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Sample records for brain metastases clinical

  1. Comparing Postoperative Radiation Therapies for Brain Metastases

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    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.

  2. Viral Immunotherapy to Eradicate Subclinical Brain Metastases

    Science.gov (United States)

    2014-05-01

    metastases is highlighted in the case of breast cancer. Since the introduction of Herceptin , several groups have reported a high incidence of brain...brain4,5 but is probably also due to the disparity of effectiveness of Herceptin in the brain versus 40 systemically. Herceptin is effective...systemically and may prolong survival to such an extent that brain metastases, which manifest late in the clinical course, become apparent.2 Herceptin

  3. 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.

  4. Targeting Brain Metastases in Patients with Melanoma

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    Dionysis Papadatos-Pastos

    2013-01-01

    Full Text Available Patients with brain metastases from malignant melanoma historically have a very poor outcome. Surgery and radiotherapy can be used, but for the majority of patients the disease will progress quickly. In the recent past, patients with brain metastases derived only minimal benefit from cytotoxic chemotherapy. Novel therapies that have been shown to be superior to chemotherapy in metastatic melanoma have made their way in clinic and data regarding their use in patients with treated or untreated brain metastases are encouraging. In this paper we describe the use of vemurafenib, dabrafenib, and ipilimumab in patients with melanoma disseminated to the brain in addition to other treatments currently in development.

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

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    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.

  6. 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.

  7. Brain metastases: A single institute experience

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    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.

  8. Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study.

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    Bulut, Olcay Cem; Lindel, Katja; Hauswald, Henrik; Brandt, Regine; Klauschen, Frederick; Wolf, Janina; Wolf, Thomas; Plinkert, Peter K; Simon, Christian; Weichert, Wilko; Stenzinger, Albrecht

    2014-06-01

    Among the metastasis patterns of head and neck squamous cell carcinoma (HNSCC), intracranial spread is a rare but dreaded event. To date only very few cases have been reported and clinical and molecular data are sparse. We screened our archives for HNSCC patients from 1992 to 2005 who were diagnosed with brain metastases (BM). For retrospective analysis, all clinico-pathological data including disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) were compiled. Additionally, we assessed the mutational status of the TP53 gene and the prevalence of HPV serotypes by PCR and Sanger sequencing. Immunohistochemistry was applied to detect p16INK4A expression levels as surrogate marker for HPV infection. The prevalence rate of BM in our cohort comprising 193 patients with advanced HNSCC was 5.7%. Of 11 patients with BM, 3 were female and 9 were male. Seven of the primary tumors were of oropharyngeal origin (OPSCC). LPFS of the cohort was 11.8 months, DFS was 12.1 months and OS was 36.0 months. After the diagnosis of BM, survival was 10.5 months. Five tumors showed a mutation in the TP53 gene, while five of the seven OPSCC tumors had a positive HPV status displaying infection with serotype 16 in all cases. Compared with patients who harbored TP53wt/HPV-positive tumors, patients with TP53 mutations showed a poor prognosis. Compared with the whole cohort, the interval between diagnosis of the primary and the detection of BM was prolonged in the HPV-infected OPSCC subgroup (26.4 vs. 45.6 months). The prognosis of HNSCC patients with BM is poor. In our cohort, most tumors were OPSCC with the majority being HPV positive. Our study points toward a putatively unusual metastatic behavior of HPV-positive OPSCC.

  9. Brain metastases from colorectal cancer

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    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....

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

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    Wu S

    2016-12-01

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

  11. Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation

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    Iguchi, Yohei; Mano, Kazuo; Goto, Yoji; Nakano, Tomonobu [Japanese Red Cross Nagoya First Hospital, Department of Neurology Medicine, Nagoya, Aichi (Japan); Nomura, Fumio; Shimokata, Tomoya [Japanese Red Cross Nagoya First Hospital, Department of Respiratory Medicine, Nagoya, Aichi (Japan); Iwamizu-Watanabe, Sachiko [Nagoya University Graduate School of Medicine, Department of Pathology of Molecular Diagnosis, Nagoya (Japan); Hashizume, Yoshio [Aichi Medical University, Institute for Medical Science of Aging, Nagakute, Aichi (Japan)

    2007-01-15

    Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness. (orig.)

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

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

    2016-11-15

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

  13. [Radiation therapy in simultaneous choroidal and brain metastases].

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    Conill, C; Jorcano, S; Planas, I; Marruecos, J; Casas, F; Fontenla, J R

    2005-09-01

    Choroidal metastases from lung cancer can be the initial clinical manifestation of metastasic disease, although they generally coexist with at least two more metastasic sites. The most common symptom is decreased vision, however 20% of brain metastases can present with visual alterations. A differential diagnosis within brain metastases and/or choroidal is necessary. We present the case of a patient with lung cancer and decreased vision who was diagnosed as simultaneous choroidal and brain metastases. Radiation therapy (20Gy/5fractions) significantly improves decreased vision. This case shows that, although life expectancy of patients with metastasic lung cancer is short, an adequate diagnosis and treatment, can improve the quality of life of those patients.

  14. 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.

  15. Brain nodules with lung mass: are they always metastases?

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    Jorcano, Sandra; Farrús, Blanca; Pujol, Teresa; Verger, Eugenia; Marruecos, Jordi; Conill, Carlos

    2008-08-01

    In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment.

  16. Stereotactic radiosurgery for multiple brain metastases

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    Lee, Anna; (Josh Yamada, Yoshiya

    2017-01-01

    Whole brain radiation therapy has been the traditional treatment of choice for patients with multiple brain metastases. Although stereotactic radiosurgery is widely accepted for the management to up to 4 brain metastases, its use is still controversial in cases of 5 or more brain metastases. Randomized trials have suggested that stereotactic radiosurgery alone is appropriate in up to 4 metastases without concomitant whole brain radiation. Level 1 evidence also suggests that withholding whole brain radiation may also reduce the impact of radiation on neurocognitive function and also may even offer a survival advantage. A recent analysis of a large multicentre prospective database has suggested that there are no differences in outcomes such as the likelihood of new metastasis or leptomeningeal disease in cases of 2-10 brain metastases, nor in overall survival. Hence in the era of prolonged survival with stage IV cancer, stereotactic radiosurgery is a reasonable alternative to whole brain radiation in order to minimize the impact of treatment upon quality of life without sacrificing overall survival.

  17. 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.

  18. Treatment of breast cancer brain metastases.

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    Hofer, Silvia; Pestalozzi, Bernhard C

    2013-10-05

    Breast cancer represents the second most frequent cause of brain metastases. Treatment planning should consider several tumor and patient factors to estimate prognosis based on the Karnofsky Performance Status (KPS), age, extent of extra-cerebral disease as well as genetic subtype. When systemic disease is under control patients with up to three metastases qualify for local therapy, such as surgical excision or stereotactic radiotherapy. After the local treatment the addition of whole brain radiation therapy may be postponed until disease progression in the brain is observed and overall survival will not be compromised. Asymptomatic brain metastases may be first approached with a systemic treatment to which the primary tumor is considered to be sensitive.

  19. [Systemic treatment of melanoma brain metastases].

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    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).

  20. Radiosurgery for brain metastases and cerebral edema.

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    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.

  1. 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

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    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.

  2. Role of palliative radiotherapy in brain metastases

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    Ramesh S Bilimagga

    2009-01-01

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

  3. Targeted Therapies for Brain Metastases from Breast Cancer

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    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.

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

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    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.

  5. 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.

  6. [Management of brain metastases from urological malignancies].

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    Gaillard, S; Lebret, T; Scarone, P; Lepeintre, J-F; Méjean, A; Aldea, S

    2008-11-01

    Brain metastases account for 30 to 40% of all brain tumors in adults. Even if urological carcinomas are not very common, anti-angiogenic drugs have transformed their prognosis, leading physicians to consider their specific treatment. For the majority of cases, surgery is quite simple with low associated morbidity. Depending on the size and the location, surgery or stereotaxic radiotherapy should be discussed. As soon as the metastasis is suspected a neurosurgerical opinion must be sought before beginning any treatment to coordinate the global management.

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

    Science.gov (United States)

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

    2015-02-01

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

  8. Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases.

    Science.gov (United States)

    Li, Yingmei; Pan, Wenying; Connolly, Ian D; Reddy, Sunil; Nagpal, Seema; Quake, Stephen; Gephart, Melanie Hayden

    2016-05-01

    Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAF (V600E) mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient's clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTEN (R130*) at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD.

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

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

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

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

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    A. A. Tryakin

    2014-07-01

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

  11. Whole brain radiotherapy with radiosensitizer for brain metastases

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    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.

  12. 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...

  13. Multiple cutaneous melanomas associated with gastric and brain metastases*

    Science.gov (United States)

    Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

    2016-01-01

    The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified.

  14. 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.

  15. 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

  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. 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

  18. 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.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    Hanson Peter W

    2012-08-01

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

  1. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  3. Leptomeningeal disease following stereotactic radiosurgery for brain metastases from breast cancer.

    Science.gov (United States)

    Trifiletti, Daniel M; Romano, Kara D; Xu, Zhiyuan; Reardon, Kelli A; Sheehan, Jason

    2015-09-01

    Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients with brain metastases from breast cancer treated with SRS from 1995 to 2014 at our institution. Clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cerebrospinal fluid (CSF) cytology or MRI demonstrating CSF seeding. Comparative statistical analyses were conducted using Cox proportional hazards regression, binary logistic regression, and/or log-rank test. 126 patients met inclusion criteria. Eighteen patients (14 %) developed LMD following SRS. From the time of SRS, the actuarial rate of LMD at 12 months from diagnosis of brain metastasis was 9 % (11 patients). Active disease in the chest at the time of SRS was associated with development of LMD (p = 0.038). Factors including receptor status, tumor size, number of intra-axial tumors, cystic tumor morphology, prior WBRT, active bone metastases, and active liver metastases were not significantly associated with the development of LMD. In patients with brain metastasis from breast cancer that undergo SRS, there is a relatively low rate of LMD. We found that while tumor hormonal status, bone metastases, and hepatic metastases were not associated with the development of LMD, active lung metastases at SRS was associated with LMD. Further research may help to delineate a causative relationship between metastatic lung disease and LMD.

  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. 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.

  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. 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...

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

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

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

  10. 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

  11. The Current and Future Treatment of Brain Metastases

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    Douglas A Hardesty

    2016-05-01

    Full Text Available Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment.

  12. The Current and Future Treatment of Brain Metastases.

    Science.gov (United States)

    Hardesty, Douglas A; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment.

  13. Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?

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    Arruda Viani, Gustavo, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo, SP (Brazil); Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo, SP (Brazil)

    2012-07-01

    Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural data consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the

  14. 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

  15. Challenges in the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with brain metastases.

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    Liu, Minetta C; Cortés, Javier; O'Shaughnessy, Joyce

    2016-06-01

    Brain metastases are a major cause of morbidity and mortality for women with hormone receptor (HR)-positive breast cancer, yet little is known about the optimal treatment of brain disease in this group of patients. Although these patients are at lower risk for brain metastases relative to those with HER2-positive and triple-negative disease, they comprise the majority of women diagnosed with breast cancer. Surgery and radiation continue to have a role in the treatment of brain metastases, but there is a dearth of effective systemic therapies due to the poor penetrability of many systemic drugs across the blood-brain barrier (BBB). Additionally, patients with brain metastases have long been excluded from clinical trials, and few studies have been conducted to evaluate the safety and effectiveness of systemic therapies specifically for the treatment of HER2-negative breast cancer brain metastases. New approaches are on the horizon, such as nanoparticle-based cytotoxic drugs that have the potential to cross the BBB and provide clinically meaningful benefits to patients with this life-threatening consequence of HR-positive breast cancer.

  16. 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.

  17. 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.

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

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    Forder Peta M

    2011-04-01

    treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07, and the Trans Tasman Radiation Oncology Group (TROG but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12607000512426

  19. Melanoma brain metastases: an unmet challenge in the era of active therapy.

    Science.gov (United States)

    Gorantla, Vikram; Kirkwood, John M; Tawbi, Hussein A

    2013-10-01

    Metastatic disease to the brain is a frequent manifestation of melanoma and is associated with significant morbidity and mortality and poor prognosis. Surgery and stereotactic radiosurgery provide local control but less frequently affect the overall outcome of melanoma brain metastases (MBM). The role of systemic therapies for active brain lesions has been largely underinvestigated, and patients with active brain lesions are excluded from the vast majority of clinical trials. The advent of active systemic therapy has revolutionized the care of melanoma patients, but this benefit has not been systematically translated into intracranial activity. In this article, we review the biology and clinical outcomes of patients with MBM, and the evidence supporting the use of radiation, surgery, and systemic therapy in MBM. Prospective studies that included patients with active MBM have shown clinical intracranial activity that parallels systemic activity and support the inclusion of patients with active MBM in clinical trials involving novel agents and combination therapies.

  20. 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.

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

    Science.gov (United States)

    Refaat, Tamer; Sachdev, Sean; Desai, Brijal; Bacchus, Ian; Hatoum, Saleh; Lee, Plato; Bloch, Orin; Chandler, James P; Kalapurakal, John; Marymont, Maryanne Hoffman

    2016-04-01

    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 with lung cancer in November, 2002, and histopathologically confirmed brain metastases in January, 2005. The patient received 5 treatments with Gamma Knife SRS for recurring brain metastases between 2005 and 2014. The patient remains highly functional, with stable intracranial disease at 10 years since first developing brain metastases, and with stable lung disease. Therefore, Gamma Knife SRS is a safe and effective treatment modality for patients with recurrent intracranial metastases, with durable local control and minimal cognitive impairment.

  2. 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

  3. 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...... within 2 months of the excision in patients with uncontrolled systemic disease and not subjected to adjuvant whole brain radio-therapy. MATERIALS AND METHODS: Tissue biopsies derived from 25 patients with brain metastases specifically selected to be a single totally resected lesion and not treated...... 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...

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

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    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.

  5. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.

    Science.gov (United States)

    Hamilton, Amanda M; Foster, Paula J

    2017-02-01

    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  6. 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.

  7. 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.

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

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    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.

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

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    Rades, Dirk, E-mail: rades.dirk@gmx.net [Department of Radiation Oncology, University Hospital Schleswig-Holstein, Lubeck (Germany); Department of Radiation Oncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Evers, Jasmin N. [Department of Radiation Oncology, University Hospital Schleswig-Holstein, Lubeck (Germany); Veninga, Theo [Department of Radiotherapy, Dr. Bernard Verbeeten Institute, Tilburg (Netherlands); Stalpers, Lukas J.A. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Lohynska, Radka [Department of Radiation Oncology, University Hospital, Prague (Czech Republic); Schild, Steven E. [Department of Radiation Oncology, Mayo Clinic Scottsdale, Arizona (United States)

    2011-11-15

    Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 Multiplication-Sign 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 Multiplication-Sign 3 Gy with 5 Multiplication-Sign 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 Multiplication-Sign 3 Gy were compared with 162 patients receiving 5 Multiplication-Sign 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 Multiplication-Sign 4 Gy and 21% after 10 Multiplication-Sign 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 Multiplication-Sign 4 Gy was not inferior to 10 Multiplication-Sign 3 Gy with respect to overall survival or local control in elderly patients. 5 Multiplication-Sign 4 Gy appears preferable for the majority of these patients.

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

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    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.

  11. Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases.

    Science.gov (United States)

    Niessner, Heike; Forschner, Andrea; Klumpp, Bernhard; Honegger, Jürgen B; Witte, Maria; Bornemann, Antje; Dummer, Reinhard; Adam, Annemarie; Bauer, Jürgen; Tabatabai, Ghazaleh; Flaherty, Keith; Sinnberg, Tobias; Beck, Daniela; Leiter, Ulrike; Mauch, Cornelia; Roesch, Alexander; Weide, Benjamin; Eigentler, Thomas; Schadendorf, Dirk; Garbe, Claus; Kulms, Dagmar; Quintanilla-Martinez, Leticia; Meier, Friedegund

    2013-02-01

    Brain metastases are the most common cause of death in patients with metastatic melanoma, and the RAF-MEK-ERK and PI3K-AKT signaling pathways are key players in melanoma progression and drug resistance. The BRAF inhibitor vemurafenib significantly improved overall survival. However, brain metastases still limit the effectiveness of this therapy. In a series of patients, we observed that treatment with vemurafenib resulted in substantial regression of extracerebral metastases, but brain metastases developed. This study aimed to identify factors that contribute to treatment resistance in brain metastases. Matched brain and extracerebral metastases from melanoma patients had identical ERK, p-ERK, and AKT immunohistochemistry staining patterns, but there was hyperactivation of AKT (p-AKT) and loss of PTEN expression in the brain metastases. Mutation analysis revealed no differences in BRAF, NRAS, or KIT mutation status in matched brain and extracerebral metastases. In contrast, AKT, p-AKT, and PTEN expression was identical in monolayer cultures derived from melanoma brain and extracerebral metastases. Furthermore, melanoma cells stimulated by astrocyte-conditioned medium showed higher AKT activation and invasiveness than melanoma cells stimulated by fibroblast-conditioned medium. Inhibition of PI3K-AKT signaling resensitized melanoma cells isolated from a vemurafenib-resistant brain metastasis to vemurafenib. Brain-derived factors appear to induce hyperactivation of the AKT survival pathway and to promote the survival and drug resistance of melanoma cells in the brain. Thus, inhibition of PI3K-AKT signaling shows potential for enhancing and/or prolonging the antitumor effect of BRAF inhibitors or other anticancer agents in melanoma brain metastases.

  12. 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.

  13. 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.

  14. 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....

  15. Intraoperative ultrasonography for presumed brain metastases: a case series study

    Directory of Open Access Journals (Sweden)

    Helder Picarelli

    2012-10-01

    Full Text Available Brain metastases (BM are one of the most common intracranial tumors and surgical treatment can improve both the functional outcomes and patient survival, particularly when systemic disease is controlled. Image-guided BM resection using intraoperative exams, such as intraoperative ultrasound (IOUS, can lead to better surgical results. METHODS: To evaluate the use of IOUS for BM resection, 20 consecutives patients were operated using IOUS to locate tumors, identify their anatomical relationships and surgical cavity after resection. Technical difficulties, complications, recurrence and survival rates were noted. RESULTS: IOUS proved effective for locating, determining borders and defining the anatomical relationships of BM, as well as to identify incomplete tumor resection. No complications related to IOUS were seen. CONCLUSION: IOUS is a practical supporting method for the resection of BM, but further studies comparing this method with other intraoperative exams are needed to evaluate its actual contribution and reliability.

  16. 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

  17. Clinical course of breast cancer patients with liver metastases.

    Science.gov (United States)

    Zinser, J W; Hortobagyi, G N; Buzdar, A U; Smith, T L; Fraschini, G

    1987-05-01

    Between June 1973 and November 1980, 1,171 patients with metastatic breast cancer were treated with various doxorubicin-containing regimens at our institution (M.D. Anderson Hospital and Tumor Institute, Houston). Retrospective analysis of all 233 cases (20%) with liver metastases was done to correlate various clinical and biochemical characteristics with response to treatment, survival, and causes of death. A similar analysis was performed for 58 consecutive patients with liver metastases treated at this hospital between December 1955 and December 1957 with hormone therapy or single-agent chemotherapy. Objective responses were observed in 132 of 233 patients (57%) treated with combination chemotherapy. The median survival was 14 months in the 1970s and 5 months in the 1950s. Among patients who had liver metastases at the time of initial diagnosis of breast cancer, survival was longer for the group treated with combination chemotherapy. All cases were classified according to the number of organ sites involved by metastases. Patients with only liver metastases, or liver plus bone lesions had the longest survival. Other clinical and biochemical factors that correlated significantly with longer survival were: no prior chemotherapy, performance status of 1 to 2, absence of ascites, normal bilirubin and lactic dehydrogenase (LDH), SGOT less than or equal to 2 times normal and albumin greater than 4.5 g/dL. The main cause of death was multiorgan failure, with only 20% of patients dying of liver failure. The present study shows that the presence of liver metastases in breast cancer is not by itself an ominous factor. Most patients respond to therapy, and significant palliation with extended survival is possible for several prognostic subgroups. Further improvement in length and quality of survival is expected with earlier diagnosis.

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

    Directory of Open Access Journals (Sweden)

    Tallet Agnes V

    2012-05-01

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

  19. 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

  20. 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 in the curr......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...... in the current study from two prospective cohort studies with either elevated serum HER2 levels >15 ng/ml or brain metastases verified by magnetic resonance imaging (MRI) or computer tomography (CT). Following the exclusion of six patients, the remaining 101 patients were divided into two groups: Group 0 (n=55......), patients with normal MRI results; and group 1 (n=46), patients with brain metastases. The levels of serum S100B and HER2 in the two groups were analyzed prior to MRI or CT of the brain, and no significant differences were identified in the serum HER2 (P=0.060) or S100B levels (P=0.623) between the groups...

  1. 鸦胆子油乳配合化疗治疗脑转移瘤的临床观察%Clinical observation on treating brain metastases with javanica oil emulsion plus chemotherapy

    Institute of Scientific and Technical Information of China (English)

    宋萌萌

    2014-01-01

    目的:观察鸦胆子油乳注射液联合替莫唑胺治疗脑转移瘤的疗效并进行分析。方法:41例患者随机分成观察组(21例)和对照组(20例)。观察组应用替莫唑胺加鸦胆子油乳注射液,并予支持治疗;对照组予最佳对症支持治疗。结果:观察组缓解率47.61%,对照组缓解率25.00%,两组差异有统计学意义(P<0.05)。观察组治疗后在临床症状、体征,生存质量及生存期方面均优于对照组,两组比较,差异有统计学意义(P<0.05)。结论:替莫唑胺联合鸦胆子油乳剂治疗脑转移瘤可提高患者的近期临床疗效,改善生存质量,延长生存期。%Objective: To observe and analyze the clinical efficacy of javanica oil emulsion plus temozolomide on brain metastases. Methods: 41 patients were randomly divided into the observationgroup (n=21) and the control group (n=20), the observation group was given javanica oil emulsion plus temozolomide and supportive treatment, while the control group was given symptomatic and supportive treatment. Results: The total efficiency in the observation group (47.61%) was significantly better than that (25.00%) in the control (P<0.05). Clinical symptoms, sign, survival quality and time in the observation group was better than those in the control group (P<0.05). Conclusion: Javanica oil emulsion plus temozolomide can improve clinical effects and life quality, and lengthen survival time.

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

    Science.gov (United States)

    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. |

  3. [Brain metastases: Focal treatment (surgery and radiation therapy) and cognitive consequences].

    Science.gov (United States)

    Reygagne, Emmanuelle; Du Boisgueheneuc, Foucaud; Berger, Antoine

    2017-02-01

    Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-15

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

  8. Clinical and radiologic features of extraskeletal myxoid chondrosarcoma including initial presentation, local recurrence, and metastases

    Directory of Open Access Journals (Sweden)

    Kapoor Neena

    2014-09-01

    Full Text Available Background. The aim of the study was to evaluate the clinical and imaging features of extraskeletal myxoid chondrosarcoma (EMC including initial presentation, recurrence, and metastases.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Hypofractionated stereotactic radiotherapy for brain metastases. Results from three different dose concepts

    Energy Technology Data Exchange (ETDEWEB)

    Fahrig, A.; Grabenbauer, G.; Sauer, R. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center of the Univ. of Erlangen (Germany); Ganslandt, O. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center of the Univ. of Erlangen (Germany); Dept. of Neurosurgery of the Univ. of Erlangen (Germany); Lambrecht, U. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center of the Univ. of Erlangen (Germany); Div. of Medical Physics of the Dept. of Radiation Therapy of the Univ. of Erlangen (Germany); Kleinert, G.; Hamm, K. [Dept. for Stereotactic Neurosurgery and Radiosurgery, Helios Klinikum Erfurt (Germany)

    2007-11-15

    Purpose: To evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (hfSRT) with three different dose concepts for irresectable brain metastases not amenable to radiosurgery (SRS) using non-invasive fixation of the skull. Patients and Methods: From 6/2000 to 6/2005, 150 patients with 228 brain metastases were treated at the dedicated stereotactic radiosurgery system Novalis trademark (BrainLAB, Feldkirchen, Germany) in two German treatment centers. Three different dose concepts were applied: 5 x 6-7 Gy (A: 72 brain metastases), 10 x 4 Gy (B: 59 brain metastases) and 7 x 5 Gy (C: 97 brain metastases). Median planning target volume (PTV) was 6.1 cm{sup 3} (range, 0.02-95.97). Results: Rates of complete remission (CR), partial remission (PR), no change (NC) and progressive disease (PD) were 42%, 30%, 21% and 7%, respectively (median follow-up 28 months). Median survival was 16 months. Survival at 6 and 12 months was 83% and 66%, respectively. Side effects were dependent on the PTV and on dose concept (median PTV in case of increasing edema or necrosis: 17 cm{sup 3}, A: 22%, C: 7%). HfSRT with 10 x 4 Gy (B) was well tolerated without side effects. Conclusion: Hypofractionated stereotactic radiotherapy is an effective and safe treatment. In case of brain metastases > 15 cm{sup 3} (diameter > 3 cm) and concerning toxicity, 10 x 4 Gy seem to be more advantageous than shorter fractionation with higher doses while 5 x 6-7 Gy and 7 x 5 Gy were followed by higher response rates. Further specification of tolerance doses and tolerance according to the different brain regions has to be done. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-01

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

  13. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

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    Chowdhary M

    2016-12-01

    Full Text Available Mudit Chowdhary,1,2 Kirtesh R Patel,1 Hasan H Danish,1 David H Lawson,3 Mohammad K Khan1 1Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA Abstract: Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM. Keywords: brain metastases, melanoma, radiation, BRAF inhibitors, vemurafenib, dabrafenib

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

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    Trude G. Simonsen

    2016-06-01

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

  15. 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.

  16. Prognosis and treatment of brain metastases in breast cancer%乳腺癌脑转移的预后及治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    钟颖

    2012-01-01

    This paper reviews the recent advances in the clinical research on breast cancer brain metastases. The main contents include the morbidity, risk factors, prognosis and treatment of this condition, among which the prognosis assessment system for breast cancer brain metastases is highlighted.%笔者就近年来乳腺癌脑转移的临床研究状况进行综述.主要包括乳腺癌脑转移的发病率、危险因素、预后及治疗.其中重点介绍乳腺癌脑转移的预后评价体系.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-03-01

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

  18. 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...

  19. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

    2011-01-01

    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive t

  20. 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.

  1. Risk factors for leptomeningeal carcinomatosis in patients with brain metastases who have previously undergone stereotactic radiosurgery.

    Science.gov (United States)

    Huang, Andrew J; Huang, Karen E; Page, Brandi R; Ayala-Peacock, Diandra N; Lucas, John T; Lesser, Glenn J; Laxton, Adrian W; Tatter, Stephen B; Chan, Michael D

    2014-10-01

    Our objective was to explore the hypothesis that the risk of leptomeningeal dissemination (LMD) in patients who underwent stereotactic radiosurgery (SRS) for brain metastases is influenced by the site of the primary cancer, the addition of whole brain radiation therapy (WBRT), surgical resection, and control over their systemic disease. We conducted a retrospective cohort analysis of 805 patients who were treated with SRS for brain metastases between 1999 and 2012 at the Wake Forest Baptist Medical Center, and excluded all patients with evidence of LMD before SRS. The primary outcome was LMD. Forty-nine of 795 patients developed LMD with a cumulative incidence of 6.2% (95% Confidence Interval (CI), 4.7-8.0). Median time from SRS to LMD was 7.4 months (Interquartile Range (IQR), 3.3-15.4). A colorectal primary site (Hazard Ratio (HR), 4.5; 95% CI 2.5-8.0; p LMD. There was no evidence that surgical resection before SRS altered the risk of LMD (HR, 1.1; 95 % CI 0.6-2.0, p = 0.78). In patients who underwent SRS for brain metastases, a colorectal or breast primary site, distant brain failure, younger age, and an increased number of intracranial metastases were independently associated with LMD. Given its relative rarity as an outcome, multi-institutional prospective studies will likely be necessary to validate and quantify these relationships.

  2. 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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatm......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...... retrospective thus possibly biasing data. Only three studies were identified comparing trastuzumab to lapatinib. Conclusively, no solid data exist on how to treat patients with HER2-positive disease and brain metastases. Although continuous HER2-blockade is recommended by international consensus guidelines......, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed....

  4. A Case of Lung Cancer with Brain Metastases Diagnosed After Epileptic Seizure

    Directory of Open Access Journals (Sweden)

    Hakan Simsek

    2016-04-01

    Full Text Available  LETTER TO THE EDITOR CONCERNING THE CASE REPORT “A case of lung cancer with brain metastases diagnosed after epileptic seizure” by M. Eroglu et al. J Clin Anal Med 2015; 6(3: 384-6

  5. 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.

  6. 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

  7. 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)....

  8. 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.

  9. 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

  10. 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.

