose to the hair follicles was assessed. A human cadaver was treated with both VMAT-WBRT and conventional opposed field (OF) WBRT, while the subcutaneously absorbed dose was measured by radiochromic films and calculated by the planning system. The impact of these dose reductions on temporary alopecia was examined in a prospective phase II trial, with the mean score of hair loss at 1 month after VMAT-WBRT (EORTC-QOL BN20) as a primary endpoint and delivering a dose of 20 Gy in 5 fractions. An interim analysis was planned after including 10 patients to rule out futility, defined as a mean score of hair loss exceeding 56.7. A secondary endpoint was the global alopecia areata severity score measured with the “Severity of Alopecia Tool” (SALT) with a scale of 0 (no hair loss) to 100 (complete alopecia). For VMAT-WBRT, the cadaver measurements demonstrated a dose reduction to the hair follicle volume of 20.5% on average and of 41.8% on the frontal-vertex-occipital medial axis as compared to OF-WBRT. In the phase II trial, a total of 10 patients were included before the trial was halted due to futility. The EORTC BN20 hair loss score following WBRT was 95 (SD 12.6). The average median dose to the hair follicle volume was 12.6 Gy (SD 0.9), corresponding to a 37% dose reduction compared to the prescribed dose. This resulted in a mean SALT-score of 75. Compared to OF-WBRT, VMAT-WBRT substantially reduces hair follicle dose. These dose reductions could not be related to an improved QOL or SALT score

  9. Linear accelerator based stereotactic radiosurgery for melanoma brain metastases

    Directory of Open Access Journals (Sweden)

    Mark E Bernard

    2012-01-01

    Full Text Available Purpose: Melanoma is one of the most common malignancies to metastasize to the brain. Many patients with this disease will succumb to central nervous system (CNS disease, highlighting the importance of effective local treatment of brain metastases for both palliation and survival of the disease. Our objective was to evaluate the outcomes associated with stereotactic radiosurgery (SRS in the treatment of melanoma brain metastases. Materials and Methods: We retrospectively reviewed 54 patients with a total of 103 tumors treated with SRS. Twenty patients had prior surgical resection and nine patients underwent prior whole brain radiation therapy (WBRT. 71% of patients had active extracranial disease at the time of SRS. Median number of tumors treated with SRS was 1(range: 1-6 with median radiosurgery tumor volume 2.1 cm 3 (range: 0.05-59.7 cm 3 . The median dose delivered to the 80% isodose line was 24 Gy in a single fraction. Results: The median follow-up from SRS was five months (range:1-30 months. Sixty-five percent of patients had a follow-up MRI available for review. Actuarial local control at six months and 12 months was 87 and 68%, respectively. Eighty-one percent of patients developed new distant brain metastases at a median time of two months. The six-month and 12-month actuarial overall survival rates were 50 and 25%, respectively. The only significant predictor of overall survival was surgical resection prior to SRS. Post-SRS bleeding occurred in 18% of patients and at a median interval of 1.5 months. There was only one episode of radiation necrosis with no other treatment-related toxicity. Conclusion: SRS for brain metastases from melanoma is safe and achieves acceptable local control.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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-enhance...

  11. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    Science.gov (United States)

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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.

  14. Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner

    Science.gov (United States)

    Palmieri, Diane; Duchnowska, Renata; Woditschka, Stephan; Hua, Emily; Qian, Yongzhen; Biernat, Wojciech; Sosińska-Mielcarek, Katarzyna; Gril, Brunilde; Stark, Andreas; Hewitt, Stephen; Liewehr, David J; Steinberg, Seth M; Jassem, Jacek; Steeg, Patricia S

    2014-01-01

    Purpose Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Experimental Design Temozolomide was administered in mice following earlier injection of brain-tropic human epidermal growth factor receptor 2 (HER2)-positive Jimt1-BR3 and triple negative 231-BR-EGFP sublines, the latter with and without expression of 06-methylguanine-DNA methyltransferase (MGMT). Additionally, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Results Temozolomide, when dosed at 50, 25, 10 or 5 mg/kg, 5 days/week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing Jimt-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, while in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Conclusions Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. PMID:24634373

  15. Ipilimumab and whole brain radiation therapy for melanoma brain metastases

    Science.gov (United States)

    Gerber, Naamit K.; Young, Robert J.; Barker, Christopher A.; Wolchok, Jedd D.; Chan, Timothy A.; Yamada, Yoshiya; Friguglietti, Leigh

    2016-01-01

    Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3–4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity. PMID:25273687

  16. Evaluation of the Clinical Efficacy of Chemoradiotherapy in the Treatment of Breast Cancer with Brain Metastases%放化综合治疗在乳腺癌脑转移的临床疗效评价

    Institute of Scientific and Technical Information of China (English)

    姜丽娜; 李江涛; 刘薇

    2015-01-01

    Objective To evaluate the clinical efficacy of chemoradiotherapy in the treatment of breast cancer with brain metastases. Methods 84 cases with breast cancer and brain metastases underwent hospitalization in Department of Radio-therapy of our hospital from June 2008 to July 2015 were selected for the study and randomly divided into the study group and the control group with 42 cases in each. Both groups were given radiotherapy, in addition, the study group were given capecitabine for treatment. And the clinical efficacy and incidence of adverse reactions of the two groups were recorded. Results After treatment, the study group had higher total efficiency than the control group (80.9% vs 64.29%) with statisti-cally significant difference (P0.05). Conclusion Chemoradiotherapy is safe and effective for the treatment of breast cancer with brain metastases, it is suitable for clinical application and promotion.%目的:探究放化综合治疗在乳腺癌脑转移的临床疗效。方法整群选取2008年6月—2015年7月该院放疗科乳腺癌脑转移住院患者84例进行回顾性研究,将其按治疗方法不同分为研究组和对照组各42例。对照组进行单纯放疗,研究组在此基础上予以卡培他滨联合治疗。记录两组患者的临床疗效和各不良反应。结果治疗后,研究组患者的总有效率(80.9%)明显高于对照组(64.29%),两组比较差异有统计学意义(P<0.05)。研究组患者恶心、呕吐、白细胞下降等并发症发生率为与对照组比较,差异均无统计学意义(P>0.05)。结论放化综合治疗在乳腺癌脑转移的临床应用中安全、有效,适合临床上推广应用。

  17. Brain metastases from hepatocellular carcinoma:clinical features and prognostic factors in 31 cases%31例肝癌脑转移患者的临床特点及预后影响因素

    Institute of Scientific and Technical Information of China (English)

    张瑞丽; 张华; 张仑; 肖蕾; 孙岩娜; 杨颖; 包永星

    2016-01-01

    Objective Brain metastases ( BM) from hepatocellular carcinoma ( HCC) are rare and are associated with a poor prognosis. The aim of this study was to analyze the clinical features and evaluate the prognostic factors of brain metastases from hepatocellular carcinoma. Methods The clinical data of thirty⁃one patients with HCC and BM treated in the First Affiliated Hospital of Xinjiang Medical University between January 1998 and December 2013 were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors. Results Thrity⁃one patients were diagnosed with BM from HCC, an incidence rate of 0.61%. The median age at diagnosis of brain metastases was 48.5 years. Twenty⁃six patients were male. The median interval from diagnosis of hepatocellular carcinoma to brain metastases was 14 months. The median survival after the diagnosis of BM was 10 weeks. Univariate analysis showed that treatment modality, number of brain lesions, Karnofsky performance score, recursive partitioning analysis (RPA) class, and Child⁃Pugh classification had a statistically significant impact on the survival. The multivariate analysis showed that the low RPA class and aggressive brain radiotherapy were positively associated with improved survival. Conclusion BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive brain radiotherapy.%目的:探讨肝癌脑转移患者的临床特点和预后影响因素。方法回顾性分析31例肝癌脑转移患者的临床资料,对预后影响影响因素进行单因素和多因素生存分析。结果31例肝癌患者诊断为脑转移,肝癌脑转移的发生率为0.61%。诊断肝癌脑转移时患者的平均年龄为48.5岁,其中男性患者26例。从诊断肝癌到脑转移的平均时间间隔为14个月,肝癌脑转移患者的中位生存时间为10周。单因素分析显示,脑部

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

    International Nuclear Information System (INIS)

    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

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

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    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

  20. CT evaluation of choriocarcinoma with brain metastases

    International Nuclear Information System (INIS)

    It is well established that the computed tomography(CT) is an essential part not only in screening primary brain tumors, but also in staging known malignancy. This paper reports various CT findings demonstrated in 12 cases of choriocarcinoma with brain metastasis. The CT findings such as the number, location and density of the metastatic lesions, the degree of brain edema, mass effect and effect of contrast enhancement are reviewed as well as the episode of stroke syndrome and survival duration after neurologic symptom attacks. The results were as follows: 1. The of these cases showed solitary metastatic lesion and remaining 2 cases were multiple lesions. 2. One was isodense density and the others were hemorrhagic increased density by CT. 3. All of these showed mass effect to the surrounding structures along with moderate to marked brain edema. 4. The position of the metastatic lesion were located at the supratentorially in all cases. Most of them were at the unilateral frontal or parietal area or both of them. One which noted multiple metastatic foci showed at the bilateral occipital regions. 5. Nine cases showed ring enhancement after contrast infusion. One which noted isodense density on the noninfusion scan showed also ring enhancement after contrast infusion. 6. Nine cases showed positive stroke syndrome. One of them was performed emergency craniotomy. The remaining 3 cases noted progressive neurologic symptoms. 7. Two cases were noted only brain metastasis but the others also had various degree of pulmonary metastasis and 2 of latter had hepatic metastasis, too. 8. Most of the cases were treated with CHAMOCA regimen, and one of them was taken whole brain irradiation (3000 rads/2 weeks). Another on case revealed marked regression of not only metastatic brain lesion but the pulmonary lesion after the 8th course of CHAMOCA regimen and still alive for over 460 days

  1. CT evaluation of choriocarcinoma with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sei Chul; Kim, Choon Yul; Kwon, Hyung Chul; Bahk, Young Whee; Kim, Seung Jo [Catholic Medical College, Seoul (Korea, Republic of)

    1984-03-15

    It is well established that the computed tomography(CT) is an essential part not only in screening primary brain tumors, but also in staging known malignancy. This paper reports various CT findings demonstrated in 12 cases of choriocarcinoma with brain metastasis. The CT findings such as the number, location and density of the metastatic lesions, the degree of brain edema, mass effect and effect of contrast enhancement are reviewed as well as the episode of stroke syndrome and survival duration after neurologic symptom attacks. The results were as follows: 1. The of these cases showed solitary metastatic lesion and remaining 2 cases were multiple lesions. 2. One was isodense density and the others were hemorrhagic increased density by CT. 3. All of these showed mass effect to the surrounding structures along with moderate to marked brain edema. 4. The position of the metastatic lesion were located at the supratentorially in all cases. Most of them were at the unilateral frontal or parietal area or both of them. One which noted multiple metastatic foci showed at the bilateral occipital regions. 5. Nine cases showed ring enhancement after contrast infusion. One which noted isodense density on the noninfusion scan showed also ring enhancement after contrast infusion. 6. Nine cases showed positive stroke syndrome. One of them was performed emergency craniotomy. The remaining 3 cases noted progressive neurologic symptoms. 7. Two cases were noted only brain metastasis but the others also had various degree of pulmonary metastasis and 2 of latter had hepatic metastasis, too. 8. Most of the cases were treated with CHAMOCA regimen, and one of them was taken whole brain irradiation (3000 rads/2 weeks). Another on case revealed marked regression of not only metastatic brain lesion but the pulmonary lesion after the 8th course of CHAMOCA regimen and still alive for over 460 days.

  2. The Analysis of Erlotinib on Brain Metastases in Patients with Non-small-cell Lung Cancer

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    Baohui HAN

    2009-12-01

    Full Text Available Background and objective Brain metastases are common in non-small-cell lung cancer (NSCLC and the prognosis is poor. Erlotinib is a specific inhibitor of the epidermal growth factor receptor-associated tyrosine kinase (EGFRTKI, which has been gradually used in the treatment for advanced NSCLC. The aim of this study is to evaluate the antitumor efficacy and its relevant factors of erlotinib in NSCLC patients with brain metastases. Methods The clinical data of 30 NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with erlotinib, given orally 150mg daily. These patients discontinued administration of erlotinib until disease progression, death or intolerable side effects. Results In terms of intracranial lesions, partial response (PR was observed in 2 patients (6.7%, with stable disease (SD in 17 patients (56.7%, for overall disease control rate (DCR of 63.4%. As for systemic disease, PR was observed in 2 patients (6.7%, with SD in 5 patients (16.7%, for overall DCR of 23.4%. There was no statistical difference in DCR among different subtypes of age, gender, smoking history, histology, PS score, the number of brain metastases, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects. The median time to disease progression (MTTP and median survival time (MST was 2.4 months and 7.7 months respectively. The 1 and 2 year survival rate was 38.4% and 15.2%. The univariate analysis showed that the survival time was related to the patients’ PS score, smoking history, brain radiotherapy and chemotherapy. The multivariate analysis indicated that brain radiotherapy was the independent prognostic factor and the relationship between the survival time and smoking history was near to statistical significance. Conclusion The patients receiving brain radiotherapy may have better survival benefit. Non-smokers have a trend to survive longer than smokers. Erlotinib may be effective on brain metastases

  3. 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.

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

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    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.

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

    International Nuclear Information System (INIS)

    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

  6. The role of magnetic resonance imaging in the management of brain metastases: diagnosis to prognosis

    OpenAIRE

    Zakaria, Rasheed; Das, Kumar; Bhojak, Maneesh; Radon, Mark; Walker, Carol; Jenkinson, Michael D

    2014-01-01

    This article reviews the different MRI techniques available for the diagnosis, treatment and monitoring of brain metastases with a focus on applying advanced MR techniques to practical clinical problems. Topics include conventional MRI sequences and contrast agents, functional MR imaging, diffusion weighted MR, MR spectroscopy and perfusion MR. The role of radiographic biomarkers is discussed as well as future directions such as molecular imaging and MR guided high frequency ultrasound.

  7. Multimodality treatment of brain metastases: an institutional survival analysis of 275 patients

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    Demakas John J

    2011-07-01

    Full Text Available Abstract Background Whole brain radiation therapy (WBRT, surgical resection, stereotactic radiosurgery (SRS, and combinations of the three modalities are used in the management of patients with metastatic brain tumors. We present the previously unreported survival outcomes of 275 patients treated for newly diagnosed brain metastases at Cancer Care Northwest and Gamma Knife of Spokane between 1998 and 2008. Methods The effects treatment regimen, age, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS, primary tumor histology, number of brain metastases, and total volume of brain metastases have on patient overall survival were analyzed. Statistical analysis was performed using Kaplan-Meier survival curves, Andersen 95% confidence intervals, approximate confidence intervals for log hazard-ratios, and multivariate Cox proportional hazard models. Results The median clinical follow up time was 7.2 months. On multivariate analysis, survival statistically favored patients treated with SRS alone when compared to patients treated with WBRT alone (p Conclusions In our analysis, patients benefited from a combined modality treatment approach and physicians must consider patient age, performance status, and primary tumor histology when recommending specific treatments regimens.

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

    International Nuclear Information System (INIS)

    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.

  9. Innovative therapeutic strategies in the treatment of brain metastases.

    Science.gov (United States)

    Caffo, Maria; Barresi, Valeria; Caruso, Gerardo; Cutugno, Mariano; La Fata, Giuseppe; Venza, Mario; Alafaci, Concetta; Tomasello, Francesco

    2013-01-01

    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. PMID:23340652

  10. Innovative Therapeutic Strategies in the Treatment of Brain Metastases

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    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.

  11. The Value of the History and Physical for Patients with Newly Diagnosed Brain Metastases Considering Radiosurgery

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    Ima ePaydar

    2016-03-01

    Full Text Available Background: For patients with brain metastases, systemic disease burden has historically been accepted as a major determinant of overall survival (OS. However, less research has focused on specific history and physical findings made by clinicians and how such findings pertain to patient outcomes at a given time point. The aim of this study is to determine how the initial clinical assessment of patients with brain metastases, as part of the history and physical at the time of consultation, correlates with patient prognosis.Methods: We evaluated a prospective, multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or CyberKnife from 2001-2014. Relevant history of present illness (HPI and past medical history (PMH variables included comorbidities, Eastern Cooperative Oncology Group (ECOG performance status, and seizure history. Physical exam findings included a sensory exam, motor exam, and cognitive function. Univariate and multivariate Cox regression analyses were used to identify predictors of OS.Results: 294 patients were included in the final analysis with a median OS of 10.8 months (95% C.I., 7.8-13.7 months. On univariate analysis, significant HPI predictors of OS included age, primary diagnosis, performance status, extracranial metastases, systemic disease status, and history of surgery. Significant predictors of OS from the PMH included cardiac, vascular, and infectious comorbidities. On a physical exam, findings consistent with cognitive deficits were predictive of worse OS. However, motor deficits or changes in vision were not predictive of worse OS. In the multivariate Cox regression analysis, predictors of worse OS were primary diagnosis (p=0.002, ECOG performance status (OR 1.73, p<0.001, and presence of extracranial metastases (OR 1.22, p=0.009.Conclusion: Neurologic deficits and systemic comorbidities noted at presentation are not associated with worse overall prognosis

  12. The role of whole brain radiation therapy in the management of melanoma brain metastases

    International Nuclear Information System (INIS)

    Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease

  13. Linear accelerator-based stereotactic radiosurgery in 140 brain metastases from malignant melanoma

    OpenAIRE

    Hauswald, Henrik; Stenke, Alina; Debus, Jürgen; Combs, Stephanie E

    2015-01-01

    Background: To retrospectively access outcome and prognostic parameters of linear accelerator-based stereotactic radiosurgery in brain metastases from malignant melanoma. Methods: Between 1990 and 2011 140 brain metastases in 84 patients with malignant melanoma (median age 56 years) were treated with stereotactic radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed extracerebral control. The median count of brain metastases in a single patient was 1, the median diamete...

  14. 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)

    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.

  15. Multimodal imaging of bone metastases: From preclinical to clinical applications

    Directory of Open Access Journals (Sweden)

    Stephan Ellmann

    2015-10-01

    Full Text Available Metastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.

  16. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.

    Science.gov (United States)

    Lombardi, Giuseppe; Di Stefano, Anna Luisa; Farina, Patrizia; Zagonel, Vittorina; Tabouret, Emeline

    2014-09-01

    The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results. This review focuses on systemic cytotoxic drugs and, in particular, on new targeted therapies and their clinically relevant activities in brain metastases from solid tumors in adults.

  17. Brain metastases of malignant melanoma in Chinese:report of 23 cases

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-chou; LEE Shih-tseng

    2007-01-01

    Background Patients with melanoma metastasized to the central nervous system have a poor prognosis. Because the incidence of malignant melanoma in the Oriental is lower than that in the Caucasian population, brain metastases of malignant melanoma are rarely reported in Asia. Here we present our experience of brain metastasis of melanoma in an Asian perspective.Methods From 1990 to 2003, 369 patients with melanoma were treated in our hospital, 26 of them were diagnosed as having central nervous system involvement. Of the 26 cases, the clinical history, image, and pathologic findings of 23 patients were analyzed; the other 3 were excluded because of incomplete clinical data.Results Among the 369 patients with melanoma, 45% (167/369) developed lower extremity melanoma, and 27.1%(100/369) had acral lentiginous melanoma (ALM); while in the 23 patients with brain metastases, 34.7% (8/23) had lower extremity melanoma, and 34.7% (8/23) had ALM. Among the 23 patients, 17 had acute hemorrhage into the tumor,8 initially presented with a single cerebral metastatic lesion, and 15 had multiple brain lesions. Ten of them received surgery, 3 underwent stereotactic radiosurgery, and 16 received whole brain radiation. During follow-up, only 2 patients survived for more than 1 year, the median survival period was 5 months. The longest follow-up period was 11 years.Conclusions Compared with the Caucasian, Chinese patients with melanoma have a different proportion of melanoma subtype and higher incidence rates of lower extremities melanoma and ALM. However, their clinical presentation and prognosis are similar. The patients, who have excisable single or multiple brain lesions or limited extracranial disease and who are actively treated, may survive longer.

  18. Primary cardiac sarcoma with metastases to thyroid and brain

    Directory of Open Access Journals (Sweden)

    Jyotsna Yesodharan

    2015-01-01

    Full Text Available Primary cardiac sarcomas are extremely rare with only a few large case series and isolated case reports in the literature. In spite of their aggressive nature with high chances of local recurrence and distant metastases, these tumors and their treatment strategies remain incompletely defined. We report an unsuspected case of primary cardiac pleomorphic undifferentiated sarcoma in a 52-year-old female who presented with progressive dyspnea and palpitation. In the postoperative period, she was detected to have secondaries in brain and thyroid, confirmed thereafter, by fine-needle aspiration cytology.

  19. Clinical Features of Choroidal Metastases from Carcinoid Tumour

    Institute of Scientific and Technical Information of China (English)

    Huaning She; Yuping Zheng; Xiaohua Wang; Yanlong Quan; Naixue Sun

    2004-01-01

    Purpose :To report ophthalmologic and angiographic features of choroidal metastases from carcinoid tumor and analyze their common clinical manifestation.Methods:Ophthalmologic examinations and fundus fluorescein angiography (FFA) were performed in 30 patients suffered from carcinoid tumor, and four patients diagnosed of breast cancer (2 cases), lung cancer (1 case) and maxillary sinus cancer (1 case) were confirmed with choroidal metastases.Results:Choroidal metastases were found as the initial manifestations of the malignant tumors on 2 patients whose initial and chief complaints were decreasing vision, their fundus lesions were mainly presented in the posterior pole and FFA showed high density of fluorescence of the lesions.Conclusions:This study indicated choroidal metastasis might be the first sign of metastases for patients with cancer. For patients with unknown metastastic cancers, examinations of the choroids may be useful for diagnosis and prognosis. Eye Science 2004;20:15-18.

  20. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents. Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment. Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034). Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM

  1. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Vogl Ursula M

    2010-09-01

    Full Text Available Abstract Background In the era of cytokines, patients with brain metastases (BM from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA have improved the outcome of patients with metastatic renal cell carcinoma (mRCC however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents. Methods Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR, progression free survival (PFS and overall survival (OS. All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment. Results Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC patients (10.5% were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3 and 11.4 months (95% CI 8.7 - 14.1 for BM-patients and non-BM-patients, respectively (p = 0.232. The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9 and 33.3 months (95% CI 18.6 - 47.0 (p = 0.358, respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034. Conclusions Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.

  2. Shorter-Course Whole-Brain Radiotherapy for Brain Metastases in Elderly Patients

    International Nuclear Information System (INIS)

    Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 × 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 × 3 Gy with 5 × 4 Gy in elderly patients (≥65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 × 3 Gy were compared with 162 patients receiving 5 × 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 × 4 Gy and 21% after 10 × 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS ≥ 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS ≥ 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 × 4 Gy was not inferior to 10 × 3 Gy with respect to overall survival or local control in elderly patients. 5 × 4 Gy appears preferable for the majority of these patients.

  3. Infratentorial brain metastases of pediatric non-epithelial malignant tumors: three case reports.

    Science.gov (United States)

    Osawa, Shin-ichiro; Kumabe, Toshihiro; Saito, Ryuta; Sonoda, Yukihiko; Niizuma, Hidetaka; Watanabe, Mika; Tominaga, Teiji

    2011-04-01

    Three pediatric patients with infratentorial metastatic non-epithelial malignant brain tumors were successfully treated by radical surgical resection followed by aggressive radiochemotherapy. One patient with neuroblastoma and two with rhabdomyosarcoma were successfully treated by first line multimodal treatments, but developed infratentorial metastasis after several months of remission. All patients revealed intracranial metastases manifesting as rapidly progressing neurological symptoms caused by mass effect in the posterior fossa. Radical surgical resection was performed without morbidity. The patients were then treated by adjuvant radiochemotherapy with or without autologous peripheral blood stem cell transplantation, resulting in complete remission. Two patients developed extracranial recurrences 4 months after the treatments for intracranial metastases. One patient was treated by second high-dose chemotherapy with allogeneic cord blood transplantation, again resulting in complete remission. Another patient was treated by second chemotherapy and maintaining stable disease. The other patient maintained complete remission. All three patients were alive without neurological deficit for 8, 11, and 12 months after diagnosis of brain metastasis. Patients with infratentorial brain metastases of highly malignant pediatric non-epithelial tumors are in a severe clinical state, but still can have longer and useful lives with aggressive multimodal treatments combined with radical surgical resection.

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

    International Nuclear Information System (INIS)

    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

  5. 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....

  6. Brain Metastases from Different Primary Carcinomas: an Evaluation of DSC MRI Measurements.

    Science.gov (United States)

    Zhang, H; Zhang, G; Oudkerk, M

    2012-03-01

    This study evaluated the roles of different dynamic susceptibility contrast magnetic imaging (DSC MRI) measurements in discriminating between brain metastases derived from four common primary carcinomas. Thirty-seven patients with brain metastases were enrolled. Relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and relative mean transit time (rMTT) in both tumor and peritumoral edema were measured. Metastases were grouped by their primary tumor (lung, gastrointestinal, breast and renal cell carcinoma). DSC MRI measurements were compared between groups. Mean rCBV, rCBF, rMTT in tumor and peritumoral edema of all brain metastases (n=37) were 2.79 ± 1.73, 2.56 ± 2.11, 1.21 ± 0.48 and 1.05 ± 0.53, 0.86 ± 0.40, 1.99 ± 0.41, respectively. The tumoral rCBV (5.26 ± 1.89) and rCBF (5.32 ± 3.28) of renal metastases were greater than those of the other three metastases (P0.05). Evaluating various DSC MRI measurements can provide complementary hemodynamic information on brain metastases. The tumoral rCBV, rCBF and likely rMTT can help discriminate between brain metastases originating from different primary carcinomas. The peritumoral DSC MRI measurements had limited value in discriminating between brain metastases.

  7. TENIPOSIDE FOR BRAIN METASTASES OF SMALL-CELL LUNG-CANCER - A PHASE-II STUDY

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF; HAAXMAREICHE, H; VANZANDWIJK, N; ARDIZZONI, A; QUOIX, E; KIRKPATRICK, A; SAHMOUD, T; GIACCONE, G

    1995-01-01

    Purpose: Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases. Patients and Methods: Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up evaluat

  8. Predicting brain metastases of breast cancer based on serum S100B and serum HER2

    DEFF Research Database (Denmark)

    Bechmann, Troels; Madsen, Jonna Skov; Brandslund, Ivan;

    2013-01-01

    Brain metastases are a major cause of morbidity and mortality in breast cancer. The aim of the current study was to evaluate the prediction of brain metastases based on serum S100B and human epidermal growth factor receptor 2 (HER2). A total of 107 breast cancer patients were included...

  9. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

  12. Treatment of Five or More Brain Metastases With Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Hunter, Grant K.; Suh, John H.; Reuther, Alwyn M. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Vogelbaum, Michael A.; Barnett, Gene H.; Angelov, Lilyana; Weil, Robert J. [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Neyman, Gennady [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Chao, Samuel T., E-mail: chaos@ccf.org [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States)

    2012-08-01

    Purpose: To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). Methods and Materials: Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). Results: The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of {>=}80 significantly influenced OS (median OS, 4.8 months for KPS {<=}70 vs. 8.8 months for KPS {>=}80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of {<=}70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157). Conclusions: Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with

  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)

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

    International Nuclear Information System (INIS)

    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

  15. Criteria for palliation of bone metastases - Clinical applications

    International Nuclear Information System (INIS)

    Bone metastases are a frequent complication of cancer. It is estimated that they arise in 14-70% of all tumour patients, while it was reported that they occur in 70-85% patients in autopsy material. Although they may arise from any primary malignant tumour, certain tumours such as breast, prostate, lung, thyroid, kidney and myeloma have a predilection for a spread to bone. Bone metastases frequently cause pain, but there are also clinical situations with bone metastases causing no pain at all. The overall importance of the problem of bone metastases is well recognized by the fact that each year hundreds of thousands of cancer patients develop bone metastases. For example, more than 100 000 new patients develop this condition in the United States of America, although the prevalence is estimated to be double the number of new cases. While it is virtually unknown how many cancer patients in the developing countries develop bone metastases, it is not unrealistic to expect that these figures largely surpass those coming from the developed countries. The reason is simply that more patients in the developing countries are diagnosed as having locally advanced or metastatic cancer that will eventually widely disseminate, including bone metastasis as well. Furthermore, at least some of the cancer patients may survive prolonged periods of time. They can also develop earlier and more severe symptoms than patients harbouring other types (locations) of metastases, emphasizing the importance of the overall problem of painful bone metastases. In addition, there is a big socioeconomic problem of bone metastasis, burdening health care systems worldwide, while having continuous adverse psychological effect on both patients and their families. The management of patients with metastatic bone pain must be a multidisciplinary approach and includes the use of analgesia, radiotherapy, surgery, chemotherapy, hormone treatment, radioisotopes and bisphosphonates. Analgesia, with non

  16. Brain metastases management paradigm shift: A case report and review of the literature

    OpenAIRE

    Refaat, Tamer; SACHDEV, SEAN; Desai, Brijal; Bacchus, Ian; HATOUM, SALEH; LEE, PLATO; Bloch, Orin; Chandler, James P; KALAPURAKAL, JOHN; MARYMONT, MARYANNE HOFFMAN

    2016-01-01

    Brain metastases are the most common intracranial tumors in adults, accounting for over half of all lesions. Whole-brain radiation therapy (WBRT) has been a cornerstone in the management of brain metastases for decades. Recently, stereotactic radiosurgery (SRS) has been considered as a definitive or postoperative approach instead of WBRT, to minimize the risk of cognitive impairment that may be associated with WBRT. This is the case report of a 74-year-old female patient who was diagnosed wit...

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

    OpenAIRE

    Linnert, Mette; Iversen, Helle K.; 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 electrochemotherapy (ECT) as one of the new experimental treatments for this group of patients. Conclusions Neurosurgery, stereotactic surgery, and whole-brain radiotherapy are the evidence-based treatmen...

  18. O7.02RADIOSURGERY AND BRAIN METASTASES: ADEQUATE SEQUENCE OF BRAIN MRI CAN SIGNIFICANTLY CHANGE THE INTRACRANIAL DISEASE STAGING

    OpenAIRE

    Scoccianti, S.; Greto, D.; L. Bordi; Bono, P.; Pecchioli, G.; Casati, M; E. Vanzi; Compagnucci, A; Gadda, D.; Livi, L.

    2014-01-01

    INTRODUCTION: Accurate assessment of the exact number of brain metastases is of utmost importance in the decision-making process for the appropriate treatment. The diagnostic efficacy in the detection of additional brain metastases of a double dose contrast three-dimensional, T1-Weighted Gradient-Echo Imaging was evaluated. METHODS: Before undergoing radiosurgical treatment, patients underwent a brain magnetic resonance imaging (MRI) scan to be used during the treatment planning in order to c...

  19. Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume. Conclusions: Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T1-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action

  20. 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

  1. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases.

    Science.gov (United States)

    Kohutek, Zachary A; Yamada, Yoshiya; Chan, Timothy A; Brennan, Cameron W; Tabar, Viviane; Gutin, Philip H; Yang, T Jonathan; Rosenblum, Marc K; Ballangrud, Åse; Young, Robert J; Zhang, Zhigang; Beal, Kathryn

    2015-10-01

    Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed either pathologically or radiographically. Univariate and multivariate Cox regression was performed to determine the association between radionecrosis and clinical factors available prior to treatment planning. After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8%) lesions, including 47 (17.3%) symptomatic cases. 22 of 70 cases (31.4%) were diagnosed pathologically and 48 (68.6%) were diagnosed radiographically. The actuarial incidence of radionecrosis was 5.2% at 6 months, 17.2% at 12 months and 34.0% at 24 months. On univariate analysis, radionecrosis was associated with maximum tumor diameter (HR 3.55, p 1 cm. PMID:26307446

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

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    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.

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

    International Nuclear Information System (INIS)

    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.

  4. EGFR mutations in patients with brain metastases from lung cancer: Association with the efficacy of gefitinib

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    Shimato, Shinji; Mitsudomi, Tetsuya; Kosaka, Takayuki; Yatabe, Yasushi; Wakabayashi, Toshihiko; Mizuno, Masaaki; NAKAHARA, NORIMOTO; Hatano, Hisashi; Natsume, Atsushi; Ishii, Dai; YOSHIDA, Jun

    2006-01-01

    Gefitinib—a specific inhibitor of epidermal growth factor receptor (EGFR)-associated tyrosine kinase—has demonstrated efficacy in a subgroup of patients with non-small-cell lung carcinoma (NSCLC) who fail conventional chemotherapy. It is also reported to have an antitumor effect in brain metastases from NSCLC. Additionally, EGFR mutations have shown a strong association with gefitinib sensitivity for NSCLC. Here, we assessed the efficacy of gefitinib in brain metastases from NSCLC and evaluat...