  11. Leptomeningeal metastasis after surgical resection of brain metastases

    NARCIS (Netherlands)

    T.C. van der Ree; D.W.J. Dippel (Diederik); C.J.J. Avezaat (Cees); C.J. Vecht; M.J. van den Bent (Martin); P.A.E. Sillevis Smitt (Peter)

    1999-01-01

    textabstractOBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RES

  12. 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.

  13. 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

  14. 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.

  15. Optimization of brain metastases radiotherapy with TomoHDA.

    Science.gov (United States)

    Yartsev, Slav; Bauman, Glenn

    2017-01-01

    An upgrade of the helical tomotherapy technology by introducing variable fan-field width (dynamic jaws) reduced the penumbra in superior-inferior direction for the target. Possible implementation of this upgrade even for the cases of the targets with different dose prescriptions is proposed. An example of brain metastasis in proximity to the optical apparatus in need of the whole brain irradiation of 30 Gy and higher dose to the lesion is considered.

  16. Clinical outcome, proteome kinetics and angiogenic factors in serum after thermoablation of colorectal liver metastases

    NARCIS (Netherlands)

    Wertenbroek, Marieke W. J. L. A. E.; Schepers, Marianne; Kamminga-Rasker, Hannetta J.; Bottema, Jan T.; Kobold, Anneke C. Muller; Roelofsen, Han; de Jong, Koert P.

    2013-01-01

    Background: Thermoablation is used to treat patients with unresectable colorectal liver metastases (CRLM). We analyze clinical outcome, proteome kinetics and angiogenic markers in patients treated by cryosurgical ablation (CSA) or radiofrequency ablation (RFA). Methods: 205 patients underwent CSA (n

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

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

    2015-03-15

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

  18. 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.

  19. 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

  20. 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.

  1. 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.)

  2. 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.

  3. Identification of a seasonal pattern to brain metastases

    Directory of Open Access Journals (Sweden)

    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 

  4. 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.

  5. 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

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

    Science.gov (United States)

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

    2014-02-01

    High expression of fibrinogen and platelets are often observed in non-small cell lung 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 well as to determine the overall 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 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 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.

  7. 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.

  8. 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.

  9. 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.).

  10. Bilateral sphenoid wing metastases of prostate cancer presenting with extensive brain edema.

    Science.gov (United States)

    Lindsberg, P J; Tatlisumak, T; Tienari, J; Brander, A

    1999-05-01

    A 76-year-old man insidiously developed diffuse neurological symptoms: cognitive decline, dysphagia, dysphasia and mental disturbance. Computed tomography of the cranium revealed widespread bilateral brain edema and symmetrical bilateral sphenoid wing hyperostosis. Adjacent to the hyperostosis that resembled skull base meningiomas, two separate parenchymatous temporal lobe lesions enhancing with contrast medium were observed. The patient had earlier been diagnosed to have prostatic carcinoma. Dexamethasone therapy resulted in discontinuation of the neurological symptoms. The diagnosis of metastasized adenocarcinoma of the prostate was confirmed histologically on autopsy after a sudden death from pneumonia. Intracranial metastases of prostate cancer may have a predilection site at the sphenoid wing, and can mimic a skull base meningioma. Intracranial spread of prostatic adenocarcinoma should be considered in elderly men as a treatable cause of gradual neurological deterioration, especially if cranial malignancy or hyperostosis is found.

  11. 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.)

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

    Science.gov (United States)

    Mahmood, Faisal; Johannesen, Helle H.; Geertsen, Poul; Hansen, Rasmus H.

    2017-04-01

    An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point for acquiring the DW-MRI scan during the course of treatment, since to our knowledge this important question has not been addressed directly in previous studies. Twenty-nine metastases (N  =  29) from twenty-one patients, treated with whole-brain fractionated external beam RT were analyzed. Patients were scanned with a 1 T MRI system to acquire DW-, T2*W-, T2W- and T1W scans, before start of RT, at each fraction and at follow up two to three months after RT. The DW-MRI parameters were derived using regions of interest based on high b-value images (b  =  800 s mm‑2). Both volumetric and RECIST criteria were applied for response evaluation. It was found that in non-responding metastases the mean ADC decreased and in responding metastases it increased. The volume based response proved to be far more consistently predictable by the ADC change found at fraction number 7 and later, compared to the linear response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response for brain metastases patients. The earliest response stratification can be achieved using two DW-MRI scans, one pre-treatment and one at treatment day 7–9 (equivalent to 21

  19. 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.

  20. 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

  1. Differentiation of brain metastases by percentagewise quantification of intratumoral-susceptibility-signals at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Radbruch, Alexander, E-mail: Alexander.Radbruch@med.uni-heidelberg.de [Department of Neuroradiology, University of Heidelberg Medical Center (Germany); Department of Radiology, German Cancer Research Center (DKFZ) (Germany); Graf, Markus, E-mail: m.graf@dkfz.de [Software Development for Integrated Diagnosis and Therapy, German Cancer Research Center (DKFZ) (Germany); Kramp, Linda, E-mail: linda.kramp@gmx.de [Department of Neuroradiology, University of Heidelberg Medical Center (Germany); Wiestler, Benedikt, E-mail: b.wiestler@dkfz.de [Department of Neurooncology, University of Heidelberg Medical Center (Germany); Floca, Ralf, E-mail: r.floca@dkfz.de [Software Development for Integrated Diagnosis and Therapy, German Cancer Research Center (DKFZ) (Germany); Bäumer, Philipp, E-mail: philipp.baeumer@med.uni-heidelberg.de [Department of Neuroradiology, University of Heidelberg Medical Center (Germany); Roethke, Matthias, E-mail: m.roethke@dkfz.de [Department of Radiology, German Cancer Research Center (DKFZ) (Germany); Stieltjes, Bram, E-mail: b.stieltjes@dkfz.de [Department of Radiology, German Cancer Research Center (DKFZ) (Germany); Schlemmer, Heinz-Peter, E-mail: h.schlemmer@dkfz.de [Department of Radiology, German Cancer Research Center (DKFZ) (Germany); Heiland, Sabine, E-mail: sabine.heiland@med.uni-heidelberg.de [Department of Neuroradiology, University of Heidelberg Medical Center (Germany); Bendszus, Martin, E-mail: martin.bendszus@med.uni-heidelberg.de [Department of Neuroradiology, University of Heidelberg Medical Center (Germany)

    2012-12-15

    Introduction: Evaluation of intratumoral-susceptibility-signals (ITSS) in susceptibility-weighted-imaging (SWI) has been reported to improve diagnostic performance for solitary enhancing brain lesions. Due to the distinct morphologic variability of ITSS, standardized evaluation proved to be difficult. We analyzed, if a new postprocessing method using percentagewise quantification (PQ) of ITSS enables differentiation between different entities of cerebral metastases and may thus improve differential diagnosis in cases of unknown primary. Materials and methods: SWI and contrast enhanced T1-weighted MR images were acquired from 84 patients with intracerebral metastases (20 patients with mamma carcinoma (MC), 15 patients with malignant melanoma (MM), 49 patients with bronchial carcinoma (BC)) at 3 Tesla MR. Images were co-registered and enhancing lesions were delineated on T1-weighted images and the outline transferred to the corresponding SWI map. All voxels within the lesion presenting values below a reference value placed in the ventricular system were determined and percentagewise calculated. Results: Diagnostic performance of percentagewise quantification (PQ) of ITSS, as determined with area under the receiver operating characteristic curve (AUC) was excellent (AUC = 0.96; 95% confidence interval (CI) 0.90, 1.00) to discriminate MM from MC, good for the discrimination of MM and BC (AUC = 0.81, 95% CI 0.70, 0.92) and poor for the discrimination of MC and BC (AUC = 0.60; 95% CI 0.47, 0.73). Conclusion: PQ is a new approach for the assessment of SWI that can be used for differential diagnosis of intracerebral metastases. Metastases of MM and MC or BC can be distinguished with high sensitivity and specificity.

  2. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Clara Y.H.; Chang, Steven D. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Gibbs, Iris C. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Adler, John R.; Harsh, Griffith R. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Atalar, Banu [Department of Radiation Oncology, Acibadem University School of Medicine, Istanbul (Turkey); Lieberson, Robert E. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States)

    2012-11-01

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

  4. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain

    Directory of Open Access Journals (Sweden)

    Mami Noda

    2012-12-01

    Full Text Available In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain.

  5. Clinical Features of Intradural Extramedullary Spinal Cord Metastases 
in Primary Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan XU

    2016-08-01

    Full Text Available Background and objective Intradural extramedullary spinal cord metastases in lung cancer is rare, and it leads to severe neurological damage. The aim of this study is to identify the clinical features of intradural extramedullary spinal cord metastases in primary lung cancer patients. Methods The 8 cases of lung cancer with intradural extramedullary metastases, who were hospitalized in Peking Union Medical College Hospital (PUMCH during May 2013 to May 2016, were enrolled in the retrospective study. Medical charts of the 8 patients were reviewed systematically. Results Intradural extramedullary spinal cord metastases was diagnosed in 7 cases with non-small cell lung cancer (NSCLC and 1 case with small cell lung cancer (SCLC. Cauda equina syndrome was the most common clinical manifestation. Malignant cells in cerebrospinal fluid were positive in all the 5 cases (100% who underwent lumbar puncture. Contrast-enhanced magnetic resonance imaging (MRI of spine manifested as diffuse abnormal enhancement of pial lining of spinal cordin 3 cases, intradural extramedullary nodules in 4 cases, and both of them in 1 case. Neurological symptoms were improved or stable in 4 cases who underwent targeted therapy and/or radiotherapy. The median overall survival was 5.8 months. Conclusion Intradural extramedullary spinal cord metastases can be diagnosed with caution according to its neurological symptoms and contrast-enhanced MRI presentation.Targeted therapy and/or radiotherapy may be effective for symptoms control.

  6. 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...

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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......CMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P metabolic or hemodynamic parameters...... was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia....

  9. 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.

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

    OpenAIRE

    Liu, Haisong; Andrews, David W.; Evans, James J.; Werner-Wasik, Maria; Yan YU; Dicker, Adam Paul; Shi, Wenyin

    2016-01-01

    Objectives This study compares the dosimetry and efficiency of two modern radiosurgery [stereotactic radiosurgery (SRS)] modalities for multiple brain metastases [Gamma Knife (GK) 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 to 10.5 cc. SRS doses were prescribed according to the size of ...

  11. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kocher, Martin [University Hospital Cologne, Department of Radiation Oncology, Koeln (Germany); Wittig, Andrea [Philips-University Marburg, Department of Radiotherapy and Radiation Oncology, Marburg (Germany); Piroth, Marc Dieter [University Hospital RWTH Aachen, Department of Radiotherapy and Radiation Oncology, Aachen (Germany); Helios-Klinikum Wuppertal, Klinik fuer Strahlentherapie und Radio-Onkologie, Wuppertal (Germany); Treuer, Harald; Ruge, Maximilian [University Hospital Cologne, Department of Stereotaxy and Functional Neurosurgery, Koeln (Germany); Seegenschmiedt, Heinrich [Strahlenzentrum Hamburg, Radioonkologie und Strahlentherapie, Hamburg (Germany); Grosu, Anca-Ligia [University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Guckenberger, Matthias [University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); University Hospital Zurich, Department of Radiation Oncology, Zuerich (Switzerland)

    2014-06-15

    This report from the Working Group on Stereotaktische Radiotherapie of the German Society of Radiation Oncology (Deutsche Gesellschaft fuer Radioonkologie, DEGRO) provides recommendations for the use of stereotactic radiosurgery (SRS) on patients with brain metastases. It considers existing international guidelines and details them where appropriate. The main recommendations are: Patients with solid tumors except germ cell tumors and small-cell lung cancer with a life expectancy of more than 3 months suffering from a single brain metastasis of less than 3 cm in diameter should be considered for SRS. Especially when metastases are not amenable to surgery, are located in the brain stem, and have no mass effect, SRS should be offered to the patient. For multiple (two to four) metastases - all less than 2.5 cm in diameter - in patients with a life expectancy of more than 3 months, SRS should be used rather than whole-brain radiotherapy (WBRT). Adjuvant WBRT after SRS for both single and multiple (two to four) metastases increases local control and reduces the frequency of distant brain metastases, but does not prolong survival when compared with SRS and salvage treatment. As WBRT carries the risk of inducing neurocognitive damage, it seems reasonable to withhold WBRT for as long as possible. A single (marginal) dose of 20 Gy is a reasonable choice that balances the effect on the treated lesion (local control, partial remission) against the risk of late side effects (radionecrosis). Higher doses (22-25 Gy) may be used for smaller (< 1 cm) lesions, while a dose reduction to 18 Gy may be necessary for lesions greater than 2.5-3 cm. As the infiltration zone of the brain metastases is usually small, the GTV-CTV (gross tumor volume-clinical target volume) margin should be in the range of 0-1 mm. The CTV-PTV (planning target volume) margin depends on the treatment technique and should lie in the range of 0-2 mm. Distant brain recurrences fulfilling the aforementioned criteria

  13. 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.

  14. Bone Metastases in carcinoid tumors : Clinical features, imaging characteristics, and markers of bone metabolism

    NARCIS (Netherlands)

    Meijer, WG; van der Veer, E; Jager, PL; van der Jagt, EJ; Piers, BA; Kema, IP; de Vries, EGE; Willemse, PHB

    2003-01-01

    The purpose of this study was to describe the clinical presentation of bone metastases in patients with carcinoid tumors and to determine the diagnostic value of imaging techniques and markers of bone metabolism. Methods: This retrospective study was performed on the entire group of patients with ca

  15. 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.

  16. 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.

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

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    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

  18. 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.

  19. "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

  20. [Clinical picture, diagnosis and treatment of the brain lesions in lymphosarcomas].

    Science.gov (United States)

    Setdikov, R A; Kruglova, G V

    1986-01-01

    The study group included 11 patients with brain metastases of disseminated lymphosarcoma. The most common clinical course was progression of the disease which manifested itself in the advancement of general cerebral symptoms as well as focal ones indicative of hemisphere, subcortex or cerebral trunk involvement. High single intravenous doses of cyclophosphamide and rubomycin and radiotherapy or their combination appeared highly effective in cases of brain specific involvement: complete or partial regression of neurologic symptoms was observed in 7 and 3 patients, respectively. Radiation treatment was followed by COP, COAP or CAMP polychemotherapy to curb extracerebral disease progression. Low median survival of patients with brain metastases (5.1 months) was due to extracerebral tumor progression. However, brain metastases were not immediate death-causing factors.

  1. 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

  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. Afatinib-refractory brain metastases from EGFR-mutant non-small-cell lung cancer successfully controlled with erlotinib: a case report.

    Science.gov (United States)

    Nonagase, Yoshikane; Okamoto, Kunio; Iwasa, Tsutomu; Yoshida, Takeshi; Tanaka, Kaoru; Takeda, Masayuki; Kaneda, Hiroyasu; Shimizu, Toshio; Tsurutani, Junji; Nakagawa, Kazuhiko

    2016-03-01

    Both afatinib and erlotinib are tyrosine kinase inhibitors that inhibit aberrant epidermal growth factor receptor (EGFR) signals in non-small-cell lung cancer (NSCLC). Afatinib is an irreversible inhibitor directed against EGFR, ErbB-2, and ErbB-4, whereas erlotinib is a reversible inhibitor directed against EGFR only. Although afatinib has been shown to be effective in the treatment for erlotinib-refractory and/or gefitinib-refractory central nervous system metastases from NSCLC, little is known about the efficacy of erlotinib for afatinib-refractory central nervous system metastases. In the present report we describe a case of EGFR mutation-positive NSCLC in which brain metastases developed during first-line afatinib treatment. Whole-brain radiation therapy and substitution of erlotinib for afatinib led to successful shrinkage of the brain metastases. Our report highlights the potential benefit of erlotinib for the management of brain metastases refractory over afatinib in patients with NSCLC.

  4. Cerebral control and survival after stereotactic radiotherapy of brain metastases; Zerebrale Kontrolle und Ueberleben nach stereotaktischer Strahlentherapie von Hirnmetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, Elmar Till

    2014-06-04

    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.

  5. Comparison of computed tomography and radionuclide scanning for detection of brain metastases in small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Crane, J.M.; Nelson, M.J.; Ihde, D.C.; Makuch, R.W.; Glatstein, E.; Zabell, A.; Johnston-Early, A.; Bates, H.R.; Saini, N.; Cohen, M.H.

    1984-09-01

    Neurologic history and examination, radionuclide brain scans (RN), and computed tomographic brain scans (CT) were performed at diagnosis and sequentially in 153 consecutive patients with small cell lung cancer (SCLC) to assess the sensitivity and accuracy of these screening methods and to determine whether the early detection of brain metastases influences survival. CT scans (sensitivity, 98%; positive predictive accuracy, 98%) were superior to RN scans (sensitivity, 71%; positive predictive accuracy, 86%) in patients with or without neurologic signs or symptoms. However, CT scans were positive in only 6% of asymptomatic patients at diagnosis and 13% of asymptomatic patients after systemic therapy. Brain metastases detected by CT scan were the sole site of extensive-stage disease in 6% of patients at diagnosis. Despite the enhanced ability of CT scans to detect asymptomatic lesions, survival after therapeutic cranial irradiation was similar for asymptomatic and symptomatic patients. The results suggest that CT brain scans should be used routinely in SCLC patients with neurologic signs or symptoms, at diagnosis (when treatment decisions are based on stage), and at six-month intervals in patients with prior brain metastases and in whom erratic follow-up is likely.

  6. 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.

  7. 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.

  8. 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.

  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. Clinical use of brain volumetry.

    Science.gov (United States)

    Giorgio, Antonio; De Stefano, Nicola

    2013-01-01

    Magnetic resonance imaging (MRI)-based brain volumetry is increasingly being used in the clinical setting to assess brain volume changes from structural MR images in a range of neurologic conditions. Measures of brain volumes have been shown to be valid biomarkers of the clinical state and progression by offering high reliability and robust inferences on the underlying disease-related mechanisms. This review critically examines the different scenarios of the application of MRI-based brain volumetry in neurology: 1) supporting disease diagnosis, 2) understanding mechanisms and tracking clinical progression of disease, and 3) monitoring treatment effect. These aspects will be discussed in a wide range of neurologic conditions, with particular emphasis on Alzheimer's disease and multiple sclerosis.

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-15

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

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-15

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

  15. 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.

  16. 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.

  17. BM-16INCREASED ACUTE RADIATION EFFECT (ARE) WITH IPILUMUMAB AND RADIOSURGERY IN PATIENTS WITH MELANOMA BRAIN METASTASES

    Science.gov (United States)

    Khoja, Leila; Kurtz, Goldie; Zadeh, Gelareh; Laperriere, Normand; Menard, Cynthia; Millar, Barbara-Ann; Bernstein, Mark; Kongkham, Paul; Joshua, Anthony; Hogg, David; Butler, Marcus; Chung, Caroline

    2014-01-01

    BACKGROUND: Ipilumumab (Ipi), an antibody that enhances T-cell activation, has been shown to improve survival in patients with metastatic melanoma. Ipilumumab may have synergistic effects with radiotherapy but this may result in increased toxicity. This study investigated the incidence of acute radiation effect (ARE) in patients with melanoma brain metastases treated with Ipi and radiosurgery (SRS) or whole brain radiotherapy (WBRT). METHODOLOGY: This retrospective study included metastatic melanoma patients treated at our institution from 2008-2013 who received SRS or WBRT for brain metastases within 4 months of Ipi treatment. We evaluated the incidence, timing and factors associated with acute radiation effect (ARE). RESULTS: From 159 patients treated with Ipi, 22 patients also received brain RT within 4 months of treatment. Three patients were excluded for lack of follow-up brain imaging, thus 19 were analysed: 14 males and 5 females, with median age 58 years (range 24-82). Ten were treated with SRS, 7 with WBRT, and 2 with SRS plus WBRT. Median dose for SRS was 21 Gy (range: 15-24 Gy). Five of 13 patients treated with SRS (38%) experienced symptomatic edema requiring steroids within 1 month of starting Ipi, and within 4 months of RT. One patient had a haemorrhage and 1 required surgical resection, which demonstrated viable disease. Therefore 3 patients (23%) treated with SRS developed isolated ARE. These metastases had volumes less than 4.2 cm3 and were treated within 4 months of Ipi to a median dose of 19.5 Gy (range 15-21 Gy). No patients with WBRT alone developed ARE. CONCLUSIONS: Following SRS for brain mets and Ipi, ARE was seen in 23% of patients within 4 months of starting Ipi treatment. This is greater than the commonly reported 10% risk of ARE after SRS alone for brain metastasis. No increased toxicity was seen with WBRT and Ipi.

  18. Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2015-10-01

    SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT...blood-brain barrier (BBB) at concentrations sufficient to successfully treat metastatic disease. The objective of the proposed work is to use an active ...We hypothesize that monocytes/macrophages are actively recruited to metastases by cytokines elaborated by the tumors and that these cells can be

  19. 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.

  20. Stereotactic radiosurgery in the palliative treatment of brain metastases; Radiocirurgia estereotatica no tratamento paliativo das metastases cerebrais

    Energy Technology Data Exchange (ETDEWEB)

    Faria, Sergio L.; Souhami, Luis; Bahary, Jean-Paul; Clark, Brenda; Adamson, Nelson; Podgorsak, Ervin B. [McGill Univ., Montreal, PQ (Canada). Dept. of Oncology; Caron, Jean-Louis; Villemure, Jean-Guy; Olivier, Andre [McGill Univ., Montreal, PQ (Canada). Dept. of Neurosurgery

    1995-09-01

    Between October, 1988 and November, 1993, 57 patients with metastatic brain disease underwent stereotactic radiosurgery at McGill University, canada. Four patients were excluded from this analysis leaving a total of 53 evaluable patients (with 57 lesions). Radiosurgery was performed with the dynamic rotation technique which uses an isocentric, 10 MV, linear accelerator. A median dose of 1,800 c Gy was given in a single session. In 89% of the cases radiosurgery was used after failure to conventional brain radiotherapy. With a median follow-up of 6 months, the response rate was 65% . Treatments were well tolerated and only 4 patients (7%) developed late complications related to the therapy, with one patient requiring a surgical resection of an area of radionecrose. Radiosurgery appears to be and effective and safe treatment for selected patients with metastatic brain disease, recurrent post-conventional radiotherapy. Its value as a single treatment modality for patients with isolated brain metastasis is now being studied in prospective trials. (author). 29 refs., 4 figs., 4 tabs.

  1. Outcome Evaluation of Oligometastatic Patients Treated with Surgical Resection Followed by Hypofractionated Stereotactic Radiosurgery (HSRS) on the Tumor Bed, for Single, Large Brain Metastases

    Science.gov (United States)

    Pessina, Federico; Navarria, Pierina; Cozzi, Luca; Ascolese, Anna Maria; Maggi, Giulia; Riva, Marco; Masci, Giovanna; D’Agostino, Giuseppe; Finocchiaro, Giovanna; Santoro, Armando; Bello, Lorenzo; Scorsetti, Marta

    2016-01-01

    Purpose The aim of this study was to evaluate the benefit of a combined treatment, surgery followed by adjuvant hypofractionated stereotactic radiosurgery (HSRS) on the tumor bed, in oligometastatic patients with single, large brain metastasis (BM). Methods and Materials Fom January 2011 to March 2015, 69 patients underwent complete surgical resection followed by HSRS with a total dose of 30Gy in 3 daily fractions. Clinical outcome was evaluated by neurological examination and MRI 2 months after radiotherapy and then every 3 months. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume, and brain distant progression as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Surgical morbidity and radiation-therapy toxicity, local control (LC), brain distant progression (BDP), and overall survival (OS) were evaluated. Results The median preoperative volume and maximum diameter of BM was 18.5cm3 (range 4.1–64.2cm3) and 3.6cm (range 2.1-5-4cm); the median CTV was 29.0cm3 (range 4.1–203.1cm3) and median PTV was 55.2cm3 (range 17.2–282.9cm3). The median follow-up time was 24 months (range 4–33 months). The 1-and 2-year LC in site of treatment was 100%; the median, 1-and 2-year BDP was 11.9 months, 19.6% and 33.0%; the median, 1-and 2-year OS was 24 months (range 4–33 months), 91.3% and 73.0%. No severe postoperative morbidity or radiation therapy toxicity occurred in our series. Conclusions Multimodal approach, surgery followed by HSRS, can be an effective treatment option for selected patients with single, large brain metastases from different solid tumors. PMID:27348860

  2. Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with {sup 18}F-ML-10

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Aaron M. [Rabin Medical Center, Department of Radiation Oncology, Nuclear Medicine, Radiology and Neurology, Petach-Tikvah (Israel); Tel Aviv University, Sackler School of Medicine, Tel-Aviv (Israel); Rabin Medical Center, Department of Oncology, Radiotherapy Unit Davvidoff Center, Petach-Tikvah (Israel); Ben-Ami, Miri; Reshef, Ayelet; Davidson, Tal [Aposense Ltd., Petach-Tikvah (Israel); Steinmetz, Adam; Kundel, Yulia; Inbar, Edna; Djaldetti, Ruth; Fenig, Eyal [Rabin Medical Center, Department of Radiation Oncology, Nuclear Medicine, Radiology and Neurology, Petach-Tikvah (Israel); Tel Aviv University, Sackler School of Medicine, Tel-Aviv (Israel); Ziv, Ilan [Rabin Medical Center, Department of Radiation Oncology, Nuclear Medicine, Radiology and Neurology, Petach-Tikvah (Israel); Tel Aviv University, Sackler School of Medicine, Tel-Aviv (Israel); Aposense Ltd., Petach-Tikvah (Israel)

    2012-09-15

    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 {sup 18}F-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 {sup 18}F-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 {sup 18}F-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 {sup 18}F-ML-10 PET scan. A highly significant correlation was found between early changes on the {sup 18}F-ML-10 scan and later changes in tumor anatomical dimensions (r = 0.9). These results support the potential of {sup 18}F-ML-10 PET as a novel tool for the early detection of response of brain metastases to WBRT. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. 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.

  6. Time-delayed contrast-enhanced MRI improves detection of brain metastases: a prospective validation of diagnostic yield.

    Science.gov (United States)

    Cohen-Inbar, Or; Xu, Zhiyuan; Dodson, Blair; Rizvi, Tanvir; Durst, Christopher R; Mukherjee, Sugoto; Sheehan, Jason P

    2016-12-01

    The radiological detection of brain metastases (BMs) is essential for optimizing a patient's treatment. This statement is even more valid when stereotactic radiosurgery, a noninvasive image guided treatment that can target BM as small as 1-2 mm, is delivered as part of that care. The timing of image acquisition after contrast administration can influence the diagnostic sensitivity of contrast enhanced magnetic resonance imaging (MRI) for BM. Investigate the effect of time delayed acquisition after administration of intravenous Gadavist® (Gadobutrol 1 mmol/ml) on the detection of BM. This is a prospective IRB approved study of 50 patients with BM who underwent post-contrast MRI sequences after injection of 0.1 mmol/kg Gadavist® as part of clinical care (time-t0), followed by axial T1 sequences after a 10 min (time-t1) and 20 min delay (time-t2). MRI studies were blindly compared by three neuroradiologists. Single measure intraclass correlation coefficients were very high (0.914, 0.904 and 0.905 for time-t0, time-t1 and time-t2 respectively), corresponding to a reliable inter-observer correlation. The delayed MRI at time-t2 delayed sequences showed a significant and consistently higher diagnostic sensitivity for BM by every participating neuroradiologist and for the entire cohort (p = 0.016, 0.035 and 0.034 respectively). A disproportionately high representation of BM detected on the delayed studies was located within posterior circulation territories (compared to predictions based on tissue volume and blood-flow volumes). Considering the safe and potentially high yield nature of delayed MRI sequences, it should supplement the standard MRI sequences in all patients in need of precise delineation of their intracranial disease.

  7. [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

    Science.gov (United States)

    Udagawa, Masaru; Tominaga, Ben; Kobayashi, Daisuke; Ishikawa, Yuuya; Watanabe, Shuuichi; Adikrisna, Rama; Okamoto, Hiroyuki; Yabata, Eiichi

    2015-11-01

    We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases.

  8. A systematic review of clinical outcomes for patients diagnosed with skin cancer spinal metastases.

    Science.gov (United States)

    Goodwin, C Rory; Sankey, Eric W; Liu, Ann; Elder, Benjamin D; Kosztowski, Thomas; Lo, Sheng-Fu L; Fisher, Charles G; Clarke, Michelle J; Gokaslan, Ziya L; Sciubba, Daniel M

    2016-05-01

    OBJECT Surgical procedures and/or adjuvant therapies are effective modalities for the treatment of symptomatic spinal metastases. However, clinical results specific to the skin cancer spinal metastasis cohort are generally lacking. The purpose of this study was to systematically review the literature for treatments, clinical outcomes, and survival following the diagnosis of a skin cancer spinal metastasis and evaluate prognostic factors in the context of spinal skin cancer metastases stratified by tumor subtype. METHODS The authors performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles since 1950 that reported survival, clinical outcomes, and/or prognostic factors for the skin cancer patient population with spinal metastases. The methodological quality of reviews was assessed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) tool. RESULTS Sixty-five studies met the preset criteria and were included in the analysis. Of these studies, a total of 25, 40, 25, and 12 studies included patients who underwent some form of surgery, radiotherapy, chemotherapy, or observation alone, respectively. Sixty-three of the 65 included studies were retrospective in nature (Class of Evidence [CoE] IV), and the 2 prospective studies were CoE II. Based on the studies analyzed, the median overall survival for a patient with a spinal metastasis from a primary skin malignancy is 4.0 months; survival by tumor subtype is 12.5 months for patients with basal cell carcinoma (BCC), 4.0 months for those with melanoma, 4.0 months for those with squamous cell carcinoma, 3.0 months for those with pilomatrix carcinoma, and 1.5 months for those with Merkel cell carcinoma (p cancer lesion was 3.5% (n = 21/608, range 0.2%-100.0%), and the rate of known spine metastasis recurrence despite treatment for all skin malignancies was 2.8% (n = 17/608, range 0.0%-33.3%). Age greater than 65 years, sacral spinal involvement, presence

  9. Cognitive Predictors of Reasoning through Treatment Decisions in Patients with Newly Diagnosed Brain Metastases.

    Science.gov (United States)

    Gerstenecker, Adam; Duff, Kevin; Meneses, Karen; Fiveash, John B; Nabors, Louis B; Triebel, Kristen L

    2015-07-01

    To examine the association between reasoning through medical treatment decisions and cognition in a sample of patients with brain metastasis. The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results indicate that measures of episodic memory and processing speed were associated with reasoning. Using these two predictors, actuarial equations were constructed that can be used to help screen for impaired reasoning ability in patients' with brain metastasis. The equations presented in this study have clinical significance as they can be used to help identify patients at risk for possessing a diminished ability to reason through medical treatment decisions and, thus, are in need of a more comprehensive evaluation of their medical decision-making capacity.

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

    OpenAIRE

    2012-01-01

    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, respect...

  11. 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.

  12. A multidisciplinary bone metastases clinic at Toronto Sunnybrook Regional Cancer Centre - A review of the experience from 1999 to 2005.

    Science.gov (United States)

    Li, Kathy K; Sinclair, Emily; Pope, Joan; Farhadian, Macey; Harris, Kristin; Napolskikh, Julie; Yee, Albert; Librach, Lawrence; Wynnychuk, Lesia; Danjoux, Cyril; Chow, Edward; Bone, On Behalf Of The; Team, Metastases

    2008-09-01

    Our objective in this study was to review the experience of a one-stop multidisciplinary bone metastases clinic (BMC) that offers a coordinated multidisciplinary approach to the care of cancer patients with bone metastases in a tertiary cancer centre. Patients with symptomatic bone metastases were referred to BMC and assessed by a team of specialists in various disciplines - interventional radiology, orthopedic surgery, palliative medicine, and radiation oncology. At initial consultation, patient demographics, reasons for referral, and case disposition were recorded. From January 1999 to February 2005, a total of 272 patients with bone metastases were referred to the BMC. The median age was 65 years (range 28-95) and median KPS score at consultation was 60 (range 30-90). The majority of patients came from home (74%), while others came from a nursing home or the hospital (9%). Almost a third (28%) of patients had 2 or more reasons of referral, yielding a total of 354 reasons. The most common reason for referral was bone pain (42%), bone metastases (21%), high risk for pathological fracture (12%), and pathological fracture (10%). Of the 272 patients who received consultation, 40% received palliative radiotherapy, 19% received interventional surgery, 7% were referred to other support services such as palliative care, physiotherapy, and 7% had further investigation or imaging. A multidisciplinary clinic is useful for co-coordinating the management of bone metastatic disease in symptomatic patients.

  13. Whole brain radiation therapy with simultaneously integrated brain metastases boost a planning and effect study%脑转移癌螺旋断层放疗剂量学特点和近期疗效分析

    Institute of Scientific and Technical Information of China (English)

    路娜; 王雅棣; 姚波; 陈点点; 刘清智

    2014-01-01

    included cerebral edema ,asthenia ,alopecia ,decreased hearing and memory.Conclusion Whole brain radiotherapy combined with simultaneous integrated boost-tomotherapy has bet-ter dosimetric characteristics and safe in clinics ,and can be used in radiotherapy for brain metastases.

  14. 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.

  15. 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

  16. Central nervous system metastases from breast carcinoma: a clinical and laboratorial study in 47 patients

    Directory of Open Access Journals (Sweden)

    MACHADO ALUÍZIO B.B.

    1998-01-01

    Full Text Available In this retrospective study, 47 patients with clinical diagnosis of central nervous system metastases of breast cancer were evaluated by computerized tomography (CT, magnetic resonance imaging (MRI and cerebrospinal fluid (CSF examination. The patients were divided in 2 groups: 1, without leptomeningeal neoplasm and 2, with leptomeningeal neoplasm. In the group 2, the time interval between the primary disease and the central nervous system metastasis as well as the survival time were shorter than in group 1 (40 and 4.3 months in group 2 versus 57 and 10 months respectively, in group 1. In both groups the most common neurological symptoms and signs were intracranial hypertension and motor deficits. The most sensitive diagnostic methods were CT and MRI in group 1, and the CSF examination in group 2. The use of the tumor markers CEA and CA-15.3 in the routine examination of CSF showed promising results, mainly in leptomeningeal forms.

  17. Cognitive Predictors of Understanding Treatment Decisions in Patients with Newly Diagnosed Brain Metastases

    Science.gov (United States)

    Gerstenecker, Adam; Meneses, Karen; Duff, Kevin; Fiveash, John B.; Marson, Daniel C.; Triebel, Kristen L.

    2015-01-01

    Background Medical decision-making capacity is a higher-order functional skill that refers to a patient’s ability to make informed, sound decisions related to care and treatment. In a medical context, understanding is the most cognitively demanding consent standard and refers to a patient’s ability to comprehend information to the extent that informed decisions can be made. Methods The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically-matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results Results indicate that measures of simple attention, verbal fluency, verbal memory, processing speed, and executive functioning were all associated with understanding, and that verbal memory and phonemic fluency were the primary cognitive predictors. Using these two primary predictors, equations can be constructed to predict the ability to understand treatment decisions in patients with brain metastasis. Conclusions Although preliminary, these data demonstrate how cognitive measures can estimate understanding as it relates to medical decision-making capacities in these patients. Clinically, these findings suggest that poor verbal memory and expressive language function could serve as “red flags” for reduced consent capacity in this patient population, and, thus, signal that a more comprehensive medical decision-making capacity evaluation is warranted. PMID:25735262

  18. 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.

  19. {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.)

  20. [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 %).

  1. Distant Metastases Following Permanent Interstitial Brachytherapy for Patients With Clinically Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taira, Al V. [Western Radiation Oncology, Mountain View, California (United States); Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, West Virginia (United States); Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, West Virginia (United States); Adamovich, Edward [Department of Pathology, Wheeling Hospital, Wheeling, West Virginia (United States); Wallner, Kent E. [Puget Sound Healthcare Corporation, Group Health Cooperative, University of Washington, Seattle, Washington (United States)

    2012-02-01

    Purpose: Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving definitive external beam radiation therapy (XRT). To date, none of these studies has compared distant metastases and CSS in brachytherapy patients. In this study, we evaluate such parameters in a consecutive cohort of brachytherapy patients. Methods and Materials: From April 1995 to June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with brachytherapy. Risk groups were stratified according to National Comprehensive Cancer Network ( (www.nccn.org)) guidelines. Subgroups of 658, 893, and 289 patients were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.2 years. Along with brachytherapy implantation, 901 (49.0%) patients received supplemental XRT, and 670 (36.4%) patients received androgen deprivation therapy (median duration, 4 months). The mode of failure (biochemical, local, or distant) was determined for each patient for whom therapy failed. Cause of death was determined for each deceased patient. Multiple parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. Conclusions: Excellent CSS and MFS rates are achievable with high

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

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    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.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

  9. Clinical outcome in patients with intramedullary spinal cord metastases from lung cancer.

    Science.gov (United States)

    Conill, C; Marruecos, J; Verger, E; Berenguer, J; Lomeña, F; Domingo-Domènech, J; Grau, J J; Casas, F

    2007-03-01

    Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual.

  10. SU-E-T-395: Evaluation of Multiple Brain Metastases Stereotactic Treatment Planning in Cyberknife Versus Linac

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    Vikraman, S; Rajesh, Thiyagarajan; Karrthick, Kp; Sambasivaselli, R; Senniandavar, V; Ramu, M; Maragathaveni, S; Dhivya, N; Tejinder, K [Medanta The Medicity Hospital, Gurgaon (India); Manigandan, D [Fortis Hospital, Mohali, Punjab (India); Muthukumaran, M [Apollo Speciality Hospitals, Chennai, TN (India)

    2015-06-15

    Purpose: The purpose of this study was to evaluate multiple brain metastases stereotactic treatment planning of Cyberknife versus linac using dose volume based indices. Methods: Fifteen multiple brain metastases patients were taken for this study from Cyberknife Multiplan TPSv4.6.0. All these patients underwent stereotactic treatment in Cyberknife. For each patient VMAT stereotactic treatment plan was generated in MONACO TPSv5.0 using Elekta beam modulator MLC and matched the delivered plan. A median dose of 8.5Gy(range 7–12Gy) per fraction was prescribed. Tumor volume was in the range of 0.06–4.33cc. Treatment plan quality was critically evaluated by comparing DVH indices such as D98, D95, CI, and HI for target volumes. Maximum point doses and volume doses were evaluated for critical organs. Results: For each case, target coverage of D98 was achieved with 100% prescription dose with SD of 0.29% and 0.41% in Linac and Cyberknife respectively. The average conformity index(CI) of 1.26±0.0796 SD for Cyberknife and 1.92±0.60SD for linac were observed. Better homogeneity Index (HI) of 1.17±0.09SD was observed in linac as compared to Cyberknife HI of 1.24±0.05SD.All the critical organ doses were well within tolerance limit in both linac and Cyberknife plans. There is no significant difference of maximum point doses for brainstem and optic chiasm. Treatment time and number of monitor units are more in Cyberknife compared to linac. The average volume receiving 12Gy in whole brain was 6% and 12% for Cyberknife and linac respectively. 1000cc of whole brain received 60% lesser dose in Linac compared to Cyberknife in all cases. Conclusion: The study shows that dosimetrically comparable plans are achievable Cyberknife and Linac. However, a better conformity, target coverage, lesser OAR dose is achieved with Cyberknife due to greater degrees of freedom with robotic gantry and smaller collimator for multiple targets.

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

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    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.)

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

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    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.

  13. A phase 2 study of radiosurgery and temozolomide for patients with 1 to 4 brain metastases

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    John B. Fiveash, MD

    2016-04-01

    Conclusions: In this study, there was a relatively low risk of distant brain failure observed in the nonmelanoma subgroup receiving temozolamide. However, patient selection factors rather than chemotherapy treatment efficacy are more likely the reason for the relatively low risk of distant brain failure observed in this study. Future trial design should account for these risk factors.

  14. Value of C-11-methionine PET in imaging brain tumours and metastases

    NARCIS (Netherlands)

    Glaudemans, Andor W J M; Enting, Roeline; Heesters, Martinus; Dierckx, Rudi A J O; van Rheenen, Ronald W J; Walenkamp, Annemiek M E; Slart, Riemer H J A

    2013-01-01

    C-11-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The Introduct

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

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    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

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

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    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.

  17. Institutional, Retrospective Analysis of 777 Patients With Brain Metastases: Treatment Outcomes and Diagnosis-Specific Prognostic Factors

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    Antoni, Delphine, E-mail: Dantoni@strasbourg.unicancer.fr [Radiotherapy Department, Paul Strauss Cancer Center, Strasbourg (France); Clavier, Jean-Baptiste; Pop, Marius; Schumacher, Catherine [Radiotherapy Department, Paul Strauss Cancer Center, Strasbourg (France); Lefebvre, François [Biostatistics Department, Strasbourg University, Strasbourg (France); Noël, Georges [Radiotherapy Department, Paul Strauss Cancer Center, Strasbourg (France)

    2013-07-15

    Purpose: To retrospectively evaluate the prognostic factors and survival of a series of 777 patients with brain metastases (BM) from a single institution. Methods and Materials: Patients were treated with surgery followed by whole-brain radiation therapy (WBRT) or with WBRT alone in 16.3% and 83.7% of the cases, respectively. The patients were RPA (recursive partitioning analysis) class I, II, and III in 11.2%, 69.6%, and 18.4% of the cases, respectively; RPA class II-a, II-b, and II-c in 8.3%, 24.8%, and 66.9% of the cases, respectively; and with GPA (graded prognostic assessment) scores of 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 in 35%, 27.5%, 18.2%, and 8.6% of the cases, respectively. Results: The median overall survival (OS) times according to RPA class I, II, and III were 20.1, 5.1, and 1.3 months, respectively (P<.0001); according to RPA class II-a, II-b, II-c: 9.1, 8.9, and 4.0 months, respectively (P<.0001); and according to GPA score 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0: 2.5, 4.4, 9.0, and 19.1 months, respectively (P<.0001). By multivariate analysis, the favorable independent prognostic factors for survival were as follows: for gastrointestinal tumor, a high Karnofsky performance status (KPS) (P=.0003) and an absence of extracranial metastases (ECM) (P=.003); for kidney cancer, few BM (P=.002); for melanoma, few BM (P=.01), an absence of ECM (P=.002), and few ECM (P=.0002); for lung cancer, age (P=.007), a high KPS (P<.0001), an absence of ECM (P<.0001), few ECM and BM (P<.0001 and P=.0006, respectively), and control of the primary tumor (P=.004); and for breast cancer, age (P=.001), a high KPS (P=.007), control of the primary tumor (P=.05), and few ECM and BM (P=.01 and P=.0002, respectively). The triple-negative subtype was a significant unfavorable factor (P=.007). Conclusion: Prognostic factors varied by pathology. Our analysis confirms the strength of prognostic factors used to determine the GPA score, including the genetic subtype for breast cancer.

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

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    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)

  19. Perillyl Alcohol and Its Drug-Conjugated Derivatives as Potential Novel Methods of Treating Brain Metastases

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    Thomas C. Chen

    2016-09-01

    Full Text Available Metastasis to the central nervous system remains difficult to treat, and such patients are faced with a dismal prognosis. The blood-brain barrier (BBB, despite being partially compromised within malignant lesions in the brain, still retains much of its barrier function and prevents most chemotherapeutic agents from effectively reaching the tumor cells. Here, we review some of the recent developments aimed at overcoming this obstacle in order to more effectively deliver chemotherapeutic agents to the intracranial tumor site. These advances include intranasal delivery to achieve direct nose-to-brain transport of anticancer agents and covalent modification of existing drugs to support enhanced penetration of the BBB. In both of these areas, use of the natural product perillyl alcohol, a monoterpene with anticancer properties, contributed to promising new results, which will be discussed here.

  20. The clinical implication of cancer-associated microvasculature and fibroblast in advanced colorectal cancer patients with synchronous or metachronous metastases.

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    Yoonjin Kwak

    Full Text Available BACKGROUND: We aimed to evaluate the clinical significance of microvessel density (MVD, lymphatic vessel density (LVD, and cancer-associated fibroblasts (CAFs in relation to tumor location in advanced colorectal cancer (CRC. METHODS: Using immunohistochemistry, we examined 181 advanced CRC patients for CD31 and D2-40 to measure MVD and LVD, respectively, α-smooth muscle actin (SMA and desmin to identify CAFs, and PTEN to examine genetic changes of CAFs. To evaluate the regional heterogeneity of these properties, we examined tissue from four sites (the center and periphery of the primary cancer, a distant metastasis, and a lymph node metastasis in each patient. RESULTS: MVD, LVD, and CAFs showed significant heterogeneity with respect to the tumor location. LVD was the greatest in the center of the primary cancers and the amount of CAFs was the lowest in distant metastases. In distant metastases, those from the lung had higher LVD and MVD, but fewer CAFs than those from the liver, peritoneum, or ovary. Patients with low MVD and LVD in the center of the primary cancer had worse outcomes and patients with few CAFs in distant metastases and in the primary tumor had a lower survival rate. PTEN expression in CAFs in distant metastases was lost in 11 of 181 CRC patients (6.1%, which was associated with a worse prognosis. CONCLUSIONS: The microenvironment, including cancer-associated microvasculature and fibroblasts, is heterogeneous with respect to the tumor location in CRC patients. Therefore, heterogeneity of microenvironments should be taken into account when managing CRC patients.

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

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    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

  2. Radiation Therapy without Surgery for Spinal Metastases: Clinical Outcome and Prognostic Factors Analysis for Pain Control.

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    Matsumura, Akira; Hoshi, Manabu; Takami, Masatsugu; Tashiro, Takahiko; Nakamura, Hiroaki

    2012-09-01

    The purpose of radiation therapy (RT) for patients with spinal metastases is pain relief and control of paralysis. The aim of the present study was to assess pain relief using RT and to evaluate prognostic factors for pain control. We evaluated 97 consecutive patients, of mean age 62.7 years (range 28 to 86), with spinal metastases that had been treated by RT. We evaluated the effects of RT using pain level assessed using a drug grading scale based on the World Health Organization standards. The following potential prognostic factors for pain control of RT were evaluated using multivariate logistic regression analysis: age, gender, tumor type, performance status (PS), number of spinal metastases, and a history of chemotherapy. Among the 97 patients who underwent RT for pain relief, 68 patients (70.1%) presented with pain reduction. PS (odds ratio: 1.931; 95% confidence interval: 1.244 to 2.980) was revealed by multivariate logistic regression analysis to be the most important prognostic factor for pain control using RT. In conclusion, we found that RT was more effective for patients with spinal metastases while they maintained their PS.

  3. Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis

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    Ali Rae, BS

    2016-10-01

    Conclusion: Our results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.

  4. Management of unknown origin cerebral metastases

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    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

  5. 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.

  6. 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

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    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.

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

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    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

  8. Risk of nodal metastases at laparoscopic pelvic lymphadenectomy using PSA, Gleason score, and clinical stage in men with localized prostate cancer.

    Science.gov (United States)

    Hoenig, D M; Chi, S; Porter, C; Tackett, L; Smith, D S; Cohen, S I; Stein, B S

    1997-08-01

    Laparoscopic pelvic lymph node dissection (LPLND) is a low-morbidity procedure used to stage prostate cancer accurately prior to definitive local therapy. To better select patients for LPLND, we reviewed the clinical features of 120 patients with clinically localized prostate cancer who underwent LPLND to define significant risk factors for nodal metastases. The age ranged from 43 to 79 years (mean 68). Serum prostate specific antigen (PSA) concentration ranged from 1.3 to 329 ng/mL, Gleason score ranged from 2 to 9, and clinical stage ranged from T1b to T3c. Nodal metastases were discovered in 15 patients (13%). Among men with a Gleason score > or = 7, 21% had nodal metastases (P = 0.004). A serum PSA > 20 ng/mL and clinical stage T1b, T2b, or greater also were statistically significant predictors of lymph node metastases (20% and 19%, respectively). In multivariate analysis, Gleason score significantly predicted nodal metastases when controlling for all other clinical measures. Therefore, LPLND is indicated for any patient with a Gleason score > or = 7, PSA > 20 ng/mL, and advanced clinical T stage, independently or in combination.

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

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    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.

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

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    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.)

  11. 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.

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

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    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.

  13. Development and Preclinical Application of an Immunocompetent Transplant Model of Basal Breast Cancer with Lung, Liver and Brain Metastases.

    Directory of Open Access Journals (Sweden)

    Olga Aprelikova

    Full Text Available Triple negative breast cancer (TNBC is an aggressive subtype of breast cancer that is associated with a poor prognosis and for which no targeted therapies currently exist. In order to improve preclinical testing for TNBC that relies primarily on using human xenografts in immunodeficient mice, we have developed a novel immunocompetent syngeneic murine tumor transplant model for basal-like triple-negative breast cancer. The C3(1/SV40-T/t-antigen (C3(1/Tag mouse mammary tumor model in the FVB/N background shares important similarities with human basal-like TNBC. However, these tumors or derived cell lines are rejected when transplanted into wt FVB/N mice, likely due to the expression of SV40 T-antigen. We have developed a sub-line of mice (designated REAR mice that carry only one copy of the C3(1/Tag-antigen transgene resulting from a spontaneous transgene rearrangement in the original founder line. Unlike the original C3(1/Tag mice, REAR mice do not develop mammary tumors or other phenotypes observed in the original C3(1/Tag transgenic mice. REAR mice are more immunologically tolerant to SV40 T-antigen driven tumors and cell lines in an FVB/N background (including prostate tumors from TRAMP mice, but are otherwise immunologically intact. This transplant model system offers the ability to synchronously implant the C3(1/Tag tumor-derived M6 cell line or individual C3(1/Tag tumors from various stages of tumor development into the mammary fat pads or tail veins of REAR mice. C3(1/Tag tumors or M6 cells implanted into the mammary fat pads spontaneously metastasize at a high frequency to the lung and liver. M6 cells injected by tail vein can form brain metastases. We demonstrate that irradiated M6 tumor cells or the same cells expressing GM-CSF can act as a vaccine to retard tumor growth of implanted tumor cells in the REAR model. Preclinical studies performed in animals with an intact immune system should more authentically replicate treatment

  14. CURRENT TREATMENT POLICY FOR RECTAL CANCER WITH SYNCHRONOUS DISTANT METASTASES (A CLINICAL CASE

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    M. I. Davydov

    2014-01-01

    Full Text Available Treatment results of low rectal cancer patient with internal sphincter involvement and synchronous liver metastases is presented. After combined treatment including preoperative targeted therapy, chemotherapy, chemoradiotherapy a synchronous resection of primary tumour and liver metastases was carried out (R0. Synchronous right hepihepatectomy and proctectomy was performed with resection of the deep part of external sphincter, neorectum creation by transverse coloplasty, neoanal sphincter creation using colonic smooth muscle layer without preventive colostomy. A possibility of synchronous plastic sphincter-sparing surgery in metastatic rectal cancer patient with locally advanced tumour is demonstrated. Such treatment allows to remove the risk of primary tumour complications, facilitates further chemotherapy treatment and improves quality of life and long-term treatment outcome.

  15. 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.

  16. A multidisciplinary bone metastases clinic at Toronto Sunnybrook Regional Cancer Centre – A review of the experience from 1999 to 2005

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    Kathy K Li

    2008-11-01

    Full Text Available Kathy K Li, Emily Sinclair, Joan Pope, Macey Farhadian, Kristin Harris, Julie Napolskikh, Albert Yee, Lawrence Librach, Lesia Wynnychuk, Cyril Danjoux, Edward Chow. On behalf of the Bone Metastases Team.Bone Metastases Site Group, Toronto-Sunnybrook Regional Cancer Centre, University of Toronto, Toronto, ON, CanadaAbstract: Our objective in this study was to review the experience of a one-stop multidisciplinary bone metastases clinic (BMC that offers a coordinated multidisciplinary approach to the care of cancer patients with bone metastases in a tertiary cancer centre. Patients with symptomatic bone metastases were referred to BMC and assessed by a team of specialists in various disciplines – interventional radiology, orthopedic surgery, palliative medicine, and radiation oncology. At initial consultation, patient demographics, reasons for referral, and case disposition were recorded. From January 1999 to February 2005, a total of 272 patients with bone metastases were referred to the BMC. The median age was 65 years (range 28–95 and median KPS score at consultation was 60 (range 30–90. The majority of patients came from home (74%, while others came from a nursing home or the hospital (9%. Almost a third (28% of patients had 2 or more reasons of referral, yielding a total of 354 reasons. The most common reason for referral was bone pain (42%, bone metastases (21%, high risk for pathological fracture (12%, and pathological fracture (10%. Of the 272 patients who received consultation, 40% received palliative radiotherapy, 19% received interventional surgery, 7% were referred to other support services such as palliative care, physiotherapy, and 7% had further investigation or imaging. A multidisciplinary clinic is useful for co-coordinating the management of bone metastatic disease in symptomatic patients.Keywords: bone metastases, multidisciplinary approach, experience

  17. [Brain metastasis: clinical and cognitive assessments].

    Science.gov (United States)

    Ramirez, Carole; Blonski, Marie; Belin, Catherine; Carpentier, Antoine; Taillia, Hervé

    2013-01-01

    The incidence of brain metastases (BM) has increased due to the improvement of therapeutics and diagnostic imaging, but also to an aging population. The initial symptoms may develop suddenly or insidiously over weeks or months. The symptoms depend on the location of the BM and related complications (hydrocephalus, tumor hemorrhage, cerebral herniation). Headaches are the most frequent symptoms (50%); they are related to intracranial hypertension. Cognitive deficits are commonly described at diagnosis (67 to 90.5%). Cognitive assessment is essential because of its impact on patients' prognosis and quality of life. Nevertheless, these deficits remain underestimated. The Karnofsky Perfomance Scale and the Mini Mental State Examination (MMSE) seem inadequate. A short battery was proposed and internationally validated, assessing seven domains: attention (Digit Symbol Test WAIS-III), episodic memory (Hopkins Verbal Learning Test [HVLT]), working memory (Digit Span Test WAIS-III), verbal fluency (Controlled Oral Word Association Test [COWA]), fine motor dexterity (Grooved Pegboard Test), information processing speed (Trail Making Test [TMT] A) and executive functions (TMT B). This battery is relevant, feasible and associated with a good compliance. These cognitive tests are currently recommended to assess cognitive functions in patients with BM.

  18. Time to biochemical recurrence after radical prostatectomy is an important predictor of clinical progression, distant metastases and cancer-specific death

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    E. I. Veliev

    2014-01-01

    Full Text Available Prostate-specific antigen is a sensitive marker for recurrent prostate cancer (PC after radical prostatectomy (RPE, which can predict thedevelopment of clinical progression and distant metastases well long before they occur. The objective of the investigation was to analyze the relationship of the time to biochemical recurrence (BCR after RPE to the development of clinical progression, distant metastases, and PC death. The vast majority (80.5 % of BCRs was common within the first 2 years after RPE and the recurrence was attended by the highest rate of clinical progression, metastases, and PC death during the first year. Correlation analysis shows that there is a statistically significant inverse correlation between the time to BCR following RPE with the development of clinical progression (rs = -0.43; p < 0.001, metastases (rs = -0.46; p < 0.001, and PC death (rs = -0.41; p < 0.001. Regardless of the time to recurrence, none of 27 patients with favorable histological characteristics (a total of post-RPE Gleason scores of ≤ 6, organ-confined disease, and a negative surgical margin developed distant metastases; only one case had a local tumor recurrence.

  19. 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 initial phase in a clinical setting with emphasis on pathway criteria....

  20. 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.

  1. EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

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    Pascale Tomasini

    2016-12-01

    Full Text Available Background: Lung cancer is the leading cause of brain metastases (BM. The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients’ outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA (Odds ratio OR = 8.745 [1.743–43.881], p = 0.008. Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078–0.699], p = 0.009. Among patients with untreated BM, overall survival (OS was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240–41.012], p = 0.028, but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM.

  2. EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Tomasini, Pascale; Serdjebi, Cindy; Khobta, Nataliya; Metellus, Philippe; Ouafik, L’Houcine; Nanni, Isabelle; Greillier, Laurent; Loundou, Anderson; Fina, Frederic; Mascaux, Celine; Barlesi, Fabrice

    2016-01-01

    Background: Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients’ outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian) were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA) (Odds ratio OR = 8.745 [1.743–43.881], p = 0.008). Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078–0.699], p = 0.009). Among patients with untreated BM, overall survival (OS) was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240–41.012], p = 0.028), but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM. PMID:27999344

  3. The role of microRNA-21 in predicting brain metastases from non-small cell lung cancer

    Science.gov (United States)

    Dong, Jing; Zhang, Zhi; Gu, Tao; Xu, Shu-Feng; Dong, Li-Xin; Li, Xin; Fu, Bao-Hong; Fu, Zhan-Zhao

    2017-01-01

    Objective This study aimed at exploring the role of microRNA-21 (miR-21) in predicting brain metastases (BM) from non-small cell lung cancer (NSCLC). Methods A total of 132 NSCLC patients, including 68 patients with BM and 64 patients without BM, were included in the study. NSCLC cells were collected and assigned to the inhibitor (IN) group, the mock group, and the negative control (NC) group. The quantitative real-time polymerase chain reaction assay was used to detect the miR-21 expression. Cell proliferation, migration, invasion, and apoptosis were detected by colony-forming assay, MTT assay, transwell assay, and flow cytometry, respectively. Angiogenesis was measured by endothelial cell tube formation assay. Results The miR-21 expression was higher in NSCLC patients with BM than in those without BM. The miR-21 expression in the IN group was lower than that in the NC and mock groups. Compared with the NC and mock groups, the values of optical density (OD) and the colony-forming number decreased in the IN group. Compared with the NC and mock groups, cell invasion and migration abilities significantly reduced in the IN group. The IN group had higher apoptosis rate than the NC and mock groups. The tube length was shorter and the number of junction points was less in the IN group in comparison to the NC and mock groups. Conclusion miR-21 might be a potential biomarker for the development of BM in NSCLC patients and could promote the proliferation, migration, invasion, and angiogenesis of NSCLC cells.