  5. MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases | Division of Cancer Prevention

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    Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. |

  6. Rare Aggressive Behavior of MDM2-Amplified Retroperitoneal Dedifferentiated Liposarcoma, with Brain, Lung and Subcutaneous Metastases

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    Ben Salha, Imen; Zaidi, Shane; Noujaim, Jonathan; Miah, Aisha B.; Fisher, Cyril; Jones, Robin L.; Thway, Khin

    2016-01-01

    Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, non-lipogenic 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.

  7. Whole Brain Radiotherapy With Hippocampal Avoidance and Simultaneously Integrated Brain Metastases Boost: A Planning Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the feasibility of using tomotherapy to deliver whole brain radiotherapy with hippocampal avoidance, hypothesized to reduce the risk of memory function decline, and simultaneously integrated boost to brain metastases to improve intracranial tumor control. Methods and Materials: Ten patients treated with radiosurgery and whole brain radiotherapy underwent repeat planning using tomotherapy with the original computed tomography scans and magnetic resonance imaging-computed tomography fusion-defined target and normal structure contours. The individually contoured hippocampus was used as a dose-limiting structure (2 and 5.8 ± 1.9 Gy2 for 2.5- and 1.0-cm FW, respectively. The mean treatment delivery time for the 2.5- and 1.0-cm FW plans was 10.2 ± 1.0 and 21.8 ± 1.8 min, respectively. Conclusion: Composite tomotherapy plans achieved three objectives: homogeneous whole brain dose distribution equivalent to conventional whole brain radiotherapy; conformal hippocampal avoidance; and radiosurgically equivalent dose distributions to individual metastases

  8. DVHs evaluation in brain metastases stereotactic radiotherapy treatment plans

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    Purpose: The aim of this work is to report a retrospective study of radiobiological indicators based on Dose-Volume Histograms analysis obtained by stereotactic radiotherapy treatments. Methods and materials: Fifty-five patients for a total of sixty-seven brain metastases with a mean target volume of 8.49 cc were treated by Dynamic Conformal Arc Therapy (DCAT) and Intensity-Modulated Stereotactic Radiotherapy (IMRST). The Delivered prescription dose was chosen on the basis of tumor size and location so as to ensure a 100% isodose coverage to the target volume. Results: The treatment plans reported a mean value of 10% and 2.19% for the inhomogeneity and conformal index, respectively. The F factor showed we overdosed sixty-three patients delivering an additional 7% dose more than calculated values. The radiobiological parameters: TCP and NTCP showed a complete tumor control limiting the organs at risk damage. Conclusion: One goal of stereotactic radiotherapy is to design a treatment plan in which the steep dose gradient achievable minimizes the amount of radiation delivered outside the tumor region. This technique allows to deliver a much larger dose to the target without exceeding the radiation-related tolerance of normal tissues and improving patients' quality of life

  9. 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

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    Ameer L. Elaimy

    2012-01-01

    Full Text Available 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.

  10. Targeting bone metastases in prostate cancer: improving clinical outcome.

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    Body, Jean-Jacques; Casimiro, Sandra; Costa, Luís

    2015-06-01

    Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development. PMID:26119830

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

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    Ebi, Junko, E-mail: junkoe@fmu.ac.jp [Department of Radiology, Fukushima Medical University, Fukushima (Japan); Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio [Department of Radiology, Fukushima Medical University, Fukushima (Japan)

    2013-04-01

    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.

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

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    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.

  13. Fractionated Helical Tomotherapy as an alternative to radiosurgery in patients unwilling to undergo additional radiosurgery for recurrent brain metastases

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    Sanghera, P; Lightstone, A W; Hyde, D.E.; Davey, P.

    2010-01-01

    Our clinic routinely treats brain metastases with stereotactic radiosurgery using a 6 megavoltage (MV) linear accelerator, cones, and a surgically attached head frame. Four patients declined repeat radiosurgery for new lesions due to their previous discomfort and a fifth patient could not complete radiosurgery because of uncontrolled nausea. Instead patients were treated with Helical Tomotherapy (HT). This report discusses the spatial dose distribution of HT as measured in a head phantom and ...

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

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    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.

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

    International Nuclear Information System (INIS)

    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 1H MR spectroscopy and spectroscopic imaging (1H 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. 1H 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 1H 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 1H MR spectroscopy in differentiating radiation effects from tumor progression. (orig.)

  16. Management of brain metastases with stereotactic radiosurgery alone versus whole brain irradiation alone versus both

    International Nuclear Information System (INIS)

    This prospective randomized study aimed to evaluate the role of WBRT + SRS compared to SRS alone and to WBRT alone in improvement of overall survival, brain local control and neurologic manifestations. The trial included 60 patients with 1 to 3 brain metastases treated at the Radiotherapy Department, National Cancer Institute. 21 patients received WBRT + SRS, 18 patients received SRS alone and 21 patients received WBRT alone. Median local control was significantly better for WBRT + SRS compared to SRS alone & WBRT alone (10 vs 6 vs 5 months, respectively, P = 0.04). There was non significant survival benefit for WBRT + SRS compared to SRS alone & WBRT alone. Survival was significantly better for patients with controlled primary tumor who received WBRT + SRS compared to SRS alone & WBRT alone (median survival was 12 vs 5.5 vs 8 months, respectively. P = 0.027). Regardless of the treatment group, median survival and median local control were highly significantly better for single brain site involvement compared to multiple brain sites involvement (P = 0.003 & P = 0.001, respectively), and median brain local control was significantly better for single lesion compared to multiple lesions (P = 0.05). WBRT + SRS is an effective, safe tool in treatment of patients with 1 to 3 brain metastses improving the brain local control, but further studies with larger number of patients is recommended

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

    International Nuclear Information System (INIS)

    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

  18. Evaluation of brain metastases with dynamic susceptibility-contrast MR imaging

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    Objective: To study the characteristics of dynamic susceptibility-contrast (DSC) MR perfusion curves, color images and perfusion values in pre-operative brain metastasis. Methods: Twenty- eight brain metastases underwent DSC MR perfusion imaging by using a first-pass T2* echo-planar sequence. The patients' data were transferred to on-line workstation. Time-signal intensity curves, color perfusion maps and rCBV, rMTT values in both tumor parenchyma and peri-tumor edema were analyzed, and independent t- test was used and P0.05). Conclusion: Different originated brain metastases have nearly same characteristics in DSC MR perfusion imaging. (authors)

  19. A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

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    Carsten Nieder

    2012-01-01

    Full Text Available Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes 3.1×109/L. The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

  20. 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

  1. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

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    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  2. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain.

    Science.gov (United States)

    Kanojia, Deepak; Morshed, Ramin A; Zhang, Lingjiao; Miska, Jason M; Qiao, Jian; Kim, Julius W; Pytel, Peter; Balyasnikova, Irina V; Lesniak, Maciej S; Ahmed, Atique U

    2015-05-01

    Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells.

  3. An unusual Case of Transitional Cell Carcinoma of Renal Pelvis Presenting with Brain Metastases

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    MR Razzaghi

    2009-04-01

    Full Text Available ABSTRACT: Introduction & Objective: Transitional cell carcinoma of renal pelvis presenting with brain metastases is a very rare case which should be diagnosed and treated in order to prevent further damages. Case: We report a rare case, who had presented with a constellation of neurological symptoms (due to multiple brain metastases, but without any urological symptoms. During evaluation of patient, we found transitional cell carcinoma (TCC of left renal pelvis, for which palliative radical nephroureterectomy was performed . Conclusion: Although transitional cell carcinoma of renal pelvis presenting with brain metastases is a very rare case, but the patient was managed with gamma knife stereotactic radiosurgery for the metastatic lesions. Afterward he received four cycles of paclitaxel and carboplatin chemotherapy. The patient is alive with stable disease at 32- months’ follow-up.

  4. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis

    International Nuclear Information System (INIS)

    to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 - V16 Gy) as predictors for brain radionecrosis. Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant'Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications. Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm3 and V12 Gy >10.9 cm3 the risk of radionecrosis was 47%. SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm3 carries a risk of radionecrosis >10% and should be considered for

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

    International Nuclear Information System (INIS)

    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

  6. A phase II study of thalidomide in patients with brain metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Vestermark, Lene; Larsen, Susanne; Lindeløv, Birgit;

    2008-01-01

    Introduction. Brain metastases develop in nearly half of the patients with advanced melanoma and in 15 to 20% of these patients CNS is the first site of relapse. Overall median survival is short, ranging from 2 to 4 months. Thalidomide has antiangiogenic and immunomodulatory effects. Results...... obtained in prior trials indicate that Thalidomide acts as a cytostatic agent in metastatic melanoma. We evaluated single agent antitumour activity and toxicity of Thalidomide in a phase II setting in patients with brain metastases associated with metastatic melanoma. Material and methods. Patients...

  7. The benefit of whole brain reirradiation in patients with multiple brain metastases

    International Nuclear Information System (INIS)

    To assess the outcomes, symptom palliation and survival rates in patients who received repeat whole brain radiotherapy (WBRT). Twenty-eight patients who had progression of brain metastasis received a second course of WBRT. Univariate log-rank testing and multivariate Cox regression analysis were used to determine the factors for death among several variables (cumulative BED [BEDcumulative], primary tumor site, Karnofsky performance scale [KPS], previous SRS, number of metastases and absence of extracranial metastases). Correlations between variables and treatment response were evaluated with the Chi-squared test. The median KPS was 60 (range 50 to 100) at the initiation of reirradiation. The median time interval between the two courses of WBRT was 9.5 months (range 3–27 months). The median doses of the first course and the second course of WBRT were 30 Gy (range 20 to 30 Gy) and 25 Gy (range 20 to 30 Gy), respectively. The mean BEDcumulative was 129.5 Gy (range 110 to 150 Gy). Severe or unexpected toxicity was not observed. Symptomatic response was detected in 39% of the patients. The median overall survival following reirradiation was 3 months (range 1 to 12 months, 95% CI 1.82-4.118). Survival was significantly better in responders (median 10 months, 95% CI 3.56-16.43) compared with non-responders (median 2 months, 95% CI 1.3-2.64) (p = 0.000). In multivariate analysis, patients that had lung cancer (p = 0.01), initial KPS ≥60 (p = 0.03) or longer intervals to reirradiation (p = 0.01) had significantly better survival rates. A careful second course of whole brain irradiation might provide a symptomatic and survival benefit in patients with good performance status and longer cranial progression-free intervals

  8. Turbo STIR magnetic resonance imaging as a whole-body screening tool for metastases in patients with breast carcinoma: preliminary clinical experience.

    Science.gov (United States)

    Walker, R; Kessar, P; Blanchard, R; Dimasi, M; Harper, K; DeCarvalho, V; Yucel, E K; Patriquin, L; Eustace, S

    2000-04-01

    This study was undertaken to assess the utility of whole-body turbo short tau inversion recovery (STIR) magnetic resonance imaging (MRI) to detect metastases to liver, brain, and bone as a single examination in women with breast cancer. Seventeen patients with biopsy-proven breast cancer and suspected metastatic disease attending over a 12-month period referred for both conventional imaging and whole-body MRI were included in the study. Three patients were found to be free of metastases at both conventional and MR imaging. Appendicular or axial skeletal metastases were identified in 11 of 17 patients, with correlation between findings at whole-body MRI and scintigraphy in 15 of the 17 patients. Five patients had evidence of hepatic metastases on whole-body MRI, of which metastases were identified in only three patients at CT despite contrast enhancement. Four patients had brain abnormalities (metastases in three patients, meningioma in one patient) detected on both whole-body and dedicated brain MRI. Preliminary clinical experience suggests that turbo STIR whole-body MRI may represent a convenient and cost-effective method of total body screening for metastases in patients with breast carcinoma.

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

    Directory of Open Access Journals (Sweden)

    Steinmann Diana

    2012-07-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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

  10. Clinical radiodiagnosis of metastases of central lung cancer in regional lymph nodes using computers

    International Nuclear Information System (INIS)

    On the basis of literary data and clinical examination (112 patients) methods of clinical radiodiagnosis of metastases of central lung cancer in regional lymph nodes using computers are developed. Methods are tested on control clinical material (110 patients). Using computers (Bayes and Vald methods) 57.3% and 65.5% correct answers correspondingly are obtained, that is by 14.6% and 22.8% higher the level of clinical diagnosis of metastases. Diagnostic errors are analysed. Complexes of clinical-radiological signs of symptoms of metastases are outlined

  11. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    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

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. Miliary brain metastases from papillary adenocarcinoma of the lung – unusual MRI pattern with histopathologic correlation

    International Nuclear Information System (INIS)

    Miliary brain metastases are very rarely described in the literature but if they are, they are quite obvious on magnetic resonance imaging (MRI) and enhance after intravenous administration of the contrast medium. The authors presented a case of miliary metastatic spread to the brain which was invisible on computed tomography and hardly visible on MRI, i.e. as countless, tiny, slightly T1-hyperintense foci that did not enhance. The authors discussed a few T1-hyperintense brain lesions which did not include metastases (except for metastatic melanoma which was a radiological suggestion after brain MRI). Autopsy revealed papillary adenocarcinoma of the lung with numerous metastatic lesions in both cerebral and cerebellar hemispheres and the meninges

  15. Treatment outcomes in patients with multiple brain metastases: A prospective randomized study

    OpenAIRE

    Animesh Saha; Sajal Kumar Ghosh; Chhaya Roy; Priyanjit Kayal

    2014-01-01

    Context: There is controversy regarding the radiotherapeutic dose fractionation in brain metastases (bm). Aims: The aim of this study is to analyze the treatment outcomes in patients with multiple bm. Settings and Design: Prospective, randomized study. Subjects and Methods: Patients with multiple bm with Eastern Cooperative Oncology Group performance status ≤2 were included. In arm-A patient received whole brain radiotherapy (WBRT) 30 GY in 10# over 2 weeks and in arm-B patients received 20 G...

  16. 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

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

    International Nuclear Information System (INIS)

    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

  18. Immunohistochemical study of IOT-10 natural killer cells in brain metastases.

    Science.gov (United States)

    Vaquero, J; Coca, S; Escandón, J; Magallón, R; Martínez, R

    1990-01-01

    The presence of NK-cells in a series of 40 metastatic brain tumours has been studied by means of the monoclonal antibody IOT-10. There appeared IOT-10 NK-cells in all tumours studied, but in most cases these cells represented less than 10% of the tumour infiltrating lymphocytes (TIL). In the present series, the obtained data suggest that the number of NK-cells in brain metastases can be influenced by other factors than the mere quantity of TIL.

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

    International Nuclear Information System (INIS)

    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

  20. Imaging of brain metastases of bronchial carcinomas with 7 T MRI. Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Moenninghoff, C. [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Maderwald, S.; Theysohn, J.M.; Kraff, O.; Ladd, S.C.; Wanke, I. [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Duisburg-Essen Univ. (Germany). Erwin L. Hahn Inst. fuer Magnetresonanztomographie; Schuett, P.; Gauler, T. [Universitaetsklinikum Essen (Germany). Klinik fuer Innere Medizin, Konservative Onkologie; Ladd, M.E. [Duisburg-Essen Univ. (Germany). Erwin L. Hahn Inst. fuer Magnetresonanztomographie

    2010-09-15

    Purpose: To compare the depiction of brain metastases of bronchial carcinomas on susceptibility-weighted and contrast-enhanced images with 7 T and at 1.5 T MRI. Materials and Methods: Twelve patients with brain metastases of bronchial carcinomas underwent 7 T and 1.5 T MRI. Minimum intensity projections (MinIP) of a 1.5 T SWI sequence (voxel size = 0.9 x 0.9 x 2.0 mm{sup 3}) were compared to 7 T SWI MinIPs (voxel size = 0.4 x 0.4 x 1.5 mm{sup 3}). A T 1-w 3D MPRAGE at 1.5 T (voxel size = 1 x 1 x 1 mm{sup 3} after double-dose (DD) gadoterate meglumine, Gd-DOTA) was compared to a 7 T MPRAGE sequence (voxel size = 0.7 x 0.7 x x 0.7 mm{sup 3}, single dose (SD) Gd-DOTA) in all patients, and to DD Gd-DOTA in 6 patients after a 10 minute delay. The number of intracranial microhemorrhages in SWI MinIPs and the number of contrast-enhancing metastases in MPRAGE images were compared in each patient grouped into three size ranges ({<=} 2 mm, > 2 mm and < 6 mm, {>=} 6 mm) by two radiologists in consensus. Results: In all 12 patients the 7 T SWI with spatially higher resolution allowed the identification of 87 versus 67 cerebral microhemorrhages at 1.5 T. 7 T T 1-w images after SD Gd-DOTA depicted 198 brain metastases versus 238 at 1.5 T after DD Gd-DOTA. After doubling the contrast dose in six patients, 4 additional brain metastases were identified at 7 T. Conclusion: Our preliminary results indicate that despite the higher spatial resolution the detection of brain metastases on 7 T MPRAGE images is almost equal to 1.5 T MPRAGE images. The 7 T SWI sequence with spatially higher resolution allowed the detection of 20 % more microhemorrhages in brain metastases compared to the 1.5 T SWI sequence. (orig.)

  1. Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    Full Text Available We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT combined with temozolomide (TMZ versus RT alone as first-line treatment for brain metastases (BM.Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs. Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS. Secondary outcomes included progression-free survival (PFS, objective response rate (ORR, and adverse events.Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR of 2.27 (95% CI, 1.29 to 4.00; P = 0.005 compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232. However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia.Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage.

  2. Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis

    Science.gov (United States)

    Zhao, Qian; Qin, Qin; Sun, Jinglong; Han, Dan; Wang, Zhongtang; Teng, Junjie; Li, Baosheng

    2016-01-01

    Objective We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM). Methods Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events. Results Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia. Conclusion Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage. PMID:26930609

  3. Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation

    Directory of Open Access Journals (Sweden)

    Esin Oktay

    2013-01-01

    Full Text Available Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an effective treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine.

  4. A placebo-controlled, randomized phase II study of maintenance enzastaurin following whole brain radiation therapy in the treatment of brain metastases from lung cancer

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Ciuleanu, Tudor; Fløtten, Øystein;

    2012-01-01

    Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs).......Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs)....

  5. 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.

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

    International Nuclear Information System (INIS)

    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

  7. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases

    International Nuclear Information System (INIS)

    The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases

  8. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases

    Science.gov (United States)

    2012-01-01

    Background The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). Methods Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). Results The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. Conclusions Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases. PMID:23110940

  9. MRI diagnosis of brain metastases%脑转移瘤的MRI诊断

    Institute of Scientific and Technical Information of China (English)

    贾福艳; 宋伟兴; 白振武

    2012-01-01

    目的 研究脑转移瘤的MRI表现,探讨其对脑转移瘤的诊断价值.方法 回顾分析经临床及病理证实的脑转移瘤50例,所有的病例均行颅脑MRI平扫及增强扫描,都包括T1WI、T2WI、FLAIR及DWI.结果 50例脑转移瘤中单发12例,多发38例;其中MRI平扫T1WI发现病灶95个,平扫FLAIR发现病灶120个,增强T1WI发现病灶156个,增强FLAIR发现病灶192个.结论 MRI增强扫描比平扫能发现更多的脑转移瘤病灶,尤其是增强FLAIR序列;脑转移瘤MRI表现具有一定的特征性,结合临床病史大部分能做出正确诊断.%Objective To study the MRI manifestation of brain metastasis, and to discuss the diagnostic value of brain metastasis. Methods The clinical data of fifty patients with clinically and pathologically proved brain metastasis was retrospectively analyzed. Plain MRI scan and enhanced MRI scan were performed in all the cases, including T1WI、T2WI、FLAIR and DWI. Results There were 12 cases of single focus and 38 cases of multiple foci, a total of 192 foci. Non-enhanced T1WI images, non-enhanced FLAIR images, enhanced T1W images and enhanced FLAIR images showed 95 foci, 120 foci, 156 foci, and 192 foci, respectively. Conclusion Enhanced MR images are significantly more efficient than non-enhanced MR images in the diagnosis of brain metastatic foci, especially enhanced FLAIR images. Brain metastases can be diagnosed correctly according to the MRI characteristic findings combined with disease history of the patients.

  10. 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

  11. Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kiminori Uka; Kazuaki Chayama; Hiroshi Aikata; Shintaro Takaki; Hiroo Shirakawa; Soo Cheol Jeong; Keitaro Yamashina; Akira Hiramatsu; Hideaki Kodama; Shoichi Takahashi

    2007-01-01

    AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients.METHODS: After the diagnosis of HCC, all 995consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features,prognosis, and treatment strategies.RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%).The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure.CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly,treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatic tumor stage (T0-T2), and are free of portal venous invasion may improve survival.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Hypofractionated radiosurgery for intact or resected brain metastases: defining the optimal dose and fractionation

    International Nuclear Information System (INIS)

    Hypofractionated Radiosurgery (HR) is a therapeutic option for delivering partial brain radiotherapy (RT) to large brain metastases or resection cavities otherwise not amenable to single fraction radiosurgery (SRS). The use, safety and efficacy of HR for brain metastases is not well characterized and the optimal RT dose-fractionation schedule is undefined. Forty-two patients treated with HR in 3-5 fractions for 20 (48%) intact and 22 (52%) resected brain metastases with a median maximum dimension of 3.9 cm (0.8-6.4 cm) between May 2008 and August 2011 were reviewed. Twenty-two patients (52%) had received prior radiation therapy. Local (LC), intracranial progression free survival (PFS) and overall survival (OS) are reported and analyzed for relationship to multiple RT variables through Cox-regression analysis. The most common dose-fractionation schedules were 21 Gy in 3 fractions (67%), 24 Gy in 4 fractions (14%) and 30 Gy in 5 fractions (12%). After a median follow-up time of 15 months (range 2-41), local failure occurred in 13 patients (29%) and was a first site of failure in 6 patients (14%). Kaplan-Meier estimates of 1 year LC, intracranial PFS, and OS are: 61% (95% CI 0.53 – 0.70), 55% (95% CI 0.47 – 0.63), and 73% (95% CI 0.65 – 0.79), respectively. Local tumor control was negatively associated with PTV volume (p = 0.007) and was a significant predictor of OS (HR 0.57, 95% CI 0.33 - 0.98, p = 0.04). Symptomatic radiation necrosis occurred in 3 patients (7%). HR is well tolerated in both new and recurrent, previously irradiated intact or resected brain metastases. Local control is negatively associated with PTV volume and a significant predictor of overall survival, suggesting a need for dose escalation when using HR for large intracranial lesions

  15. Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single–Isocenter Volumetric Modulated Arc Therapy

    Science.gov (United States)

    Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J.; Wen, Ning

    2016-01-01

    Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly. PMID:27688047

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

    Directory of Open Access Journals (Sweden)

    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. Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England

    International Nuclear Information System (INIS)

    Aim: To determine current practice regarding brain imaging for newly diagnosed lung cancer patients without symptoms of brain metastases. Materials and methods: A survey questionnaire was sent by e-mail to all the lung cancer lead clinicians in England currently on the National Cancer Intelligence Network database. The survey asked whether brain imaging was used in new lung cancer patients without symptoms or signs to suggest brain metastases; and if so, which patient subgroups were imaged according to cell type, stage of disease, and intention to treat, and which techniques were used to image these patients. Responses were received between February and May 2014. Results: Fifty-nine of 154 centres replied to the survey (38%). Thirty of the 59 centres (51%) did not image the brain in these patients. Twenty-nine of the 59 (49%) centres imaged the brain in at least certain subgroups. Of those centres that did image the brain 21 (72%) used CT as the first-line imaging technique and six (20%) used MRI. Twenty-five of 59 (42%) centres stated that the 2011 NICE guidelines had led to a change in their practice. Conclusion: There is wide variation in practice regarding brain imaging in this patient group in England, with no brain imaging at all in approximately half of centres and a spectrum of imaging in the other half. When the brain is imaged, CT is the technique most commonly used. The 2011 NICE guidelines have led to some change in practice but not to national uniformity. - Highlights: • Ascertain current practice in brain imaging for staging asymptomatic lung cancer patients. • Survey questionnaire sent to all the lung cancer lead clinicians in England. • Wide variation in practice with regard to brain imaging in this patient group. • No brain imaging at all in approximately half of centres and a spectrum of imaging in the other half • The 2011 NICE guidelines have led to some change in practice but not to national uniformity

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

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. O7.02RADIOSURGERY AND BRAIN METASTASES: ADEQUATE SEQUENCE OF BRAIN MRI CAN SIGNIFICANTLY CHANGE THE INTRACRANIAL DISEASE STAGING

    Science.gov (United States)

    Scoccianti, S.; Greto, D.; Bordi, L.; Bono, P.; Pecchioli, G.; Casati, M.; Vanzi, E.; Compagnucci, A.; Gadda, D.; Livi, L.

    2014-01-01

    INTRODUCTION: Accurate assessment of the exact number of brain metastases is of utmost importance in the decision-making process for the appropriate treatment. The diagnostic efficacy in the detection of additional brain metastases of a double dose contrast three-dimensional, T1-Weighted Gradient-Echo Imaging was evaluated. METHODS: Before undergoing radiosurgical treatment, patients underwent a brain magnetic resonance imaging (MRI) scan to be used during the treatment planning in order to contour the targets and to locate the brain lesions as they relate to the stereotactic frame. All the patients underwent a post-contrast study with T1-weighted, 3D Magnetization-Prepared Rapid Acquisition Gradient Echo (MP RAGE) sequence. We used a double dose of gadobenate dimeglumine and slice thickness of 0.9 mm. RESULTS: Starting from October 2012 to February 2014, we treated with Gamma Knife radiosurgery (GKRS) 62 patients with brain metastases. On the diagnostic MRI, all the patients had a number of lesions ≤4. Median time interval between diagnostic MRI scan and the day of GKRS was 11 days (range 5-20) A total of 54 additional lesions were detected on MR imaging performed in the same day of the GKRS in twenty-two patients out of 62 (35.5%). A median number of 2 additional lesions were detected (range 1-8). Among these 22 patients only 14 patients had a number of lesions ≤4 on the day of treatment. Patients with a total number of lesions ≤10 were treated with GKRS. Two patients with a total number of lesions > 10 were treated with whole brain radiotherapy (WBRT). CONCLUSIONS: A double-contrast study with T1-weighted, volumetric MPRAGE sequence may offer better staging for patients with brain metastases. In our opinion, it should be recommended in all the patients with newly diagnosed brain metastases because the detection of the real number of lesions is crucial for an adequate treatment and it also may lead to choose different therapeutic strategies.

  1. Determinants of survival in patients with brain metastases from cutaneous melanoma

    OpenAIRE

    M. Staudt; Lasithiotakis, K.; Leiter, U; Meier, F.; Eigentler, T; Bamberg, M; Tatagiba, M; Brossart, P; Garbe, C

    2010-01-01

    Background: This retrospective study aimed to identify prognostic factors in patients with brain metastases from cutaneous melanoma. Methods: In all, 265 patients under regular screening according to valid national surveillance guidelines were included in the study. Kaplan–Meier analyses were performed to estimate and to compare overall survival. Cox modeling was used to identify independent determinants of the overall survival, which were used in explorative classification and regression tre...

  2. Safety and Efficacy of High-Dose Interleukin-2 Therapy in Patients With Brain Metastases

    OpenAIRE

    Guirguis, Lisa M.; Yang, James C.; White, Donald E.; Steinberg, Seth M.; Liewehr, David J.; Rosenberg, Steven A.; Schwartzentruber, Douglas J.

    2002-01-01

    The authors determined the safety and efficacy of recombinant high-dose interleukin-2 administration in patients with brain metastases. This retrospective review included 1,069 patients with metastatic melanoma or renal cell carcinoma who received high-dose interleukin-2 alone or in combination with other immunotherapy or chemotherapy from July 1985–July 2000. All patients were evaluated for both toxicity and response. Only the first exposure to interleukin-2 was considered. Parameters evalua...

  3. 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)

    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

  4. 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.)

  5. Identification of a seasonal pattern to brain metastases

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    Sakellakis M

    2016-03-01

    Full Text Available Minas Sakellakis,1 Angelos Koutras,1 Maria Pittaka,2 Dimitrios Kardamakis,2 Melpomeni Kalofonou,1 Haralabos P Kalofonos,1 Despina Spyropoulou2 1Division of Oncology, Department of Medicine, 2Department of Radiation Oncology, University Hospital, Patras Medical School, Rion, Patras, GreeceWe have previously tested our hypothesis that there is a seasonality in the incidence of carcinomatous meningitis.1 Although further validation is needed in a larger cohort, we found that leptomeningeal metastasis occurred more often during warm months of the year which, in the case of Greece, is the period generally marked with the larger daytime length.1 Carcinomatous meningitis is closely related to brain metastasis, and a logical question is whether warm season is marked by a greater propensity also for brain metastasis.2 

  6. Single brain metastases of low-field MRI diagnosis%单发脑转移瘤的低场MRI诊断

    Institute of Scientific and Technical Information of China (English)

    司道广; 时振杰

    2009-01-01

    Objective To analyse the single brain metastases of MRI features, Methods To collect 37 cases of single brain metastases diagnosed by clinical and surgical pathology, and to retrospectively analyse their MRI characteris-tics. Results Single brain metastases were mostly found in male, male to female ratio was 2.97:1, the average age was 52.5 years old. This group of single brain metastases of MRI performance can be divided into two types: nodular mass (83. 7%), and pouch with nodular type (16.2%). Conclusions Single brain metastases is easily misdiagnosed,it need a comprehensive analysis of various aspects to get correct diagnosis.%目的 分析单发脑转移瘤的MRI表现特点.方法 搜集经临床、手术病理证实的37例单发脑转移瘤,回顾性分析其MRI表现的特点.结果 单发脑转移瘤以男性多见,男女之比为2.97:1,平均年龄52.5岁.本组单发脑转移瘤的MRI表现可分为肿块结节型(83.7%)和囊伴结节型(16.2%).结论 单发脑转移瘤易于误诊,需多方面综合分析才能达到正确诊断.

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

    International Nuclear Information System (INIS)

    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

  8. [Whole Brain Irradiation and Hypo-fractionation Radiotherapy for the Metastases in Non-small Cell Lung Cancer].

    Science.gov (United States)

    Gu, Xingting; Zhao, Yaqin; Xu, Feng

    2016-04-20

    Up to 40% non-small cell lung cancer patients developed brain metastasis during progression. Multiple brain metastases are common in non-small cell lung cancer. The prognosis of brain metastasis is poor with median survival of less than 1 year. Radio therapy for brain metastases has gradually developed from whole brain radiotherapy (WBRT) to various radiation strategies. WBRT, surgery+WBRT, stereotactic radiotherapy+WBRT or WBRT with simultaneous integrated boost (SIB), etc. have better overall survival than those untreated patients. The damage of the cognitive function from WBRT has been realized recently, however, options of radiation strategies for long expected survival patients remain controversial. This paper will discuss different WBRT strategies and treatment side effects of non-small cell lung cancer with brain metastases. PMID:27118651

  9. Hypofractionated stereotactic radiotherapy of limited brain metastases: a single-centre individualized treatment approach

    Directory of Open Access Journals (Sweden)

    Märtens Bettina

    2012-10-01

    Full Text Available Abstract Background We retrospectively report treatment results of our single-centre experience with hypofractionated stereotactic radiotherapy (hfSRT of limited brain metastases in primary and recurrence disease situations. Our aim was to find the most effective and safe dose concept. Methods From 04/2006 to 12/2010, 75 patients, with 108 intracranial metastases, were treated with hfSRT. 52 newly diagnosed metastases (48%, without up-front whole brain radiotherapy (WBRT, received hfSRT as a primary treatment. 56 metastases (52% received a prior WBRT and were treated in this study in a recurrence situation. Main fractionation concepts used for primary hfSRT were 6-7x5 Gy (61.5% and 5x6 Gy (19.2%, for recurrent hfSRT 7-10x4 Gy (33.9% and 5-6x5 Gy (33.9%. Results Median overall survival (OS of all patients summed up to 9.1 months, actuarial 6-and 12-month-OS was 59% and 35%, respectively. Median local brain control (LC was 11.9 months, median distant brain control (DC 3.9 months and intracranial control (IC 3.4 months, respectively. Variables with significant influence on OS were Gross Tumour Volume (GTV (p = 0.019, the biological eqivalent dose (calculated on a 2 Gy single dose, EQD2, α/β = 10 35 Gy (p = 0.004 in both uni- and multivariate Cox regression analysis. Median LC was 14.9 months for EQD2 >35 Gy and 3.4 months for doses ≤35 Gy, respectively. Early treatment related side effects were usually mild. Nevertheless, patients with a EQD2 >35 Gy had higher rates of toxicity (31% than ≤35 Gy (8.3%, p=0.026. Conclusion Comparing different dose concepts in hfSRT, a cumulative EQD2 of ≥35 Gy seems to be the most effective concept in patients with primary or recurrent limited brain metastases. Despite higher rates of only mild toxicity, this concept represents a safe treatment option.