  4. Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases

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    James J. Cody

    2012-01-01

    Full Text Available The metastasis of breast cancer to the brain and central nervous system (CNS is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are limited by deleterious side effects and are generally palliative. We have previously described an oncolytic herpes simplex virus (HSV, designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12 expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors. However, M002 has not been yet evaluated for use against metastatic brain tumors. Here, we demonstrate the following: both human breast cancer and murine mammary carcinoma cells support viral replication and IL-12 expression from M002; M002 replicates in and destroys breast cancer cells from a variety of histological subtypes, including “triple-negative” and HER2 overexpressing; M002 improves survival in an immunocompetent model more effectively than does a non-cytokine control virus. Thus, we conclude from this proof-of-principle study that a γ134.5-deleted IL-12 expressing oncolytic HSV may be a potential new therapy for breast cancer brain metastases.

  5. 伽玛刀治疗脑转移瘤的疗效观察%Research of radiosurgery for brain metastases

    Institute of Scientific and Technical Information of China (English)

    王宏伟; 窦长武; 张国荣; 何占彪; 李明洙

    2011-01-01

    Objective To explore the efficacy of gamma knife radiosurgery for brain metastases.Method 112 cases with brain metastases were treated by gamma knife.Among them, most cases were combined surgery with whole brain radiation therapy and chemotherapy.Results 85 cases were followed up for 36-72 months,the total local control rate was 95%, the mean survival time of all patients was 12 months,0.5 year survival rate was 86%, 1 year survival rate was 59%, 2 year survival rate was 21%.Conclusions The treatment of gamma knife radiosurgery for brain metastases is an effective and safe method.%目的 观察伽玛刀治疗脑转移瘤的临床治疗效果.方法 采用国产OUR-XGD型头部伽玛刀,结合手术、放疗、化疗等综合治疗手段治疗112例脑转移瘤患者.结果 随访85例患者,随访期36-72个月,肿瘤控制率95%.生存期1-48个月,平均生存期14.3个月,中位生存期12个月,0.5年生存率86%,1年生存率59%,2年生存率21%.结论 伽玛刀治疗脑转移瘤是一种安全有效的治疗手段,配合科学合理的综合治疗措施可进一步提高疗效.

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

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    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.

  7. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

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    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  8. Robotic radiosurgery for the treatment of 1-3 brain metastases: a pragmatic application of cost-benefit analysis using willingness-to-pay.

    Science.gov (United States)

    Greenspoon, Jeffrey Noah; Whitton, Anthony; Whelan, Timothy; Sharieff, Waseem; Wright, James; Sussman, Jonathan; Gafni, Amiram

    2013-12-01

    With the emergence of radiosurgery as a new radiotherapeutic technique, health care decision makers are required to incorporate community need, cost and patient preferences when allocating radiosurgery resources. Conventional patient utility measures would not reflect short term preferences and would therefore not inform decision makers when allocating radiosurgery treatment units. The goal of this article is to demonstrate the feasibility of cost-benefit analysis to elicit the yearly net monetary benefit of robotic radiosurgery. To calculate the yearly incremental cost of robotic radiosurgery as compared to fixed gantry radiosurgery we used direct local cost data. We assumed a standard 10 year replacement and 5% amortization rate. Decision boards summarizing the clinical scenario of brain metastases and the difference between robotic and fixed gantry radiosurgery in terms of immobilization, comfort and treatment time were then presented to a sample of 18 participants. Participants who preferred robotic radiosurgery were randomly assigned to either a low ($1) or high ($5) starting point taxation based willingness-to-pay algorithm. The yearly incremental cost of providing robotic radiosurgery was $99,177 CAD. The mean community yearly willingness-to-pay for robotic radiosurgery was $2,300,000 CAD, p = 0.03. The calculated yearly net societal benefit for robotic radiosurgery was $2,200,823 CAD. Among participants who preferred robotic radiosurgery there was no evidence of starting point bias, p = 0.8. We have shown through this pilot study that it is feasible to perform cost-benefit analysis to evaluate new technologies in Radiation Oncology. Cost-benefit analysis offers an analytic method to evaluate local preferences and provide accountability when allocating limited healthcare resources.

  9. 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

  10. AKT1 Activation Promotes Development of Melanoma Metastases

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    Joseph H. Cho

    2015-11-01

    Full Text Available Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAFV600E/Cdkn2aNull mouse melanomas in vivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of our mice, respectively. Silencing of PTEN in BRAFV600E/Cdkn2aNull melanomas cooperated with activated AKT1, resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and reveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance our knowledge of the mechanisms driving melanoma metastasis and may provide valuable insights for clinical management of this disease.

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

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

    2014-06-01

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

  12. Comprehensive clinic-pathological characteristics of cervical cancer in southwestern China and the clinical significance of histological type and lymph node metastases in young patients.

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    LingYun Yang

    Full Text Available OBJECTIVE: To analyze the clinic-pathological characteristics of women with cervical cancers in southwestern China and discuss the features and prognosis of young patients. METHODS: A retrospective study was performed, which consisted of 1,543 patients diagnosed with cervical cancer and underwent treatment at West China Second University Hospital between November 2005 and December 2010. Among them, 154 young patients with surgical procedures between November 2005 and December 2008 were selected for a 5-year follow-up and prognostic analysis. RESULTS: The proportion of advanced FIGO stage in patients aged over 35 years was higher than in patients aged 35 years or younger (55.1% vs 38.8%, P<0.001, and strong correlation was found between FIGO stages and the postoperative pathological risk factors (P<0.05. 312 patients (20.2% were under 35 years old in the last 5 years. The proportion of cervical adenocarcinoma remained high in young patients (13.6%, and young women with adenocarcinoma had a higher rate of LN metastases, comparing with those with squamous cell carcinoma (42.9% vs 15.8%, P = 0.004. Young patients with adenocarcinoma had shorter progression-free survival than those who had squamous cell carcinoma (P = 0.024. Patients aged 35 years or younger with positive postoperative pathological risk factors had shorter progression-free survival, comparing with those with negative factors (P<0.01. CONCLUSION: Patients over 35 years were preliminarily diagnosed as advanced FIGO stage and they were more likely to have deep stromal invasion, LVSI, LN metastases, parametrial and surgical margin involvement. Regarding to young patients, cervical adenocarcinoma increased the risk of LN metastases and positive postoperative pathological risk factors could apparently worsen the prognosis. Histological type and LN metastases were independent prognostic factors for young patients in southwestern China. We re-emphasize the importance of health

  13. 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

  14. 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.

  15. 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

  16. Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies

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    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.)

  17. 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

  18. 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?

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    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.

  19. 脑转移癌全脑放疗相关认知功能损害%Cognitive impairment associated with whole brain radiotherapy for brain metastases

    Institute of Scientific and Technical Information of China (English)

    董标; 李薇; 王尚虎; 程怀东; 解佳奇; 陈振东

    2014-01-01

    目的探讨脑转移癌( BM)患者全脑放疗( WBRT)后认知功能的改变。方法以41例接受WBRT的BM患者为研究对象,以简易精神状态量表( MMSE)作为认知评估工具,对其放疗前1周、放疗后1周、1~6个月进行总体认知评估,并观察有无神经系统症状的BM患者(各12例)放疗前后的总体认知功能的改变。结果41例患者放疗前与放疗后1周比较差异有统计学意义(28.146±0.528 vs 27.585±0.290,P=0.006);放疗前无神经系统症状组,放疗后4个月MMSE减低最明显,其后有所提高,放疗后4个月与放疗前患者的 MMSE 成绩(29.125±0.579 vs 26.500±0.524)比较,差异有统计学意义( P<0.01);而有神经系统症状组放疗后4个月MMSE成绩提高,与放疗前(25.000±0.524 vs S27.500±0.370)比较,差异有统计学意义(P=0.001)。结论 WBRT对认知功能有损害,放疗后约4个月认知功能损害最明显,其后有所恢复。且放疗前有无神经系统症状与其放疗后的认知功能改变存在单分离。%Objective To investigate the change of cognitive function associated with whole brain radiotherapy for brain metastases after treatment. Methods The study was based on patients (n=41) of brain metastases who re-ceived whole brain radiotherapy, and MMSE was used as a cognitive assessment tool. Cognitive assessments were taken for the patients the week before radiotherapy, one week after radiotherapy and monthly after that, until 6 months later, to observe overall cognitive changes. And in which the change of cognitive function of the patients be-fore and after treatment with and without neurological symptoms group (12cases per group) was observed. Results there was significafint difference between Baseline MMSE score and the score one week after radiotherapy in the 41 patients (28. 146±0.528 vs 27.585±0.290, P=0.006). In no-neurological symptoms group(n=12 ),cog-nitive decline was predominant in the fourth month, but improved subsequently, baseline

  20. 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.

  1. Metabolic brain imaging correlated with clinical features of brain tumors

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    Alavi, J.; Alavi, A.; Dann, R.; Kushner, M.; Chawluk, J.; Powlis, W.; Reivich, M.

    1985-05-01

    Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1 enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.

  2. 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

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

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    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

  4. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors.

    Directory of Open Access Journals (Sweden)

    Michael C Burger

    Full Text Available Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV. This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma. In these patients progression-free survival (PFS intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors.

  5. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors.

    Science.gov (United States)

    Burger, Michael C; Zeiner, Pia S; Jahnke, Kolja; Wagner, Marlies; Mittelbronn, Michel; Steinbach, Joachim P

    2016-01-01

    Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors.

  6. 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.

  7. Intracranial metastases: spectrum of MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  8. 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.

  9. 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

  10. 皮肤转移癌62例临床特征分析∗%Clinical analysis of 62 cases of cutaneous metastases from internal cancers

    Institute of Scientific and Technical Information of China (English)

    王婧; 赵磊; 李卉惠; 车娟娟; 庞歆桥; 吴军; 马妮娜

    2016-01-01

    Objective To analyze the clinical characteristics of cutaneous metastases from internal cancers, and enhance the understanding of cutaneous metastases. Methods In the retrospective study, the clinical features, primary sites of cancers, morpho-logical features and occurence of 62 cases of cutaneous metastases from internal cancers diagnosed in Beijing Friendship Hospital from January 2002 to December 2015 were analyzed. Results There were 40 males and 22 females among the 62 patients. The median age at the onset of skin lesions was 60. 0 years( range 33-82 years) . Cutaneous metastases occurred at various locations of the body, inclu-ding abdomen, chest, back, scalp, limbs and etc. Abdominal wall was the most common site of cutaneous metastases, accounting for 72. 6% of patients with cutaneous metastases. The most common types of primary cancer were lung cancer, gastric cancer and colorectal cancer. Pathological biopsy showed that 40 cases were in complete agreement with the pathologic types of the primary lesions, and 3 ca-ses were consistent with the morphology of the primary tumors, but the degree of tumor differentiation was different. One case was con-firmed with second primary cancer by skin biopsy. Seventeen patients were comfirmed with cutaneous metastases when the primary cancers were diagnosed. Most patients were diagnosed with cutaneous metastases within 4 years after the primary cancers were com-firmed. Conclusion With increasing incidence of cancers, cutaneous metastases from internal cancers increased in recent years. Rai-sing awareness of cutaneous metastases is helpful for early diagnosis, treatment and prolonging patients’ life.%目的:探讨皮肤转移癌的临床特征,加深对皮肤转移癌的认识。方法回顾性分析首都医科大学附属北京友谊医院2002年1月至2015年12月诊治的62例皮肤转移癌患者的临床表现、形态特征、肿瘤来源和发生时间。结果62例患者中男性40例,女性22

  11. 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.

  12. 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.

  13. 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)

  14. 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.

  15. 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

  16. 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.

  17. 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.

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

    Science.gov (United States)

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

    2016-09-02

    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.

  19. 乳腺癌骨转移临床相关因素的研究%Clinical factors related to bone metastases from breast cancer

    Institute of Scientific and Technical Information of China (English)

    张卫红; 田钢龙; 何继民; 周凤飞; 关宏霞; 高聪明; 吕平欣

    2010-01-01

    目的 研究乳腺癌骨转移的临床和影像学资料,寻找影响骨转移的相关因素,为早期诊断提供依据.方法 对334例乳腺癌患者全身骨显像、临床分期、病理、免疫组织化学及血清学检-查结果进行回顾性分析,并对数据行χ2检验.结果 有淋巴结转移者骨转移率71.0%(152/214),没有淋巴结转移者骨转移率为22.5%(27/120),两者比较差异有统计学意义(χ2=72.80,P=0.000);浸润性非特殊性癌骨转移率69.0%(203/294),浸润性特殊性癌骨转移率41.7%(5/12),两者比较差异有统计学意义(χ2=3.97,P=0.046);骨转移中碱性磷酸酶(ALP)升高者占28.5%(51/179),非骨转移中ALP升高者占14.9%(11/74),两者比较差异也有统计学意义(χ2=5.25,P=0.022);而骨转移中肿瘤标志物[癌胚抗原(CEA)、糖类抗原(CA)15-3、CA125、CA19-9]升高者占68.7%(123/179),非骨转移中肿瘤标志物升高者占27.0%(20/74)(χ2=37.03,P=0.000).结论 乳腺癌骨转移的发生率与原发灶的病理类型、发病时有无淋巴结转移有关,浸润性非特殊性癌或有淋巴结转移者骨转移率较高.动态监测血清ALP、CEA、CA15-3、CA125、CA19-9有助于早期诊断.%Objective To study the clinical and imaging features of patients with bone metastases from breast cancer and identify the factors related to the incidence of bone metastases. Methods Three hundred and thirty-four patients with breast cancer were recruited into this study. Whole-body 99Tcm-methylene disphosphonate (MDP) bone scan, clinical staging, pathological, immunohistochemical and serological test results were analyzed retrospectively. χ2 test was used for statistical analysis. Results The incidence rate of bone metastases for patients with and without lymph node metastases was 71% (152/214) and 22. 5% (27/120), respectively (χ2 =72.80, P =0.000). The incidence rate of bone metastases from infiltrated non-specified and specified breast cancer was 69% (203/294) and 41.7% (5

  20. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos

    2014-01-01

    in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may...

  1. 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.

  2. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Atalar, Banu [Department of Radiation Oncology, Acibadem University School of Medicine, Istanbul (Turkey); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Choi, Clara Y.H.; Adler, John R. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Gibbs, Iris C. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Nagpal, Seema [Department of Neurology, Stanford University Medical Center, Stanford, California (United States); Hanlon, Alexandra [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States)

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  3. 18F-FDG PET/CT在原发灶不明的脑转移瘤中的诊断价值%The value of 18F-FDG PET/CT in diagnosing brain metastases from unknown primary tumor

    Institute of Scientific and Technical Information of China (English)

    刘春利; 李毅红

    2013-01-01

    目的 探讨18F-FDG PET/CT在查找原发灶不明的脑转移瘤中的价值.方法 回顾性分析17例原发灶不明的脑转移瘤患者的全身18F-FDG PET/CT检查资料.结果 17例患者均经活检确诊原发灶,准确率100%.原发性肺癌13例,占76%,其中有2例在第二次行PET/CT检查时才检出原发灶;原发性肝癌2例,占12%;原发性贲门癌1例,占6%;原发性升结肠癌1例,占6%.在检查到原发灶的基础上,18F-FDG PET/CT亦发现10例合并转移者,其中合并肺转移者2例、合并淋巴结转移者3例、合并骨转移者2例及合并其他部位转移者3例,共发现病灶61处;2例肝癌患者单发脑转移灶中均有脑卒中.结论 18F-FDG PET/CT在查找原发灶不明的脑转移瘤原发灶中有重要价值,并为临床分期及治疗提供有利帮助.%Objective To investigate the value of 18F-FDG PET/CT in diagnosis of brain metastases from unknown primary tumor.Method The 18F-FDG PET/CT findings of 17 patients with brain metastases from unknown primary tumor were retrospectively analyzed.Results Primary tumors of the seventeen cases were confirmed by biopsy,the accuracy rate was 100%.There were thirteen cases with primary lung cancer,accounted for 76%,including two cases of lung cancer which were found in the second PET/CT examination,two cases with liver cancer,accounted for 12%,one case with cardia cancer,accounted for 6%,one case with the ascending colon cancer,accounted for 6%.On the base of founding the primary tumor,18F-FDG PET/CT also found 10 cases accompanied by lung metastasis (2 cases),lymph node metastases (3 cases),bone metastases (2 cases)and other sites of metastases (3 cases),a total of 61 lesions were detected.Two cases of liver cancer patients with single brain metastases had cerebral apoplexy.Conclusion 18F-FDG PET/CT contributes important value in finding brain metastases from unknown primary tumor,and is very helpful for clinical staging and treatment.

  4. Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2015-12-01

    from figures 2 and 3. Fig. 1. Calibration curve of Spectrophotometer absorbance versus Concentration of India ink. In order to determine the... Calibration of the probe was performed in air and water-based phantoms using a calorimeter (considered a Gold Standard). Second, a voxel- based Monte Carlo...skull and brain tissue phantom using the fluence probe. b. Results i. Calibration of the Optical Dosimetry Probe (ODP) [1,3]: The objective was to

  5. 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.

  6. 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

  7. SU-E-T-213: Comparison of Treatment Efficiency of Gamma Knife SRS Plans for Brain Metastases with Different Planning Methods

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Y [East Carolina Univ, Greenville, NC (United States); Huang, Z [East Carolina University, Greenville, NC (United States); Lo, S [Case Western Reserve University, Cleveland, OH (United States); Mayr, N; Yuh, W [University of Washington, Seattle, WA (United States)

    2015-06-15

    Purpose: To improve Gamma Knife SRS treatment efficiency for brain metastases and compare the differences of treatment time and radiobiological effects between two different planning methods of automatic filling and manual placement of shots with inverse planning. Methods: T1-weighted MRI images with gadolinium contrast from five patients with a single brain metastatic-lesion were used in this retrospective study. Among them, two were from primary breast cancer, two from primary melanoma cancer and one from primary prostate cancer. For each patient, two plans were generated in Leksell GammaPlan10.1.1 for radiosurgical treatment with a Leksell GammaKnife Perfexion machine: one with automatic filling, automatic sector configuration and inverse optimization (Method1); and the other with manual placement of shots, manual setup of collimator sizes, manual setup of sector blocking and inverse optimization (Method2). Dosimetric quality of the plans was evaluated with parameters of Coverage, Selectivity, Gradient-Index and DVH. Beam-on Time, Number-of-Shots and Tumor Control Probability(TCP) were compared for the two plans while keeping their dosimetric quality very similar. Relative reduction of Beam-on Time and Number-of-Shots were calculated as the ratios among the two plans and used for quantitative analysis. Results: With very similar dosimetric and radiobiological plan quality, plans created with Method 2 had significantly reduced treatment time. Relative reduction of Beam-on Time ranged from 20% to 51 % (median:29%,p=0.001), and reduction of Number-of-Shots ranged from 5% to 67% (median:40%,p=0.0002), respectively. Time of plan creation for Method1 and Method2 was similar, approximately 20 minutes, excluding the time for tumor delineation. TCP calculated for the tumors from differential DVHs did not show significant difference between the two plans (p=0.35). Conclusion: The method of manual setup combined with inverse optimization in LGP for treatment of brain

  8. 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.

  9. 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.

  10. The antibacterial substance, taurolidine in the second/third-line treatment of very advanced stage IV melanoma including brain metastases: results of a phase 2, open-label study.

    Science.gov (United States)

    Imhof, Laurence; Goldinger, Simone M; Baumann, Katrin; Schad, Karin; French, Lars E; Röthlisberger, Peter; Dummer, Reinhard

    2011-02-01

    The efficacy and tolerability of taurolidine, an antibacterial substance, was evaluated in a phase 2 trial enrolling patients with advanced melanoma. The treatment schedule consisted of daily taurolidine (20 g) administered intravenously for 5 days per week for 3 consecutive weeks followed by 1 week of rest. One cycle comprised of 28 days. A maximum of six cycles could be administered. Sixteen patients were assessable for tumor response, seven of whom had brain metastases. Three patients (18.8%) achieved disease stabilization, including a patient with a primary mucosal melanoma of the nasal cavity who had a marked locoregional response with disease stabilization of the distant metastases. Thirteen patients had disease progression. Median overall survival was 46±1 days. Adverse events were moderate and mainly gastrointestinal. Treatment with taurolidine has no activity in patients with advanced melanoma.

  11. 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.

  12. 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

  13. Pan-encephalic irradiation of brain metastases: dosimetric impact of the technique with a rotating collimator without mask in comparison with a multi-blade collimator; Irradiation pan encephalique des metastases cerebrales: impact dosimetrique de la technique avec rotation du collimateur sans cache par comparaison a celle avec collimateur mutilame

    Energy Technology Data Exchange (ETDEWEB)

    Loos, G.; Paulon, R.; Achard, J.L.; Belliere, A.; Biau, J.; Bourry, N.; Chilles, A.; Toledano, I.; Verrelle, O.; Lapeyre, M. [Centre Jean-Perrin, 63 - Clermont-Ferrand (France)

    2010-10-15

    The authors report the dosimetric impacts of two techniques (collimator without mask and multi-blade collimator) on organs at risk as well as the influence of meningeal dead ends when using the technique of conventional pan-encephalic irradiation of brain metastases. Data have been acquired for 10 patients. The use of a multi-blade collimator is better for a pan-encephalic irradiation by two lateral beams in order to reduce the average dose received by the parotids, and particularly if meningeal dead ends are to be treated. The dose received by other organs at risk is equivalent, whichever method is used. Short communication

  14. [Bone metastases treated with radiopharmaceuticals].

    Science.gov (United States)

    Giammarile, Francesco

    2013-11-01

    The administration of a radionuclide in unsealed source whose radiation will destroy cells that have selectively accumulated product is called radiometabolic therapy. The management of bone pain is a major problem, particularly in cases of breast or prostate where the presence of metastases can remain compatible with long-term survival of cancer patients. In this context, the radiometabolic therapy reduces the pain secondary to bone metastases, in association or not with analgesics. This technique is rarely prescribed as first-line. It can also be combined with external beam radiotherapy or chemotherapy, if clinical conditions permit (due to the increased risk of hematologic toxicity). In this setting, the currently used substances are Metastron® and Quadramet®. Recently, a new product, radium chloride (or Alpharadin®) has shown efficacy in bone metastases from prostate cancer, particularly in terms of bone pain palliation, but also of increased overall survival. In addition, this product has virtually no hematologic toxicity.

  15. Calibration of clinical cerebellar and deep brain stimulation systems.

    Science.gov (United States)

    McLellan, D L; Wright, G D; Renouf, F

    1981-01-01

    The increasing use of electrical stimulation of the brain for relief of pain, spasticity and epilepsy has introduced unfamiliar techniques into clinical neurological and neurosurgical practice. In view of the evidence that excessive levels of stimulation can damage brain tissue, it is of great importance to monitor the dose of stimulation. A review of recent clinical papers suggests that many centres do not measure the dose accurately, relying on arbitrary dial settings on external transmitters. This paper reviews that factors that affect the dose received by the patient and suggests methods of measuring them, at operation and subsequently, which should routinely be employed by clinicians implanting stimulators. Images PMID:6973614

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

    Institute of Scientific and Technical Information of China (English)

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

    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.

  17. 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.

  18. 多发脑转移瘤VMAT计划中MLC插指功能剂量学研究%A dosimetric study of multileaf collimator interdigitation in volumetric modulated arc therapy plans for multiple brain metastases

    Institute of Scientific and Technical Information of China (English)

    段敬豪; 李成强; 王若峥; 巩贯忠; 陶城; 刘潇; 朱健; 尹勇

    2016-01-01

    目的 通过比较有无MLC插指功能的VMAT计划剂量学差异,探究MLC插指在多发脑转移瘤VMAT计划中的优势.方法 回顾本院15例多发脑转移瘤患者数据.首先在定位CT图像上设计有MLC插指功能权限的双弧VMAT计划(VMAT-1).随后不改变计划参数,摒弃插指功能权限,重新优化计算得到无MLC插指功能的VMAT-2计划.比较两种计划在靶区CI和HI、OAR受量、机器跳数、控制点数、计划执行时间和计划耗时方面差异.采用Wilcoxon符号秩和检验.结果 VMAT-1的均匀性优于VMAT-2(P=0.04),两种计划的适形度基本相当(P=0.33).VMAT-1计划中PTV的D98%高于VMAT-2(P=0.04).VMAT-1中的脑干Dmean比VMAT-2降低了4%(P=0.04),其他OAR参数基本相当.部分病例显示VMAT-1计划有着相邻横断面的肿瘤交界处正常组织受量更少的特点.VMAT-1计划机器跳数比VMAT-2增加了4%(P=0.01).两种计划的控制点数和预估执行时间相近(P=0.81、0.73).VMAT-1的计划制作耗时较VMAT-2减少了26%(P=0.00).结论 在多发脑转移瘤VMAT计划中,MLC插指功能可缩短VMAT优化时间,提高优化效率.%Objective To evaluate the dosimetric difference between volumetric modulated arc therapy (VMAT) plans with and without an interdigitating multileaf collimator (MLC) in the treatment of multiple brain metastases, and to investigate the advantages of MLC interdigitation in VMAT plans for multiple brain metastasis. Methods A retrospective study was performed on clinical data from 15 patients with multiple brain metastases in our hospital. A dual arc VMAT plan with an interdigitating MLC ( VMAT-1) was designed on computed tomography ( CT) images. Then, keeping all parameters unchanged, another VMAT plan with a non-interdigitating MLC ( VMAT-2) was made after re-optimization. The conformity index ( CI) and homogeneity index ( HI) of the planning target volume ( PTV) , doses to organs at risk ( OARs) , monitor units (MUs), control points, delivery time

  19. [Metastasizing esthesioneuroblastoma].

    Science.gov (United States)

    Alanin, Mikkel Christian; Hahn, Christoffer Holst

    2011-01-24

    Esthesioneuroblastoma is a rare malignant tumour that originates from the olfactory region. Its incidence is about 0.4 per million per year. The most common symptoms include epistaxis, headache, nasal obstruction, hyposmia and eye symptoms. Diagnosis of this rare tumour is often delayed. We present a case in which a 61-year-old male was referred due to proptosis and loss of vision. Magnetic resonance imaging showed a tumour in the nasal cavity involving the orbit, the frontal lope of the brain and lymph nodes in the neck. The case was staged according to Kadish as a stage C. Surgery was performed and postoperative radiotherapy planned.

  20. I BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 2: APPROACH TO RESECTABLE METASTASES

    Science.gov (United States)

    RIBEIRO, Héber Salvador de Castro; TORRES, Orlando Jorge Martins; MARQUES, Márcio Carmona; HERMAN, Paulo; KALIL, Antonio Nocchi; FERNANDES, Eduardo de Souza Martins; de OLIVEIRA, Fábio Ferreira; CASTRO, Leonaldson dos Santos; HANRIOT, Rodrigo; OLIVEIRA, Suilane Coelho Ribeiro; BOFF, Marcio Fernando; da COSTA, Wilson Luiz; GIL, Roberto de Almeida; PFIFFER, Tulio Eduardo Flesch; MAKDISSI, Fabio Ferrari; ROCHA, Manoel de Souza; do AMARAL, Paulo Cezar Galvão; COSTA, Leonardo Atem Gonçalves de Araújo; ALOIA, Tomas A.; D'ALBUQUERQUE, Luiz Augusto Carneiro; COIMBRA, Felipe José Fernandez

    2016-01-01

    Background: Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients. Aim: In the second module of this consensus, management of resectable liver metastases was discussed. Method: Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities. Results: Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions. Conclusion: Were presented validated ressectional strategies, to be taken into account in clinical practice. PMID:27120731

  1. Clinical and pathological features of alcohol-related brain damage.

    Science.gov (United States)

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.

  2. Physiological and pathological clinical conditions and light scattering in brain

    Science.gov (United States)

    Kurata, Tsuyoshi; Iwata, Sachiko; Tsuda, Kennosuke; Kinoshita, Masahiro; Saikusa, Mamoru; Hara, Naoko; Oda, Motoki; Ohmae, Etsuko; Araki, Yuko; Sugioka, Takashi; Takashima, Sachio; Iwata, Osuke

    2016-08-01

    MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μs’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μs’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μs’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μs’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3‑ at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3‑ at the time of study were correlated with smaller μs’. Brain μs’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

  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. 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.

  6. Assessment of function and quality of life in a phase II multi-institutional clinical trial of fractionated simultaneous in-field boost radiotherapy for patients with 1-3 metastases.

    Science.gov (United States)

    Bauman, Glenn; Yartsev, Slav; Roberge, David; MacRae, Robert; Roa, Wilson; Panet-Raymond, Valerie; Masucci, Laura; Yaremko, Brian; D'Souza, David; Palma, David; Sexton, Tracy; Yu, Edward; Pantarotto, Jason R; Ahmad, Belal; Fisher, Barbara; Dar, A Rashid; Lambert, Carole; Pond, Gregory; Stitt, Larry; Tay, Keng Yeow; Rodrigues, George

    2016-07-01

    We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to <27) ranged from 26 to 38 % for KPS, 32-59 % for FACT-Br and 0-16 % for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6 months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRT + simultaneous FSRT were similar to other published series combining WBRT + radiosurgery.

  7. Multiple sclerosis brain lesion measurements in clinical practice

    OpenAIRE

    2014-01-01

    Jain S., Smeets D., Sima D., Van Hecke W., Loeckx D., Van Huffel S., Maes F., ''Multiple sclerosis brain lesion measurements in clinical practice'', European journal of neurology, vol. 21 suppl. s1, pp. 345, 2014 (Joint congress of European neurology, May 31 - June 3, 2014, Istanbul, Turkey).

  8. Umbilical metastases: current viewpoint

    Directory of Open Access Journals (Sweden)

    Egidi Federico

    2005-02-01

    Full Text Available Abstract Background Umbilical metastases from a malignant neoplasm, also termed Sister Mary Joseph's nodule, are not commonly reported in the English literature, and they have usually been considered as a sign of a poor prognosis for the patient. The present article reports on the current view point on umbilical metastasis besides discussing the epidemiology, clinical presentation, pathophysiology and treatment. Method A search of Pubmed was carried out using the term 'umblic*' and 'metastases' or metastasis' revealed no references. Another search was made using the term "Sister Joseph's nodule" or sister Joseph nodule" that revealed 99 references. Of these there were 14 review articles, however when the search was limited to English language it yielded only 20 articles. Articles selected from these form the basis of this report along with cross references. Results The primary lesions usually arise from gastrointestinal or genitourinary tract malignancies and may be the presenting symptom or sign of a primary tumour in an unknown site. Conclusion A careful evaluation of all umbilical lesions, including an early biopsy if appropriate, is recommended. Recent studies suggest an aggressive surgical approach combined with chemotherapy for such patients may improve survival.

  9. 同步加量放疗技术在非小细胞肺癌脑转移患者中的应用%Simultaneous integrated boost conformal radiotherapy in non -small cell lung cancer patients with brain metastases

    Institute of Scientific and Technical Information of China (English)

    王浩; 吴磊; 王天昶; 李涛; 王亚丽; 高艳梅; 刘秋芳

    2014-01-01

    evaluation criteria,the clinical symptom remission rate was 95.2%(40/42)in group A,97.1%(33/34)in group B.There was no significantly difference between group A and group B.There was no significantly difference in hematological toxicity,gastrointes-tional reaction,nervous system damage and alopecia in two groups.The median survival time,six months and 1 -year survival rates of the patients in group A were 8.94 months,71.4% and 35.7%,respectively showing no significant differences to group B were 9.47 months,82.4% and 38.2%,respectively.There was no significantly difference be-tween group A and group B in remission rate,toxic reaction and survival time.Conclusion:Whole brain irradiation with simultaneous integrated boost conformal radiotherapy technique is effective in patients with brain metastases with shorter the total radiotherapy duration and can be well tolerated.

  10. Automated metastatic brain lesion detection: a computer aided diagnostic and clinical research tool

    Science.gov (United States)

    Devine, Jeremy; Sahgal, Arjun; Karam, Irene; Martel, Anne L.

    2016-03-01

    The accurate localization of brain metastases in magnetic resonance (MR) images is crucial for patients undergoing stereotactic radiosurgery (SRS) to ensure that all neoplastic foci are targeted. Computer automated tumor localization and analysis can improve both of these tasks by eliminating inter and intra-observer variations during the MR image reading process. Lesion localization is accomplished using adaptive thresholding to extract enhancing objects. Each enhancing object is represented as a vector of features which includes information on object size, symmetry, position, shape, and context. These vectors are then used to train a random forest classifier. We trained and tested the image analysis pipeline on 3D axial contrast-enhanced MR images with the intention of localizing the brain metastases. In our cross validation study and at the most effective algorithm operating point, we were able to identify 90% of the lesions at a precision rate of 60%.

  11. Proton magnetic resonance spectroscopy in brain tumours: clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Burtscher, I.M.; Holtaas, S. [Lund Univ. (Sweden). Dept. of Diagnostic Radiology

    2001-05-01

    Parallel to the rapid development of clinical MRI, MR spectroscopy (MRS) has, after starting as an analytical tool used in chemistry and physics, evolved to a noninvasive clinical examination. Most common neuroradiological diagnostic indications for MRS are functional inborn errors, neonatal hypoxia, ischaemia, metabolic diseases, white matter and degenerative diseases, epilepsy, inflammation, infections and intracranial neoplasm. Compared to CT and MRI, well-established morphological diagnostic tools, MRS provides information on the metabolic state of brain tissue. We review the clinical impact of MRS in diagnosis of tumours and their differentiation from non-neoplastic lesions. (orig.)

  12. 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.

  13. Clinical Application of Neuroplastic Brain Research in Eating Disorder Treatment

    Directory of Open Access Journals (Sweden)

    Abigail H. Natenshon

    2016-12-01

    Neurophysiological and psychophysiological treatment interventions, by carving new neuronal pathways and creating connectivity that augments brain circuitry, carry the potential to remediate body image and self-image distortions, reintegrating the fragmented eating disordered core self. To date, intentional partnering between therapist, ED patient, and neuroplastic brain has been rarely applied in the clinical milieu and minimally referenced in the treatment literature. By bringing current neuroplasticity research into frontline practice, ED practitioners not only bridge the research/practice gap, but redefine new directions for future ED research.

  14. 脑转移瘤合理治疗模式的Meta分析%Meta analysis of brain metastases ideal treatment mode

    Institute of Scientific and Technical Information of China (English)

    李颖; 房晓萌; 姜达; 董倩; 张增叶; 郑飞

    2015-01-01

    Objective To explore the ideal treatment mode of brain metastases by Meta-analysis.Methods Articles were searched for from the databases at home and abroad using English and Chinese keywords.Searching time limited from the databases setting up to December 30,2012.Jadad score was applied to evaluate the qualities of literatures.RevMan5.0 software was applied to perform the Meta-analysis.A totle of 25 articles including 2 750 patients were eligible for the Meta-analysis,which divided into groups with different treatment.Results Compared with monotherapy,combined therapy improved 1-year survival (OR =0.58,95% CI:0.46 ~0.71,P <0.000 01).In combined therapy groups,compared with two methods,three kinds of therapies improved 1-year survival (OR =0.63,95 % CI:0.50 ~ 0.80,P =0.000 1).Compared with local therapy only or systemic therapy only,systemic combined local therapy improved 1-year survival (OR =0.68,95% CI:0.53 ~ 0.86,P =0.001 ; OR =0.59,95% CI:0.41 ~ 0.86,P =0.006).In systemic combined local therapy groups,three kinds of treatments improved 1-year survival compared with two methods (OR =0.52,95% CI:0.35 ~ 0.78,P =0.002).Compared with non-molecular targeted therapy,molecular targeted therapy improved 1-year survival (OR =0.76,95% CI:0.67 ~ 0.87,P < 0.000 1).Conclusion The reasonable treatment for patients with brain metastases is combined treatment with operation,radiotherapy and chemotherapy.There is better curative effect added molecular targeted therapy based on original scheme,if patients have targeted therapy indications.%目的 应用Meta分析的方法探讨脑转移瘤的合理治疗模式.方法 以中英文关键词检索中外数据库,检索时限为自各数据库建立起至2012年12月30日.以Jadad评分评价文献质量,采用RevMan5.0软件完成统计分析.共纳入25篇文献,2 750例患者,依据不同的治疗方法进行分组.结果 与单一治疗相比,综合治疗能提高患者的1年生存率(OR =0.58,95

  15. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Berghoff, A.S. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Ilhan-Mutlu, A.; Preusser, M. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Woehrer, A.; Hainfellner, J.A. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Hackl, M. [Austrian National Cancer Registry, Statistics Austria, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, K. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Melchardt, T. [Paracelsus Medical University Hospital Salzburg, Third Medical Department, Salzburg (Austria); Dome, B. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Heinzl, H. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Vienna (Austria); Birner, P. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Institute of Clinical Pathology, Vienna (Austria)

    2014-07-15

    Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. (orig.) [German] Die Ueberlebensprognose von Patienten mit zerebralen Metastasen eines nicht-kleinzelligen Lungenkarzinoms (NSCLC) ist sehr variabel. Bisher werden gewebsbasierte Parameter nicht in die prognostische Beurteilung inkludiert. Neurochirurgische Resektate zerebraler NSCLC-Metastasen wurden in dieser Studie untersucht. Die Gefaessdichte (''microvascular density'', MVD), der Ki67-Proliferationsindex sowie der HIF-1α-Index wurden mittels

  16. 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.

  17. Interventional Management of Vertebral Body Metastases

    OpenAIRE

    Prince, Ethan A.; Ahn, Sun Ho

    2013-01-01

    Metastases to the vertebral column are often due to hypervascular primary tumors, the most common of which is renal cell carcinoma. Clinical symptoms attributed to vertebral body metastases include localized pain, mechanical instability of the vertebral column, and neurologic deficits resulting from mass effect. Treatment options include targeted radiotherapy, percutaneous vertebral augmentation with or without thermal ablation, and surgical resection with subsequent fusion. Overall, surgical...

  18. Isolated pleural metastases from renal cell carcionoma

    DEFF Research Database (Denmark)

    Eckardt, Jens; Ladegaard, Lars; Licht, Peter Bjorn

    2011-01-01

    A 71-year-old female was referred with three right-sided intrathoracic tumours. In 2003, she underwent radical left nephrectomy for renal cell cancer (RCC) clinical stage 1. She was since followed at her local hospital with annual computed tomography (CT)-scans during the first five years and did....... Histology demonstrated metastases from RCC which apparently can reach the parietal pleura without lung metastases. Keywords: Pleural metastasis; Renal cell cancer....

  19. Incidental ferumoxytol artifacts in clinical brain MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bowser, Bruce A.; Campeau, Norbert G.; Carr, Carrie M.; Diehn, Felix E.; McDonald, Jennifer S.; Miller, Gary M.; Kaufmann, Timothy J. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2016-11-15

    Ferumoxytol (Feraheme) is a parenteral therapy approved for treatment of iron deficiency anemia. The product insert for ferumoxytol states that it may affect the diagnostic ability of MRI for up to 3 months. However, the expected effects may not be commonly recognized among clinical neuroradiologists. Our purpose is to describe the artifacts we have seen at our institution during routine clinical practice. We reviewed the patients at our institution that had brain MRI performed within 90 days of receiving intravenous ferumoxytol. The imaging was reviewed for specific findings, including diffusion-weighted imaging vascular susceptibility artifact, gradient-echo echo-planar T2*-weighted vascular susceptibility artifact, SWI/SWAN vascular susceptibility artifact, hypointense vascular signal on T2-weighted images, pre-gadolinium contrast vascular enhancement on magnetization-prepared rapid acquisition gradient echo (MPRAGE) imaging, and effects on post-gadolinium contrast T1 imaging. Multiple artifacts were observed in patients having a brain MRI within 3 days of receiving intravenous ferumoxytol. These included susceptibility artifact on DWI, GRE, and SWAN/SWI imaging, pre-gadolinium contrast increased vascular signal on MPRAGE imaging, and decreased expected enhancement on post-gadolinium contrast T1-weighted imaging. Ferumoxytol can create imaging artifacts which complicate clinical interpretation when brain MRI is performed within 3 days of administration. Recognition of the constellation of artifacts produced by ferumoxytol is important in order to obviate additional unnecessary examinations and mitigate errors in interpretation. (orig.)

  20. Clinical topographical correlation upon brain tumors in children

    Directory of Open Access Journals (Sweden)

    A.M. Dolgov

    2014-01-01

    Full Text Available The aim of the study was to explore the most characteristic clinical manifestations of brain tumors in children, depending on their localization, and to detect the earliest of them. Patients and methods. A total of 56 children (32 boys and 24 girls with brain tumor, aged from 1.5 months to 15 years, were examined. The time elapsed between the onset of disease to the emergence of clinical symptoms was assessed. Neurological symptomatology was compared to the localization of a tumor diagnosed using neuroimaging techniques (computed tomography or magnetic resonance imaging and during surgery. Surgery was performed in 18 children (in all of them, localization of the process was observed in the posterior cranial fossa, PCF. Results. The highest incidence of brain tumors was revealed in children aged 3–13 years; most patients became ill at the age between 3 and 6 years. Tumors of the PCF predominated in terms of their localization (67.9% of cases. Intracerebral tumors of the hemispheres or vermis were observed in most (63.2% patients with tumors of the PCF. In 11 (61% of the 18 operated children with subtentorial tumors, astrocytomas of various degrees of differentiation and medulloblastomas were detected using the histological examination. Tumors of the IV ventricle were ependymal. Tumors of the cerebral hemispheres (19.6%, of the pineal and chiasmosellar regions (8.9% predominated among supratentorial tumors. The time between the emergence of initial symptoms of a disease and admission to hospital ranged from 1 month to 3 years. The most characteristic and earliest symptoms for tumors of the PCF and brain ventricles were headache, nausea and vomiting. For tumors of the cerebellar vermis and hemispheres, these symptoms included impairment of the coordination of movements and the muscle tone change. For brain stem tumors, these symptoms included dysfunction of the cranial nerves. For tumors of the cerebral hemispheres, these were seizures and motor

  1. New molecular targets in bone metastases.

    Science.gov (United States)

    Santini, D; Galluzzo, S; Zoccoli, A; Pantano, F; Fratto, M E; Vincenzi, B; Lombardi, L; Gucciardino, C; Silvestris, N; Riva, E; Rizzo, S; Russo, A; Maiello, E; Colucci, G; Tonini, G

    2010-11-01

    Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future. Targeting the bone by preventing skeletal related events (SREs) and bone metastases has major clinical impact in improving survival in bone metastatic patients and in preventing disease relapse in adjuvant setting.

  2. 骨转移前列腺癌的临床诊治研究报道%Clinical features and management of prostate cancer with bone metastases: the first report of our Institute

    Institute of Scientific and Technical Information of China (English)

    Zhijian Shen; Honglin Xie; Chaojun Wang; Songliang Cai; Liping Xie; Suo Wang; Zhigen Zhang

    2008-01-01

    Objective: To summarize the experience of diagnosis and treatment outcomes for bone metastatic prostate cancer. Methods: A retrospective study with a total of 128 prostate cancer (Pca) was performed from 2000 to 2005, in our institute. We analyzed the clinical features and outcomes of patients with bone metastases and the data and follow-up of 63 bone metastases was collected by one registrar. Cochran Armitage trend test was used for statistic analysis and a P-value of < 0.05 was taken as statistically significant. Results: The mean age was 73 (range 55 to 87) years. The PSA level was from 0.083 ng/mL to 6462 ng/mL. Bone metastases morbidity had good relationship with PSA level. With the mean follow up of 30 (range 6 to 72) months for 52/63 (82.5%) patients, 15 (28.8%) died from Pea with a mean survival of 21 months and 1 patient with PSA less than 4 ng/mL at the time died from cerebrovascular suddenness 6 months post-treatment. Conclusion: The early effect of endocrine treatment for bone metastases is obvious, and palliative prostatectomy is satisfactory and able to improve the quality of life rapidly for patients with obstructive symptoms.

  3. Cutaneous metastases of hepatocellular carcinoma.

    Science.gov (United States)

    Lazaro, M; Serrano, M L; Allende, I; Ratón, J A; Acebo, E; Diaz-Perez, J L

    2009-12-01

    Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

  4. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Fulp, William J.; Berglund, Anders E. [Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Dilling, Thomas J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Shridhar, Ravi [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2015-07-15

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  5. 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.

  6. Pulmonary nodules and metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i.......e. synchronous metastases. Most common are hepatic metastases followed by pulmonary involvement. The optimal staging modality for detecting synchronous pulmonary metastases is debated. It has been argued, that synchronous pulmonary metastases (SPCM) are rare in CRC and that the consequence of detecting SPCM...... is minimal. Furthermore, the current staging practice is complicated by a high number of incidental findings on the thoracic CT, so-called indeterminate pulmonary nodules (IPN). IPN can potentially represent SPCM. The purpose of this thesis was to estimate the prevalence, characteristics and clinical...

  7. 口服替莫唑胺同步放射治疗脑转移瘤的疗效评价%Evaluation of the Efficacy of Temozolomide plus Concomitant Radiotherapy in the Patients with Brain Metastases

    Institute of Scientific and Technical Information of China (English)

    晏党; 欧阳艳君; 陈小英; 高素杰; 陈英杰

    2012-01-01

    Objective To evaluate the efficacy and adverse reactions of temozolomide plus concomitant radiotherapy in the patients with brain metastases. Methods 95 patients with brain metastases were divided into the treatment group and the control group randomly. 47 patients were treated by temozolomide plus concomitant radiotherapy in the treatment group. And 48 patients were treated by radiotherapy alone. The efficacy and the adverse reactions in the two groups were compared. Results The overall remission rates were 100% in the treatment group, 89. 5% in the control group, significant difference between these two groups( P0. 05 ). All the patients can tolerate the treatment. Conclusion For brain metastases , temozolomide plus concomitant radiotherapy is safe and efficient, and can increase the metastasis control rate and prolong the median survival time.%目的 评价替莫唑胺化疗同步放射治疗脑转移瘤疗效及不良反应.方法 95例脑转移瘤患者随机分为治疗组和对照组,治疗组47例口服替莫唑胺化疗同步放疗;对照组48例单纯放疗.比较两组患者的临床疗效和不良反应情况.结果 治疗组总缓解率为100%,对照组总缓解率为89.5%,差异有统计学意义(P<0.05);治疗组复发中位时间和中位生存时间均长于对照组,差异有统计学意义(P<0.05);两组不良反应情况比较差异无统计学意义(P>0.05),患者均能耐受.结论 口服替莫唑胺化疗同步放疗治疗脑转移瘤安全、有效,可提高脑转移瘤控制率和延长中位生存期.

  8. Neuroplasticity and Clinical Practice: Building Brain Power for Health.

    Science.gov (United States)

    Shaffer, Joyce

    2016-01-01

    The focus of this review is on driving neuroplasticity in a positive direction using evidence-based interventions that also have the potential to improve general health. One goal is to provide an overview of the many ways new neuroscience can inform treatment protocols to empower and motivate clients to make the lifestyle choices that could help build brain power and could increase adherence to healthy lifestyle changes that have also been associated with simultaneously enhancing vigorous longevity, health, happiness, and wellness. Another goal is to explore the use of a focus in clinical practice on helping clients appreciate this new evidence and use evolving neuroscience in establishing individualized goals, designing strategies for achieving them and increasing treatment compliance. The timing is urgent for such interventions with goals of enhancing brain health across the lifespan and improving statistics on dementia worldwide.

  9. Neural Imaginaries and Clinical Epistemology: Rhetorically Mapping the Adolescent Brain in the Clinical Encounter

    Science.gov (United States)

    Buchbinder, Mara

    2014-01-01

    The social work of brain images has taken center stage in recent theorizing of the intersections between neuroscience and society. However, neuroimaging is only one of the discursive modes through which public representations of neurobiology travel. This article adopts an expanded view toward the social implications of neuroscientific thinking to examine how neural imaginaries are constructed in the absence of visual evidence. Drawing on ethnographic fieldwork conducted over 18 months (2008–2009) in a United States multidisciplinary pediatric pain clinic, I examine the pragmatic clinical work undertaken to represent ambiguous symptoms in neurobiological form. Focusing on one physician, I illustrate how, by rhetorically mapping the brain as a therapeutic tool, she engaged in a distinctive form of representation that I call neural imagining. In shifting my focus away from the purely material dimensions of brain images, I juxtapose the cultural work of brain scanning technologies with clinical neural imaginaries in which the teenage brain becomes a space of possibility, not to map things as they are, but rather, things as we hope they might be. These neural imaginaries rely upon a distinctive clinical epistemology that privileges the creative work of the imagination over visualization technologies in revealing the truths of the body. By creating a therapeutic space for adolescents to exercise their imaginative faculties and a discursive template for doing so, neural imagining relocates adolescents’ agency with respect to epistemologies of bodily knowledge and the role of visualization practices therein. In doing so, it provides a more hopeful alternative to the dominant popular and scientific representations of the teenage brain that view it primarily through the lens of pathology. PMID:24780561

  10. Neural imaginaries and clinical epistemology: Rhetorically mapping the adolescent brain in the clinical encounter.

    Science.gov (United States)

    Buchbinder, Mara

    2015-10-01

    The social work of brain images has taken center stage in recent theorizing of the intersections between neuroscience and society. However, neuroimaging is only one of the discursive modes through which public representations of neurobiology travel. This article adopts an expanded view toward the social implications of neuroscientific thinking to examine how neural imaginaries are constructed in the absence of visual evidence. Drawing on ethnographic fieldwork conducted over 18 months (2008-2009) in a United States multidisciplinary pediatric pain clinic, I examine the pragmatic clinical work undertaken to represent ambiguous symptoms in neurobiological form. Focusing on one physician, I illustrate how, by rhetorically mapping the brain as a therapeutic tool, she engaged in a distinctive form of representation that I call neural imagining. In shifting my focus away from the purely material dimensions of brain images, I juxtapose the cultural work of brain scanning technologies with clinical neural imaginaries in which the teenage brain becomes a space of possibility, not to map things as they are, but rather, things as we hope they might be. These neural imaginaries rely upon a distinctive clinical epistemology that privileges the creative work of the imagination over visualization technologies in revealing the truths of the body. By creating a therapeutic space for adolescents to exercise their imaginative faculties and a discursive template for doing so, neural imagining relocates adolescents' agency with respect to epistemologies of bodily knowledge and the role of visualization practices therein. In doing so, it provides a more hopeful alternative to the dominant popular and scientific representations of the teenage brain that view it primarily through the lens of pathology.

  11. BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

    Directory of Open Access Journals (Sweden)

    A. Kh. Bekyashev

    2012-01-01

    Full Text Available Hepatocellular carcinoma ranks 5th in prevalence and 3rd in cancer mortality worldwide. The prognosis of this disease is very poor: the 5-year survival rate was not more than 3–5%. Metastases generally occur in the lung, in the lymph nodes of the abdomen, chest, and neck, in the vertebrae, kidneys, and adrenals. The cases of brain metastasis from hepatocellular cancer are very rare. Overall, the prognosis is very poor for patients with brain metastases from hepatocellular carcinoma. Nevertheless, solitary brain metastases and good hepatic function are favorable survival criteria; thus, the treatment of this group of patients may lead to their better survival. The paper describes a clinical case of brain metastasis from hepatocellular carcinoma in a patient receiving the combination treatment involving neurosurgical treatment and targeted therapy. 

  12. Synthetic MRI of the brain in a clinical setting

    Energy Technology Data Exchange (ETDEWEB)

    Blystad, I.; Smedby, O. [Center for Medical Image Science and Visualization, CMIV, Linkoeping University, Linkoeping (Sweden); Radiology, Department of Medical and Health Sciences, Linkoeping University, Department of Radiology, UHL, County Council of Oestergoetland, Linkoeping (Sweden)], E-mail: ida.blystad@lio.se; Warntjes, J.B.M. [Center for Medical Image Science and Visualization, CMIV, Linkoeping University, Linkoeping (Sweden); Clinical Physiology, Department of Medical and Health Sciences, Linkoeping University, Department of Clinical Physiology, UHL, County Council of Oestergoetland, Linkoeping (Sweden); Landtblom, A.-M. [Center for Medical Image Science and Visualization, CMIV, Linkoeping University, Linkoeping (Sweden); Neurology, Department of Clinical and Experimental Medicine, Linkoeping University, Division of Neurology, UHL, LiM, County Council of Oestergoetland, Linkoeping (Sweden); Lundberg, P. [Center for Medical Image Science and Visualization, CMIV, Linkoeping University, Linkoeping (Sweden); Radiation Physics, Department of Medical and Health Sciences, Linkoeping University, Department of Radiation Physics, UHL, County Council of Oestergoetland, Linkoeping (Sweden); Larsson, E.-M. [Center for Medical Image Science and Visualization, CMIV, Linkoeping University, Linkoeping (Sweden); Department of Radiology, Oncology and Radiation Science/Radiology, Uppsala University, Uppsala (Sweden)

    2012-12-15

    Background. Conventional magnetic resonance imaging (MRI) has relatively long scan times for routine examinations, and the signal intensity of the images is related to the specific MR scanner settings. Due to scanner imperfections and automatic optimizations, it is impossible to compare images in terms of absolute image intensity. Synthetic MRI, a method to generate conventional images based on MR quantification, potentially both decreases examination time and enables quantitative measurements. Purpose. To evaluate synthetic MRI of the brain in a clinical setting by assessment of the contrast, the contrast-to-noise ratio (CNR), and the diagnostic quality compared with conventional MR images. Material and Methods. Twenty-two patients had synthetic imaging added to their clinical MR examination. In each patient, 12 regions of interest were placed in the brain images to measure contrast and CNR. Furthermore, general image quality, probable diagnosis, and lesion conspicuity were investigated. Results. Synthetic T1-weighted turbo spin echo and T2-weighted turbo spin echo images had higher contrast but also a higher level of noise, resulting in a similar CNR compared with conventional images. Synthetic T2-weighted FLAIR images had lower contrast and a higher level of noise, which led to a lower CNR. Synthetic images were generally assessed to be of inferior image quality, but agreed with the clinical diagnosis to the same extent as the conventional images. Lesion conspicuity was higher in the synthetic T1-weighted images, which also had a better agreement with the clinical diagnoses than the conventional T1-weighted images. Conclusion. Synthetic MR can potentially shorten the MR examination time. Even though the image quality is perceived to be inferior, synthetic images agreed with the clinical diagnosis to the same extent as the conventional images in this study.

  13. A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases

    Directory of Open Access Journals (Sweden)

    Rodrigues George

    2012-03-01

    Full Text Available Abstract Background Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. A phase I trial has been now completed at our institution with a total of 60 enrolled patients and 48 evaluable patients. The phase II dose has been determined to be the final phase I cohort dose of 60 Gy/10 fractions. Methods/Design The objective of this clinical trial is to subject the final phase I cohort dose to a phase II assessment of the endpoints of overall survival, intracranial control (ICC and intralesional control (ILC. We hypothesize HT would be considered unsuitable for further study if the median OS for patients treated with the HT SIB technique is degraded by 2 months, or the intracranial progression-free rates (ICC and ILC are inferior by 10% or greater compared to the expected results with treatment by whole brain plus SRS as defined by the RTOG randomized trial. A sample size of 93 patients was calculated based on these parameters as well as the statistical assumptions of alpha = 0.025 and beta = 0.1 due to multiple statistical testing. Secondary assessments of toxicity, health-related quality-of-life, cognitive changes, and tumor response are also integrated into this research protocol. Discussion To summarize, the purpose of this phase II trial is to assess this non-invasive alternative to SRS in terms of central nervous system (CNS control when compared to SRS historical controls. A follow-up phase III trial may be required depending on the results of this trial in order to definitively assess non-inferiority/superiority of this approach

  14. Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials.

    Science.gov (United States)

    Silverberg, Noah D; Crane, Paul K; Dams-O'Connor, Kristen; Holdnack, James; Ivins, Brian J; Lange, Rael T; Manley, Geoffrey T; McCrea, Michael; Iverson, Grant L

    2017-01-15

    Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint.

  15. Early application of deep brain stimulation: clinical and ethical aspects.

    Science.gov (United States)

    Woopen, Christiane; Pauls, K Amande M; Koy, Anne; Moro, Elena; Timmermann, Lars

    2013-11-01

    Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinson's disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, (1) DBS early in the course of the disease, and (2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome.

  16. NMO in pediatric patients: brain involvement and clinical expression

    Directory of Open Access Journals (Sweden)

    Joaquín A. Peña

    2011-02-01

    Full Text Available OBJECTIVE: To analyze the clinical, neuroimaging characteristics and positivity of the acquaporin water channel (NMO-IgG in pediatric patients with neuromyelitis optica (NMO. This disorder could have a variable clinical expression. To address such variability, the term NMO spectrum has been suggested. METHOD: We evaluated six pediatric patients, with a median age of 11 years at the time of the study, with the diagnosis of NMO by the Wingerchuck criteria. RESULTS: All the cases exhibited bilateral optic neuritis (ON. Four patients had abnormalities on brain MRI from the onset,although only three of them developed symptoms correlated to those lesions during the course of their disorder. NMO-IgG was positive in 80%. CONCLUSION: Optic neuropathy is the most impaired feature in NMO patients. Brain MRI lesions are not compatible with multiple sclerosis and positivity of the NMO-IgG are also present in NMO pediatric patients, confirming the heterogeneity in the expression of this disorder.