  10. 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.

  11. Clinical observation of intrathecal chemotherapy combined with concurrent radiotherapy for leptomeningeal metastases from malignant solid tumors

    Institute of Scientific and Technical Information of China (English)

    潘振宇

    2014-01-01

    Objective To investigate the efficacy and safety of intrathecal chemotherapy combined with concurrent radiotherapy in patients with leptomeningeal metastases from solid tumors.Methods The clinical and follow-up data of 29 patients with leptomeningeal metastases frommalignant solid tumor who had intrathecal chemotherapy combined with concurrent radiotherapy were retrospectively analyzed.The treatment regimen was that 12.5-15.0 mg of methotrexate intrathecal injection once a week for 8

  12. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

    Directory of Open Access Journals (Sweden)

    Nobuhiro Morinaga

    2016-05-01

    Full Text Available Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT/calcium folinate (leucovorin, LV was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

  13. Stereotactic radiosurgery for the treatment of brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Hiyama, Hirofumi; Arai, Koji; Izawa, Masahiro; Takakura, Kintomo [Tokyo Women`s Medical Coll. (Japan). Neurological Inst.

    1996-02-01

    The treatment outcome of the metastatic brain tumor in Tokyo Women`s Medical College was reported, and it was described on present state and problem of radiosurgery (RS). One hundred five lesions of 50 patients (male 36, female 12, age 27-85 years) undertaken RS by gamma knife were studied. The primary lesions were the lungs in 23 patients, digestive tract in 12, mammary gland in 4, kidney in 3, thyroid gland in 13, prostate gland in 2 and the other in 3. Thirty nine patients had primary tumor, and 11 patients had recurrent tumor. The volume of 105 lesions was 0.03-56 ml (mean 6.4 ml), and the treatment was carried out for these tumors at average maximum dose 47Gy, average limbic dosage 23Gy. In the image findings, elimination of 46 lesions (44%), reduction of 39 lesions (37%), unchangeable 7 lesions (7%), increase of 13 lesions (13%) were recognized, and tumor reduction rate 81%, local control rate 88% were obtained. The local control rate was around 90% of the tumor, which seize was 15 ml or less. After the treatment, radionecrosis were suspected in 2 lesions of 1 patient. Appearance or aggravation of the edema by the radiation were observed 1-2 month after the treatment in 6 lesions of 5 patients. By the treatment, the following were improved: the hemiplegia in 9 patients, the aphasia in 2, the vertigo in 3. On prognosis, 21 of 46 patients except for the uncertain 4 were alive and 25 died. Through RS is the therapy which is very effective for the metastatic brain tumor, it also exists on some problems to be reached. (A.N.).

  14. THE CLINICAL COURSE AND TREATMENT RESULTS OF LUNG METASTASES FROM BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Xu Binghe; Zhou Jichang; Zhou Aiping; Wang Yan; Feng Fengyi; Sun yan

    1998-01-01

    Objective:To analyze the clinical course and treatment result of lung metastases from breast cancer. Method:122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus endocrine therapy, response was assessed according to WHO criteria and survival rate estimated using the life Table. Results: The median time from initial treatment of primary tumor to lung metastases was 22 months. Sites of common consecutive metastases were lung, liver and bone. The overall response rate was 48% with a CR rate of 15%. Compared to non- DDP- encompassing regimen, the CR rate was higher in DDP-based chemotherapy (7%versus 21%, P<0.05) with a longer median survival time (MST). The PR rate was higher in regimens containing anthracycline (48%) than in those without anthracycline (20%, P<0.01). The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy (P>0.05). No difference in MST was observed between patients receiving anthracycline-and non-anthracyclineencompassing regimens. The 1-, 3-, 5-, and 10-year survival rate was 77%, 22 %, 11%, and 10%, respectively.Conclusion: Size of primary tumor, the length of diseasefree interval, the number of lung metastases may provide additional information for predicting patients survival after treatment of lung metastases. Combination chemotherapy, especially DDP-based chemotherapy may prolong survival time of patients with lung metastases from breast cancer.

  15. High-Dose Interleukin-2 (HD IL-2 Therapy Should Be Considered for Treatment of Patients with Melanoma Brain Metastases

    Directory of Open Access Journals (Sweden)

    Melinda B. Chu

    2013-01-01

    Full Text Available A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8–61.1 years. One patient started treatment with lung lesions only (after resection of melanoma brain disease and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS for entire cohort ( was 8.7 months (2.1 to 19.0 months. All patients with brain metastases at first dose ( showed progressive disease; mOS was 6.7 months (range 2.1–18.2 months for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patient's symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.

  16. Patterns of Practice of Palliative Radiotherapy in Africa, Part 1: Bone and Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: To provide data on the pattern of practice of palliative radiotherapy (RT) on the African continent. Methods and Materials: A questionnaire was distributed to participants in a regional training course of the International Atomic Energy Agency in palliative cancer care and sent by e-mail to other institutions in Africa. Requested information included both infrastructure and human resources available and the pattern of RT practice for metastatic and locally advanced cancers. Results: Of 35 centers contacted, 24 (68%) completed the questionnaire. Although RT is used by most centers for most metastatic cancers, liver and lung metastases are treated with chemotherapy. Of 23 centers, 14 (61%) had a single RT regimen as an institutional policy for treating painful bone metastases, but only 5 centers (23%) of 23 used 8 Gy in 1 fraction. Brain metastases were being treated by RT to the whole brain to 30 Gy in 10 fractions, either exclusively (n = 13, 56%) or in addition to the use of 20 Gy in 5 fractions (n = 3, 14%). Conclusion: Radiotherapy is a major component of treatment of cancer patients in African countries. There is consensus among few centers for treatment schedules for almost all sites regarding time and dose-fractionation characteristics of RT regimens used and/or indications for the use of RT in this setting

  17. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Xu Zhiyuan [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Schlesinger, David [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Toulmin, Sushila [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Rich, Tyvin [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Sheehan, Jason, E-mail: jps2f@virginia.edu [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States)

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  18. Adjuvant therapy after resection of brain metastases. Frameless image-guided LINAC-based radiosurgery and stereotactic hypofractionated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Broemme, J.; Aebersold, D.M.; Pica, A. [Bern Univ., Bern Univ. Hospital (Switzerland). Dept. of Radiation Oncology; Abu-Isa, J.; Beck, J.; Raabe, A. [Bern Univ., Bern Univ. Hospital (Switzerland). Neurosurgery; Kottke, R.; Wiest, R. [Bern Univ., Bern Univ. Hospital (Switzerland). Neuroradiology; Malthaner, M.; Schmidhalter, D. [Bern Univ., Bern Univ. Hospital (Switzerland). Div. of Medical Radiation Physics

    2013-09-15

    Background: Tumor bed stereotactic radiosurgery (SRS) after resection of brain metastases is a new strategy to delay or avoid whole-brain irradiation (WBRT) and its associated toxicities. This retrospective study analyzes results of frameless image-guided linear accelerator (LINAC)-based SRS and stereotactic hypofractionated radiotherapy (SHRT) as adjuvant treatment without WBRT. Materials and methods: Between March 2009 and February 2012, 44 resection cavities in 42 patients were treated with SRS (23 cavities) or SHRT (21 cavities). All treatments were delivered using a stereotactic LINAC. All cavities were expanded by {>=} 2 mm in all directions to create the clinical target volume (CTV). Results: The median planning target volume (PTV) for SRS was 11.1 cm{sup 3}. The median dose prescribed to the PTV margin for SRS was 17 Gy. Median PTV for SHRT was 22.3 cm{sup 3}. The fractionation schemes applied were: 4 fractions of 6 Gy (5 patients), 6 fractions of 4 Gy (6 patients) and 10 fractions of 4 Gy (10 patients). Median follow-up was 9.6 months. Local control (LC) rates after 6 and 12 months were 91 and 77 %, respectively. No statistically significant differences in LC rates between SRS and SHRT treatments were observed. Distant brain control (DBC) rates at 6 and 12 months were 61 and 33 %, respectively. Overall survival (OS) at 6 and 12 months was 87 and 63.5 %, respectively, with a median OS of 15.9 months. One patient treated by SRS showed symptoms of radionecrosis, which was confirmed histologically. Conclusion: Frameless image-guided LINAC-based adjuvant SRS and SHRT are effective and well tolerated local treatment strategies after resection of brain metastases in patients with oligometastatic disease. (orig.)

  19. Pseudo-progression after stereotactic radiotherapy of brain metastases: lesion analysis using MRI cine-loops.

    Science.gov (United States)

    Wiggenraad, Ruud; Bos, Petra; Verbeek-de Kanter, Antoinette; Lycklama À Nijeholt, Geert; van Santvoort, Jan; Taphoorn, Martin; Struikmans, Henk

    2014-09-01

    Stereotactic radiotherapy (SRT) of brain metastasis can lead to lesion growth caused by radiation toxicity. The pathophysiology of this so-called pseudo-progression is poorly understood. The purpose of this study was to evaluate the use of MRI cine-loops for describing the consecutive events in this radiation induced lesion growth. Ten patients were selected from our department's database that had received SRT of brain metastases and had lesion growth caused by pseudo-progression as well as at least five follow-up MRI scans. Pre- and post SRT MRI scans were co-registered and cine-loops were made using post-gadolinium 3D T1 axial slices. The ten cine loops were discussed in a joint meeting of the authors. The use of cine-loops was superior to evaluation of separate MRI scans for interpretation of events after SRT. There was a typical lesion evolution pattern in all patients with varying time course. Initially regression of the metastases was observed, followed by an enlarging area of new contrast enhancement in the surrounding brain tissue. Analysis of consecutive MRI's using cine-loops may improve understanding of pseudo-progression. It probably represents a radiation effect in brain tissue surrounding the irradiated metastasis and not enlargement of the metastasis itself.

  20. Treatment outcomes in patients with multiple brain metastases: A prospective randomized study

    Directory of Open Access Journals (Sweden)

    Animesh Saha

    2014-01-01

    Full Text Available Context: There is controversy regarding the radiotherapeutic dose fractionation in brain metastases (bm. Aims: The aim of this study is to analyze the treatment outcomes in patients with multiple bm. Settings and Design: Prospective, randomized study. Subjects and Methods: Patients with multiple bm with Eastern Cooperative Oncology Group performance status ≤2 were included. In arm-A patient received whole brain radiotherapy (WBRT 30 GY in 10# over 2 weeks and in arm-B patients received 20 GY in 5# over 1 week. Assessment of improvement in clinical symptoms was done using Barthel′s adjusted daily live (ADL score. Assessment of radiological response was done using magnetic resonance imaging scan of brain after 3 months of completion of external beam radiation therapy. Acute radiation toxicity was assessed using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer acute radiation morbidity scoring. Statistical Analysis Used: Chi-square test was used to compare categorical variables between groups. Overall survival was computed by Kaplan-Meier survival analysis and Log-Rank test used for comparison of survival plots. For change in quality-of-life during treatment and follow-up, repeated measures ANOVA were used. Results: In both arms, there was a significant improvement in ADL score after treatment, but when two arms were compared, no significant difference was found between the two treatment arms. There was no statistically significant difference in response or morbidity between the two treatment arms. Median survival was 29 weeks in arm-A compared to 25.86 weeks in patients arm-B. Kaplan-Meier Survival curve analysis shows no significant difference in survival between the two arms. Conclusions: 20 GY in 5 fractions is equally effective with that of the 30 GY in 10 fractions for WBRT in bm. In the palliative setting short duration of treatment with minimum discomfort to the patient is desirable. Hence, we

  1. 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.

  2. Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases.

    Science.gov (United States)

    Thorsen, Frits; Fite, Brett; Mahakian, Lisa M; Seo, Jai W; Qin, Shengping; Harrison, Victoria; Johnson, Sarah; Ingham, Elizabeth; Caskey, Charles; Sundstrøm, Terje; Meade, Thomas J; Harter, Patrick N; Skaftnesmo, Kai Ove; Ferrara, Katherine W

    2013-12-28

    Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.

  3. Clinical features and prognostic factors for patients with bone metastases from prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jian He; Zhao-Chong Zeng; Ping Yang; Bing Chen; We Jiang; Shi-Suo Du

    2012-01-01

    To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer (PCa).We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009.The overall survival rate after bone metastases was calculated using the Kaplan-Meier method.The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models.The follow-up rate was 100%,the follow-up cases during 1,3 and 5 years were 103,79 and 55,respectively.The 1-,3- and 5-year survival rates were 89.1%,60.9% and 49.8%,respectively,with a median survival time of 48.5 months for patients with bone metastases from PCa.In univariate analysis,age,Gleason score,clinical stage,the number of bone lesions,alkaline phosphatase (ALP) level,invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis.By multivariate analysis using Cox regression,ALP level,Gleason score and non-regional lymph node metastases were independent prognostic factors.These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.

  4. Clinical effect of percutaneous radiofrequency ablation for residual lung metastases from breast cancer after systemic chemotherapy

    International Nuclear Information System (INIS)

    Objective: To determine the clinical effect of Radiofrequency Ablation (RFA) for residual lung metastases from breast cancer after systemic chemotherapy. Study Design: An experimental study. Place and Duration of Study: The Second Affiliated Hospital of Soochow University, Suzhou, Fudan University Shanghai Cancer Center, Shanghai, China, from January 2008 to October 2014. Methodology: Thirty-five breast cancer patients with 67 pulmonary metastases were involved in this study. All lesions were treated by RFA and followed by CT-scan. Primary endpoint of this clinical study was local control; secondary endpoints were overall survival and treatment-related toxicities. Results: Complete Response (CR) was observed in 59 lesions, with Partial Response (PR) in 4 lesions, Stable Disease (SD) in 1 lesion and Progression Disease (PD) in 3 lesions. The lesion diameter > 2 cm was related to poor local control (p=0.04). The median Overall Survival (OS) was 33 months (95%CI: 21.6 - 44.4). One, 2-, and 3-year OS rates were 88.6%, 59.3% and 42.8% respectively. The mumber of pulmonary metastases (2), the diameter of lesion (> 2 cm) and coexisting with liver metastases were significantly correlated to poor OS by multivariate analysis. Log-rank test showed statistically significant difference of OS in diameter of lesion and coexisting with other metastases. Conclusion: RFA is a promising treatment option for patients with residual lung metastases from breast cancer after systemic chemotherapy in selected patients. (author)

  5. 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

  6. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

    Science.gov (United States)

    Niwińska, Anna

    2016-10-01

    The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

  7. Preoperative diffusion-weighted imaging of single brain metastases correlates with patient survival times.

    Directory of Open Access Journals (Sweden)

    Anna Sophie Berghoff

    Full Text Available BACKGROUND: MRI-based diffusion-weighted imaging (DWI visualizes the local differences in water diffusion in vivo. The prognostic value of DWI signal intensities on the source images and apparent diffusion coefficient (ADC maps respectively has not yet been studied in brain metastases (BM. METHODS: We included into this retrospective analysis all patients operated for single BM at our institution between 2002 and 2010, in whom presurgical DWI and BM tissue samples were available. We recorded relevant clinical data, assessed DWI signal intensity and apparent diffusion coefficient (ADC values and performed histopathological analysis of BM tissues. Statistical analyses including uni- and multivariate survival analyses were performed. RESULTS: 65 patients (34 female, 31 male with a median overall survival time (OS of 15 months (range 0-99 months were available for this study. 19 (29.2% patients presented with hyper-, 3 (4.6% with iso-, and 43 (66.2% with hypointense DWI. ADCmean values could be determined in 32 (49.2% patients, ranged from 456.4 to 1691.8*10⁻⁶ mm²/s (median 969.5 and showed a highly significant correlation with DWI signal intensity. DWI hyperintensity correlated significantly with high amount of interstitial reticulin deposition. In univariate analysis, patients with hyperintense DWI (5 months and low ADCmean values (7 months had significantly worse OS than patients with iso/hypointense DWI (16 months and high ADCmean values (30 months, respectively. In multivariate survival analysis, high ADCmean values retained independent statistical significance. CONCLUSIONS: Preoperative DWI findings strongly and independently correlate with OS in patients operated for single BM and are related to interstitial fibrosis. Inclusion of DWI parameters into established risk stratification scores for BM patients should be considered.

  8. Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge.

    Science.gov (United States)

    N Cagney, Daniel; Alexander, Brian M; Hodi, F Stephen; Buchbinder, Elizabeth I; Ott, Patrick A; Aizer, Ayal A

    2016-09-01

    Novel systemic therapies with anti-tumor activity in the brain including small molecules targeting BRAF and MEK, and immune checkpoint inhibition, offer the possibility of improved control of intracranial disease. A number of prospective trials support the judicious use of modern systemic therapies in patients with melanoma and limited brain metastases .The intracranial clinical course of patients who progress extracranially on BRAF/MEK inhibition remains poorly described in the literature. In this report, we highlight a series of clinical cases, with rapid progression of intracranial disease following discontinuation of dabrafenib/trametinib for extracranial disease progression or toxicity, a previously unreported finding in the medical literature with significant implications for patient care.

  9. The prognostic value of tumor necrosis in patients undergoing stereotactic radiosurgery of brain metastases

    International Nuclear Information System (INIS)

    This retrospective study investigated the outcome of patients with brain metastases after radiosurgery with special emphasis on prognostic impact of visible intratumoral necrosis on survival and local control. From 1998 through 2008, 149 patients with brain metastases from solid tumors were treated with stereotactic radiotherapy at Luebeck University. Median age was 58.4 years with 11%, 78%, 10% in recursive partitioning analysis (RPA) classes I, II, III, respectively. 70% had 1 metastasis, 29% 2-3 metastases, 2 patients more than 3 metastases, 71% active extracranial disease. Median volume of metastatic lesions was 4.7 cm3, median radiosurgery dose 22 Gy (single fraction). 71% of patients received additional whole-brain irradiation (WBI). All patients were analyzed regarding survival, local, distant failure and prognostic factors, side effects and changes in neurologic symptoms after radiotherapy. The type of contrast-enhancement in MR imaging was also analyzed; metastatic lesions were classified as containing necrosis if they appeared as ring-enhancing with central areas of no or minimal contrast enhancement. Median survival was 7.0 months with 1-year and 5-year survival rates of 33% and 0.4%, respectively. Tumor necrosis (ring-enhancement) was visible on pretreatment MRI scans in 56% of all lesions and lesions with necrosis were larger than non-necrotic lesions (6.7 cm3 vs. 3.2 cm3, p = 0.01). Patients with tumor necrosis had a median survival of 5.4 months, patients without tumor necrosis 7.2 months. Local control rate in the irradiated volume was 70%, median survival without local failure 17.8 months. Control in the brain outside the irradiated volume was 60%, median survival without distant failure 14.0 months. Significant prognostic factors for overall survival were KPS (p = 0.001), presence of tumor necrosis on pretreatment MRI (p = 0.001) with RPA-class and WBI reaching marginal significance (each p = 0.05). Prognostic impact of tumor necrosis remained

  10. The Radiation Technique of 69 Cases with Brain Metastases%69例脑转移癌的放射治疗技术

    Institute of Scientific and Technical Information of China (English)

    丁秋娥; 孔梅; 王思阳; 刘巧丹; 程志斌

    2010-01-01

    Objective To investigate the clinical application of radiotherapy technique of brain metastases. Methods We analyzed the quality control, announcements and irradiation techniques of 69 cases with brain metastases who had received brain radiotherapy. Results The radiotherapy treatment planning had been smoothly accomplished by using the simulator, linear accelerator, thermoplastic mask and fixation apparatus.Conclusion The quality control of radiation is the foundation to guarantee the performance of radiotherapy of brain metastases.%目的 研究脑转移癌放射治疗技术的临床应用.方法 实施并分析69例脑转移癌放射治疗过程的质量控制、注意事项及照射技术.结果 使用模拟定位机、直线加速器、热塑面膜及固定架等设备,规范质量控制过程,顺利完成放射治疗计划.结论 脑转移癌放射治疗质量控制是保证放疗实施的基础.

  11. 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

  12. OP09STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES AT THE CHRISTIE AT SALFORD ROYAL HOSPITAL: OUR TWO-YEAR EXPERIENCE

    Science.gov (United States)

    Helbrow, J.; McBain, C.; Gattamaneni, R.; Tran, A.; McCarthy, C.; Edwards, R.; Redikin, J.; Handley, J.; O'Hara, C.; Kennedy, J.; Mills, S.; Soh, C.; Leggate, J.; Whitfield, G.

    2014-01-01

    INTRODUCTION: Stereotactic radiosurgery (SRS) for brain metastases (BMs) commenced at The Christie at Salford in Dec 11 using the Novalis TxTM and BrainLab ExacTrac® system. We report our first 2 years' data. METHOD: Patients meeting NHS commissioning criteria were referred via MDT for assessment and if suitable consent. We used the BrainLab mask, CT and MRI. Gross tumour volumes (GTVs) were grown by 2mm if 4cm3 to a planning target volume. The dose to the 80% isodose was 21Gy/1 fraction(#), 18Gy/1# and 25.5Gy/3# alternate days for PTVs 13cm3 respectively and 30Gy/5# on alternate days to the 90% isodose in critical locations or where organ at risk constraints were exceeded. Follow up was 3-monthly with MRI and clinic review. Radiological response was classified as complete, unequivocal, enlargement consistent with treatment, enlargement suspicious of progression or unequivocal progression. RESULTS: Between Dec 11-Jan 14, 89 patients were consented, 51% female. Median age was 61 years (range 16-81). Primaries included lung (34%), breast (22%) and melanoma (15%), which was controlled in 67%; 42% had no extracranial metastases. A total of 170 BMs were treated (1 a retreat); per course a median of 2 (1-5) BMs were treated with median total GTV 4.87cm3 (0.05-29.9cm3). Prescribed dose was 21Gy/1# in 101 BMs, 18Gy/1# in 43, 25.5Gy/3# in 10 and 30Gy/5# in 16. One year survival from first SRS was: overall 48% (95% CI 34%-60%), lung 39% (18%-59%), breast 89% (62%-97%) and melanoma 44% (10%-75%). CONCLUSION: Overall survival results are encouraging and suggest appropriate patient selection. More detailed analysis including toxicity and time to intracranial progression will be presented.

  13. EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients

    OpenAIRE

    Villalva, Claire; Duranton-Tanneur, Valérie; Guilloteau, Karline; Burel-Vandenbos, Fanny; Wager, Michel; Doyen, Jérôme,; Levillain, Pierre Marie; Fontaine, Denys; Blons, Hélène; Pedeutour, Florence; Karayan-Tapon, Lucie

    2013-01-01

    The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France. The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NS...

  14. 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

    2016-01-01

    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

  15. Gamma knife radiosurgery for multiple brain metastases from non-small cell lung cancer. Comparison with whole brain radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi [Chiba Cardiovascular Center (Japan); Iuchi, Toshihiko; Osato, Katsunobu

    2001-04-01

    The purpose of this retrospective study is to compare the effectiveness of gamma knife radiosurgery (GKS) with that of whole-brain radiation therapy (WBRT) for multiple cerebral metastases from non-small cell lung cancer. Among 302 cases with cerebral metastases from non-small cell lung cancer treated at the Chiba Cardiovascular Center and Chiba Cancer Center between 1990 and 1999, 100 consecutive patients filling the following 4 entry criteria were analyzed in this study: Up to 10 multiple brain lesions at initial MRI study; No surgically inaccessible tumors with more than 30 mm in diameter; No carcinomatous meningitis; More than 3 months of life expectancy. The patients were divided into two groups: the GKS group (66 patients) and the WBRT group (34 patients). In the GKS group, large lesions ({>=}30mm) were removed microsurgically and all other small lesions (<30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, gender, initial Karnofsky Performance Scale (KPS) score, pathology of lung caner, number, and size of brain lesion, systemic control, and chemotherapy. Overall survival (OS), neurological survival (NS) and qualitative survival (QS) of the GKS group were longer than those of the WBRT group according to Kaplan-Meier's method. In a multivariate analysis the WBRT group also had significant poor prognostic factors for OS, NS and QS. GKS without prophylactic WBRT could be a primary choice of treatment method for patients with as many as 10 cerebral metastases from non-small cell lung cancer. (author)

  16. Gamma knife radiosurgery for multiple brain metastases from non-small cell lung cancer. Comparison with whole brain radiation therapy

    International Nuclear Information System (INIS)

    The purpose of this retrospective study is to compare the effectiveness of gamma knife radiosurgery (GKS) with that of whole-brain radiation therapy (WBRT) for multiple cerebral metastases from non-small cell lung cancer. Among 302 cases with cerebral metastases from non-small cell lung cancer treated at the Chiba Cardiovascular Center and Chiba Cancer Center between 1990 and 1999, 100 consecutive patients filling the following 4 entry criteria were analyzed in this study: Up to 10 multiple brain lesions at initial MRI study; No surgically inaccessible tumors with more than 30 mm in diameter; No carcinomatous meningitis; More than 3 months of life expectancy. The patients were divided into two groups: the GKS group (66 patients) and the WBRT group (34 patients). In the GKS group, large lesions (≥30mm) were removed microsurgically and all other small lesions (<30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, gender, initial Karnofsky Performance Scale (KPS) score, pathology of lung caner, number, and size of brain lesion, systemic control, and chemotherapy. Overall survival (OS), neurological survival (NS) and qualitative survival (QS) of the GKS group were longer than those of the WBRT group according to Kaplan-Meier's method. In a multivariate analysis the WBRT group also had significant poor prognostic factors for OS, NS and QS. GKS without prophylactic WBRT could be a primary choice of treatment method for patients with as many as 10 cerebral metastases from non-small cell lung cancer. (author)

  17. MRI在肺癌脑转移中的诊断价值评价%The MRI Diagnostic Value of Brain Metastases of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    姜波; 薛婷

    2014-01-01

    目的:探讨肺癌脑转移的MRI表现,提高认识和诊断水平。方法回顾性分析164例经病理证实的肺癌患者脑转移的MRI表现,分析转移病灶的部位、数目、形态、大小、水肿程度等,同时分析不同病理学类型肺癌脑转移的MRI表现。结果所有肺癌脑转移患者中,单发病灶47例,多发病灶117例。共有257个转移灶,大多分布在幕上(73.2%)。灶体直径≥1cm,多表现为中、重度水肿(68.8%)。腺癌脑转移病灶以中度、重度水肿比例最高(68.2%)。结论肺癌脑转移灶具有典型脑转移瘤的MRI特征,有利于临床早期干预。%Objective To explore the MRI features of brain metastases of lung cancer in order to improve the knowledge and diagnostic accuracy rate. Methods MRI characteristics of 164 patients with brain metastases of lung cancer which proven by pathology were reviewed retrospectively. The location, size, shape, peri-tumoral edema were analyzed. The relationship between MRI characteristics of brain metastasis and pathological type also analyzed. Results Of the 164 patients, 47 cases had solitary lesion, 117 cases had multiple metastases. In 257 metastases, most of it (73.2%) distributed in supratentorial. 68.8%of metastases which were larger or equal to 1cm showed moderate or serious peri-tumoral edema. Moreover, brain metastasis from adenocarcinoma performed with high rates (68.2%) in moderate or serious peri-tumoral edema. Conclusion MRI imaging could obviously reflect the characteristics of brain metastases of lung cancer. It is benefit for the clinical early intervention.

  18. Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

    International Nuclear Information System (INIS)

    To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT) in patients with multiple brain metastases (BM) from malignant melanoma (MM). 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. 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 < 0.001) as well as RPA class (p < 0.001) influenced significantly on OS and patients had a significantly longer OS after surgical resection (p = 0.001, median 3.0 vs. 5.8 months, multivariate p = 0.007). Having extra-cerebral metastases didn't significantly impact on OS (p = 0.21). 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

  19. Glutathione in metastases: From mechanisms to clinical applications.

    Science.gov (United States)

    Estrela, José M; Ortega, Angel; Mena, Salvador; Sirerol, J Antoni; Obrador, Elena

    2016-08-01

    Metastatic spread, not primary tumors, is the leading cause of cancer death. Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is particularly relevant in cancer cells as it is involved in regulating carcinogenic mechanisms, growth and dissemination, and multidrug and radiation resistance. Upon interaction of metastatic cells with the vascular endothelium, a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium. GSH release from different organs, mainly the liver, and its interorgan transport through the blood circulation to metastatic foci, promote their growth. This review focuses on the relationship among GSH and different key mechanisms that facilitate metastatic cell survival and growth, i.e. adaptive responses to stress, cell death evasion and utilization of physiological neuroendocrine mechanisms. Different strategies that are aimed at sensitizing metastases to cancer therapy by depleting metastatic cell GSH are analyzed. PMID:26754151

  20. Repeat stereotactic radiosurgery in the management of brain metastases from NSCLC: A case report and review of the literature

    OpenAIRE

    Marvaso, Giulia; BARONE, AGNESE; VACCARO, CATERINA; Bruzzaniti, Vicente; GRESPI, SILVIA; SCOTTI, VALERIO; Bianco, Cataldo

    2013-01-01

    The aims of radiotherapeutic treatment of brain metastases include maintaining neurocognitive function and improvement of survival. Based on these premises, we present a case report in which the role of repeat stereotactic radiosurgery (SRS) was investigated in a patient with a recurrent brain metastasis from non-small cell lung cancer in the same area as previously treated with radiosurgery. A 40-year-old male caucasian patient was diagnosed with brain metastasis from non-small cell lung can...

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

    CERN Document Server

    Fortunati, M K S

    2001-01-01

    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 Co...

  2. THE MANAGEMENT OF BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Scott eOwen

    2014-09-01

    Full Text Available Brain metastases (BM are a common and lethal complication of non-small cell lung cancer (NSCLC which portend a poor prognosis. In addition, their management implies several challenges including preservation of neurological and neuro-cognitive function during surgery or radiation -therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood brain barrier (BBB. Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Moreover, new drugs harnessing our greater understanding of tumour biology promise to build on this hope. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy.

  3. Treatment of brain metastases of lung cancer in the era of precision medicine.

    Science.gov (United States)

    Haughton, Michael E; Chan, Michael D; Watabe, Kounosuke; Bonomi, Marcelo; Debinski, Waldemar; Lesser, Glenn J; Ruiz, Jimmy

    2016-01-01

    Common and deadly complications of non-small cell lung cancer (NSCLC) are brain metastases (BM). BM portends a poorer prognosis with limited effective treatment options and current management strategies present several challenges from iatrogenic complications of supportive medications, optimal delivery of drug across the blood-brain barrier, and preservation of neurocognitive function. Long term side effects and survivorship issues have become more evident in the era of targeted therapy where a systemic disease is much better controlled. Targeted therapies and immunotherapy are beginning to provide improvements in responses and survival rates. With further advancements and experience, our knowledge in this era of precision medicine will likely lead to strides in improving the quality of life and overall survival of patients with BM from NSCLC. In this review, we present the most recent updates in treatment of BM in NSCLC in regards to targeted and immunotherapy. PMID:26709658

  4. 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)

    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

  5. Liver metastases

    Science.gov (United States)

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver ...

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

    OpenAIRE

    Haisong eLiu; Andrews, David W; Evans, James J.; Maria eWerner-wasik; Yan eYu; Adam Paul Dicker; Wenyin eShi

    2016-01-01

    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 Kn...

  7. Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Caballero, Jorge A. [Stanford University School of Medicine, Stanford, CA (United States); Sneed, Penny K., E-mail: psneed@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, CA (United States); Lamborn, Kathleen R. [Department of Neurological Surgery, University of California, San Francisco, CA (United States); Ma, Lijun [Department of Radiation Oncology, University of California, San Francisco, CA (United States); Denduluri, Sandeep [Department of Radiology, Tulane School of Medicine, New Orleans, LA (United States); Nakamura, Jean L.; Barani, Igor J. [Department of Radiation Oncology, University of California, San Francisco, CA (United States); McDermott, Michael W. [Department of Radiation Oncology, University of California, San Francisco, CA (United States); Department of Neurological Surgery, University of California, San Francisco, CA (United States)

    2012-05-01

    Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.

  8. Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non–small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age 60, and controlled primary in non–small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.

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

    International Nuclear Information System (INIS)

    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

  10. 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 treatment of brain metastases in breast cancer. We searched PUBMED for all human studies published 1998-2012 using the following search terms: breast neoplasm/cancer, human epidermal growth factor receptor 2/HER2, ErbB2, trastuzumab, lapatinib, brain/cerebral neoplasm/metastases and blood-brain barrier. We...

  11. Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hong Qin

    Full Text Available The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST and toxicity in patients with brain metastases (BM originating from non-small cell lung cancer (NSCLC and who were treated using either whole brain radiotherapy (WBRT plus concurrent chemotherapy or WBRT alone.PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.In total, six randomized controlled trials (RCT involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019 than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233 or time of neurological progression (CNS-TTP (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543, and increased adverse events (Grade≥3 (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000. There were no significant differences in Grade 3-5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92.The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Liu, B; Zhang, L; Rigor, N; Kim, J [City of Hope Foundation, CA (United States)

    2015-06-15

    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.