  17. [Distant metastases of malignant tumors of head and neck].

    Science.gov (United States)

    Totan, C; Dincă, O; Negureanu, M; Vlădan, C; Bucur, Al

    2010-01-01

    The charts of 176 previously untreated patients with head and neck squamous cell carcinoma who completed treatment during 2006 in Oro-Maxillo-Facial Clinic, UMF "Carol Davila" Bucharest were reviewed. These patients had no evidence of distant metastases when initially evaluated. The overall incidence of distant metastases was 27.84%, varying from 10.52% for buccal mucosa to 63.63% for tongue and floor of the mouth (p < 0.05). 80% of the metastases were detected within two years after treatment. The rate also increased with the T and N classification; however, the N stage had greater influence on the rate of metastases than the T stage.

  18. Ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics.

    Science.gov (United States)

    Corben, Adriana D; Uddin, Mohammad M; Crawford, Brooke; Farooq, Mohammad; Modi, Shanu; Gerecitano, John; Chiosis, Gabriela; Alpaugh, Mary L

    2014-10-02

    The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

  19. Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Hao [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Shu-Lian, E-mail: wsl20040118@yahoo.com [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Jing; Xue, Mei; Xiong, Zu-Kun [Department of Radiology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Jin, Jing; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Yu, Zi-Hao; Liu, Xin-Fan [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Ye-Xiong, E-mail: yexiong12@163.com [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2015-10-01

    Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.

  20. Breast carcinoma metastases.

    Science.gov (United States)

    Bodzin, G A; Staren, E D; Faber, L P

    1998-02-01

    With careful selection of patients, complete resection of pulmonary metastases from breast carcinoma may be a useful therapeutic option. Such a treatment appears to offer a significant survival benefit when compared with medical treatment alone, or with incomplete resection.

  1. Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy.

    Science.gov (United States)

    Smalley, Keiran S M; Fedorenko, Inna V; Kenchappa, Rajappa S; Sahebjam, Solmaz; Forsyth, Peter A

    2016-09-15

    Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ∼30% of patients (as high as 75% at autopsy). In ∼5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a "sanctuary" sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that (1) Cancer cells migrating to the CNS may have unique molecular properties and (2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review, we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma.

  2. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    Science.gov (United States)

    2016-11-15

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  3. Sjælden metastase fra sjælden hjernetumor

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior...

  4. Multiple intradural spinal metastases of esthesioneuroblastoma: A case report.

    Science.gov (United States)

    Mohindra, Sandeep; Tripathi, Manjul; Mohindra, Satyawati; Savardekar, Amey; Radotra, Bishan D

    2015-01-01

    Spinal metastases from esthesioneuroblastoma (ENB) might have variable presentations. Discrete lesions, even when multiple, warrant radical excision, followed by radiotherapy. The authors present a case of anterior skull base ENB, metastasizing to spine at muliple levels. Clinical and radiological pictures are described with intraoperative findings.

  5. CEREBRAL METASTASES CANCER OF THE LARYNX: TWO CASE REPORTS

    OpenAIRE

    N. V. Sevyan; V. B. Karakhan; Ju. A. Tsybulskaya; Belov, D. M.; Ju. V. Bondarenko; D. R. Naskhletashvili; S. V. Medvedev; B. I. Polyakov

    2013-01-01

    Cerebral metastases cancer of the larynx are rare and poorly understood pathology, many questions of diagnostics and treatment of this pathology remain open. In the work presents clinical cases сerebral metastases cancer of the larynx. Special attention is paid to surgical treatment in complex with chemotherapy.

  6. CEREBRAL METASTASES CANCER OF THE LARYNX: TWO CASE REPORTS

    Directory of Open Access Journals (Sweden)

    N. V. Sevyan

    2013-01-01

    Full Text Available Cerebral metastases cancer of the larynx are rare and poorly understood pathology, many questions of diagnostics and treatment of this pathology remain open. In the work presents clinical cases сerebral metastases cancer of the larynx. Special attention is paid to surgical treatment in complex with chemotherapy.

  7. Clinical characteristics of 15 glioma cases with leptomeninges and spinal cord metastases%恶性神经胶质瘤脑膜脊髓播散转移15例临床病例分析

    Institute of Scientific and Technical Information of China (English)

    李珊; 陈建新; 李岩; 康庄; 康勋; 张红梅; 李文斌

    2016-01-01

    Objective:To retrospectively analyze and summarize the clinical characteristics of 15 glioma cases that led to leptomenin-ges and spinal cord metastases in Department of Glioma, Beijing Shijitan Hospital, Capital Medical University since 2011. Methods:A total of 15 cases were considered, including 5 patients with World Health Organization gradeⅡ, 6 patients with gradeⅢ, and 4 pa-tients with gradeⅣ. One patient had a tumor at the brain stem, two patients had tumors at the spinal cords, and the other patients had tumors at the hemispheres. One case received biopsy, 4 cases received subtotal resection, and 10 cases received complete resec-tion. Results: Symptoms included low back pain, sensory and motor dysfunction, incontinence, and seizures. After the metastases spread to the cerebrospinal region, patients were treated with chemotherapy, whole spine radiotherapy, intrathecal chemotherapy, and target therapy. The median time of leptomeninges and spinal cord metastasis dissemination appearance was 10 months (1.5-80 months) since surgery. The median overall survival time of the 15 patients was 20 months (9-83 months), and the median survival time was 6 months (2-48 months) after leptomeninges and spinal cord metastases. Conclusion:The prognosis of glioma patients with lepto-meninges and spinal cord metastases was poor, and a proportion of the patients who received appropriate treatment might have a better survival.%目的:通过分析15例发生脑膜脊髓播散转移的脑胶质瘤患者的临床表现,对其特点进行归纳总结。方法:回顾性分析首都医科大学附属北京世纪坛医院脑胶质瘤科2011年1月至2015年9月收治15例发生脑膜脊髓播散转移的脑胶质瘤患者,其中WHOⅡ级5例,Ⅲ级6例,Ⅳ级4例;原发于脑干1例,原发于脊髓2例,原发于幕上12例。15例患者中行活检术1例,近全切除4例,完全切除10例。结果:患者出现的症状包括:腰背疼痛、浅感觉异

  8. Management of posttraumatic brain swelling based on clinical typing

    Institute of Scientific and Technical Information of China (English)

    刘伟国; 裘五四; 沈宏; 王卫民

    2004-01-01

    Objective: To investigate the clinical typing and prophylactico-therapeutic measures for acute posttraumatic brain swelling (BS).Methods: A retrospective study was performed in 66 cases of acute posttraumatic BS. There were 3 groups based on computered tomography (CT) scanning: 23 cases of hemisphere brain swelling (HBS) with middle line shift for less than 5 mm within 24 hours ( Group A), 20 with middle line shift for more than 5 mm (Group B ), and 23 with bilateral diffuse brain swelling (Group C).Results : (1) The mortality rates of the operative and nonoperative management in Group A, Group B, and Group C were 20.0%, 31.6%, and 75.0% versus 44.4%,0, and 85.7 %, respectively ( P > 0.05 ); while the rates in subgroups with different middle line shift ( more than 5 mm and less or equal 5 mm) were 29.2% and 75.0% versus 75.0% and 44.4%, respectively (0.05 >P >0.01). (2) The good recovery rate and mortality in Group A were 47.8 % and 39.1%, respectively and in Group C, 8.7 % and 78.3%, respectively. There was a very significant difference between Group A and Group C (P <0.01). (3) The total survival rate of the selective comprehensive therapy was 53.1%.Conclusions : ( 1 ) Acute posttraumatic BS needs to be diagnosed correctly and promptly with CT scanning within 4 hours. (2) For patients with midline shift for more than 5 mm, especially with thin-layered subdural hematoma,surgical intervention is essential to reduce the fatality of acute posttraumatic BS.

  9. The preventive effect of temozolomide on brain metastases from small-cell lung cancer%替莫唑胺对小细胞肺癌脑转移的预防作用

    Institute of Scientific and Technical Information of China (English)

    陈晨; 王浩渊

    2016-01-01

    Objective This study aimed to explore the preventive effect of temozolomide on brain metastases from small-cell lung cancer. Methods A total of 50 patients with small-cell lung cancer who achieved complete remission or partial response after radiation and chemotherapy were divided into treatment group and control group. 30 patients of the treatment group received maintain chemotherapy using temozolomide. 20 patients of the control group received prophylactic cranial irradiation (PCI). The brain metastases positive rate, overall survival rate and 1 year survival rate were analyzed. The adverse reactions of the two treatments were recorded. Results There were no significant differences between temozolomide chemotherapy group and PCI group in brain metastases positive rate (16.7%vs. 15.0%, P>0.05). There were no significant differences of the overall survival rate and 1 year survival rate between the two groups (31 months vs. 24 months, 86.3% vs. 79.1%, P>0.05). The adverse reactions of temozolomide chemotherapy group were mainly hematology and gastrointestinal reaction which was mild to moderate. The acute reactions of PCI group were mainly dizziness and nausea, and some patients had long-term nervous system adverse reaction. Conclusion The effect of temozolomide on maintaining chemotherapy to reduce brain metastasis from small-cell lung cancer is not worse than the traditional treatment of PCI and it is safe and feasible.%目的:探讨替莫唑胺维持化疗对小细胞肺癌脑转移的预防作用。方法采用前瞻、对照研究,将初治放化疗后达到完全缓解或部分缓解的小细胞肺癌患者50例分为治疗组(n=30)和对照组(n=20)。治疗组在放化疗结束后使用替莫唑胺维持化疗,对照组行预防性全脑照射(PCI)。统计分析两组患者脑转移阳性率,总生存期及1年生存率。分别记录两种治疗方案发生的不良反应。结果替莫唑胺化疗组与PCI组脑转移阳性

  10. Congenital malformations of the brain: Pathological, embryological, clinical, radiological, and genetic aspects

    Energy Technology Data Exchange (ETDEWEB)

    Norman, M.G.; McGillivray, B.; Kalousek, D.K.; Hill, A.; Poskitt, K.

    1995-12-31

    Although I can quibble with the treatment of a few topics, this is by far the best book ever written on human brain malformations. The senior author has studied the pathology of human brain malformations throughout her career and has strengthened the book greatly by seeking coauthors to help with critical areas such as brain imaging, clinical management, and, especially, genetics.

  11. A Variational Framework for Joint Detection and Segmentation of Ovarian Cancer Metastases

    OpenAIRE

    Liu, Jianfei; Wang, Shijun; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M.

    2013-01-01

    Detection and segmentation of ovarian cancer metastases have great clinical impacts on women’s health. However, the random distribution and weak boundaries of metastases significantly complicate this task. This paper presents a variational framework that combines region competition based level set propagation and image matching flow computation to jointly detect and segment metastases. Image matching flow not only detects metastases, but also creates shape priors to reduce over-segmentation. ...

  12. Bony Calvarium as the Sole Site ofMetastases in Squamous Cell Carcinomaof the Uterine Cervix

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadianpanah

    2010-10-01

    Full Text Available Isolated skeletal metastasis to the bony calvarium is extremely rare in patients with squamous cell carcinoma of the uterine cervix. We describe the clinical and imaging findings in a case of squamous cell carcinoma of the uterine cervix with metastases tothe bony calvarium as the sole site of metastasis. The patient was a 65-year-old woman with squamous cell carcinoma of the uterine cervix, FIGO stage IIIb, whose initial treatement was chemoradiation therapy. After 22 sessions of external-beam radiation,she developed headaches. On physical examination she had skull bone tenderness. On plain skull X-ray, there were osteolytic bony lesions. Brain MRI showed multiple enhancing skull bone metatstses. Eventually, a whole body bone scintigraphy revealed isolated diffuse increased activity in the bony calvarium. In the literature review, wefound only three similar cases of cervical cancer with scalp metastases and involvement of the bony calvarium.

  13. Whole brain radiation with supplementary boost for patients for unique brain metastasis from a primitive lung cancer; Experience de l'irradiation encephalique totale avec escalade de dose focalisee pour le traitement des metastases cerebrales uniques d'un carcinome bronchopulmonaire

    Energy Technology Data Exchange (ETDEWEB)

    Levy, A.; Lamproglou, I. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Chargari, C. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Service de radiotherapie, hopital d' instruction des armees Val-de-Grace, 75005 Paris (France); Mazeron, J.J. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Universite Pierre-et-Marie-Curie Paris 6, 4, place Jussieu, 75005 Paris (France); Krzisch, C. [Service de radiotherapie, CHU d' Amiens-Picardie, place Victor-Pauchet, 80054 Amiens cedex (France); Assouline, A. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Universite Pierre-et-Marie-Curie Paris 6, 4, place Jussieu, 75005 Paris (France); Service de radiotherapie, CHU d' Amiens-Picardie, place Victor-Pauchet, 80054 Amiens cedex (France)

    2011-08-15

    Purpose. - To assess the potential benefit of a boost in patients treated with whole brain irradiation by a conventional linear accelerator for lung cancer solitary brain metastasis. Patients and methods. - From 2002 to 2006, a retrospective analysis was carried out from 64 unselected consecutive patients with secondary brain metastasis from lung cancer, treated with whole brain irradiation without surgical resection. Thirty patients (47%) received a boost in their brain metastases. Three potential prognostic factors were studied: sex, RPA score and improvement of neurological symptoms after radiotherapy. An analysis was conducted to determine whether an additional dose may improve survival in the absence of surgical resection. Results. - The mean follow-up was 4.9 months. The median overall survival was 8.5 months (6.4 to 10.7 months). The total dose of radiotherapy was the only significant prognostic factor for overall survival. The median overall survival was 6.2 months for patients without additional radiation versus 11.2 months for patients receiving a boost dose (p = 0.011). Sex, RPA score and improvement of neurological symptoms after radiotherapy were not found as prognostic factors for overall survival. Conclusions. - Boost delivered after whole brain radiation therapy by a conventional particle accelerator may provide a benefit in selected patients, especially for centres that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment. (authors)

  14. Clinical application of magnetic resonance in acute traumatic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Morais, Dionei F.; Gaia, Felipe F.P. [Hospital de Base de Sao Jose do Rio Preto, SP (Brazil). Servico de Neurocirurgia]. E-mail: centro@cerebroecoluna.com.br; Spotti, Antonio R.; Tognola, Waldir A. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Ciencias Neurologicas; Andrade, Almir F. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Neurocirurgia da Emergencia

    2008-07-01

    Purpose: To evaluate the clinical applications of magnetic resonance imaging (MRI) in patients with acute traumatic brain injury (TBI): to identify the type, quantity, severity; and improvement clinical-radiological correlation. Method: Assessment of 55 patients who were imaged using CT and MRI, 34 (61.8%) males and 21 (38.2%) females, with acute (0 to 5 days) and closed TBI. Results: Statistical significant differences (McNemar test): occurred fractures were detected by CT in 29.1% and by MRI in 3.6% of the patients; subdural hematoma by CT in 10.9% and MRI in 36.4 %; diffuse axonal injury (DAI) by CT in 1.8% and MRI in 50.9%; cortical contusions by CT in 9.1% and MRI in 41.8%; subarachnoid hemorrhage by CT in 18.2% and MRI in 41.8%. Conclusion: MRI was superior to the CT in the identification of DAI, subarachnoid hemorrhage, cortical contusions, and acute subdural hematoma; however it was inferior in diagnosing fractures. The detection of DAI was associated with the severity of acute TBI. (author)

  15. Ethical brain stimulation - neuroethics of deep brain stimulation in research and clinical practice.

    Science.gov (United States)

    Clausen, Jens

    2010-10-01

    Deep brain stimulation (DBS) is a clinically established procedure for treating severe motor symptoms in patients suffering from end-stage Parkinson's disease, dystonia and essential tremor. Currently, it is tested for further indications including psychiatric disorders like major depression and a variety of other diseases. However, ethical issues of DBS demand continuing discussion. Analysing neuroethical and clinical literature, five major topics concerning the ethics of DBS in clinical practice were identified: thorough examination and weighing of risks and benefits; selecting patients fairly; protecting the health of children in paediatric DBS; special issues concerning patients' autonomy; and the normative impact of quality of life measurements. In exploring DBS for further applications, additionally, issues of research ethics have to be considered. Of special importance in this context are questions such as what additional value is generated by the research, how to realise scientific validity, which patients should be included, and how to achieve an acceptable risk-benefit ratio. Patients' benefit is central for ethical evaluation. This criterion can outweigh very serious side-effects, and can make DBS appropriate even in paediatrics. Because standard test procedures evade central aspects of patients' benefits, measuring quality of life should be supplemented by open in-depth interviews to provide a more adequate picture of patients' post-surgical situation. To examine its entire therapeutic potential, further research in DBS is needed. Studies should be based on solid scientific hypotheses and proceed cautiously to benefit severely suffering patients without putting them to undue risks.

  16. Efficacy evaluation of radiotherapy and temozolomide in patients with brain metastases%替莫唑胺联合全脑放疗治疗脑转移瘤的疗效评价

    Institute of Scientific and Technical Information of China (English)

    毕卓菲; 刘宜敏; 何艳; 廖恺

    2012-01-01

    Objective; To assess the efficacy and safety of temozolomide combined with radiotherapy in patients with brain metastases. Methods; Fifty-five patients with more than three brain metastases were randomized to oral temozolomide (75 mg-m"2-d"1) combined with 40-Gy fractionated conventional external-beam radiotherapy (2 Gyd"1, 5 days per week) for 4 weeks versus 40-Gy radiotherapy alone. In the group receiving combined therapy, patients took temozolomide (200 mg-m~2 -d"1 ) for 5 days for six cycles of 28 days after radiotherapy. Overall and progression-free survival curves were estimated by Kaplan-Meier technique and compared by two-sided log-rank test. Results; The objective response rate was significantly improved in patients receiving temozolomide + radiotherapy versus radiotherapy alone (76.9% vs 48.0% , P =0.033). The median overall survival and median progression-free survival were 5.5 vs 8.0 months (P =0.025) and 3. 1 vs 5.0 months (P =0.020) for the radiotherapy-alone and the combined groups, respectively. Daily temozolomide combined with radiotherapy was generally well tolerated; however, nausea and vomiting were significantly increased in combined group. Conclusion; Temozolomide is safe, and shows significant improvements in response rate, progression-free survival and overall survival when administered in combination with radiotherapy in patients with brain metastases.%目的:评价替莫唑胺联合全脑放疗治疗脑转移瘤患者的疗效及安全性.方法:将55例脑转移瘤患者(转移灶>3个)随机分为替莫唑胺联合放疗组及放疗组.替莫唑胺联合放疗组予以常规分割行全脑放疗,DT:40 Gy(2 Gy·d-1,每周5d),于放疗dl开始给予替莫唑胺口服治疗(75 mg·m-2·d-1),放疗结束后每28 d予以替莫唑胺口服5d(200 mg·m-2 ·d-1)化疗,共6周期.放疗组全脑放疗,DT:40 Gy(2 Gy·d-1,每周5d).使用Kaplan-Meier方法计算生存率、无进展生存率及生存曲线,组间生存率比较应用Log-rank检

  17. Brain imaging with synthetic MR in children: clinical quality assessment

    Energy Technology Data Exchange (ETDEWEB)

    Betts, Aaron M.; Serai, Suraj [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Leach, James L.; Jones, Blaise V. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); University of Cincinnati College of Medicine, Cincinnati, OH (United States); Zhang, Bin [Cincinnati Children' s Hospital Medical Center, Biostatistics and Epidemiology, Cincinnati, OH (United States)

    2016-10-15

    Synthetic magnetic resonance imaging is a quantitative imaging technique that measures inherent T1-relaxation, T2-relaxation, and proton density. These inherent tissue properties allow synthesis of various imaging sequences from a single acquisition. Clinical use of synthetic MR imaging has been described in adult populations. However, use of synthetic MR imaging has not been previously reported in children. The purpose of this study is to report our assessment of diagnostic image quality using synthetic MR imaging in children. Synthetic MR acquisition was obtained in a sample of children undergoing brain MR imaging. Image quality assessments were performed on conventional and synthetic T1-weighted, T2-weighted, and FLAIR images. Standardized linear measurements were performed on conventional and synthetic T2 images. Estimates of patient age based upon myelination patterns were also performed. Conventional and synthetic MR images were evaluated on 30 children. Using a 4-point assessment scale, conventional imaging performed better than synthetic imaging for T1-weighted, T2-weighted, and FLAIR images. When the assessment was simplified to a dichotomized scale, the conventional and synthetic T1-weighted and T2-weighted images performed similarly. However, the superiority of conventional FLAIR images persisted in the dichotomized assessment. There were no statistically significant differences between linear measurements made on T2-weighted images. Estimates of patient age based upon pattern of myelination were also similar between conventional and synthetic techniques. Synthetic MR imaging may be acceptable for clinical use in children. However, users should be aware of current limitations that could impact clinical utility in the software version used in this study. (orig.)

  18. Hydrocephalus following severe traumatic brain injury in adults. Incidence, timing, and clinical predictors during rehabilitation

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Linnemann, Mia; Tibæk, Maiken

    2013-01-01

    To investigate timing and clinical predictors that might predict hydrocephalus emerging during rehabilitation until 1 year following severe traumatic brain injury (TBI).......To investigate timing and clinical predictors that might predict hydrocephalus emerging during rehabilitation until 1 year following severe traumatic brain injury (TBI)....

  19. Effect of cocaine dependence on brain connections: Clinical implications

    Science.gov (United States)

    Ma, Liangsuo; Steinberg, Joel L.; Moeller, F. Gerard; Johns, Sade E.; Narayana, Ponnada A.

    2015-01-01

    Cocaine dependence (CD) is associated with several cognitive deficits. Accumulating evidence, based on human and animal studies, has led to models for interpreting the neural basis of cognitive functions as interactions between functionally related brain regions. In this review, we focus on the magnetic resonance imaging (MRI) studies using brain connectivity techniques as related to CD. The majority of these brain connectivity studies indicated that cocaine use is associated with altered brain connectivity between different structures, including cortical-striatal regions and default mode network. In cocaine users, some of the altered brain connectivity measures are associated with behavioral performance, history of drug use, and treatment outcome. The implications of these brain connectivity findings to the treatment of CD and the pros and cons of the major brain connectivity techniques are discussed. Finally potential future directions in cocaine use disorder research using brain connectivity techniques are briefly described. PMID:26512421

  20. Intestinal perforation secondary to metastasic lung carcinoma

    Directory of Open Access Journals (Sweden)

    M. C. Álvarez Sánchez

    2014-11-01

    Full Text Available Secondary symptomatic gastrointestinal metastases from lung primary tumor are rare. They can cause a variety of clinical conditions such as perforation, obstruction and bleeding. Intestinal perforations of intestinal metastases have a very poor prognosis. We present a case of a patient with metastatic lung cancer who presents with intestinal perforation and pneumoperitoneum. A 67 year old male, immunosuppressed and smoker is diagnosed with acute abdomen secondary to perforation of a tumor of the terminal ileum, as well as three other similar injuries. Resection and anastomosis. The patient died two months after surgery. The final pathological diagnosis supports epidermoidide poorly differentiated lung carcinoma. It was concluded that given an intestinal perforation in a patient diagnosed with lung carcinoma, it shouldn´t be excluded the metastases origen . Surgery is a purely palliative procedure.

  1. Clinical science workshop: targeting the gut-liver-brain axis.

    Science.gov (United States)

    Patel, Vishal C; White, Helen; Støy, Sidsel; Bajaj, Jasmohan S; Shawcross, Debbie L

    2016-12-01

    A clinical science workshop was held at the ISHEN meeting in London on Friday 11th September 2014 with the aim of thrashing out how we might translate what we know about the central role of the gut-liver-brain axis into targets which we can use in the treatment of hepatic encephalopathy (HE). This review summarises the integral role that inter-organ ammonia metabolism plays in the pathogenesis of HE with specific discussion of the roles that the small and large intestine, liver, brain, kidney and muscle assume in ammonia and glutamine metabolism. Most recently, the salivary and gut microbiome have been shown to underpin the pathophysiological changes which culminate in HE and patients with advanced cirrhosis present with enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across a leaky gut epithelial barrier. Resident macrophages within the liver are able to sense bacterial degradation products initiating a pro-inflammatory response within the hepatic parenchyma and release of cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-8 into the systemic circulation. The endotoxemia and systemic inflammatory response that are generated predispose both to the development of infection as well as the manifestation of covert and overt HE. Co-morbidities such as diabetes and insulin resistance, which commonly accompany cirrhosis, may promote slow gut transit, promote bacterial overgrowth and increase glutaminase activity and may need to be acknowledged in HE risk stratification assessments and therapeutic regimens. Therapies are discussed which target ammonia production, utilisation or excretion at an individual organ level, or which reduce systemic inflammation and endotoxemia which are known to exacerbate the cerebral effects of ammonia in HE. The ideal therapeutic strategy would be to use an agent that can reduce hyperammonemia and reduce systemic inflammation or perhaps to adopt a combination of

  2. 脑转移瘤再次放疗联合替莫唑胺化疗的疗效分析%Brain Metastases Again for the Efifcacy of Radiotherapy Combined with Temozolomide Chemotherapy Analysis

    Institute of Scientific and Technical Information of China (English)

    陈晓泉; 张永彤; 李量

    2014-01-01

    [ABSTRACT]Objective:Analysis of brain metastases in patients with radiotherapy combined again for the effect of temozolomide chemotherapy treatment. Methods:108 cases of patients with brain metastasis group, control group 64 cases, given a three-dimensional conformal radiation therapy; observation group of 44 cases, based on the radiotherapy combined with temozolomide oral treatment, and the incidence of adverse reaction to evaluate the therapeutic effect of two groups of patients. Results:The effective rate was significantly higher than that of control group, the observation of patients in the treatment group, P0.05. Conclusion: Patients with brain metastasis again radiotherapy combined with temozolomide therapy is safe and effective.%目的::分析脑转移瘤患者再次放疗治疗中联合应用替莫唑胺化疗的效果。方法:将108例对脑转移瘤患者分组,对照组64例,给予三维适形放疗治疗;观察组44例,在放疗的基础上配合替莫唑胺口服治疗,评估两组患者的治疗效果及不良反应发生情况。结果:观察组患者的治疗有效率明显高于对照组,P<0.05。两组间不良反应发生率相比无明显差异,P>0.05。结论:脑转移瘤患者再次放疗联合替莫唑胺治疗安全有效。

  3. First clinical experience with intranasal cooling for hyperthermia in brain-injured patients

    DEFF Research Database (Denmark)

    Springborg, Jacob Bertram; Springborg, Karoline Kanstrup; Romner, Bertil

    2013-01-01

    Hyperthermia is common in brain-injured patients and associated with a worse outcome. As brain rather than body temperature reduction, theoretically, is the most important in cerebral protection, there is logic in targeting cooling at the brain. Selective brain cooling can, in theory, be obtained...... by cooling the skull or by heat loss from the upper airways. In this preliminary safety and efficacy study, we report clinical data from brain-injured patients who because of hyperthermia were treated with intranasal cooling.......Hyperthermia is common in brain-injured patients and associated with a worse outcome. As brain rather than body temperature reduction, theoretically, is the most important in cerebral protection, there is logic in targeting cooling at the brain. Selective brain cooling can, in theory, be obtained...

  4. Inguinal metastases from testicular cancer

    DEFF Research Database (Denmark)

    Daugaard, Gedske; Karas, Vladimir; Sommer, Peter

    2006-01-01

    To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease.......To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease....

  5. Clinical Features and Misdiagnosis Analysis of Lung Cancer with Symptoms of Bone Metastases as the First Manifestation%以骨转移症状首发的肺癌临床特征及误诊分析

    Institute of Scientific and Technical Information of China (English)

    何玉明; 李良平; 张海琳; 黄忠达

    2012-01-01

    目的 探讨以骨转移症状首发的肺癌临床特点,分析误诊原因及预后.方法 回顾分析我院2001年6月~2010年6月诊治的50例以骨转移症状首发的肺癌临床资料.结果 50例均有骨痛,20例伴神经系统症状,6例发生病理性骨折.骨转移以多发、溶骨性骨破坏为主.本组初诊时误诊46例,误诊率92%,误诊时间3d~3个月,误诊疾病前3位为腰椎间盘突出症、椎体骨质增生和原发性骨肿瘤.经手术病理确诊46例,细胞学作出恶性肿瘤诊断但未明确分型2例,影像学确诊2例.本组1年生存率为10%,中位生存期为4个月.结论 以骨转移症状为首发表现的肺癌以多发性、溶骨性骨破坏为特征,腺癌骨转移发生率高,预后差,误诊率高.临床医生对此应高度重视,以减少误诊.%Objective To discuss the clinical features of lung cancer with symptoms of bone metastases as the first manifestation and analyze misdiagnosis and prognosis factors. Methods The clinical records of SO lung cancer patients with symptoms of bone metastases as the first manifestation during June 2001 and June 2010 in our hospital were retrospectively analyzed. Results All 50 patients had bone pain, 20 suffered from neurologic symptoms and 6 had pathologic bone fracture. The main clinical features of bone metastases were multiple locations and osteolytic bone destruction. 46 cases were initially misdiagnosed, with a misdiagnosis rate of 92% , and the duration of the misdiagnosis period varied from 3 days to 3 months- The top 3 misdiagnosed diseases were lumbar disc herniation( LDH) , hyperostosis and primary bone tumors. Among the 50 cases, 46 were pathologically diagnosed, 2 were cytological diagnosed as having malignant tumors and 2 were diagnosed by imaging tests. The 1 -year survival rate of 50 patients was 10% with a mediam survival time of 4 months. Conclusion The main clinical features of lung cancer with symptoms of bone metastases as the first

  6. Systematic Evaluation of Stereotactic Radiotherapy for Brain Metastases of Breast Cancer%立体定向放疗在乳腺癌脑转移瘤中的系统评价

    Institute of Scientific and Technical Information of China (English)

    简红梅; 吴英

    2016-01-01

    目的:应用系统评价方法评价立体定向放疗在乳腺癌脑转移瘤中的疗效和安全性。方法检索PubMed、MEDILINE,EMBASE and Cochrane图书馆以及中国生物医学文献数据库等数据库,纳入接受单独立体定向放疗治疗(SRS)对比SRS联合全脑放疗(WBRT)的乳腺癌脑转移的随机对照试验或队列对照研究,检索日期截止至2014年6月。以Cochrane系统评价方法评价纳入研究,提取有效数据后使用RevMan 5.2软件对总生存期、局部控制生存期进行meta分析。结果共纳入2个回顾性队列研究,包括103例患者,meta分析结果显示SRS对比SRS联合WBRT在总生存期(HR=0.85,95%CI[0.56,1.29],=0.44),局部控制生存期(HR=1.25,95%CI[0.82,1.90],=0.30)方面均无明显差别。结论目前证据表明单独SRS对比SRS联合WBRT在乳腺癌脑转移患者中并无明显的生存差别,但在不良反应和局部缓解率方面尚不清楚,需要更多高质量随机对照试验进一步证实。%Objective The role of stereotactic radiosurgery (SRS)has became an effective treatment for patients of metastases from breast cancer. Methods Electronic (PubMed,MEDILINE,EMBASE and Cochrane library databases)was conducted throughout June 2014 to identify trails for patients underwent SRS alone or in combination with WBRT for newly diagnosed of brain metastases from breast cancer . The Cochrane Collaboration Review Manage 5.2 statistical software was used for this meta-analysis.Results A total of two retrospective cohort including 103 patients. No significant difference both in overall survival(OS) (HR=0.85,95%CI[0.56,1.29],p=0.44)and local control(LC) time (HR=1.25,95%CI[0.82,1.90],p=0.30)between these two therapies was observed . Conclusion Our finding suggest both SRS and SRS plus WBRT can be selected for newly diagnosed brain metastases patients for breast cancer .But in term of adverse reactions and long-term effects is not clear,the need for

  7. SURGICAL TACTICS REGARDING CEREBRAL METASTASES WITH HEMORRHAGES

    Directory of Open Access Journals (Sweden)

    E. V. Prozorenko

    2015-01-01

    Full Text Available Cerebral metastases occur with 10 to 30 % of all oncological patients. Hemorrhages into cerebral metastases are one of the most dangerous complications of the metastatic process. With that, cerebral metastases of such widespread solid malignant tumors as melanoma, kidney cancer, germ cell tumors, less frequently, lung cancer and breast cancer are prone to hemorrhages. The purpose of the work is to improve the results of surgical treatment of patients with brain metastases complicated with hemorrhages.Materials  and  methods. Surgical  treatment  of  69  patients  with  brain  metastases complicated  with  hemorrhages was  performed in N.N. Blokhin Russian Cancer Research Center. Hemorrhage on the macroscopic level was confirmed intraoperatively and in accordance with the results of the morphological study of surgical drugs. Total microsurgical resection of one or several cerebral metastases with hemor rhages was performed regarding all patients studied. The time interval of observation of patients after the surgical treatment comprises 1 to 72 months. There were 27 women and 42 men. The age range was from 18 to 74 y.o. Besides, the state of veins of lower extremities and the state of the coagulation blood system in accordance with the data of coagulograms was studies. The analysis of the macrostructure and the microstructure of metastases with hemorrhages as well as the morphological study of the brain tissue adjacent to hematomas was performed with a morphological study and histological techniques. The patients were distributed in accordance with the RPA (recursive partitioning analysis classes: I class (n = 7, II class (n = 39, III class (n = 23; in accordance with the hemorrhage type: intratumoral type (26 metastases, perifocal type (20, mixed type (32; in accordance with the histological principle: melanoma (n = 25, lung cancer (n = 13, kidney cancer (n = 17, breast cancer (n = 4, colorectal cancer (n = 1, soft tissue sarcoma (n

  8. 小细胞肺癌脑转移全脑放疗失败后挽救性分次立体定向放疗疗效分析%Fractionated stereotactic radiotherapy for recurrent small cell lung cancer brain metastases after whole brain radiotherapy

    Institute of Scientific and Technical Information of China (English)

    李祥攀; 李晔雄; 肖建平; 陈秀军; 姜雪松; 张烨; 徐英杰; 郇福奎; 方浩; 万宝

    2012-01-01

    Objective Evaluation the Fractionated Stereotactic Radiotherapy (FSRT) for the patients with small-cell lung cancer (SCLC) after the whole brain radiotherapy (WBRT) failure.Methods We retrospectively analyzed 35 patients with brain metastases from small-cell lung cancer treated with linear accelerator FSRT after the WBRT failure. Multivariate analysis was used to determine significant prognostic factor related to survival.Results The following-up rate was 100%.The median following-up time was 11 months.The median over-all survival (OS) time was 10.3( 1 -30) months after FSRT.Controlled extra cranial disease was the only identified significant predictor of increased median OS time (χ2 =4.02,P =0.045 ).The median OS time from the diagnosis of brain metastasis was 22 (6 - 134 )months.14 patients died from brain metastasis,14 from extra-cranial progression,1 from leptomeningeal metastases,and 3 from other causes. Local control at 6 months and 12 months was 91% and 76%,respectively.No significant late complications.New brain metastases outside of the treated area developed in 17% of patients at a median time of 4(2 -20) months; all patients had received previous WBRT.Conclusions Fractionated stereotactic radiotherapy was safe and effective treatment for recurrent small-cell lung carcinoma brain metastases.%目的 评价小细胞肺癌( SCLC)全脑放疗(WBRT)后颅内失败分次立体定向放疗(FSRT)挽救的价值.方法 回顾分析WBRT失败后使用FSRT挽救的35例SCLC脑转移患者的生存情况,多因素分析确定和生存相关的预后因素.结果 随访率为100%,中位随访时间11个月.全组总中位生存期为10.3个月,多因素分析显示颅外疾病控制状态和患者的生存相关(χ2=4.02,P=0.045).自诊断脑转移开始中位生存期为22.0个月,未发现严重晚期不良反应.6、12个月局部控制率分别为91%、76%.6例局部未控患者中3例行二程FSRT挽救,挽救治疗后生存时间分别为3、9

  9. A rare case of asymptomatic radioiodine-avid renal and brain metastases 20 years after hemi-thyroidectomy for adenomatous goiter.

    Science.gov (United States)

    Santhosh, Sampath; Bhattacharya, Anish; Verma, Roshan Kumar; Lal, Anupam; Mittal, Bhagwant Rai

    2016-01-01

    A 65-year-old patient, with a history of left hemi-thyroidectomy for adenomatous goiter 20 years previously, was found to have pulmonary lesions on chest X-ray, a brain lesion on computerized tomography (CT), and elevated serum thyroglobulin (Tg). While completion thyroidectomy revealed that no pathological evidence of thyroid malignancy, radioiodine-avid pulmonary, brain, and renal and bone lesions were identified on diagnostic as well as posttherapy whole body planar scintigraphy and single photon emission computed tomography-CT. Subsequent ultrasonography-guided biopsy of a renal nodule showed thyroid follicular cells. This case suggests that metastatic differentiated thyroid carcinoma should be suspected in asymptomatic patients with incidentally detected lesions, raised serum Tg, and history of thyroid lesions.

  10. A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases

    OpenAIRE

    Rodrigues George; Yartsev Slav; Tay Keng; Pond Gregory R; Lagerwaard Frank; Bauman Glenn

    2012-01-01

    Abstract Background Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT) to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS) boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT) was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. ...

  11. Diagnosis and prognosis of brain tumors in clinical trials

    NARCIS (Netherlands)

    T.S. Gorlia (Thierry)

    2013-01-01

    textabstractAccording to the Central Brain Registry Of The United States (CBTRUS) statistical report (February 2012) the incidence rate of all primary non malignant and malignant brain and central nervous system tumors is 19.89 cases per 100.000 (11.58 for non-malignant tumors and 7.31 for malignant

  12. EEG abnormalities in clinically diagnosed brain death organ donors in Iranian tissue bank.

    Science.gov (United States)

    Tavakoli, Seyed Amir Hossein; Khodadadi, Abbas; Azimi Saein, Amir Reza; Bahrami-Nasab, Hasan; Hashemi, Behnam; Tirgar, Niloufar; Nozary Heshmati, Behnaz

    2012-01-01

    Brain death is defined as the permanent, irreversible and concurrent loss of all brain and brain stem functions. Brain death diagnosis is based on clinical criteria and it is not routine to use paraclinical studies. In some countries, electroencephalogram (EEG) is performed in all patients for the determination of brain death while there is some skepticism in relying on EEG as a confirmatory test for brain death diagnosis. In this study, we assessed the validity of EEG and its abnormalities in brain death diagnosis. In this retrospective study, we used 153 EEGs from medical records of 89 brain death patients in organ procurement unit of the Iranian Tissue Bank admitted during 2002-2008. We extracted and analyzed information including EEGs, which were examined by a neurologist for waves, artifacts and EEG abnormalities. The mean age of the patients was 27.2±12.7 years. The most common cause of brain death was multiple traumas due to accident (65%). The most prevalent artifact was electrical transformer. 125 EEGs (82%) were isoelectric (ECS) and seven EEGs (5%) were depictive of some cerebral activity which upon repeat EEGs, they showed ECS patterns too. There was no relationship between cause of brain death and cerebral activity in EEGs of the patients. In this study, we could confirm ECS patterns in all brain death patients whose status had earlier been diagnosed clinically. Considering the results of this study, it seems sensible to perform EEG as a final confirmatory test as an assurance to the patients' families.

  13. Epidemiology and clinical characteristics of traumatic brain injury in Lebanon

    Science.gov (United States)

    Abou-Abbass, Hussein; Bahmad, Hisham; Ghandour, Hiba; Fares, Jawad; Wazzi-Mkahal, Rayyan; Yacoub, Basel; Darwish, Hala; Mondello, Stefania; Harati, Hayat; El Sayed, Mazen J.; Tamim, Hani; Kobeissy, Firas

    2016-01-01

    Abstract Background: Traumatic brain injury (TBI) is a debilitating medical and emerging public health problem that is affecting people worldwide due to a multitude of factors including both domestic and war-related acts. The objective of this paper is to systematically review the status of TBI in Lebanon – a Middle Eastern country with a weak health system that was chartered by several wars and intermittent outbursts of violence - in order to identify the present gaps in knowledge, direct future research initiatives and to assist policy makers in planning progressive and rehabilitative policies. Methods: OVID/Medline, PubMed, Scopus databases and Google Scholar were lastly searched on April 15th, 2016 to identify all published research studies on TBI in Lebanon. Studies published in English, Arabic or French that assessed Lebanese patients afflicted by TBI in Lebanon were warranting inclusion in this review. Case reports, reviews, biographies and abstracts were excluded. Throughout the whole review process, reviewers worked independently and in duplicate during study selection, data abstraction and methodological assessment using the Downs and Black Checklist. Results: In total, 11 studies were recognized eligible as they assessed Lebanese patients afflicted by TBI on Lebanese soils. Considerable methodological variation was found among the identified studies. All studies, except for two that evaluated domestic causes such as falls, reported TBI due to war-related injuries. Age distribution of TBI victims revealed two peaks, young adults between 18 and 40 years, and older adults aged 60 years and above, where males constituted the majority. Only three studies reported rates of mild TBI. Mortality, rehabilitation and systemic injury rates were rarely reported and so were the complications involved; infections were an exception. Conclusion: Apparently, status of TBI in Lebanon suffers from several gaps which need to be bridged through implementing more basic

  14. Clinical factors adversely affecting early outcome after brain infarction

    Directory of Open Access Journals (Sweden)

    Charles André

    1994-06-01

    Full Text Available PURPOSE AND METHODS: One-hundred-and-nine consecutive patients admitted during the acute phase of a CT-confirmed brain infarction (BI were studied. Putative adverse influence of demographic and stroke risk factors, previous medical history, clinical presentation, initial and follow-up neurological examination, initial general evaluation, laboratory findings, chest X-ray and electrocardiographic findings, treatment, and topography and etiology of the ischemic insult was analysed. The end-point for assessment was early death (within 30 days. Statistical analysis was performed with univariate analysis and multiple regression. RESULTS: The main adverse factors related to an increased death risk during the first 30 days were, in decreasing order of importance: coma 48-72 hours after admission; stroke occuring in already hospitalized patients; Babinski sign on admission; minor degrees of impairment of consciousness 48-72 hours after admission; stroke related to large artery atherothrombosis and to embolism; a history of early impairment of consciousness; cardiac failure on admission. In 53 lucid patients on admission, only a history of congestive heart failure (CHF was associated with a reduced survival rate. In 56 patients with impaired consciousness, the presence of a Babinski sign increased death risk, but the main factor predicting a high case-fatality rate was the persistence of consciousness disturbances after48-72 hours. CONCLUSIONS: The presence of impairment of consciousness, especially coma, 2-3 days after disease onset, and a history of CHF greatly increase the early case fatality rate in patients with acute BI presenting with or without consciousness disturbances at admission, respectively. The use of a prognostic algorythm considering these few variables seems to predict the approximate 30-day fatality rates.

  15. [The German Ethics Council and the Brain Death--Some Clinical Remarks].

    Science.gov (United States)

    Mindach, M

    2015-08-01

    In February 2015, the German Ethics Council released a statement on brain death and organ removal. The Council has decided to adhere to the criterion of brain death as a condition for organ removal, and the majority of the Council holds the view of brain death as the criterion of death. The German medical associations have welcomed this statement, but there is room for further discussion of some aspects of this statement from a clinical point of view.

  16. Brain metastases: epidemiological profile and therapeutic results, about a cohort of patients treated in a radiotherapy department in Algiers; Les metastases cerebrales: profil epidemiologique et resultats therapeutiques, a propos d'une serie de patients traites dans un service de radiotherapie a Alger

    Energy Technology Data Exchange (ETDEWEB)

    Chami, S.; Mekki, F. [Service de radiotherapie, hopital d' Alger, Alger (Algeria)

    2010-10-15

    The authors report a retrospective study of the epidemiological profile, clinic characteristics, and mainly palliative therapeutic treatments, more particularly in terms of life quality, and improvement of clinic symptomatology and performance index. This study is based on 38 patients (17 women and 21 men), with a median age of 58.6, and a Karnofsky index greater than 70 per cent. Various data have been collected: brain metastasis number and topography, time interval between cancer diagnosis and metastasis diagnosis, impact on neuro-cognitive function. Survival has been analysed with the Kaplan-Meier method. Short communication

  17. Late-Onset Meningeal Metastases in Liposarcoma: A Case Report and Review of the Literature

    OpenAIRE

    2006-01-01

    Intracranial metastases from liposarcoma are rare and almost always preceded by the development of systemic tumour spread. We report here a case of liposarcoma with spread to the cranial nervous system 23 years after treatment of the primary tumour. The literature on brain metastases from soft tissue sarcoma is also reviewed.

  18. Late-Onset Meningeal Metastases in Liposarcoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michelle Ferguson

    2006-01-01

    Full Text Available Intracranial metastases from liposarcoma are rare and almost always preceded by the development of systemic tumour spread. We report here a case of liposarcoma with spread to the cranial nervous system 23 years after treatment of the primary tumour. The literature on brain metastases from soft tissue sarcoma is also reviewed.

  19. Annual Research Review: Progress in Using Brain Morphometry as a Clinical Tool for Diagnosing Psychiatric Disorders

    Science.gov (United States)

    Haubold, Alexander; Peterson, Bradley S.; Bansal, Ravi

    2012-01-01

    Brain morphometry in recent decades has increased our understanding of the neural bases of psychiatric disorders by localizing anatomical disturbances to specific nuclei and subnuclei of the brain. At least some of these disturbances precede the overt expression of clinical symptoms and possibly are endophenotypes that could be used to diagnose an…

  20. Clinical Significance of Brain SPECT in Zipeprol Abusers

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Dai Ok; Kim, Jae Phil; Kim, Deog Yoon; Yang, Hyung In; Koh, Eun Mi; Kim, Kwang Won; Choi, Young Kil [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

    1993-03-15

    Drug abuse is widespread in worldwide and has been associated with neurologic complication. Zipeprol is one of drugs which been abused for psychological satisfaction in some adolescents. This agent is non-opioid antitussive agent, which is not legally considered as being capable of creating dependence or abuse liability at therapeutic serum levels. But it has been reported that acute or chronic overdose create neurologic complication such as convulsion as well as dependence. Recently we experienced six zipeprol abusers who admitted due to convulsion and variable neurologic symptoms. The aim of our study was to determine the role of Tc-99m- HMPAO brain SPECT in those patients. EEG and brain CT showed no abnormal finding, but brain SPECT showed focal or multiple perfusion abnormalities in frontal, parietal, occipital cortex, basal ganglia, thalamus and especially at temporal cortex. These results suggest that brain SPECT may be a useful diagnostic tool to evaluate the cerebral dysfunction induced by zipeprol abuse.

  1. Endobronchial metastases from extrathoracic malignancies.

    Science.gov (United States)

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, Oğuz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient.

  2. Adolescent Brain and Cognitive Developments: Implications for Clinical Assessment in Traumatic Brain Injury

    Science.gov (United States)

    Ciccia, Angela Hein; Meulenbroek, Peter; Turkstra, Lyn S.

    2009-01-01

    Adolescence is a time of significant physical, social, and emotional developments, accompanied by changes in cognitive and language skills. Underlying these are significant developments in brain structures and functions including changes in cortical and subcortical gray matter and white matter tracts. Among the brain regions that develop during…

  3. Clinical evaluation of metastases of malignant melanoma imaging with 99Tcm-glutathione and 99Tcm-anti-melanoma antibody: a comparative study.

    Science.gov (United States)

    Duman, Y; Burak, Z; Ercan, M T; Dirlik, A; Bilkay, B C; Akin, Y; Taner, M; Bekdik, C F

    1995-11-01

    The aim of this investigation was to test for the scintigraphic detection of metastases of malignant melanoma with a new radiopharmaceutical, 99Tcm-glutathione (99Tcm-GSH), in comparison with 99Tcm-anti-melanoma antibody (99Tcm-AMAb). Glutathione was labelled with 99Tcm by a Sn2+ reduction method with an efficiency of > 99% as determined by instant thin layer chromatography (ITLC). Anti-melanoma antibody was obtained as a kit from SORIN (Italy) and labelled with 99TcmO-4. Forty-three patients with a total of 55 biopsy-proven metastatic melanoma foci, 1 ocular melanoma and 20 benign pathologic foci, also confirmed by ultrasound, computed tomography and magnetic resonance imaging, were included in the study after giving their informed consent. Following the intravenous (i.v.) injection of 500 MBq 99Tcm-AMAb, scintigraphic images of the involved areas were obtained 6 h post-injection. Three days later, the same patients were given 500 MBq 99Tcm-GSH i.v. and images were obtained 6 and 24 h post-injection. The images were classified as positive (focal abnormal accumulation) or negative. Quantitative evaluation was also applied. Regions of interest were drawn over the involved areas and nearby soft tissues and the target-to-nontarget (T/NT) ratios obtained with 99Tcm-AMAb (T/NT: 1.92 +/- 0.2) and 99Tcm-GSH (T/NT: 1.84 +/- 0.2) were compared (0.1 < P < or = 0.3). The sensitivity (and specificity) of 99Tcm-AMAb and 99Tcm-GSH in the detection of malignant melanoma metastases were 91% (95%) and 84% (90%), respectively. Compared with 99Tcm-AMAb, the advantages of 99Tcm-GSH are lower levels of blood radioactivity, lower costs and easy in-house preparation. In conclusion, our results show that 99Tcm-GSH is a potentially useful radiopharmaceutical for the detection of metastases of malignant melanoma.

  4. Radiotherapy for pain management of bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Rezende Junior, Ismar de; Mattos, Marcos Duarte de; Nakamura, Ricardo; Lemes Junior, Joaquim; Vanzelli, Talita Lozano, E-mail: rezende.med@terra.com.br [Radioterapia do Hospital de Cancer de Barretos, SP (Brazil)

    2011-07-01

    Purpose: This is the first Brazilian study intended to evaluate the response of pain relief with radiotherapy in three different fractionation and the clinical differences in managing pain in patients with painful bone metastases. Methods: Prospective study of patients with painful bone metastases referred to the Radiotherapy Sector of the Hospital de Cancer de Barretos for pain-relieving radiotherapy between March and December 2010. It is known that radiotherapy seems to alter the activation of osteoclast-mediated bone resorption, relieving pain in cases of painful bone metastases. Patients were assessed in relation to the status of pain intensity before and after the initiation of radiotherapy. Either a single fraction of 8Gy, five fractions of 4Gy or ten fractions of 3Gy were given. A visual analog scale (VAS) was applied by doctors, nurses and nursing technicians to assess pain intensity at each session of radiotherapy, and follow-up at 8, 30 and 90 days from the end of treatment. Results: We evaluated 92 consecutive patients, 48 male and 44 female, with a median age of 58 years. We found that 14% of patients referred from the Palliative Care or Clinical Oncology sectors need better pharmacological analgesia due to severe pain, compared with 40.5% of patients from the other sectors (p = 0.004). We also found that the onset of pain relief to patients receiving 10 fractions of 300cGy analgesia without changing the pre-radiotherapy analgesia occurred with significance after the fifth fraction. Improvement in pain experienced within 90 days of follow-up was found in eighty percent of patients, independent of fractionated radiotherapy, site of metastases and the clinical condition of the patient. Discussion/Conclusion: The Palliative Care and Clinical Oncology sectors expressed greater concern in regards to analgesia for the patient with painful bone metastases. Radiotherapy is an effective pain-relieving treatment in different fractionation studied, even though the

  5. Ablative Approaches for Pulmonary Metastases.

    Science.gov (United States)

    Boyer, Matthew J; Ricardi, Umberto; Ball, David; Salama, Joseph K

    2016-02-01

    Pulmonary metastases are common in patients with cancer for which surgery is considered a standard approach in appropriately selected patients. A number of patients are not candidates for surgery due to a medical comorbidities or the extent of surgery required. For these patients, noninvasive or minimally invasive approaches to ablate pulmonary metastases are potential treatment strategies. This article summarizes the rationale and outcomes for non-surgical treatment approaches, including radiotherapy, radiofrequency and microwave ablation, for pulmonary metastases.

  6. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute-Designated Comprehensive Cancer Center Network

    Energy Technology Data Exchange (ETDEWEB)

    Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rodgers, Edwin [Via Oncology, Pittsburgh, PA (United States); Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical

  7. Pneumonic benign metastasizing leiomyoma: a case report and clinical treatment%肺良性转移性平滑肌瘤一例:病例分析与临床治疗

    Institute of Scientific and Technical Information of China (English)

    Fuxin Zhu; Heng Sun; Linlin Cheng

    2012-01-01

    Benign metastasizing leiomyoma (BML) is a rare entity usually occuring in females with history of uterus leiomyoma. It appears as a histopathologic benign smooth muscle tumors, distant from the uterus. It is hormone dependent and progresses slowly. Operation is the main clinical treatment. The article was reported one case who was a thirty-eight years old female. She was found to have bilateral lung nodules after hysterectomy of uterine leiomyoma seven years ago. An open lung biopsy revealed that the nodules consist of proliferating smooth muscle cells with a histopathologic feature which was similar to her uterus leiomyoma. Positive staining of estrogen and progesterone receptors were detected, which proved the tumer originate from uterine. The patient did not accept operation, chemotherapy, radiotherapy or other treatment. We still follow up the development of the case.

  8. Functional brain network changes associated with clinical and biochemical measures of the severity of hepatic encephalopathy.

    Science.gov (United States)

    Jao, Tun; Schröter, Manuel; Chen, Chao-Long; Cheng, Yu-Fan; Lo, Chun-Yi Zac; Chou, Kun-Hsien; Patel, Ameera X; Lin, Wei-Che; Lin, Ching-Po; Bullmore, Edward T

    2015-11-15

    Functional properties of the brain may be associated with changes in complex brain networks. However, little is known about how properties of large-scale functional brain networks may be altered stepwise in patients with disturbance of consciousness, e.g., an encephalopathy. We used resting-state fMRI data on patients suffering from various degrees of hepatic encephalopathy (HE) to explore how topological and spatial network properties of functional brain networks changed at different cognitive and consciousness states. Severity of HE was measured clinically and by neuropsychological tests. Fifty-eight non-alcoholic liver cirrhosis patients and 62 normal controls were studied. Patients were subdivided into liver cirrhosis with no outstanding HE (NoHE, n=23), minimal HE with cognitive impairment only detectable by neuropsychological tests (MHE, n=28), and clinically overt HE (OHE, n=7). From the earliest stage, the NoHE, functional brain networks were progressively more random, less clustered, and less modular. Since the intermediate stage (MHE), increased ammonia level was accompanied by concomitant exponential decay of mean connectivity strength, especially in the primary cortical areas and midline brain structures. Finally, at the OHE stage, there were radical reorganization of the topological centrality-i.e., the relative importance-of the hubs and reorientation of functional connections between nodes. In summary, this study illustrated progressively greater abnormalities in functional brain network organization in patients with clinical and biochemical evidence of more severe hepatic encephalopathy. The early-than-expected brain network dysfunction in cirrhotic patients suggests that brain functional connectivity and network analysis may provide useful and complementary biomarkers for more aggressive and earlier intervention of hepatic encephalopathy. Moreover, the stepwise deterioration of functional brain networks in HE patients may suggest that hierarchical

  9. Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play.

    Science.gov (United States)

    Savitz, J B; Rauch, S L; Drevets, W C

    2013-05-01

    In response to queries about whether brain imaging technology has reached the point where it is useful for making a clinical diagnosis and for helping to guide treatment selection, the American Psychiatric Association (APA) has recently written a position paper on the Clinical Application of Brain Imaging in Psychiatry. The following perspective piece is based on our contribution to this APA position paper, which specifically emphasized the application of neuroimaging in mood disorders. We present an introductory overview of the challenges faced by researchers in developing valid and reliable biomarkers for psychiatric disorders, followed by a synopsis of the extant neuroimaging findings in mood disorders, and an evidence-based review of the current research on brain imaging biomarkers in adult mood disorders. Although there are a number of promising results, by the standards proposed below, we argue that there are currently no brain imaging biomarkers that are clinically useful for establishing diagnosis or predicting treatment outcome in mood disorders.

  10. STUDY AND PREPARATION ON "PAIN TAN NING" AND ITS CLINICAL APPLICATION AND STUDY ON BRAIN ATLAS

    Institute of Scientific and Technical Information of China (English)

    LIU Mingshun; GU Lanjie; LIU Qingrui

    2004-01-01

    Objective: To observe clinical effect of combined mixture of traditional chineses and western medicine "PIAN TAN NING" in treatment of ischemic cerebrovascular diseases and change of brain atlas. Methods:In 6660 patients with ischemic cerebrovascular disease, the curative effect of "PIAN TAN NING" and brain atlas were observed and other 30 cases were compared with treatment of Dextran. Results:After treatment, patient's clinical symptoms and recovered degree of myodynamia and brain atlas improved significantly. Total effective rate was 96. 7%. But the contral group was 80. 0%. There was a significant difference between them ( p < 0. 05 ). Conclusion: The "PIAN TAN NING" produced a good clinical curative effect in treatment of ischemic cerebrovascular diseases and the side effect was only a few. So it can be applied very well in patients with ischemic cerebrovascular disease. The applied value of brain atlas was very good.