  14. Hippocampal avoidance with volumetric modulated arc therapy in melanoma brain metastases – the first Australian experience

    International Nuclear Information System (INIS)

    Volumetric modulated arc therapy (VMAT) can deliver intensity modulated radiotherapy (IMRT) like dose distributions in a short time; this allows the expansion of IMRT treatments to palliative situations like brain metastases (BMs). VMAT can deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) to achieve stereotactic radiotherapy (SRT) for BMs. This study is an audit of our experience in the treatment of brain metastases with VMAT in our institution. Metastases were volumetrically contoured on fused diagnostic gadolinium enhanced T1 weighted MRI/planning CT images. Risk organs included hippocampus, optic nerve, optic chiasm, eye, and brain stem. The hippocampi were contoured manually as one paired organ with assistance from a neuroradiologist. WBRT and SIB were integrated into a single plan. Thirty patients with 73 BMs were treated between March 2010 and February 2012 with VMAT. Mean follow up time was 3.5 months. For 26 patients, BMs arose from primary melanoma and for the remaining four patients from non-small cell lung cancer (n= 2), primary breast cancer, and sarcoma. Mean age was 60 years. The male to female ratio was 2:1. Five patients were treated without hippocampal avoidance (HA) intent. The median WBRT dose was 31 Gy with a median SIB dose for BMs of 50 Gy, given over a median of 15 fractions. Mean values for BMs were as follows: GTV = 6.9 cc, PTV = 13.3 cc, conformity index = 8.6, homogeneity index = 1.06. Mean and maximum hippocampus dose was 20.4 Gy, and 32.4 Gy, respectively, in patients treated with HA intent. Mean VMAT treatment time from beam on to beam off for one fraction was 3.43 minutes, which compared to WBRT time of 1.3 minutes. Twenty out of 25 assessable lesions at the time of analysis were controlled. Treatment was well tolerated; grade 4 toxicity was reported in one patient. The median overall survival was 9.40 months VMAT for BMs is feasible, safe and associated with a similar

  15. Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases

    International Nuclear Information System (INIS)

    Stereotactic radiosurgery (SRS) is an alternative to post-operative whole brain radiation therapy (WBRT) following resection of brain metastases. At our institution, CyberKnife (CK) is considered for local treatment of large cavities ≥2 cm. In this study, we aimed to evaluate patterns of failure and characterize patients best suited to treatment with this approach. We retrospectively reviewed 30 patients treated with CK to 33 resection cavities ≥2 cm between 2011 and 2014. Patterns of intracranial failure were analyzed in 26 patients with post-treatment imaging. Survival was estimated by the Kaplan-Meier method and prognostic factors examined with log-rank test and Cox proportional hazards model. The most frequent histologies were lung (43 %) and breast (20 %). Median treatment volume was 25.1 cm3 (range 4.7–90.9 cm3) and median maximal postoperative cavity diameter was 3.8 cm (range 2.8–6.7). The most common treatment was 30 Gy in 5 fractions prescribed to the 75 % isodose line. Median follow up for the entire cohort was 9.5 months (range 1.0–34.3). Local failure developed in 7 treated cavities (24 %). Neither cavity volume nor CK treatment volume was associated with local failure. Distant brain failure occurred in 20 cases (62 %) at a median of 4.2 months. There were increased rates of distant failure in patients who initially presented with synchronous metastases (p = 0.02). Leptomeningeal carcinomatosis (LMC) developed in 9 cases, (34 %). Salvage WBRT was performed in 5 cases (17 %) at a median of 5.2 months from CK. Median overall survival was 10.1 months from treatment. This study suggests that adjuvant CK is a reasonable strategy to achieve local control in large resection cavities. Patients with synchronous metastases at the time of CK may be at higher risk for distant brain failure. The majority of cases were spared or delayed WBRT with the use of local CK therapy

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

    Energy Technology Data Exchange (ETDEWEB)

    Hartford, Alan C., E-mail: Alan.C.Hartford@Hitchcock.org [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Paravati, Anthony J. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Spire, William J. [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Li, Zhongze [Biostatistics Shared Resource, Norris Cotton Cancer Center, Lebanon, New Hampshire (United States); Jarvis, Lesley A. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Fadul, Camilo E. [Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Rhodes, C. Harker [Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Erkmen, Kadir [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Friedman, Jonathan [Department of Surgery, Texas A and M College of Medicine, College Station, Texas (United States); Gladstone, David J. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Hug, Eugen B. [ProCure, New York, New York (United States); Roberts, David W.; Simmons, Nathan E. [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States)

    2013-03-01

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. "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

  19. BRAF Mutation is Associated with Improved Local Control of Melanoma Brain Metastases Treated with Gamma Knife Radiosurgery

    Directory of Open Access Journals (Sweden)

    Ian S Gallaher

    2016-05-01

    Full Text Available Objectives: Evidence has implicated a possible role of tumor mutation status on local control (LC with radiotherapy. BRAF is a proto-oncogene that is mutated in approximately 50% of patients with melanoma. We sought to analyze the influence of BRAF status on LC of melanoma brain metastases following Gamma Knife radiosurgery (GK. Methods: Among 125 patients treated with GK for melanoma brain metastases at our institution between 2006 and 2015, we identified 19 patients with 69 evaluable metastases whose BRAF mutation status was known and follow-up imaging was available. LC of individual metastases was compared based on BRAF mutation status using statistical techniques to control for measurements of multiple metastases within each patient. CNS progression was defined as either local failure or development of new lesions. Results: Of the 69 metastases, BRAF was mutated in 30, and wild-type in 39. With a median follow-up of 30 months for all patients and a median follow-up of 5.5 months for treated lesions, one-year LC was significantly better among metastases with mutated vs. wild-type BRAF (69% vs. 34%, RR = 0.3, 95% CI = 0.1-0.7, p = 0.01. BRAF mutation was found to be a significant predictor of LC after SRS in both univariate (RR=0.3, [95% CI 0.1-0.7, p = 0.01] and multivariate (RR=0.2, [95% CI 0.1-0.7, p = 0.01] analyses. There was also a trend towards improved CNS progression free survival (PFS at one year (26% vs. 0%, p=0.06, favoring BRAF-mutated patients. Conclusions: In this retrospective study, melanoma brain metastases treated with GK had significantly improved local control for patients with BRAF mutation vs. wild-type. Our data suggest that BRAF mutation may sensitize tumors to radiosurgery, and that BRAF wild-type tumors may be more radioresistant. Results: Of the 69 metastases, BRAF was mutated in 30, and wild-type in 39. With a median follow-up of 30 months for all patients and a median follow-up of 5.5 months for treated lesions

  20. Glioblastoma, brain metastases and soft tissue sarcoma of extremities: Candidate tumors for BNCT

    International Nuclear Information System (INIS)

    10B-concentration ratios between human glioblastoma multiforme (U87MG), sarcoma (S3) and melanoma (MV3) xenografted in nu/nu mice and selected normal tissues were investigated to test for preferential 10B-accumulation. Animals received BSH, BPA or both compounds sequentially. Mean 10B-concentration ratios between tumor and normal tissues above 2 were found indicating therapeutic ratios. In addition to glioblastoma, brain metastases and soft tissue sarcoma appear to be promising targets for future BNCT research. - Highlights: • BSH leads to high 10B concentration ratios between sarcoma, muscle and brain as well as between glioblastoma and brain. • The 10B concentration in tumors is quite low as is the 10B concentration ratio between tumors and blood. • BPA-f leads to 10B accumulation in tumors relative to blood and advantageous absolute 10B concentrations in tumors. • The 10B concentration ratios between tumors and brain and sarcoma and muscle, are modest. • The advantage of the sequential injection of both compounds is an enhanced intratumoral 10B concentration

  1. Novel risk scores for survival and intracranial failure in patients treated with radiosurgery alone to melanoma brain metastases

    International Nuclear Information System (INIS)

    Stereotactic radiosurgery (SRS) alone is an increasingly common treatment strategy for brain metastases. However, existing prognostic tools for overall survival (OS) were developed using cohorts of patients treated predominantly with approaches other than SRS alone. Therefore, we devised novel risk scores for OS and distant brain failure (DF) for melanoma brain metastases (MBM) treated with SRS alone. We retrospectively reviewed 86 patients treated with SRS alone for MBM from 2009-2014. OS and DF were estimated using the Kaplan-Meier method. Cox proportional hazards modeling identified clinical risk factors. Risk scores were created based on weighted regression coefficients. OS scores range from 0-10 (0 representing best OS), and DF risk scores range from 0-5 (0 representing lowest risk of DF). Predictive power was evaluated using c-index statistics. Bootstrapping with 200 resamples tested model stability. The median OS was 8.1 months from SRS, and 54 (70.1 %) patients had DF at a median of 3.3 months. Risk scores for OS were predicated on performance status, extracranial disease (ED) status, number of lesions, and gender. Median OS for the low-risk group (0-3 points) was not reached. For the moderate-risk (4-6 points) and high-risk (6.5-10) groups, median OS was 7.6 months and 2.4 months, respectively (p < .0001). Scores for DF were predicated on performance status, ED status, and number of lesions. Median time to DF for the low-risk group (0 points) was not reached. For the moderate-risk (1-2 points) and high-risk (3-5 points) groups, time to DF was 4.8 and 2.0 months, respectively (p < .0001). The novel scores were more predictive (c-index = 0.72) than melanoma-specific graded prognostic assessment or RTOG recursive partitioning analysis tools (c-index = 0.66 and 0.57, respectively). We devised novel risk scores for MBM treated with SRS alone. These scores have implications for prognosis and treatment strategy selection (SRS versus whole-brain radiotherapy)

  2. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases

    Institute of Scientific and Technical Information of China (English)

    Jian-Fei Zhu; Ling Cai; Xue-Wen Zhang; Yin-Sheng Wen; Xiao-Dong Su; Tie-Hua Rong; Lan-Jun Zhang

    2014-01-01

    High expression of fibrinogen and platelets are often observed in non-smal celllung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as wel as to determine the overal survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months;P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months;P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698,P < 0.001 andR2 = 1.699,P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  3. Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases.

    Science.gov (United States)

    Patel, Bindiya G; Ahmed, Kamran A; Johnstone, Peter A S; Yu, Hsiang-Hsuan Michael; Etame, Arnold B

    2016-08-01

    The combined use of the BRAF inhibitor dabrafenib and MEK inhibitor trametinib has been found to improve survival over dabrafenib alone. The management of melanoma brain metastases continues to present challenges. In this study, we report our initial experience in the management of melanoma brain metastases with stereotactic radiosurgery (SRS) with the use of BRAF and MEK inhibitors. We identified six patients treated with SRS for 17 brain metastases within 3 months of BRAF and MEK inhibitor administration. The median planning target volume was 0.42 cm (range: 0.078-2.08 cm). The median treatment dose was 21 Gy (range 18-24 Gy). The median follow-up of all lesions from SRS was 10.6 months (range 5.8-28.5 months). One lesion was found to undergo local failure 21.7 months following SRS treatment. The median overall survival was 20.0 months (range 6.1-31.8 months) from the time of SRS treatment and 23.1 months (range: 12.1-30.9 months) from the date of BRAFi and MEKi administration. There was no evidence of increased nor unexpected toxicity with the two modalities combined. In this initial experience of melanoma brain metastases treated with BRAF and MEK inhibition with SRS, we find the two modalities can be combined safely. These outcomes should be assessed further in prospective evaluations. PMID:26926151

  4. 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

    10.3 months in the EGFR mutation group than in the unselected group. Conclusion: This pooled analysis strongly suggests that EGFR-TKIs are an effective treatment for NSCLC patients with brain metastases, particularly in those patients harboring EGFR mutations. Larger prospective randomized clinical trials are warranted to confirm our conclusion and identify the most appropriate treatment model. Keywords: NSCLC, brain metastases, epidermal growth factor receptor, tyrosine kinase inhibitors

  5. Clinically apparent and occult metastasized seminoma: almost indistinguishable on the transcriptional level.

    Directory of Open Access Journals (Sweden)

    Christian G Ruf

    Full Text Available PURPOSE: The aim of the present study was to examine the biological differences between seminomas with occult and clinically apparent metastases at the time of diagnosis of the primary tumor to gain insight into the biology of these tumors and facilitate the identification of novel predictors of seminoma metastasis. MATERIALS AND METHODS: Total RNA including small RNAs was isolated from testicular tumors of patients with pure seminoma presenting with lymphogenic metastasis (n = 5, clinical stage IIb/c and occult metastasis (n = 5, clinical stage I. The regulation of biological processes was examined (1 throughout the mRNA transcriptome (whole genome microarrays, 8×60 K Array, Agilent with 4 samples/group and (2 the miRNA transcriptome employing small RNA next generation sequencing (SOLID, Life Technologies with 5 samples/group. Protein coding genes (mRNAs and small RNAs showing a significant (≥2-fold difference between the groups were identified. Finally (3, we examined 95 candidate miRNAs in 36 apparent metastasized and another 5 occult metastasized seminoma using logistic regression analysis. RESULTS: Among 19,596 genes, on average 12,894 mRNAs appeared expressed (65.8%, SD+/-2.4; range, 62.0-69.3% and 16.99×106/13.94×106 small RNA reads were identified for apparent/occult metastasized seminoma. These reads on average convert into 9,901/9,675 small RNAs including 422/404 mature microRNAs. None of these mRNAs/small RNAs met our selection criteria for candidate genes. From 95 candidate miRNAs 44 appeared expressed, with 3 of them showing weak but significant (p = 0.05 differences among both groups. CONCLUSIONS: Occult and apparent metastasized seminomas are biologically almost indistinguishable and probably represent no separate tumor entities. These findings may simplify future research on seminoma metastasis.

  6. 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. PMID:27405041

  7. Breast cancer brain metastases responding to lapatinib plus capecitabine as second-line primary systemic therapy.

    Science.gov (United States)

    Bergen, Elisabeth S; Berghoff, Anna S; Rudas, Margaretha; Preusser, Matthias; Bartsch, Rupert

    2015-06-01

    Brain metastases (BM) are diagnosed in up to 40% of HER2-positive breast cancer patients. Standard treatment includes local approaches such as whole-brain radiotherapy (WBRT), radiosurgery, and neurosurgery. The landscape trial established primary systemic therapy as an effective and safe alternative to WBRT in selected patients with Her2-positive BM. We aim to further focus on the role of systemic therapy in oligosymptomatic patients by presenting this case report. We report on a 50-year-old patient diagnosed with multiple BM 5 years after early breast cancer diagnosis. As the patient was asymptomatic and had a favorable diagnosis-specific GPA score, she received primary systemic treatment with T-DM1. She achieved partial remission within the brain for eight treatment cycles and then progressed despite stable extracranial disease. As the patient remained asymptomatic and refused WBRT, we decided upon trastuzumab, lapatinib plus capecitabine as second-line therapy. Another partial remission of BM was observed; to date, she has received 11 treatment cycles without any sign of disease progression. In this case, WBRT was delayed by at least 14 months, again indicating the activity of systemic treatment in BM. Apparently, in selected patients, BM can be controlled with multiple lines of systemic therapy similar to extracranial disease. Further investigation of systemic treatment approaches is therefore warranted.

  8. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Steinmann, D. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Vordermark, D. [Halle-Wittenberg Univ. (Germany). Dept. of Radiation Oncology; Geinitz, H. [Technische Univ. Munich (Germany). Dept. of Radiation Oncology; Aschoff, R. [St.-Josef-Hospital, Gelsenkirchen-Horst (Germany). Dept. of Radiation Oncology; Bayerl, A. [Krems Hospital, Krems (Austria). Dept. of Radiation Oncology; Gerstein, J. [Frankfurt Univ. (Germany). Dept. of Radiation Oncology; Hipp, M.; Schaefer, C. [Regensburg Univ. (Germany). Dept. of Radiation Oncology; Oorschot, B. van [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Wypior, H.J. [Landshut Hospital, Landshut (Germany). Dept. of Radiation Oncology

    2013-01-15

    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.)

  10. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    International Nuclear Information System (INIS)

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  11. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Hoskin, Peter [Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Mitera, Gunita; Zeng Liang [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Lutz, Stephen [Department of Radiation Oncology, Blanchard Valley Regional Cancer Center, Findlay, OH (United States); Roos, Daniel [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Linden, Yvette van der [Radiotherapeutic Institute Friesland, Leeuwarden (Netherlands); Hartsell, William [Department of Radiation Oncology, Advocate Good Samaritan Cancer Center, Downers Grove, IL (United States); Kumar, Eshwar [Department of Oncology, Atlantic Health Sciences Cancer Centre, Saint John Regional Hospital, Saint John, NB (Canada)

    2012-04-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  12. A pure non-gestational ovarian choriocarcinoma with delayed solitary brain metastases: Case report and review of the literature.

    Science.gov (United States)

    Rao, K V L Narasinga; Konar, Subhas; Gangadharan, Jagathlal; Vikas, V; Sampath, S

    2015-01-01

    Choriocarcinoma is the most malignant tumour of gestational trophoblastic origin. Most ovarian choriocarcinomas are gestational in origin and usually metastasize to the ovary from uterine or tubal choriocarcinoma. Non gestational choriocarcinoma (NGOC) of the ovary is exceedingly rare and usually seen along with other germ cell tumors. Non gestational choriocarcinoma has been found to be resistant to single-agent chemotherapy and has a worse prognosis than gestational choriocarcinoma. We are reporting long term follow up of published rare case of pure non gestational ovarian choriocarcinoma (NGOC) with concurrent metastases to the spleen and adrenal glands, who developed a delayed solitary brain metastases, two years after completion of primary treatment. Surgery along with triple agent chemotherapy and radiotherapy was found to give good remission in this aggressive disease. PMID:26752905

  13. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?

    Science.gov (United States)

    Colaco, Rovel J; Martin, Pierre; Kluger, Harriet M; Yu, James B; Chiang, Veronica L

    2016-07-01

    OBJECT Radiation necrosis (RN), or its imaging equivalent, treatment-related imaging changes (TRIC), is an inflammatory reaction to high-dose radiation in the brain. The authors sought to investigate the hypothesis that immunotherapy increases the risk of developing RN/TRIC after stereotactic Gamma Knife (GK) radiosurgery for brain metastases. METHODS A total of 180 patients who underwent GK surgery for brain metastases between 2006 and 2012 were studied. The systemic therapy they received was classified as cytotoxic chemotherapy (CT), targeted therapy (TT), or immunotherapy (IT). The timing of systemic therapy in relation to GK treatment was also recorded. Logistic regression was used to calculate the odds of developing RN according to type of systemic therapy received. RESULTS The median follow-up time was 11.7 months. Of 180 patients, 39 (21.7%) developed RN/TRIC. RN/TRIC rates were 37.5% (12 of 32) in patients who received IT alone, 16.9% (14 of 83) in those who received CT only, and 25.0% (5 of 20) in those who received TT only. Median overall survival was significantly longer in patients who developed RN/TRIC (23.7 vs 9.9 months, respectively). The RN/TRIC rate was increased significantly in patients who received IT alone (OR 2.40 [95% CI 1.06-5.44]; p = 0.03), whereas receipt of any CT was associated with a lower risk of RN/TRIC (OR 0.38 [95% CI 0.18-0.78]; p = 0.01). The timing of development of RN/TRIC was not different between patients who received IT and those who received CT. CONCLUSIONS Patients who receive IT alone may have an increased rate of RN/TRIC compared with those who receive CT or TT alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era. PMID:26544782

  14. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Z

    2015-04-01

    Full Text Available Zhenye Li,1,3,* Xiangheng Zhang,1,* Xiaobing Jiang,1 Chengcheng Guo,1 Ke Sai,1 Qunying Yang,1 Zhenqiang He,1 Yang Wang,1 Zhongping Chen,1 Wei Li,2 Yonggao Mou1 1Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China *These authors have contributed equally to this work Purpose: Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases is hitherto controversial. Patients and methods: We retrospectively analyzed the cases of NSCLC patients with brain metastases who underwent neurosurgical resection at the Sun Yat-sen University Cancer Center, and assessed the efficacy of surgical resection and the necessity of aggressive treatment for primary NSCLC in synchronous brain metastases patients. Results: A total of 62 patients, including 47 men and 15 women, with brain metastases from NSCLC were enrolled in the study. The median age at the time of craniotomy was 54 years (range 29–76 years. At the final follow-up evaluation, 50 patients had died. The median OS time was 15.1 months, and the survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS

  15. Radiosurgery of multiple brain metastases with single-isocenter dynamic conformal arcs (SIDCA)

    International Nuclear Information System (INIS)

    Purpose: To propose single-isocenter dynamic conformal arcs (SIDCA), a novel technique for radiosurgery of multiple brain metastases, and to compare SIDCA with volumetric modulated arc therapy (VMAT) and multiple-isocenter dynamic conformal arcs (MIDCA) for plan quality. Methods and materials: SIDCA, MIDCA, and VMAT plans were created on 6 patients with 3–5 metastases. Plans were evaluated using Radiation Therapy Oncology Group conformity index (RCI), Paddick conformity index (PCI), gradient index (GI), volumes that received more than 100% (V100%), 50% (V50%), 25% (V25%) and 10% (V10%) of prescription dose, total monitor units (MUs), and delivery time (DT). Results: SIDCA achieved conformal plans (RCI = 1.38 ± 0.12, PCI = 0.72 ± 0.06) with steep dose fall-off (GI = 3.97 ± 0.51). MIDCA plans had comparable plan quality and MUs as SIDCA, but 52% longer DT. The VMAT plans had better conformity (RCI = 1.15 ± 0.09, p < 0.01 and PCI = 0.86 ± 0.06, p < 0.01) than SIDCA, worse GI (4.34 ± 0.46, p < 0.01), higher V25% (p = 0.05) and V10% (p = 0.02), 49% less MUs and 46% shorter DT. Conclusions: All three techniques achieved conformal plans with steep dose fall-off from targets. SIDCA plans had similar plan quality as MIDCA but more efficient to delivery. SIDCA plans had lower peripheral dose spread than VMAT; VMAT plans had better conformity and faster delivery time than SIDCA

  16. OP09STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES AT THE CHRISTIE AT SALFORD ROYAL HOSPITAL: OUR TWO-YEAR EXPERIENCE

    OpenAIRE

    Helbrow, J.; McBain, C.; Gattamaneni, R.; A. Tran; McCarthy, C.; Edwards, R; Redikin, J.; Handley, J; O'Hara, C; Kennedy, J.; Mills, S; Soh, C; Leggate, J.; Whitfield, G.

    2014-01-01

    INTRODUCTION: Stereotactic radiosurgery (SRS) for brain metastases (BMs) commenced at The Christie at Salford in Dec 11 using the Novalis TxTM and BrainLab ExacTrac® system. We report our first 2 years' data. METHOD: Patients meeting NHS commissioning criteria were referred via MDT for assessment and if suitable consent. We used the BrainLab mask, CT and MRI. Gross tumour volumes (GTVs) were grown by 2mm if 4cm3 to a planning target volume. The dose to the 80% isodose was 21Gy/1 fraction(#), ...

  17. Cell proliferation index predicts relapse of brain metastases in non-irradiated patients

    DEFF Research Database (Denmark)

    Peev, N A; Tonchev, A B; Penkowa, M;

    2008-01-01

    BACKGROUND: Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site...... subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing of...... the patients with lesions which had not relapsed or which had relapsed more than 2 months after first craniotomy (n = 12). The synchronous brain metastasis (that is, those occurring before or within 2 months of the primary cancer diagnosis) had a significantly higher proliferation index than the...

  18. Patterns of distant brain recurrences after radiosurgery alone for newly diagnosed brain metastases: Implications for salvage therapy

    International Nuclear Information System (INIS)

    Introduction: Single modality radiosurgery (RS) is an established treatment option for patients with brain metastases (BM) with the aim of achieving optimal local control while avoiding toxicity from whole brain radiotherapy (WBRT). Published studies generally lack detailed data on distant brain recurrence (DBR) rates and characteristics. This study describes the patterns of DBR and consequences for salvage treatment in a group of patients treated with RS alone for 1–3 BM. Materials and methods: Between 2002 and 2012, 443 patients were treated with RS alone in doses ranging 15–24 Gy in 1–3 fractions. Patient selection for RS was performed using triple dose gadolinium-enhanced MRI scans, obtained with slice distance of 2 mm (until 2008), 1.5 mm (2008–2012), and of 1 mm (from 2012). During follow-up, a DBR was observed in 147 patients, but in 20 of these patients (14%) these “new lesions” could retrospectively be seen on the planning MRI scan. These missed metastases had a median size of 2 mm, and in order to study real DBR patterns, these patients were excluded from analysis. Results: Actuarial DBR rates at 6, 12 and 24 months in the remaining 423 patients were 21%, 41% and 54%, respectively, with a median time to DBR of 5.6 months. In 42% of DBR, a single new lesion was seen, in 70% there were ⩽3 new lesions. Median diameter of the DBR was 6 mm; 97% of lesions were ⩽30 mm. Salvage therapy was delivered in 82% of DBR patients, consisting of WBRT (46%), repeated RS (27%), or systemic treatment (9%). A RPA classification system (DBR-RPA), based on WHO performance status and interval between initial RS and diagnosis of DBR, was developed to estimate life expectancy after the development of DBR, which can be used to guide salvage therapy. Conclusions: In this study of patients treated with RS alone, only 25% of treated patients needed salvage treatment for DBR, and ultimately only 18% of all patients underwent WBRT at any time during follow-up. A three

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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.

  1. 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.

  2. 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.

  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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, S; Hildebrand, K; Ahmad, S [University of Oklahoma Health Science Center, Oklahoma City, OK (United States); Larson, D; Ma, L [University of California San Francisco, San Francisco, CA (United States); Sahgal, A [University of Toronto, Toronto, Ontario (Canada)

    2014-06-01

    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.

  5. Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions <3, and history of EGFR-TKI treatment had better survival. Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades 2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found to be associated with these late toxicities. Patients received EGFR-TKI treatment had higher incidence of grades 2–3 cognitive impairment with grade

  6. Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind, placebo-controlled clinical trial

    OpenAIRE

    Azar Hosseini; Seyed Hamed Mousavi; Anis Ghanbari; Fatemeh Homaei-Shandiz; Hamid-Reza Raziee; Masoud Pezeshki-Rad; Seyed Hadi Mousavi

    2015-01-01

    Objective: Cancer represents the second cause of mortality in the world. Saffron as a medicinal plant is known for its anti-cancer and anti-depressant properties. In this randomized double blind clinical trial, the effects of saffron on response to treatment in patients suffering from liver metastasis were evaluated. Materials and Methods: Thirteen patients suffering from liver metastases who referred to Ghaem and Imam Reza hospital, Mashhad, Iran were included in this study and then divided ...

  7. Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

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    Yang, T. Jonathan [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Oh, Jung Hun [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Folkert, Michael R.; Gupta, Gaorav [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Morikawa, Aki; Seidman, Andrew [Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Brennan, Cameron [Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Yamada, Yoshiya; Chan, Timothy A. [Department of Radiation Oncology, 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)

    2014-11-01

    Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system was used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.

  8. Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with 18F-ML-10

    International Nuclear Information System (INIS)

    Early assessment of tumor response to therapy is vital for treatment optimization for the individual cancer patient. Induction of apoptosis is an early and nearly universal effect of anticancer therapies. The purpose of this study was to assess the performance of 18F-ML-10, a novel PET radiotracer for apoptosis, as a tool for the early detection of response of brain metastases to whole-brain radiation therapy (WBRT). Ten patients with brain metastases treated with WBRT at 30 Gy in ten daily fractions were enrolled in this trial. Each patient underwent two 18F-ML-10 PET scans, one prior to the radiation therapy (baseline scan), and the second after nine or ten fractions of radiotherapy (follow-up scan). MRI was performed at 6-8 weeks following completion of the radiation therapy. Early treatment-induced changes in tumor 18F-ML-10 uptake on the PET scan were measured by voxel-based analysis, and were then evaluated by correlation analysis as predictors of the extent of later changes in tumor anatomical dimensions as seen on MRI scans 6-8 weeks after completion of therapy. In all ten patients, all brain lesions were detected by both MRI and the 18F-ML-10 PET scan. A highly significant correlation was found between early changes on the 18F-ML-10 scan and later changes in tumor anatomical dimensions (r = 0.9). These results support the potential of 18F-ML-10 PET as a novel tool for the early detection of response of brain metastases to WBRT. (orig.)

  9. 18F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    International Nuclear Information System (INIS)

    We report the biodistribution and radiation dosimetry of an integrin αvβ3 specific PET tracer 18F-AlF-NOTA-E[PEG4-c(RGDfk)]2 (denoted as 18F-Alfatide II). We also assessed the value of 18F-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 18F-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 18F-FDG (5.55 MBq/kg) and 18F-Alfatide II. Injection of 18F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18F-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 18F-Alfatide II PET, while only ten lesions were visualized by 18F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18F-Alfatide II is feasible for human studies. 18F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  10. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33–78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm3 (range, 0.01–35.1 cm3), and the mean marginal dose prescribed was 20.8 Gy (range, 12–25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 ± 0.4 months (95% confidence interval, 9.1–10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209–0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  11. Microinvasion of liver metastases from colorectal cancer: predictive factors and application for determining clinical target volume

    International Nuclear Information System (INIS)

    This study evaluates the microscopic characteristics of liver metastases from colorectal cancer (LMCRC) invasion and provides a reference for expansion from gross tumor volume (GTV) to clinical targeting volume (CTV). Data from 129 LMCRC patients treated by surgical resection at our hospital between January 2008 and September 2009 were collected for study. Tissue sections used for pathology and clinical data were reviewed. Patient information used for the study included gender, age, original tumor site, number of tumors, tumor size, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199), synchronous or metachronous liver metastases, and whether patients received chemotherapy. The distance of liver microinvasion from the tumor boundary was measured microscopically by two senior pathologists. Of 129 patients evaluated, 81 (62.8 %) presented microinvasion distances from the tumor boundary ranging between 1.0 − 7.0 mm. A GTV-to-CTV expansion of 5, 6.7, or 7.0 mm was required to provide a 95, 99, or 100 % probability, respectively, of obtaining clear resection margins by microscopic observation. The extent of invasion was not related to gender, age, synchronous or metachronous liver metastases, tumor size, CA199 level, or chemotherapy. The extent of invasion was related to original tumor site, CEA level, and number of tumors. A scoring system was established based on the latter three positive predictors. Using this system, an invasion distance less than 3 mm was measured in 93.4 % of patients with a score of ≤1 point, but in only 85.7 % of patients with a score of ≤2 points. The extent of tumor invasion in our LMCRC patient cohort correlated with original tumor site, CEA level, and number of tumors. These positive predictors may potentially be used as a scoring system for determining GTV-to-CTV expansion

  12. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

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    Xu Zhiyuan [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Marko, Nicholas F. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Chao, Sam T. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Angelov, Lilyana; Vogelbaum, Michael A. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Suh, John H. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Barnett, Gene H. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Weil, Robert J., E-mail: weilr@ccf.org [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States)

    2012-04-01

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2- breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2- lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2- and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  13. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

    International Nuclear Information System (INIS)

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2− breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2− lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2− and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  14. Advances in Treatment of Brain Metastases 
from Primary Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Gen LIN

    2014-12-01

    Full Text Available Metastatic tumors involving the brain are an important complication in the overall management of non-small cell lung cancers. Surgery and radiation remain the cornerstones of the therapy, however, the burgeoning knowledge of tumor biology has facilitated the entry of systemically administered therapies into the clinic. This review mainly summarizes the current applications of these data to surgery, radiation therapy, chemotherapy and targeted therapy.

  15. Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios

    Science.gov (United States)

    Kaneko, T. S.; Sehgal, V.; Skinner, H. B.; Al-Ghazi, M. S. A. L.; Ramsinghani, N. S.; Marquez Miranda, M.; Keyak, J. H.

    2012-07-01

    Vertebral metastases are a common manifestation of many cancers, potentially leading to vertebral collapse and neurological complications. Conventional treatment often involves percutaneous vertebroplasty/kyphoplasty followed by external beam radiation therapy. As a more convenient alternative, we have introduced radioactive bone cement, i.e. bone cement incorporating a radionuclide. In this study, we used a previously developed Monte Carlo radiation transport modeling method to evaluate dose distributions from phosphorus-32 radioactive cement in simulated clinical scenarios. Isodose curves were generally concentric about the surface of bone cement injected into cadaveric vertebrae, indicating that dose distributions are relatively predictable, thus facilitating treatment planning (cement formulation and dosimetry method are patent pending). Model results indicated that a therapeutic dose could be delivered to tumor/bone within ∼4 mm of the cement surface while maintaining a safe dose to radiosensitive tissue beyond this distance. This therapeutic range should be sufficient to treat target volumes within the vertebral body when tumor ablation or other techniques are used to create a cavity into which the radioactive cement can be injected. With further development, treating spinal metastases with radioactive bone cement may become a clinically useful and convenient alternative to the conventional two-step approach of percutaneous strength restoration followed by radiotherapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Garsa, Adam A. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Barani, Igor J. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Robinson, Clifford G., E-mail: crobinson@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-10-01

    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

  17. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ding Xiao

    2012-07-01

    Full Text Available Abstract Background Brain metastases (BM is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2 NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Results Fifty-three (24.4 % patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001 and the ratio of metastatic to examined nodes or lymph node ratio (LNR ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000 were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

  18. 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.

  19. 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)

    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

  20. Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors

    OpenAIRE

    WEI, HANGPING; Su, Meng; LIN, RUIFANG; Li, Huifang; ZOU, CHANGLIN

    2016-01-01

    The survival time of non-small cell lung cancer (NSCLC) patients with brain metastases has been previously reported to be 6.5–10.0 months, even with systematic treatment. Patients that possess a certain epidermal growth factor receptor (EGFR) mutation alongside NSCLC with brain metastases also have a short survival rate, and a reliable prognostic model for these patients demonstrates a strong correlation between the outcome and treatment recommendations. The Cox proportional hazards regressio...

  1. Defining the Optimal Planning Target Volume in Image-Guided Stereotactic Radiosurgery of Brain Metastases: Results of a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Kirkpatrick, John P., E-mail: john.kirkpatrick@dm.duke.edu [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); Wang, Zhiheng [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Sampson, John H. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); McSherry, Frances; Herndon, James E. [Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina (United States); Allen, Karen J.; Duffy, Eileen [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Hoang, Jenny K. [Department of Radiology, Duke University, Durham, North Carolina (United States); Chang, Zheng; Yoo, David S.; Kelsey, Chris R.; Yin, Fang-Fang [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)

    2015-01-01

    Purpose: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. Methods and Materials: Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board–approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator–based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). Results: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non–small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in

  2. Use of CT perfusion to discriminate between brain metastases from different primaries.

    Science.gov (United States)

    Dolgushin, Mikhail B; Pronin, Igor N; Holodny, Elena A; Fadeeva, Liudmila M; Holodny, Andrei I; Kornienko, Valeri N

    2015-01-01

    Thirty-six metastases in 22 patients were studied prospectively using computed tomography perfusion. Regions of interests were drawn around: the enhancing part of the tumor, necrotic central part, periphery, peritumoral edema, and normal white matter. Cerebral blood volume, cerebral blood flow, and mean transit time were calculated for each zone. The enhancing part of the tumor significantly differed from the other zones in 11 of 12. Metastases of different primaries can be differentiated from one another with statistically significance (Pperfusion parameter in 57% of cases.

  3. Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study

    International Nuclear Information System (INIS)

    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 cm3 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 cm3 for individual lesions. Univariate and multivariate analyses were conducted. As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm3 (median, 16.2 cm3) 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 cm3, 2) 20–29.9 cm3 and 3) ≥30 cm3. 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 cm3 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 of

  4. {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.)

  5. Evaluation of MRI findings and short-term outcome in lung cancer patients with brain metastases after stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Objective: To evaluate the treatment outcomes in lung cancer patients with brain metastases (BM) after stereotactic radiotherapy (SRT) according to magnetic resonance imaging (MRI) findings and the Response Evaluation Criteria In Solid Tumors (RECIST). Methods: A retrospective analysis was performed on 31 lung cancer patients with 60 BM lesions who were treated with SRT. Tumor responses were evaluated according to MRI findings and the RECIST. Results: The MRI after SRT showed that (1) 14 lesions recurred, with nodular enhancement in 8 lesions, homogeneous enhancement in 5 lesions, and inhomogeneous enhancement in 1 lesion; (2) 11 lesions (18%) had suspected progression, with homogeneous enhancement in 5 lesions, inhomogeneous enhancement in 3 lesions, peripheral enhancement in 2 lesions,and nodular enhancement in 1 lesion; (3) 35 lesions were controlled, with decreased volume or disappearance in 19 lesions, insignificant volume change in 10 lesions, and increased volume in 6 lesions; (4) the overall response rate was 76.7% (suspected progression + controlled). According to the RECIST, 15 lesions (25%) achieved a complete response (CR), 9 lesions (15%) achieved a partial response (PR), 12 lesions (20%) had stable disease,and 24 lesions (40%) had progressive disease, and the response rate (CR + PR) was 40%. Conclusions: There are various MRI findings for brain metastases in lung cancer patients after SRT, and 18% of the lesions are difficult to evaluate by MRI. RECIST underestimates the short-term effect of SRT. (authors)

  6. 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.

  7. Risk factors of distant brain failure for patients with newly diagnosed brain metastases treated with stereotactic radiotherapy alone

    International Nuclear Information System (INIS)

    To explore the risk factors of distant brain failure (DBF) for patients with brain metastasis (BM) who were treated with stereotactic radiotherapy alone and to group the patients on the basis of their risk levels. We retrospectively analyzed 132 newly diagnosed BM patients who were treated with stereotactic radiotherapy alone from May 2000 to April 2010. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses. The 1-year incidence rate of DBF was 44.7%, and the median DBF time (MDBFT) was 18 months. In multivariate analysis, the risk factors of DBF were the number of BMs greater than 1 (p = 0.041), uncontrolled extracranial disease (p = 0.005), interval time (IT) of less than 60 months between the diagnosis of primary tumor and BM (p = 0.024), and total volume of BM was greater than 6 cc (p = 0.049). Each risk factor was assigned 1 score. The median survival times for the patients with scores of 0-1, 2-3, and 4 were 31, 12, and 10 months, respectively, and the corresponding MDBFTs were not reached, 13, and 3 months, respectively, (p < 0.001). The crude DBF incidence rates in patients with scores of 0-1, 2-3, and 4 were 14.8%, 50.0%, and 76.9%, respectively, (p < 0.001). The patients with scores of 0-1 had a lower risk of DBF than the patients with higher scores did, and it may be reasonable to treat these patients with SRS alone and resort to whole-brain radiation therapy only for salvage. The patients with a score of 4 had the highest risk of developing DBF after stereotactic radiotherapy alone, these patients may be candidates for initial whole-brain radiation therapy or clinical trials. The patients with a score of 2-3 had a moderate risk of developing DBF, SRT alone combined with close clinical monitoring would be the optimal treatment regimen for such patients, and for those patients with difficulties in receiving close clinical mornitoring, SRT combined with WBRT will be more suitable

  8. 64Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients

    OpenAIRE

    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

    2015-01-01

    Background 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 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. Methods 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 64Cu-DOTA-trastuzumab. Radioactivity in metastatic bra...

  9. Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis.

    Science.gov (United States)

    Palmieri, Diane; Fitzgerald, Daniel; Shreeve, S Martin; Hua, Emily; Bronder, Julie L; Weil, Robert J; Davis, Sean; Stark, Andreas M; Merino, Maria J; Kurek, Raffael; Mehdorn, H Maximilian; Davis, Gary; Steinberg, Seth M; Meltzer, Paul S; Aldape, Kenneth; Steeg, Patricia S

    2009-09-01

    Brain metastases of breast cancer seem to be increasingin incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser-captured epithelial cells from resected human brain metastases of breast cancer compared with unlinked primary breast tumors. The tumors were matched for histology, tumor-node-metastasis stage, and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases, which included, surprisingly, many genes associated with metastasis. Quantitative real-time PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMgamma3, SIAH, STHMN3, and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P) in vitro. Knockdown of HK2 expression in 231-BR cells using short hairpin RNA reduced cell proliferation when cultures were maintained in glucose-limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival after craniotomy (P = 0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. PMID:19723875

  10. Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain

    Directory of Open Access Journals (Sweden)

    Anna Koumarianou

    2016-01-01

    Full Text Available Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2-positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases.

  11. Cone-beam computed tomography in hypofractionated stereotactic radiotherapy for brain metastases

    Directory of Open Access Journals (Sweden)

    Ingrosso Gianluca

    2012-04-01

    Full Text Available Abstract Background To assess interfraction translational and rotational setup errors, in patients treated with image-guded hypofractionated stereotactic radiotherapy, immobilized by a thermoplastic mask and a bite-block and positioned using stereotactic coordinates. Methods 37 patients with 47 brain metastases were treated with hypofractionated stererotactic radiotherapy. All patients were immobilized with a combination of a thermoplastic mask and a bite-block fixed to a stereotactic frame support. Daily cone-beam CT scans were acquired for every patient before the treatment session and were matched online with planning CT images, for 3D image registration. The mean value and standard deviation of all translational (X, Y, Z and rotational errors (θx, θy, θz were calculated for the matching results of bone matching algorithm. Results A total of 194 CBCT scans were analyzed. Mean +/- standard deviation of translational errors (X, Y, Z were respectively 0.5 +/- 1.6 mm (range -5.7 and 5.9 mm in X; 0.4 +/- 2.7 mm (range -8.2 and 12.1 mm in Y; 0.4 +/- 1.9 mm (range -7.0 and 14 mm in Z; median and 90th percentile were respectively within 0.5 mm and 2.4 mm in X, 0.3 mm and 3.2 mm in Y, 0.3 mm and 2.2 mm in Z. Mean +/- standard deviation of rotational errors (θx, θy, θz were respectively 0.0 degrees+/- 1.3 degrees (θx (range -6.0 degrees and 3.1 degrees; -0.1 degrees +/- 1.1 degrees (θy (range -3.0 degrees and 2.4 degrees; -0.6 degrees +/- 1.4 degrees (θz (range -5.0 degrees and 3.3 degrees. Median and 90th percentile of rotational errors were respectively within 0.1 degrees and 1.4 degrees (θx, 0.0 degrees and 1.2 degrees (θy, 0.0 degrees and 0.9 degrees (θz. Mean +/- SD of 3D vector was 3.1 +/- 2.1 mm (range 0.3 and 14.9 mm; median and 90th percentile of 3D vector was within 2.7 mm and 5.1 mm. Conclusions Hypofractionated stereotactic radiotherapy have the significant limitation of uncertainty in interfraction repeatability of the patient

  12. Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases

    Science.gov (United States)

    Vatansever, Fatma; Kawakubo, Masayoshi; Chung, Hoon; Hamblin, Michael R.

    2013-02-01

    We have previously shown that photodynamic therapy mediated by a vascular regimen of benzoporphyrin derivative and 690nm light is capable of inducing a robust immune response in the mouse CT26.CL25 tumor model that contains a tumor-rejection antigen, beta-galactosidase (β-gal). For the first time we show that PDT can stimulate the production of serum IgG antibodies against the β-gal antigen. It is known that a common cause of death from cancer, particularly lung cancer, is brain metastases; especially the inoperable ones that do not respond to traditional cytotoxic therapies either. We asked whether PDT of a primary tumor could stimulate immune response that could attack the distant brain metastases. We have developed a mouse model of generating brain metastases by injecting CT26.CL25 tumor cells into the brain as well as injecting the same cancer cells under the skin at the same time. When the subcutaneous tumor was treated with PDT, we observed a survival advantage compared to mice that had untreated brain metastases alone.

  13. [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 %).

  14. Preliminary clinical study of 89Sr in palliation in painful skeletal metastases

    International Nuclear Information System (INIS)

    89Sr has shown to produce significant pain relief in patients with skeletal metastases from advanced cancer. According to the requirements from the drug agency of Chinese ministry of health, we had treated 27 patients with painful bone metastases to testify the safety and efficiency of Metastron (89Sr injection solution imported from the Amersham company, UK). Strontium was used for the treatment of painful bone metastasis in 27 patients. 2 cases was excluded by missed follow-up, the other 25 cases with metastatic prostate carcinoma, lung cancer, breast cancer have been evaluated in a standard quantitative pain measures before the treatment. Pain scores of these patients were between 6 ∼ 16. According to the guideline of this pharmaceutical, Metastron was given intravenously to these patients as a 1.48 MBq/kg dose. All the patients were monitored at least 3 months. Pain score, radiotoxocity and immediately reaction were observed in the follow-up. Clinically significant metastatic pain relief can be observed in most patients. Total efficiency is 77.8% respectively, patients' life quality have been improved. No clinically significant adverse effects or myelosuppression were observed in most patients. The mild decrease of white blood cell can be seen in 32% patients and platelet counts in 60% patients. Most of these patients can recover except 1 case. For the case, further clinical data show a little change in liver function. Absolute granulocyte counts did not fall bellow 2000 in any patients. Significant increased pain (flare) occurred in 55.5% patients after the injection of Metastron. The flare had been lasting 3-7 days. Only one patient's pain last more than 20 days. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in-patients with prostate or breast carcinoma. More than 3 months pain relief can be observed in 94.4% patients. There is only one patient lasted for 2 months. 7 cases had repeated the bone scan before

  15. Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

    Directory of Open Access Journals (Sweden)

    Yu-Mu Chen

    Full Text Available Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKIs, although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs and proton pump inhibitors (PPIs as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.Fifty-seven patients (57/269, 21.2% were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234. However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002. Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041. Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

  16. An Institutional Retrospective Analysis of 93 Patients with Brain Metastases from Breast Cancer: Treatment Outcomes, Diagnosis-Specific Prognostic Factors

    Directory of Open Access Journals (Sweden)

    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.

  17. P-glycoprotein Mediated Efflux Limits Substrate and Drug Uptake in a Preclinical Brain Metastases of Breast Cancer Model

    Directory of Open Access Journals (Sweden)

    Chris E Adkins

    2013-11-01

    Full Text Available The blood-brain barrier (BBB is a specialized vascular interface that restricts the entry of many compounds into brain. This is accomplished through the sealing of vascular endothelial cells together with tight junction proteins to prevent paracellular diffusion. In addition, the BBB has a high degree of expression of numerous efflux transporters which actively extrude compounds back into blood. However, when a metastatic lesion develops in brain the vasculature is typically compromised with increases in passive permeability (blood-tumor barrier; BTB. What is not well documented is to what degree active efflux retains function at the BTB despite the changes observed in passive permeability. In addition, there have been previous reports documenting both increased and decreased expression of P-gp in lesion vasculature. Herein, we simultaneously administer a passive diffusion marker (14C-AIB and a tracer subject to P-gp efflux (rhodamine 123 into a murine preclinical model of brain metastases of breast cancer. We observed that the metastatic lesions had similar expression (p>0.05; n=756-1214 vessels evaluated at the BBB and the BTB. Moreover, tissue distribution of R123 was not significantly (p>0.05 different between normal brain and the metastatic lesion. It is possible that the similar expression of P-gp on the BBB and the BTB contribute to this phenomenon. Additionally we observed P-gp expression at the metastatic cancer cells adjacent to the vasculature which may also contribute to reduced R123 uptake into the lesion. The data suggest that despite the disrupted integrity of the BTB, efflux mechanisms appear to be intact, and may be functionally comparable to the normal BBB. The BTB is a significant hurdle to delivering drugs to brain metastasis.

  18. Risk factors for level V lymph node metastases in solitary papillary thyroid carcinoma with clinically lateral lymph node metastases.

    Science.gov (United States)

    Yang, Jing; Gong, Yanping; Yan, Shuping; Zhu, Jingqiang; Li, Zhihui; Gong, Rixiang

    2016-08-01

    The extent of lateral neck dissection (LND) in surgical resection of papillary thyroid carcinoma (PTC) with clinically lateral LNM (LLNM) remains controversial. We aimed to explore the frequency of and risk factors for level V LNM in patients with solitary PTC and clinically LLNM. To analyze the frequency and risk factors for level V LNM, we retrospectively reviewed 220 solitary PTC patients who underwent total thyroidectomy, bilateral central neck dissection, and therapeutic LND. LLNM were present in 82.3% patients, and levels II-V LNM were present in 45.9%, 62.7%, 55.5%, and 12.3% patients, respectively. Ipsilateral level V LNM was significantly associated with tumor size >10 mm, extrathyroidal extension, ipsilateral central LNM ratio ≥50%, and contralateral central LNM (CLNM), bilateral CLNM, and simultaneous levels II-IV LNM. Contralateral CLNM was an independent risk factor for level V LNM. In patients with solitary PTC and clinically LLNM, level V LNM was relatively uncommon. Therefore, routine level V lymphadenectomy may be unnecessary in these patients unless level V LNM is suspected on preoperative examination or associated risk factors, especially contralateral CLNM, are present.

  19. 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.

  20. 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)

    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/m2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab (123I-Erbi) on scintigraphy; 123I-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.)

  1. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents. PMID:27496068

  2. Radium-223 in the Treatment of Osteoblastic Metastases: A Critical Clinical Review

    Energy Technology Data Exchange (ETDEWEB)

    Humm, John L. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Sartor, Oliver [Departments of Medicine and Urology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana (United States); Parker, Chris [Department of Clinical Oncology, Institute of Cancer Research, Sutton (United Kingdom); Bruland, Oyvind S. [Department of Oncology, Norwegian Radium Hospital and Institute for Clinical Medicine, University of Oslo, Oslo (Norway); Macklis, Roger, E-mail: rmmacklis@gmail.com [Department of Radiation Oncology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio (United States)

    2015-04-01

    The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for {sup 226}Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer.

  3. Repeat stereotactic radiosurgery in the management of brain metastases from NSCLC: A case report and review of the literature.

    Science.gov (United States)

    Marvaso, Giulia; Barone, Agnese; Vaccaro, Caterina; Bruzzaniti, Vicente; Grespi, Silvia; Scotti, Valerio; Bianco, Cataldo

    2013-10-01

    The aims of radiotherapeutic treatment of brain metastases include maintaining neurocognitive function and improvement of survival. Based on these premises, we present a case report in which the role of repeat stereotactic radiosurgery (SRS) was investigated in a patient with a recurrent brain metastasis from non-small cell lung cancer in the same area as previously treated with radiosurgery. A 40-year-old male caucasian patient was diagnosed with brain metastasis from non-small cell lung cancer (NSCLC) and underwent SRS. The patient developed a recurrence of the disease and a second SRS on the same area was performed. After 8 months, tumor restaging demonstrated a lesion compatible with a recurrence and the patient underwent surgery. Histological diagnosis following surgery revealed only the occurrence of radionecrosis. Radiotherapy was well-tolerated and no grade 3/4 neurological toxicity occurred. To date, no consensus exists on the efficacy of retreatment with SRS. Despite the limited number of studies in this field, in the present case report, we outline the outcomes of this unconventional approach. PMID:24137433

  4. Unusual Clinical Course of Papillary Thyroid Microcarcinoma: Metastases of Bone and Lung

    OpenAIRE

    Ufuk Özuğuz; Serhat Işık; Ferhat Gökay; Hatice Özcan Nursun; Gül Türkcü; Dilek Berker; Serdar Güler

    2011-01-01

    AbstractPapillary thyroid microcarcinomas are slow-growing tumours; distant metastases causing mortality is very rare. Case presentation We report the case of a 35-year-old woman with lung and bone metastases of a multifocal papillary thyroid microcarcinoma (PTMC). She had undergone a subtotal thyroidectomy due to euthyroide multinodular goitre without fine needlle aspiration biopsy. Iodine-131-whole body scan showed markedly iodine retention in the neck, lung and pelvis. Chest computed tomog...

  5. SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

    International Nuclear Information System (INIS)

    Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPT vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue

  6. SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

    Energy Technology Data Exchange (ETDEWEB)

    Keeling, V; Hossain, S; Hildebrand, K; Ahmad, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Larson, D; Ma, L [University of California San Francisco, San Francisco, CA (United States); Sahgal, A [University of Toronto, Toronto, ON (Canada)

    2015-06-15

    Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPT vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.

  7. Assessment of irradiated brain metastases using dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Almeida-Freitas, Daniela B. [University of Sao Paulo, Department of Radiology, Sao Paulo (Brazil); University of California, Department of Radiology, San Diego, CA (United States); Pinho, Marco C. [University of Texas Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Otaduy, Maria C.G.; Costa Leite, Claudia da [University of Sao Paulo, Department of Radiology, Sao Paulo (Brazil); Braga, Henrique F. [University of Sao Paulo, Department of Radiotherapy, Sao Paulo (Brazil); Meira-Freitas, Daniel [Federal University of Sao Paulo, Sao Paulo (Brazil)

    2014-06-15

    The purpose of this study was to evaluate the effect of stereotactic radiosurgery (SRS) on cerebral metastases using the transfer constant (K{sub trans}) assessed by dynamic contrast-enhanced (DCE) MRI. Furthermore, we aimed to evaluate the ability of K{sub 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{sub 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{sub trans} value was 0.13 ± 0.11 min{sup -1} at baseline and 0.08 ± 0.07 min{sup -1} after 4-8 weeks post-treatment (p < 0.001). The mean (±SD) total follow-up time was 7.9 ± 4.7 months. Seventeen patients (22 lesions) underwent midterm MRI. Of those, nine (41 %) lesions had progressed at the midterm follow-up. An increase in K{sub trans} after SRS was predictive of tumor progression (hazard ratio = 1.50; 95 % CI = 1.16-1.70, p < 0.001). An increase of 15 % in K{sub 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{sub trans} values of the cerebral metastases in the early post-treatment period. Furthermore, K{sub trans} variation as assessed using DCE MRI may be helpful to predict midterm outcomes after SRS. (orig.)

  8. 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)

    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

  9. Five-fraction stereotactic radiosurgery (SRS) for single inoperable high-risk non-small cell lung cancer (NSCLC) brain metastases

    International Nuclear Information System (INIS)

    Achieving durable local control while limiting normal tissue toxicity with definitive radiation therapy in the management of high-risk brain metastases remains a radiobiological challenge. The objective of this study was to examine the local control and toxicity of a 5-fraction stereotactic radiosurgical approach for treatment of patients with inoperable single high-risk NSCLC brain metastases. This retrospective analysis examines 20 patients who were deemed to have “high-risk” brain metastases. High-risk tumors were defined as those with a maximum diameter greater than 2 cm and/or those located within an eloquent cortex. Patients were evaluated by a neurosurgeon prior to treatment and determined to be inoperable due to tumor or patient characteristics. Patients were treated using the CyberKnife® SRS system in 5 fractions to a total dose of 30 Gy, 35 Gy, or 40 Gy. Twenty patients with a median age of 65.5 years were treated from April 2010 to August 2014 in 5 fractions to a median total dose of 35 Gy. At a median follow up of 11.3 months local tumor control was observed in 18 of 20 metastases (90 %). Both local failures were observed in patients receiving a lower dose of 30 Gy. Median pre-treatment dexamethasone dose was 10 mg/day and median post-treatment nadir dose was 0 mg/day. Salvage intracranial therapy was required in 45 % of patients. Symptomatic radionecrosis was observed in 4 of 20 patients (20 %), two of which were treated to 40 Gy and the remainder to 35 Gy. Kaplan-Meier 1-year, 2-year, and median survival were calculated to be 45 %, 20 %, and 13.2 months, respectively. Five-fraction SRS to a total dose of 35 Gy appears to be a safe and effective management strategy for single high-risk NSCLC brain metastases, while a total dose of 40 Gy leads to an excess risk of neurotoxicity

  10. The application of DWI in the differential diagnosis between malignant glioma and solitary metastases

    International Nuclear Information System (INIS)

    Glioma and brain metastases are common tumors in clinical practice. It's difficult to diagnose and differentiate glioma from solitary metastases, because they have similar clinical characters and conventional imaging manifestations. Because of different treatments and prognosis for the two types of tumor, it's important for us to accurately diagnose and differentiate them. Some scholars have used diffusion weighted imaging in diagnosis and differential diagnosis of brain tumors. In this paper, we reviewed the usefulness of diffusion weighted imaging in diagnosis and differential diagnosis between glioma and solitary metastases. (authors)

  11. 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

  12. Functional brain imaging - baric and clinical questions

    International Nuclear Information System (INIS)

    The advancing biological knowledge of disease processes plays a central part in the progress of modern psychiatry. An essential contribution comes from the functional and structural brain imaging techniques (CT, MRI, SPECT, PET). Their application is important for biological oriented research in psychiatry and there is also a growing relevance in clinical aspects. This development is taken into account by recent diagnostic classification systems in psychiatry. The capabilities and limitations of functional brain imaging in the context of research and clinic will be presented and discussed by examples and own investigations. (orig.)

  13. Implications for preserving neural stem cells in whole brain radiotherapy and prophylactic cranial irradiation. A review of 2270 metastases in 488 patients

    International Nuclear Information System (INIS)

    This study delineated the incidence of metastatic involvement of neural stem cell (NSC) regions and further aimed to explore the feasibility of selectively sparing the NSC compartments during whole brain radiotherapy (WBRT) and prophylactic cranial irradiation (PCI). A total of 2270 intracranial metastases in 488 patients were identified. Lesions were classified according to locations, including lesions in the NSC compartments (subventricular zone, SVZ, or hippocampus) and those in the rest of the brain/brainstem. The incidence of involvement of NSC regions was compared between oligometastatic patients (those with 1-4 lesions) and non-oligometastatic patients (those with 5 or more lesions) using a chi-square test. The volume of the NSC regions accounted for 2.23% of the whole brain, and the overall rate of metastatic lesions in NSC regions was 1.1% in 2270 metastases (25/2270), and 4.7% in 488 patients (23/488). Of the NSC region metastases, 7 (0.3%) involved the hippocampus and 18 (0.8%) occurred in the SVZ. Among the 7 hippocampal metastases identified in this study, 1/7 (14.3%) were found in oligometastatic patients, while 6/7 (85.7%) metastases were in non-oligometastatic patients. For metastases in the SVZ, all lesions occurred in non-oligometastatic patients with none in oligometastatic patients. Metastatic involvement of the NSC compartments was significantly lower in oligometastatic patients (0.15%, 1/670) than in non-oligometastatic patients (1.5%, 24/1600) (P<0.001). Our retrospective review of 2270 metastases in 488 patients is that the volume of the compartments of NSC regions was 2.23% relative to the whole brain, but the incidence of involvement of the NSC compartments was 1.1%, and the vast majority of NSC lesions were found in non-oligometastatic patients. We believe our data supports selective reduction of doses for these aforementioned structures, when treating oligometastatic patients with WBRT and locally advanced-stage small-cell lung cancer

  14. Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Azar Hosseini

    2015-08-01

    Full Text Available Objective: Cancer represents the second cause of mortality in the world. Saffron as a medicinal plant is known for its anti-cancer and anti-depressant properties. In this randomized double blind clinical trial, the effects of saffron on response to treatment in patients suffering from liver metastasis were evaluated. Materials and Methods: Thirteen patients suffering from liver metastases who referred to Ghaem and Imam Reza hospital, Mashhad, Iran were included in this study and then divided into two different groups. Both groups received chemotherapy regimen. Patients in group one were treated with saffron capsule (50 mg, twice daily during chemotherapy periods whereas patients in group two received placebo. A sum of the longest diameter were calculated and compared for all lesions in IV contrast CT scan before and after the treatment. Results: from 13 patients included in this study, six patients quit and seven continued until the end. In saffron-treated group, two patients showed partial and complete response (50% whereas in placebo group, no response was seen. Also, two deaths in placebo and one in saffron group occurred. Conclusion: This research suggests that saffron might be useful in patients suffering from liver metastasis. However, further investigations with larger sample size are required.

  15. Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions

    Directory of Open Access Journals (Sweden)

    Fabio Ynoe de Moraes

    2016-02-01

    Full Text Available Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurgery is an increasingly utilized treatment method that improves local control and pain relief after delivering ablative doses of radiation. Here, we present a review highlighting the use of spinal radiosurgery for the treatment of metastatic tumors of the spine. The data used in the review were collected from both published studies and ongoing trials. We found that spinal radiosurgery is safe and provides excellent tumor control (up to 94% local control and pain relief (up to 96%, independent of histology. Extensive data regarding clinical outcomes are available; however, this information has primarily been generated from retrospective and nonrandomized prospective series. Currently, two randomized trials are enrolling patients to study clinical applications of fractionation schedules spinal Radiosurgery. Additionally, a phase I clinical trial is being conducted to assess the safety of concurrent stereotactic body radiotherapy and ipilimumab for spinal metastases. Clinical trials to refine clinical indications and dose fractionation are ongoing. The concomitant use of targeted agents may produce better outcomes in the future.

  16. Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Moraes, Fabio Ynoe de; Neves-Junior, Wellington Furtado Pimenta; Hanna, Samir Abdallah; Carvalho, Heloisa de Andrade [Hospital Sirio-Libanes, Sao Paulo, SP (Brazil). Departamento de Radioterapia; Taunk, Neil Kanth; Yamada, Yoshiya [Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Laufer, Ilya, E-mail: fymoraes@gmail.com [Memorial Sloan Kettering Cancer Center, Department of Neurosurgery, New York, NY (United States)

    2016-02-15

    Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurgery is an increasingly utilized treatment method that improves local control and pain relief after delivering ablative doses of radiation. Here, we present a review highlighting the use of spinal radiosurgery for the treatment of metastatic tumors of the spine. The data used in the review were collected from both published studies and ongoing trials. We found that spinal radiosurgery is safe and provides excellent tumor control (up to 94% local control) and pain relief (up to 96%), independent of histology. Extensive data regarding clinical outcomes are available; however, this information has primarily been generated from retrospective and non randomized prospective series. Currently, two randomized trials are enrolling patients to study clinical applications of fractionation schedules spinal Radiosurgery. Additionally, a phase I clinical trial is being conducted to assess the safety of concurrent stereotactic body radiotherapy and ipilimumab for spinal metastases. Clinical trials to refine clinical indications and dose fractionation are ongoing. The concomitant use of targeted agents may produce better outcomes in the future. (author)

  17. [Electrochemotherapy: mechanism of action and clinical results in the locoregional treatment of patients with skin cancers and superficial metastases].

    Science.gov (United States)

    Campana, Luca Giovanni; Marconato, Roberto; Sieni, Elisabetta; Valpione, Sara; Corti, Luigi; Mocellin, Simone; Rossi, Carlo Riccardo

    2016-08-01

    Electrochemotherapy (ECT) has emerged among European centers as an innovative locoregional treatment for patients with unresectable skin cancers or superficial metastases from any histotype. The combined administration of a cytotoxic agent (bleomycin or cisplatin) with properly tuned electric pulses results in locally-enhanced drug delivery (reversible electroporation) into malignant cells and sustained tumor response. Reversible electroporation represents the basis of ECT and allows the potentiation of two low permeant cytotoxic agents such as bleomycin (~8000 fold) and cisplatin (~80 fold). The procedure was standardized in 2006 - thanks to a European project - and shortly after introduced in the clinical practice. In recent years, experience with ECT has accumulated mainly in melanoma and breast cancer patients with cutaneous metastases, in whom complete response rates of 20-50% and 40-75% have been reported, respectively, depending on tumor size. Currently, this therapy is being investigated in deep-seated (i.e. bone, soft tissue) metastases and visceral malignancies (i.e. locally advanced pancreatic cancer), with encouraging results. PMID:27571558

  18. Clinical and laboratory toxicity after intra-arterial radioembolization with (90y-microspheres for unresectable liver metastases.

    Directory of Open Access Journals (Sweden)

    Maarten L J Smits

    Full Text Available OBJECTIVE: To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization ((90Y-RE. METHODS: Patients with liver metastases treated with (90Y-RE, between February 1(st 2009 and March 31(st 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts. Laboratory investigations at baseline and during a four-month follow-up were used to assess laboratory toxicity according to the Common Terminology Criteria for Adverse Events version 4.02. The occurrence of grade 3-4 laboratory toxicity was stratified according to treatment strategy (whole liver treatment in one session versus sequential sessions. Response assessment was performed at the level of target lesions, whole liver and overall response in accordance with RECIST 1.1 at 3- and 6 months post-treatment. Median time to progression (TTP and overall survival were calculated by Kaplan-Meier analysis. RESULTS: A total of 59 patients, with liver metastases from colorectal cancer (n = 30, neuroendocrine tumors (NET (n = 6 and other primary tumors (n = 23 were included. Clinical toxicity after (90Y-RE treatment was confined to grade 1-2 events, predominantly post-embolization symptoms. No grade 3-4 clinical toxicity was observed, whereas laboratory toxicity grade 3-4 was observed in 38% of patients. Whole liver treatment in one session was not associated with increased laboratory toxicity. Three-months disease control rates for target lesions, whole liver and overall response were 35%, 21% and 19% respectively. Median TTP was 6.2 months for target lesions, 3.3 months for the whole liver and 3.0 months for overall response. Median overall survival was 8.9 months. CONCLUSION: The risk of severe complications or grade 3-4 clinical toxicity in patients with liver metastases of various primary tumors undergoing (90Y-RE is low. In contrast, laboratory toxicity grade 3

  19. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer.

    NARCIS (Netherlands)

    Harisinghani, M.G.; Barentsz, J.O.; Hahn, P.F.; Deserno, W.M.L.L.G.; Tabatabaei, S.; Hulsbergen-van de Kaa, C.A.; Rosette, J.J.M.H.C. de la; Weissleder, R.

    2003-01-01

    BACKGROUND: Accurate detection of lymph-node metastases in prostate cancer is an essential component of the approach to treatment. We investigated whether highly lymphotropic superparamagnetic nanoparticles, which gain access to lymph nodes by means of interstitial-lymphatic fluid transport, could b

  20. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    International Nuclear Information System (INIS)

    Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  1. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Heekyoung [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Yoon, Su Jin [Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Jin, Juyoun [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Choi, Seung Ho [Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Seol, Ho Jun; Lee, Jung-Il [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); and others

    2011-03-04

    Research highlights: {yields} The most important therapeutic tool in brain metastasis is radiation therapy. {yields} Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. {yields} Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. {yields} Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  2. 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)

    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.

  3. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

    Science.gov (United States)

    Mansfield, A. S.; Aubry, M. C.; Moser, J. C.; Harrington, S. M.; Dronca, R. S.; Park, S. S.; Dong, H.

    2016-01-01

    Background The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases. Experimental design Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ2 or Fisher's exact test were used for analysis. Results We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009). Conclusions We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment. PMID:27502709

  4. 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

  5. Quality of Life in Patients With Brain Metastases Using the EORTC QLQ-BN20+2 and QLQ-C15-PAL

    International Nuclear Information System (INIS)

    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

  6. The Characteristics of Celiac Trunk Lymph-node Metastases of Esophageal Cancer in the Thoracic Segment and Clinical Significance for Wide-Excision

    Institute of Scientific and Technical Information of China (English)

    Hongjiang Wang; Zuoliang Pang; Sikandaer; Wei Sun; Warasijiang; Zhiqin Fan; Feng Xue

    2006-01-01

    OBJECTIVE To understand the characteristics of celiac trunk lymph-node metastases of thoracic esophageal carcinoma and their influence on prognosis of the patients, and to investigate a reasonable range for regional celiac trunk lymph-node clearance.METHODS Clinical specimens of 241 patients receiving resection of a thoracic esophageal carcinoma were analyzed retrospectively.RESULTS The rate of the patient celiac lymph-node metastases was 32.4%(78/241), and of the lymph nodes examined, 9.8% were found to have metastasis. The extent of metastases adjacent to the common hepatic artery and celiac trunk and within the hepatoduodenal ligaments was 6.6%, 6.9% and 6.3%, respectively. The tumor site, extent of invasion and level of cell differentiation were the factors influencing lymph-node metastases, but they were unrelated to the length of the tumor. The overall rate of regional celiac recurrence for the patients 3 years after operation was 5.4%. The 3-year survivals for the patients with metastases of the celiac lymph nodes was 42.3%, which was lower compared to the non-metastatic patients (70.6%) (P<0.01).CONCLUSION Celiac lymph-node metastases are one of key factors affecting the prognosis of the patients receiving resection of esophageal cancer, and extensive clearance of the celiac-trunk lymph nodes can reduce the rate of postoperative regional metastases.

  7. 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.

  8. MRI对肺癌脑转移的诊断价值分析%Analysis the Value of MRI in Diagnosis of Brain Metastases in Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    黄志成; 孙双燕; 孙志强

    2015-01-01

    目的:分析MRI对肺癌脑转移的诊断价值。方法76例肺癌脑转移患者均采取MRI诊断,分析MIR表现。结果76例患者148个转移病灶,78.4%病灶分布在幕上,21.6%分布在幕下。以实质性病灶为主,瘤周水肿是其主要特征,33.1%为重度瘤周水肿。结论 MRI对肺癌脑转移的诊断价值显著。%ObjectiveTo analyze the diagnostic value of MRI on brain metastases of lung cancer.MethodsSeventy-six patients with brain metastases from lung cancer were taken to MRI diagnosis,MIR analysis.Results Of the 76 patients with 148 metastatic lesions,78.4% lesions were located in supratentorial,infratentorial in 21.6%. The substantive focus,peritumoral edema are the main features,and 33.1% with severe peritumoral edema. Conclusion The value of MRI in diagnosis of brain metastases of lung cancer is significantl.

  9. Management of unknown origin cerebral metastases

    Directory of Open Access Journals (Sweden)

    F.M. Gramada

    2011-03-01

    Full Text Available Aim: The present study attempts todetermine the steps for obtaining theetiological diagnosis of brain metastaseswith unknown origin.Material and methods: A total of 190patients with brain metastases diagnosed inthe Department of Neurosurgery inEmergency Hospital ”N. Oblu” Iasibetween 2007-2010 were included in thisstudy. The clinical characteristics andpathological features were analyzed.Results: There were 102 males and 88females with a M:F ratio of 1.15:1. Themedian age of patients was 47.07 years(range 31-77 years. Females patients wereolder (mean age 57.21 years than malespatients (49.15 years. 154 patients (81.05%had single brain metastasis, and 36 patients(18.95% had more than two. The lesionswere supratentorial in 142 patients(74.73%, infratentorial in 18 (9.47%, andboth infratentorial and supratentorial in 30patients (15.78%. Surgical treatmentinvolved complete resection in 47.9% ofcases, subtotal resection in 26.8%, andbiopsy alone in the remainder (25.3%.Brain metastases originating in lung cancerrepresented the most common type(47.39%, followed by those from breastcancer (19.79%, then those from skin(melanoma (8.33%, genitourinarycarcinoma (6.30%, and gastrointestinalcarcinoma (2.62%. In 16.31% of cases, theprimary tumor remained unknown, despiteextensive investigation.Conclusion: The primary cancer leadingto brain metastases can be detected eitherby obtaining a sample of tumoral tissuethrough a neurosurgical operation on theintracerebral tumor (total ablation orstereotactic biopsy with histopathologicalexamination, or by additional tests of thewhole body. Taken into consideration theresults of our own study, the managementof the patients with brain metastases shouldinclude a thoracic CT scan oranteroposterior and lateral chest X-ray,clinical breast examination andmammography, abdominal ultrasoundexploration, and skin, kidney and prostateexamination. With the most sophisticatedmethods of diagnosis in approximately 16%of cases the

  10. Variable dose interplay effects across radiosurgical apparatus in treating multiple brain metastases

    OpenAIRE

    Ma, Lijun; Nichol, Alan; Hossain, Sabbir; Wang, Brian; Petti, Paula; Vellani, Rosemin; Higby, Chris; Ahmad, Salahuddin; Barani, Igor; Shrieve, Dennis C; Larson, David A.; Sahgal, Arjun

    2014-01-01

    Purpose Normal brain tissue doses have been shown to be strongly apparatus dependent for multi-target stereotactic radiosurgery. In this study, we investigated whether inter-target dose interplay effects across contemporary radiosurgical treatment platforms are responsible for such an observation. Methods For the study, subsets ( \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepack...

  11. 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.

  12. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    International Nuclear Information System (INIS)

    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

  13. Effects of radiotherapy for brain metastases on quality of life (QoL). Prospective pilot study of the DEGRO QoL working party

    International Nuclear Information System (INIS)

    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 (T0) and at 3 months (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 T3mo, 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 T0 was better in those alive than in those deceased at T3mo, 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.)

  14. Brain metastases from lung cancer show increased expression of DVL1, DVL3 and beta-catenin and down-regulation of E-cadherin.

    Science.gov (United States)

    Kafka, Anja; Tomas, Davor; Beroš, Vili; Pećina, Hrvoje Ivan; Zeljko, Martina; Pećina-Šlaus, Nives

    2014-06-13

    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.

  15. 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.

  16. 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.)

  17. QL-11HEALTH-RELATED QUALITY OF LIFE, COGNITIVE FUNCTIONING AND SURVIVAL IN PATIENTS TREATED WITH STEREOTACTIC RADIOTHERAPY FOR BRAIN METASTASES: A PROSPECTIVE STUDY

    OpenAIRE

    Habets, Esther; Dirven, Linda; Wiggenraad, Ruud; Zwinkels, Hanneke; Nijeholt, Geert Lycklama á; Taphoorn, Martin

    2014-01-01

    BACKGROUND: Although stereotactic radiotherapy (SRT) for brain metastases is expected to have a less detrimental effect on cognition and health-related quality of life (HRQoL) than whole-brain radiotherapy (WBRT), the precise effect is largely unknown. METHODS: Cognition and HRQoL were measured prior to SRT, 3 and 6 months follow-up. Four cognitive domains and seven preselected scales of the EORTC-QLQC30 and BN20 were analysed. Survival analysis was performed and effect of total volume of bra...

  18. Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection

    OpenAIRE

    Navarria, Pierina; Pessina, Federico; Cozzi, Luca; Ascolese, Anna Maria; De Rose, Fiorenza; Fogliata, Antonella; Franzese, Ciro; Franceschini, Davide; Tozzi, Angelo; D’Agostino, Giuseppe; Comito, Tiziana; Iftode, Cristina; Maggi, Giulia; Reggiori, Giacomo; Bello, Lorenzo

    2016-01-01

    Background Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS). Methods From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1–3 cm and 32Gy/4 fractions for lesions 3.1–5 cm. L...

  19. A clinical study of metastasized rectal cancer treatment: assessing a multimodal approach

    OpenAIRE

    Jung, Michaela; Holmqvist, Annica; Sun, Xiao-Feng; Albertsson, Maria

    2014-01-01

    Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, ...

  20. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying

    2007-01-01

    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  1. Clinical efficacy of stereotactic ablative radiotherapy for lung metastases arising from colorectal cancer

    International Nuclear Information System (INIS)

    Limited data describe the prognosis after stereotactic ablative radiotherapy for lung metastases arising from colorectal cancer. Thus, we evaluated treatment outcomes of stereotactic ablative radiotherapy for those patients. The study involved patients received stereotactic ablative radiotherapy for one to three lung metastases arising from colorectal cancer at a single institution. A total dose of 40–60 Gy (median, 48 Gy) in three or four fractions was prescribed. A total of 79 metastatic lung lesions from 50 patients who underwent curative resection for their primary colorectal cancer or salvage treatment at a recurrent site were included. The one- and three-year local control rates were 88.7 % and 70.6 %, respectively. The three-year overall survival and progression-free survival rates were 64.0 % and 24.0 %, respectively. Patients with tumor volume ≤1.5 mL had a significantly better overall survival rate than those with tumor volume >1.5 mL (68.0 % vs. 60.0 % at three-year, p = 0.02). Local control was associated with a trend towards better survival (p = 0.06). No pulmonary complications greater than grade 2 were observed. Stereotactic ablative radiotherapy is a competitive treatment modality for the management of lung metastases arising from colorectal cancer

  2. 非小细胞肺癌脑转移调强放射治疗可行性研究%Feasibity study for brain metastases of non-small cell lung cancer treated with IMRT

    Institute of Scientific and Technical Information of China (English)

    王靖; 卢冰; 胡银祥; 欧阳伟炜; 苏胜发; 王刚; 龙金华; 栗蕙芹

    2013-01-01

    OBJECTIVE:To investigate the feasibility of clinical prospective study for brain metastases from non-small cell lung cancer (NSCLC) treated with intensity modulated radiotherapy (IMRT).METHODS:Thirty NSCLC untreated patients with brain metastases treated with IMRT.Through evaluating the response,quality of life before and after treatment,toxicity and normal brain tissue adjacent to the tumor dose-volume parameters,the advantages of IMRT was analyzed and compared to redesigned three-dimesional conformal radiation therapy (3D-CRT) or stereotactic radiotherapy (SRT) plans.RESULTS:Complete remission was 16.7% (5/30),partial remission was 33.3% (10/30).Minimental state examination score (all patients 25.67 ±2.73,three to five metastases patients 24.77 ±3.24) and activities of daily living score (all patients 79.00 ±14.82,three to five metastases patients 72.31 ±15.63) after treatment were higher than that before treatment(the former all patients 22.9 ±4.94,three to five metastases patients 19.23± 4.64; the later all patients 68.67 ± 19.60,three to five metastases patients 55.77 ±19.13),especially with three to five brain metastases lesions (P<0.05).Acute injury of grade Ⅱ was 10%(3/30) and late injury of grade Ⅱ,Ⅳ was in one patient.Dose volume V35 (147.56±80.77),V40 (50.86±32.33) and V45 (22.32± 15.40) in normal tissue adjacent to the brain tumor was obviously decreased in IMRT,especially within three to five metastases lesions(V35 214.56±58.09,V40 79.29 ± 22.76,V45 34.17±12.64,P<0.05).CONCLUSIONS:IMRT treatment of NSCLC brain metastases is effective and the toxicity can be tolerated.For the patients with 3-5 brain metastases lesions selecting IMRT may be a better choice.%目的:探讨调强放射治疗(intensity modulated radiation therapy,IMRT)非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移的可行性.方法:选择NSCLC脑转移初治患者30例,分析近期疗效、治疗前后生活质量和毒副作用,与重新设计

  3. Skin metastases of lung cancer:

    OpenAIRE

    Kecelj, Peter; Košnik, Mitja; Požek, Igor; Triller Vadnal, Katja; Triller, Nadja

    2008-01-01

    Skin metastases of lung cancer are rare. In over a 3-year period we found only14 cases of skin metastases among 1,614 patients with lung cancer admittedto the University Clinic of Respiratory and Allergic Diseases in Golnik. The metastases are usually manifested on the skin of the chest. Skin metastases are symptoms of progressive disease, and usually a sign of a poor prognosis. The median survival time of lung cancer patients with skin metastases was 85 days from the time of detection of the...

  4. 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)

    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

  5. Targeting SRC in glioblastoma tumors and brain metastases: rationale and preclinical studies

    OpenAIRE

    Ahluwalia, Manmeet; de Groot, John; Liu, Wei; Gladson, Candece L.

    2010-01-01

    Glioblastoma (GBM) is an extremely aggressive, infiltrative tumor with a poor prognosis. The regulatory approval of bevacizumab for recurrent GBM has confirmed that molecularly targeted agents have potential for GBM treatment. Preclinical data showing that SRC and SRC-family kinases (SFKs) mediate intracellular signaling pathways controlling key biologic/oncogenic processes provide a strong rationale for investigating SRC/SFK inhibitors, eg, dasatinib, in GBM and clinical studies are underway...

  6. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases.

    Science.gov (United States)

    Chen, Xilin; Han, Jianfeng; Chu, Jianhong; Zhang, Lingling; Zhang, Jianying; Chen, Charlie; Chen, Luxi; Wang, Youwei; Wang, Hongwei; Yi, Long; Elder, J Bradley; Wang, Qi-En; He, Xiaoming; Kaur, Balveen; Chiocca, E Antonio; Yu, Jianhua

    2016-05-10

    Breast cancer brain metastases (BCBMs) are common in patients with metastatic breast cancer and indicate a poor prognosis. These tumors are especially resistant to currently available treatments due to multiple factors. However, the combination of chimeric antigen receptor (CAR)-modified immune cells and oncolytic herpes simplex virus (oHSV) has not yet been explored in this context. In this study, NK-92 cells and primary NK cells were engineered to express the second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells, oHSV-1, and their combination were tested in vitro and in a breast cancer intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed enhanced cytotoxicity and IFN-γ production when co-cultured with breast cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also capable of lysing and destroying these cells. However, a higher cytolytic effect of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA-MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92 cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK-92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells and significantly longer survival of tumor-bearing mice when compared to monotherapies. These results demonstrate that regional administration of EGFR-CAR NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to treat BCBMs.

  7. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

    OpenAIRE

    Morinaga, Nobuhiro; Tanaka, Naritaka; Shitara, Yoshinori; Ishizaki, Masatoshi; Yoshida, Takatomo; Kouga, Hideaki; Wakabayashi, Kazuki; Fukuchi, Minoru; Tsunoda, Yoshiyuki; Kuwano, Hiroyuki

    2016-01-01

    Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. De...

  8. Clinical results of mean GTV dose optimized robotic guided SBRT for liver metastases

    International Nuclear Information System (INIS)

    We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean-dose-optimized and real-time motion-compensated robotic stereotactic body radiation therapy (SBRT) in the treatment of liver metastases. Between March 2011 and July 2015, 52 patients were treated with SBRT for a total of 91 liver metastases (one to four metastases per patient) with a median GTV volume of 12 cc (min 1 cc, max 372 cc). The optimization of mean GTV dose was prioritized during treatment planning at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The delivered median GTV biological effective dose (BED10) was 142.1 Gy10 (range, 60.2 Gy10 –165.3 Gy10) and the prescribed PTV BED10 ranged from 40.6 Gy10 to 112.5 Gy10 (median, 86.1 Gy10). We analyzed local control (LC), progression-free interval (PFI), overall survival (OS), and toxicity. Median follow-up was 17 months (range, 2–49 months). The 2-year actuarial LC, PFI, and OS rates were 82.1, 17.7, and 45.0 %, and the median PFI and OS were 9 and 23 months, respectively. In univariate analysis histology (p < 0.001), PTV prescription BED10 (HR 0.95, CI 0.91–0.98, p = 0.002) and GTV mean BED10 (HR 0.975, CI 0.954–0.996, p = 0.011) were predictive for LC. Multivariate analysis showed that only extrahepatic disease status at time of treatment was a significant factor (p = 0.033 and p = 0.009, respectively) for PFI and OS. Acute nausea or fatigue grade 1 was observed in 24.1 % of the patients and only 1 patient (1.9 %) had a side effect of grade ≥ 2. Robotic real-time motion-compensated SBRT is a safe and effective treatment for one to four liver metastases. Reducing the PTV prescription dose and keeping a high mean GTV dose allowed the reduction of toxicity while maintaining a high local control probability for the treated lesions

  9. Clinical neurorestorative progress in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Huang H

    2015-03-01

    Full Text Available Huiling Huang,1 Lin Chen,2,3 Hongyun Huang4–61Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin Neurosurgical Institute, Tianjin, People's Republic of China; 2Medical Center, Tsinghua University, Beijing, People's Republic of China; 3Tsinghua University Yuquan Hospital, Beijing, People's Republic of China; 4General Hospital of Chinese people's Armed Police Forces, 5Beijing Rehabilitation Hospital of Capital Medical University, Beijing, People's Republic of China; 6Beijing Hongtianji Neuroscience Academy, Beijing, People's Republic of ChinaAbstract: Traumatic brain injury (TBI is a leading cause of death and disability from trauma to the central nervous system. Besides the surgical interventions and symptomatic management, the conventional therapies for TBI and its sequelae are still limited. Recently emerging evidence suggests that some neurorestorative treatments appear to have a potential therapeutic role for TBI and improving the patient's quality of life. The current clinical neurorestorative strategies available in TBI include pharmacological treatments (recombinant human interleukin-1 receptor antagonist, amantadine, lithium, and valproate, the neuromodulation treatments (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and low-level laser therapy, cell transplantation (bone marrow stromal cells and umbilical cord stromal cells, and combined neurorehabilitation. In this review, we summarize the recent clinical neurorestorative progress in the management of neurodegeneration as well as cognitive and motor deficits after TBI; indeed further clinical trials are required to provide more robust evidence.Keywords: brain trauma, neurorestorative treatment, cell transplantation, clinical study

  10. Quantitative analysis of CT-perfusion parameters in the evaluation of brain gliomas and metastases

    Directory of Open Access Journals (Sweden)

    Di Nallo Anna

    2009-03-01

    Full Text Available Abstract Background The paper reports a quantitative analysis of the perfusion maps of 22 patients, affected by gliomas or by metastasis, with the aim of characterizing the malignant tissue with respect to the normal tissue. The gold standard was obtained by histological exam or nuclear medicine techniques. The perfusion scan provided 11 parametric maps, including Cerebral Blood Volume (CBV, Cerebral Blood Flow (CBF, Average Perfusion (Pmean and Permeability-surface area product (PS. Methods The perfusion scans were performed after the injection of 40 ml of non-ionic contrast agent, at an injection rate of 8 ml/s, and a 40 s cine scan with 1 s interval was acquired. An expert radiologist outlined the region of interest (ROI on the unenhanced CT scan, by using a home-made routine. The mean values with their standard deviations inside the outlined ROIs and the contralateral ROIs were calculated on each map. Statistical analyses were used to investigate significant differences between diseased and normal regions. Receiving Operating Characteristic (ROC curves were also generated. Results Tumors are characterized by higher values of all the perfusion parameters, but after the statistical analysis, only the PS, PatRsq (Patlak Rsquare and Tpeak (Time to Peak resulted significant. ROC curves, confirmed both PatRsq and PS as equally reliable metrics for discriminating between malignant and normal tissues, with areas under curves (AUCs of 0.82 and 0.81, respectively. Conclusion CT perfusion is a useful and non invasive technique for evaluating brain neoplasms. Malignant and normal tissues can be accurately differentiated using perfusion map, with the aim of performing tumor diagnosis and grading, and follow-up analysis.

  11. A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Asher, Anthony L., E-mail: asher@cnsa.com [Department of Neurosurgery, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States); Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (United States); Burri, Stuart H. [Department of Radiation Oncology, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States); Wiggins, Walter F. [Wake Forest School of Medicine MD/PhD Program, Winston-Salem, North Carolina (United States); Kelly, Renee P. [Brain Tumor Fund for the Carolinas, Charlotte, North Carolina (United States); Boltes, Margaret O.; Mehrlich, Melissa [Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (United States); Norton, H. James [Department of Biostatistics, Carolinas Medical Center, Charlotte, North Carolina (United States); Fraser, Robert W. [Department of Radiation Oncology, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States)

    2014-03-15

    Purpose: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong

  12. Brain Metastases in Patients With Germ Cell Tumors: Prognostic Factors and Treatment Options—An Analysis From the Global Germ Cell Cancer Group

    Science.gov (United States)

    Feldman, Darren R.; Lorch, Anja; Kramar, Andrew; Albany, Costantine; Einhorn, Lawrence H.; Giannatempo, Patrizia; Necchi, Andrea; Flechon, Aude; Boyle, Helen; Chung, Peter; Huddart, Robert A.; Bokemeyer, Carsten; Tryakin, Alexey; Sava, Teodoro; Winquist, Eric William; De Giorgi, Ugo; Aparicio, Jorge; Sweeney, Christopher J.; Cohn Cedermark, Gabriella; Powles, Thomas

    2016-01-01

    Purpose To define characteristics, treatment response, and outcomes of men with brain metastases (BM) from germ cell tumors (GCT). Patients and Methods Data from 523 men with BM from GCT were collected retrospectively from 46 centers in 13 countries by using standardized questionnaires. Clinical features were correlated with overall survival (OS) as the primary end point. Results BM were present at initial diagnosis in 228 men (group A) and at relapse in 295 men (group B). OS at 3 years (3-year OS) was superior in group A versus group B (48% v 27%; P < .001). Multiple BM and the presence of liver or bone metastasis were independent adverse prognostic factors in both groups; primary mediastinal nonseminoma (group A) and elevations of α-fetoprotein of 100 ng/mL or greater or of human chorionic gonadotropin of 5,000 U/L or greater (group B) were additional independent adverse prognostic factors. Depending on these factors, the 3-year OS ranged from 0% to 70% in group A and from 6% to 52% in group B. In group A, 99% of patients received chemotherapy; multimodality treatment or high-dose chemotherapy was not associated with statistically improved survival in multivariable analysis. In group B, only 54% of patients received chemotherapy; multimodality treatment was associated with improved survival compared with single-modality therapy (hazard ratio, 0.51; 95% CI, 0.36 to 0.73; P < .001), as was high-dose compared with conventional-dose chemotherapy (hazard ratio, 0.41; 95% CI, 0.24 to 0.70; P = .001). Conclusion Men with BM from GCT have poor OS, particularly if additional risk factors are present. High-dose chemotherapy and multimodality treatment seemed to improve survival probabilities in men with BM at relapse. PMID:26460295

  13. Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases

    Science.gov (United States)

    Berghoff, Anna S; Fuchs, Elisabeth; Ricken, Gerda; Mlecnik, Bernhard; Bindea, Gabriela; Spanberger, Thomas; Hackl, Monika; Widhalm, Georg; Dieckmann, Karin; Prayer, Daniela; Bilocq, Amelie; Heinzl, Harald; Zielinski, Christoph; Bartsch, Rupert; Birner, Peter; Galon, Jerome; Preusser, Matthias

    2016-01-01

    The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density (p > 0.05). TIL density was not associated with corticosteroid administration (p > 0.05). A significant difference in infiltration density according to TIL subtype was present (p < 0.001; Chi Square); high infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%; p < 0.001). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). The density of CD8+ TILs correlated positively with the extent of peritumoral edema seen on pre-operative magnetic resonance imaging (p = 0.031). The density of CD3+ (15 vs. 6 mo; p = 0.015), CD8+ (15 vs. 11 mo; p = 0.030) and CD45RO+ TILs (18 vs. 8 mo; p = 0.006) showed a positive correlation with favorable median OS times. Immunoscore showed significant correlation with survival prognosis (27 vs. 10 mo; p < 0.001). The prognostic impact of Immunoscore was independent from established prognostic parameters at multivariable analysis (HR 0.612, p < 0.001). In conclusion, our data indicate that dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and survival prognosis, thus identifying the immune system as potential biomarker for cancer patients with CNS affection. Further studies are needed to substantiate our findings. PMID:26942067

  14. Stereotactic Radiosurgery for Melanoma Brain Metastases in Patients Receiving Ipilimumab: Safety Profile and Efficacy of Combined Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Kiess, Ana P. [Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (United States); Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolchok, Jedd D. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Christopher A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Tabar, Viviane [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Huse, Jason T. [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A.; Yamada, Yoshiya [Department of Radiation Oncology, 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)

    2015-06-01

    Purpose: Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials: From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results: Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients. Conclusion: Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly

  15. Dural metastases from disseminated prostate cancer clinically mimicking a benign reactive condition of the dura: case report and review of the literature.

    Science.gov (United States)

    Gunia, S; Ecke, T; Wohlfarth, B; Koch, S; Erbersdobler, A

    2011-01-01

    Dural spread from prostate cancer (PC) is exceedingly uncommon. We report on a 62-year-old man suffering from disseminated PC with osseous metastases who presented with a parietal skull metastasis along with a circumscribed nodular thickening of the adjacent dura. Magnetic resonance imaging findings suggested a benign reactive condition of the dura which, however, histologically turned out to be a dural metastasis. Therefore, the present case report stresses the notion that very rarely, disseminated PC might present with clinically unsuspected dural metastases radiologically mimicking a benign condition.

  16. STUDY ABOUT CLINICAL APPLICATION OF BRAIN ATLAS IN PAEDIATRICS

    Institute of Scientific and Technical Information of China (English)

    MENG Fanhang; LIU Cuiping; RENG Xiaoping; JIANG Lian

    2002-01-01

    Objectives To explore clinical application on brain atlas in paediatrics. Methode: Brain atlas was applied in diagnosis and treatment of paediatric diseases and its clinical value was discussed in 1990 ~2001. The manifestation of these diseases in brain atlas were analysed and the manifestation of CT of 67 cases and manifestations of EEG of 37 cases with that of BA were compared. Results The changes of cerebral electrical activity of these diseases were reflected objectively and showed directly in BA. Conclusion Brain atlas not only can point out quality of disease but also define position of disease. Therefore, brain atlas has important clinical value in paediatrics.

  17. Postoperative ectopic pregnancy with choriocarcinoma of brain metastases(a report of 1 case and review of literature)%异位妊娠术后绒癌脑转移1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    刘东媛; 曾小君; 孙彦辉; 汪向红; 刘妮英; 范妮娜; 王丹; 张红波; 陈小奇; 穆林森; 张锦

    2014-01-01

    Objective To report one case of postoperative ectopic pregnancy with choriocarcinoma of brain metastases and rexiew the literature .Methods Combined with gynecological ,neurological,pathology and imaging examination the results clearly confirmed choriocarcinoma .By undergone emergency ectopic pregnancy laparoscopic surgery to remove the lesion Oviduct and Gestational sac ,the postoperative pathology showed normal embryos .The follow up from 6 to 12 months showed a case was diagnosed brain metastases by craniotomy and pathological reports showed as choriocarcinoma .Lumbar puncture methotrexate chemotherapy , dehydration , hormones and other symptomatic treatment were underwent .Results The patients ’ symptoms improved and no recurrent lesions were followed up for 6 months.Conclusions The postoperative ectopic pregnancy with choriocarcinoma of brain metastases occurrs in childbearing women age with atypical clinical manifestations and high misdiagnosis . Chemotherapy combined therapy may improve symptoms in postoperative .%目的:报告1例异位妊娠术后绒癌脑转移瘤的病例并回顾文献。方法通过妇科及神经系统检查,病理及影像学结果确诊绒癌。急诊行腹腔镜下异位妊娠手术,切除孕囊及病变侧输卵管,术后病理示正常胚胎。术后随访6~12个月1例发生脑转移,予以开颅手术,病理报告绒癌。术后腰穿甲氨蝶呤化疗、脱水、激素等对症治疗。结果患者术后症状改善,随访6个月未见病变复发。结论异位妊娠术后发生绒癌脑转移瘤可见于育龄妇女,临床表现不典型,误诊率高。术后化疗为主的综合治疗可改善患者症状。

  18. Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy?

    Directory of Open Access Journals (Sweden)

    Valeria Barresi

    2014-04-01

    Full Text Available Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD, a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p = 0.0043; p = 0.0063. Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA positive pericytes (r = −0.693; p < 0.0001. Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should

  19. Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

    Energy Technology Data Exchange (ETDEWEB)

    Lucas, John T., E-mail: jolucas@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Colmer, Hentry G.; White, Lance [Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Fitzgerald, Nora; Isom, Scott [Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Bourland, John D. [Department of Radiation Oncology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina (United States); Laxton, Adrian W. [Department of Neurosurgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina (United States); Tatter, Stephen B. [Department of Neurosurgery, 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)

    2015-08-01

    Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model. Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultant model was converted into an online calculator for ease of clinical use. Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death. Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.

  20. Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

    International Nuclear Information System (INIS)

    Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model. Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultant model was converted into an online calculator for ease of clinical use. Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death. Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes

  1. A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

    Energy Technology Data Exchange (ETDEWEB)

    Sperduto, Paul W., E-mail: psperduto@mropa.com [Metro MN CCOP, Minneapolis, Minnesota (United States); Wang, Meihua [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Robins, H. Ian [University of Wisconsin Medical School Cancer Center, Madison, Wisconsin (United States); Schell, Michael C. [Wilmot Cancer Center, University of Rochester, Rochester, New York (United States); Werner-Wasik, Maria [Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Souhami, Luis [McGill University, Montreal, Quebec (Canada); Buyyounouski, Mark K. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Khuntia, Deepak [University of Wisconsin Hospital, Madison, Wisconsin (United States); Demas, William [Akron City Hospital, Akron, Ohio (United States); Shah, Sunjay A. [Christiana Care Health Services, Inc, CCOP, Newark, Delaware (United States); Nedzi, Lucien A. [University of Texas Southwestern Medical School, Dallas, Texas (United States); Perry, Gad [The Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada); Suh, John H. [Cleveland Clinic Foundation, Cleveland, Ohio (United States); Mehta, Minesh P. [Northwestern Memorial Hospital, Chicago, Illinois (United States)

    2013-04-01

    Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

  2. 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)

    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.)

  3. 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.)

  4. Lung metastases

    Science.gov (United States)

    Metastases to the lung; Metastatic cancer to the lung ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs) and spread through the ...

  5. Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

    Energy Technology Data Exchange (ETDEWEB)

    Prabhu, Roshan; Shu, Hui-Kuo [Department of Radiation Oncology, Emory University, Atlanta, GA (United States); Winship Cancer Institute, Emory University, Atlanta, GA (United States); Hadjipanayis, Constantinos [Winship Cancer Institute, Emory University, Atlanta, GA (United States); Department of Neurosurgery, Emory University, Atlanta, GA (United States); Dhabaan, Anees; Hall, William [Department of Radiation Oncology, Emory University, Atlanta, GA (United States); Winship Cancer Institute, Emory University, Atlanta, GA (United States); Raore, Bethwel; Olson, Jeffrey [Winship Cancer Institute, Emory University, Atlanta, GA (United States); Department of Neurosurgery, Emory University, Atlanta, GA (United States); Curran, Walter [Department of Radiation Oncology, Emory University, Atlanta, GA (United States); Winship Cancer Institute, Emory University, Atlanta, GA (United States); Oyesiku, Nelson [Winship Cancer Institute, Emory University, Atlanta, GA (United States); Department of Neurosurgery, Emory University, Atlanta, GA (United States); Crocker, Ian, E-mail: icrocke@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, GA (United States); Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2012-05-01

    Purpose: To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Methods and Materials: Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm{sup 3}. Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planning target volume expansion of {>=}1 mm. Results: Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if {>=}90% of recurrence within the prescription isodose and marginal if {>=}90% outside of the prescription isodose). Conclusions: The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.

  6. Risk factors for brain metastases of patients with breast cancer%乳腺癌脑转移患者危险因素分析

    Institute of Scientific and Technical Information of China (English)

    曲明阳; 李森; 赵胜男; 邢光明

    2011-01-01

    Objective To determine the risk factors of brain metastases of patients with breast cancer. Methods Follow-up surveys were carried out in the patients with breast cancer who were treated at our hospital from 1997 to 2007. Of the patients, 133 cases having brain metastasis were considered as the study group and the other 145 cases without brain metastasis served as the control group. The factors related to brain metastasis were comparatively analyzed. Results The likelihood of brain metastasis of patients with breast cancer was increased in the conditions of histological grade 3 , tumor diameter more than 5 cm, estrogen receptor (ER) negative and human epidermal growth factor receptor 2 ( HER-2 ) positive. Other factors, including tumor stage, histological classification, progesterone receptor ( PR ) status, presence or absence of axillary lymph node metastases and menopausat status, were not obviously related to brain metastasis. Conclusions Histological grade, tumor size and HER-2 status are independent risk factors for breast cancer brain metastasis, while ER may be an independent protective factor against breast cancer brain metastasis.%目的 探讨影响乳腺癌脑转移的危险因素.方法 对1997-2007年收治的乳腺癌患者进行随访,以发生脑转移的133例患者作为脑转移组,以未发生脑转移的145例患者作为对照组,就脑转移的相关因素进行对照分析.结果 组织学分级为3级,肿瘤长径大于5 cm,雌激素受体(ER)阴性,人表皮生长因子受体(HER-2)阳性的乳腺癌患者容易发生脑转移;肿瘤分期,病理类型,孕激素受体(PR),腋窝淋巴结转移情况及绝经与否与脑转移无关(P>0.05).结论 组织学分级,肿瘤大小,HER-2是乳腺癌患者发生脑转移的独立危险因子;ER可能是乳腺癌脑转移的独立保护因子.

  7. X-ray stereotactic radiosurgery for brain metastases%X线立体定向放射治疗脑转移瘤的疗效分析

    Institute of Scientific and Technical Information of China (English)

    张可领; 肖作平; 刘永明; 伏少华

    2001-01-01

    目的观察立体定向放射手术治疗脑转移瘤的疗效。方法 X线立体定向放射治疗脑转移瘤患者47例,采用10MV 的直线加速器多个非共面弧旋转照射,肿瘤剂量为18~25Gy(平均22.1Gy)。40例患者在术后接受了肿瘤剂量30~40Gy的全脑放疗。结果中位生存期为11个月,1年生存率37.5%,疗后3个月的肿瘤控制率为90.7%,KPS≥70、原发肿瘤已控和无颅外转移患者的预后较好(P<0.05)。结论立体定向放射治疗脑转移瘤是安全和有效的。%Objective To evaluate the effectiveness of X-ray stereotactic radiosurgery (SRS) for brain metastases.Methods Retrospective analysis of 47 patients with brain metastases who underwent SRS un der a 10 MV linear accelerator was carried out.Tumor diameter varied from 12 mm t o 40 mm (mean 27mm ).Tumor dose varied from 18~25Gy (mean 22.1Gy).Fractionated whole brain ra diotherapy was delivered to 40 patients after SRS.32 patients were examined by CT and (or) MRI.Results Median survival from SRS was 11 months.Tumor control rate was 90.7% after SRS.Tu mor complete response rate was 68.8%.Tumor recurrence was found by CT or MRI.The re was longer survival in KPS≥70,primary tumor was controlled and no extracrani al metastases was found.The main complication was brain edema(18.8%).Conclusion The results of this report shows that SRS is an effective and safe treatment option.

  8. Assessment of Local Control after Laser-Induced Thermotherapy of Liver Metastases from Colorectal Cancer: Contribution of FDG-PET in Patients with Clinical Suspicion of Progressive Disease

    Energy Technology Data Exchange (ETDEWEB)

    Denecke, T.; Steffen, I.; Hildebrandt, B.; Ruehl, R.; Streitparth, F.; Lehmk uhl, L.; Langrehr, J.; Ricke, J.; Amthauer, H.; Lopez Haenninen, E. [Klinik fuer Strahlenheilkunde, Bereiche Radiologie und Nuklearmedizin, Medizinische Klinik mit Schwerpunkt Haematologie Onkologie, and Klinik fuer Allgemein-, Viszeral-, und T ransplantationschirurgie, Campus Virchow-Klinikum, Charite - Universitaetsmedizi n Berlin, (Germany)

    2007-10-15

    Background: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with {sup 18}F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Purpose: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. Material and Methods: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semi quantitatively (maximal standard uptake value [SUVmax], tumor-to-normal ratio [T/N]). The standard of reference was histopathology (n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. Results: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUVmax (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients (P = 0.007). Conclusion: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with

  9. Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer. Evaluation of indications and predictors of local control

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Takeaki [Kobe University Graduate School of Medicine, Division of Radiation Oncology, Hyogo (Japan); Seirei Mikatahara General Hospital, Department of Radiation Oncology, Shizuoka (Japan); Yamada, Kazunari; Isogai, Kenta; Tonosaki, Yoshihiro [Seirei Mikatahara General Hospital, Department of Radiation Oncology, Shizuoka (Japan); Harada, Aya [Kobe Minimum Invasive Cancer Medical Center, Department of Radiation Oncology, Hyogo (Japan); Demizu, Yusuke [Hyogo Ion Beam Medical Center, Department of Radiology, Hyogo (Japan); Miyawaki, Daisuke; Yoshida, Kenji; Ejima, Yasuo; Sasaki, Ryohei [Kobe University Graduate School of Medicine, Division of Radiation Oncology, Hyogo (Japan)

    2016-06-15

    To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs) from lung cancer, and to explore prognostic factors associated with local control (LC) and indication. We evaluated patients who were treated with linac-based HSRT for BMs from lung cancer. Lesions treated with stereotactic radiosurgery (SRS) in the same patients during the same periods were analysed and compared with HSRT in terms of LC or toxicity. There were 53 patients with 214 lesions selected for this analysis (HSRT: 76 lesions, SRS: 138 lesions). For HSRT, the median prescribed dose was 35 Gy in 5 fractions. The 1-year LC rate was 83.6 % in HSRT; on multivariate analysis, a planning target volume (PTV) of <4 cm{sup 3}, biologically effective dose (BED{sub 10}) of ≥51 Gy, and adenocarcinoma were significantly associated with better LC. Moreover, in PTVs ≥ 4 cm{sup 3}, there was a significant difference in LC between BED{sub 10} < 51 Gy and ≥ 51 Gy (p = 0.024). On the other hand, in PTVs < 4 cm{sup 3}, both HSRT and SRS had good LC with no significant difference (p = 0.195). Radiation necrosis emerged in 5 of 76 lesions (6.6 %) treated with HSRT and 21 of 138 (15.2 %) lesions treated with SRS (p = 0.064). Linac-based HSRT was safe and effective for BMs from lung cancer, and hence might be particularly useful in or near an eloquent area. PTV, BED{sub 10}, and pathological type were significant prognostic factors. Furthermore, in BMs ≥ 4 cm{sup 3}, a dose of BED ≥ 51 Gy should be considered. (orig.) [German] Beurteilung von Wirksamkeit und Toxizitaet einer hypofraktionierten stereotaktischen Strahlentherapie (HSRT) zur Behandlung von Hirnmetastasen (HM) eines Lungenkarzinoms und Erforschung von mit der lokalen Kontrolle (LK) und der Indikation assoziierten Prognosefaktoren. Analysiert wurden Daten von Patienten (n = 53), die sich einer Linearbeschleuniger-basierten HSRT unterzogen (mit HSRT behandelte Laesionen n = 76; Median der

  10. Injection of recombinant tumor necrosis factor directly into liver metastases: an experimental and clinical approach

    NARCIS (Netherlands)

    J.N.M. IJzermans (Jan); M. Scheringa (Marcel); G. van der Schelling; R.A. Geerling; R.L. Marquet (Richard); J. Jeekel (Hans)

    1992-01-01

    markdownabstract__Abstract__ Systemic treatment with tumor necrosis factor (TNF) is associated with side-effects, limiting its clinical use in the treatment of malignancies. To investigate the feasibility of other routes of administration experimental and clinical studies were started to establish

  11. Cerebral metastases--a therapeutic update.

    Science.gov (United States)

    Cavaliere, Robert; Schiff, David

    2006-08-01

    Cerebral metastases remain a common complication among patients with cancer. Historically, whole-brain radiotherapy has remained the standard of care, with surgery being reserved for selected cases. Recent advances have changed our practice, however. In particular, stereotactic radiosurgery has emerged as a vital treatment modality for this disease. In addition, chemotherapy, including temozolomide, topoisomerase inhibitors and antimetabolites, and treatment sensitizers, such as efaproxiral and motexafin gadolinium, are actively being assessed in clinical trials, and are likely to play an increasing role in the management of cerebral metastases in the future. Nonetheless, many uncertainties remain, such as the optimal combination and timing of therapeutics. As the arsenal of therapeutics expands, it will be increasingly important to select appropriate patients for a particular treatment paradigm. Understanding the efficacy and toxicity of treatment is essential to this task. PMID:16932601

  12. 替莫唑胺联合放疗治疗脑转移瘤的疗效评价%Evaluation of the Efficacy of Radiotherapy Concurrent Temozolomide Chemotherapy in Brain Metastases Patients

    Institute of Scientific and Technical Information of China (English)

    邹育超

    2014-01-01

    Objective :To investigate the the efficacy of radiotherapy concurrent Temozolomide chemotherapy in Brain metastases patients .Methods :Sixty Brain metastases patients were selected and divided into 2 groups each group with 30 patients :A group was treated by radiotherapy alone ,including whole brain radiotherapy (WBRT) and stereotatic radiotherapy (SRT) ,and B group was treated by radiotherapy concurrent Temozolomide chemotherapy .The clinical ef‐ficacy was evaluated by WHO solid tumors using clinical efficacy evaluation criteria ,and efficiency and disease control rate were calculated .The complication during the therapy including headache ,nausea and vomiting ,bone marrow sup‐pression ,liver damage ,kidney damage ,mortality were compared .Results:(1)There were no significant differences of age ,weight ,sex ratio and pathological type of the primary tumor between the 2 groups (P>0 .05) .(2)Compared with A group ,the complete remission rate (CR) ,response rate (RR) ,disease control rate (DCR) were significantly higher than those in A group (P0 .05) .Conclusion:Radiother‐apy concurrent Temozolomide chemotherapy was safe and efficient in Brain metastases patients and worthy of clinical application .%目的:探讨替莫唑胺联合放疗治疗脑转移瘤的临床疗效。方法:选择我院放疗科住院的脑转移瘤患者60例,随机分为两组:单纯放疗组(包括全脑放射治疗+立体定向放射治疗,A组)、替莫唑胺联合放疗组(B组)每组30例。采用WHO实体瘤评价标准比较两组的临床疗效,并计算有效率和疾病控制率;同时比较两组不良反应(头痛、恶心、呕吐、骨髓抑制、肝功能损害、肾功能损害等)的发生率和死亡率。结果:(1)两组患者年龄、体重、身高、性别比以及原发肺癌病理类型的比较均无显著差异(P>0.05);(2)B组治疗后完全缓解率、治疗有效率、疾病控制率均比A组明显改善(P<0

  13. 根治性治疗后非小细胞肺癌的预防性脑照射%Prophylactic Cranial Irradiation for Preventing Brain Metastases in Patients Undergoing Radical Treatment for Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    李伟雄; 黄玉娟

    2008-01-01

    @@ 1 文献来源 Lester JF,Coles B,Macbeth FR.Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small cell lung cancer[DB/CD].The Cochrane Library 2007,Issue 3.

  14. Comparison of the effectiveness of whole-brain radiotherapy plus temozolomide versus whole-brain radiotherapy in treating brain metastases based on a systematic review of randomized controlled trials.

    Science.gov (United States)

    Bai, Gui-Rong; An, Jin-Bing; Chu, Yang; Wang, Xiang-Yang; Li, Shu-Ming; Yan, Kai-Jing; Lü, Fu-Rong; Gu, Ning; Griffin, Amanda N; Sun, Bin-Yuan; Li, Wei; Wang, Guo-Cheng; Zhou, Shui-Ping; Sun, He; Liu, Chang-Xiao

    2016-01-01

    Temozolomide (TMZ) combination with whole-brain radiotherapy (WBRT) has been tested by many randomized controlled trials in the treatment of brain metastases (BMs) in China and other countries. We performed an up-to-date meta-analysis to determine (i) the log odds ratios (LORs) of objective response (ORR) and adverse effects (AEs) for all-grade, and (ii) the T value of mean overall survival in patients with BMs treated with WBRT combined with TMZ versus WBRT alone. PubMed, Chinese National Knowledge Infrastructure, and WanFang Data were searched for articles published up to 28 January 2015. Eligible studies were selected according to the PRISMA statement. ORR, AEs, and 95% confidence intervals were calculated using random-effects models. Eighteen studies were included in our analysis. A total of 1028 participants were enrolled. Summary LORs of ORR were 1.0239 (Pimproves the ORR and is statistically insignificant in prolonging the survival of patients with BMs. In addition, an increase in the incidence of gastrointestinal toxicity and myelosuppression was significant for all-grade. PMID:26426520

  15. Radiotherapy for asymptomatic brain metastasis in epidermal growth factor receptor mutant non-small cell lung cancer without prior tyrosine kinase inhibitors treatment: a retrospective clinical study

    International Nuclear Information System (INIS)

    Non-small cell lung cancer (NSCLC) with brain metastasis (BM) harboring an epidermal growth factor receptor (EGFR) mutation shows good response to tyrosine kinase inhibitors (TKIs). This study is to assess the appropriate timing of brain radiotherapy (RT) for asymptomatic BM in EGFR mutant NSCLC patients. There were 628 patients diagnosed with EGFR mutant NSCLC between October 2005 and December 2011. Treatment outcomes had been retrospectively evaluated in 96 patients with asymptomatic BM without prior TKI treatment. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT. With a median follow-up of 26 months, the 2-year OS was 40.6 %. Univariate analyses revealed that ECOG performance status (p = 0.006), other distant metastases (p = 0.002) and first line systemic treatment (p = 0.032) were significantly associated with overall survival (OS). Multivariate analyses revealed that other sites of distant metastases (p = 0.030) were prognostic factor. The timing of brain RT was not significantly related to OS (p = 0.246). The 2-year BM progression-free survival (PFS) was 26.9 %. Brain RT as first-line therapy failed to demonstrate a significant association with BM PFS (p = 0.643). First-line brain RT failed to improve long-term survival in TKI-naïve EGFR mutant NSCLC patients with asymptomatic BM. Prospective studies are needed to validate these clinical findings

  16. Clinical impact of different detection methods for disseminated tumor cells in bone marrow of patients undergoing surgical resection of colorectal liver metastases: a prospective follow-up study

    International Nuclear Information System (INIS)

    Large number of patients with colorectal liver metastasis show recurrent disease after curative surgical resection. Identification of these high-risk patients may guide therapeutic strategies. The aim of this study was to evaluate whether the presence of disseminated tumor cells in bone marrow from patients undergoing surgical resection of colorectal liver metastases can predict clinical outcome. Sixty patients with colorectal liver metastases were planned for a curative resection between 2001 and 2007. All patients underwent bone marrow aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC) combined with automated microscopy or indirectly using reverse transcription-polymerase chain reaction (RT-PCR). Disseminated tumor cells were found in 15 of the 46 patients (33%) using CK-ICC and in 9 of 44 of the patients (20%) using RT-PCR. Patients with negative results for RT-PCR had a significant better disease-free survival after resection of their liver metastases (p = 0.02). This group also showed significant better overall survival (p = 0.002). CK-ICC did not predict a worse clinical outcome. The presence of disseminated tumor cells in bone marrow detected using RT-PCR did predict a worse clinical outcome. The presence of cells detected with CK-ICC did not correlate with poor prognosis

  17. 三维适形放疗配合全脑照射治疗脑转移瘤的疗效观察%The effects of three-dimensional conformal radiotherapy combined with whole brain irradiation on brain metastases

    Institute of Scientific and Technical Information of China (English)

    Jin Hu; Yeqing Zhou; Mi Liu

    2009-01-01

    Objective: To observe the recently therapeutic effects and toxicity of three-dimensional conformal radiotherapy combined with whole brain irradiation for patients with brain metastasis. Methods: 33 cases were treated by whole brain irradiation at first, the dose of which was 36-40 Gy (18-20 f). Then three-dimensional conformal radiotherapy was added to the focus with a total dose of 20-25 Gy, whose fractionated dose was 2-5 Gy/time, 5 times/week or 3 times/week. Results: Within 1 month after radiotherapy, according to imaging of the brain, the CR of all patients was 45.5%, PR 36.4%, NC 15.1%, and PD 3%. For the 32 cases with neural symptoms before radiation, the CR of the symptoms was 40.6% and PR 59.4%. All patients gained different increases in KPS grade. By the end of the follow-up period, there were 22 deaths with the mean survival time up to 9.3 months. Conclusion: Three-dimensional conformal radiotherapy combined with whole brain irradiation can not only effectively control brain metastases and improve life quality, but also tends to prolong survival time.

  18. Distribution pattern of lymph node metastases and its implication in individualized radiotherapeutic clinical target volume delineation of regional lymph nodes in patients with stage IA to IIA cervical cancer

    International Nuclear Information System (INIS)

    To study the distribution pattern of lymph node metastases of stage IA to IIA cervical cancer and to clarify the individualized clinical target volume delineation of regional lymph nodes (CTVn). A total of 665 cases with International Federation Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The clinicopathological factors related to lymph node metastases were analyzed using logistic regression analysis. Pelvic lymph node metastases were found in 168 of 665 patients resulting in a metastasis rate of 25.3%. Binary logistic regression analysis showed that age, lymph vascular space involvement, and deep stromal invasion statistically influenced pelvic lymph node metastases (p = 0.017, < 0.001, < 0.001, respectively). Pathological morphology type, lymph node metastases of the obturator, the external iliac and internal iliac, and the para-aortic had a strong influence on lymph node metastases of the common iliac (p = 0.022, 0.003, < 0.001, 0.009, respectively). Tumor size and lymph node metastases of the common iliac were significantly related to lymph node metastases of the para-aortic (p = 0.045, < 0.001, respectively). Lymph node metastases of the obturator, the external iliac and internal iliac were strongly correlated to lymph node metastases of the circumflex iliac node distal to the external iliac node (CINDEIN; p = 0.027, 0.024, respectively). Factors related to lymph node metastases should be comprehensively considered to design and tailor CTVn for radiotherapy of cervical cancer. Selective regional irradiation including the correlated lymphatic drainage regions should be performed

  19. The role of radiotherapy in patients with brain metastasis

    International Nuclear Information System (INIS)

    Brain metastases are the most frequent metastatic neurologic complication of systemic cancer. Even if the prognosis of brain metastases is grave, with available treatments, most patients experience effective palliation of neurologic symptoms and meaningful extension of life. We evaluated the clinical features and prognostic factors of the patients who were diagnosed as solid tumors with brain metastasis and received radiotherapy for brain metastases. Between January 1987 and January 1998, 71 patients with brain metastases from solid malignancy were included. We reviewed neurologic symptoms and signs of patients and evaluated improvement of neurologic symptoms and signs. Survival durations after brain metastasis were analysed according to several factors such as age, performance status, primary malignancies, the presence of brain metastasis at initial diagnosis of primary tumor, multiplicity of brain metastases, the presence of metastases other than brain, and treatment method. Frequent symptoms associated with brain metastasis were headache (47.9%), motor weakness (40.8%), nausea and vomiting (19.7%) and mental change (19.7%). Palliation of these symptoms was accomplished in 64.9% of cases. The overall median survival time was 16 weeks and 1- and 2-year survival rates were 15.0% and 5.1 % respectively. Patients without extra cranial metastases (n==27) had longer median survival than patients with extracranial metastases (33 weeks vs 10 weeks, P=(WJ18). In patients with single brain metastasis (n=37), the median survival time was longer in patients treated with surgery plus radiotherapy than in patients treated with radiotherapy alone (40 weeks vs 16 weeks, p=O.0438L Patients who has. brain metastases only constitute a prognostically favorable group and they may be benefited from radiotherapy and surgery if indicated

  20. A multichannel time-domain brain oximeter for clinical studies

    Science.gov (United States)

    Contini, Davide; Spinelli, Lorenzo; Caffini, Matteo; Cubeddu, Rinaldo; Torricelli, Alessandro

    2009-07-01

    We developed and optimized a multichannel dual-wavelength time-domain brain oximeter for functional studies in the clinical environment. The system, mounted on a 19"-rack, is interfaced with instrumentation for monitoring physiological parameters and for stimuli presentation.

  1. Preliminary clinical study of 89Sr in palliation in painful skeletal metastases

    International Nuclear Information System (INIS)

    According to the requirements of department of special drug, bureau of drug administration, Chinese Ministry of Health, the safety and efficiency of metastron injection solution imported from the Amersham Company, U.K. were tested. 27 patients were treated with metastron for metastatic bony pain (MBP). 2 cases were excluded by interrupted follow-up, the other 25 cases with metastatic prostate carcinoma, lung cancer, breast cancer were evaluated in a standard quantitative pain measurement before the treatment.Pain scores of these patients were between 6 - 16. 1.48 MBq/kg metastron was given intravenous. All the patients were observed at least 3 months. Pain score, immediate adverse reaction were observed . Results shown that clinical significant metastatic pain relief can be observed in most patients. Total efficiency was 72%, patients' life quality have been improved. There was mild decrease of white blood cell in 32% and platelet counts in 60% patients, but can recovered in most patients temporary except 1. In this case liver function abnormal was also appeared. Significant increased pain (flare) occurred in 55.5% patients after the injection, the flare up pain had been lasting 3 - 7 days, only one lasting more than 20 days. It was concluded that 89Sr is most effective in palliative therapy for MBP in-patient with prostate or breast carcinoma. In 94.4 % patients, the pain relief can lasted more than 3 months, but only one patient for 2 months. 7 cases had repeated the bone scan after therapy, but no significant changes can be observed. There by 89 Sr was safe and effective for the treatment of MBP

  2. Clinical and ethical perspectives on brain death

    OpenAIRE

    Nair-Collins, Michael

    2015-01-01

    Michael Nair-Collins Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, USA Abstract: Death determined by neurological criteria, or brain death, is an accepted legal standard for death throughout much of the world. However, brain death has also been a source of controversy ever since its inception, and recently it has been subjected to increased scrutiny, both in academia and in the public domain. The purpose of this paper is to provide an...

  3. Stromal expression of heat-shock protein 27 is associated with worse clinical outcome in patients with colorectal cancer lung metastases.

    Directory of Open Access Journals (Sweden)

    Thomas Schweiger

    Full Text Available Pulmonary metastases are common in patients with primary colorectal cancer (CRC. Heat-shock protein 27 (Hsp27 is upregulated in activated fibroblasts during wound healing and systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs are also thought to play a role as prognostic and predictive markers in various malignancies including CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. Therefore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical implications in patients with CRC lung metastases.FFPE tissue samples from 51 pulmonary metastases (PMs and 33 paired primary tumors were evaluated for alpha-SMA, CD31, Hsp27 and vimentin expression by immunohistochemistry and correlated with clinicopathological variables. 25 liver metastases served as control group. Moreover, serum samples (n=10 before and after pulmonary metastasectomy were assessed for circulating phospho-Hsp27 and total Hsp27 by ELISA.Stromal expression of Hsp27 was observed in all PM and showed strong correlation with alpha-SMA (P<0.001 and vimentin (P<0.001. Strong stromal Hsp27 was associated with higher microvessel density in primary CRC and PM. Moreover, high stromal Hsp27 and αSMA expression were associated with decreased recurrence-free survival after pulmonary metastasectomy (P=0.018 and P=0.008, respectively and overall survival (P=0.031 and P=0.017, respectively. Serum levels of phospho- and total Hsp27 dropped after metastasectomy to levels comparable to healthy controls.Herein we describe for the first time that Hsp27 is highly expressed in tumor stroma of CRC. Stromal α-SMA and Hsp27 expressions correlate with the clinical outcome after pulmonary metastasectomy. Moreover, serum Hsp27 might pose a future marker for metastatic disease in CRC.

  4. MRI-guided laser-induced thermotherapy (LITT) of liver metastases: clinical evaluation; MR-gesteuerte laserinduzierte Thermotherapie (LITT) von Lebermetastasen: Klinische Evaluierung

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Weinhold, N. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Mueller, P. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Mack, M. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Scholz, W. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Philipp, C. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Roggan, A. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany); Felix, R. [Strahlenklinik und Poliklinik, Virchow-Klinikum, Medizinische Fakultaet, Humboldt-Univ., Berlin (Germany)

    1996-07-01

    The goal was to perform an evaluation of MRI-guided laser-induced thermotherapy (LITT) of liver metastases as a clinical method. In a prospective study, 50 patients with liver metastases of colorectal carcinoma (35 patients), or other primary tumors (15 patients) were treated with LITT. For preparation and intermittent controls of therapy, standardized MRI examinations were made. Online monitoring during the the LITT was done with temperature-sensitive T1-weighted sequences (FLASH-2D, TurboFLASH). All in all, 83 metastases of a volume between 1 and 282 cubic centimeters (median = {+-} 10 cm{sup 3}) were treated.During performance of the LITT, a decrease of signal intensity in the thermosensitive sequences was measured for the application area, and was correlated with fluorine-optical temperature measurements. The MRI-guided LITT is a novel, potential modality for treatment of liver metastases, and poses only minimal clinical risks. (orig./VHE) [Deutsch] Ziel: Evaluierung der MR-gesteuerten laserinduzierten Thermotherapie (LITT) von Lebermetastasen im klinischen Einsatz. Material und Methodik: Im Rahmen einer prospektiven Studie wurden 50 Patienten mit Lebermetastasen kolorektaler Karzinome (35 Patienten) und anderer Primaertumoren (15 Patienten) mittels LITT behandelt. Zur Vorbereitung und Verlaufskontrolle der Therapie wurden standardisierte MRT-Untersuchungen vorgenommmen. Das On-Line Monitoring waehrend der LITT wurde mit temperatursensitiven T1-gewichteten Sequenzen (FLASH-2D, TurboFLASH) durchgefuehrt. Es wurden 83 Metastasen mit einem Volumen von 1 bis 282 cm{sup 3} (Median = {+-} 10 cm{sup 3}) therapiert. Waehrend der LITT wurde im Applikationsbereich eine Signalintensitaetsabnahme in den thermosensitiven Sequenzen dokumentiert und mit fluoroptischer Temperaturmessung korreliert. Schlussfolgerung: Die MR-gesteuerte LITT stellt eine neue potente Therapieform fuer Lebermetastasen dar und kann mit klinisch minimalem Risiko eingesetzt werden. (orig./VHE)

  5. P08.11SURGICAL MANAGEMENT OF BRAIN METASTASES FROM LUNG ADENOCARCINOMA: A SINGLE CENTER EXPERIENCE AND REFLECTIONS ON MULTIPLE LESIONS

    Science.gov (United States)

    Fornaro, R.; Agnoletti, A.; Specchia, F.M. Calamo; Garbossa, D.; Lanotte, M.; Ducati, A.

    2014-01-01

    INTRODUCTION: Metastases are the most common intracerebral tumors, and they're expected to increase in the next years. Prognosis is linked to the progression of systemic and cerebral disease. Among patients in good conditions, removal of the cerebral metastasis represents the first treatment to apply. To evaluate the ideal conditions for surgery and its results we performed this single-center study on patients with solitary and multiple cerebral metastases. MATERIALS AND METHODS: We analyzed patients treated for cerebral metastasis between January 2004 and 2011. We considered only cases with non-small cell lung carcinoma (NSCLC) as primary tumor. We collected mortality and complication rates and analyzed the early outcomes before adjuvant therapy. Finally we used a χ2 test (p = 0.05) to assess if better early outcomes (improved or stable KPS) were significantly related to the presence of solitary VS multiple lesions. RESULTS: Our series included 199 patients; mean survival was 11.08 months. 95 patients harbored a single brain metastasis (Group 1) and 104 had more than one localization (Group 2). 67 patients underwent surgical operation. The mean pre-operative KPS was 75/100 in Group 1 and 65/100 in Group 2. After surgery in Group 1 the score improved in 69% of patients, was unchanged in 20% and worsened in 11%. In Group 2 the post-operative KPS was increased in 66% of cases, unchanged in 17% and worsened in 17% of cases. Statistical analysis did not show significant differences in the rates of good (KPS improved or stable) and poor outcomes in the two groups of operated patients. Patients with lesions in the posterior fossa improved after surgery more than those with supratentorial metastases. DISCUSSION: Observation of an high mortality for not-neurological causes confirms that modern treatments allow a significant control of the disease within the nervous system. Surgery entails the additional advantage of large tissue-samples availability for histological

  6. Potential applications of image-guided radiotherapy for brain metastases and glioblastoma to improve patient quality of life

    Directory of Open Access Journals (Sweden)

    Nam Phong Nguyen

    2013-11-01

    Full Text Available Treatment of glioblastoma multiforme (GBM and brain metastasis remains a challenge because of the poor survival and the potential for brain damage following radiation. Despite concurrent chemotherapy and radiation dose escalation, local recurrence remains the predominant pattern of failure in GBM most likely secondary to repopulation of cancer stem cells. Even though radiotherapy is highly effective for local control of radio-resistant tumors such as melanoma and renal cell cancer, systemic disease progression is the cause of death in most patients with brain metastasis. Preservation of quality of life of cancer survivors is the main issue for patients with brain metastasis. Image-guided radiotherapy (IGRT by virtue of precise radiation dose delivery may reduce treatment time of patients with GBM without excessive toxicity and potentially improve neurocognitive function with preservation of local control in patients with brain metastasis. Future prospective trials for primary brain tumors or brain metastasis should include IGRT to assess its efficacy to improve patient quality of life.

  7. Hypofractionated image-guided breath-hold SABR (Stereotactic Ablative Body Radiotherapy of liver metastasesclinical results

    Directory of Open Access Journals (Sweden)

    Boda-Heggemann Judit

    2012-06-01

    Full Text Available Abstract Purpose Stereotactic Ablative Body Radiotherapy (SABR is a non-invasive therapy option for inoperable liver oligometastases. Outcome and toxicity were retrospectively evaluated in a single-institution patient cohort who had undergone ultrasound-guided breath-hold SABR. Patients and methods 19 patients with liver metastases of various primary tumors consecutively treated with SABR (image-guidance with stereotactic ultrasound in combination with computer-controlled breath-hold were analysed regarding overall-survival (OS, progression-free-survival (PFS, progression pattern, local control (LC, acute and late toxicity. Results PTV (planning target volume-size was 108 ± 109cm3 (median 67.4 cm3. BED2 (Biologically effective dose in 2 Gy fraction was 83.3 ± 26.2 Gy (median 78 Gy. Median follow-up and median OS were 12 months. Actuarial 2-year-OS-rate was 31%. Median PFS was 4 months, actuarial 1-year-PFS-rate was 20%. Site of first progression was predominantly distant. Regression of irradiated lesions was observed in 84% (median time to detection of regression was 2 months. Actuarial 6-month-LC-rate was 92%, 1- and 2-years-LC-rate 57%, respectively. BED2 influenced LC. When a cut-off of BED2 = 78 Gy was used, the higher BED2 values resulted in improved local control with a statistical trend to significance (p = 0.0999. Larger PTV-sizes, inversely correlated with applied dose, resulted in lower local control, also with a trend to significance (p-value = 0.08 when a volume cut-off of 67 cm3 was used. No local relapse was observed at PTV-sizes 3 and BED2 > 78 Gy. No acute clinical toxicity > °2 was observed. Late toxicity was also ≤ °2 with the exception of one gastrointestinal bleeding-episode 1 year post-SABR. A statistically significant elevation in the acute phase was observed for alkaline-phosphatase; in the chronic phase for alkaline-phosphatase, bilirubine, cholinesterase and C

  8. Difference of Clinical and Radiological Characteristics According to Radioiodine Avidity in Pulmonary Metastases of Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dohoon; Jung, Jihoon; Song, Seung Hyun; Kim, Choonyoung; Hong, Chae Moon; Jeong, Shin Young; Lee, Sangwoo; Lee, Jaetae; Ahn, Byeongcheol [Kyungpook National Univ., Daegu (Korea, Republic of)

    2014-03-15

    To evaluate differences in clinical, radiological and laboratory findings between pulmonary metastasis with and without radioiodine avidity in thyroidectomized differentiated thyroid cancer (DTC) patients with pulmonary metastasis who underwent high-dose I-131 treatment. A total of 105 DTC patients with pulmonary metastasis (age, 48.7±16.8 years; women/men, 78/27) were included. Clinical characteristics, chest computed tomography (CT), F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET)/CT and thyroid-stimulating hormone (TSH)-stimulated serum thyroglobulin (s-Tg) level were compared between patients with and without radioiodine uptake in metastatic lung lesions. The response to I-131 treatment was evaluated with follow-up study. Eighty-nine patients (84.8 %, whole-body scan positive [WBSP] group) showed radioiodine uptake at pulmonary metastasis on post I-131 treatment whole-body scan (WBS) and 16 patients (15.2 %, WBS negative [WBSN] group) did not show uptake at pulmonary lesions on the WBS. Ninety percent and 87 % of the WBSP group had visible metastatic lesions on CT and F-18 FDG PET/CT; however, all of the patients in the WBSN group showed lesions on CT and F-18 FDG PET/CT. In seven (6.7 %) of 105 patients, CT and F-18 FDG PET/CT could not detect pulmonary lesions, which were diagnosed by post I-131 treatment WBS. Complete disease remission was achieved in six (5.7 %) patients and all of them were in the WBSP group. Metastatic lesion was not visualized on chest CT or F-18 FDG PET/CT in 6.7 % of DTC patients with pulmonary metastasis and the lesion was visualized only on post I-131 treatment WBS. Complete remission was achieved in 5.7 % of DTC patients with pulmonary metastasis and the cured metastases were non-visualizing or micronodular lesions on chest CT and demonstrated radioiodine avidity on post I-131 treatment WBS.

  9. Clinical anatomy of the canine brain using magnetic resonance imaging.

    Science.gov (United States)

    Leigh, Edmund J; Mackillop, Edward; Robertson, Ian D; Hudson, Lola C

    2008-01-01

    The purpose of this study was to produce an magnetic resonsnce (MR) image atlas of clinically relevant brain anatomy and to relate this neuroanatomy to clinical signs. The brain of a large mixed breed dog was imaged in transverse, sagittal, and dorsal planes using a 1.5 T MR unit and the following pulse sequences: Turbo (fast) spin echo (TSE) T2, T1, and T2- weighted spatial and chemical shift-encoded excitation sequence. Relevant neuroanatomic structures were identified using anatomic texts, sectioned cadaver heads, and previously published atlases. Major subdivisions of the brain were mapped and the neurologic signs of lesions in these divisions were described. TSE T2-weighted images were found to be the most useful for identifying clinically relevant neuroanatomy. Relating clinical signs to morphology as seen on MR will assist veterinarians to better understand clinically relevant neuroanatomy in MR images. PMID:18418990

  10. Extraneural metastases in medulloblastoma

    OpenAIRE

    V M F Muoio; S O Shinjo; H Matushita; Rosemberg, S.; M J Teixeira; S K N Marie

    2011-01-01

    Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of fi...

  11. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works...

  12. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works in the...

  13. Efficacy and nursing of stereotactic radiotherapy in lung cancer patients with brain metastases%立体定向放射治疗肺癌脑转移的疗效观察及护理

    Institute of Scientific and Technical Information of China (English)

    Xiaoxia Zhang; Wenrong Yin; Yueqin Liu

    2008-01-01

    Objective:To observe the efficacy of stereotactic radiotherapy (SRT) in lung cancer patients with brain metastases and explore the nursing for those patients.Methods:From June 2002 to December 2006,43 patients of lung cancer with brain metastases were treated with SRT,8 of them were treated with the association of whole-brain radiotherapy (WBRT) and 6 of them were treated with combination of chemotherapy.During the period of SRT,the patients were applied with active psychological nursing and diet nursing.We also tried to prevent patients from epicranium injury,and meanwhile,patients were asked to took active convalesce exercise.Results:All patients finished SRT without serious reaction and complication.Local control rate was 81.4%,nervous system symptoms relief rate was 76.7% and KPS score was raised significantly.Survival time ranged from 2 to 34 months,median survival time was 8.5 months,and 6-month,1-and 2-year survival rates were 58.9%,26.2%,and 6.0% respectively.Conclusion:SRT was one of the effective palliation treatments for the lung cancer patients with brain metastases,and with the assistance of effective nursing,which would prolong their survival time and improved quality of life.

  14. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    Science.gov (United States)

    Kircher, David A; Silvis, Mark R; Cho, Joseph H; Holmen, Sheri L

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  15. Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer:phase I trial

    Institute of Scientific and Technical Information of China (English)

    HUANG Yu-juan; WU Yi-long; XIE Song-xi; YANG Jing-ji; HUANG Yi-sheng; LIAO Ri-qiang

    2007-01-01

    Background Conventional treatment for non-small cell lung cancer (NSCLC) brain metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It might be increased by a Potent radiosensitizer such as gemcitabine,which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose (MTD) of weekly gemcitabine given concurrently with WBRT.Methods Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks).Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m2, escalated by100 mg/m2 increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached.Results A total of 16 patients were included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m2(Ievel 3) no neurology toxicity was observed. At 600 mg/m2 two out of 9 patients developed grade 4 thrombocytopenia.One of the two patients' thrombocytopenia was confused with disseminated intravascular coagulation (DIC). At 700mg/m2 two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness.Conclusions The MTD was reached at a dose of 700 mg/m2. The dose of 600 mg/m2 would be considered for further study.

  16. Clinical features of depressive disorders in patients with brain tumors

    Directory of Open Access Journals (Sweden)

    Ogorenko V.V.

    2014-03-01

    Full Text Available The aim of the study was to examine the structure of psychopathology and clinical features of depressive disorders in patients with brain oncopathology. Polymorphic mental disorders of various clinical content and severity in most cases not only are comorbid to oncological pathology of the brain, but most often are the first clinical signs of early tumors. The study was conducted using the following methods: clinical psychiatric, questionnaire Simptom Check List- 90 -Revised-SCL- 90 -R, Luscher test and mathematical processing methods. Sample included 175 patients with brain tumors with non-psychotic level of mental disorders. The peculiarities of mental disorders and psychopathological structure of nonpsychotic depressive disorders have been a clinical option of cancer debut in patients with brain tumors. We found that nonpsychotic depression is characterized by polymorphism and syndromal incompletion; this causes ambiguity of diagnoses interpretation on stages of diagnostic period. Features of depressive symptoms depending on the signs of malignancy / nonmalignancy of brain tumor were defined.

  17. Diagnosis of brain death: confirmatory tests after clinical test

    Institute of Scientific and Technical Information of China (English)

    Su Yingying; Yang Qinglin; Liu Gang; Zhang Yan; Ye Hong; Gao Daiquan; Zhang Yunzhou

    2014-01-01

    Background The brain death confirmation tests occupy a different position in each country's diagnostic criteria (or guideline); the choices of tests are also different.China brain death criteria include clinical judgment and confirmation tests.This study aimed to confirm the preferred confirmatory test and complementary confirmatory tests.Methods We did a clinical brain death determination on deep coma patients,and then divided them into brain death group and non-brain death group.According to the Chinese standards for determining brain death,both the groups accepted confirmatory tests including electroencephalograph (EEG),somatosensory evoked potentials (SEP),and transcranial Doppler (TCD).The sensitivity,specificity,false positive rate,and false negative rate were calculated to evaluate the accuracy of the confirmatory tests.Results Among the 131 cases of patients,103 patients met the clinical criteria of brain death.Respiratory arrest provocation test was performed on 44 cases and 32 cases (73%) successfully completed and confirmed that they have no spontaneous breathing.Of the three confirmation tests,EEG had the highest completion rate (98%) and good sensitivity (83%) and specificity (97%); TCD had followed completion rate (54%) and not good sensitivity (73%) and specificity (75%); SEP had the lowest completion rate (49%),good sensitivity (100%),and not good specificity (78%).After the combination of SEP or TCD with EEG,the specificity can increase to 100%.Conclusions The completion rate of respiratory arrest provocation test remains a problem in the clinical diagnosis of brain death.If the test cannot be completed,whether to increase a confirmatory test is debatable.SEP had an ideal sensitivity,and the specificity will reach 100% after combining with TCD or EEG.When a confirmed test was uncertain,we suggest increasing another confirmatory test.

  18. Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions

    OpenAIRE

    Fabio Ynoe de Moraes; Neil Kanth Taunk; Ilya Laufer; Wellington Furtado Pimenta Neves-Junior; Samir Abdallah Hanna; Heloisa de Andrade Carvalho; Yoshiya Yamada

    2016-01-01

    Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurge...

  19. Intraosseous Metastasizing of Pineoblastoma into the Anterior Skull Base, Calvarial Bones, and Vertebrae.

    Science.gov (United States)

    Golbin, Denis; Nikitin, Konstantin V; Konovalov, Alexander N; Pitskhelauri, David I; Shishkina, Liudmila V; Golanov, Andrey V; Cherekaev, Vasily A; Kobiakov, Grigory L; Absalyamova, Oksana V; Lasunin, Nikolay; Antipina, Natalia

    2015-01-01

    Pineoblastoma is a rare malignant tumor of the central nervous system (CNS), which arises from the parenchyma of the pineal gland. It is characterized by aggressive clinical behavior and frequent metastases along the craniospinal axis. Extraneural metastases may occur due to surgical seeding of tumor cells beyond the dura and/or hematogenous spread, ventriculoperitoneal shunting, or through Batson's plexus. To our knowledge, only six documented cases of intraosseous metastases of pineoblastoma are described in the literature. A 23-year-old female patient presented with clinical and radiological symptoms of a pineal tumor causing secondary hydrocephalus. After initial surgical treatment, chemotherapy, and local radiotherapy with craniospinal irradiation, she developed multiple metastases affecting the anterior skull base, intracranial meninges, frontal bone, and finally, the entire vertebral column. The patient received surgical treatment for the anterior skull base metastasis, repeated irradiation of the neuraxis, radiosurgical and radiotherapeutic procedures, and chemotherapy. The patient survived 57 months after the primary disease manifestation and died of multiple metastases. This presented case is the first known description of metastasis of pineoblastoma in the anterior cranial base. Multiple intracranial metastases were suppressed using CyberKnife radiation treatment and chemotherapy until massive involvement of spinal column occurred. Interestingly, no signs of brain radiation necrosis after repeated radiation treatments were observed, and the patient developed only moderate neurocognitive decline. PMID:26858918

  20. Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

    Energy Technology Data Exchange (ETDEWEB)

    Sperduto, Paul W., E-mail: psperduto@mropa.com [Metro-Minnesota CCOP and Minneapolis Radiation Oncology, Minneapolis, Minnesota (United States); Shanley, Ryan [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Luo, Xianghua [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota (United States); Andrews, David [Thomas Jefferson University, Department of NeuroOncology, Philadelphia, Pennsylvania (United States); Werner-Wasik, Maria [Thomas Jefferson University, Department of Radiation Oncology, Philadelphia, Pennsylvania (United States); Valicenti, Richard [UC Davis Medical Center, Department of Radiation Oncology, Sacramento, California (United States); Bahary, Jean-Paul [CHUM Hospital Notre Dame, Quebec (Canada); Souhami, Luis [McGill University, Montreal, Quebec (Canada); Won, Minhee [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Mehta, Minesh [University of Maryland Medical System, Baltimore, Maryland (United States)

    2014-11-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.

  1. Clinical Significance of KISS1 Protein Expression for Brain Invasion and Metastasis

    Science.gov (United States)

    Ulasov, Ilya V.; Kaverina, Natalya V.; Pytel, Peter; Thaci, Bart; Liu, FeiFei; Hurst, Douglas R.; Welch, Danny R.; Sattar, Husein A.; Olopade, Olufunmilayo I.; Baryshnikov, Anatoly Y.; Kadagidze, Zaira G.; Lesniak, Maciej S.

    2013-01-01

    BACKGROUND Metastases to the brain represent a feared complication and contribute to the morbidity and mortality of breast cancer. Despite improvements in therapy, prognostic factors for development of metastases are lacking. KISS1 is a metastasis suppressor that demonstrates inhibition of metastases formation in several types of cancer. The purpose of this study was to determine the importance of KISS1 expression in breast cancer progression and the development of intracerebral lesions. METHODS In this study, we performed a comparative analysis of 47 brain metastases and 165 primary breast cancer specimens by using the antihuman KISS1 antibody. To compare KISS1 expression between different groups, we used a 3-tier score and the automated score computer software (ACIS) evaluation. To reveal association between mRNA and protein expression, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Significance of immunohistochemistry stainings was correlated with clinicopathological data. RESULTS We identified that KISS1 expression is significantly higher in primary breast cancer compared with brain metastases (P < .05). The mRNA analysis performed on 33 selected ductal carcinoma brain metastatic lesions and 36 primary ductal carcinomas revealed a statistically significant down-regulation of KISS1 protein in metastatic cases (P = .04). Finally, we observed a significant correlation between expression of KISS1 and metastasis-free survival (P = .04) along with progression of breast cancer and expression of KISS1 in primary breast cancer specimens (P = .044). CONCLUSIONS In conclusion, our study shows that breast cancer expresses KISS1. Cytoplasmic expression of KISS1 may be used as a prognostic marker for increased risk of breast cancer progression. PMID:21928364

  2. In Vivo Single Scan Detection of Both Iron-Labeled Cells and Breast Cancer Metastases in the Mouse Brain Using Balanced Steady-State Free Precession Imaging at 1.5 T

    Science.gov (United States)

    Ribot, Emeline J.; Martinez-Santiesteban, Francisco M.; Simedrea, Carmen; Steeg, Patricia S.; Chambers, Ann F.; Rutt, Brian K.; Foster, Paula J.

    2012-01-01

    Purpose To simultaneously detect iron-labeled cancer cells and brain tumors in vivo in one scan, the balanced steady-state free precession (b-SSFP) imaging sequence was optimized at 1.5 T on mice developing brain metastases subsequent to the injection of micron-sized iron oxide particle-labeled human breast cancer cells. Materials and Methods b-SSFP sequence parameters (repetition time, flip angle, and receiver bandwidth) were varied and the signal-to-noise ratio, contrast between the brain and tumors, and the number of detected iron-labeled cells were evaluated. Results Optimal b-SSFP images were acquired with a 26 msec repetition time, 35° flip angle, and bandwidth of ±21 kHz. b-SSFP images were compared with T2-weighted 2D fast spin echo (FSE) and 3D spoiled gradient recalled echo (SPGR) images. The mean tumor-brain contrast-to-noise ratio and the ability to detect iron-labeled cells were the highest in the b-SSFP images. Conclusion A single b-SSFP scan can be used to visualize both iron-labeled cells and brain metastases. PMID:21698713

  3. Bottlenecks to Clinical Translation of Direct Brain-Computer Interfaces

    Directory of Open Access Journals (Sweden)

    Mijail Demian Serruya

    2014-12-01

    Full Text Available Despite several decades of research into novel brain-implantable devices to treat a range of diseases, only two- cochlear implants for sensorineural hearing loss and deep brain stimulation for movement disorders- have yielded any appreciable clinical benefit. Obstacles to translation include technical factors (e.g., signal loss due to gliosis or micromotion, lack of awareness of current clinical options for patients that the new therapy must outperform, traversing between federal and corporate funding needed to support clinical trials, and insufficient management expertise. This commentary reviews these obstacles preventing the translation of promising new neurotechnologies into clinical application and suggests some principles that interdisciplinary teams in academia and industry could adopt to enhance their chances of success.

  4. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials

    Science.gov (United States)

    Tétreault, Pascal; Mansour, Ali; Vachon-Presseau, Etienne; Schnitzer, Thomas J.; Apkarian, A. Vania

    2016-01-01

    Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active

  5. Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases

    International Nuclear Information System (INIS)

    Stereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose–response relationship is analyzed based on Biologically Equivalent Dose (BED). 50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5x12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed. The median BED2 was 83 Gy. 12 lesions were treated with a BED2 of <80 Gy, and 38 lesions with a BED2 of >80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%. Intensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control

  6. Normal feline brain: clinical anatomy using magnetic resonance imaging.

    Science.gov (United States)

    Mogicato, G; Conchou, F; Layssol-Lamour, C; Raharison, F; Sautet, J

    2012-04-01

    The purpose of this study was to provide a clinical anatomy atlas of the feline brain using magnetic resonance imaging (MRI). Brains of twelve normal cats were imaged using a 1.5 T magnetic resonance unit and an inversion/recovery sequence (T1). Fourteen relevant MRI sections were chosen in transverse, dorsal, median and sagittal planes. Anatomic structures were identified and labelled using anatomical texts and Nomina Anatomica Veterinaria, sectioned specimen heads, and previously published articles. The MRI sections were stained according to the major embryological and anatomical subdivisions of the brain. The relevant anatomical structures seen on MRI will assist clinicians to better understand MR images and to relate this neuro-anatomy to clinical signs.

  7. A clinical trial of progesterone for severe traumatic brain injury

    NARCIS (Netherlands)

    van der Naalt, Joukje

    2014-01-01

    BACKGROUND: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clin

  8. Monomorphic cutaneous metastases with different primaries

    Directory of Open Access Journals (Sweden)

    Muthukumaran R

    1998-01-01

    Full Text Available Telangiectatic type of secondary cutaneous metastases is described with primary malignancies in different organs in a female and in a male. The clinical and histopathological features of the secondary metastases are described along with the features of the primaries manifesting as adenocarcinoma of breast in the former and squamous cell carcinoma in the larynx in the latter.

  9. Extraneural metastases in medulloblastoma

    Directory of Open Access Journals (Sweden)

    V M F Muoio

    2011-01-01

    Full Text Available Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature.

  10. Extraneural metastases in medulloblastoma.

    Science.gov (United States)

    Muoio, Valéria Marques Figueira; Shinjo, Sueli Oba; Matushita, Hamilton; Rosemberg, Sérgio; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi

    2011-01-01

    Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature. PMID:21625760

  11. Clinical applications of 7 T MRI in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Kolk, Anja G. van der, E-mail: A.G.vanderKolk@umcutrecht.nl [Department of Radiology, University Medical Center Utrecht, Postbox 85500, 3508 GA Utrecht (Netherlands); Hendrikse, Jeroen, E-mail: J.Hendrikse@umcutrecht.nl [Department of Radiology, University Medical Center Utrecht, Postbox 85500, 3508 GA Utrecht (Netherlands); Zwanenburg, Jaco J.M., E-mail: J.J.M.Zwanenburg@umcutrecht.nl [Department of Radiology, University Medical Center Utrecht, Postbox 85500, 3508 GA Utrecht (Netherlands); Image Sciences Institute, University Medical Center Utrecht (Netherlands); Visser, Fredy, E-mail: F.Visser-2@umcutrecht.nl [Department of Radiology, University Medical Center Utrecht, Postbox 85500, 3508 GA Utrecht (Netherlands); Philips Healthcare, Best (Netherlands); Luijten, Peter R., E-mail: P.Luijten@umcutrecht.nl [Department of Radiology, University Medical Center Utrecht, Postbox 85500, 3508 GA Utrecht (Netherlands)

    2013-05-15

    This review illustrates current applications and possible future directions of 7 Tesla (7 T) Magnetic Resonance Imaging (MRI) in the field of brain MRI, in clinical studies as well as clinical practice. With its higher signal-to-noise (SNR) and contrast-to-noise ratio (CNR) compared to lower field strengths, high resolution, contrast-rich images can be obtained of diverse pathologies, like multiple sclerosis (MS), brain tumours, aging-related changes and cerebrovascular diseases. In some of these diseases, additional pathophysiological information can be gained compared to lower field strengths. Because of clear depiction of small anatomical details, and higher lesion conspicuousness, earlier diagnosis and start of treatment of brain diseases may become possible. Furthermore, additional insight into the pathogenesis of brain diseases obtained with 7 T MRI could be the basis for new treatment developments. However, imaging at high field comes with several limitations, like inhomogeneous transmit fields, a higher specific absorption rate (SAR) and, currently, extensive contraindications for patient scanning. Future studies will be aimed at assessing the advantages and disadvantages of 7 T MRI over lower field strengths in light of clinical applications, specifically the additional diagnostic and prognostic value of 7 T MRI.

  12. Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence

    Directory of Open Access Journals (Sweden)

    Li S

    2015-06-01

    Full Text Available Shasha Li,1,2 Ana Luiza Zaninotto,2,3 Iuri Santana Neville,4 Wellingson Silva Paiva,4 Danuza Nunn,2 Felipe Fregni21Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Spaulding Neuromodulation Center, Harvard Medical School, Boston, MA, USA; 3Division of Psychology, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil; 4Division of Neurosurgery, University of São Paulo Medical School, São Paulo, São Paulo, BrazilAbstract: Traumatic brain injury (TBI remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery.Keywords: traumatic brain injury, brain stimulation, neuroplasticity

  13. Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

    Science.gov (United States)

    Sun, Ji-Yuan; Gebre, Wondwossen; Dong, Yi-Min; Shaun, Xiao; Robbins, Rachel; Podrumar, Alida

    2016-01-01

    Primary peritoneal carcinoma (PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote organs. PPCs have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer (OvCa), because it shares the same common embryonic origin, the coelomic epithelium (mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer, using experimental and animal model.

  14. A correlation of clinical, MRI and brain SPECT in dementia

    International Nuclear Information System (INIS)

    Background: Dementia is a clinical syndrome characterised by acquired impairment in multiple neuropsycologic and behavior domains including memory, language, speech, visuospatial ability, cognition and mood/personality. Dementia produces deficits in perfusion reflecting decreased metabolic needs. Neuroimaging techniques help in determining whether the cognitive symptoms are organic and in which pattern of cognitive loss the patient may evolve. AIM: To differentiate various types of Dementia, based on the regional perfusion abnormalities seen in Brain SPECT and correlate this with Clinical and MRI findings. Material and methods: Patients suffering from memory impairment and memory loss were referred to our department for Brain SPECT as a part of work up for Dementia. They had undergone a detailed clinical examination, psychometry, mini mental status examination (MMSE), memory/cognitive testing and an MRI. Brain SPECT was done after injecting Tc 99m ECD (Ethylene Cysteinate Dimer ) and imaging after 45 minutes. The images obtained were reconstructed in a conventional way. The various patterns of perfusion abnormalities seen in the SPECT images was studied and correlated with MRI and clinical findings. The patients were thus classified as having Multi Infarct Dementia, Alzheimer's disease, Fronto-Temporal Dementia and Mixed variety. Results: Twenty One Patients were included in our study from February 2003 to February 2004. The mean age of the patients was 73 years ( 37 to 81). 15 were males and 6 were females. Out of 21 patients, 12 had Multi Infarct Dementia, 4 had Alzheimer's disease, 1 had Fronto- Temporal Dementia and 4 had Mixed variety. Conclusion: Brain SPECT aids in substantiating the clinical findings and in correlation with MRI helps in distinguishing various types of Dementia and thus has prognostic implications and helps in instituting early appropriate treatment to the patient. In our study, the majority of the patients have Multi Infarct Dementia

  15. Leptomeningeal metastases in breast cancer

    OpenAIRE

    Scott, Brian J.; Kesari, Santosh

    2013-01-01

    Central nervous system (CNS) metastasis from breast cancer may be characterized as either parenchymal brain metastasis (BM) or leptomeningeal (LM) metastasis. BM are much more common (about 80% of all CNS metastases), and have been more extensively studied than LM. CNS metastasis in breast cancer has been associated with reduced overall survival, with the shortest survival generally observed in cases of LM. Here, we review the epidemiology, prognostic factors, diagnostic tools, currently avai...

  16. Clinical value of 18F-FDG PET/CT in detecting viable tumor, recurrence and metastases of hepato-cellular carcinoma after transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Objective: Accurate evaluation of treatment result of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) by conventional imaging is difficult. The objective of this study was to investigate the clinical value of 18F-fluorodeoxyglucose (FDG) PET/CT for detecting residual viable tumor, recurrence and metastases in patients with HCC after TACE. Methods: Twenty-two patients with HCC after TACE were investigated with 18F-FDG PET/CT. The accuracy of FDG PET/CT was determined by the histopathological results or evidences of clinical follow-up. Results: Of all 22 HCC patients after TACE, 18 had intra- and (or) extrahepatic lesions, detected by FDG PET/CT. Six-teen patients had intrahepatic FDG-avid lesion(s). Of the 16 patients, five had intrahepatic FDG-avid lesions located at both lipiodol-rich and -deprive regions, 13 had associated extrahepatic metastases. Of the two HCC patients who had no intrahepatic FDG-avid lesion, there were extrahepatic FDG-avid lesions at the retroperitoneal lymph nodes. In all, 15 HCC had extrahepatic lesions identified by FDG PET/CT. There were lung and lymph nodes (n = 9), bone (n = 2), tumor thrombus at portal vein (n - 1) and diaphragm crus (n = 1). Two patients were false negative. The sensitivity, specificity, accuracy of FDG PET/CT in detecting intra- and (or) extrahepatic lesions after TACE were 88.9% (16/18) vs 94.7 % (18/19), 4/4 vs 3/3, and 90.9% (20/22) vs 95.5% (21/22), respectively. Conclusion: 18F-FDG PET/CT is potential useful for detection both intra- and (or) extrahepatic lesions in HCC patients after TACE. (authors)

  17. Brain death in ICU patients: Clinical significance of endocrine changes

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa

    2014-01-01

    Full Text Available Numerous studies have been carried out among patients admitted in intensive care unit (ICU having primary endocrine pathology, endocrine manifestations of systemic diseases or post-endocrine tissue surgery. However, minimal literary evidence is available highlighting the endocrine changes occurring during brain death in critically ill patients. A precise and timely diagnosis of brain death is required to convey the relatives about the prognosis and also to possibly plan for organ retrieval for transplantation purposes. The diagnosis of this condition as of today remains largely a clinical one. Brain death is associated with a multitude of endocrinological alterations which are yet to be completely unraveled and understood. Evaluating these endocrinological modifications lends us an added vista to add to the existing clinical parameters which might help us to confirm the diagnosis of brain death with a higher degree of precision. Moreover, since the efficacy of hormone replacement therapy to benefit in organ retrieval remains yet unproven, newer diagnostic modalities and research studies are definitely called for to strategize the optimal dosage and duration of such therapies.

  18. Control study of GKRT and IMRT boost for brain metastases from lung cancer%伽玛刀与IMRT推量技术治疗肺癌脑转移瘤的临床结果分析

    Institute of Scientific and Technical Information of China (English)

    蒋爱军; 曹欢; 章炳蔚; 汪雪咏; 李忠喜

    2015-01-01

    目的:比较单纯伽玛刀(GKRT)和IMRT全脑同步放疗或缩野推量技术治疗肺癌脑转移瘤的临床疗效。方法回顾分析我院2008年1月—2014年1月收治的76例肺癌脑转移瘤患者,54例初治行伽玛刀治疗,22例初治行IMRT全脑放疗同步或缩野推量技术治疗。结果 GKRT组近期客观有效率为85.2%,不良反应率14.8%,中位生存时间11个月;IMRT组近期客观有效率为77.3%,不良反应率36.4%,中位生存时间10个月。结论伽玛刀治疗肺癌脑转移瘤安全有效,并发症少,生存期长,可作为肺癌脑转移瘤的主要治疗手段。%Objective To investigate the effect of Gamma Knife (GKRT)and IMRT boost(SIB or SB)technique for brain metastases from lung cancer. Methods From January 2008 to January 2014,99 lung cancer patients with brain metastases received GKRT or IMRT (SIB or SB-IMRT).The initial treatment for 71 cases was GKRT,and for other 28 cases was IMRT. Results The follow-up of 76 cases was effective. In GKRT group,the objective response rate (ORR) was 85.2%,the adverse reaction rate was14.8%,the median survival time was 11 months. In IMRT group,the objective response rate was 77.3% ,the adverse reaction rate was 36.4% ,the median survival time was 10 months. Conclusions Compared with IMRT boost,Gamma Knife is safe and effective for brain metastases from lung cancer, with fewer complications and longer survival.It can be used as the main treatment for brain metastases from lung cancer.

  19. 18F-fluoro-deoxyglucose positron emission tomography-computed tomography in initial assessment and diagnosis of right atrial angiosarcoma with widespread visceral metastases: A rare case report and review of the literature

    International Nuclear Information System (INIS)

    Cardiac angiosarcoma is the most common primary cardiac sarcoma in adults. Primary cardiac tumors are rare and have nonspecific clinical presentation, thus making its diagnosis challenging. Clinically, patients present with advanced disease demonstrating metastatic disease at initial presentation itself. It commonly metastasizes to lung, liver, brain, and bone; however metastases to lymph nodes, adrenal glands, spleen and skin has also been seen. We describe a case of right atrial angiosarcoma with extensive visceral metastases involving brain, lungs, liver, pancreas, kidney, and lymph nodes, demonstrated on contrast-enhanced 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (FDG PET-CT). To the best of our knowledge metastases to pancreas and kidney have not been reported so far in the literature. With our report, we emphasize on the initial use of FDG PET-CT in workup of cardiac angiosarcoma for accurate staging and prognostication of this disease

  20. First clinical experience of intra-operative high intensity focused ultrasound in patients with colorectal liver metastases: a phase I-IIa study.

    Directory of Open Access Journals (Sweden)

    Aurélien Dupré

    Full Text Available Surgery is the only curative treatment in patients with colorectal liver metastases (CLM, but only 10-20% of patients are eligible. High Intensity Focused Ultrasound (HIFU technology is of proven value in several indications, notably prostate cancer. Its intra-operative use in patients with CLM has not previously been studied. Preclinical work suggested the safety and feasibility of a new HIFU device capable of ablating volumes of up to 2cm x 2cm in a few seconds.We conducted a prospective, single-centre phase I-IIa trial. HIFU was delivered immediately before scheduled hepatectomy. To demonstrate the safety and efficacy of rapidly ablating liver parenchyma, ablations were performed on healthy tissue within the areas scheduled for resection.In total, 30 ablations were carried out in 15 patients. These ablations were all generated within 40 seconds and on average measured 27.5mm x 21.0mm. The phase I study (n = 6 showed that use of the HIFU device was feasible and safe and did not damage neighbouring tissue. The phase IIa study (n = 9 showed both that the area of ablation could be precisely targeted on a previously implanted metallic mark (used to represent a major anatomical structure and that ablations could be undertaken deliberately to avoid such a mark. Ablations were achieved with a precision of 1-2 mm.HIFU was feasible, safe and effective in ablating areas of liver scheduled for resection. The next stage is a phase IIb study which will attempt ablation of small metastases with a 5 mm margin, again prior to planned resection.ClinicalTrials.govNCT01489787.

  1. [Brain-Computer Interface: the First Clinical Experience in Russia].

    Science.gov (United States)

    Mokienko, O A; Lyukmanov, R Kh; Chernikova, L A; Suponeva, N A; Piradov, M A; Frolov, A A

    2016-01-01

    Motor imagery is suggested to stimulate the same plastic mechanisms in the brain as a real movement. The brain-computer interface (BCI) controls motor imagery by converting EEG during this process into the commands for an external device. This article presents the results of two-stage study of the clinical use of non-invasive BCI in the rehabilitation of patients with severe hemiparesis caused by focal brain damage. It was found that the ability to control BCI did not depend on the duration of a disease, brain lesion localization and the degree of neurological deficit. The first step of the study involved 36 patients; it showed that the efficacy of rehabilitation was higher in the group with the use of BCI (the score on the Action Research Arm Test (ARAT) improved from 1 [0; 2] to 5 [0; 16] points, p = 0.012; no significant improvement was observed in control group). The second step of the study involved 19 patients; the complex BCI-exoskeleton (i.e. with the kinesthetic feedback) was used for motor imagery trainings. The improvement of the motor function of hands was proved by ARAT (the score improved from 2 [0; 37] to 4 [1; 45:5] points, p = 0.005) and Fugl-Meyer scale (from 72 [63; 110 ] to 79 [68; 115] points, p = 0.005). PMID:27188145

  2. Clinical results of BNCT for malignant brain tumors in children

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yoshinobu [Department of Neurosurgery, Kagawa National Children' s Hospital, Kagawa 765-8501 (Japan)], E-mail: ynakagawa0517@yahoo.co.jp; Kageji, Teruyoshi; Mizobuchi, Yoshifumi [Department of Neurosurgery, University of Tokushima, Tokushima 770-8503 (Japan); Kumada, Hiroaki [Department of Research Reactor, Japan Atomic Energy Research Institute, Ibaragi 319-1195 (Japan); Nakagawa, Yoshiaki [Department of Medical Informatics, Post Graduated School, Kyoto University, Kyoto (Japan)

    2009-07-15

    It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

  3. Clinical Traumatic Brain Injury in the Preclinical Setting.

    Science.gov (United States)

    Berkner, Justin; Mannix, Rebekah; Qiu, Jianhua

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability for people under 45 years of age. Clinical TBI is often the result of disparate forces resulting in heterogeneous injuries. Preclinical modeling of TBI is a vital tool for studying the complex cascade of metabolic, cellular, and molecular post-TBI events collectively termed secondary injury. Preclinical models also provide an important platform for studying therapeutic interventions. However, modeling TBI in the preclinical setting is challenging, and most models replicate only certain aspects of clinical TBI. This chapter details the most widely used models of preclinical TBI, including the controlled cortical impact, fluid percussion, blast, and closed head models. Each of these models replicates particular critical aspects of clinical TBI. Prior to selecting a preclinical TBI model, it is important to address what aspect of human TBI is being sought to evaluate. PMID:27604710

  4. 脑转移瘤合理治疗模式的Meta分析%Meta analysis o