  11. A Clinical Study on Temozolomide Combined with Radiotherapy in Treating Metastatic Brain Tumors%替莫唑胺联合放疗治疗脑转移瘤的临床研究

    Institute of Scientific and Technical Information of China (English)

    肖勇辉; 郑志坚; 曾黄辉

    2013-01-01

    Objective To study the clinical efficacy and adverse reactions of temozolomide combined with radiotherapy for brain metastases. Methods 44 patients with brain metastases were selected and divided equally into treatment group and control group, 22 cases in each group. The treatment group received temozolomide combined with radiotherapy while the control group was treated with radiotherapy alone. The tumor regression, survival time and changes of KPS were observed and analyzed. The clinical efficacy and toxicity occurrence were evaluated after treatments. Results All patients were success-fully completed the treatment program. The treatment group had a total effective rate of 68.18% and the control group had a total effective rate of 36.36%; there was a significant difference between the two groups (P0.05). Conclusion Temozolomide combined with radiotherapy had a better effect and less toxicity than simple whole-brain radiation therapy on brain metastases, therefore, it is worth being generalized and applied in clinic.%  目的研究替莫唑胺联合放疗治疗脑转移瘤的临床疗效和不良反应.方法选取44例脑转移瘤患者,配对分为治疗组和对照组,每组22例.治疗组采用替莫唑胺联合放疗,对照组采用单纯放疗,通过观察肿瘤消退情况、生存时间、卡氏评分(KPS)变化等指标评价临床疗效和毒副反应发生情况.结果所有患者均顺利完成治疗计划.治疗组总有效率为68.18%,对照组总有效率为36.36%,差异有统计学意义(P0.05).结论替莫唑胺联合放疗方案治疗脑转移瘤疗效优于单纯全脑放射治疗,毒副反应较小,值得推广.

  12. Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer.

    Science.gov (United States)

    Zhao, Ren; Kong, Wei; Shang, Jun; Zhe, Hong; Wang, Yan-Yang

    2017-03-01

    Brain metastases occur in 20% to 40% of lung cancer patients. Whole-brain radiotherapy (WBRT) has long been considered the treatment of choice for many patients with lung cancer, because of its wide availability, ease of delivery, and effectiveness in prolonging survival. However, WBRT is also associated with several side effects, such as decline in memory and other cognitive functions. There exists significant preclinical and clinical evidence that radiation-induced injury to the hippocampus correlates with neurocognitive decline of patients who receive WBRT. Technological advances in treatment planning and delivery facilitate the use of hippocampal-sparing (HS) WBRT as prophylactic cranial irradiation or the primary treatment modality for lung cancer patients with brain metastases. In this review, we provide a detailed and comprehensive discussion of the safety profile, techniques for hippocampus-sparing, and the clinical evidence of HS-WBRT for lung cancer patients.

  13. Long-term global and regional brain volume changes following severe traumatic brain injury: A longitudinal study with clinical correlates

    DEFF Research Database (Denmark)

    Sidaros, Annette; Skimminge, Arnold Jesper Møller; Liptrot, Matthew George;

    2009-01-01

    Traumatic brain injury (TBI) results in neurodegenerative changes that progress for months, perhaps even years post-injury. However, there is little information on the spatial distribution and the clinical significance of this late atrophy. In 24 patients who had sustained severe TBI we acquired 3D...... scan time point using SIENAX. Regional distribution of atrophy was evaluated using tensor-based morphometry (TBM). At the first scan time point, brain parenchymal volume was reduced by mean 8.4% in patients as compared to controls. During the scan interval, patients exhibited continued atrophy...... with percent brain volume change (%BVC) ranging between − 0.6% and − 9.4% (mean − 4.0%). %BVC correlated significantly with injury severity, functional status at both scans, and with 1-year outcome. Moreover, %BVC improved prediction of long-term functional status over and above what could be predicted using...

  14. Treatment of choroid metastases.

    Science.gov (United States)

    Dobrowsky, W

    1988-02-01

    Sixteen patients with choroid secondary tumours were treated with irradiation consisting of 40-50 Gy in 3-5 weeks. There were 14 female patients with breast cancer, one male patient with prostatic cancer and one male patient with cancer of unknown origin. In four cases bilateral ocular metastases were seen. Ten out of 20 treated eyes showed complete response to treatment, seven out of 20 showed partial response and three out of 20 were not influenced by irradiation. Survival of patients, all having widespread metastatic disease, was 3-48 months (median 20 months). All patients responding to treatment showed increased quality of life.

  15. Current Standards in the Management of Cerebral Metastases

    Directory of Open Access Journals (Sweden)

    Pablo Goetz

    2012-01-01

    Full Text Available The last 30 years have seen major changes in attitude toward patients with cerebral metastases. This paper aims to outline the major landmarks in this transition and the therapeutic strategies currently used. The controversies surrounding control of brain disease are discussed, and two emerging management trends are reviewed: tumor bed radiosurgery and salvage radiation.

  16. Neuromyelitis optica with clinical and histopathological involvement of the brain.

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Wesseling, P.; Frenken, C.W.; Jongen, P.J.H.

    2007-01-01

    Diagnostic criteria for neuromyelitis optica (NMO) state that there should be no active disease outside the optic nerves and spinal cord. However, several cases have been described with symptomatic brain involvement. We describe an autopsy case of a patient with NMO and symptomatic involvement of th

  17. Clinical presentation, treatment and outcome of patients with cerebral metastases: the University of São Paulo series Apresentação clínica, tratamento e desfecho de pacientes com metástases cerebrais: a experiência da Universidade de São Paulo

    Directory of Open Access Journals (Sweden)

    Fernanda Andrade

    2004-09-01

    Full Text Available INTRODUCTION: Secondary neoplasias are the most common tumors affecting the central nervous system and several clinical aspects of this disease are still controversial. METHOD: Forty-seven consecutive patients with the diagnosis of cerebral metastases (CM were retrospectively studied at the Clinical Hospital of São Paulo University Medical School. Mean age was 53.9 years and 25 patients were female. RESULTS: The most frequent primary sites were breast, lung and skin. Symptoms were related to increased intracranial pressure (ICP in 48.9%, focal neurological events in 27.7% and both in 17.0%. Single brain metastases were found in 57.4% of those cases, the frontal lobe being most frequently affected. Surgical treatment was performed in 68.1%, radiotherapy in 40.4% and chemotherapy in 17.0%. CONCLUSION: After statistical analysis, there was a trend towards prolonged survival of female patients, patients with ICP symptoms and the surgical group. Data from different centers are essential to establish the best management of CM.INTRODUÇÃO: As neoplasias secundárias são o principal grupo de tumores que afetam o sistema nervoso central. Diversos aspectos da evolução e tratamento desta doença são controversos. MÉTODO: Quarenta e sete pacientes com metástase cerebral foram estudados retrospectivamente no Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo. A idade média foi 53,9 anos e 25 pacientes eram do sexo feminino. RESULTADOS: Os sítios primários mais freqüentes foram mama, pulmão e pele. Os sintomas apresentados foram relacionados à hipertensão intracraniana (HIC em 48,9%, sintomas focais em 27,7% e ambos em 17,0%. Metástases únicas foram encontradas em 57,8% dos casos. O tratamento foi cirurgia em 68,1% dos casos, radioterapia em 40,4% e quimioterapia em 17,0%. CONCLUSÃO: Após análise estatística, foram encontradas tendências a maior sobrevida nos pacientes do sexo feminino, no grupo de pacientes que

  18. Brain stimulation and brain repair--rTMS: from animal experiment to clinical trials--what do we know?

    Science.gov (United States)

    Platz, Thomas; Rothwell, John C

    2010-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of stimulating the brain that changes excitability at the site of stimulation as well as at distant anatomically connected sites. Since the effects can outlast the period of stimulation for minutes or hours and are thought to be depend, at least in part, on changes in the efficiency of synaptic connections in the cortex, the method has generated much interest as a potential therapeutic intervention in a wide range of neurological and psychiatric conditions. A symposium on brain stimulation and brain recovery was held in Greifswald (Germany) in 2010 to exchange of state-of-the-art knowledge about rTMS effects from animal experiments to clinical trials in conditions such as stroke, Parkinson disease, and depression. There was enormous interest in the effects of rTMS and signs of therapeutic success in mainly small clinical trials. However, it was also clear that some of our models of the effects of rTMS, such as upregulation or downregulation of specific brain areas may need further development if they are to account for all the observations that have been made so far. The results of the symposium are made available by lab reviews of members of the symposium's faculty. This editorial provides an overview.

  19. Predictive value of clinical evaluation in the follow-up of children with a brain tumor.

    NARCIS (Netherlands)

    Graaf, N. de; Hew, J.M.; Fock, J.M.; Kamps, W.A.; Graaf, S.S.N. de

    2002-01-01

    BACKGROUND: During follow-up of children with a brain tumor, traditionally surveillance-imaging studies are done in addition to clinical evaluations. The purpose of this study was to determine the role of clinical evaluations by a multidisciplinary team for the detection of recurrent tumor. PROCEDUR

  20. Predictive value of clinical evaluation in the follow-up of children with a brain tumor

    NARCIS (Netherlands)

    Hew, JM; Fock, JM; Kamps, WA

    2002-01-01

    Background. During follow-up of children with a brain tumor, traditionally surveillance-imaging studies are done in addition to clinical evaluations, The purpose of this study was to determine the role of clinical evaluations by a multidisciplinary team for the detection of recurrent tumor. Procedur

  1. Brain herniations into the dural venous sinus or calvarium: MRI findings, possible causes and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Battal, Bilal; Hamcan, Salih; Akgun, Veysel; Sari, Sebahattin; Tasar, Mustafa [Gulhane Military Medical School, Department of Radiology, Ankara (Turkey); Oz, Oguzhan [Gulhane Military Medical School, Department of Neurology, Ankara (Turkey); Castillo, Mauricio [University of North Carolina School of Medicine, Division of Neuroradiology, Department of Radiology, Chapel Hill, NC (United States)

    2016-06-15

    To determine frequency, imaging features and clinical significance of herniations of brain parenchyma into dural venous sinuses (DVS) and/or calvarium found on MRI. A total of 6160 brain MRI examinations containing at least one high-resolution T1- or T2-weighted sequence were retrospectively evaluated to determine the presence of incidental brain herniations into the DVS or calvarium. MRI sequences available for review were evaluated according to their capability to demonstrate these herniations. Patients' symptoms and clinical findings were recorded. Twenty-one (0.32 %) brain parenchyma herniations into the DVS (n = 18) or calvarium (n = 3) in 20 patients were detected. The most common locations of the herniations were the transverse sinuses (n = 13) and those involving inferior gyrus of the temporal lobe (n = 9). High-resolution T1- and T2-weighted sequences were equally useful in the detection of these brain herniations. According to clinical symptoms, brain herniations were considered to be incidental but headaches were present in nine patients. Brain herniations with surrounding cerebrospinal fluid (CSF) into the DVS and/or calvarium are incidental findings and not proven to be associated with any symptoms. Although rare, these herniations are more common than previously recognized and should not be confused with arachnoid granulations, clots or tumours. (orig.)

  2. Early monitoring of PtiO2, PtiCO2, pH and brain temperat ure in patients with brain injuries and the clinical significanc e

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To explore the regulation of early br ain tissue metabolic changing after brain injuries and the clinical significance .   Methods: There were 17 patients with brain injuries. Early dire ct monitoring of PtiO2, PtiCO2, pH and brain temperature, dynami c observation of the relation between various parameters and clinics after brai n injuries were performed.   Results: Early changes of PtiO2, PtiCO2 and pH we re closely correlated with outcome. The death rate obviously increased when P tiO2 was continuously lower than 9 mm?Hg within 24 hours after injuries. Secondary brain injury prolonged and aggravated brain tissue metabolic disturban ce. When intracerebral pressure was over 30 mm?Hg PtiO2 began to de crea se. The brain temperature in brain death patients was evidently lower than axill ary temperature.   Conclusions: The direct monitoring of PtiO2, PtiC O2, pH and brain temperature is safe and accurate and can find early anoxia da mage to brain tissue and provide reliable basis for clinical therapy. It ha s an instructive significance in selecting and studying a new treatment method i n brain injuries. And it can be taken as a criterion in clinical judging brain d eaths.

  3. [Introduction of neuroethics: out of clinic, beyond academia in human brain research].

    Science.gov (United States)

    Fukushi, Tamami; Sakura, Osamu

    2008-11-01

    Higher cognitive function in human brain is one of well-developed fields of neuroscience research in the 21st century. Especially functional magnetic resonance imaging (fMRI) and near infrared recording system have brought so many non-clinical researchers whose background is such as cognitive psychology, economics, politics, pedagogy, and so on, to the human brain mapping study. Authors have introduced the ethical issues related to incidental findings during the fMRI recording for non-clinical purpose, which is a typical problem derived from such expanded human brain research under non clinical condition, that is, neuroethics. In the present article we would introduce neuroethical issues in contexts of "out of clinic" and "beyond academia".

  4. Location of brain lesions predicts conversion of clinically isolated syndromes to multiple sclerosis

    DEFF Research Database (Denmark)

    Giorgio, Antonio; Battaglini, Marco; Rocca, Maria Assunta

    2013-01-01

    : In CIS patients with hemispheric, multifocal, and brainstem/cerebellar onset, lesion probability map clusters were seen in clinically eloquent brain regions. Significant lesion clusters were not found in CIS patients with optic nerve and spinal cord onset. At 1 year, clinically definite MS developed......OBJECTIVES: To assess in a large population of patients with clinically isolated syndrome (CIS) the relevance of brain lesion location and frequency in predicting 1-year conversion to multiple sclerosis (MS). METHODS: In this multicenter, retrospective study, clinical and MRI data at onset...... in 26% of patients. The converting group, despite a greater baseline lesion load compared with the nonconverting group (7 ± 8.1 cm(3) vs 4.6 ± 6.7 cm(3), p brain voxels occupied by lesions). High lesion frequency was found...

  5. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  6. [Cardiac myxoma with cerebral metastases].

    Science.gov (United States)

    Bazin, A; Peruzzi, P; Baudrillard, J C; Pluot, M; Rousseaux, P

    1987-01-01

    A 56 year old woman developed multiple metastases in the cerebrum and cerebellum, four years after cardiac intervention on a left atrial myxoma. The absence of stroke is noteworthy. Multiple high density lesions with contrast enhancement were seen by CT scan, suggesting metastatic neoplasms. Histological examination confirmed the diagnosis of metastases of cardiac myxoma. Only four cases were recorded in the literature.

  7. Solitary calvarial metastases : An unusual presentation of thoracic neuroblastoma

    Directory of Open Access Journals (Sweden)

    Grover S

    2003-01-01

    Full Text Available A primary thoracic origin occurs only in 20% of neuroblastomas, and their classical presentation is mediastinal or cord compression. Skeletal metastases of neuroblastomas are characteristically multiple, and calvarial deposits usually show simultaneous involvement of orbit. Solitary metastases in neuroblastoma, is an unusual entity and its presentation as a large calvarial mass, especially from a thoracic primary, is rare. Furthermore, calvarial metastases are relatively uncommon in children compared to adults. We discuss the clinical, radiographic, CT features, and differential diagnosis of a large calvarial mass with sunray spiculation in a child, which was due to a solitary metastases from an occult thoracic neuroblastoma. The possibility of neuroblastoma presenting in this unique fashion and the importance of considering a chemosensitive tumor such as neuroblastoma in the differential diagnosis of a solitary calvarial mass in a child is highlighted by our report.

  8. CNS Metastases from Bone and Soft Tissue Sarcomas in Children, Adolescents, and Young Adults: Are They Really So Rare?

    Directory of Open Access Journals (Sweden)

    Monika Bekiesinska-Figatowska

    2017-01-01

    Full Text Available Purpose. To check whether primary involvement of brain/spinal cord by bone/soft tissue sarcomas’ metastases in children is as rare as described and to present various morphological forms of bone/soft tissue sarcomas’ CNS metastases. Methods. Patients with first diagnosis in 1999–2014 treated at single center were included with whole course of disease evaluation. Brain/spinal canal magnetic resonance imaging (MRI/computed tomography were performed in cases suspicious for CNS metastases. Extension from skull/vertebral column metastases was excluded. Results. 550 patients were included. MRI revealed CNS metastases in 19 patients (incidence 3.45%, 14 boys, aged 5–22 years. There were 12/250 osteosarcoma cases, 2/200 Ewing’s sarcoma, 1/50 chondrosarcoma, 3/49 rhabdomyosarcoma (RMS, and 1/1 malignant mesenchymoma. There were 10 single metastases and 7 cases of multiple ones; in 2 RMS cases only leptomeningeal spread in brain and spinal cord was found. Calcified metastases were found in 3 patients and hemorrhagic in 4. In one RMS patient there were numerous solid, cystic, hemorrhagic lesions and leptomeningeal spread. Conclusions. CNS metastases are rare and late in children with bone/soft tissue sarcomas, although in our material more frequent (3.45% than in other reports (0.7%. Hematogenous spread to brain and hemorrhagic and calcified lesions dominated in osteosarcoma. Ewing sarcoma tended to metastasize to skull bones. Soft tissue sarcomas presented various morphological forms.

  9. CNS Metastases from Bone and Soft Tissue Sarcomas in Children, Adolescents, and Young Adults: Are They Really So Rare?

    Science.gov (United States)

    Duczkowska, Agnieszka; Duczkowski, Marek; Bragoszewska, Hanna; Romaniuk-Doroszewska, Anna; Iwanowska, Beata; Szkudlinska-Pawlak, Sylwia; Madzik, Jaroslaw; Bilska, Katarzyna; Raciborska, Anna

    2017-01-01

    Purpose. To check whether primary involvement of brain/spinal cord by bone/soft tissue sarcomas' metastases in children is as rare as described and to present various morphological forms of bone/soft tissue sarcomas' CNS metastases. Methods. Patients with first diagnosis in 1999–2014 treated at single center were included with whole course of disease evaluation. Brain/spinal canal magnetic resonance imaging (MRI)/computed tomography were performed in cases suspicious for CNS metastases. Extension from skull/vertebral column metastases was excluded. Results. 550 patients were included. MRI revealed CNS metastases in 19 patients (incidence 3.45%), 14 boys, aged 5–22 years. There were 12/250 osteosarcoma cases, 2/200 Ewing's sarcoma, 1/50 chondrosarcoma, 3/49 rhabdomyosarcoma (RMS), and 1/1 malignant mesenchymoma. There were 10 single metastases and 7 cases of multiple ones; in 2 RMS cases only leptomeningeal spread in brain and spinal cord was found. Calcified metastases were found in 3 patients and hemorrhagic in 4. In one RMS patient there were numerous solid, cystic, hemorrhagic lesions and leptomeningeal spread. Conclusions. CNS metastases are rare and late in children with bone/soft tissue sarcomas, although in our material more frequent (3.45%) than in other reports (0.7%). Hematogenous spread to brain and hemorrhagic and calcified lesions dominated in osteosarcoma. Ewing sarcoma tended to metastasize to skull bones. Soft tissue sarcomas presented various morphological forms.

  10. The clinical spectrum of sport-related traumatic brain injury.

    Science.gov (United States)

    Jordan, Barry D

    2013-04-01

    Acute and chronic sports-related traumatic brain injuries (TBIs) are a substantial public health concern. Various types of acute TBI can occur in sport, but detection and management of cerebral concussion is of greatest importance as mismanagement of this syndrome can lead to persistent or chronic postconcussion syndrome (CPCS) or diffuse cerebral swelling. Chronic TBI encompasses a spectrum of disorders that are associated with long-term consequences of brain injury, including chronic traumatic encephalopathy (CTE), dementia pugilistica, post-traumatic parkinsonism, post-traumatic dementia and CPCS. CTE is the prototype of chronic TBI, but can only be definitively diagnosed at autopsy as no reliable biomarkers of this disorder are available. Whether CTE shares neuropathological features with CPCS is unknown. Evidence suggests that participation in contact-collision sports may increase the risk of neurodegenerative disorders such as Alzheimer disease, but the data are conflicting. In this Review, the spectrum of acute and chronic sport-related TBI is discussed, highlighting how examination of athletes involved in high-impact sports has advanced our understanding of pathology of brain injury and enabled improvements in detection and diagnosis of sport-related TBI.

  11. Bone metastases from differentiated thyroid carcinoma.

    Science.gov (United States)

    Muresan, M M; Olivier, P; Leclère, J; Sirveaux, F; Brunaud, L; Klein, M; Zarnegar, R; Weryha, G

    2008-03-01

    The presence of distant metastases from differentiated thyroid carcinoma decreases the 10-year survival of patients by 50%. Bone metastases represent a frequent complication especially of follicular thyroid cancer and severely reduce the quality of life causing pain, fractures, and spinal cord compression. Diagnosis is established by correlating clinical suspicion with imaging. Imaging is essential to detect, localize, and assess the extension of the lesions and should be used in conjunction with clinical evidence. Bone metastases are typically associated with elevated markers of bone turnover, but these markers have not been evaluated in differentiated thyroid cancer. Skeletal and whole-body magnetic resonance imaging and fusion 2-deoxy-2-[18F]fluoro-D-glucose whole-body positron emission tomography/computed tomography (PET/CT) are the best anatomic and functional imaging techniques available in specialized centers. For well-differentiated lesions, iodine-PET scan combined (124)I-PET/CT is the newest imaging development and (131)I is the first line of treatment. Bisphosphonates reduce the complications rate and pain, alone or in combination with radioiodine, radionuclides, or external beam radiotherapy and should be employed. Surgery and novel minimally invasive consolidation techniques demand an appropriate patient selection for best results on a multimodal approach. Basic research on interactions between tumor cells and bone microenvironment are identifying potential novel targets for future more effective therapeutic interventions for less differentiated tumors.

  12. Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors

    Directory of Open Access Journals (Sweden)

    Ethan A. Ferrel

    2016-03-01

    Full Text Available Patients with brain metastasis from renal cell carcinoma (RCC or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS, number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 ± 3.06 and 12.70 ± 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 ± 2.45 months than the reference group (1 metastasis, 10.70 ± 13.40 months, p = 0.024. Patients with KPS ≤ 60 experienced significantly shorter survival than the reference group (KPS = 90–100, with median survival times of 5.80 ± 2.46 months (p < 0.001 and 45.20 ± 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5 and lower KPS were statistically significant predictors of a lower OS prognosis.

  13. MULTIVARIATE ANALYSIS OF BONE METASTASES IN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the risk factors of bone metastases in breast carcinoma. Methods: By cross sectional study, the data of 225 breast cancer patients who were inpatients in four hospitals in Hangzhou were analyzed. All patients underwent total body bone scan with single photon emission computed tomography (SPECT) at least once during 1995 to 2000. Results: All patients were followed-up to 294 months after operation, bone metastases were found in 113 cases, suspected bone metastases 3 cases, with a bone metastases rate of 50.9% (113/222). Multivariate analysis by Cox's proportional hazards regression model showed that there were four risk factors of bone metastases in breast cancer: (1) clinical stage, I(IV stages with a hazard ratio of bone metastases of 1.945, 95% confidence interval 1.396(2.710; (2) number of invaded axillary lymph nodes, with a hazard ratio of 1.039, 95% confidence interval 1.0142(1.068; (3) skeletal complications (yes vs. no), with a hazard ratio of bone metastases of 1.722, 95% confidence interval 1.060(2.796; (4) age at the time of surgery or diagnosis, with a hazard ratio of 2.048, 95% confidence interval 1.123(3.876 for patients of age 40(50 y versus patients bellow 40 y of age and 2.837, 95% confidence interval 1.473(5.465 for patients of age above 50 y versus patients of ages between 40 and 50. Kaplan-Meier curves showed that for patients with more than 5 invasive axillary lymph nodes, compared with those with 1(5, the bone metastasis rates increased significantly ((2 =6.3319, P=0.012). Conclusion: The clinical stage, number of metastatic axillary lymph nodes, age at the time of operation and skeletal complications are essential risk factors of bone metastases.

  14. Simultaneous pulmonary metastases from colon and prostate cancer to the same lobe

    OpenAIRE

    Nakamura, Toru; Oki, Tomonari; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kobayashi, Yasuyuki; Funai, Kazuhito; Toyoda, Futoru

    2015-01-01

    Simultaneous pulmonary metastases from different primary tumors to the same lobe are extremely rare, and we herein report the case. Surgical specimen of the pulmonary metastasis from colon cancer contained two additional nodules that were confirmed as metastases from prostate cancer. Pulmonary metastasis from prostate cancer rarely forms nodules, and there is a discrepancy in the incidence of pulmonary metastases between autopsy and clinical findings. This case suggests that different maligna...

  15. Clinical Feature And Pathogeny Analysis Of Brain Hemorrhage In Young Adult Group

    Institute of Scientific and Technical Information of China (English)

    Wang Jianming; Zeng Xiaoyun

    2000-01-01

    Objection: The trend of brain hemorrhage cases of young adults have increased recently. In this article, We studied brain hemorrhage clinical feature and pathogenic causes of 72 young adults, Whose ages are all beneath 45Y. We found That the major pathogen reasons of young adult brain hemorrhage are blood system diseases、 arteriovenous malformation of cerebral blood vessel、 hypertension arteriosclerosis、 arteritis and rheumatic heart disease et. We also found that the trend can be related to hard work、 tense life、 drinking too much alcohol and eating high lipid food, and cercbral vascular disease family history. So in order to reduce the incidence of young adult brain hemorrhage, Young adults should not drink and smoke heavily, should not eat too much high lipid food. Young adults who have hypertension and brain vessel disease family history should be regularly measured blood pressure and blood lipid. If they had hypertension, should be treated regularly.

  16. [Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

    Science.gov (United States)

    Buchner, H; Ferbert, A

    2016-02-01

    Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

  17. [QEEG and brain mapping. Historial develoment, clinical practices and epistemological issues].

    Science.gov (United States)

    Matusevich, Daniel; Ruiz, Martín; Vairo, María Carolina

    2002-01-01

    Although it has been more than two decades since brain mapping was introduced in medicine, its scientific value and clinical practice have not been proved. This paper makes an overview about the historical development of brain mapping, its usefulness in psychiatry and lays epistemological issues concerning the role of technology in medical settings. Both historical and technological development of qEEG gives us the opportunity to think about complexity between ethics, science, technology and medicine.

  18. Optogenetically inspired deep brain stimulation: linking basic with clinical research.

    Science.gov (United States)

    Lüscher, Christian; Pollak, Pierre

    2016-01-01

    In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders. By extension, the technique has also been used to propose blueprints for innovative rational treatment of these diseases. The goal is to design manipulations that disrupt pathological circuit function or restore normal activity. This can be achieved by targeting specific projections in order to apply specific stimulation protocols validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a number of cases, specific forms of pathological synaptic plasticity have been implicated. For example, addictive drugs via strong increase of dopamine trigger a myriad of alterations of glutamate and γ-aminobutyric acid transmission, also called drug-evoked synaptic plasticity. This opens the way to the design of optogenetic reversal protocols, which might restore normal transmission with the hope to abolish the pathological behaviour. Several proof of principle studies for this approach have recently been published. However, for many reasons, optogenetics will not be translatable to human applications in the near future. Here, we argue that an intermediate step is novel deep brain stimulation (DBS) protocols that emulate successful optogenetic approaches in animal models. We provide a roadmap for a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand to novel indications.

  19. Apnoea testing to confirm brain death in clinical practice.

    Science.gov (United States)

    van Donselaar, C A; Meerwaldt, J D; van Gijn, J

    1986-01-01

    In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute. PMID:3093640

  20. Apnoea testing to confirm brain death in clinical practice.

    OpenAIRE

    van Donselaar, C. A.; Meerwaldt, J D; van Gijn, J

    1986-01-01

    In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute.

  1. Apnoea testing to confirm brain death in clinical practice.

    Science.gov (United States)

    van Donselaar, C A; Meerwaldt, J D; van Gijn, J

    1986-09-01

    In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute.

  2. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2016-03-01

    Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

  3. Brain-derived neurotrophic factor and its clinical implications.

    Science.gov (United States)

    Bathina, Siresha; Das, Undurti N

    2015-12-10

    Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

  4. Clinical application value of bone turnover markers in non-small-cell lung cancer patients with bone metastases%骨转换标志物在非小细胞肺癌骨转移临床应用价值的研究

    Institute of Scientific and Technical Information of China (English)

    Zhiyu Wang; Chen Yang; Yumei Yang; Zan Shen; Hui Zhao; Yang Yao

    2011-01-01

    Objective: The purpose of this study was to assess the clinical application value of bone turnover markers in non-small-cell lung cancer (NSCLC) patients with bone metastases. Including diagnosing bone metastases, detecting bone metastatic spread. Methods: Alkaline phosphatase (AKP), β-C-terminal telopeptide of type Ⅰ collagen (β-CTx), osteocalcin (OST) and bone alkaline phosphatase (BALP) were measured in 76 patients with bone metastases from NSCLC and 44 normal people. Results: The level of AKP, β-CTx and BALP in patients with bone metastasis was significantly higher than in the normal people. Significant correlation was observed among bone turnover markers. The levels of BALP and OST were significantly correlated with the extent of bone metastasis. The patients with high-level CTx and low-level BALP had higher risk of pathologic fracture. Conclusion: In NSCLC patients with bone metastases, bone turnover markers can help to make diagnosis and evaluate the severity. It will have a wide range of use in clinical practice.

  5. Quality of life measurement in bone metastases: A literature review

    Directory of Open Access Journals (Sweden)

    Sukirtha Tharmalingam

    2008-12-01

    Full Text Available Sukirtha Tharmalingam, Edward Chow, Kristin Harris, Amanda Hird, Emily SinclairRapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto,