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Sample records for brain metastases clinical

  1. Clinical analysis of novalis stereotactic radiosurgery for brain metastases.

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    Gu, Hae-Won; Sohn, Moon-Jun; Lee, Dong-Joon; Lee, Hye Ran; Lee, Chae-Heuck; Whang, C Jin

    2009-09-01

    The authors analyzed the effectiveness and therapeutic response of Novalis shaped beam radiosurgery for metastatic brain tumors, and the prognostic factors which influenced the outcome. We performed a retrospective analysis of 106 patients who underwent 159 treatments for 640 metastatic brain lesions between January 2000 and April 2008. The pathologies of the primary tumor were mainly lung (45.3%), breast (18.2%) and GI tract (13.2%). We classified the patients using Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and then analyzed the survival and prognostic factors according to the Kaplan Meier method and univariate analysis. The overall median actuarial survival rate was 7.3 months from the time of first radiosurgery treatment while 1 and 2 year actuarial survival estimates were 31% and 14.4%, respectively. Median actuarial survival rates for RPA classes I, II, and III were 31.3 months, 7.5 months and 1.7 months, respectively. Patients' life spans, higher Karnofsky performance scores and age correlated closely with RPA classes. However, sex and the number of lesions were not found to be significantly associated with length of survival. This result suggests that Novalis radiosurgery can be a good treatment option for treatment of the patients with brain metastases.

  2. Stereotactic radiosurgery alone for multiple brain metastases? A review of clinical and technical issues.

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    Sahgal, Arjun; Ruschin, Mark; Ma, Lijun; Verbakel, Wilko; Larson, David; Brown, Paul D

    2017-04-01

    Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Brain metastasization of breast cancer.

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    Custódio-Santos, Tânia; Videira, Mafalda; Brito, Maria Alexandra

    2017-08-01

    Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain. The phenotypic change in malignant cells, and the importance of the microenvironment in the formation of brain metastases are also inspected. Finally, the importance of genetic and epigenetic changes, and the recently disclosed effects of microRNAs in brain metastasization of breast cancer are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Clinical trial design for systemic agents in patients with brain metastases from solid tumours: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

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    Camidge, D Ross; Lee, Eudocia Q; Lin, Nancy U; Margolin, Kim; Ahluwalia, Manmeet S; Bendszus, Martin; Chang, Susan M; Dancey, Janet; de Vries, Elisabeth G E; Harris, Gordon J; Hodi, F Stephen; Lassman, Andrew B; Macdonald, David R; Peereboom, David M; Schiff, David; Soffietti, Ricardo; van den Bent, Martin J; Wefel, Jeffrey S; Wen, Patrick Y

    2018-01-01

    Patients with active CNS disease are often excluded from clinical trials, and data regarding the CNS efficacy of systemic agents are usually obtained late in the drug development process or not at all. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we provide detailed recommendations on when patients with brain metastases from solid tumours should be included or excluded in clinical trials of systemic agents. We also discuss the limitations of retrospective studies in determining the CNS efficacy of systemic drugs. Inclusion of patients with brain metastases early on in the clinical development of a drug or a regimen is needed to generate appropriate CNS efficacy or non-efficacy signals. We consider how to optimally incorporate or exclude such patients in systemic therapy trials depending on the likelihood of CNS activity of the agent by considering three scenarios: drugs that are considered very unlikely to have CNS antitumour activity or efficacy; drugs that are considered very likely to have CNS activity or efficacy; and drugs with minimal baseline information on CNS activity or efficacy. We also address trial design issues unique to patients with brain metastases, including the selection of appropriate CNS endpoints in systemic therapy trials. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Wong Rebecca KS

    2005-04-01

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

  6. A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience.

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    McKee, Megan J; Keith, Kevin; Deal, Allison M; Garrett, Amy L; Wheless, Amy A; Green, Rebecca L; Benbow, Julie M; Dees, E Claire; Carey, Lisa A; Ewend, Matthew G; Anders, Carey K; Zagar, Timothy M

    2016-01-01

    Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years. Clinical and demographic data were collected from patients in a prospectively maintained database. Descriptive statistics are reported as percentages and means. The Kaplan-Meier method was used to estimate time-to-event outcomes. Sixty-five patients were seen between January 2012 and January 2015. At the time of presentation to the BCBM clinic, most patients (74%) had multiple (≥2) brain metastases and had received prior systemic (77%) and whole-brain radiation therapy and/or central nervous system stereotactic radiosurgery (65%) in the metastatic setting. Seventy-eight percent returned for a follow-up visit; 32% were enrolled in a clinical trial. Median time from diagnosis of brain metastasis to death was 2.11 years (95% confidence interval [CI] 1.31-2.47) for all patients, 1.15 years (95% CI 0.4-2.43) for triple-negative breast cancer, 1.31 years (95% CI 0.51-2.52) for hormone receptor-positive/HER2- breast cancer, and 3.03 years (95% CI lower limit 1.94, upper limit not estimable) for HER2+ breast cancer (p = .0037). Patients with BCBM have unique and complex needs that require input from several oncologic disciplines. The development of the UNC-CH multidisciplinary BCBM clinic is a model that can be adapted at other centers to provide coordinated care for patients with a challenging and complex disease. Patients with breast cancer brain metastases often require unique multidisciplinary care to meet the numerous and uncommon challenges associated with their conditions. Here, the

  7. Metabolic advantages and vulnerabilities in brain metastases.

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    Ciminera, Alexandra K; Jandial, Rahul; Termini, John

    2017-10-23

    Metabolic adaptations permit tumor cells to metastasize to and thrive in the brain. Brain metastases continue to present clinical challenges due to rising incidence and resistance to current treatments. Therefore, elucidating altered metabolic pathways in brain metastases may provide new therapeutic targets for the treatment of aggressive disease. Due to the high demand for glucose in the brain, increased glycolytic activity is favored for energy production. Primary tumors that undergo Warburg-like metabolic reprogramming become suited to growth in the brain microenvironment. Indeed, elevated metabolism is a predictor of metastasis in many cancer subtypes. Specifically, metabolic alterations are seen in primary tumors that are associated with the formation of brain metastases, namely breast cancer, lung cancer, and melanoma. Because of this selective pressure, inhibitors of key metabolic factors may reduce tumor cell viability, thus exploiting metabolic pathways for cancer therapeutics. This review summarizes the metabolic advantages and vulnerabilities of brain metastases.

  8. Future directions in treatment of brain metastases.

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    Barani, Igor J; Larson, David A; Berger, Mitchel S

    2013-01-01

    Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

  9. [Breast cancer brain metastases: clinical and prognostic characteristics of different biological subtypes].

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    Zhang, Tongtong; Li, Qing; Xu, Binghe; Zhang, Pin; Yuan, Peng; Ma, Fei; Wang, Jiayu; Fan, Ying

    2014-09-01

    To analyze the clinical characteristics and survival depending on biological subtypes in breast cancer patients with brain metastases (BM). A retrospective analysis was performed on 152 breast cancer patients with BM admitted to the Cancer Institute & Hospital, Chinese Academy of Medical Sciences from January 2003 to December 2012. Depending on the biological characteristics, these patients were divided into three subtypes: Luminal, human epidermal growth factor receptor 2 (HER-2)-overexpressing, and triple-negative subtypes. The clinicopathological characteristics, recurrence status, and prognostic factors were analyzed at the initial diagnosis. The systemic therapy after BM was further studied. Among the 152 patients, the number of Luminal, HER-2-overexpressing, and triple-negative breast cancer (TNBC) subtypes were 60, 53, and 39 cases, respectively. The median time from first recurrence to BM of all patients was 7.3 months, the median time of Luminal, HER-2-overexpressing, and TNBC subtypes was 11.0 months, 9.6 months, and 5.5 months, respectively (P cancer patients (17.1 vs. 1.7 months, P brain meatastases occurr earlier in HER-2-overexpressing and TNBC subtypes. Trastuzumab can delay the occurrence of BM from advanced breast cancer, and systemic therapy can improve the survival of patients after brain metastasis.

  10. Stereotactic Radiosurgery for Melanoma Brain Metastases: A Comprehensive Clinical Case Series.

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    Feng, Rui; Oermann, Eric K; Shrivastava, Raj; Gold, Ariel; Collins, Brian T; Kondziolka, Douglas; Collins, Sean P

    2017-04-01

    Melanoma has high propensity to metastasize to the brain. With recent gains in improving patient survival, stereotactic radiosurgery (SRS) may offer an effective and less neurotoxic alternative to whole-brain radiation. In the study, we report on the safety and efficacy of SRS in treating melanoma brain metastases in 87 patients. This retrospective multicenter study examined 87 patients with 309 metastases who underwent single-dose or multifractionated SRS for treatment of intracranial metastases from malignant melanoma. A total of 87 patients with a median age of 62 years (26-85) were treated from 2007-2014. Eighty patients (92%) also had extracranial metastases at time of treatment, and 69 patients (79%) had uncontrolled systemic disease. Seventy-nine patients (91%) underwent single-dose fractions, 7 (8%) underwent 3 fractions, and 1 (1%) was treated in 5 fractions. The mean tumor volume (GTV) treated was 1.92 cc. Five patients developed symptoms of acute phase toxicity, and 4 developed late phase toxicity. None had radionecrosis. The median survival was 6 months. The Kaplan-Meier 1-year survival rate was 31%, and the 1-year local control rate was 91%. The 1-year survival rate for BRAF-positive patients was 42%, and for BRAF-negative patients it was 27%. Forty-two patients (48%) had distant intracranial recurrences, and 1-year distant control rate was 32%. SRS is a safe and effective treatment option for intracranial metastases from malignant melanoma. This paper serves as a reference for what is achievable in the absence of highly effective systemic therapy. Copyright © 2017. Published by Elsevier Inc.

  11. Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review.

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    Ghidini, Michele; Petrelli, Fausto; Hahne, Jens Claus; De Giorgi, Annamaria; Toppo, Laura; Pizzo, Claudio; Ratti, Margherita; Barni, Sandro; Passalacqua, Rodolfo; Tomasello, Gianluca

    2017-04-01

    The aim of the study was to collect the available data on central nervous system (CNS) metastases from esophageal and gastric cancer. A PubMed, EMBASE, SCOPUS, Web of Science, LILACS, Ovid and Cochrane Library search was performed. Thirty-seven studies including 779 patients were considered. Among the data extracted, treatment of tumor and brain metastases (BMs), time to BMs development, number and subsite, extracerebral metastases rate, median overall survival (OS) and prognostic factors were included. For esophageal cancer, the median OS from diagnosis of BMs was 4.2 months. Prognostic factors for OS included: performance status, multimodal therapy, adjuvant chemotherapy, single BM, brain only disease and surgery. For gastric cancer, median OS was 2.4 months. Prognostic factors for OS included: recursive partitioning analysis class 2, stereotactic radiosurgery (SRT) and use of intrathecal therapy. HER2-positive gastric cancer was shown to be associated with a higher risk and shorter time to CNS relapse. Patients harboring BMs from gastric and esophageal tumors, except cases with single lesions that are treated aggressively, have a poor prognosis. SRT (plus or minus surgery and whole brain radiotherapy) seems to give better results in terms of longer OS after brain relapse.

  12. Stereotactic Radiosurgery for Treatment of Brain Metastases.

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    Badiyan, Shahed N; Regine, William F; Mehta, Minesh

    2016-08-01

    Brain metastases are the most common intracranial malignancy. Incidence of brain metastases has risen as systemic therapies have improved and patients with metastatic disease live longer. Whole-brain radiation therapy, for many years, has been the standard treatment approach. Stereotactic radiosurgery has become an increasingly popular option because of its relatively short, convenient, and noninvasive treatment course. Although recently published data have renewed interest in use of whole-brain radiation therapy or systemic therapies for control of micrometastatic disease, stereotactic radiosurgery continues to be an important modality, capable of delivering ablative doses of radiation for long-term control of macroscopic disease. The purpose of this review is to explore the different paradigms for incorporation of stereotactic radiosurgery into management of brain metastases. Current uses for stereotactic radiosurgery include delivery as a boost with whole-brain radiation therapy; alone for patients with a limited number of brain metastases; in pre- or postoperative settings; and in combination with systemic, targeted, and immune-based therapies. Mature prospective data on use of stereotactic radiosurgery in combination with whole-brain radiation therapy is available; however, prospective, randomized data on stereotactic radiosurgery for patients with a greater number of brain metastases, its use in pre- and postoperative settings, and its use in combination with systemic therapies are limited. Data from ongoing and future studies are needed to define the appropriate use of stereotactic radiosurgery in these settings. Copyright © 2016 by American Society of Clinical Oncology.

  13. Clinical interrogation and application of super-selective intracranial artery infusion chemotherapy for lung cancer patients with brain metastases.

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    Rong, J; Chunhua, M; Yuan, L; Ning, M; Jinduo, L; Bin, W; Liwei, S

    2015-11-01

    The purpose of this study was to evaluate the clinical efficacy of super-selective intracranial artery infusion chemotherapy and to determine correlated prognostic parameters for advanced lung cancer patients with brain metastases. Fifty-four lung cancer patients with brain metastasis who had no previous treatment were enrolled for the study. These patients received super-selective intracranial artery infusion chemotherapy, as well as arterial infusion chemotherapy for primary and metastatic lesions. The procedure was performed once every 4 weeks. Patients were monitored to evaluate short-term clinical outcomes 4 weeks after the first 2 treatments, and follow-up visits performed every 4 weeks after the first 4 treatments until the appearance of disease progression or intolerable toxicity. All 54 cases were treated at least 4 times. The overall response rate was 55.56% (30/54), and the disease control rate was 85.19% (46/54). The median overall survival was 7 months, with a 95% confidence interval (CI) of 5.87-8.13 months, and the median progression-free survival was 4 months, with a 95% CI of 3.20-4.80 months. The 6-month survival rate and 1-year survival rate were 81.48% (44/54) and 18.52% (10/54), respectively. Super-selective intracranial artery infusion chemotherapy provides a clinically efficacious avenue of treatment for lung cancer patients with brain metastases. Pathological classification, Karnofsky performance status, and extracranial metastases may serve as reliable prognostic parameters in determining the clinical outcomes for lung cancer patients with brain metastases.

  14. Brain Metastases from Endometrial Carcinoma

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    Piura, Ettie; Piura, Benjamin

    2012-01-01

    This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

  15. 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....

  16. 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

  17. Postoperative stereotactic radiosurgery to the resection cavity for large brain metastases: clinical outcomes, predictors of intracranial failure, and implications for optimal patient selection.

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    Ling, Diane C; Vargo, John A; Wegner, Rodney E; Flickinger, John C; Burton, Steven A; Engh, Johnathan; Amankulor, Nduka; Quinn, Annette E; Ozhasoglu, Cihat; Heron, Dwight E

    2015-02-01

    Postoperative stereotactic radiosurgery for brain metastases potentially offers similar local control rates and fewer long-term neurocognitive sequelae compared to whole brain radiation therapy, although patients remain at risk for distant brain failure (DBF). To describe clinical outcomes of adjuvant stereotactic radiosurgery for large brain metastases and identify predictors of intracranial failure and their implications on optimal patient selection criteria. We performed a retrospective review on 100 large (>3 cm) brain metastases in 99 patients managed by resection followed by postoperative stereotactic radiosurgery to a median dose of 22 Gy (range, 10-28) in 1 to 5 fractions (median, 3). Primary histology was nonsmall cell lung in 40%, breast cancer in 18%, and melanoma in 17%. Forty (40%) patients had uncontrolled systemic disease. With a median follow-up of 12.2 months (range, 0.6-87.4), the 1-year Kaplan-Meier local control was 72%, DBF 64%, and overall survival 55%. Nine patients (9%) developed evidence of radiation injury, and 6 (6%) developed leptomeningeal disease. Uncontrolled systemic disease (P=.03), melanoma histology (P=.04), and increasing number of brain metastases (Pstereotactic radiosurgery to the resection cavity safely and effectively augments local control of large brain metastases. Patients with <4 metastases and controlled systemic disease have significantly lower rates of DBF and are ideal treatment candidates.

  18. 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

  19. Modern radiosurgery equipment for treating brain metastases.

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    Chung, Hyun-Tai; Kim, Dong Gyu

    2012-01-01

    Radiosurgery plays an important role in the management of brain metastases, which are the most common indication for such treatment in many centers. Because brain metastases are well enhanced on magnetic resonance images and show clear margins from the surrounding normal brain, they are suitable for radiosurgery. The dedicated radiosurgery machines used for treating brain metastases have different characteristics from the conventional external beam radiotherapy machines, although the same gamma rays are used in both methods. In a radiosurgery procedure, highly concentrated radiation is given to a predefined target so that every cell inside it is affected. To achieve this, a radio-surgery machine should provide a highly accurate and precise delivery of radiation to the target with a steep dose gradient relative to surrounding tissues. Among the diverse dedicated machines that are in clinical use for radiosurgery of brain metastases, three - the Gamma Knife(®), CyberKnife(®), and Novalis(TM) - will be reviewed in this report. The basic principles of each machine for achieving a high convergence of radiation and for adjusting the radiation beam to conform to the target are described. The mechanical accuracy and characteristics of treatment plans are discussed briefly. Copyright © 2012 S. Karger AG, Basel.

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

    National Research Council Canada - National Science Library

    Kress, Marie-Adele S; Ramakrishna, Naren; Makgoeng, Solomon B; Unger, Keith R; Potosky, Arnold L

    2012-01-01

    Limited data guide radiotherapy choices for patients with brain metastases. This survey aimed to identify patient, physician, and practice setting variables associated with reported preferences for different treatment techniques...

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

    Science.gov (United States)

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

    2016-04-01

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

  2. Molecular insights into melanoma brain metastases.

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    Westphal, Dana; Glitza Oliva, Isabella C; Niessner, Heike

    2017-06-01

    Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases. Cancer 2017;123:2163-75. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

    Directory of Open Access Journals (Sweden)

    Kress Marie-Adele S

    2012-11-01

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

  4. Radiosurgery for Large Brain Metastases

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    Han, Jung Ho [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr [Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of); Chung, Hyun-Tai; Paek, Sun Ha; Park, Chul-Kee; Jung, Hee-Won [Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-05-01

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

  5. Leukoencephalopathy After Stereotactic Radiosurgery for Brain Metastases

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    Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com [Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia (United States); Lee, Cheng-Chia [Department of Neurosurgery, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Schlesinger, David [Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia (United States); Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia (United States); Larner, James M. [Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia (United States); Xu, Zhiyuan [Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia (United States); Sheehan, Jason P. [Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia (United States); Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia (United States)

    2015-11-15

    Purpose: Although the use of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases has increased dramatically during the past decade to avoid the neurocognitive dysfunction induced by whole brain radiation therapy (WBRT), the cumulative neurocognitive effect of numerous SRS sessions remains unknown. Because leukoencephalopathy is a sensitive marker for radiation-induced central nervous system damage, we studied the clinical and dosimetric predictors of SRS-induced leukoencephalopathy. Methods and Materials: Patients treated at our institution with at least 2 sessions of SRS for brain metastases from 2007 to 2013 were reviewed. The pre- and post-SRS magnetic resonance imaging sequences were reviewed and graded for white matter changes associated with radiation leukoencephalopathy using a previously validated scale. Patient characteristics and SRS dosimetric parameters were reviewed for factors that contributed to leukoencephalopathy using Cox proportional hazards modeling. Results: A total of 103 patients meeting the inclusion criteria were identified. The overall incidence of leukoencephalopathy was 29% at year 1, 38% at year 2, and 53% at year 3. Three factors were associated with radiation-induced leukoencephalopathy: (1) the use of WBRT (P=.019); (2) a higher SRS integral dose to the cranium (P=.036); and (3) the total number of intracranial metastases (P=.003). Conclusions: Our results have established that WBRT plus SRS produces leukoencephalopathy at a much higher rate than SRS alone. In addition, for patients who did not undergo WBRT before SRS, the integral dose was associated with the development of leukoencephalopathy. As the survival of patients with central nervous system metastases increases and as the neurotoxicity of chemotherapeutic and targeted agents becomes established, these 3 potential risk factors will be important to consider.

  6. Preliminary clinical outcomes of image-guided 3-dimensional conformal radiotherapy for limited brain metastases instead of stereotactic irradiation referral.

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    Ohtakara, Kazuhiro; Hoshi, Hiroaki

    2014-06-01

    To determine the preliminary clinical outcomes of image-guided 3-dimensional conformal radiotherapy (IG-3DCRT) for limited but variably-sized brain metastases (BM). Sixty-two lesions in 24 patients were retrospectively evaluated; out of these patients 75% were ≥ 65 years of age, and 37.5% were categorized into recursive partitioning analysis (RPA) class 3. The median value for the maximum diameter of the lesions was 19 mm (range=4-72 mm). The median sole treatment dose was 36 Gy in 10 fractions. The median survival durations after IG-3DCRT were 12.0 months and 3.2 months for patients categorized into RPA classes ≤ 2 and 3, respectively. Local recurrences occurred in two lesions with a 6-month local control probability of 93.0%. Major toxicities included radiation necrosis in two patients. IG-3DCRT is feasible even for patients with limited BM who are categorized into RPA class 3, and confers clinical outcomes comparable to those of stereotactic radiosurgery, including excellent local control and minimal toxicity even for large tumors. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Targeted Therapies for Brain Metastases from Breast Cancer.

    Science.gov (United States)

    Venur, Vyshak Alva; Leone, José Pablo

    2016-09-13

    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.

  12. Value of oncogenes for the prediction of brain metastases at initial diagnosis: a review of published data.

    Science.gov (United States)

    Huang, Qian; Ouyang, Xuenong

    2014-12-09

    Identifying cancer patients who are at high risk of developing brain metastases at initial diagnosis and applying effective intervention or monitoring strategies is of vital importance. Recent advances in the biology of brain metastases revealed that some oncogenes from primary tumors may be potential markers for identifying cancer patients likely to metastasize to the brain. We here summarize data on the mechanisms of brain metastases supporting the involvement of oncogene changes in the brain metastatic evolution. We also review the available evidence on clinical studies of oncogenes in the prediction of cancer patients with high incidence of brain metastases.

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

    NARCIS (Netherlands)

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

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

  14. Drug-Resistant Brain Metastases: A Role for Pharmacology, Tumor Evolution, and Too-Late Therapy.

    Science.gov (United States)

    Stricker, Thomas; Arteaga, Carlos L

    2015-11-01

    Two recent studies report deep molecular profiling of matched brain metastases and primary tumors. In both studies, somatic alterations in the brain metastases were frequently discordant with those in the primary tumor, suggesting divergent evolution at metastatic sites and raising questions about the use of biomarkers in patients in clinical trials with targeted therapies. ©2015 American Association for Cancer Research.

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

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    Hintz, Mandy

    2017-10-01

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

  16. Viral Immunotherapy to Eradicate Subclinical Brain Metastases

    Science.gov (United States)

    2014-05-01

    cells - of which most were Thy1.2+CD8+ (i.e., FITC (green) and PE (red/purple) double-positive and therefore appearing orange ) were seen after E...Dense infiltration of D2F2/E2 brain metastases at 4 days after intrathecal injection of VSV-HER2. CD8=green, CD4= orange , NKp46 = purple. Please...narcotic anesthesia in rats. Brain, Behav Immun. 1989 Jun;3(2):129–37. 19. Griffith CD, Rees RC, Platts A, Jermy A, Peel J, Rogers K. The nature of

  17. Genetic Characterization of Brain Metastases in the Era of Targeted Therapy

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    Catherine H. Han

    2017-09-01

    Full Text Available In the current era of molecularly targeted therapies and precision medicine, choice of cancer treatment has been increasingly tailored according to the molecular or genomic characterization of the cancer the individual has. Previously, the clinical observation of inadequate control of brain metastases was widely attributed to a lack of central nervous system (CNS penetration of the anticancer drugs. However, more recent data have suggested that there are genetic explanations for such observations. Genomic analyses of brain metastases and matching primary tumor and other extracranial metastases have revealed that brain metastases can harbor potentially actionable driver mutations that are unique to them. Identification of genomic alterations specific to brain metastases and targeted therapies against these mutations represent an important research area to potentially improve survival outcomes for patients who develop brain metastases. Novel approaches in genomic testing such as that using cell-free circulating tumor DNA (ctDNA in the cerebrospinal fluid (CSF facilitate advancing our understanding of the genomics of brain metastases, which is critical for precision medicine. CSF-derived ctDNA sequencing may be particularly useful in patients who are unfit for surgical resection or have multiple brain metastases, which can harbor mutations that are distinct from their primary tumors. Compared to the traditional chemotherapeutics, novel targeted agents appear to be more effective in controlling the CNS disease with better safety profiles. Several brain metastases-dedicated trials of various targeted therapies are currently underway to address the role of these agents in the treatment of CNS disease. This review focuses on recent advances in genomic profiling of brain metastases and current knowledge of targeted therapies in the management of brain metastases from cancers of the breast, lung, colorectum, kidneys, and ovaries as well as melanoma.

  18. The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: The US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases.

    Science.gov (United States)

    Slade, Alexander N; Stanic, Sinisa

    2016-03-01

    Two recent clinical trials, phase III RTOG 0614 and phase II RTOG 0933, showed some effectiveness of Memantine and IMRT planning for hippocampus sparing, among patients receiving whole brain radiotherapy (WBRT) for brain metastases; however, their use in routine clinical practice is unknown. A survey was sent to 1933 radiation oncologists in the US. Data collected included utilization of Memantine and hippocampus sparing, reasons for adoption and non-adoption, and demographic variables. A total of 196 radiation oncologists responded to the survey, with 64% reporting using Memantine in almost none of the patients receiving WBRT for brain metastases, and only 11% considering Memantine for trial was supported by 71% of radiation oncologists, whereas further exploration of Memantine for this purpose in a phase III trial was supported by 42%. At this time, the majority of surveyed radiation oncologists in the US do not use Memantine, or IMRT planning for hippocampus sparing in patients receiving WBRT. Further validation of the hippocampus sparing concept in a phase III trial was supported, before adopting it in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. [Experience with the radiosurgical treatment of brain metastases].

    Science.gov (United States)

    Fernández-de Aspe, Pablo; Fernández-Quinto, Alejandro; Guerro-Moya, Andrea; Arán-Echabe, Eduardo; Varela-Pazos, Ana; Peleteiro-Higuero, Paula; Cascalla-Caneda, Luis; Gelabert-González, Miguel

    To analyse the survival rate of a cohort of patients with intracranial metastases treated with radiosurgery, and to determine the factors that influence the results. Retrospective analysis performed on a cohort of 126 patients undergoing radiosurgery for brain metastases. Patients treated with surgery before or after radiosurgery were excluded. Survival is analysed based on clinical (age, sex, primary tumour), radiological (number, location and volume of lesions), and radiotherapy factors (treatment dose, holocraneal radiation). Univariate and multivariate analyses were performed to determine significant prognostic factors. A total of 225 brain metastases in 126 patients, with a mean age of 59.8±11.6years, were treated between February 2008 and April 2015. The mean survival was 8.2 months. The overall survival rates at 6months, 1year, and 2years were 60.3%, 31.5%, and 12.8%, respectively. Lung (59.5%) and breast (14.3) were the most common primary tumours, and the most common site for metastases was the cerebral hemisphere (77%) and the average volume was 10.35 cc (0.2-43.5). Significant survival factors were: age under 60 (P=.046), female (P80 (P=.001), SIR6 >5 (P=.031), and GPA ≥2.5 (P=.003). Radiosurgery is an appropriate technique for the treatment of brain metastases, and the main prognostic factors include being age under 65, female, breast cancer, and good scores on Karnofsky, SIR, and GPA scales. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. 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.

  1. Attributes of brain metastases from breast and lung cancer.

    Science.gov (United States)

    Hengel, Kyle; Sidhu, Gurinder; Choi, Jai; Weedon, Jeremy; Nwokedi, Emmanuel; Axiotis, Constantine A; Song, Xianyuan; Braverman, Albert S

    2013-06-01

    Most brain metastases arise from breast and lung cancers. Few studies compare the brain regions they involve, their numbers and intrinsic attributes. Records of all patients referred to Radiation Oncology for treatment of symptomatic brain metastases were obtained. Computed tomography (n = 56) or magnetic resonance imaging (n = 72) brain scans were reviewed. Data from 68 breast and 62 lung cancer patients were compared. Brain metastases presented earlier in the course of the lung than of the breast cancer patients (p = 0.001). There were more metastases in the cerebral hemispheres of the breast than of the lung cancer patients (p = 0.014). More breast than lung cancer patients had cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases and presence of cerebellar metastases were positively correlated (p = 0.001). The prevalence of at least one metastasis surrounded with >2 cm of edema was greater for the lung than for the breast patients (p = 0.019). The primary tumor type, rather than the scanning method, correlated with differences between these variables. Brain metastases from lung occur earlier, are more edematous, but fewer in number than those from breast cancers. Cerebellar brain metastases are more frequent in breast cancer.

  2. 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.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  4. How Does Brainstem Involvement Affect Prognosis in Patients with Limited Brain Metastases? Results of a Matched-Cohort Analysis.

    Science.gov (United States)

    Trifiletti, Daniel M; Lee, Cheng-Chia; Shah, Neil; Patel, Nirav V; Chen, Shao-Ching; Sheehan, Jason P

    2016-04-01

    Although brainstem metastases are thought to portend an inferior prognosis compared to non-brainstem brain metastases, there is limited evidence to support this claim, particularly in the modern radiosurgical era. We collected the clinical data for 500 patients with brain metastases treated at our institution with stereotactic radiosurgery (SRS). All patients received SRS to at least one brain metastasis, and all brainstem metastases underwent SRS. After propensity score matching, clinical characteristics and overall survival were calculated and compared between groups. Three hundred sixteen patients with brain metastases were analyzed after matching (143 with brainstem involvement and 173 without). Patients with brainstem metastases lived shorter after first SRS than patients without brainstem metastases did (median 4.4 and 6.5 months, respectively; P = 0.01), and they were more likely to have received whole brain irradiation (P = 0.003). Patients with a single metastasis did not survive longer than patients with multiple brain metastases if there was brainstem involvement (P = 0.45). The incidence of new extracranial disease and severe toxicity after SRS did not differ between groups. The survival of patients with brain metastases is inferior after a metastatic lesion develops within the brainstem, despite favorable local control with brainstem SRS. The brainstem location should be considered a negative prognostic factor for survival after SRS, and it could result from the eloquence of this location. Future research could identify the clinically life-limiting component of brainstem metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. [Establish and analyze the predictive model of early stage brain metastases in patients with breast cancer].

    Science.gov (United States)

    Wang, Qiusheng; Wu, Shikai; Sun, Bing; Huang, Zhou; Meng, Xiangying; Huang, Yan

    2015-12-19

    To investigate the risk factors of cerebral metastasis of breast cancer and to provide guidance for the early diagnosis and treatment of brain metastases. Clinical data of postoperative patients with breast cancer were collected in our hospital from 2005 to 2009. All the patients were divided into two groups, with or without brain metastasis. The risk factors of brain metastases of patients with breast cancer were analyzed by the logistic regression. Eight hundred and twenty four early postoperative patients with breast cancer were enrolled. The median follow-up time was 68 months and 199 cases had brain metastasis. The univariate logistic regression results showed that higher grade of tumor, metastases. This model has the predictive value for the occurrence of brain metastases from breast cancer.

  6. Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer

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    Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Arizona (United States); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Khoa, M.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam)

    2014-04-15

    This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases. (orig.) [German] Diese Studie soll zur Abschaetzung des Vorliegens extrakranieller Metastasen bei Patienten mit primaer zerebral metastasierter Tumorerkrankung beitragen. Daten von 659 Patienten mit primaer zerebral metastasierter Tumorerkrankung wurden retrospektiv analysiert. Insgesamt 359 Patienten mit extrakraniellen Metastasen wurden mit 300 Patienten ohne extrakranielle Metastasierung hinsichtlich Alter, Geschlecht, Karnofsky-Performance-Score (KPS), Art des Primaertumors und der Anzahl der Hirnmetastasen miteinander verglichen. Weitere Analysen erfolgten bei Patienten mit den unguenstigsten und bei Patienten mit den guenstigsten

  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. Copyright © 2015. Published by Elsevier SAS.

  8. Tumor Cells and Micro-environment in Brain Metastases

    Directory of Open Access Journals (Sweden)

    Wen ZHONG

    2016-09-01

    Full Text Available Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis ”seed and soil”, that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well. In this assay, we reviewed documents concerning tumor cells, brain micro-environments and their interactions in brain metastases, aiming to provide novel insight into the treatments of brain metastases.

  9. Stereotactic Radiosurgery With or Without Whole-Brain Radiotherapy for Brain Metastases: Secondary Analysis of the JROSG 99-1 Randomized Clinical Trial.

    Science.gov (United States)

    Aoyama, Hidefumi; Tago, Masao; Shirato, Hiroki

    2015-07-01

    It remains uncertain whether treatment with stereotactic radiosurgery (SRS) alone can be safely applied to all patient populations with 1 to 4 brain metastases (BMs) exhibiting heterogeneous prognoses. To investigate the feasibility of SRS alone for patients with different prognoses determined by the diagnosis-specific Graded Prognostic Assessment (DS-GPA). A secondary analysis (performed in September 2014) of the Japanese Radiation Oncology Study Group (JROSG) 99-1, a phase 3 randomized trial, comparing SRS alone and whole-brain radiotherapy (WBRT) + SRS conducted in 1999 to 2003. Among a total of 132 patients, 88 with non-small-cell lung cancer (NSCLC) and 1 to 4 BMs were included and poststratified by DS-GPA scores to avoid potential bias from BMs from different primary cancer types. The median follow-up time was 8.05 months. The WBRT schedule was 30 Gy in 10 fractions over 2 to 2.5 weeks. The mean SRS dose was 21.9 Gy in SRS alone and 16.6 Gy in WBRT + SRS. The primary end point was overall survival (OS), and the secondary end points included brain tumor recurrence (BTR), salvage treatment, and radiation toxic effects. Forty-seven patients had a favorable prognosis, with DS-GPA scores of 2.5 to 4.0 (26 SRS-alone and 21 WBRT + SRS [DS-GPA 2.5-4.0 group]), and 41 had an unfavorable prognosis, with DS-GPA scores of 0.5 to 2.0 (19 SRS-alone and 22 WBRT + SRS [DS-GPA 0.5-2.0 group]). Significantly better OS was observed in the DS-GPA 2.5-4.0 group in WBRT + SRS vs the SRS alone, with a median survival time of 16.7 (95% CI, 7.5-72.9) months vs 10.6 (95% CI, 7.7-15.5) months (P = .04) (hazard ratio [HR], 1.92; 95% CI, 1.01-3.78). However, no such difference was observed in the DS-GPA 0.5-2.0 group (HR, 1.05; 95% CI, 0.55-1.99) (P = .86). This benefit could be explained by the differing BTR rates, in that the prevention against BTR by WBRT had a more significant impact in the DS-GPA 2.5-4.0 group (HR, 8.31; 95% CI, 3.05-29.13) (P 1) vs the

  10. Brain metastases of choriocarcinoma: A report on two cases

    Directory of Open Access Journals (Sweden)

    Milenković Vera

    2013-01-01

    Full Text Available Introduction. Gestational trophoblastic diseases (GTD are a spectrum of tumors with a various of biological behavior and potential for metastases. It consists of hydatiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor. Choriocarcinoma presents a very aggressive tumor with high malignant potential. Case report. We presented the two cases of choriocarcinoma with brain metastases. The first one was manifested by neurological deterioration as the first sign of metastasis, while the second patient had firstly metrorrhagia and in the further couse neurological disturbances that suggested the presence of brain tumor. In both cases we applied a combined treatment of surgery, chemotherapy and radiation therapy. Both patient survived with high quality of life. Conclusion. A successful outcome of brain metastases of choriocarcinoma was obtained by the use of a combined treatment of surgery, chemotherapy and radiation therapy. In cases of young women with brain metastases, gynecological malignancy should be always considered.

  11. SRC family kinases as novel therapeutic targets to treat breast cancer brain metastases.

    Science.gov (United States)

    Zhang, Siyuan; Huang, Wen-Chien; Zhang, Lin; Zhang, Chenyu; Lowery, Frank J; Ding, Zhaoxi; Guo, Hua; Wang, Hai; Huang, Suyun; Sahin, Aysegul A; Aldape, Kenneth D; Steeg, Patricia S; Yu, Dihua

    2013-09-15

    Despite better control of early-stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer and we show how Src-targeting combinatorial regimens can treat HER2(+) brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat patients with breast cancer suffering from brain metastasis. ©2013 AACR.

  12. A pathology-based substrate for target definition in radiosurgery of brain metastases.

    Science.gov (United States)

    Baumert, Brigitta G; Rutten, Isabelle; Dehing-Oberije, Cary; Twijnstra, Albert; Dirx, Miranda J M; Debougnoux-Huppertz, Ria M T L; Lambin, Philippe; Kubat, Bela

    2006-09-01

    To investigate the need of a margin other than for accuracy reasons in stereotactic radiosurgery (SRS) of brain metastases by means of histopathology. Evaluation of 45 patients from two pathology departments having had brain metastases and an autopsy of the brain. Growth patterns were reviewed with a focus on infiltration beyond the metastases boundary and made visible with immunohistochemical staining: the metastasis itself with tumor-specific markers, surrounding normal brain tissue with a glial marker, and a possible capsule with a soft tissue marker. Measurements were corrected by a tissue-shrinkage correction factor taken from literature. Outcomes parameters for infiltration were mean and maximum depths of infiltration and number of measured infiltration sites. In 48 of 76 metastases, an infiltration was present. The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC) and melanoma showed a maximum depth of infiltration of > or =1 mm, and other histologies melanoma, and sarcoma, the highest number of infiltrative sites were observed (median, 2; range, 1-8). SCLC showed significantly larger infiltrative growth, compared with other diagnostic groups. In NSCLC, the highest percentage of infiltration was present (70%). Infiltrative growth beyond the border of the brain metastasis was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore, has an impact in defining the clinical target volume for SRS of brain metastases, and a margin of approximately 1 mm should be added to the visible lesion.

  13. The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

    Science.gov (United States)

    Moraes, Fabio Ynoe; Taunk, Neil K.; Marta, Gustavo Nader; Suh, John H.

    2016-01-01

    Brain metastases are the most common intracranial malignancy. Many approaches, including radiation therapy, surgery, and cytotoxic chemotherapy, have been used to treat patients with brain metastases depending on the patient’s disease burden and symptoms. However, stereotactic surgery (SRS) has revolutionized local treatment of brain metastases. Likewise, targeted therapies, including small-molecule inhibitors and monoclonal antibodies that target cancer cell metabolism or angiogenesis, have transformed managing systemic disease. Prospective data on combining these treatments for synergistic effect are limited, but early data show favorable safety and efficacy profiles. The combination of SRS and targeted therapy will further individualize treatment, potentially obviating the need for cytotoxic chemotherapy or whole-brain radiation. There is a great need to pursue research into these exciting modalities and novel combinations to further improve the treatment of patients with brain metastases. This article discusses reported and ongoing clinical trials assessing the safety and efficacy of targeted therapy during SRS. Implications for Practice: Treatment of patients with brain metastases requires a multidisciplinary approach. Stereotactic radiosurgery is increasingly used in the upfront setting to treat new brain metastasis. Targeted therapies have revolutionized systemic treatment of many malignancies and may sometimes be used as initial treatment in metastatic patients. There is sparse literature regarding safety and efficacy of combining these two treatment modalities. This article summarizes the supporting literature and highlights ongoing clinical trials in combining radiosurgery with targeted therapy. PMID:26764249

  14. Prognostic stratification of brain metastases from hepatocellular carcinoma.

    Science.gov (United States)

    Kim, Kyung Su; Kim, Kyubo; Chie, Eui Kyu; Kim, Yoon Jun; Yoon, Jung Hwan; Lee, Hyo-Suk; Ha, Sung W

    2014-10-01

    The aim of this study is to evaluate prognostic factors of brain metastases from hepatocellular carcinoma. Medical records of 95 patients who have been diagnosed of brain metastases from hepatocellular carcinoma between January 2000 and December 2011 were retrospectively reviewed. The median age at diagnosis of brain metastases is 56.1 years. Eighty-two patients were male. Median interval from diagnosis of hepatocellular carcinoma to brain metastases was 29.5 months. Eighty-eight patents had extracranial metastases, and the lung was the most frequent involved organ. Motor weakness was the most frequent presenting symptom (49.5%). Intracranial hemorrhage was present in 71 patients (74.7%). Brain metastases were treated with whole brain radiation therapy (WBRT) alone in 57 patients, radiosurgery alone in 18, surgery and WBRT in 6, surgery and radiosurgery in 3, surgery alone in 3, radiosurgery and WBRT in 2, and conservative management only in 6. Median overall survival was 3.0 months. Multivariate analysis showed ECOG performance status, Child-Pugh class, AFP level, number of brain lesions, and treatment modality were associated with survival (p < 0.05). When patients were stratified with four prognostic factors including ECOG performance status, Child-Pugh class, AFP level, and number of brain lesions, median survival time for patients with 0-1, 2, 3-4 risk factors were 5.8 months, 2.5 months and 0.6 months, respectively (p < 0.001). In conclusion, we can estimate the survival of patients by prognostic stratification, although overall prognosis of patients with brain metastases from hepatocellular carcinoma is poor.

  15. DIAGNOSTIC PITFALLS OF BRAIN METASTASES AFTER BRAIN IRRADIATION

    Directory of Open Access Journals (Sweden)

    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.

  16. Stereotactic Radiosurgery for Metastases in Eloquent Central Brain Locations.

    Science.gov (United States)

    Hsu, Fred; Nichol, Alan; Ma, Roy; Kouhestani, Para; Toyota, Brian; McKenzie, Michael

    2015-09-01

    To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.

  17. Surgical resection and permanent iodine-125 brachytherapy for brain metastases.

    Science.gov (United States)

    Huang, Kim; Sneed, Penny K; Kunwar, Sandeep; Kragten, Annemarie; Larson, David A; Berger, Mitchel S; Chan, Albert; Pouliot, Jean; McDermott, Michael W

    2009-01-01

    To evaluate the efficacy and toxicity of surgical resection and permanent iodine-125 brachytherapy without adjuvant whole brain radiation therapy (WBRT) for brain metastases. Forty patients were treated with permanent iodine-125 brachytherapy at the time of resection of brain metastases from 1997 to 2003. Actuarial freedom from progression (FFP) and survival were measured from the date of surgery and estimated using the Kaplan-Meier method, with censoring at last imaging for FFP endpoints. The median survival was 11.3 months overall, 12.0 months in 19 patients with newly diagnosed brain metastases and 7.3 months in 21 patients with recurrent brain metastases. Twenty-two patients (55%) remained free of progression of brain metastases, three failed at the resection cavity (including one with leptomeningeal dissemination), two failed with leptomeningeal spread only, and 13 failed elsewhere in the brain including two who also had leptomeningeal disease. The 1-year resection cavity FFP probabilities were 92%, 86% and 88%; and brain FFP probabilities were 29%, 43% and 37% for the newly diagnosed, recurrent and all patients, respectively. Symptomatic necrosis developed 7.4-40.0 months (median, 19.5 months) after brachytherapy in 9 patients (23%), confirmed by resection in 6 patients. Excellent local control was achieved using permanent iodine-125 brachytherapy for brain metastasis resection cavities, although there is a high risk of radiation necrosis over time. These data support consideration of permanent brachytherapy without adjuvant WBRT as a treatment option in patients with symptomatic or large newly diagnosed or recurrent brain metastases.

  18. 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...... to clinical cerebral progression. Conclusion. We identified four prognostic factors related to survival after SRT for brain metastases. The grouping of patients by these factors is useful to determine the level of treatment. We discourage the delivery of SRT to patients with 3-4 unfavourable prognostic...

  19. Ganging Up on Brain Metastases | Center for Cancer Research

    Science.gov (United States)

    When primary tumors metastasize to the brain, the prognosis for patients is poor. The currently accepted treatment is whole-brain radiation therapy, and the median survival time is several months. Since these types of tumors form in 10 to 30 percent of adult cancer patients, improvements in treatment methods are a necessity.  

  20. Mutations targeting the coagulation pathway are enriched in brain metastases

    NARCIS (Netherlands)

    Richichi, C. (Cristina); Fornasari, L. (Lorenzo); Melloni, G.E.M. (Giorgio E. M.); Brescia, P. (Paola); Patanè, M. (Monica); Del Bene, M. (Massimiliano); D.A.M. Mustafa (Dana); J.M. Kros (Johan); Pollo, B. (Bianca); Pruneri, G. (Giancarlo); Sciandivasci, A. (Angela); Munzone, E. (Elisabetta); Dimeco, F. (Francesco); Pelicci, P.G. (Pier Giuseppe); Riva, L. (Laura); Pelicci, G. (Giuliana)

    2017-01-01

    textabstractBrain metastases (BMs) are the most common malignancy of the central nervous system. Recently it has been demonstrated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggesting that mutations in serpins or other members of the coagulation cascade can

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

    Science.gov (United States)

    2014-01-01

    In many patients with brain metastases, the primary therapeutic aim is symptom palliation and maintenance of neurologic function, but in a subgroup, long-term survival is possible. Local control in the brain, and absent or controlled extracranial sites of disease are prerequisites for favorable survival. Stereotactic radiosurgery (SRS) is a focal, highly precise treatment option with a long track record. Its clinical development and implementation by several pioneering institutions eventually rendered possible cooperative group randomized trials. A systematic review of those studies and other landmark studies was undertaken. Most clinicians are aware of the potential benefits of SRS such as a short treatment time, a high probability of treated-lesion control and, when adhering to typical dose/volume recommendations, a low normal tissue complication probability. However, SRS as sole first-line treatment carries a risk of failure in non-treated brain regions, which has resulted in controversy around when to add whole-brain radiotherapy (WBRT). SRS might also be prescribed as salvage treatment in patients relapsing despite previous SRS and/or WBRT. An optimal balance between intracranial control and side effects requires continued research efforts. PMID:25016309

  2. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

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

  3. Pathologic complete response in renal cell carcinoma brain metastases treated with stereotactic radiosurgery.

    Science.gov (United States)

    Teh, Bin S; Bloch, Charles; Paulino, Arnold C; Shen, Steven; Hinckley, Lisa; Baskin, David; Butler, Edward B; Amato, Robert

    2007-06-01

    Renal cell carcinoma (RCC) is often regarded as a radiation-resistant tumor. However, radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole-brain irradiation has been used to treat brain metastases from RCC. To date, there have been no clinical pathologic correlative findings before and after RT. Herein, we present a case of a patient with brain metastases from RCC treated with SRS. The diagnosis of clear-cell RCC was made in 2001 after right radical nephrectomy. He was also found to have lung metastases at diagnosis. He presented with neurologic symptoms in 2004, and magnetic resonance imaging showed 3 brain lesions with a significant amount of edema consistent with brain metastases. The largest lesion caused a midline shift and was surgically resected. Pathology revealed metastatic RCC. The other 2 smaller brain lesions were treated at 20 Gy respectively with shaped-beam SRS using the BrainLab Novalis system. No whole-brain irradiation was delivered. However, the patient had difficulty weaning off his steroids, and a magnetic resonance imaging performed 6 months after SRS was read as "progression of the lesions." He then underwent resection of both the irradiated brain lesions. Pathologic examination revealed necrotic tissues without any viable tumor identified. The patient has since been doing very well, now 18 months after SRS and 5 years from the initial diagnosis. This is the first reported case that demonstrates that precise high-dose radiation in the form of SRS can cause significant tumor cell death (pathologic complete response) in radiation-resistant brain metastases from RCC. This finding also provides a rationale to deliver stereotactic body RT for primary and metastatic RCC extracranially. A prospective clinical trial using stereotactic body RT for primary and metastatic RCC is under way.

  4. 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.

  5. Current challenges in the management of breast cancer brain metastases.

    Science.gov (United States)

    O'Sullivan, Ciara C; Davarpanah, Nicole N; Abraham, Jame; Bates, Susan E

    2017-04-01

    Approximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop breast cancer brain metastases (BCBM), which are associated with significant morbidity and mortality. The advent of HER2-directed therapy resulted in greatly improved survival outcomes, but unfortunately at the price of an increased cumulative incidence of BCBM. We review challenges in the management of BCBM, and potential treatment strategies, including novel agents such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (olaparib, veliparib), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, abemaciclib), and taxane derivatives (eg, ANG1005 and TPI-287). The utility of human epidermal growth factor 2 (HER2)-directed therapies-lapatinib, ado-trastuzumab emtansine (T-DM1), neratinib and tucatinib-is also being studied in this setting. We address the need for improved imaging techniques and innovation in clinical trial design. For example, the current practice is to initially administer whole-brain radiotherapy (WBRT) as treatment for patients with multiple BCBM. However, in selected circumstances, first-line systemic treatment may be more appropriate in order to avoid neurocognitive toxicities, and potential options should be evaluated in window of opportunity trials. Other strategies that may aid development of more effective clinical trials and expedite the development of promising agents include the use of different clinical endpoints and different imaging tools. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Patrick N Harter

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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Renal carcinoma with brain metastases. Prognostic factors and treatment outcomes

    Directory of Open Access Journals (Sweden)

    A. V. Golanov

    2016-01-01

    Full Text Available Introduction. Surgical excision followed by whole-brain radiotherapy (WBRT is a traditional treatment option for solitary brain metastases (SBM of renal carcinoma. In the presence of multiple brain metastases of renal carcinoma WBRT remains to be the most common treatment option in this group of patients. However, the effectiveness of WBRT is insufficient due to radioresistance of renal carcinoma. After introduction of the standards in the radiosurgical practice, treatment options of renal carcinoma have been changed, since radiosurgery may overcome WBRT limitations in the treatment of brain metastases of radioresistant tumorsObjective: to study the effectiveness of stereotactic radiosurgery by using “Gamma Knife” device in the treatment of brain metastases of renal carcinoma.Materials and methods. We have analyzed results of the treatment of 112 patients with brain metastases of renal carcinoma who underwent radiosurgical treatment in Moscow Center “Gamma Knife”. Age median of the patients was 58 (33 –77 years. Total number of irradiated metastatic foci – 444, an average number of brain metastases in 1 patient was 4 (1–30. Twenty eight (25.0 % patients had a single brain metastasis. A median of cumulative volume of brain metastases for each patient was 5.9 (0.1–29.1 cm3. An average value of the marginal dose for metastatic lesion was 22 (12–26 Gy, mean value of isodose used for treatment planning was 64 (39-99 %.Results. An overall survival (OS rate after radiosurgical treatment was 37.7; 16.4 and 9.3 % for 12, 24 and 36 months, respectively. A median OS was 9.1 months (95% confidence interval (CI 7.1–11.8. New brain metastases (distant recurrences following radiosurgical treatment occurred in 44 (54.3 % patients, with a median of 10.1 months (95 % CI:7-18. Local recurrences after radiosurgical treatment were detected in 19 (17 % patients with a median time of 6.6 months (95 % CI 4.0–9.6. Factors associated with the best

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Liyan QU

    2016-08-01

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

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

    DEFF Research Database (Denmark)

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

    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...

  13. Management of patients with ≥4 brain metastases using stereotactic radiosurgery boost after whole brain irradiation.

    Science.gov (United States)

    Dincoglan, Ferrat; Sager, Omer; Gamsiz, Hakan; Uysal, Bora; Demiral, Selcuk; Oysul, Kaan; Sirin, Sait; Caglan, Ayca; Beyzadeoglu, Murat

    2014-01-01

    Brain metastases are a prevalent consequence of systemic cancer, and patients suffering from brain metastases usually present with multiple metastatic lesions. An overwhelming majority of the available literature assessing the role of stereotactic radiosurgery in brain metastasis management includes patients with up to 4 metastases. Given the significant benefit of stereotactic radiosurgery for the treatment of 1 to 3 brain metastases, we evaluated the use of stereotactic radiosurgery boost after whole brain irradiation in the management of patients with ≥4 brain metastases. In this retrospective analysis, outcomes of 50 patients who underwent linear accelerator-based stereotactic radiosurgery boost within 4 to 6 weeks of whole brain irradiation for ≥4 brain metastases were assessed in terms of local control, overall survival, primary involved organ, recursive partitioning analysis class and Karnofsky performance status at the time of stereotactic radiosurgery, number of lesions, age, status of the primary cancer (controlled vs uncontrolled), presence of extracranial disease and toxicity. Fifty patients with ≥4 brain metastases were treated using linear accelerator-based stereotactic radiosurgery boost after whole brain irradiation between April 1998 and April 2013. Mean and median number of intracranial lesions was 6.02 and 6, respectively. Median lesion volume was 10.9 cc (range, 0.05-32.6). Median survival time after radiosurgery was 10.1 months (range, 1-25). Status of the primary cancer (controlled vs uncontrolled), recursive partitioning analysis class, Karnofsky performance status, and extracranial metastasis showed statistically significant correlations with overall survival (P stereotactic radiosurgery included temporary edema (n = 14, 28%), hemiparesis (n = 1, 2%), seizure (n = 1, 2%), leukoencephalopathy (n = 2, 4%), and radiation necrosis (n = 6, 12%). Linear accelerator-based stereotactic radiosurgery boost within 4 to 6 weeks after whole brain

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

    Science.gov (United States)

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

    2015-10-13

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

  15. Novel Treatment Strategies for Brain Metastases in Non-small-cell Lung Cancer.

    Science.gov (United States)

    Bui, Nam; Woodward, Brian; Johnson, Anna; Husain, Hatim

    2016-05-01

    Brain metastases are common in patients with non-small cell lung cancer (NSCLC), and due to associated poor prognosis, this field is an important area of need for the development of innovative medical therapies. Therapies including local approaches through surgical intervention and/or radiation and evolving systemic therapies have led to improvements in the treatment of brain metastases in patients with lung cancer. Strategies that consider applying advanced radiation techniques to minimize toxicity, intervening early with effective systemic therapies to spare radiation/surgery, testing radiosensitization combinations, and developing drug penetrant molecules have and will continue to define new practice patterns. We believe that in carefully considered asymptomatic patients, first-line systemic therapy may be considered before radiation therapy and small-molecule targeted therapy may provide an opportunity to defer radiation therapy for recurrence or progression of disease. The next several years in oncology drug development will see the reporting on of brain penetrant molecules in oncogene-defined non-small cell lung cancer. Ongoing studies will evaluate immunotherapies in patients with brain metastases with associated endpoints. We hope that continued drug development and carefully designed clinical trials may afford an opportunity to improve the lives of patients with brain metastases.

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

    Science.gov (United States)

    Liu, Yan; Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lau, Steven; Lu, Weiguo; Yan, Yulong; Jiang, Steve B; Zhen, Xin; Timmerman, Robert; Nedzi, Lucien; Gu, Xuejun

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yan Liu

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

  18. 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

  19. Control of brain metastases using frameless image-guided radiosurgery.

    Science.gov (United States)

    Chen, Joseph C T; Bugoci, Darlene M; Girvigian, Michael R; Miller, Michael J; Arellano, Alonso; Rahimian, Javad

    2009-12-01

    Radiosurgery is an important and well-accepted method in the management of brain metastases. Using conventional frame-based techniques, high lesional control rates are expected. The introduction of image-guided techniques allows for improved patient comfort and workflow. Some controversy exists as to the accuracy of imageguided techniques and consequently the impact they might have on control of brain metastases (as opposed to the level of control achieved with frame-based methods). The authors describe their initial 15-month experience with image-guided radiosurgery (IGRS) using Novalis with ExacTrac for management of brain metastases. The authors reviewed the cases of brain metastasis treated by means of IGRS in their tertiary regional radiation oncology service over a 15-month period. During the study period 54 patients (median age 57.9 years) harboring 108 metastases were treated with IGRS. The median time from cancer diagnosis to development of brain metastasis was 12 months (range 0-144 months). The median tumor volume was 0.98 cm(3) (range 0.03-19.07 cm(3)). The median prescribed dose was 18 Gy to the 80% isodose line (range 14-20 Gy). Lesions were followed with postradiosurgery MR imaging every 2-3 months following treatment. The median follow-up period was 9 months (range 0-20 months). Median actuarial survival was 8.6 months following IGRS. Eight patients with 18 lesions died within the first 2 months after the procedure, before scheduled follow-up imaging. Thus 90 lesions (in 46 patients) were followed up with imaging studies. Lesions that were unchanged or reduced in size were considered to be under control. The 6-month actuarial lesion control rate was 88%. Smaller lesions (Novalis with ExacTrac is equivalent to frame-based radiosurgery methods.

  20. Patient-derived xenografts from non-small cell lung cancer brain metastases are valuable translational platforms for the development of personalized targeted therapy.

    Science.gov (United States)

    Lee, Hye Won; Lee, Jung-Il; Lee, Se Jeong; Cho, Hyun Jung; Song, Hye Jin; Jeong, Da Eun; Seo, Yun Jee; Shin, Sang; Joung, Je-Gun; Kwon, Yong-Jun; Choi, Yoon-La; Park, Woong-Yang; Lee, Hyun Moo; Seol, Ho Jun; Shim, Young Mog; Joo, Kyeung Min; Nam, Do-Hyun

    2015-03-01

    The increasing prevalence of distant metastases from non-small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies. We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment. NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions. Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments. ©2014 American Association for Cancer Research.

  1. [Biology of brain metastases: current concepts].

    Science.gov (United States)

    Kehrli, P

    1999-12-01

    Brain metastasis results from complex interactions between host cells and primitive tumor cells. An analysis of the molecular pathways at the cellular level is provided in this review of the literature. The principal new therapeutic modalities are directly based on our comprehension of those molecular biology hypothesis.

  2. Multiple brain metastases irradiation with Eleka Axesse stereotactic system

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-12-04

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1-3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p=0.59). Age ≤59 years showed a trend towards improved local control on univariate (p=0.066) and multivariate analysis (p=0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p=0.040) and ECOG 0-1 (p=0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p=0.039) and performance status (p=0.028) maintained significance on multivariate analysis. ECOG 0-1 was positively correlated with survival on univariate analysis (pbreast cancer patients with few brain metastases, radiosurgery plus whole-brain radiotherapy resulted in significantly better freedom from new brain metastases than radiosurgery alone. However, this advantage did not lead to significantly better survival.

  5. Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Yasojima, Hiroyuki; Iwasa, Tsutomu; Kanbayashi, Chizuko; Oshitanai, Risa; Tsuneizumi, Michiko; Watanabe, Ken-Ichi; Matsui, Akira; Fujisawa, Tomomi; Saji, Shigehira; Masuda, Norikazu; Tokuda, Yutaka; Iwata, Hiroji

    2017-11-28

    Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored. The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P L1, PD-L2, and HLA class I was also performed. There are significantly fewer TILs in brain metastases than in primary breast tumors.

  6. Rare clinical experiences for surgical treatment of melanoma with osseous metastases in Taiwan

    Directory of Open Access Journals (Sweden)

    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.

  7. Clinical features of choroidal metastases from carcinoid tumour.

    Science.gov (United States)

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

    2004-03-01

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

  8. Treatment of Single or Multiple Brain Metastases by Hypofractionated Stereotactic Radiotherapy Using Helical Tomotherapy

    Directory of Open Access Journals (Sweden)

    Aiko Nagai

    2014-04-01

    Full Text Available This study investigated the clinical outcomes of a 4-fraction stereotactic radiotherapy (SRT study using helical tomotherapy for brain metastases. Between August 2009 and June 2013, 54 patients with a total of 128 brain metastases underwent SRT using tomotherapy. A total dose of 28 or 28.8 Gy at 80% isodose was administered in 4 fractions for all tumors. The mean gross tumor volume (GTV was 1.9 cc. Local control (LC rates at 6, 12, and 18 months were 96%, 91%, and 88%, respectively. The 12-month LC rates for tumors with GTV ≤0.25, >0.25 and ≤1, and >1 cc were 98%, 82%, and 93%, respectively; the rates were 92% for tumors >3 cc and 100% for >10 cc. The 6-month rates for freedom from distant brain failure were 57%, 71%, and 55% for patients with 1, 2, and >3 brain metastases, respectively. No differences were significant. No major complications were observed. The 4-fraction SRT protocol provided excellent tumor control with minimal toxicity. Distant brain failure was not so frequent, even in patients with multiple tumors. The results of the current study warrant a prospective randomized study comparing single-fraction stereotactic radiosurgery (SRS with SRT in this patient population.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Clinical Characteristics of Lung Cancer with Pancreatic Metastases

    Directory of Open Access Journals (Sweden)

    Jianchun DUAN

    2017-08-01

    Full Text Available Background and objective Lacking of typical symptoms, more than 70% of patients with lung cancer are diagnosed as advanced-stage disease. Patients suffer from solid organs metastasis with different clinical features and prognosis. With development of new technology, more and more lung cancer patients are diagnosed with pancreatic metastasis. The aim of this study was to investigate clinicopathologic and survival difference by retrospective analysis among lung cancer patients with pancreatic metastases. Methods Of the patients with lung cancer diagnosed by pathology and thorough staging evaluation and treated at Beijing Cancer Hospital with long follow-up during July 1996 and June 2017, 35 cases had pancreatic metastases. Results There were 28 cases diagnosed as small cell lung cancer, 3 cases diagnosed as adenocarcinoma and 4 cases diagnosed as squamous cell carcinoma. There were 15 cases with pancreatic metastases in head of pancreas and 20 cases in body and tail of pancreas, 23 cases presented with isolated metastasis and 12 cases with multiple metastases. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases. Conclusion Pancreatic metastases represents an uncommon site of extrathoracic spread of disease for part of patients with advanced lung cancer. Lung cancer with pancreatic metastases should be treated by combined therapy, especially by systemic chemotherapy. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases.

  11. Undiagnosed Esophageal Adenocarcinoma Presenting as Multiple Brain Metastases

    Directory of Open Access Journals (Sweden)

    Vincent Grzywacz

    2017-10-01

    Full Text Available Brain metastases from gastrointestinal malignancies are exceedingly rare occurrences that carry a very poor prognosis. This holds especially true in cases where brain metastases from esophageal primaries are the initial presentation of a previously unidentified gastrointestinal malignancy. Our patient, a 60-year-old male with a past history of a right temporal teratoma, family history of breast cancer, and no smoking history, presented with a chief complaint of recurrent headaches. His history of present illness and physical examination included a two-month history of frontal headache, progressive fatigue, and unintentional weight loss. He underwent an extensive initial workup including CT-head, CT-abdomen/pelvis, CT-chest, bone scan, tumor marker analysis, and MRI-brain. The initial head CT revealed multiple intracranial lesions suspicious for malignancy. A PET scan later revealed his primary to be a malignancy of the distal esophagus. His treatment course thus far has been aggressive, consisting of surgical resection, systemic chemotherapy with capcetibine-oxaliplatin as well as paclitaxel-carboplatin, and radiation therapy. He has had several recurrences since starting treatment, but has continued to maintain a good performance status with only minor symptoms. Currently, the patient has survived for 17 months after his diagnosis of stage IV (T3, N2, M1 moderately differentiated adenocarcinoma and is undergoing treatment with trastuzumab and stereotactic radiosurgery. This report demonstrates that although cases of esophageal adenocarcinoma that present as brain metastases typically carry a poor prognosis, with early and aggressive treatment patients can survive well past one year after diagnosis.

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

  14. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study

    NARCIS (Netherlands)

    Postmus, PE; Haaxma-Reiche, H; Gregor, A; Groen, HJM; Lewinski, T; Scolard, T; Kirkpatrick, A; Curran, D; Sahmoud, T; Giaccone, G

    Background and purpose: To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. Patients and methods: The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Stephan Ellmann

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

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

  18. Rationale for the use of upfront whole brain irradiation in patients with brain metastases from breast cancer.

    Science.gov (United States)

    Tallet, Agnes V; Azria, David; Le Rhun, Emilie; Barlesi, Fabrice; Carpentier, Antoine F; Gonçalves, Antony; Taillibert, Sophie; Dhermain, Frédéric; Spano, Jean-Philippe; Metellus, Philippe

    2014-05-08

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

  19. Mutations targeting the coagulation pathway are enriched in brain metastases.

    Science.gov (United States)

    Richichi, Cristina; Fornasari, Lorenzo; Melloni, Giorgio E M; Brescia, Paola; Patanè, Monica; Del Bene, Massimiliano; Mustafa, Dana A M; Kros, Johan M; Pollo, Bianca; Pruneri, Giancarlo; Sciandivasci, Angela; Munzone, Elisabetta; DiMeco, Francesco; Pelicci, Pier Giuseppe; Riva, Laura; Pelicci, Giuliana

    2017-07-26

    Brain metastases (BMs) are the most common malignancy of the central nervous system. Recently it has been demonstrated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggesting that mutations in serpins or other members of the coagulation cascade can provide critical advantages during BM formation. We performed whole-exome sequencing on matched samples of breast cancer and BMs and found mutations in the coagulation pathway genes in 5 out of 10 BM samples. We then investigated the mutational status of 33 genes belonging to the coagulation cascade in a panel of 29 BMs and we identified 56 Single Nucleotide Variants (SNVs). The frequency of gene mutations of the pathway was significantly higher in BMs than in primary tumours, and SERPINI1 was the most frequently mutated gene in BMs. These findings provide direction in the development of new strategies for the treatment of BMs.

  20. Stereotactic Radiosurgery Alone for One to Two Brain Metastases from Cancer of Unknown Primary.

    Science.gov (United States)

    Dziggel, Liesa; Bajrovic, Amira; Schild, Steven E; Rades, Dirk

    2018-01-01

    The use of stereotactic radiosurgery (SRS) alone has become popular for treating patients with a limited number of brain metastases. In very few patients, the primary tumor leading to cerebral spread is unknown. This study investigated the role of SRS for this rare situation. Eight patients with 1-2 brain metastases from cancer of unknown primary (CUP) received SRS alone (median dose 20 Gy). Five clinical factors were evaluated for association with local control of the irradiated lesions, freedom from new cerebral lesions and survival. Six-month and 12-month survival rates were 63% and 63%, respectively. Improved survival was associated with male gender and only one cerebral lesion. Local control rates at 6 and 12 months were 100%. Six-month rate of freedom from new cerebral lesions was 86%. SRS appeared effective and resulted in promising local control and survival rates in patients with 1-2 brain metastases from CUP. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Prevalence of detecting unknown cerebral metastases in fluorodeoxyglucose positron emission tomography/computed tomography and its potential clinical impact.

    Science.gov (United States)

    Kung, Boom Ting; Auyong, T K; Tong, C M

    2014-05-01

    To determine the prevalence of incidental finding of unknown cerebral metastases and explore the clinical impact of detecting unknown brain metastases among individuals underwent whole body fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) with brain included in field of view. A retrospective review of 1876 patients who underwent whole body PET/CT examination in our clinical PET center for oncological evaluation from January 2009 to September 2009 was performed. The total number and prevalence of unknown brain metastases detected by PET/CT were calculated. Patients diagnosed with cerebral metastases by PET/CT were further analyzed via the electronic patient record system for relevant clinical and radiological findings. Positive predictive value of PET/CT for the diagnosis of cerebral metastases was calculated with reference to contrast enhanced magnetic resonance imaging (MRI) or contrast enhanced CT. Of the 1876 subjects, 71 patients (3.8%) were diagnosed with cerebral metastases by PET/CT. 31 patients were already diagnosed with brain metastases before PET/CT. Among the 40 patients with unknown brain metastasis, 24 (60.0%) underwent either MRI (n = 5) or CT (n = 19) after PET/CT, of which 17 patients were confirmed with cerebral metastases. The true positive rate was 70.8% (17/24), while the false positive rate of PET/CT was 29.2% (7/24). Nearly 94.1% (16/17) patients with confirmed cerebral metastases on MRI or CT had subsequent change in management. Among the remaining 16 patients with positive findings of cerebral metastases without further radiological correlation, 43.8% (7/16) patients had change in management after PET/CT. A total of 57.5% (23/40) patients had change in management after PET/CT. The point prevalence of detecting unknown cerebral metastases by PET/CT was 2.1% (40/1876). 94.1% patients with newly diagnosed brain metastases confirmed with either MRI or CT received immediate treatment for cerebral

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

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

  4. 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.

  5. Predicting compliance and survival in palliative whole-brain radiotherapy for brain metastases.

    Science.gov (United States)

    Sabater, Sebastià; Mur, Encarna; Müller, Katrin; Arenas, Meritxell

    2012-01-01

    Brain radiotherapy is the main treatment for patients with brain metastases but its goal is just symptom control. Our aim was to study if different performance tools, used in geriatric practice, could improve patient selection for decision-making in the palliative brain radiotherapy setting. Data from 61 consecutive patients were analysed. In addition to Karnofsky Performance Status (KPS) their physical activity was assessed by means of the activity of daily living (ADL) and instrumental ADL (IADL) scales. A neurocognitive evaluation was performed with the Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) and with the Mini-Mental Status Exam (MMSE). Radiotherapy compliance and short survival were the endpoints of the study. High rates of cognitive impairment were found by both neurocognitive tools (Pfeiffer: 19.7% of patients; MMSE: 30%). Dependence was also highly prevalent, either measured by the ADL (50.8%) or by the IADL (43.3%). Nearly one third (27.9%) of patients died soon after radiotherapy evaluation. Longer survival was related to female, younger than 60 years, breast cancer primary tumour, steroid response, RPA class, and higher performance and neurocognitive score tools. A premature death was associated with neurocognitive tools, IADL and longer interval from brain metastatic diagnosis to radiotherapy. Twenty-three percent of patients were not able to finish the WBRT course due to clinical deterioration. The only variable related to compliance was a low MMSE score. Results suggest that the geriatric tools analysed could offer information on brain palliative radiotherapy complementary to that offered by the more usual tools. It will be interesting to study if our data could be extrapolated to the general palliative oncological field.

  6. Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer.

    Science.gov (United States)

    Nayak, Lakshmi; DeAngelis, Lisa M; Robins, H Ian; Govindan, Ramaswamy; Gadgeel, Shirish; Kelly, Karen; Rigas, James R; Peereboom, David M; Rosenfeld, Steven S; Muzikansky, Alona; Zheng, Ming; Urban, Patrick; Abrey, Lauren E; Omuro, Antonio; Wen, Patrick Y

    2015-12-01

    Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. Adult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m(2) every 3 weeks. The primary endpoint of this multinomial 2-stage study combined early progression (EP; death or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w) to determine drug activity. Fifty patients with a median age of 60 years (range, 33-74 years) were enrolled; the majority were men (58%), and most had received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas under the concentration-time curve from time zero to 504 hours for cycles 1 and 3 of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution volume of 755 L/m(2) . Grade 3/4 adverse events (AEs), regardless of their relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of 32 deaths were due to brain metastases. The median time to progression and the overall survival were 3.2 and 8.8 months, respectively. This is the first prospective study of chemotherapy for recurrent brain metastases from NSCLC. In this population, patupilone demonstrated activity in heavily treated patients. © 2015 American Cancer Society.

  7. Strategies for preservation of memory function in patients with brain metastases.

    Science.gov (United States)

    Dye, Nicholas B; Gondi, Vinai; Mehta, Minesh P

    2015-06-01

    Cognitive decline, particularly in memory, is a side effect seen in patients with brain metastases and when severe, can have a significant impact on their quality of life. It is most often the result of multiple intersecting etiologic factors, including the use of whole brain radiation therapy, effects of which, in part, are mediated by damage within the hippocampus. A variety of clinical factors and comorbidities may impact the likelihood and severity of this cognitive decline, and affected patients should be considered for evaluation in a comprehensive neuro-rehabilitation or "brain fitness" program. Avoiding WBRT is warranted for some patients with brain metastases; particularly those memory decline compared to historical controls without compromising treatment efficacy. Additionally, the NMDA receptor antagonist memantine and renin-angiotensin-aldosterone system (RAAS) blockers have shown promise as neuroprotective agents that could be used prophylactically with radiation. After the onset of neurocognitive decline the treatment is largely symptom-driven, however simply screening for and treating depression, fatigue, anxiety, cognitive slowing, and other processes may alleviate some impairment. Stimulants such as methylphenidate may be useful in treating symptoms of fatigue and cognitive slowing. Other treatments including donepezil and cognitive rehabilitation have been extensively tested in the population at risk for dementia, although they have not been adequately studied in patients following cranial radiotherapy. An innovative hypothetical approach is the use of intranasal metabolic stimulants such as low dose insulin, which could be valuable in improving cognition and memory, by reversing impaired brain metabolic activity. Prevention of neurocognitive decline in patients with brain metastases requires a multimodal approach tailored to each patient's need, avoiding WBRT in some, altering the WBRT plan in others, and/or using neuroprotective prophylaxis in

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

    Science.gov (United States)

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

    2015-07-23

    To retrospectively access outcome and prognostic parameters of linear accelerator-based stereotactic radiosurgery in brain metastases from malignant melanoma. Between 1990 and 2011 140 brain metastases in 84 patients with malignant melanoma (median age 56 years) were treated with stereotactic radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed extracerebral control. The median count of brain metastases in a single patient was 1, the median diameter was 12 mm. The median dose applied was 20 Gy/80 % isodose enclosing. The median follow-up was 7 months and the median overall survival 9 months. The 6-, 12- and 24 month overall survival rates were 71 %, 39 % and 25 % respectively. Cerebral follow-up imaging showed complete remission in 20 brain metastases, partial remission in 39 brain metastases, stable disease in 54 brain metastases, progressive disease in 24 brain metastases and pseudo-progression in 3 brain metastases. Median intracerebral control was 5.3 months and the 6- and 12-month intracerebral progression-free survival rates 48 % and 38 %, respectively. Upon univariate analysis, extracerebral control (log-rank, p stereotactic radiosurgery (log-rank, p stereotactic radiosurgery high dose region. Stereotactic radiosurgery is a well-tolerated and effective treatment option for brain metastases in malignant melanoma and was able to achieve local remissions in several cases. Furthermore, especially patients with controlled extracerebral disease and a low count of brain metastases seem to benefit from this treatment modality. Prospective trials analysing the effects of combined stereotactic radiosurgery and new systemic agents are warranted.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  11. Examination of the predictive factors of the response to whole brain radiotherapy for brain metastases from lung cancer using MRI.

    Science.gov (United States)

    Aoki, Shuri; Kanda, Tomonori; Matsutani, Noriyuki; Seki, Nobuhiko; Kawamura, Masafumi; Furui, Shigeru; Yamashita, Hideomi

    2017-07-01

    Previous studies have been conducted on the prognostic factors for overall survival in patients with brain metastases (BMs) following whole brain radiotherapy (WBRT). However, there have been a small number of studies regarding the prognostic factors for the response of tumor to WBRT. The aim of the present study was to identify the predictive factors for the response to WBRT from the point of view of reduction of tumor using magnetic resonance imaging. A retrospective analysis of 62 patients with BMs from primary lung cancer treated with WBRT was undertaken. The effects of the following factors on the response to WBRT were evaluated: Age; sex; performance status; lactate dehydrogenase; pathology; existence of extracranial metastases; activity of extracranial disease; chemo-history; chest radiotherapy history; treatment term; γ-knife radiotherapy; diffusion weighted image signal intensity; tumor diameter; extent of edema and the edema/tumor (E/T) ratio. The association between the reduction of tumors and clinical factors was evaluated using logistic regression analysis. Ppredictive factors for the reduction of tumor. The following 3 factors were significantly associated with the response of tumors to WBRT: The presence of SCLC; an E/T ratio of ≥1.5; and the presence of extracranial metastases. The E/T ratio is a novel index that provides a simple and easy predictive method for use in a clinical setting.

  12. Headache Caused by Brain Metastases of Castration-resistant Prostate Cancer during Cabazitaxel Therapy.

    Science.gov (United States)

    Watanabe, Keitaro; Kosaka, Takeo; Hongo, Hiroshi; Tamaki, Satoshi; Oya, Mototsugu

    2017-04-07

    We describe the case of a 55-year-old man who underwent four cycles of cabazitaxel therapy for castration-resistant prostate cancer (CRPC). After the fourth cycle of cabazitaxel, the patient experienced severe headaches. Brain gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) revealed multiple brain metastases. A few days later, the patient suffered impaired consciousness that progressed rapidly. The patient was treated for the symptoms of increased intracranial pressure and underwent whole-brain radiation. One month later, the patient's consciousness level and headache had improved. Although brain metastases of prostate cancer are rare, the possibility of brain metastases should be considered for prostate cancer patients, especially when a CRPC patient complains of headache. Additionally, even if major conditions such as cerebral hemorrhage are excluded by the use of non-contrast-enhanced computed tomography, brain Gd contrast-enhanced MRI should be performed in consideration of the possibility of brain metastases of prostate cancer.

  13. 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....... Patients diagnosed postpartum were excluded. We summarised the demographic features, treatment decisions, obstetrical and neonatal outcomes. RESULTS: The mean age of the 27 eligible patients was 31years (range 23-41years), of which 13 and 12 patients were diagnosed in the second and third trimesters...... 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....

  14. [Surgical treatment of tumor metastases in the lungs, brain or liver].

    Science.gov (United States)

    van den Berkmortel, F W P J; Ruers, Th J M; Bootsma, G P; Verhagen, A F T; de Mulder, P H M

    2003-05-10

    Metastases are generally an expression of widespread disease and therefore warrant systemic treatment. However, clinical observations have revealed that local surgical treatment might be beneficial in the case of organ-confined metastatic disease. Randomised studies have revealed that in the case of brain metastases, metastasectomy followed by radiotherapy, has a favourable outcome with respect to both the quality of life and overall survival. Retrospective non-randomised studies in selected patient groups show prolonged post-treatment survival in the case of both lung and liver metastasectomy. The most important prognostic factors for metastasectomy are: disease control elsewhere in the body, tumour species, the patient's general condition, and the possibility of a total resection of the metastasis. These factors form the basis of the separate decision-making process for each individual patient.

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

    Energy Technology Data Exchange (ETDEWEB)

    Menassa, L. [Dept. of Radiology, Hotel-Dieu de France, Beirut (Lebanon); Haddad, S. [Dept. of Radiology, Hotel-Dieu de France, Beirut (Lebanon); Aoun, N. [Dept. of Radiology, Hotel-Dieu de France, Beirut (Lebanon); Slaba, S. [Dept. of Radiology, Hotel-Dieu de France, Beirut (Lebanon); Atallah, N. [Dept. of Radiology, Hotel-Dieu de France, Beirut (Lebanon)

    1997-04-01

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

  16. Clinical and molecular complexity of breast cancer metastases.

    Science.gov (United States)

    Kimbung, Siker; Loman, Niklas; Hedenfalk, Ingrid

    2015-12-01

    Clinical oncology is advancing toward a more personalized treatment orientation, making the need to understand the biology of metastasis increasingly acute. Dissecting the complex molecular, genetic and clinical phenotypes underlying the processes involved in the development of metastatic disease, which remains the principal cause of cancer-related deaths, could lead to the identification of more effective prognostication and targeted approaches to prevent and treat metastases. The past decade has witnessed significant progress in the field of cancer metastasis research. Clinical and technological milestones have been reached which have tremendously enriched our understanding of the complex pathways undertaken by primary tumors to progress into lethal metastases and how some of these processes might be amenable to therapy. The aim of this review article is to highlight the recent advances toward unraveling the clinical and molecular complexity of breast cancer metastases. We focus on genes mediating breast cancer metastases and organ-specific tropism, and discuss gene signatures for prediction of metastatic disease. The challenges of translating this information into clinically applicable tools for improving the prognostication of the metastatic potential of a primary breast tumor, as well as for therapeutic interventions against latent and active metastatic disease are addressed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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    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.

  18. Brain Metastases in Gastrointestinal Cancers: Is there a Role for Surgery?

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    Lemke, Johannes; Scheele, Jan; Kapapa, Thomas; von Karstedt, Silvia; Wirtz, Christian Rainer; Henne-Bruns, Doris; Kornmann, Marko

    2014-01-01

    About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is cancer and cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients. PMID:25247579

  19. Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center.

    Science.gov (United States)

    Suki, Dima; Khoury Abdulla, Rami; Ding, Minming; Khatua, Soumen; Sawaya, Raymond

    2014-10-01

    Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only

  20. Risk factors for brain metastases in patients with metastatic colorectal cancer

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    Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

    2017-01-01

    Background: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict...... patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue. Results: Totally...

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

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    Kevin B. Harris

    2017-05-01

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

  2. More than Just the Number of Brain Metastases: Evaluating the Impact of Brain Metastasis Location and Relative Volume on Overall Survival After Stereotactic Radiosurgery.

    Science.gov (United States)

    Emery, Ashley; Trifiletti, Daniel M; Romano, Kara D; Patel, Nirav; Smolkin, Mark E; Sheehan, Jason P

    2017-03-01

    Most evidence describing outcomes of patients with brain metastases is based on number of brain metastases, rather than location or volume. We evaluated the impact of tumor location and relative volume on overall survival (OS) among a large cohort of patients treated with stereotactic radiosurgery. Clinical, radiographic, and dosimetric data were collected on patients treated with first (if multiple) stereotactic radiosurgery for brain metastases. Multivariate analyses were performed to investigate the impact of brain metastasis relative location and volume on OS after stereotactic radiosurgery. Analysis included 300 patients with 817 tumors (116 patients with single brain metastasis). The most common tumor locations were supratentorial (75% of tumors), cerebellar (19%), and brainstem (5%). Median tumor volume was 0.4 mL (range, 0.003-65.0 mL). Tumor-specific factors associated with inferior OS included brainstem location versus both supratentorial and cerebellum locations for particular assumed values of cube root tumor volume (P < 0.001 for each) and increasing total supratentorial tumor volume (P = 0.004). Patients with supratentorial tumors and cerebellar tumors demonstrated similar OS, and cube root total tumor volume within the cerebellum and brainstem did not predict for OS. The presence of brainstem metastases and cumulative supratentorial tumor volume are adverse features that result in inferior survival. These results can be used to inform patient prognosis and future clinical trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Three or More Courses of Stereotactic Radiosurgery for Patients with Multiply Recurrent Brain Metastases.

    Science.gov (United States)

    Kotecha, Rupesh; Damico, Nicholas; Miller, Jacob A; Suh, John H; Murphy, Erin S; Reddy, Chandana A; Barnett, Gene H; Vogelbaum, Michael A; Angelov, Lilyana; Mohammadi, Alireza M; Chao, Samuel T

    2017-06-01

    Although patients with brain metastasis are treated with primary stereotactic radiosurgery (SRS), the use of salvage therapies and their consequence remains understudied. To study the intracranial recurrence patterns and salvage therapies for patients who underwent multiple SRS courses. A retrospective review was performed of 59 patients with brain metastases who underwent ≥3 SRS courses for new lesions. Cox regression analyzed factors predictive for overall survival. The median age at diagnosis was 52 years. Over time, patients underwent a median of 3 courses of SRS (range: 3-8) to a total of 765 different brain metastases. The 6-month risk of distant intracranial recurrence after the first SRS treatment was 64% (95% confidence interval: 52%-77%). Overall survival was 40% (95% confidence interval: 28%-53%) at 24 months. Only 24 patients (41%) had a decline in their Karnofsky Performance Status ≤70 at last office visit. Quality of life was preserved among 77% of patients at 12 months, with 45% experiencing clinically significant improvement during clinical follow-up. Radiation necrosis developed in 10 patients (17%). On multivariate analysis, gender (males, Hazard Ratio [HR]: 2.0, P < .05), Karnofsky Performance Status ≤80 (HR 3.2, P < .001), extracranial metastases (HR: 3.6, P < .001), and a distant intracranial recurrence ≤3 months from initial to repeat SRS (HR: 3.8, P < .001) were associated with a poorer survival. In selected patients, performing ≥3 SRS courses controls intracranial disease. Patients may need salvage SRS for distant intracranial relapse, but focal retreatments are associated with modest toxicity, do not appear to negatively affect a patient's performance status, and help preserve quality of life.

  4. 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

  5. Functional dynamic contrast-enhanced magnetic resonance imaging in an animal model of brain metastases: a pilot study.

    Directory of Open Access Journals (Sweden)

    Linfeng Zheng

    Full Text Available Brain metastasis is a common disease with a poor prognosis. The purpose of this study is to test feasibility and safety of the animal models for brain metastases and to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI to enhance detection of brain metastases.With approval from the institutional animal ethics committee, 18 New Zealand rabbits were randomly divided into three groups: Group A received an intra-carotid infusion (ICI of mannitol followed by VX2 cells; group B received successive ICI of mannitol and heparin followed by VX2 cells; and group C received an ICI of normal saline. The survival rate and clinical symptoms were recorded after inoculation. After two weeks, conventional MRI and DCE-MRI were performed using 3.0 Tesla scanner. The number of tumors and detection rate were analyzed. After MRI measurements, the tumors were stained with hematoxylin-eosin.No rabbits died during the procedure. The rabbits had common symptoms, including loss of appetite, lassitude and lethargy, etc. at 10.8±1.8 days and 8.4±1.5 days post-inoculation in group A and B, respectively. Each animal in groups A and B re-gained the lost weight within 14 days. Brain metastases could be detected by MRI at 14 days post-inoculation in both groups A and B, with metastases manifesting as nodules in the brain parenchyma and thickening in the meninges. DCE-MRI increased the total detection of tumors compared to non-contrast MRI (P<0.05. The detection rates of T1-weighted image, T2-weighted image and DCE-MRI were 12%, 32% and 100%, respectively (P<0.05. Necropsy revealed nodules or thickening meninges in the gross samples and VX2 tumor cytomorphologic features in the slides, which were consistent with the MRI results.The VX2 rabbit model of brain metastases is feasible, as verified by MRI and pathologic findings, and may be a suitable platform for future studies of brain metastases. Functional DCE-MRI can be used to evaluate brain metastases in a

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

    Science.gov (United States)

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

    2017-04-01

    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. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    1983-04-01

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

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

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

    2013-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Ameer L. Elaimy

    2012-01-01

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

  10. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.

    Science.gov (United States)

    Martin, Allison M; Cagney, Daniel N; Catalano, Paul J; Warren, Laura E; Bellon, Jennifer R; Punglia, Rinaa S; Claus, Elizabeth B; Lee, Eudocia Q; Wen, Patrick Y; Haas-Kogan, Daphne A; Alexander, Brian M; Lin, Nancy U; Aizer, Ayal A

    2017-08-01

    Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort. Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer. We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR

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

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

    2013-07-15

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

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

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

    2013-02-01

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

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

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    Pagani, J.J. (Univ. of Texas System Cancer Center, Houston); Hayman, L.A.; Bigelow, R.H.; Libshitz, H.I.; Lepke, R.A.; Wallace, S.

    1983-04-01

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

  14. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

    Science.gov (United States)

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-06-10

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    BACKGROUND: Due to the advanced oncological treatments of cancer, an overall increase in cancer incidence, and better diagnostic tools, the incidence of brain metastases is on the rise. This review addresses the current treatment options for patients with multiple brain metastases, presenting...... electrochemotherapy (ECT) as one of the new experimental treatments for this group of patients. CONCLUSIONS: Neurosurgery, stereotactic surgery, and whole-brain radiotherapy are the evidence-based treatments that can be applied for patients with multiple brain metastases. Treatment with chemotherapy and molecularly...... targeted agents may also be warranted. Several experimental treatments are emerging, one of which is ECT, an effective cancer treatment comprising electric pulses given by electrodes in the tumor tissue, causing electroporation of the cell membrane, and thereby augmenting uptake and the cytotoxicity...

  17. 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.

  18. miR-20b is up-regulated in brain metastases from primary breast cancers

    Science.gov (United States)

    Ahmad, Aamir; Ginnebaugh, Kevin R.; Sethi, Seema; Chen, Wei; Ali, Rouba; Mittal, Sandeep; Sarkar, Fazlul H.

    2015-01-01

    Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target. PMID:25893380

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

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

  1. 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.)

  2. 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

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

    Science.gov (United States)

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

    2015-07-01

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

  4. DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations.

    Science.gov (United States)

    Marzese, Diego M; Scolyer, Richard A; Roqué, Maria; Vargas-Roig, Laura M; Huynh, Jamie L; Wilmott, James S; Murali, Rajmohan; Buckland, Michael E; Barkhoudarian, Garni; Thompson, John F; Morton, Donald L; Kelly, Daniel F; Hoon, Dave S B

    2014-11-01

    The brain is a common target of metastases for melanoma patients. Little is known about the genetic and epigenetic alterations in melanoma brain metastases (MBMs). Unraveling these molecular alterations is a key step in understanding their aggressive nature and identifying novel therapeutic targets. Genome-wide DNA methylation analyses of MBMs (n = 15) and normal brain tissues (n = 91) and simultaneous multigene DNA methylation and gene deletion analyses of metastatic melanoma tissues (99 MBMs and 43 extracranial metastases) were performed. BRAF and NRAS mutations were evaluated in MBMs by targeted sequencing. MBMs showed significant epigenetic heterogeneity. RARB, RASSF1, ESR1, APC, PTEN, and CDH13 genes were frequently hypermethylated. Deletions were frequently detected in the CDKN2A/B locus. Of MBMs, 46.1% and 28.8% had BRAF and NRAS missense mutations, respectively. Compared with lung and liver metastases, MBMs exhibited higher frequency of CDH13 hypermethylation and CDKN2A/B locus deletion. Mutual exclusivity between hypermethylated genes and CDKN2A/B locus deletion identified 2 clinically relevant molecular subtypes of MBMs. CDKN2A/B deletions were associated with multiple MBMs and frequently hypermethylated genes with shorter time to brain metastasis. Melanoma cells that colonize the brain harbor numerous genetically and epigenetically altered genes. This study presents an integrated genomic and epigenomic analysis that reveals MBM-specific molecular alterations and mutually exclusive molecular subtypes. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-01

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

  6. Comparison of short-course versus long-course whole-brain radiotherapy in the treatment of brain metastases

    NARCIS (Netherlands)

    Rades, Dirk; Bohlen, Guenther; Dunst, Juergen; Lohynska, Radka; Veninga, Theo; Stalpers, Lukas; Schild, Steven E.; Dahm-Daphi, Jochen

    2008-01-01

    Whole-brain radiotherapy (WBRT) is the most common treatment for brain metastases. Most of these patients have a poor survival prognosis. Therefore, a short radiation program is preferred, if it provides a similar outcome as longer programs. This study compares 20 Gy in five fractions (treatment

  7. Fractionated SRT using VMAT and Gamma Knife for brain metastases and gliomas--a planning study.

    Science.gov (United States)

    Huss, Marie; Barsoum, Pierre; Dodoo, Ernest; Sinclair, Georges; Toma-Dasu, Iuliana

    2015-11-08

    Stereotactic radiosurgery using Gamma Knife (GK) or linear accelerators has been used for decades to treat brain tumors in one fraction. A new positioning system, Extend™, was introduced by Elekta AB for fractionated stereotactic radiotherapy (SRT) with GK. Another option for fractionated SRT is advanced planning and delivery using linacs and volumetric modulated arc therapy (VMAT). This project aims to assess the performance of GK Extend™ for delivering fractionated SRT by comparing GK treatments plans for brain targets performed using Leksell GammaPlan (LGP) with VMAT treatment plans. Several targets were considered for the planning: simulated metastasis- and glioma-like targets surrounding an organ at risk (OAR), as well as three clinical cases of metastases. Physical parameters such as conformity, gradient index, dose to OARs, and brain volume receiving doses above the threshold associated with risk of damaging healthy tissue, were determined and compared for the treatment plans. The results showed that GK produced better dose distributions for target volumes below 15 cm3, while VMAT results in better dose conformity to the target and lower doses to the OARs in case of fractionated treatments for large or irregular volumes. The volume receiving doses above a threshold associated with increased risk of damage to normal brain tissue was also smaller for VMAT. The GK consistently performed better than VMAT in producing a lower dose-bath to the brain. The above is subjected only to margin-dependent fractionated radiotherapy (CTV/PTV). The results of this study could lead to clinically significant decisions regarding the choice of the radiotherapy technique for brain targets.

  8. The effect of contouring variability on dosimetric parameters for brain metastases treated with stereotactic radiosurgery.

    Science.gov (United States)

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

    2013-12-01

    To quantify the effect of contouring variation on stereotactic radiosurgery plan quality metrics for brain metastases. Fourteen metastases, each contoured by 8 physicians, formed the basis of this study. A template-based dynamic conformal 5-arc dose distribution was developed for each of the 112 contours, and each dose distribution was applied to the 7 other contours in each patient set. Radiation Therapy Oncology Group (RTOG) plan quality metrics and the Paddick conformity index were calculated for each of the 896 combinations of dose distributions and contours. The ratio of largest to smallest contour volume for each metastasis varied from 1.25 to 4.47, with a median value of 1.68 (n=8). The median absolute difference in RTOG conformity index between the value for the reference contour and the values for the alternative contours was 0.35. The variation of the range of conformity index for all contours for a given tumor varied with the tumor size. The high degree of interobserver contouring variation strongly suggests that peer review or consultation should be adopted to standardize tumor volume prescription. Observer confidence was not reflected in contouring consistency. The impact of contouring variability on plan quality metrics, used as criteria for clinical trial protocol compliance, was such that the category of compliance was robust to interobserver effects only 70% of the time. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

    Science.gov (United States)

    Yamamoto, Masaaki; Serizawa, Toru; Shuto, Takashi; Akabane, Atsuya; Higuchi, Yoshinori; Kawagishi, Jun; Yamanaka, Kazuhiro; Sato, Yasunori; Jokura, Hidefumi; Yomo, Shoji; Nagano, Osamu; Kenai, Hiroyuki; Moriki, Akihito; Suzuki, Satoshi; Kida, Yoshihisa; Iwai, Yoshiyasu; Hayashi, Motohiro; Onishi, Hiroaki; Gondo, Masazumi; Sato, Mitsuya; Akimitsu, Tomohide; Kubo, Kenji; Kikuchi, Yasuhiro; Shibasaki, Toru; Goto, Tomoaki; Takanashi, Masami; Mori, Yoshimasa; Takakura, Kintomo; Saeki, Naokatsu; Kunieda, Etsuo; Aoyama, Hidefumi; Momoshima, Suketaka; Tsuchiya, Kazuhiro

    2014-04-01

    We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiorityStereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    MR Razzaghi

    2009-04-01

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

  12. 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. ©2015 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

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

  14. Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

    Science.gov (United States)

    Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

    1984-06-01

    One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    Schild Steven E

    2010-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Trasimeni Guido

    2011-05-01

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

  18. Diagnostic value of gadobutrol versus gadopentetate dimeglumine in enhanced MRI of brain metastases.

    Science.gov (United States)

    Fan, Bing; Li, Meijiao; Wang, Xiaoying; Xu, Yufeng; Li, Feiyu; Zhang, Laiyun; Jiang, Jian; Jiang, Yanyan

    2017-06-01

    .9-26.5%)." Objective evaluation showed that at 3, 7, and 10 minutes the SNR (214.17 ± 85.70 vs. 199.57 ± 85.08, 214.80 ± 86.03 vs. 199.19 ± 84.74, and 213.83 ± 82.46 vs. 193.68 ± 79.59, respectively), CNR (68.64 ± 50.18 vs. 57.88 ± 51.06, 75.42 ± 53.19 vs. 63.74 ± 53.91, and 77.13 ± 51.86 vs. 63.21 ± 51.71, respectively), CE (101.76 ± 63.31 vs. 87.61 ± 64.85, 99.85 ± 61.56 vs. 85.08 ± 64.98, and 100.33 ± 58.63 vs. 82.73 ± 61.73, respectively), CBR (0.48 ± 0.32 vs. 0.40 ± 0.33, 0.54 ± 0.34 vs. 0.46 ± 0.35, and 0.56 ± 0.34 vs. 0.47 ± 0.34, respectively), and CER (0.99 ± 0.69 vs. 0.88 ± 0.81, 0.97 ± 0.68 vs. 0.86 ± 0.84, and 0.98 ± 0.65 vs. 0.85 ± 0.80, respectively) were all higher when using gadobutrol compared with Gd-DTPA in the enhanced MR (repeated measures ANOVA, all P < 0.0001). On Gd-DTPA enhanced images, 289, 292, and 292 lesions at 3, 7, and 10 minutes were detected by the two radiologists, while 295, 301, and 301 lesions were detected on gadobutrol-enhanced images, respectively. Using a 3T T1 FLAIR sequence, gadobutrol (0.1 mmol/kg body weight)-enhanced MR resulted in more conspicuous brain metastases, and more metastases compared with the same dose of Gd-DTPA. A delay time of 7 minutes for postcontrast MRI in patients with brain metastases is suggested in clinical practice. 2 J. MAGN. RESON. IMAGING 2017;45:1827-1834. © 2016 International Society for Magnetic Resonance in Medicine.

  19. [Colorectal liver metastases: history, sciences and clinical practices].

    Science.gov (United States)

    Evrard, Serge

    2014-04-01

    Colorectal liver metastasis is one of the best-known clinical models of multidisciplinary approach. Chemotherapy, targeted therapies, surgery and interventional radiology permitted to obtain up to 40 months of survival in palliative intent for liver metastases only and between 40 to 50% of overall survival in curative intent. Genetic, epigenetic, cellular and tissular processes are more and more well described but attempts to link biological knowledge to clinical practice are still faint. The cut-off between curative and palliative intents is progressively pushed away but consequently, its signification is less clear. Maybe an additional intermediary new concept should be added, the metastatic disease chronicisation? Evaluating the patient benefice is difficult and should stand on progression free survival as surrogate marker.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [University Hospital Schleswig-Holstein, Luebeck (Germany). Dept. of Radiation Oncology; Schild, S.E. [Mayo Clinic, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2012-08-15

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

  1. 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 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...

  2. Stereotactic radiation therapy of brain metastases from colorectal cancer: A single institution cohort.

    Science.gov (United States)

    Paix, A; Antoni, D; Adeduntan, R; Noël, G

    2017-05-01

    The brain remains an uncommon site of colorectal cancer metastases. Due to the improvement of overall colorectal cancer patient survival, the incidence of brain metastases will likely rise. We report the efficacy and safety of hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery, and its role in colorectal cancer brain metastasis management. Between June 2010 and December 2014, fifteen consecutive patients received hypofractionnated stereotactic radiation therapy or stereotactic radiosurgery as first local therapy or following surgical removal for colorectal cancer brain metastases. The primary endpoint was overall survival. Secondary endpoints were brain progression free survival, in field control rates and safety. Median follow-up was 41 months (95% confidence interval [CI]: [8.9-73.1 months]), median overall survival was 8 months (95% CI [4.7-11.3 months]), and median brain progression-free survival was 5 months (95% CI [3.9-6.1 months]). Five in field recurrences were observed, which makes a control rate per metastases at 6 and 12 months of 77.8% (95% CI [74.34%-81.26%]), 51.9% (95% CI [44.21%-59.59%]) respectively. Over the 19 treatment sequences, five in field recurences were observed: 6, 12 and 18 months control rate per treatment sequence were 93.3% (95% CI [90.42%-96.18%]), 68.1% (95% CI [62.03%-74.17%]) and 45.4% (95% CI [36.14%-54.66%]) respectively. Immediate tolerance was good with no toxicity grade III or more. Long-term toxicity included two radionecrosis among which, one was symptomatic. The results of this retrospective analysis suggest that hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery are effective and safe treatment modalities for single and multiple small brain metastases from colorectal cancer. However, results need to be confirmed by multicenter, collected data. Copyright © 2017. Published by Elsevier SAS.

  3. Androgen receptor status predicts development of brain metastases in ovarian cancers.

    Science.gov (United States)

    Mittica, Gloria; Senetta, Rebecca; Scotto, Giulia; Aglietta, Massimo; Maggiorotto, Furio; Ghisoni, Eleonora; Genta, Sofia; Boldorini, Renzo; Manini, Claudia; Morra, Isabella; Buosi, Roberta; Sapino, Anna; Cassoni, Paola; Valabrega, Giorgio

    2017-06-20

    Brain metastases are uncommon localizations in epithelial ovarian cancer (EOC), their reported incidence is increasing and no predictive biomarkers have been identified yet. Goals of this study were: i) to define a possible association between Estrogen Receptor (ER), Progesterone Receptor (PR), Androgen Receptor (AR),human EGF receptor 2 (HER2) and brain progression in EOC patients, and ii) to identify differences in ER, PR, AR and HER2 protein expression from primary EOC and its matched resected brain metastasis. A retrospective series of 11 EOC with matched brain metastasis surgically removed was collected. For comparison, a "Control dataset" of 22 patients, without evidence of brain involvement after an adequate follow up was matched. ER, PR, AR and HER2 status were analyzed by means of immunohistochemistry forCases (both primary and metastatic lesions) and Controls.Univariate analysis showed that AR status was significantly associated with brain localization, both considered as discrete variable (cut-off: 10%, p=0.013) and as continuous one (p=0.035). Multivariate analysis confirmed this trend (p=0.053). When considered as continuous variables, ER and AR showed greater expression in primary tumors in comparison with brain metastases (p=0.013 and p=0.032, respectively).In our series, AR predicts brain involvement, with a 9.5 times higher propensity for AR-negative EOC. Moreover, brain dissemination is probably the result of progressive dedifferentiation of primary tumor, shown by reduction of ER and AR expression in metastases. Further studies are required, in order to anticipate and improve multimodal treatment of brain metastases.

  4. 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

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

    Science.gov (United States)

    2014-01-01

    Background When treating cerebral metastases all involved multidisciplinary oncological specialists have to cooperate closely to provide the best care for these patients. For the resection of brain metastasis several studies reported a considerable risk of new postoperative paresis. Pre- and perioperative chemotherapy (Ctx) or radiotherapy (Rtx) alter vasculature and adjacent fiber tracts on the one hand, and many patients already present with paresis prior to surgery on the other hand. As such factors were repeatedly considered risk factors for perioperative complications, we designed this study to also identify risk factors for brain metastases resection. Methods Between 2006 and 2011, we resected 206 brain metastases consecutively, 56 in eloquent motor areas and 150 in non-eloquent ones. We evaluated the influences of preoperative paresis, previous Rtx or Ctx as well as recursive partitioning analysis (RPA) class on postoperative outcome. Results In general, 8.7% of all patients postoperatively developed a new permanent paresis. In contrast to preoperative Ctx, previous Rtx as a single or combined treatment strategy was a significant risk factor for postoperative motor weakness. This risk was even increased in perirolandic and rolandic lesions. Our data show significantly increased risk of new deficits for patients assigned to RPA class 3. Even in non-eloquently located brain metastases the risk of new postoperative paresis has not to be underestimated. Despite the microsurgical approach, our cohort shows a high rate of unexpected residual tumors in postoperative MRI, which supports recent data on brain metastases’ infiltrative nature but might also be the result of our strict study protocol. Conclusions Surgical resection is a safe treatment of brain metastases. However, preoperative Rtx and RPA score 3 have to be taken into account when surgical resection is considered. PMID:24422871

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-01

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

  7. Treatment planning of stereotactic radiosurgery for single brain metastases: impact of leaf width

    NARCIS (Netherlands)

    Emmy Lamers

    2015-01-01

    Purpose/objective: Stereotactic radiosurgery of brain metastases requires highly conformal dose distributions. Besides beams setup, characteristics of the linear accelerator collimator may also play a role. In this study we compared the impact of leaf width on the dose outside the target for

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

    African Journals Online (AJOL)

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

  9. Increased incidence of brain metastases in cutaneous head and neck melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; de Jong, MA; Haaxma-Reiche, H; Nap, R; Kuiper, H; Hoekstra, HJ

    The incidence of cutaneous melanoma is increasing, and 10-20% of these melanomas are located in the head and neck region. The incidence of brain metastases, risk factors and outcome were analysed for melanomas originating in the head and neck region. During the period 1965-2000, 324 patients [12

  10. Osseous metastases of chordoma: imaging and clinical findings

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Connie; Torriani, Martin; Bredella, Miriam [Massachusetts General Hospital, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); Chebib, Ivan [Massachusetts General Hospital, Department of Pathology, Boston, MA (United States)

    2017-03-15

    To describe the imaging and clinical characteristics of chordoma osseous metastases (COM). Our study was IRB approved and HIPAA compliant. A retrospective search of our pathology database for pathology-proven COM yielded 15 patients who had undergone MRI, CT, bone scan, and/or FDG-PET/CT. The imaging and clinical features of the COMs were recorded. A control group of age and gender matched chordoma patients without osseous metastasis was evaluated. The COM mean maximal dimension was 6.4 ± 4.0 cm. The majority (60%) of patients had one lesion. Extra-osseous soft tissue component was present in 85% and was larger than intra-osseous component in 76%. On MRI the lesions were heterogeneous but predominantly T2 hyperintense with hypointense septae, and with variable enhancement. On CT the lesions were typically destructive or permeative; calcifications were rare. The extent of the soft tissue component was isodense to muscle on CT and therefore better evaluated on MRI. COM was in a body part contiguous to the site of the primary tumor. Compared to the controls, COM patients were more likely to have local recurrence (P = 0.0009) and positive resection margins (P = 0.002). At 1 year, 33% of COM patients were deceased and 13% had progressive metastases. COM are associated with large extra-osseous soft tissue components, which are better visualized by MRI. They are often located in a body part contiguous to the site of the primary tumor, portend poor prognosis, and are associated with positive resection margins and local recurrence. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-15

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

  12. 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

    Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...... 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

  13. 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.

  14. The Effects of smoking status and smoking history on patients with brain metastases from lung cancer.

    Science.gov (United States)

    Shenker, Rachel F; McTyre, Emory R; Ruiz, Jimmy; Weaver, Kathryn E; Cramer, Christina; Alphonse-Sullivan, Natalie K; Farris, Michael; Petty, William J; Bonomi, Marcelo R; Watabe, Kounosuke; Laxton, Adrian W; Tatter, Stephen B; Warren, Graham W; Chan, Michael D

    2017-05-01

    There is limited data on the effects of smoking on lung cancer patients with brain metastases. This single institution retrospective study of patients with brain metastases from lung cancer who received stereotactic radiosurgery assessed whether smoking history is associated with overall survival, local control, rate of new brain metastases (brain metastasis velocity), and likelihood of neurologic death after brain metastases. Patients were stratified by adenocarcinoma versus nonadenocarcinoma histologies. Kaplan-Meier analysis was performed for survival endpoints. Competing risk analysis was performed for neurologic death analysis to account for risk of nonneurologic death. Separate linear regression and multivariate analyses were performed to estimate the brain metastasis velocity. Of 366 patients included in the analysis, the median age was 63, 54% were male and, 60% were diagnosed with adenocarcinoma. Current smoking was reported by 37% and 91% had a smoking history. Current smoking status and pack-year history of smoking had no effect on overall survival. There was a trend for an increased risk of neurologic death in nonadenocarcinoma patients who continued to smoke (14%, 35%, and 46% at 6/12/24 months) compared with patients who did not smoke (12%, 23%, and 30%, P = 0.053). Cumulative pack years smoking was associated with an increase in neurologic death for nonadenocarcinoma patients (HR = 1.01, CI: 1.00-1.02, P = 0.046). Increased pack-year history increased brain metastasis velocity in multivariate analysis for overall patients (P = 0.026). Current smokers with nonadenocarcinoma lung cancers had a trend toward greater neurologic death than nonsmokers. Cumulative pack years smoking is associated with a greater brain metastasis velocity. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-15

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

  16. Characterisation of Lesions after Stereotactic Radiosurgery for Brain Metastases: Impact of Delayed Contrast Magnetic Resonance Imaging.

    Science.gov (United States)

    Wagner, S; Gufler, H; Eichner, G; Lanfermann, H

    2017-03-01

    To investigate if brain metastases and radiation injuries after stereotactic radiosurgery (SRS) have different signal intensity (SI) time courses up to 55 min after contrast agent application and if delayed contrast magnetic resonance imaging (MRI) contributes to improve diagnostic accuracy. Thirty-four consecutive patients treated with SRS for cerebral metastases were prospectively enrolled in the study. T1-weighted images were acquired on a 3-Tesla MR unit at three time points, at 2 (TP1), 15 (TP2) and 55 (TP3) min after administering contrast agent. A simultaneous, matched-pairs approach was used for region of interest analysis of the entire contrast-enhancing lesion (SI-e), the centre (SI-c), the border of the lesion (SI-b) and the adjacent non-contrast-enhancing tissue (SI-p). SIs of brain metastases and radiation injuries after SRS were compared using a two-level, linear, mixed-effects regression model. In total, 41 lesions were analysed: 16 metastases and 25 radiation injuries. The SI time course of SI-e, SI-c and SI-b proved to be significantly different for both entities (P < 0.001) from TP2 to TP3. The SI of 39/41 lesions increased from TP1 to TP2 for the three parameters. Radiation injuries showed a further signal increase at least for SI-c from TP2 to TP3, whereas for all the three parameters SI decreased in all metastases. Brain metastases and radiation injuries after SRS have a characteristic and statistically significantly different SI time course on sequential gadolinium enhancement MRI when late MR studies are included. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  17. 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)....

  18. Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hao; Zou, Tianyu; Wang, Xianlong; Du, Yongxing; Jiang, Chunxiu; Ma, Ling; Zhu, Jianbin; He, Wen; Rui, Qihong; Wen, Zhibo [Zhujiang Hospital, Southern Medical University, Department of Radiology, Guangzhou, Guangdong (China); Lou, Huiling [The First People' Hospital of Guangzhou, Department of Geriatrics, Guangzhou, Guangdong (China); Jiang, Shanshan [Zhujiang Hospital, Southern Medical University, Department of Radiology, Guangzhou, Guangdong (China); Johns Hopkins University School of Medicine, Division of MR Research, Department of Radiology, Baltimore, MD (United States); Huang, Zhongqing [Shantou University Medical College, Department of Medical Image Center, Yuebei People' s Hospital, Shantou, Guangdong (China); Zhou, Jianyuan [Johns Hopkins University School of Medicine, Division of MR Research, Department of Radiology, Baltimore, MD (United States)

    2017-11-15

    To determine the utility of amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs). Forty-five patients with SBMs and 43 patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumour core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver-operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups. The APTw{sub max}, APTw{sub min}, APTw{sub mean}, rAPTw{sub max}, rAPTw{sub min} or rAPTw{sub mean} values in the tumour core were not significantly different between the SBM and GBM groups (P = 0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTw{sub max}, APTw{sub min}, APTw{sub mean}, rAPTw{sub max}, rAPTw{sub min} or rAPTw{sub mean} values in the PBZ were significantly lower in the SBM group than in the GBM group (P < 0.001). The APTw{sub min} values had the highest area under the ROC curve 0.905 and accuracy 85.2% in discriminating between the two neoplasms. As a noninvasive imaging method, APT-weighted MR imaging can be used to distinguish SBMs from GBMs. (orig.)

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

    Science.gov (United States)

    Chowdhary, Mudit; Patel, Kirtesh R; Danish, Hasan H; Lawson, David H; Khan, Mohammad K

    2016-01-01

    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.

  20. Predicting brain metastases for non-small cell lung cancer based on magnetic resonance imaging.

    Science.gov (United States)

    Yin, Gang; Li, Churong; Chen, Heng; Luo, Yangkun; Orlandini, Lucia Clara; Wang, Pei; Lang, Jinyi

    2017-02-01

    In this study the relationship between brain structure and brain metastases (BM) occurrence was analyzed. A model for predicting the time of BM onset in patients with non-small cell lung cancer (NSCLC) was proposed. Twenty patients were used to develop the model, whereas the remaining 69 were used for independent validation and verification of the model. Magnetic resonance images were segmented into cerebrospinal fluid, gray matter (GM), and white matter using voxel-based morphometry. Automatic anatomic labeling template was used to extract 116 brain regions from the GM volume. The elapsed time between the MRI acquisitions and BM diagnosed was analyzed using the least absolute shrinkage and selection operator method. The model was validated using the leave-one-out cross validation (LOOCV) and permutation test. The GM volume of the extracted 11 regions of interest increased with the progression of BM from NSCLC. LOOCV test on the model indicated that the measured and predicted BM onset were highly correlated (r = 0.834, P = 0.0000). For the 69 independent validating patients, accuracy, sensitivity, and specificity of the model for predicting BM occurrence were 70, 75, and 66%, respectively, in 6 months and 74, 82, and 60%, respectively, in 1 year. The extracted brain GM volumes and interval times for BM occurrence were correlated. The established model based on MRI data may reliably predict BM in 6 months or 1 year. Further studies with larger sample size are needed to validate the findings in a clinical setting.

  1. Improved motion-sensitized driven-equilibrium preparation for 3D turbo spin echo T1 weighted imaging after gadolinium administration for the detection of brain metastases on 3T MRI.

    Science.gov (United States)

    Lee, Sangjoon; Park, Dong Woo; Lee, Ji Young; Lee, Young-Jun; Kim, Taeyoon

    2016-07-01

    To evaluate the clinical usefulness of an improved motion-sensitized driven-equilibrium (iMSDE) preparation for three-dimensional turbo spin echo (TSE) T1 weighted imaging after gadolinium administration in 3.0-T MRI for the detection of brain metastases compared with conventional gradient echo (C-GRE) T1 weighted imaging with gadolinium. 40 patients with suspected brain metastases underwent MR studies, including two contrast-enhanced sequences, iMSDE-TSE and C-GRE. Post-enhancement images of 14 patients with suspected metastatic brain lesions were retrospectively analyzed, and comparisons between iMSDE-TSE and C-GRE were made using the Wilcoxon signed-rank test. C-GRE detected 86 metastatic lesions, whereas iMSDE-TSE detected 97, including one false-positive lesion on both sequences. 11 of 96 metastases were detected on iMSDE-TSE only. On C-GRE, 15 of 85 metastases were equivocal. There was a significant difference between C-GRE and iMSDE-TSE in terms of the number of detected lesions (p = 0.024). Notably, the interobserver agreement for diagnosing metastases and identifying non-metastases was nearly identical. Overall, iMSDE-TSE achieves higher detectability of metastatic brain lesions, especially equivocal lesions. Compared with C-GRE, iMSDE-TSE detected more brain metastases. This method is especially helpful in discerning equivocal metastases. Previous studies have offered limited clinically useful information because they have all been preliminary studies such as comparing the contrast-to-noise ratio of each sequence without evaluating iMSDE-TSE. This study, however, is unique because we evaluate the clinical usefulness of iMSDE-TSE for the detection of brain metastases, and we compare these results to C-GRE.

  2. [Asymptomatic skull base metastases: clinical course and therapeutic alternatives].

    Science.gov (United States)

    Vargas, A; Paulazo, C; Oleaga, L; Verger, E

    2017-03-01

    Skull base metastases (SBM) are an infrequent and late type of cancer progression that are associated to poor prognosis. Its clinical manifestations may be grouped in five clinical syndromes and radiotherapy is its more frequent treatment. Because of the improvement in imaging tests and the close follow up of cancer patients, SBM can be diagnosed incidentally. In this group the best option of treatment has not been established. To analyze the clinical features and outcomes of patients with SBM diagnosed incidentally. Between January 2012 and December 2015, 31 patients with diagnoses of SBM from solid primary tumor were reviewed. SBM were diagnosed due to skull base syndromes (n = 24) or incidentally (n = 7). Symptomatic patients were treated with radiotherapy. Patients diagnosed incidentally remained without symptoms of craneal base involvement during the follow up, although they frequently had other types of intracranial progression. A statistically significant difference in survival was observed between symptomatic and asymptomatic patients (p = 0.001). The incidentally diagnosed SBM were frequently associated to other types of intracranial progression, limiting the options of treatment.

  3. Health Care Professionals' Evaluation of Quality of Life Issues in Patients With Brain Metastases.

    Science.gov (United States)

    Lauzon, Natalie; Bedard, Gillian; Zhang, Liying; Sahgal, Arjun; Zeng, Liang; Koo, Kaitlin; Chow, Edward

    2012-12-01

    The Functional Assessment of Cancer Therapy - Brain (FACT-Br) is a brain specific Quality of life (QOL) tool used for patients in the primary and metastatic cancer population. The purpose of this report is to evaluate the QOL issues health care professionals (HCPs) find most important when caring for brain metastases patients. HCPs were asked to rate whether each of the 23 FACT-Br subscale items were relevant to patients or not. In the survey, HCPs indicated the 5 to 10 top issues affecting the QOL of patients with brain metastases. Demographic information such as gender, years of experience, and health care specialty were recorded. A total of 46 HCPs participated in the study, 89% of HCPs ranked the need for help in caring for themselves as the most relevant item for patients with brain metastases. Other highly relevant items included the concern of getting headaches (81%) and weakness in arms or legs (78%). The lowest rated items included the ability to put thoughts together (8%), ability to write as they used to (11%) and also the ability to read as they used to (14%). It is very important to determine the issues that HCPs think are most important to patients in an attempt to harmonize these with those of patients. Future studies should compare the items that HCPs rate as most relevant to those that patients rate to ensure agreeability.

  4. CXCL12, CXCR4 and CXCR7 expression in brain metastases.

    Science.gov (United States)

    Salmaggi, Andrea; Maderna, Emanuela; Calatozzolo, Chiara; Gaviani, Paola; Canazza, Alessandra; Milanesi, Ida; Silvani, Antonio; DiMeco, Francesco; Carbone, Antonino; Pollo, Bianca

    2009-09-01

    Brain metastases occur in about 25% of patients who die of cancer. The most common sources of brain metastases in adults are lung, breast, kidney, colorectal cancer and melanoma. The chemokine/receptor system CXCL12/CXCR4 plays a key role in multiple biological functions; among these, homing of neoplastic cells from the primary site to the target and metastasis progression. Recently, an alternative CXCL12 receptor CXCR7 has been discovered. The aim of our study was to investigate the expression of CXCL12 and its receptors CXCR4 and CXCR7 by immunohistochemistry in 56 patients with metastatic brain disease from different non-CNS primary tumors and evaluate their prognostic relevance as well as that of other patient/treatment-related features on patient survival. CXCL12 showed an expression in tumor cells and in tumor vessels; CXCR7 was expressed by tumor and endothelial cells (both within the tumor and in the adjacent brain tissue), while CXCR4 showed a positivity in all samples with a nuclear pattern. Among the investigated immunohistochemical parameters, only CXCL12 expression in tumor endothelial cells showed a statistically significant correlation with shorter survival (p = 0.04 log-rank), perhaps identifying more aggressive tumors. Thus, this is the first study evaluating at the same time the expression of CXCL12 and its two receptors in a cohort of brain metastases.

  5. Brain metastases from malignant melanoma; ZNS-Metastasen beim malignen Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Willner, J. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie; Bohndorf, W. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie

    1995-03-01

    Between 1985 and 1993 30 patients underwent radiation therapy for brain metastases from malignant melanoma. In 9 patients they had been surgically resected. All except 1 patient received whole brain irradiation with a total dose of 20 to 46 Gy/2 to 5 weeks using daily fractions of 2,0 to 4,0 Gy. In 5 patients a local boost of 20 to 25 Gy/2 weeks was administered. Survival rates were compared using the Cox-method. Univariate and multivariate analyses were performed to define prognostic subgroups. In 6/30 patients (20%) brain metastases were diagnosed at the time of primary manifestation of melanoma. In 83% of patients brain metastases developed during the first 5 years following primary diagnosis. Late manifestation was observed (18 years). Overall survival rate of the whole group was 39% at 6 months and 23% at 1 year. Univariate analysis revealed that age at diagnosis of brain metastases, time to manifestation, number of intracranial metastases and existence of extracerebral distant metastases had significant influence on survival. Sex was not found to influence survival rate. Multivariate analysis identified the existence of extracerebral distant metastases at the time of diagnosis of brain metastases as the most important prognostic factor for survival, followed by age and surgical resection. The role of fractionation was studied separately in a subgroup of patients receiving whole brain irradiation to a total dose of 39 to 42 Gy. Survival rates deteriorated when overall treatment time exceeded 3 weeks. (orig./MG) [Deutsch] Zwischen 1985 und 1993 wurden 30 Patienten mit ZNS-Metastasen bei malignem Melanom einer strahlentherapeutischen Behandlung unterzogen. Bei neun Patienten war eine operative Metastasenresektion vorausgegangen. Alle bis auf einen Patienten erhielten eine Ganzschaedelbestrahlung mit 20 bis 46 Gy in zwei bis fuenf Wochen bei Einzeldosen von 2,0 bis 4,0 Gy. In fuenf Faellen erfolgte eine lokale Aufsaettigung mit 20 bis 25 Gy/2 Wochen. Die

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

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

    Science.gov (United States)

    Kim, Kyung Su; Kim, Kyubo; Chie, Eui Kyu; Kim, Yoon Jun; Yoon, Jung Hwan; Lee, Hyo-Suk; Ha, Sung W

    2015-03-01

    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.

  9. 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.

  10. Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade.

    Science.gov (United States)

    Choy, Cecilia; Raytis, John L; Smith, David D; Duenas, Matthew; Neman, Josh; Jandial, Rahul; Lew, Michael W

    2016-06-01

    In response to recent studies, we investigated an association between perioperative β-blockade and breast cancer metastases. First, a retrospective study examining perioperative β-blocker use and cancer recurrence and metastases was conducted on 1,029 patients who underwent breast cancer surgery at the City of Hope Cancer Center between 2000 and 2010. We followed the clinical study and examined proliferation, migration, and invasion in vitro of primary and brain-metastatic breast cancer cells in response to β2-activation and inhibition. We also investigated in vivo the metastatic potential of propranolol-treated metastatic cells. For stage II breast cancer patients, perioperative β-blockade was associated with decreased cancer recurrence using Cox regression analysis (hazard's ratio =0.51; 95% CI: 0.23-0.97; p=0.041). Triple-negative (TN) brain-metastatic cells were found to have increased β2-adrenergic receptor mRNA and protein expression relative to TN primary cells. In response to β2-adrenergic receptor activation, TN brain-metastatic cells also exhibited increased cell proliferation and migration relative to the control. These effects were abrogated by propranolol. Propranolol decreased β2-adrenergic receptor-activated invasion. In vivo, propranolol treatment of TN brain-metastatic cells decreased establishment of brain metastases. Our results suggest that stress and corresponding β2-activation may promote the establishment of brain metastases of TN breast cancer cells. In addition, our data suggest a benefit to perioperative β-blockade during surgery-induced stress with respect to breast cancer recurrence and metastases.

  11. Synergetic responses after administration of interleukin-2 and Interferon-alpha combined with gamma knife radiosurgery in a patient with multiple lung and brain metastases: a case report

    National Research Council Canada - National Science Library

    Takada, Toshihiko; Yamada, Yoshiteru; Uno, Masahiro; Komeda, Hisao; Fujimoto, Yoshinori

    2005-01-01

    ...). Initially, Interferon-alpha (IFN-alpha) therapy was started for lung metastases. About 40 days after surgery, head magnetic resonance imaging revealed brain metastases, and therefore gamma knife radiosurgery(GKS) was performed...

  12. [Dosimetric stereotactic radiosurgical accident: Study of 33 patients treated for brain metastases].

    Science.gov (United States)

    Borius, P-Y; Debono, B; Latorzeff, I; Lotterie, J-A; Plas, J-Y; Cassol, E; Bousquet, P; Loubes, F; Duthil, P; Durand, A; Caire, F; Redon, A; Berry, I; Sabatier, J; Lazorthes, Y

    2010-10-01

    The consequences of a dosimetric radiosurgery accident are not the same as a conventional radiotherapy accident. The objective of this study was to estimate the clinical and radiological outcome of patients treated by radiosurgery for metastasis during the period of the overexposure accident that occurred in the Toulouse Radiosurgery Unit. Between April 2006 and March 2007, 33 patients with 57 metastases were treated in the Toulouse Radiosurgery Unit (Novalis(®), BrainLab). An initial error in the estimation of the scatter factors led to an overexposure to radiation. The median age was 55 years [range, 35-85]. Twenty-one patients (64%) harbored a single metastasis. The primary tumor location was lung (16 cases), kidney (nine cases), breast (four cases), and others (four cases). The mean tumoral volume was 3.2cm(3) [0.04-14.07]. The mean prescribed dose at the isocenter was 20 Gy [range, 10-23], the mean delivered dose was 31.5 Gy [range, 13-52], and the mean overdose was 61.2% [range, 5.6-226.8]. In order to evaluate the consequences of the overdose, three parameters were analyzed: a risk index using dose and volume, the volume of parenchyma that received more than 12 Gy, and the mean dose in a sphere of 20cm(3) surrounding the target volume. Median actuarial survival was 14.1 months, the survival rate was 79.4 % at six months, 59.1% at 12 months, and 27.2% at 24 months. The rate of tumor control was 80.7%. No morbidity was observed. There was no correlation between death and the parameters studied. The survival rates and times observed in our study of the patients treated for brain metastases by radiosurgery and overexposed were among the good results of the international literature. Deaths were not related to the overdose and no side effect was noted. This dosimetric accident has not had worse consequences in this population. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  13. 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.

  14. The surgical manegement of metastases to humerus-clinical evaluation.

    Science.gov (United States)

    Chrobok, Adam; Spindel, Jerzy; Miszczyk, Leszek; Koczy, Bogdan; Pilecki, Bogdan; Jarosz, Adam; Mrozek, Tomasz

    2003-06-30

    Background. The humerus is a common localisation of cancer metastases. The restoration of anatomical order and tumor resection within humerus is important for patients quality of everyday life and for their pain relief. The surgical treatment is one of the most important part of the whole oncological ways of tratment. The study objective was a clinical assesment of tumor resection and reconstruction within humerus according to matastasis localisation and the choice of surgical technique. Material and methods. In the years 1999-2002 19 patients underwent surgery due to pathological fracture or/and cancer metastasis within humerus. The shaft localisation of the tumor was found in 8 cases and in 11 patients the metastatic foci were found in proximnal diaphysis. In patients with proximal diaphysis localisation of the tumor the partial resection with subsequent joint exchange procedure was made. The humeral shaft metastatic cancer changes were treated by the segmental resection with subsequent surgical cement filling or auto/allogenical bone grafting combined with intramedullary nail or AO/ASIF plate stabilisation. The average follow-up period was 8,5 months. Results. In patients after resection with shoulder joint alloplasty according to the Enneking test a very good result was found in 7 and very good in 4 cases. In patients with femoral shaft metastatic tumor locaslisation, 6 good and 2 fair results were found. In 1 patient after 2 months rehabilitation a reoperation was needed due to the mechanical destabilisation. The best results were found in patients after intramedullary nailing.An acute soft tissue inflamation requiering surgical treatment was found in 1 patient after shoulder joint replacement. Conclusions. After clinical analysis of the material we highly recomend the partial humeral bone resection with subsequent shoulder alloplasty in patients with proximal humeral diaphysis metastatic localisation. In cases with shaft localisation a better results were

  15. 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

  16. 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

    of diagnosis of brain metastasis as compared to the primary cancer diagnosis, and the perifocal brain oedema. RESULTS: Statistical evaluation of the indexes in the patients with brain metastases relapsing within 2 months after the first craniotomy (n = 13) revealed significantly higher values as compared...... to the patients with lesions which had not relapsed or which had relapsed more than 2 months after first craniotomy (n = 12). The synchronous brain metastasis (that is, those occurring before or within 2 months of the primary cancer diagnosis) had a significantly higher proliferation index than the metachronous...... lesions (those occurring more than 2 months after primary cancer diagnosis). CONCLUSIONS: The synchronous brain metastasis relapses within 2 months of primary resection and have a significantly higher proliferation index than the metachronous lesions which did not recur within 2 months. These results...

  17. 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 

  18. Single fraction stereotactic radiosurgery for multiple brain metastases

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    Dror Limon, MD

    2017-10-01

    Conclusion: In single-fraction SRS for patients with multiple BM, smaller total tumor volume, higher total dose, and lower volume of normal brain receiving >12 Gy were associated with increased survival. These data suggest that using SRS for the treatment of multiple BM is efficacious and that outcomes may be affected more by total tumor volume than by the number of lesions.

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

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    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.)

  20. Brain metastases in metastatic breast cancer patients receiving trastuzumab-based therapies.

    Science.gov (United States)

    Puente Vázquez, Javier; López-Tarruella Cobo, Sara; García-Sáenz, José A; Casado Herráez, Antonio; Moreno Antón, Fernando; Sampedro Gimeno, Teresa; Bueno Muiño, Coralia; Grande Pulido, Enrique; Martín Jiménez, Miguel; Díaz-Rubio, Eduardo

    2006-01-01

    CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.

  1. 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 brain metastasis in patients with solitary brain metastasis, with and without 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.

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

    Science.gov (United States)

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

    2017-12-15

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

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

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    Aibek E. Mirrakhimov

    2012-01-01

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

  4. Management of breast cancer brain metastases: Focus on human epidermal growth factor receptor 2-positive breast cancer.

    Science.gov (United States)

    Yuan, Peng; Gao, Song-Lin

    2017-03-25

    After the introduction of trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), the overall survival (OS) among patients with HER2-positive breast cancer has been substantially improved. However, among these patients, the incidence of brain metastases (BM) has been increasing and an increased proportion of them have died of intracranial progression, which makes HER2-positive breast cancer brain metastases (BCBM) a critical issue of concern. For local control of limited BM, stereotactic radiosurgery (SRS) and surgical resection are available modalities with different clinical indications. Postoperative or preoperative radiation is usually delivered in conjunction with surgical resection to boost local control. Adjuvant whole-brain radiotherapy (WBRT) should be deferred for limited BM because of its impairment of neurocognitive function while having no benefit for OS. Although WBRT is still the standard treatment for local control of diffuse BM, SRS is a promising treatment for diffuse BM as the technique continues to improve. Although large molecules have difficulty crossing the blood brain barrier, trastuzumab-containing regimens are critical for treating HER2-positive BCBM patients because they significantly prolong OS. Tyrosine kinase inhibitors are more capable of crossing into the brain and they have been shown to be beneficial for treating BM in HER2-positive patients, especially lapatinib combined with capecitabine. The antiangiogenic agent, bevacizumab, can be applied in the HER2-positive BCBM scenario as well. In this review, we also discuss several strategies for delivering drugs into the central nervous system and several microRNAs that have the potential to become biomarkers of BCBM.

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

    Directory of Open Access Journals (Sweden)

    Nobuhiro Morinaga

    2016-05-01

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

  6. WITHDRAWN: Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission.

    Science.gov (United States)

    2018-02-06

    Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized trials conducted on patients in complete remission were unable to clarify whether this treatment improves survival. This study aims to test whether prophylactic cranial irradiation prolongs survival of patients with small cell lung cancer in complete remission. Published and unpublished trials were eligible. Electronic databases (Medline, Cancerlit, Excerpta Medica, Biosis from 1965 to 1998), reference lists of trial publications, review articles and relevant books were used to identify potentially eligible trials. The search was also guided by discussions with investigators and experts, and the examination of meeting proceedings and of the Physician Data Query clinical trial registry. Randomized trials comparing prophylactic cranial irradiation with no prophylactic cranial irradiation in patients with small cell lung cancer in complete remission. Meta-analysis based on updated individual data. The main endpoint was survival. Seven trials with a total of 987 participants were included. The relative risk of death in the treatment group compared to the control group was 0.84 (95% confidence interval=0.73 to 0.97, P=0.01), corresponding to a 5.4 percent increase in the 3-year survival rate (from 15.3 percent in the control group to 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased disease-free survival (relative risk=0.75, 95% confidence interval=0.65 to 0.86, P<0.001) and decreased the risk of brain metastases (relative risk=0.46, 95% confidence interval=0.38 to 0.57, P<0.001). Increasing doses of irradiation decreased the risk of brain metastases when four groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed [trend test, P=0.02], but the effect on survival did not differ significantly according to the dose. We found a trend (P=0.01) for a decrease in the brain metastasis risk in favour of earlier

  7. Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

    Science.gov (United States)

    Takano, Koji; Kinoshita, Manabu; Takagaki, Masatoshi; Sakai, Mio; Tateishi, Souichirou; Achiha, Takamune; Hirayama, Ryuichi; Nishino, Kazumi; Uchida, Junji; Kumagai, Toru; Okami, Jiro; Kawaguchi, Atsushi; Hashimoto, Naoya; Nakanishi, Katsuyuki; Imamura, Fumio; Higashiyama, Masahiko; Yoshimine, Toshiki

    2016-05-01

    The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases. CT or MR images of 200 patients with a total of 1033 treatment-naive brain metastases from lung cancer were retrospectively reviewed (23 by CT and 177 by MRI). All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Locations, depths from the brain surface, and sizes of the lesions after image standardization were analyzed. The posterior fossa, the anatomic "watershed areas," and the gray-white matter junction were confirmed to be more commonly affected by lung cancer brain metastases, and brain metastases with epidermal growth factor receptor (EGFR) L858R mutation occurred more often in the caudate, cerebellum, and temporal lobe than those with exon 19 deletion of EGFR. Median depths of the lesions from the brain surface were 13.7 mm (range, 8.6-21.9) for exon 19 deleted EGFR, 11.5 mm (6.6-16.8) for L858R mutated, and 15.0 mm (10.0-20.7) for wild-type EGFR. Lesions with L858R mutated EGFR were located significantly closer to the brain surface than lesions with exon 19 deleted or wild-type EGFR (P = .0032 and P < .0001, respectively). Furthermore, brain metastases of adenocarcinoma lung cancer patients with a history of chemotherapy but not molecular targeted therapy were located significantly deeper from the brain surface (P = .0002). This analysis is the first to reveal the relationship between EGFR mutation status and the spatial distribution of brain metastases of lung cancer. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    Science.gov (United States)

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

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

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    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.

  10. 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.).

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

    Directory of Open Access Journals (Sweden)

    Melinda B. Chu

    2013-01-01

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

  12. Clinical and genetic determinants of ovarian metastases from colorectal cancer.

    Science.gov (United States)

    Ganesh, Karuna; Shah, Ronak H; Vakiani, Efsevia; Nash, Garrett M; Skottowe, Hugh P; Yaeger, Rona; Cercek, Andrea; Lincoln, Anne; Tran, Christina; Segal, Neil H; Reidy, Diane L; Varghese, Anna; Epstein, Andrew S; Sonoda, Yukio; Chi, Dennis; Guillem, Jose; Temple, Larissa; Paty, Philip; Hechtman, Jaclyn; Shia, Jinru; Weiser, Martin; Aguilar, Julio Garcia; Kemeny, Nancy; Berger, Michael F; Saltz, Leonard; Stadler, Zsofia K

    2017-04-01

    Ovarian metastases from colorectal cancer (OM-CRC) often are unresponsive to chemotherapy and are associated with poor survival. To the authors' knowledge, the clinicopathologic and genomic predictors of OM-CRC are poorly characterized and optimal clinical management remains unclear. Women with a histopathological diagnosis of OM-CRC who were treated at Memorial Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next-generation somatic mutation profiling (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]) was performed on 38 OM-CRC cases, including 21 matched tumor pairs/trios. Regression models were used to analyze variables associated with progression-free survival and overall survival (OS). Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations were more frequent in cases of OM-CRC than in instances of CRC occurring without OM. SMAD4 and lysine methyltransferase 2D (KMT2D) mutations were associated with reduced OS. Matched multisite tumor sequencing did not identify OM-specific genomic alterations. Of the 195 patients who underwent oophorectomy for OM-CRC (median age, 49 years with a progression-free survival of 9.4 months and an OS of 23 months from oophorectomy), 76% had extraovarian metastasis (EOM). In multivariable analysis, residual disease after surgery (R2 resection) was associated with worse survival. Patients with EOM were less likely to achieve R0/R1 surgical resection status (complete macroscopic resection without clinical/radiological evidence of disease) (48% vs 94%). However, if R0/R1 resection status was achieved, both patients with (35.9 months vs 12 months) and without (43.2 months vs 14.5 months) EOM were found to have better OS. Among 114 patients with R0/R1 resection status, 23 (20%) had no disease recurrence, including 10 patients (9%) with > 3 years of follow-up. Loss

  13. Evaluation of Biomarkers Predictive of Benefit From PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases

    Science.gov (United States)

    2016-07-01

    Society of Clinical Oncology Annual Meeting 2015, Chicago, IL. Poster Presentation: “Activity and safety of pembrolizumab in patients with metastatic...impact on the field of oncology as we now know that patients with brain metastases can benefit from immunotherapy. b. What was the impact on other...AWARD NUMBER: W81XWH-15-1-0203 TITLE: Evaluation of Biomarkers Predictive of Benefit From PD-1 Inhibitor MK-3475 in Patients with Non-Small

  14. Patterns of relapse and late toxicity after resection and whole-brain radiotherapy for solitary brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C.; Schnabel, K. [Univ. Hospital, Homburg/Saar (Germany). Dept. of Radiotherapy; Schwerdtfeger, K.; Steudel, W.I. [Univ. Hospital, Homburg/Saar (Germany). Dept. of Neurosurgery

    1998-05-01

    From a total of 66 patients, 52 received 10 x 3 Gy and 10 were treated with 20 x 2 Gy whole-brain radiotherapy after resection of their brain metastases. The actuarial probablity of relapse was 27% and 55% after 1 and 2 year(s), respectively. The local relapse rate (at the original site of resected brain metastases) was rather high for melanoma, non-breast adenocarcinoma, and squamous-cell carcinoma. No local relapse occurred in breast cancer and small-cell carcinoma. Failure elsewhere in the brain seemed to be influenced by extracranial disease activity. Size of brain metastases and total dose showed no correlation with relapse rate. Occurrence of brain relapse was not associated with a reduced survival time, because 10/15 patients who developed a relapse received salvage therapy. Of the patients, 11 had symptoms of late radiation toxicity (the actuarial probability was 42% after 2 years). Most results of surgical and radiosurgical studies are comparable to ours. Several randomized trials investigate surgical resection versus radiosurgery, as well as the effects of additional whole-brain radiotherapy in order to define the treatment of choice. Some data support the adjuvant application of 10 x 3 Gy over 2 weeks as a reasonable compromise when local control, toxicity, and treatment time have to be considered. (orig./MG) [Deutsch] Nach der Resektion der Hirnmetastase erhielten 52 von 66 Patienten eine Ganzhirnbestrahlung mit zehn Fraktionen von 3 Gy in zwei Wochen und zehn eine solche mit 20 Fraktionen von 2 Gy in vier Wochen. Die Kaplan-Meier-Analyse ergab eine Rezidivrate von insgesamt 27% nach einem bzw. 55% nach zwei Jahren. Rezidive im Bereich der resezierten Metastase wurden am haeufigsten bei Melanomen, Adenokarzinomen (mit Ausnahme der Mammakarzinome) und Plattenepithelkarzinomen beobachtet. Dagegen traten bei Mammakarzinomen und kleinzelligen Karzinomen keine solchen Rezidive auf. Das Auftreten von Hirnmetastasen anderer Lokalisation schien vom

  15. [Immunohistochemical hormonal mismatch and human epidermal growth factor type 2 [HER2] phenotype of brain metastases in breast cancer carcinoma compared to primary tumors].

    Science.gov (United States)

    Joubert, C; Boissonneau, S; Fina, F; Figarella-Branger, D; Ouafik, L; Fuentes, S; Dufour, H; Gonçalves, A; Charaffe-Jauffret, E; Metellus, P

    2016-06-01

    Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer. This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records. Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test). the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. 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.)

  17. CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG Oncology RTOG 0933.

    Science.gov (United States)

    Caine, Chip; Deshmukh, Snehal; Gondi, Vinai; Mehta, Minesh; Tomé, Wolfgang; Corn, Benjamin W; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey Noah; Konski, Andre A; Bauman, Glenn S; Raben, Adam; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa

    2016-01-01

    Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.

  18. 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

  19. Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm.

    Science.gov (United States)

    Angelov, Lilyana; Mohammadi, Alireza M; Bennett, Elizabeth E; Abbassy, Mahmoud; Elson, Paul; Chao, Samuel T; Montgomery, Joshua S; Habboub, Ghaith; Vogelbaum, Michael A; Suh, John H; Murphy, Erin S; Ahluwalia, Manmeet S; Nagel, Sean J; Barnett, Gene H

    2017-09-22

    OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days

  20. 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 Gy).

  1. Predictors of Survival in Contemporary Practice After Initial Radiosurgery for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Likhacheva, Anna; Pinnix, Chelsea C. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Parikh, Neil R. [Baylor College of Medicine, Houston, Texas (United States); Allen, Pamela K.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chiu, Max S. [University of Nebraska-Lincoln, Lincoln, Nebraska (United States); Sulman, Erik P.; Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guha-Thakurta, Nandita [Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Prabhu, Sujit S. [Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cahill, Daniel P. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Luo, Dershan; Shiu, Almon S. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L., E-mail: eric.chang@med.usc.edu [Department of Radiation Oncology, University of Southern California, Los Angeles, Los Angeles, California (United States)

    2013-03-01

    Purpose: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone. Methods and Materials: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS). Results: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm{sup 3} (HR, 1.98; P<.001), age ≥60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm{sup 3}). The number of BM was not predictive of DBF, LC, or OS. Conclusions: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT.

  2. Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer.

    Science.gov (United States)

    Halasz, Lia M; Uno, Hajime; Hughes, Melissa; D'Amico, Thomas; Dexter, Elisabeth U; Edge, Stephen B; Hayman, James A; Niland, Joyce C; Otterson, Gregory A; Pisters, Katherine M W; Theriault, Richard; Weeks, Jane C; Punglia, Rinaa S

    2016-07-01

    The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. This study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. © 2016 American Cancer Society. © 2016 American Cancer Society.

  3. A survival score for patients with brain metastases from less radiosensitive tumors treated with whole-brain radiotherapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Dziggel, L.; Rades, D. [University Hospital Schleswig-Holstein, Department of Radiation Oncology, Luebeck (Germany); Segedin, B.; Podvrsnik, N.H.; Oblak, I. [Institute of Oncology, Division of Radiation Oncology, Ljubljana (Slovenia); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, Arizona (United States)

    2014-01-15

    This study aimed to develop and validate a scoring system to predict the survival of patients receiving whole-brain radiotherapy (WBRT) alone for brain metastases from less radiosensitive tumors. The study included data from 176 patients with brain metastasis from renal cell carcinoma, malignant melanoma or colorectal cancer. Patients were divided into a test group (N=88) and a validation group (N=88). In the multivariate analysis of the test group, age, Karnofsky Performance Status and extracranial metastasis were significantly associated with survival. These three factors were included in the scoring system. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the three scores. According to the total scores - which ranged from 5 to14 points - three prognostic groups were created. The 6-month survival rates in the test group were 11% for 5-8 points (N=47, group A), 38% for 9-11 points (N=29, group B) and 83% for 12-14 points (N=12, group C). In the validation group the 6-month survival rates were 12, 31 and 75%, respectively. Comparisons between the prognostic groups A, B and C of the test group with those of the validation group did not reveal any significant differences. The new scoring system based on three independent prognostic factors can help to estimate the survival of patients with brain metastases from a less radiosensitive tumor. The score appears to be valid and reproducible. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-02-01

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

  5. MO-G-201-04: Knowledge-Based Planning for Single-Isocenter Stereotactic Radiosurgery to Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ziemer, B [University of California, San Diego, La Jolla, CA (United States); Shiraishi, S [Mayo Clinic, Rochester, MN (United States); Hattangadi-Gluth, J; Sanghvi, P; Moore, K

    2016-06-15

    Purpose: Single-isocenter, linac-based SRS for multiple brain metastases (multi-mets) can deliver highly conformal radiation doses and reduce overall patient treatment time compared to other therapy techniques. This study aims to quantify the dosimetric benefits of knowledge-based planning (KBP) for multi-met treatments. Methods: Using a previously-published KBP methodology (an artificial neural network (ANN) trained on single-target linac-based SRS plans), 3D dose distribution predictions for multi-met patients were obtained by treating each brain lesion as a solitary target and subsequently combining individual predictions into a single distribution using a dose-weighted geometric averaging to obtain the best results in the inter-target space. 17 previously-treated multi-met plans, with target numbers ranging from N=2–5, were used to validate the ANN predictions and subsequent KBP auto-planning routine. The fully-deliverable KBP plans were developed by converting dose distribution predictions into patient-specific optimization objectives while maintaining identical target normalizations (typically PTV V100%=D98%). Plan quality improvements were quantified by the difference between SRS quality metrics (QMs): δdQM=QM(clinical)-QM(KBP). QMs of interest were: gradient measure (GM), conformity index (CI), brain V10 and V5, brainstem D0.1cc and heterogeneity index (HI). Finally, overall plan quality was judged via blinded plan comparison by SRS-specializing physicians. Results: Two clinical plans were found to be significant outliers wherein plan quality was dramatically worse than KBP. Despite indicating KBP superiority, these were removed from the QM analysis to prevent skewing the results. In the remaining cases, clinical and KBP QMs were nearly identical with modest improvements in the KBP sample: δGM=0.12±0.56mm, δCI=−0.01±0.04, Brain δV10=0.8±2.6cc, brain δV5=6.3 ±10.7cc, brainstem δD0.1cc=0.06±1.19Gy and δHI= −0.04±0.05. Ultimately, 13/17 KBP

  6. Adenoid cystic carcinoma of the breast - an aggressive presentation with pulmonary, kidney, and brain metastases: a case report.

    Science.gov (United States)

    Mhamdi, Hasnae Alaoui; Kourie, Hampig Raphael; Jungels, Christiane; Aftimos, Philippe; Belbaraka, Rhizlane; Piccart-Gebhart, Martine

    2017-10-29

    Adenoid cystic carcinoma of the breast is a rare malignant neoplasm associated with an excellent prognosis and a very rare occurrence of metastases. We report the case of an aggressive presentation in a 65-year-old woman, of Belgian origin, who was diagnosed as having adenoid cystic carcinoma of the breast and developed metastases to her lung, kidney, and brain. We describe similar cases reported in the literature and discuss the molecular characteristics and treatment paradigm of this controversially aggressive disease entity.

  7. Target definition by C11-methionine-PET for the radiotherapy of brain metastases.

    Science.gov (United States)

    Matsuo, Masayuki; Miwa, Kazuhiro; Shinoda, Jun; Kako, Nobuo; Nishibori, Hironori; Sakurai, Kouta; Yano, Hirohito; Iwama, Toru; Kanematsu, Masayuki

    2009-07-01

    To evaluate the ability of 11C-methionine positron emission tomography (MET-PET) to delineate target volumes for brain metastases and to investigate to what extent tumor growth is presented by magnetic resonance imaging (MRI) and MET-PET. Three observers undertook target definition in 19 patients with 95 brain metastases by MRI and MET-PET images. MRI gross target volume (GTV) (GTV-MRI) was defined as the contrast-enhanced area on gadolinium-enhanced T1-weighted MRI. MET-PET GTV (GTV-PET) was defined as the area of an accumulation of MET-PET apparently higher than that of normal tissue on MET-PET images. The size of occupation ratio was determined using the following equation: SOR (%) of MET are within x mm margin outside GTV-MRI = the volume of the GTV-PET within x mm outside the GTV-MRI/the volume of the GTV-PET. For GTV-MRI volumes of 0.5 mL, GTV-PET volumes were larger than GTV-MRI volumes and a significant correlation was found between these variables by linear regression. For all tumor sizes and tumor characteristics, a 2-mm margin outside the GTV-MRI significantly improved the coverage of the GTV-PET. Although there were some limitations in our study associated with spatial resolution, blurring effect, and image registrations with PET images, MET-PET was supposed to have a potential as a promising tool for the precise delineation of target volumes in radiotherapy planning for brain metastases.

  8. Incidence of local in-brain progression after supramarginal resection of cerebral metastases.

    Science.gov (United States)

    Kamp, Marcel A; Rapp, Marion; Slotty, Philipp J; Turowski, Bernd; Sadat, Hosai; Smuga, Maria; Dibué-Adjei, Maxine; Steiger, Hans-Jakob; Szelényi, Andrea; Sabel, Michael

    2015-06-01

    Microsurgical circumferential stripping of intracerebral metastases is often insufficient in achieving local tumor control. Supramarginal resection may improve local tumor control. A retrospective analysis was performed for patients who underwent supramarginal resection of a cerebral metastasis by awake surgery with intraoperative cortical and subcortical stimulation, MEPs, and SSEPs. Supramarginal resection was achieved by circumferential stripping of the metastasis and additional removal of approximately 3 mm of the surrounding tissue. Pre- and postsurgical neurological status was assessed by the NIH Stroke Scale. Permanent deficits were defined by persistence after 3-month observation time. Supramarginal resection of cerebral metastases in eloquent brain areas was performed in 34 patients with a mean age of 60 years (range, 33-83 years). Five out of 34 patients (14.7%) had a new transient postoperative neurological deficit, which improved within a few days due to supplementary motor area (SMA) syndrome. Five out of 34 patients (14.7%) developed a local in-brain progression and nine patients (26.4%) a distant in-brain progression. Supramarginal resection of cerebral metastases in eloquent locations is feasible and safe. Safety might be increased by intraoperative neuromonitoring. The better outcome in the present series may be entirely based on other predictors than extend of surgical resection and not necessarily on the surgical technique applied. However, supramarginal resection was safe and apparently did not lead to worse results than regular surgical techniques. Prospective, controlled, and randomized studies are mandatory to determine the possible benefit of supramarginal resection on local tumor control and overall outcome.

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

    Science.gov (United States)

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

    2017-04-01

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

  10. Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases.

    Science.gov (United States)

    Kanojia, Deepak; Balyasnikova, Irina V; Morshed, Ramin A; Frank, Richard T; Yu, Dou; Zhang, Lingjiao; Spencer, Drew A; Kim, Julius W; Han, Yu; Yu, Dihua; Ahmed, Atique U; Aboody, Karen S; Lesniak, Maciej S

    2015-10-01

    The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation. © 2015 AlphaMed Press.

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

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

    2015-01-16

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

  12. The influence of lung metastases on the clinical course of gestational trophoblastic neoplasia: a historical cohort study.

    Science.gov (United States)

    Vree, M; van Trommel, N; Kenter, G; Sweep, F; Ten Kate-Booij, M; Massuger, L; Lok, C

    2016-10-01

    To evaluate whether gestational trophoblastic neoplasia (GTN) patients with lung metastases have more adverse outcomes such as resistance to chemotherapy, recurrence or death of disease compared with patients without lung metastases. Historical observational cohort study. The Netherlands. We identified 434 GTN patients (72 patients with lung metastases, 362 patients without metastases) between 1990 and 2012 registered in the Dutch national databases. Baseline characteristics, recurrence rates, Methotrexate (MTX) remission rates and deaths from disease were compared between patients with lung metastases (group I) and without lung metastases (group II) using the Fisher exact test or Mann-Whitney U-test where applicable. Methotrexate resistance, recurrences and survival. Methotrexate resistance did not differ between group I and group II (62.9 versus 72.7% P = 0.19). However, the observed recurrence rate was significantly increased in patients with lung metastases compared with patients without metastases (16.7 versus 2.2% P Disease-specific survival was 91.7% in the group with lung metastases and 100% in the patients without metastases (P disease. Further research is needed to evaluate whether the presence of lung metastases is an independent risk factor that needs adjustment in the FIGO scoring system and clinical classification system. In gestational trophoblastic neoplasia (GTN) recurrence is more often observed in the case of lung metastases. © 2015 Royal College of Obstetricians and Gynaecologists.

  13. Estimating Survival in Melanoma Patients With Brain Metastases: An Update of the Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma-molGPA).

    Science.gov (United States)

    Sperduto, Paul W; Jiang, Wen; Brown, Paul D; Braunstein, Steve; Sneed, Penny; Wattson, Daniel A; Shih, Helen A; Bangdiwala, Ananta; Shanley, Ryan; Lockney, Natalie A; Beal, Kathryn; Lou, Emil; Amatruda, Thomas; Sperduto, William A; Kirkpatrick, John P; Yeh, Norman; Gaspar, Laurie E; Molitoris, Jason K; Masucci, Laura; Roberge, David; Yu, James; Chiang, Veronica; Mehta, Minesh

    2017-11-15

    To update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for a markedly heterogeneous patient population, patients with melanoma and brain metastases, using a larger, more current cohort, including molecular markers. The original Melanoma-GPA is based on data from 483 patients whose conditions were diagnosed between 1985 and 2005. This is a multi-institutional retrospective database analysis of 823 melanoma patients with newly diagnosed brain metastases from January 1, 2006, to December 31, 2015. Multivariable analyses identified significant prognostic factors, which were weighted and included in the updated index (Melanoma-molGPA). Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios to design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated with the best and worst prognoses, as with all of the diagnosis-specific GPA indices. Log-rank tests were used to compare adjacent classes. There were 5 significant prognostic factors for survival (age, Karnofsky performance status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF status), whereas only KPS and the number of brain metastases were significant in the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months between the 2 treatment eras, and the median survival times for patients with Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9, 8.3, 15.8, and 34.1 months (Pmelanoma patients with brain metastases has improved significantly. The updated Melanoma-molGPA, a user-friendly tool to estimate survival, will facilitate clinical decision making regarding whether and which treatment is appropriate and will also be useful for stratification of future clinical trials. To further simplify use, a free online/smart phone app is available at brainmetgpa.com. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

    Science.gov (United States)

    Rades, Dirk; Janssen, Stefan; Dziggel, Liesa; Blanck, Oliver; Bajrovic, Amira; Veninga, Theo; Schild, Steven E

    2017-01-06

    This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

  15. Treatment of brain metastases of renal cell cancer with combined hypofractionated stereotactic radiotherapy and whole brain radiotherapy with hippocampal sparing.

    Science.gov (United States)

    Vrána, David; Študentová, Hana; Matzenauer, Marcel; Vlachová, Zuzana; Cwiertka, Karel; Gremlica, David; Kalita, Ondřej

    2016-06-01

    Renal cell cancer patients with brain metastatic disease generally have poor prognosis. Treatment options include surgery, radiotherapy, targeted therapy or best supportive care with respect to disease burden, patient preference and performance status. In the present case report the radiotherapy technique combining whole brain radiotherapy with hippocampal sparing (hippocampal avoidance whole brain radiotherapy HA-WBRT) and hypofractionated stereotactic radiotherapy (SRT) of the brain metastases is performed in a patient with metastatic renal cell carcinoma. HA-WBRT was administered to 30 Gy in 10 fractions with sparing of the hippocampal structures and SRT of 21 Gy in 3 fractions to brain metastases which has preceded the HA-WBRT. Two single arc volumetric modulated arc radiotherapy (VMAT) plans were prepared using Monaco planning software. The HA-WBRT treatment plan achieved the following results: D2=33.91 Gy, D98=25.20 Gy, D100=14.18 Gy, D50=31.26 Gy. The homogeneity index was calculated as a deduction of the minimum dose in 2% and 98% of the planning target volume (PTV), divided by the minimum dose in 50% of the PTV. The maximum dose to the hippocampus was 17.50 Gy and mean dose was 11.59 Gy. The following doses to organs at risk (OAR) were achieved: Right opticus Dmax, 31.96 Gy; left opticus Dmax, 30.96 Gy; chiasma D max, 32,76 Gy. The volume of PTV for stereotactic radiotherapy was 3,736 cm3, with coverage D100=20.95 Gy and with only 0.11% of the PTV being irradiated to dose below the prescribed dose. HA-WBRT with SRT represents a feasible technique for radiotherapy of brain metastatic disease, however this technique is considerably demanding on departmental equipment and staff time/experience.

  16. Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma after liver transplantation

    Directory of Open Access Journals (Sweden)

    He Jian

    2011-11-01

    Full Text Available Abstract Background Little is known about the clinical features and prognostic factors of bone metastases of hepatocellular carcinoma (HCC following liver transplantation (LT. Methods All adult patients undergoing LT from 2001 to 2010 were reviewed. Patients with HCC bone metastases after LT received external beam radiotherapy(EBRT during this period. Demographic variables, laboratory values, and tumor characteristics were determined before LT and EBRT. Total radiation dose ranged from 8 to 60 Gy(median dose 40.0 Gy. Results The trunk was the most common site of bone metastases with finding of expansile soft-tissue masses in 23.3% of patients. Overall pain relief from EBRT occurred in 96.7% (29/30. No consistent dose-response relationship was found for palliation of with doses between 30 and 56 Gy (P = 0.670. The median survivals from the time of bone metastases was 8.6 months. On univariate and multivariate analyses, better survival was significantly associated with a better Karnofsky performance status (KPS and well-controlled intrahepatic tumor, but not with lower alpha-fetoprotein levels. The median time from LT to bone metastases was 7.1 months. Patients exceeding the Shanghai criteria presented with bone metastases earlier than those within the Fudan criteria. Patients with soft-tissue extension always had later bone metastases. The majority of deaths were caused by liver failure due to hepatic decompensation or tumor progression. Conclusion The prognostic factors of bone metastases of HCC following LT are KPS and well-controlled intrahepatic. Even though survival is shorter for these patients, EBRT provides effective palliation of pain.

  17. Germ cell cancer presenting as gastrointestinal bleeding and developing brain metastases: case report and review of the literature.

    Science.gov (United States)

    Fu, Shuang; Avezbakiyev, Boris; Zhi, Wanqing; Kodali, Sreenath; Rizvon, Kaleem; Alaverdian, Artur; Freedman, Lester; Mejia, Jose; Shahzad, Ghulamullah; Gotlieb, Vladimir

    2012-11-01

    This paper describes a rare case of germ cell cancer with duodenum, brain and lung metastases. The patient presented with melena and left testicle enlargement. Orchiectomy revealed mixed germ cell cancer, enteroscopy revealed duodenal choriocarcinoma, and chest x-ray and computed tomography (CT) showed bilateral lung metastases. The patient received and tolerated cisplatinum-based chemotherapy, and responded well. However, he developed seizures 3 months later. MRI showed brain metastases and he was treated with whole-brain radiation. One month later, he developed progressive dyspnea. Chest CT showed worsening lung metastases. He received second-line chemotherapy, but died due to multiorgan failure. Germ cell cancer with nonpulmonary metastases has poor prognosis and the management of these patients requires a multimodal approach. Head CT should be considered as routine screening for all germ cell cancer patients on initial diagnosis and brain MRI should be considered for high-risk patients (with an embryo- or choriocarcinoma histology, dramatically elevated β-human chorionic gonadotropin and lung involvement).

  18. 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...

  19. Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

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    Johnson, Matthew D., E-mail: Matthewjohnson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Avkshtol, Vladimir [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Baschnagel, Andrew M. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Meyer, Kurt; Ye, Hong; Grills, Inga S.; Chen, Peter Y.; Maitz, Ann [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Olson, Rick E.; Pieper, Daniel R. [Department of Neurosurgery, William Beaumont Hospital, Royal Oak, Michigan (United States); Krauss, Daniel J. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2016-03-01

    Purpose: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. Methods and Materials: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. Results: With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06). Conclusions: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an

  20. Intensity-modulated radiation therapy for patients with 1 to 3 brain metastases in recursive partitioning analysis class 3.

    Science.gov (United States)

    Yang, Jia; Zhan, Wenming; Zhang, Haibo; Song, Tao; Jia, Yongshi; Xu, Hongen; Lin, Baihua; Lv, Shiliang; Liang, Xiaodong

    2017-10-01

    The prognosis is extremely poor for patients with brain metastases in recursive partitioning analysis (RPA) class 3. It is not clear whether dose elevation for brain lesions in addition to whole-brain radiotherapy could improve survival for those patients. This study aimed to assess the efficacy and safety of dose elevation with intensity-modulated radiation therapy (IMRT) for patients with 1 to 3 brain metastases in RPA class 3.From January 2013 to December 2015, 24 patients with 1 to 3 brain metastases in RPA class 3 were included in this study. The median age was 60 (range 41-85) years and the mean graded prognostic assessment (GPA) score was 1.25 (range 0.5-2). Whole-brain radiotherapy (30 Gy) with a simultaneous integrated boost (SIB) to the brain metastases (totaling 40 Gy) was delivered in 10 fractions using IMRT technique. Survival times and overall safety were assessed. The significance of prognostic variables on survival was assessed by both univariate and multivariate analyses.All of the patients completed the planned SIB schedule. The overall response rate was 66.7%. The median survival time (MST) was 8 months for the entire group of patients. The MST was 5 months for patients with a GPA score of 0.5 to 1 (n = 11 patients) and 12 months with a GPA score of 1.5 to 2 (n = 13 patients). No acute or late toxicities greater than grade 2 were detected. Age and subsequent chemotherapy were significantly associated with MST on univariate and multivariate analyses.It is feasible to elevate radiation doses to 40 Gy using the IMRT technique in RPA class 3 patients with 1 to 3 brain metastases without serious toxicities. The preliminary results are encouraging and further studies with larger cohorts are warranted.

  1. Phase I/II trial of simultaneous whole-brain irradiation and dose-escalating topotecan for brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kocher, M.; Eich, H.T.; Semrau, R.; Guener, S.A.; Mueller, R.P. [Dept. of Radiation Oncology, Univ. Hospital, Univ. of Cologne, Cologne (Germany)

    2005-01-01

    Background and purpose: topotecan penetrates the blood-brain barrier and sensitizes tumor cells against radiation. A phase I/II dose-escalating trial of repetitive daily i.v. topotecan application simultaneously with whole-brain irradiation (WBRT) was conducted to estimate toxicity, maximum tolerated dose and survival in patients with inoperable brain metastases. Patients and methods: in 47 patients suffering from previously untreated brain metastases, topotecan was applied on a daily i.v. schedule simultaneously with WBRT (36 Gy/3-Gy fractions). The infusion schedule started at the beginning of WBRT and was discontinued during weekends. Each infusion was completed within 1-2 h before irradiation. In a dose-finding study, topotecan was escalated from 5 x 0.5 mg/m{sup 2}, 8 x 0.5 mg/m{sup 2}, 12 x 0.5 mg/m{sup 2} to 12 x 0.6 mg/m{sup 2}. Results: altogether, 38/47 patients (81%) completed the prescribed schedule. Leukopenia and thrombocytopenia were dose-limiting. Grade 3/4 hematologic toxicity occurred in 5/32 chemonaive patients (16%) and 7/15 patients (47%) with previous chemotherapy. At 12 x 0.6 mg/m{sup 2}, 2/4 patients experienced grade 4 leukopenia/thrombopenia. Nonhematologic toxicities were generally mild to moderate and unrelated to topotecan. Response evaluation was possible in 26/47 patients, overall response rate was 58% (CR [complete remission] 5/26, PR [partial remission] 10/26, NC [no change] 8/26). Median survival amounted to 5.1 months. In 15/42 patients (36%), brain metastases were the dominant cause of death. Conclusion: for a daily topotecan schedule simultaneous to WBRT, the maximum tolerated dose is 12 x 0.5 mg/m{sup 2} in chemonaive patients. For chemo-pretreated patients, daily doses should be reduced to 0.4 mg/m{sup 2}. A phase III trial has now been started to find out whether WBRT + topotecan increases survival compared to WBRT alone. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-01

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

  3. Treatment of brain metastases of small-cell lung cancer : Comparing teniposide and teniposide with whole-brain radiotherapy - A phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

    NARCIS (Netherlands)

    Postmus, PE; Haaxma-Reiche, H; Smit, EF; Groen, HJM; Karnicka, H; Lewinski, T; van Meerbeeck, J; Clerico, M; Gregor, A; Curran, D; Sahmoud, T; Kirkpatrick, A; Giaccone, G

    2000-01-01

    Purpose: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases, Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Ian S Gallaher

    2016-05-01

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

  6. Timing of Whole Brain Radiotherapy on Survival of Patients with EGFR-mutated 
Non-small Cell Lung Cancer and Brain Metastases

    Directory of Open Access Journals (Sweden)

    Guimei LIU

    2016-08-01

    Full Text Available Background and objective There is no high-level evidence for the time of whole brain radiotherapy (WBRT for patients with epidermal growth factor receptor (EGFR-mutated non-small cell lung cancer (NSCLC and brain metastases. The aim of this study is to assess the appropriate timing of WBRT for patients with EGFR-mutated NSCLC and brain metastases (BM. Methods There were 78 patients diagnosed with EGFR-mutated NSCLC and BM in Beijing Chest Hospital between August 2009 and May 2015. 48 untreated patients who received both WBRT and EGFR-tyrosine kinase inhibitors (TKIs therapy. Prognostic factors of intracranial progression-free survival (PFS and overall survival (OS were identified by Cox proportional hazards modeling. Results Intracranial objective response rate was 81.3% and disease control rate was 93.8%. Median intracranial PFS was 10 months. Median OS was 18 months. Multivariate analysis of intracranial PFS revealed that Eastern Cooperative Oncology Group (ECOG performance status (PS 0-1 (HR=30.436, 95%CI: 4.721-196.211, P<0.001 and early WBRT (HR=3.663, 95%CI: 1.657-8.098, P=0.001 had a better intracranial PFS. Multivariate analysis of OS revealed that PS 0-1 (HR=57.607, 95%CI: 6.135-540.953, P<0.001, early WBRT (HR=2.757, 95%CI: 1.140-6.669, P=0.024, and stereotactic radiosurgery (HR=5.964, 95%CI: 1.895-18.767, P=0.002 were independent prognostic factors of OS. Conclusion Early WBRT combined with EGFR-TKIs can improve outcomes of patients with EGFR-mutated NSCLC and BM, but it needs to be confirmed by large-sample-size and multicenter prospective clinical trials.

  7. 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.

  8. "Term delivery following successful treatment of choriocarcinoma with brain metastases, (a case report"

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    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

  9. A New Predictive Tool for Optimization of the Treatment of Brain Metastases from Colorectal Cancer After Stereotactic Radiosurgery.

    Science.gov (United States)

    Rades, Dirk; Dahlke, Markus; Gebauer, Niklas; Bartscht, Tobias; Hornung, Dagmar; Trang, Ngo Thuy; Phuong, Pham Cam; Khoa, Mai Trong; Gliemroth, Jan

    2015-10-01

    To develop a predictive tool for survival after stereotactic radiosurgery of brain metastases from colorectal cancer. Out of nine factors analyzed for survival, those showing significance (pradiosurgery (p=0.026) achieved significance, extracranial metastases showed a trend (p=0.06). These factors were included in the tool. Total scores were 0-3 points. Six-month survival rates were 17% for patients with 0, 25% for those with 1, 67% for those with 2 and 100% for those with 3 points; 12-month rates were 0%, 0%, 33% and 67%, respectively. Two groups were created: 0-1 and 2-3 points. Six- and 12-month survival rates were 20% vs. 78% and 0% vs. 44% (p=0.002), respectively. This tool helps optimize the treatment of patients after stereotactic radiosurgery for brain metastases from colorectal cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Clinical features of patients with non-Hodgkin?s lymphoma metastasizing to the pituitary glands

    OpenAIRE

    Yang, Junjie; Zhao, Na; Zhang, Guangsen; Zheng, Wenli

    2013-01-01

    It is rare for systemic non-Hodgkin?s lymphoma (NHL) to metastasize to the hypothalamus and pituitary glands. The present study describes two patients with NHL and diabetes insipidus (DI) and 17 patients from the literature in order to analyze the clinical features of patients with NHL metastasizing to the pituitary glands. Diffuse large B cell lymphoma (DLBCL) was observed to be the most common type of NHL involving the hypothalamus-pituitary axis. A total of 11 patients (57.9%) had been dia...

  11. Nomogram prediction of survival in patients with brain metastases from hepatocellular carcinoma treated with whole-brain radiotherapy: a multicenter retrospective study.

    Science.gov (United States)

    Park, Younghee; Kim, Kyung Su; Kim, Kyubo; Chie, Eui Kyu; Kim, Jin Ho; Kim, Jae-Sung; Kim, Tae Hyun; Kim, Dae Yong; Jang, Won Il; Kim, Mi-Sook; Koo, Tae Ryool; Chang, Ah Ram

    2015-11-01

    The incidence of brain metastasis from hepatocellular carcinoma (HCC) is increasing because of the improved survival outcome of HCC patients, but the prognosis of these patients is extremely poor. HCC patients with brain metastasis were investigated to identify their prognostic factors for overall survival. Patients with brain metastasis from HCC who had been treated with whole-brain radiotherapy (WBRT) in five hospitals were enrolled in the study. The medical records of the patients were reviewed, and the clinical factors were analyzed to identify the prognostic factors for overall survival. Of the total of 97 patients who were enrolled in the study, 83 were male and the median age at the brain metastases was 56.6 years. Motor weakness (43.3 %) and headache (41.2 %) were common presenting symptoms. The median AFP level was 4180 ng/ml, and 81 patients were assessed as belonging to Child-Pugh classification A upon the diagnosis of brain metastasis. WBRT alone in 71 patients, surgery or radiosurgery combined with WBRT as the adjuvant setting in 18 patients, and WBRT as salvage treatment in 8 patients were performed. The median overall survival of the patients was 3.5 months. In the multivariate analysis, the ECOG performance status (PS), Child-Pugh classification, AFP, and treatment aim showed significant association with the overall survival of the patients. Based on these factors, a nomogram predicting the prognosis was developed. The concordance index of the nomogram was 0.74, and the prediction was well calibrated. In conclusion, the survival outcome of patients with brain metastasis from HCC can be predicted with the nomogram constructed from the ECOG PS, Child-Pugh classification, AFP, and treatment aim.

  12. Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

    Directory of Open Access Journals (Sweden)

    Wen-Chih Liu

    2012-05-01

    Full Text Available A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

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

    Science.gov (United States)

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

    2015-08-01

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

  14. Edema is not a reliable diagnostic sign to exclude small brain metastases.

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    Tanja Schneider

    Full Text Available No prior systematic study on the extent of vasogenic edema (VE in patients with brain metastases (BM exists. Here, we aim to determine 1 the general volumetric relationship between BM and VE, 2 a threshold diameter above which a BM shows VE, and 3 the influence of the primary tumor and location of the BM in order to improve diagnostic processes and understanding of edema formation. This single center, retrospective study includes 173 untreated patients with histologically proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images was conducted. Statistical analyses were performed using a paired-samples t-test, linear regression/generalized mixed-effects model, and receiver-operating characteristic (ROC curve controlling for the possible effect of non-uniformly distributed metastases among patients. For BM with non-confluent edema (n = 545, there was a statistically significant positive correlation between the volumes of the BM and the VE (P < 0.001. The optimal threshold for edema formation was a diameter of 9.4 mm for all BM. The primary tumors as interaction term in multivariate analysis had a significant influence on VE formation whereas location had not. Hence VE development is dependent on the volume of the underlying BM and the site of the primary neoplasm, but not from the location of the BM.

  15. Edema is not a reliable diagnostic sign to exclude small brain metastases.

    Science.gov (United States)

    Schneider, Tanja; Kuhne, Jan Felix; Bittrich, Paul; Schroeder, Julian; Magnus, Tim; Mohme, Malte; Grosser, Malte; Schoen, Gerhard; Fiehler, Jens; Siemonsen, Susanne

    2017-01-01

    No prior systematic study on the extent of vasogenic edema (VE) in patients with brain metastases (BM) exists. Here, we aim to determine 1) the general volumetric relationship between BM and VE, 2) a threshold diameter above which a BM shows VE, and 3) the influence of the primary tumor and location of the BM in order to improve diagnostic processes and understanding of edema formation. This single center, retrospective study includes 173 untreated patients with histologically proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images was conducted. Statistical analyses were performed using a paired-samples t-test, linear regression/generalized mixed-effects model, and receiver-operating characteristic (ROC) curve controlling for the possible effect of non-uniformly distributed metastases among patients. For BM with non-confluent edema (n = 545), there was a statistically significant positive correlation between the volumes of the BM and the VE (P edema formation was a diameter of 9.4 mm for all BM. The primary tumors as interaction term in multivariate analysis had a significant influence on VE formation whereas location had not. Hence VE development is dependent on the volume of the underlying BM and the site of the primary neoplasm, but not from the location of the BM.

  16. CARBOPLATIN AS 2ND LINE TREATMENT FOR RECURRENT OR PROGRESSIVE BRAIN METASTASES FROM SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    GROEN, HJM; SMIT, EF; HAAXMAREICHE, H; POSTMUS, PE

    1993-01-01

    Patients with brain metastases from small cell lung cancer (SCLC) have a poor prognosis. Although most patients die from metastatic disease outside the central nervous system, this disabling metastatic site often needs treatment to mitigate the signs and symptoms of intracranial disease. The effect

  17. MGMT promoter methylation status in brain metastases from colorectal cancer and corresponding primary tumors.

    Science.gov (United States)

    De Maglio, Giovanna; Casagrande, Mariaelena; Guardascione, Michela; Fontanella, Caterina; Lutrino, Stefania Eufemia; Rihawi, Karim; Pisa, Federica Edith; Tuniz, Francesco; Fasola, Gianpiero; Pizzolitto, Stefano; Aprile, Giuseppe

    2015-01-01

    Brain metastases (BM) from colorectal cancer are usually associated with poor prognosis. The aim of this retrospective study is to evaluate MGMT promoter methylation in BM and their corresponding primary colorectal cancer tumors. MGMT promoter methylation status was assessed by pyrosequencing in 53 consecutive patients resected for BM. A concordance analysis between BM and matched primary tumor was performed in 39 cases. MGMT methylation was found in 34 (64.2%) BM and in 25 corresponding primary tumors (64.1%). Median survival after neurosurgery was independent from MGMT promoter methylation (163 days for those with methylated MGMT versus 193 days for the unmethylated). Epigenetic MGMT promoter methylation was common and the concordance between primary and secondary lesions was high.

  18. 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

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

    Science.gov (United States)

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

    2017-10-01

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

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

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    Hauswald Henrik

    2012-08-01

    Full Text Available Abstract Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT in patients with multiple brain metastases (BM from malignant melanoma (MM. Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56 or 40 Gy in 20 fractions (n = 31. All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months, the 6- and 12-months overall-(OS survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11 patients showed a complete (partial remission, while 11 (17 patients had stable disease (intra-cerebral tumor progression. In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months. Furthermore, DS-GPA score (p  Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

  1. Fractionated Stereotactic Gamma Knife Radiosurgery for Large Brain Metastases: A Retrospective, Single Center Study.

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    Joo Whan Kim

    Full Text Available Stereotactic radiosurgery (SRS is widely used for brain metastases but has been relatively contraindicated for large lesions (>3 cm. In the present study, we analyzed the efficacy and toxicity of hypofractionated Gamma Knife radiosurgery to treat metastatic brain tumors for which surgical resection were not considered as the primary treatment option.Thirty-six patients, forty cases were treated with Gamma Knife-based fractionated SRS for three to four consecutive days with the same Leksell frame on their heads. The mean gross tumor volume was 18.3 cm³, and the median dose was 8 Gy at 50% isodose line with 3 fractions for three consecutive days (range, 5 to 11 Gy and 2 to 4 fractions for 2 to 4 consecutive days. Survival rates and prognostic factors were analyzed.The overall survival rate at one and two years was 66.7 and 33.1%, respectively. The median survival time was 16.2 months, and the local control rate was 90%. RTOG toxicity grade 1 was observed in 3 (8.3% patients, grade 2 in 1 (2.7% patient and grade 3 in 1 (2.7% patient respectively. Radiation necrosis was developed in 1 (2.7% patient. KPS scores and control of primary disease resulted in significant differences in survival.Our findings suggest that consecutive hypofractionated Gamma Knife SRS could be applied to large metastatic brain tumors with effective tumor control and low toxicity rates.

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

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-06-01

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

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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    KVL Narasinga Rao

    2015-01-01

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

  6. Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it [Unit of Radiation Oncology, Sant' Andrea Hospital, Sapienza University of Rome, Rome (Italy); IRCCS Neuromed, Pozzilli (Italy); Scaringi, Claudia [Unit of Radiation Oncology, Sant' Andrea Hospital, Sapienza University of Rome, Rome (Italy); Paolini, Sergio; Lanzetta, Gaetano [IRCCS Neuromed, Pozzilli (Italy); Romano, Andrea [Unit of Neuroradiology, Sant' Andrea Hospital, Sapienza University of Rome, Rome (Italy); Cicone, Francesco [Unit of Nuclear Medicine, Sant' Andrea Hospital, Sapienza University of Rome, Rome (Italy); Osti, Mattia; Enrici, Riccardo Maurizi [Unit of Radiation Oncology, Sant' Andrea Hospital, Sapienza University of Rome, Rome (Italy); Esposito, Vincenzo [IRCCS Neuromed, Pozzilli (Italy)

    2016-07-15

    Purpose: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, a propensity score analysis was used. Results: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.

  7. 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.

  8. Use of Stereotactic Radiosurgery in Elderly and Very Elderly Patients With Brain Metastases to Limit Toxicity Associated With Whole Brain Radiation Therapy.

    Science.gov (United States)

    Chen, Linda; Shen, Colette; Redmond, Kristin J; Page, Brandi R; Kummerlowe, Megan; Mcnutt, Todd; Bettegowda, Chetan; Rigamonti, Daniele; Lim, Michael; Kleinberg, Lawrence

    2017-07-15

    We evaluated the toxicity associated with stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) in elderly and very elderly patients with brain metastases, as the role of SRS in geriatric patients who would traditionally receive WBRT is unclear. We conducted a retrospective review of elderly patients (aged 70-79 years) and very elderly patients (aged ≥80 years) with brain metastases who underwent RT from 2010 to 2015 at Johns Hopkins Hospital. Patients received either upfront WBRT or SRS for metastatic solid malignancies, excluding small cell lung cancer. Acute central nervous system toxicity within 3 months of RT was graded using the Radiation Therapy Oncology Group acute radiation central nervous system morbidity scale. The toxicity data between age groups and treatment modalities were analyzed using Fisher's exact test and multivariate logistic regression analysis. Kaplan-Meier curves were used to estimate the median overall survival, and the Cox proportion hazard model was used for multivariate analysis. A total of 811 brain metastases received RT in 119 geriatric patients. The median overall survival from the diagnosis of brain metastases was 4.3 months for the patients undergoing WBRT and 14.4 months for the patients undergoing SRS. On multivariate analysis, WBRT was associated with worse overall survival in this cohort of geriatric patients (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.9-7.0, PElderly and very elderly patients did not have significantly different statistically acute toxicity rates when stratified by age. WBRT was associated with increased toxicity compared with SRS in elderly and very elderly patients with brain metastases. SRS, rather than WBRT, should be prospectively evaluated in geriatric patients with the goal of minimizing treatment-related toxicity. Copyright © 2017. Published by Elsevier Inc.

  9. Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases.

    Science.gov (United States)

    Ma, Lijun; Petti, Paula; Wang, Brian; Descovich, Martina; Chuang, Cynthia; Barani, Igor J; Kunwar, Sandeep; Shrieve, Dennis C; Sahgal, Arjun; Larson, David A

    2011-06-01

    Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent. The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator-based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain. Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted. The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.

  10. Tumor Bed Dynamics After Surgical Resection of Brain Metastases: Implications for Postoperative Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Lesley A., E-mail: lesley.a.jarvis@hitchcock.org [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Simmons, Nathan E. [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Bellerive, Marc [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Erkmen, Kadir [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Eskey, Clifford J. [Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (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. [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Hartford, Alan C. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States)

    2012-11-15

    Purpose: To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). Methods and Materials: Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed {<=}1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. Results: The mean tumor volume before surgery was 14.23 cm{sup 3}, and the mean cavity volume was 8.53 cm{sup 3} immediately after surgery and 8.77 cm{sup 3} before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of {<=}2 cm{sup 3}; 10 cavities (23.3%) collapsed by >2 cm{sup 3}; and 13 cavities (30.2%) increased by >2 cm{sup 3}. The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. Conclusions: In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi

  11. A Randomized Controlled Open-Label Pilot Study of Simvastatin Addition to Whole-Brain Radiation Therapy in Patients With Brain Metastases.

    Science.gov (United States)

    El-Hamamsy, Manal; Elwakil, Hesham; Saad, Amr S; Shawki, May A

    2016-10-27

    Statins have been reported to have a potential radiosensitizing effect that has not been evaluated in clinical trials. The aim of this study was to evaluate the efficacy and safety of simvastatin in addition to whole-brain radiation therapy (WBRT) in patients with brain metastases (BM). A prospective randomized, controlled, open-label pilot study was conducted on 50 Egyptian patients with BM who were randomly assigned to receive 30-Gy WBRT (control group: 25 patients) or 30 Gy WBRT + simvastatin 80 mg/day for the WBRT period (simvastatin group: 25 patients). The primary outcome was radiological response at 4 weeks after WBRT. Secondary outcomes were 1-year progression-free survival (PFS), 1-year overall survival (OS), and health-related quality of life (HRQL) that was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and its brain module (BN-20), at baseline, after WBRT, and 4 weeks after WBRT. The addition of simvastatin was tolerated. Twenty-one patients were not evaluated for radiological response because of death (n = 16), noncompliance to follow-up (n = 4), and clinical deterioration (n = 1). Response rates were 60% and 78.6% (p = 0.427), 1-year PFS rates were 5.2% and 17.7% (p = 0.392), and 1-year OS rates were 12% and 8% (p = 0.880) for the control group and simvastatin group, respectively. Nonsignificant differences were found between the two arms regarding HRQL scales. The addition of simvastatin 80 mg/day did not improve the clinical outcomes of patients with BM receiving WBRT.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-01

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

  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. Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target.

    Science.gov (United States)

    Chen, Guo; Chakravarti, Nitin; Aardalen, Kimberly; Lazar, Alexander J; Tetzlaff, Michael T; Wubbenhorst, Bradley; Kim, Sang-Bae; Kopetz, Scott; Ledoux, Alicia A; Gopal, Y N Vashisht; Pereira, Cristiano Goncalves; Deng, Wanleng; Lee, Ju-Seog; Nathanson, Katherine L; Aldape, Kenneth D; Prieto, Victor G; Stuart, Darrin; Davies, Michael A

    2014-11-01

    An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and quantitative analysis of protein expression and activation by reverse-phase protein array (RPPA) analysis were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors. The status of 154 previously reported hotspot mutations, including driver mutations in BRAF and NRAS, were concordant in all evaluable patient-matched pairs of tumors. Overall patterns of CNV, mRNA expression, and protein expression were largely similar between the paired samples for individual patients. However, brain metastases demonstrated increased expression of several activation-specific protein markers in the PI3K/AKT pathway compared with the extracranial metastases. These results add to the understanding of the molecular characteristics of melanoma brain metastases and support the rationale for additional testing of the PI3K/AKT pathway as a therapeutic target in these highly aggressive tumors. ©2014 American Association for Cancer Research.

  17. 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.

  18. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial

    OpenAIRE

    Cort?s, Javier; Rugo, Hope S.; Awada, Ahmad; Twelves, Chris; Perez, Edith A.; Im, Seock?Ah; G?mez-Pardo, Patricia; Schwartzberg, Lee S; Di?ras, Veronique; Yardley, Denise A.; Potter, David A.; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol

    2017-01-01

    Purpose Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Methods The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BE...

  19. P08.23MULTIPLE CALCIFIED BRAIN METASTASES IN A MALE PATIENT WITH INVASIVE DUCTAL BREAST CANCER

    OpenAIRE

    Ressl, N.; Haindl, M.; Schenk, T.; Ungersboeck, K.; Sedivy, R.; Oberndorfer, S.

    2014-01-01

    Breast cancer in men is a rare disease and accounts for 1.6% of all malignancies of the breast. We report a case of a 51-year-old man with invasive ductal carcinoma of the breast with multiple calcified brain metastases. After modified radical mastectomy he received adjuvant chemotherapy with cyclophosphamide and doxorubicin, hormonal therapy and trastuzumab. About one year after initial diagnosis he developed a generalized epileptic seizure. Neuroradiological imaging (MRI) revealed multiple ...

  20. Clinical efficacy of liver resection after downsizing systemic chemotherapy for initially unresectable liver metastases.

    Science.gov (United States)

    Kawamura, Junichiro; Yazawa, Takefumi; Sumida, Kimiaki; Kida, Yuya; Ogawa, Ryotaro; Tani, Masaki; Kawasoe, Junya; Yamamoto, Michihiro; Harada, Hideki; Yamamoto, Hidekazu; Zaima, Masazumi

    2016-02-25

    This study sought to clarify the clinical benefits of liver resection after downsizing systemic chemotherapy for initially unresectable colorectal liver metastases (CLM). Survival and clinical characteristics of CLM patients who underwent resection between January 2001 and December 2013 were retrospectively assessed. The study cohort of 88 patients with limited liver disease who underwent curative liver resection comprised 34 with initially resectable synchronous disease (synchronous group), 38 with initially resectable metachronous disease (metachronous group), and 16 with initially unresectable converted disease (conversion group). The median duration of follow-up for the overall study population was 33 (1-98) months. Overall survival (OS) in the conversion group was not significantly different from that in the other groups. However, disease-free survival (DFS) in the conversion group was significantly shorter than that in the synchronous group. The median DFS was 19.1 months in the synchronous group, 16.6 months in the metachronous group, and 15.3 months in the conversion group. Most patients in the conversion group had recurrence shortly after liver resection in the remnant liver with or without metastases at other sites, but many could undergo repeat hepatectomy or resection of the metastases at other sites. Although the converted patients tended to have recurrence shortly after liver resection, survival could be prolonged by repeat hepatectomy or resection of metastases at other sites. Liver resection after downsizing chemotherapy appears to be efficacious for patients with initially unresectable CLM and may result in long-term outcomes equivalent to those of patients with initially resectable CLM.

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

    Science.gov (United States)

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

    2017-07-01

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

  2. Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

    Science.gov (United States)

    Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

    2017-06-15

    The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (Pbrain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

  3. 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.

  4. Stereotactic laser ablation as treatment for brain metastases that recur after stereotactic radiosurgery: a multiinstitutional experience.

    Science.gov (United States)

    Ali, Mir Amaan; Carroll, Kate T; Rennert, Robert C; Hamelin, Thomas; Chang, Leon; Lemkuil, Brian P; Sharma, Mayur; Barnholtz-Sloan, Jill S; Myers, Charlotte; Barnett, Gene H; Smith, Kris; Mohammadi, Alireza M; Sloan, Andrew E; Chen, Clark C

    2016-10-01

    OBJECTIVE Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited. METHODS The authors provide the collective experience of 4 institutions where treatment of BMs that recurred after SRS was performed with stereotactic laser ablation (SLA). RESULTS Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (2 patients each underwent 2 SLAs for separate lesions, and a third underwent 2 serial SLAs for discrete BMs). Histological findings in the BMs treated included the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2); ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1). With a median follow-up duration of 141 days (range 64-794 days), 9 of the SLA-treated BMs progressed despite treatment (35%). All cases of progression occurred in BMs in which Stereotactic laser ablation is an effective treatment option for BMs in which SRS fails. Ablation of ≥ 80% of BMs is associated with decreased risk of disease progression. The efficacy of SLA in this setting may be augmented by adjuvant hypofractionated SRS.

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

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Johannesen, Helle H; Geertsen, Poul

    2017-01-01

    An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospect......An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later....... In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point...... 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...

  6. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Advanced Mesodermal (Müllerian Adenosarcoma of the Ovary: Metastases to the Lungs, Mouth, and Brain

    Directory of Open Access Journals (Sweden)

    A. Daskalaki

    2015-01-01

    Full Text Available Background. A malignant mixed Müllerian tumor (MMMT is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes, and other parts of the body that contains both carcinomatous (epithelial tissue and sarcomatous (connective tissue components. Outcome of MMMTs is determined primarily by depth of invasion and stage. The metastatic background of these lesions is controversial and unknown. Case Report. A 75-year-old woman was admitted to the hospital with anorexia, weakness, and persistent coughing. The imaging exams revealed a solid, promiscuous lesion of 16 × 14 cm in dimensions located into the small pelvis, surrounding the uterus and the ovaries. The patient underwent exploratory laparotomy. The mass was removed and the histological examination of the specimen revealed an advanced mesodermal adenocarcinoma of the ovary (MMMT. Nine days after the operation the patient presented with metastatic lesions in the mouth as well as the lungs. Within a month after the discharge from the hospital metastatic lesions of the MMMT were also depicted in the CT brain scan. Conclusion. Despite the fact that sarcomas have a long-term metastatic potential, to our knowledge this is the first case of Müllerian adenosarcoma presenting with such extraperitoneal metastases.

  8. Brain and ocular metastases from a transmissible venereal tumour in a dog.

    Science.gov (United States)

    Ferreira, A J; Jaggy, A; Varejão, A P; Ferreira, M L; Correia, J M; Mulas, J M; Almeida, O; Oliveira, P; Prada, J

    2000-04-01

    A five-year-old crossbred dog was referred with rapidly growing masses over its penis and right popliteal lymph node. The dog had severe blepharospasm, congestion of episcleral vessels and rubeosis iridis of the left eye. A presumptive diagnosis of transmissible venereal tumour (TVT) and iridocyclitis was made based on the results of fine needle aspiration. Chemotherapy with vincristine and prednisolone was initiated and after four months the dog made a complete recovery. However, the dog subsequently relapsed, showing miosis, blepharospasm and a well defined mass within the anterior chamber of the left eye. In addition, the dog exhibited generalised 'grand mal' type seizures. Computed tomographic (CT) examination of the brain revealed two distinct masses in the left frontal lobe. Because of the poor prognosis, the owners elected to have the dog euthanased. On histopathology, metastases of TVT in the left eye and left cerebral hemisphere were found, showing no specific staining for CD3, immunoglobulin (Ig) G, IgM and lambda light chains. It was therefore concluded that the tumour growth was progressive, and that there was an absence of local humoral immune response against TVT in this case.

  9. Total encephalic radiotherapy and concomitant administering of trastuzumab for brain metastases of a mammary carcinoma with HER2 overexpression: experience of the Curie Institute; Radiotherapie encephalique totale et administration concomitante de trastuzumab pour des metastases cerebrales d'un carcinome mammaire surexprimant HER2: experience de l'institut Curie

    Energy Technology Data Exchange (ETDEWEB)

    Chargari, C.; Idrissi, H.R.; Pierga, J.Y.; Bollet, M.; Dieras, V.; Campana, F.; Cottu, P.; Fourquet, A.; Kirova, Y. [Institut Curie, 75 - Paris (France)

    2010-10-15

    The authors report a retrospective study of assessment of the tolerance to and of the activity of the trastuzumab in association with a total encephalic irradiation. The study is based on 31 patients suffering from brain metastases in relationship with a mammary cancer with HER2 expression, and who have been submitted to a total encephalic radiotherapy with a trastuzumab treatment. This medicine appears to be efficient and harmless. A clinic trial should confirm these results. Short communication

  10. Intracranial dural metastases.

    Science.gov (United States)

    Nayak, Lakshmi; Abrey, Lauren E; Iwamoto, Fabio M

    2009-05-01

    : Intracranial dural metastases (IDM) are found at autopsy in 9% of patients with advanced systemic cancer. However, to the authors' knowledge, IDM have not been studied systematically in the modern neuroimaging era. The objective of the current study was to evaluate the demographics, clinical presentation, imaging, treatment, and prognosis of patients with IDM. : The current study was a retrospective review of 122 patients with IDM diagnosed at Memorial Sloan-Kettering Cancer Center between 1999 and 2006. Patients with concurrent brain or leptomeningeal metastases were excluded. : Sixty-one percent of the patients were women; the median age at diagnosis was 59 years, the median Karnofsky performance scale (KPS) at diagnosis was 80, and the median time to IDM diagnosis from initial cancer diagnosis was 37 months. Breast (34%) and prostate (17%) cancers were the most frequent primary tumors associated with IDM. Fifty-six percent of patients had a single dural metastasis. On imaging, 70% had metastases of the overlying skull, 44% had dural tail metastases, 53% had vasogenic edema, and 34% had brain invasion. Direct extension from skull metastases was the most common mode of spread. Eighty-three percent of patients had active systemic disease at the time of IDM diagnosis. A lower KPS and lung cancer were associated with worse overall survival. Surgical resection and chemotherapy improved progression-free survival, but only resection was found to be associated with improved overall survival. : IDM affect a significant proportion of cancer patients. KPS and status of systemic cancer should guide treatment decisions. Cancer 2009. (c) 2009 American Cancer Society.

  11. Clinical features of patients with non-Hodgkin’s lymphoma metastasizing to the pituitary glands

    Science.gov (United States)

    YANG, JUNJIE; ZHAO, NA; ZHANG, GUANGSEN; ZHENG, WENLI

    2013-01-01

    It is rare for systemic non-Hodgkin’s lymphoma (NHL) to metastasize to the hypothalamus and pituitary glands. The present study describes two patients with NHL and diabetes insipidus (DI) and 17 patients from the literature in order to analyze the clinical features of patients with NHL metastasizing to the pituitary glands. Diffuse large B cell lymphoma (DLBCL) was observed to be the most common type of NHL involving the hypothalamus-pituitary axis. A total of 11 patients (57.9%) had been diagnosed with DI (post-pituitary involvement), five (26.3%) with anterior hypopituitarism and three (15.8%) with posterior and anterior hypopituitarism. Only two cases exhibited simultaneous endocrine and lymphoma manifestations; the majority of cases (68.4%) exhibited lymphoma manifestations first. To make an etiological diagnosis of NHL with metastases to the pituitary glands, it is necessary to find that NHL exists in other regions of patient’s body. Biopsy of the sellar may have significant meaning, but this examination may difficult to perform. Chemotherapy for NHL relieves pituitary impairment symptoms and improves the overall examination results. Additionally, magnetic resonance imaging (MRI) of the pituitary gland has a certain differential diagnostic value as the T1- and T2-weighted imaging (WI) signals from patients with systemic NHL with pituitary involvement are low. PMID:23760877

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

    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.; 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)

    2012-10-01

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

  13. Analysis of the expression of Kv10.1 potassium channel in patients with brain metastases and glioblastoma multiforme: impact on survival.

    Science.gov (United States)

    Martínez, Ramón; Stühmer, Walter; Martin, Sabine; Schell, Julian; Reichmann, Andrea; Rohde, Veit; Pardo, Luis

    2015-11-03

    Kv10.1, a voltage-gated potassium channel only detected in the healthy brain, was found to be aberrantly expressed in extracerebral cancers. Investigations of Kv10.1 in brain metastasis and glioblastoma multiforme (GBM) are lacking. We analyzed the expression of Kv10.1 by immunohistochemistry in these brain tumors (75 metastasis from different primary tumors, 71 GBM patients) and the influence of a therapy with tricyclic antidepressants (which are Kv10.1 blockers) on survival. We also investigated Kv10.1 expression in the corresponding primary carcinomas of metastases patients. We observed positive Kv10.1 expression in 85.3 % of the brain metastases and in 77.5 % of GBMs. Patients with brain metastases, showing low Kv10.1 expression, had a significantly longer overall survival compared to those patients with high Kv10.1 expression. Metastases patients displaying low Kv10.1 expression and also receiving tricyclic antidepressants showed a significantly longer median overall survival as compared to untreated patients. Our data show that Kv10.1 is not only highly expressed in malignant tumors outside CNS, but also in the most frequent cerebral cancer entities, metastasis and GBM, which remain incurable in spite of aggressive multimodal therapies. Our results extend the correlation between dismal prognosis and Kv10.1 expression to patients with brain metastases or GBMs and, moreover, they strongly suggest a role of tricyclic antidepressants for personalized therapy of brain malignancies.

  14. Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

    Science.gov (United States)

    Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

    2017-03-01

    The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Clinical significance of microscopic melanoma metastases in the nonhottest sentinel lymph nodes.

    Science.gov (United States)

    Luo, Su; Lobo, Alice Z C; Tanabe, Kenneth K; Muzikansky, Alona; Durazzo, Tyler; Sober, Arthur; Tsao, Hensin; Cosimi, A Benedict; Lawrence, Donald P; Duncan, Lyn M

    2015-05-01

    A practice gap exists in the surgical removal of sentinel lymph nodes, from removal of only the most radioactive (hottest) lymph node to removal of all lymph nodes with radioactivity greater than 10% of the hottest lymph node. To determine the clinical significance of melanoma in sentinel lymph nodes that are not the hottest sentinel node and to determine the risk for disease progression based on sentinel lymph node status and primary tumor characteristics. Consecutive patients with cutaneous melanoma with sentinel lymph nodes resected from January 5, 2004, to June 30, 2008, with a mean follow-up of 59 months, at Massachusetts General Hospital were included in this retrospective review. The last year of follow-up was 2012. The operative protocol led to resection of all sentinel lymph nodes with radioactivity greater than 10% of the hottest lymph node. The number of lymph nodes removed, technetium-99m counts for each sentinel lymph node, presence or absence of sentinel lymph node metastases, primary tumor characteristics, disease progression, and melanoma-specific survival were recorded. Microscopic melanoma metastases in the hottest and nonhottest sentinel lymph nodes and factors that correlate with disease progression and mortality. A total of 1575 sentinel lymph nodes were analyzed in 475 patients. Ninety-one patients (19%) had positive sentinel lymph nodes. Of these, 72 (79%) had metastases in the hottest sentinel lymph node. Of 19 cases with tumor present, but not in the hottest sentinel lymph node, counts ranged from 26% to 97% of the hottest node. Progression occurred in 43% of patients with sentinel node metastasis, regardless of whether the hottest lymph node was positive. In patients with negative sentinel lymph nodes, 11% developed metastases beyond the sentinel lymph node basin and 3.4% recurred in the basin. Mitogenicity of the primary tumor was associated with mortality (odds ratio, 2.435; 95% CI, 1.351-4.391; P negative results in 19 of 475 (4%) of

  17. Efficacy and Safety of Fractionated Stereotactic Radiosurgery for Large Brain Metastases

    Science.gov (United States)

    Jeong, Won Joo; Park, Jae Hong; Lee, Eun Jung; Kim, Jeong Hoon; Kim, Chang Jin

    2015-01-01

    Objective To investigate the efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases (BMs). Methods Between June 2011 and December 2013, a total of 38 large BMs >3.0 cm in 37 patients were treated with fractionated Cyberknife radiosurgery. These patients comprised 16 men (43.2%) and 21 women, with a median age of 60 years (range, 38-75 years). BMs originated from the lung (n=19, 51.4%), the gastrointestinal tract (n=10, 27.0%), the breast (n=5, 13.5%), and other tissues (n=3, 8.1%). The median tumor volume was 17.6 cc (range, 9.4-49.6 cc). For Cyberknife treatment, a median peripheral dose of 35 Gy (range, 30-41 Gy) was delivered in 3 to 5 fractions. Results With a median follow-up of 10 months (range, 1-37 months), the crude local tumor control (LTC) rate was 86.8% and the estimated LTC rates at 12 and 24 months were 87.0% and 65.2%, respectively. The median overall survival (OS) and progression-free survival (PFS) rates were 16 and 11 months, respectively. The estimated OS and PFS rates at 6, 12, and 18 months were 81.1% and 65.5%, 56.8% and 44.9%, and 40.7% and 25.7%, respectively. Patient performance status and preoperative focal neurologic deficits improved in 20 of 35 (57.1%) and 12 of 17 patients (70.6%), respectively. Radiation necrosis with a toxicity grade of 2 or 3 occurred in 6 lesions (15.8%). Conclusion These results suggest a promising role of fractionated stereotactic radiosurgery in treating large BMs in terms of both efficacy and safety. PMID:26539264

  18. Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases.

    Science.gov (United States)

    Frakes, Jessica M; Figura, Nicholas B; Ahmed, Kamran A; Juan, Tzu-Hua; Patel, Neha; Latifi, Kujtim; Sarangkasiri, Siriporn; Strom, Tobin J; Chinnaiyan, Prakash; Rao, Nikhil G; Etame, Arnold B

    2015-11-01

    Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with ≥5 lesions. The authors sought to determine the effectiveness of SRS in patients with ≥5 melanoma brain metastases. A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for ≥5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model. The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38-83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01-12.5 cm3). Median follow-up was 6.3 months (range 1-46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume≥0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2-292.6, pStereotactic radiosurgery for ≥5 lesions appears to be effective for selected patients with metastatic melanoma, offering excellent LC. This is particularly important for patients as new targeted systemic agents are improving outcomes but still

  19. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

    Science.gov (United States)

    Gondi, Vinai; Pugh, Stephanie L; Tome, Wolfgang A; Caine, Chip; Corn, Ben; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey N; Konski, Andre A; Bauman, Glenn S; Shah, Sunjay; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa; Mehta, Minesh P

    2014-12-01

    Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P memory and QOL as compared with historical series. © 2014 by American Society of Clinical Oncology.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Ding Xiao

    2012-07-01

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

  2. Radiological distribution of brain metastases and its implication for the hippocampus avoidance in whole brain radiotherapy approach.

    Science.gov (United States)

    Han, Yi-Min; Cai, Gang; Chai, Wei-Min; Xu, Cheng; Cao, Lu; Ou, Dan; Chen, Jia-Yi; Kirova, Youlia M

    2017-11-01

    Hippocampus avoidance in whole brain radiotherapy (HA-WBRT) offers the feasibility of less-impaired cognitive function than conventional WBRT. The study aims to assess the radiological distribution of brain metastases (BMs) with relation to the hippocampus and peri-hippocampus region as defined by the RTOG 0933 for better understanding of margin definition in HA-WBRT treatment planning. Consecutive patients with diagnosis of BM from enhanced MRI between March 2011 and July 2016 were analysed. The pre-treatment T1 weighted, T2 weighted, T2 flair, three-dimensional spoiled gradient axial and contrast-enhanced axial cranial MR images of 226 patients are examined. The closest distances between the edge of hippocampus and the margin of tumours on different planes were measured. A total of 226 patients with 1080 visible metastatic sites were reviewed. The origin of the primary tumors was in 72.6% lung (n = 164), in 45 cases (19.9%) breast cancer and in 7.5% other malignancies (n = 17). There were 758 (70.2%) lesions situated beyond the tentorium. The median size of single lesion was 13.9 ± 14.7 mm. Impossible, it seems that more of the patients are with only one lesion, to verify. The hippocampus involvement was found in 3.1% (n = 7, 95% CI 0.01-0.05) within 5 mm, 5.7% (n = 13, 95% CI 0.03-0.09) within 10mm and 8.4% (n = 19, 95% CI 0.05-0.12) within 20 mm. In multivariate analysis, the number 6 BM or higher was found to be an independent risk factor for hippocampal involvement (HI) (OR: 5.2, 5.38 and 3.84 in 5, 10 and 20 mm). This radiological study found that the incidence of hippocampus involvement is low in patients with BM. HA-WBRT can be delivered under the context of complete radiological diagnosis after careful delineation, proper margin definition and individual planning optimization. Advances in knowledge: The incidence of HI in patients with initial diagnosis of BM from solid tumours impacts the radiotherapeutic decision. Our radiological data analysed the

  3. Distant metastases following permanent interstitial brachytherapy for patients with clinically localized prostate cancer.

    Science.gov (United States)

    Taira, Al V; Merrick, Gregory S; Galbreath, Robert W; Butler, Wayne M; Lief, Jonathan; Adamovich, Edward; Wallner, Kent E

    2012-02-01

    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. 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. 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 treatment, whereas CSS was most closely associated with Gleason score. Excellent CSS and MFS rates are achievable with high-quality brachytherapy for low, intermediate, and high-risk patients. These results compare favorably to alternative treatment modalities. In particular, our MFS and CSS rates for high-risk patients appear superior to those of published radical prostatectomy series. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. 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.

  5. Clinical characteristics and risk factors for developing bone metastases in patients with breast cancer

    OpenAIRE

    Chen, Wen-Zhao; Shen, Jun-Feng; Zhou, Yang; Xuan-yin CHEN; Liu, Jia-Ming; Liu, Zhi-Li

    2017-01-01

    The risk factors for predicting bone metastases in patients with breast cancer are still controversial. Here, a total of 2133 patients with breast cancer, including 327 with bone metastases (15.33%) and 1806 without bone metastases (84.67%) were retrospective reviewed from January 2005 to December 2015. The spine was found to be the most common site for bone metastases, followed by ribs (57.5%), pelvis (54.1%) and sternum (44.3%). The results indicated that axillary lymph node metastases and ...

  6. Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.

    Science.gov (United States)

    Lee, Ho Jeong; Hanibuchi, Masaki; Kim, Sun-Jin; Yu, Hyunkyung; Kim, Mark Seungwook; He, Junqin; Langley, Robert R; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2016-04-01

    We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved

  7. SU-F-T-618: Evaluation of a Mono-Isocentric Treatment Planning Software for Stereotactic Radiosurgery of Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Sham, E; Sattarivand, M; Mulroy, L; Yewondwossen, M [Queen Elizabeth II Health Sciences Centre, Halifax, AB (Canada)

    2016-06-15

    Purpose: To evaluate planning performance of an automated treatment planning software (BrainLAB; Elements) for stereotactic radiosurgery (SRS) of multiple brain metastases. Methods: Brainlab’s Multiple Metastases Elements (MME) uses single isocentric technique to treat up to 10 cranial planning target volumes (PTVs). The planning algorithm of the MME accounts for multiple PTVs overlapping with one another on the beam eyes view (BEV) and automatically selects a subset of all overlapping PTVs on each arc for sparing normal tissues in the brain. The algorithm also optimizes collimator angles, margins between multi-leaf collimators (MLCs) and PTVs, as well as monitor units (MUs) using minimization of conformity index (CI) for all targets. Planning performance was evaluated by comparing the MME-calculated treatment plan parameters with the same parameters calculated with the Volumetric Modulated Arc Therapy (VMAT) optimization on Varian’s Eclipse platform. Results: Figures 1 to 3 compare several treatment plan outcomes calculated between the MME and VMAT for 5 clinical multi-targets SRS patient plans. Prescribed target dose was volume-dependent and defined based on the RTOG recommendation. For a total number of 18 PTV’s, mean values for the CI, PITV, and GI were comparable between the MME and VMAT within one standard deviation (σ). However, MME-calculated MDPD was larger than the same VMAT-calculated parameter. While both techniques delivered similar maximum point doses to the critical cranial structures and total MU’s for the 5 patient plans, the MME required less treatment planning time by an order of magnitude compared to VMAT. Conclusion: The MME and VMAT produce similar plan qualities in terms of MUs, target dose conformation, and OAR dose sparing. While the selective use of PTVs for arc-optimization with the MME reduces significantly the total planning time in comparison to VMAT, the target dose homogeneity was also compromised due to its simplified

  8. Treatment planning for MLC based robotic radiosurgery for brain metastases: plan comparison with circular fields and suggestions for planning strategies

    Directory of Open Access Journals (Sweden)

    Schmitt Daniela

    2017-09-01

    Full Text Available To evaluate the possible range of application of the new InCise2 MLC for the CyberKnife M6 system in brain radiosurgery, a plan comparison was made for 10 brain metastases sized between 1.5 and 9cm3 in 10 patients treated in a single fraction each. The target volumes consist of a PTV derived by expanding the GTV by 1mm and were chosen to have diversity in the cohort regarding regularity of shape, location and the structures needed to be blocked for beam transmission in the vicinity. For each case, two treatment plans were optimized: one using the MLC and one using the IRIS-collimator providing variable circular fields. Plan re-quirements were: dose prescription to the 70% isodose line (18 or 20Gy, 100% GTV coverage, ≥98% PTV coverage, undisturbed central high dose region (95% of maximum dose and a conformity index as low as possible. Plan com-parison parameters were: conformity index (CI, high-dose gradient index (GIH, low-dose gradient index (GIL, total number of monitor units (MU and expected treatment time (TT. For all cases, clinically acceptable plans could be gen-erated with the following results (mean±SD for CI, GIH, GIL, MU and TT, respectively for the MLC plans: 1.09±0.03, 2.77±0.26, 2.61±0.08, 4514±830MU and 27±5min and for the IRIS plans: 1.05±0.01, 3.00±0.35, 2.46±0.08, 8557±1335MU and 42±7min. In summary, the MLC plans were on average less conformal and had a shallower dose gradient in the low dose region, but a steeper dose gradient in the high dose region. This is accompanied by a smaller vol-ume receiving 10Gy. A plan by plan comparison shows that usage of the MLC can spare about one half of the MUs and one third of treatment time. From these experiences and results suggestions for MLC planning strategy can be de-duced.

  9. HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series

    Directory of Open Access Journals (Sweden)

    Gianpiero Fasola

    2013-01-01

    Full Text Available Brain metastases (BM from colorectal cancer (CRC are a rare but increasing event. Surgical resection of oligometastatic disease, including BM, may produce a survival benefit in selected patients. Previous studies described the HER-2 expression patterns in CRC patients, but its prognostic role still remains controversial. Information on the HER-2 expression in BM from CRC is currently lacking. Among the over 500 patients treated at our Department of Neurosurgery in the last 13 years (1999–2012, we identified a cohort of 50 consecutive CRC patients resected for BM. Clinical data were retrospectively reviewed using electronic hospital charts and surgical notes. Formalin-fixed, paraffin-embedded tissue samples were retrieved and histologically reviewed. HER-2 status was assessed on 4-μm sections by HerceptTest™, and scored by two pathologists according to gastric cancer HER-2 status guidelines. In score 2+ cases HER-2 gene copy number was analyzed by FISH, performed using the PathVysion HER-2 DNA Probe Kit. Median age at time of BM resection was 65 years (35–82; most patients were males (60% with a good performance status. The majority of the BM were single (74% and sited in the supratentorial area (64%; 2–4 lesions were diagnosed in 9 patients (18%, and >4 in 3 patients (6%. The rate of HER-2 positivity (defined as IHC score 3+ or IHC score 2+ and FISH gene amplification was 8.1% for the primary CRC tumors and 12% for their corresponding BM. The concordance rate between primary tumors and matched BM was 89%. Median overall survival after neurosurgery was 6.5 months for HER-2 IHC score 0 vs. 4.6 months for HER-2 IHC score 1+/2+/3+; the difference was statistically significant (p = 0.01, Log-rank test. HER-2 positivity of our case cohort was low but comparable to literature. Concordance rate of HER-2 expression between BM and corresponding primary tumors is high and similar to those reported for breast and gastric cancers. Our data suggest a

  10. 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.

  11. {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.)

  12. Cost-effectiveness of stereotactic radiosurgery with and without whole-brain radiotherapy for the treatment of newly diagnosed brain metastases.

    Science.gov (United States)

    Hall, Matthew D; McGee, James L; McGee, Mackenzie C; Hall, Kevin A; Neils, David M; Klopfenstein, Jeffrey D; Elwood, Patrick W

    2014-12-01

    Stereotactic radiosurgery (SRS) alone is increasingly used in patients with newly diagnosed brain metastases. Stereotactic radiosurgery used together with whole-brain radiotherapy (WBRT) reduces intracranial failure rates, but this combination also causes greater neurocognitive toxicity and does not improve survival. Critics of SRS alone contend that deferring WBRT results in an increased need for salvage therapy and in higher costs. The authors compared the cost-effectiveness of treatment with SRS alone, SRS and WBRT (SRS+WBRT), and surgery followed by SRS (S+SRS) at the authors' institution. The authors retrospectively reviewed the medical records of 289 patients in whom brain metastases were newly diagnosed and who were treated between May 2001 and December 2007. Overall survival curves were plotted using the Kaplan-Meier method. Multivariate proportional hazards analysis (MVA) was used to identify factors associated with overall survival. Survival data were complete for 96.2% of patients, and comprehensive data on the resource use for imaging, hospitalizations, and salvage therapies were available from the medical records. Treatment costs included the cost of initial and all salvage therapies for brain metastases, hospitalizations, management of complications, and imaging. They were computed on the basis of the 2007 Medicare fee schedule from a payer perspective. Average treatment cost and average cost per month of median survival were compared. Sensitivity analysis was performed to examine the impact of variations in key cost variables. No significant differences in overall survival were observed among patients treated with SRS alone, SRS+WBRT, or S+SRS with respective median survival of 9.8, 7.4, and 10.6 months. The MVA detected a significant association of overall survival with female sex, Karnofsky Performance Scale (KPS) score, primary tumor control, absence of extracranial metastases, and number of brain metastases. Salvage therapy was required in 43% of

  13. Clinical lessons from the first applications of BNCT on unresectable liver metastases.

    Science.gov (United States)

    Zonta, A.; Prati, U.; Roveda, L.; Ferrari, C.; Zonta, S.; Clerici, Am; Zonta, C.; Pinelli, T.; Fossati, F.; Altieri, S.; Bortolussi, S.; Bruschi, P.; Nano, R.; Barni, S.; Chiari, P.; Mazzini, G.

    2006-05-01

    After a long series of studies on the effects of neutron irradiation of 10B loaded neoplastic cells both in culture and in animal experiments, we started the clinical application of BNCT on humans affected by liver metastases of a radically resected colon adenocarcinoma. The procedure we adopted includes a first surgical phase, with hepatectomy; a radiotherapeutic phase, in which the isolated liver, washed and chilled, is extracorporeally irradiated with thermal neutrons; and then a second surgical phase for the reconnection of the liver to the patient. Until now two patients have been subjected to the BNCT treatment. The first one survived 44 months with a good quality of life, and died because of diffuse recurrences of his intestinal tumour. The second patient had the same early perioperative course, but after 33 days a worsening of a dilatative cardiomyopaty, from which he was suffering, determined a cardiac failure and eventually death. This clinical experience, although limited, has shown that extracorporeal neutron irradiation of the liver is a feasible procedure, able to ensure the complete destruction of liver metastases and a possible long lasting survival. In our patients neutron irradiation caused massive cellular necrosis highly specific to tumour cells, whereas normal cells were mostly spared. Nevertheless, the impact of such a traumatic operation on the patient's organism must be taken into account. Finally, we have to be aware that the fight against tumour rarely leads to a complete victory. We now have an innovative weapon which is both powerful and partly unsettled: it must be refined and above all used.

  14. Analyses of prognostic factors in cases of non-small cell lung cancer with multiple brain metastases

    Directory of Open Access Journals (Sweden)

    Gong X

    2016-03-01

    Full Text Available Xiaomei Gong,1 Daoan Zhou,1 Shixiong Liang,1 Caicun Zhou2 1Department of Radiation Oncology, 2Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Aim: To observe the therapeutic efficacy and prognostic factors that influence survival rates in non-small cell lung cancer (NSCLC patients with multiple brain metastases (BMs, more than three and less than ten. Methods: Retrospective analyses were conducted on the clinical data of 209 NSCLC patients with multiple BMs and were admitted to our hospital between March 2007 and November 2012. All BM patients received whole-brain radiotherapy. Two hundred patients received combined chemotherapy during the treatment process; 99 received targeted drug therapy; and nine got only symptomatic and supportive treatment. Survival time was defined as the period from the start of BM therapy to the patient’s death or end of the follow-up period. The Kaplan–Meier method was used to calculate the median survival time, and the 6-month, 1-, and 2-year cumulative survival rates, as well as to plot the survival curves. The patients’ cultural background included their socioeconomic status, level of education, their understanding of the disease, and the degree of care and support they received from their family members. Log-rank test was employed to test the differences in the survival rates between the subgroups. Cox multivariate regression analyses were used to analyze the various factors influencing the prognoses of NSCLC with multiple BMs. Results: The follow-up duration was between 1 and 87 months. The median survival time for all BM patients was 12.1 months (95% confidence interval 9.37–14.83. The 6-month, 1-, and 2-year cumulative survival rates were 80%, 50.2%, and 10.7%, respectively. Univariate analyses revealed that the independent factors influencing survival prognoses included Karnofsky Performance Status score, control of the

  15. Liver metastases

    Science.gov (United States)

    ... CT scan of the abdomen Liver function tests Liver biopsy MRI of the abdomen PET scan Ultrasound of ... Lung cancer - liver metastases; Melanoma - liver metastases Images Liver biopsy Hepatocellular cancer, CT scan Liver metastases, CT scan ...

  16. [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 %).

  17. Urinary bladder botryoid rhabdomyosarcoma with widespread metastases in an 8-month-old Labrador cross dog : clinical communication

    Directory of Open Access Journals (Sweden)

    K. Gerber

    2009-05-01

    Full Text Available An 8-month-old crossbred Labrador retriever was presented with a history and clinical signs suggestive of lower urinary tract obstruction. Laboratory results revealed azotaemia and hyperphosphataemia. Ultrasonographic evaluation of the urinary tract showed a mass at the bladder trigone, hydronephrosis, hyrodureter, and suspected metastases to lymph nodes and the liver. Pulmonary metastasis was identified on thoracic radiographs. A post mortem confirmed metastases to the liver, lungs and regional lymph nodes, as well as to the mesenteric lymph nodes, mediastinum, heart, subcutaneous tissue and several muscle groups. A histopathological diagnosis of metastatic botryoid rhabdomyosarcoma (sarcoma botryoides was made. A review of the literature shows that, although the bladder trigone is a well documented location for this tumour, this case was unique with its widespread metastases to previously undocumented organs. The incidence, embryology, ultrasonographic appearance and treatment of this tumour are discussed.

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

    Science.gov (United States)

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

    2013-02-01

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

  19. 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

  20. Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation.

    Science.gov (United States)

    Bernhardt, Denise; Bozorgmehr, Farastuk; Adeberg, Sebastian; Opfermann, Nils; von Eiff, Damian; Rieber, Juliane; Kappes, Jutta; Foerster, Robert; König, Laila; Thomas, Michael; Debus, Jürgen; Steins, Martin; Rieken, Stefan

    2016-11-01

    Patients with brain metastases from small-cell lung cancer (SCLC) who underwent prior prophylactic cranial irradiation (PCI) are often treated with a second course of whole brain radiation therapy (Re-WBRT) or stereotactic radiosurgery (SRS) for purposes of palliation in symptomatic patients, hope for increased life expectancy or even as an alternative to untolerated steroids. Up to date there is only limited data available regarding the effect of this treatment. This study examines outcomes in patients in a single institution who underwent cerebral re-irradiation after prior PCI. We examined the medical records of 76 patients with brain metastases who had initially received PCI between 2008 and 2015 and were subsequently irradiated with a second course of cerebral radiotherapy. Patients underwent re-irradiation using either Re-WBRT (88%) or SRS (17%). The outcomes, including symptom palliation, radiation toxicity, and overall survival (OS) following re-irradiation were analyzed. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. Treatment-related toxicity was classified according to CTCAE v4.0. Median OS of all patients was 3 months (range 0-12 months). Median OS after Re-WBRT was 3 months (range 0-12 months). Median OS after SRS was 5 months (range 0-12 months). Karnofsky performance status scale (KPS ≥50%) was significantly associated with improved OS in both univariate (HR 2772; p=0,009) and multivariate analyses (HR 2613; p=0,024) for patients receiving Re-WBRT. No unexpected toxicity was observed and the observed toxicity remained consistently low. Symptom palliation was achieved in 40% of symptomatic patients. In conclusion, cerebral re-irradiation after prior PCI is beneficial for symptom palliation and is associated with minimal side effects in patients with SCLC. Our survival data suggests that it is primarily useful in patients with adequate performance status. Copyright

  1. Radiotherapy for vertebral metastases. Analysis of symptoms and clinical effects by MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sugiyama, Akira [Shizuoka Saiseikai General Hospital (Japan)

    1994-12-01

    Fifty patients with 63 symptomatic vertebral metastasis (18 sites: pain only, 28 sites: radiculopathy with pain, 17 sites: myelopathy) were treated by radiotherapy. Primary lesions were located in the lung (9 cases), breast (9), colorectal area (9), prostate (7) and so on. We correlated the radiologic findings, symptoms and clinical effects with metastatic features which were classified into 4 types by MR imaging: non-deformity, expanding, vertebral collapse, and destructive mass. Each type of metastasis was accompanied with or without epidural tumor. Osteolytic metastases were apt to create features of deformity (expanding type: 18 vertebrae, vertebral collapse type: 17, destructive mass type: 9). The features of osteoblastic metastases were no deformity (18 vertebrae) and expanding type (2). The symptom of pain only occurred most frequently in the lumbosacral spine. The vertebral body deformity of symptomatic sites was relatively slight (non-deformity type: 6 sites, expanding type: 6, vertebral collapse type: 6), and epidural tumors were seen at only 2 sites. The effect of radiotherapy was excellent (complete pain relief: 64.7%, partial pain relief: 29.4%). Radiculopathy occurred most frequently in the lumber spine. Vertebral body deformity was noted in most symptomatic sites (expanding type: 9 sites, vertebral collapse type: 10, destructive mass type: 2). Complete relief was obtained in 6 sites (22.2%), partial relief in 18 (63.0%). Myelopathy occurred most often in the thoracic spine, followed by the lumbar spine. The vertebral body deformity was severe (expanding: 3 cases, vertebral collapse type: 3, destructive mass type: 6). Epidural tumors were also present in all but one case. Six of 13 patients treated with radiation alone improved. These 6 patients had non-deformity or expanding types with epidural tumor. No improvement was seen in the vertebral collapse type with epidural tumor or destructive mass type. (author).

  2. Multicenter Prospective Clinical Series Evaluating Radiofrequency Ablation in the Treatment of Painful Spine Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Bagla, Sandeep, E-mail: sandeep.bagla@gmail.com [Vascular Institute of Virginia, LLC (United States); Sayed, Dawood [University of Kansas Medical Center (United States); Smirniotopoulos, John [New York Presbyterian Hospital/Weill Cornell Medical Center (United States); Brower, Jayson [Providence Sacred Heart Medical Center and Children’s Hospital (United States); Neal Rutledge, J. [Seton Medical Center (United States); Dick, Bradley [Suburban Hospital (United States); Carlisle, James [St. Mark’s Hospital (United States); Lekht, Ilya [University of Southern California (United States); Georgy, Bassem [San Diego Imaging (United States)

    2016-09-15

    BackgroundRadiofrequency ablation (RFA) of vertebral body metastases (VBM) has been reported as safe and effective in retrospective studies. This single-arm prospective multicenter clinical study evaluates RFA in the treatment of painful VBM.MethodsFifty patients with VBM were prospectively enrolled during a 13-month period at eight US centers under an IRB-approved study. Percutaneous RFA was performed under imaging guidance with cement augmentation at the discretion of the operator. Pain, disability and quality of life were evaluated at baseline, prior to discharge, days 3, 7, 30 and 90 using the Numerical Pain Rating Scale, Oswestry Disability Index (ODI), the Functional Assessment of Cancer Therapy-General 7 (FACT-G7) and Functional Assessment of Cancer Therapy Quality-of-Life Measurement in Patients with Bone Pain (FACT-BP). Adverse events were monitored throughout this time interval.ResultsTwenty-six male and 24 female patients (mean age 61.0) underwent 69 treatments (30 thoracic and 39 lumbar). Cement augmentation was performed in 96 % of reported levels. Significant improvement in mean scores for pain, disability and cancer-specific health-related quality of life from baseline to all time intervals was seen. NRPS improved from 5.9 to 2.1 (p < 0.0001). ODI improved from 52.9 to 37.0 (p < 0.08). FACT-G7 improved form 10.9 to 16.2 (p = 0.0001). FACT-BP improved from 22.6 to 38.9 (p < 0.001). No complications related to the procedure were reported.ConclusionRFA with cement augmentation safely and effectively reduces pain and disability rapidly, while increasing quality of life in patients suffering from vertebral body metastases.

  3. Dosimetric and clinical impact of 3D vs. 2D planning in palliative radiotherapy for bone metastases.

    Science.gov (United States)

    Pope, Kathy; Fitzpatrick, David; Potter, Andrew; Holwell, Michael; Wang, Lisa; Lau, Michelle; Levin, Wilfred; McLean, Michael; Balaura, Laura Zurawel; Bezjak, Andrea; Wong, Rebecca K S

    2013-08-01

    The incorporation of three-dimensional (3D) planning for the treatment of bone metastases has been embraced in many North American practices with assumed superior tumor targeting, sparing of normal structures, and improvement in patient outcomes. The goal of our project was to evaluate the dosimetric and clinical impact of 3D vs. two-dimensional (2D) planning for patients who require simple palliative radiotherapy techniques (≤ 2 beams) for bone metastases. Patients undergoing palliative radiation therapy for bone metastases were eligible. The study oncologists first documented the intended treatment target, defined the treatment target/field using digital radiographs (2D), followed by using full 3D planning computerized tomography volumetric datasets. Treatment plans were compared dosimetrically, and patient-reported outcomes (pain, fatigue, anorexia, and nausea) were compared against a historical cohort treated with 2D plans. Eighty-five patients were enrolled in the study group. Review of the 3D datasets led to changes in the target area of interest in 44/85 (52 %) of cases, of which 21/85 (25 %) were clinically significant. 3D plans resulted in superior target coverage and normal tissue sparing. There was no significant difference in patient-reported outcomes however. 3D radiotherapy planning resulted in superior treatment plans but we were unable to demonstrate a significant benefit in clinical outcomes. Prospective study designs are needed to describe the contemporary expectation of palliative radiotherapy for bone metastases in the modern era of 3D planning.

  4. 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 < 0.0001). The overall percentage of known continued disease progression after spine metastasis diagnosis was 40.1% (n = 244/608, range 25.0%-88.9%), the rate of known recurrence of the primary skin cancer lesion was 3.5% (n = 21/608, range 0

  5. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    Science.gov (United States)

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  6. Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A.; Caudell, Jimmy J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); El-Haddad, Ghassan [Department of Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Berglund, Anders E.; Welsh, Eric A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Yue, Binglin [Department of Biostastistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Naghavi, Arash O.; Abuodeh, Yazan A.; Frakes, Jessica M. [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); 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)

    2016-08-01

    Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.

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

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Anna Koumarianou

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Murat Eroglu

    2014-03-01

    Full Text Available    Epileptic seizures can accompany benign diseases, also can be the first sign of malign tumors. In brain metastasis, epileptic seizures can be seen before the symptoms of the primary lesion. Brain metastasis is bad prognostic factor in all malignancies and it is determined that lung cancers are the most metastatic tumors to the brain. Especially in new onset epileptic seizures in elderly patients, metastatic brain tumors are frequent in etiology. We aimed to present a lung cancer patient with brain metastasis who admitted emergency department with first epileptic seizure.

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

    Science.gov (United States)

    MARVASO, GIULIA; BARONE, AGNESE; VACCARO, CATERINA; BRUZZANITI, VICENTE; GRESPI, SILVIA; SCOTTI, VALERIO; BIANCO, CATALDO

    2013-01-01

    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 cancer (NSCLC) and underwent SRS. The patient developed a recurrence of the disease and a second SRS on the same area was performed. After 8 months, tumor restaging demonstrated a lesion compatible with a recurrence and the patient underwent surgery. Histological diagnosis following surgery revealed only the occurrence of radionecrosis. Radiotherapy was well-tolerated and no grade 3/4 neurological toxicity occurred. To date, no consensus exists on the efficacy of retreatment with SRS. Despite the limited number of studies in this field, in the present case report, we outline the outcomes of this unconventional approach. PMID:24137433

  11. [Efficacy of gadobenate dimeglumine vs gadopentetate dimeglumine in contrast- enhanced magnetic resonance imaging for diagnosis of solitary brain metastases].

    Science.gov (United States)

    Wang, Qing-jun; Wang, Yong; Xu, Xian; Xiao, Hui; Ma, Lin

    2011-12-01

    To compare gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine (Gd-DTPA) for their efficacy as contrast agents in contrast-enhanced magnetic resonance imaging (MRI) for diagnosis of solitary brain metastases (SBM). We conducted an intra-individual study of contrast-enhanced T1-weighted MRI (T(1)WI) data from 27 Chinese patients with suspected SBM to compare the enhancement findings of two different MRI contrast agents, Gd-BOPTA and Gd-DTPA (at equivalent doses of 0.1 mmol/kg), for the detection of SBM. All the patients underwent two identical MRI examinations on a 3.0-T MRI scanner first with Gd-DTPA and then with Gd-BOPTA. Evaluation of the contrast enhancement was performed qualitatively (border delineation, extent, internal morphology, and contrast enhancement) and quantitatively (lesion-to-brain ratio, contrast-to-noise ratio, and percent enhancement) by 3 independent, fully blinded, and highly experienced neuroradiologists. Qualitative assessment by readers revealed a significant overall preference (P<0.05) for Gd-BOPTA over Gd-DOTA in terms of lesion border delineation, extent, lesion internal morphology, and contrast enhancement. Quantitative assessment also revealed a significant better performance of Gd-BOPTA in light of lesion-to-brain ratio (P<0.05), contrast-to-noise ratio (P<0.05), and percent enhancement (P<0.05). At an equivalent dose, Gd-BOPTA allows better contrast enhancement of SBM than Gd-DTPA in MRI.

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

    Science.gov (United States)

    Kwak, Yoonjin; Lee, Hee Eun; Kim, Woo Ho; Kim, Duck-Woo; Kang, Sung-Bum; Lee, Hye Seung

    2014-01-01

    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). 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. 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. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-15

    The purpose of this study was to evaluate the effect of stereotactic radiosurgery (SRS) on cerebral metastases using the transfer constant (K{sub trans}) assessed by dynamic contrast-enhanced (DCE) MRI. Furthermore, we aimed to evaluate the ability of K{sub trans} measurements to predict midterm tumor outcomes after SRS. The study received institutional review board approval, and informed consent was obtained from all subjects. Twenty-six adult patients with a total of 34 cerebral metastases underwent T1-weighted DCE MRI in a 1.5-T magnet at baseline (prior to SRS) and 4-8 weeks after treatment. Quantitative analysis of DCE MRI was performed by generating K{sub trans} parametric maps, and region-of-interest-based measurements were acquired for each metastasis. Conventional MRI was performed at least 16 weeks after SRS to assess midterm tumor outcome using volume variation. The mean (±SD) K{sub trans} value was 0.13 ± 0.11 min{sup -1} at baseline and 0.08 ± 0.07 min{sup -1} after 4-8 weeks post-treatment (p < 0.001). The mean (±SD) total follow-up time was 7.9 ± 4.7 months. Seventeen patients (22 lesions) underwent midterm MRI. Of those, nine (41 %) lesions had progressed at the midterm follow-up. An increase in K{sub trans} after SRS was predictive of tumor progression (hazard ratio = 1.50; 95 % CI = 1.16-1.70, p < 0.001). An increase of 15 % in K{sub trans} showed a sensitivity of 78 % and a specificity of 85 % for the prediction of progression at midterm follow-up. SRS was associated with a reduction of K{sub trans} values of the cerebral metastases in the early post-treatment period. Furthermore, K{sub trans} variation as assessed using DCE MRI may be helpful to predict midterm outcomes after SRS. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-01

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

  15. Radium-223 in the treatment of osteoblastic metastases: a critical clinical review.

    Science.gov (United States)

    Humm, John L; Sartor, Oliver; Parker, Chris; Bruland, Oyvind S; Macklis, Roger

    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 (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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

    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

  18. Increases in the number of brain metastases detected at frame-fixed, thin-slice MRI for gamma knife surgery planning

    Science.gov (United States)

    Nagai, Aiko; Shibamoto, Yuta; Mori, Yoshimasa; Hashizume, Chisa; Hagiwara, Masahiro; Kobayashi, Tatsuya

    2010-01-01

    For gamma knife planning, 2.4-mm-slice MRIs are taken under rigid frame fixation, so tiny tumors become visible. This study evaluated differences in the numbers of brain metastases between conventional contrast-enhanced MRI (6 ± 1 mm slice thickness) taken before patient referral and contrast-enhanced MRI for gamma knife planning. The numbers of metastases on the 2 images were counted by at least 2 oncologists. For gamma knife planning, spoiled gradient-recalled echo images were obtained after 0.1 mmol/kg gadolinium administration using a 1.5-T system. Images from 1045 patients with an interval between the 2 MRI studies of 6 weeks or less were analyzed. Increases in the number of metastases were found in 33.7% of the 1045 patients, whereas the number was identical in 62.3%. In 4.0%, the number decreased, indicating overdiagnosis at conventional MRI. These proportions did not differ significantly by the interval before gamma knife. An increase from single to multiple metastases was found in 16.0%. Meningeal dissemination was newly diagnosed in 2.3%. On planning images, the proportions of patients with 1, 2, 3, and 4 or more lesions were 37.6%, 19.3%, 9.3%, and 33.8%, respectively. In cases of colorectal cancer and hepatoma, the proportions of patients with a single metastasis (32 of 61 [52%] and 5 of 6 [83%], respectively) were higher than that of patients with other malignancies. In about one-third of the patients, an increased number of metastases were found on the thin-slice images. This should be kept in mind when deciding the treatment strategy for brain metastases. PMID:20864500

  19. Bipolar radiofrequency ablation of liver metastases during laparotomy. First clinical experiences with a new multipolar ablation concept.

    Science.gov (United States)

    Ritz, Joerg-Peter; Lehmann, Kai S; Reissfelder, Christoph; Albrecht, Thomas; Frericks, Bernd; Zurbuchen, Urte; Buhr, Heinz J

    2006-01-01

    Radiofrequency ablation (RFA) is a promising method for local treatment of liver malignancies. Currently available systems for radiofrequency ablation use monopolar current, which carries the risk of uncontrolled electrical current paths, collateral damages and limited effectiveness. To overcome this problem, we used a newly developed internally cooled bipolar application system in patients with irresectable liver metastases undergoing laparotomy. The aim of this study was to clinically evaluate the safety, feasibility and effectiveness of this new system with a novel multipolar application concept. Patients with a maximum of five liver metastases having a maximum diameter of 5 cm underwent laparotomy and abdominal exploration to control resectability. In cases of irresectability, RFA with the newly developed bipolar application system was performed. Treatment was carried out under ultrasound guidance. Depending on tumour size, shape and location, up to three applicators were simultaneously inserted in or closely around the tumour, never exceeding a maximum probe distance of 3 cm. In the multipolar ablation concept, the current runs alternating between all possible pairs of consecutively activated electrodes with up to 15 possible electrode combinations. Post-operative follow-up was evaluated by CT or MRI controls 24-48 h after RFA and every 3 months. In a total of six patients (four male, two female; 61-68 years), ten metastases (1.0-5.5 cm) were treated with a total of 14 RF applications. In four metastases three probes were used, and in another four and two metastases, two and one probes were used, respectively. During a mean ablation time of 18.8 min (10-31), a mean energy of 48.8 kJ (12-116) for each metastases was applied. No procedure-related complications occurred. The patients were released from the hospital between 7 and 12 days post-intervention (median 9 days). The post-interventional control showed complete tumour ablation in all cases. Bipolar

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

    Directory of Open Access Journals (Sweden)

    Haisong eLiu

    2016-02-01

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

  1. Inverse spatial distribution of brain metastases and white matter hyperintensities in advanced lung and non-lung cancer patients.

    Science.gov (United States)

    Quattrocchi, Carlo Cosimo; Errante, Yuri; Mallio, Carlo Augusto; Carideo, Luciano; Scarciolla, Laura; Santini, Daniele; Tonini, Giuseppe; Zobel, Bruno Beomonte

    2014-11-01

    The aim of this study was to test by means of a voxel-based approach the hypothesis that there is a different spatial distribution of brain metastases (BM) and white matter hyperintensities (WMH) and that the presence of WMH affects the location of BM in lung and non-lung cancer patients. Two-hundred consecutive cancer patients at first diagnosis of BM were included. Images were acquired using a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany). Axial FLAIR T2 weighted images and gadolinium-enhanced T1 weighted images were post-processed for segmentation, co-registration and analysis. Binary lesion masks were created for WMH and BM, using Volumes of Interest. Lesion probability maps were generated and the voxel-based lesion-symptom mapping approach was used to model each voxel and to calculate a non parametric statistics (Brunner-Munzel test) describing the differences between the groups. In the lung cancer group we found higher frequency of BM in WMH- than in WMH+ patients in the occipital lobe and the cerebellum. In contrast, BM were more frequent in the right frontal lobe in WMH+ than in WMH- patients. We suggest that there exists an inverse brain spatial distribution between WMH and BM. In lung cancer patients, the presence of WMH seems to shift the distribution of BM toward locations different than what it is expected based on primary tumor.

  2. The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis.

    Science.gov (United States)

    Petrelli, Fausto; Ghidini, Michele; Lonati, Veronica; Tomasello, Gianluca; Borgonovo, Karen; Ghilardi, Mara; Cabiddu, Mary; Barni, Sandro

    2017-10-01

    Breast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs. We searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and the European Union Clinical Trials Register for studies reporting data on L, singly or in combination with C, for the treatment of HER-2+ BC with BMs. Primary end-points were overall response rate (ORR) and disease control rate (DCR); these were pooled to provide an aggregate value. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Data were pooled using number of events/number of evaluable patients, according to a fixed or random effect model. Overall, 12 studies were included in the present meta-analysis, for a total of 799 patients with BMs. The pooled overall response rate (ORR) was 21.4% (95% CI 11.7-35.9). After exclusion of patients that received L alone, ORR reached 29.2% (95% CI 18.5-42.7). The pooled median PFS and OS were 4.1 (95% CI 3.1-6.7) and 11.2 (95% CI 8.9-14.1) months, respectively. Due to its activity on BMs, the L + C combination may be considered for HER-2+ BC that has progressed in the brain, when local therapy has been performed or failed and re-irradiation is not feasible. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Pulsatile Erlotinib in EGFR-Positive Non-Small-Cell Lung Cancer Patients With Leptomeningeal and Brain Metastases: Review of the Literature.

    Science.gov (United States)

    How, Joan; Mann, Janelle; Laczniak, Andrew N; Baggstrom, Maria Q

    2017-07-01

    Patients with epidermal growth factor receptor (EGFR)-positive (EGFR+) non-small-cell lung cancer (NSCLC) show improved response rates when treated with tyrosine kinase inhibitors (TKIs) such as erlotinib. However, standard daily dosing of erlotinib often does not reach therapeutic concentrations within the cerebrospinal fluid (CSF), resulting in progression of central nervous system (CNS) disease. Intermittent, high-dose administration of erlotinib reaches therapeutic concentrations within the CSF and is well tolerated in patients. Experience with "pulsatile" dosing, however, is limited. We review the literature on the pharmacology and clinical outcomes of pulsatile erlotinib in the treatment of EGFR+ NSCLC with brain and leptomeningeal metastases, and include available data on the use of next-generation TKIs in CNS progression. We also provide our institution's experience with patients treated with pulsatile erlotinib for CNS metastasis, and propose clinical criteria for its use. Pulsatile erlotinib is a reasonable alternative in EGFR+ patients with new or worsening CNS disease, without evidence of systemic progression, and without confirmed T790M resistance mutations within the CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Q [Wayne State University, Detroit, MI (United States); Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.

  5. Characteristics and Prognostic Factors for Patients With HER2-overexpressing Breast Cancer and Brain Metastases in the Era of HER2-targeted Therapy: An Argument for Earlier Detection.

    Science.gov (United States)

    Morikawa, Aki; Wang, Rui; Patil, Sujata; Diab, Adi; Yang, Jonathan; Hudis, Clifford A; McArthur, Heather L; Beal, Kathryn; Seidman, Andrew D

    2017-12-21

    Although brain metastases (BM) are associated with poor prognosis, patients with human epidermal growth factor receptor 2 (HER2) overexpressing (HER2 + ) breast cancer (BC) with BM who are treated with anti-HER2 therapy have a relatively longer survival after BM diagnosis compared with other subtypes and HER2 + patients previously untreated with anti-HER2 therapy. It is unclear if previously reported prognostic factors are applicable to patients with HER2 + BC in the era of HER2-targeted therapy. We evaluated 100 consecutive patients with HER2 + BC with BM who underwent radiation therapy as primary BM treatment from January 2001 to December 2011 at Memorial Sloan Kettering Cancer Center by retrospective review. Patient characteristics at the time of BM diagnosis and their associations with time from BM to death were evaluated by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models. Significantly better survival from BM was noted for patients with higher performance status, fewer BM lesions, continued use of HER2-targeted therapy after BM diagnosis, and better controlled extracranial metastatic disease. Absence of neurologic symptoms at BM diagnosis was significantly associated with fewer lesions, decreased use of whole brain radiotherapy, and longer survival in univariate and multivariate analysis (multivariate hazard ratio, 3.69; 95% confidence interval, 1.69-8.07). Our finding supports the continued use of HER2-targeted therapy after BM diagnosis. In addition, future research on the clinical impact of detecting asymptomatic BM in patients with HER2 + BC, in terms of improving prognosis, quality of life, and avoidance of whole brain radiotherapy, is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Patients with Long-Term Control of Systemic Disease Are a Favorable Prognostic Group for Treatment of Brain Metastases with Stereotactic Radiosurgery Alone.

    Science.gov (United States)

    Ebner, Daniel K; Gorovets, Daniel; Rava, Paul; Cielo, Deus; Kinsella, Timothy J; DiPetrillo, Thomas A; Hepel, Jaroslaw T

    2017-02-01

    Stereotactic radiosurgery (SRS) alone is an attractive option for treatment of brain metastases. SRS avoids whole-brain radiotherapy (WBRT)-associated morbidity, but is limited by regional central nervous system (CNS) failures and short survival in some patients. We evaluated a subgroup of patients with controlled systemic disease that could represent a favorable patient population for SRS alone. All patients with brain metastases treated with SRS without WBRT at our institution between 2004 and 2014 were grouped into two cohorts: those with controlled systemic disease (CSD) for 1 year or longer before prior to presentation with brain metastases and those without (i.e., uncontrolled systemic disease [USD]). Rates of local and regional CNS failure, and overall survival were assessed with χ2 and Student t tests. Cox regression analysis was performed to evaluate independent predictors of regional control and overall survival. Two hundred ninety-four patients underwent SRS to 697 lesions, of which 65 patients had CSD. Median follow-up was 9.7 months. There was no difference in local control between the two cohorts (P = 0.795). Regional CNS control was significantly better for patients with CSD (68% vs. 48%; P = 0.001). Overall survival at 1 and 5 years for CSD were 65% and 13% with USD yielding 41% and 7%, respectively (P < 0.001). Multivariate analysis demonstrated that USD (relative CSD) independently predicts regional failure (hazard ratio [HR], 1.75; P = 0.008) and shorter overall survival (HR, 1.55; P = 0.007). Patients with brain metastases after 1 year or longer of primary and systemic disease control represent a particularly favorable cohort, with lower regional CNS failure and prolonged survival, for an approach of SRS alone. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases From Lung Adenocarcinoma: Early Response and Dosimetric Evaluation.

    Science.gov (United States)

    Kim, Kyung Hwan; Cho, Byoung Chul; Lee, Chang Geol; Kim, Hye Ryun; Suh, Yang Gun; Kim, Jun Won; Choi, Chihwan; Baek, Jong Geal; Cho, Jaeho

    2016-02-01

    In this study, the volume response and treatment outcome after hippocampus-sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) using tomotherapy were evaluated. Patients with primary lung adenocarcinoma and multiple brain metastases who had a Karnofsky performance status ≥ 70 and exhibited well-controlled extracranial disease were treated. The prescribed dose was administered in 10 to 14 fractions as 25 to 28 Gy to whole-brain parenchyma, as 40 to 48 Gy to the gross metastatic lesion, and as 30 to 42 Gy to a 5-mm margin to the metastatic lesion. Double-dose gadolinium contrast-enhanced magnetic resonance imaging at 1-mm slice thickness was performed before treatment and at 1, 4, and 7 months post-treatment. The tumor volume reduction ratio was calculated for each follow-up. Between July 2011 and September 2012, 11 patients with 70 lesions were included in this analysis. The median number of lesions per patient was 4 (range, 2-15). The median initial tumor volume was 0.235 cm(3) (range, 0.020-10.140 cm(3)). The treatment plans were evaluated regarding conformation number (CN), target coverage (TC), and homogeneity index (HI). The median follow-up duration was 14 months (range, 3-25 months) and the 1-year intracranial control rate was 67%. The tumor volume reduction was most prominent during the first month with a median reduction rate of 0.717 (range, -0.190 to 1.000). Complete remission was seen in 22 (33%) lesions, and 45 (64%) lesions showed more than 65% reduction in tumor volume. The CN, TC, and HI values were comparable to that of previous studies, and the mean hippocampal dose was 13.65 Gy. No treatment breaks or ≥ G3 acute toxicities were observed during or after treatment. The HS-WBRT with SIB in patients with multiple brain metastases was effective and feasible for volume reduction and showed excellent intracranial control. © The Author(s) 2015.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Stereotactic radiosurgery for patients with multiple brain metastases: a case-matched study comparing treatment results for patients with 2-9 versus 10 or more tumors.

    Science.gov (United States)

    Yamamoto, Masaaki; Kawabe, Takuya; Sato, Yasunori; Higuchi, Yoshinori; Nariai, Tadashi; Watanabe, Shinya; Kasuya, Hidetoshi

    2014-12-01

    Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors. This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications. Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974-1.319, p

  10. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  12. Photoacoustic Nodal Metastases detection in a rat model using a clinical superparamagnetic iron oxide nanoparticle dispersion

    NARCIS (Netherlands)

    Grootendorst, Diederik; Fratila, R.M.; Visscher, M.; ten Haken, Bernard; van Wezel, Richard Jack Anton; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J.M.

    2012-01-01

    Background: Detection of tumor metastases in the lymphatic system is essential for accurate staging of different malignancies, however fast and accurate pre- or intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent

  13. Survival Analysis of Advanced HCC Treated with Radioembolization: Comparing Impact of Clinical Performance Status Versus Vascular Invasion/Metastases.

    Science.gov (United States)

    Ali, Rehan; Gabr, Ahmed; Abouchaleh, Nadine; Al Asadi, Ali; Mora, Ronald A; Kulik, Laura; Abecassis, Michael; Riaz, Ahsun; Salem, Riad; Lewandowski, Robert J

    2017-09-06

    In this study, we aim to compare the effects of prognostic indicators on survival analysis for Barcelona Clinic Liver Cancer (BCLC) C patients undergoing yttrium-90 radioembolization (Y-90). A prospectively acquired database (2003-2017) for BCLC C hepatocellular carcinoma (HCC) patients that underwent radioembolization with Y-90 was searched. The criteria for BCLC C status (Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or 2, metastases, and/or portal vein thrombosis (PVT)) were recorded. Kaplan-Meier survival analyses were performed from the date of the first radioembolization with Y-90, censored to curative treatment, to determine median overall survival (OS). Cox regression hazards model was used for multivariate analyses. Significance was set at P < 0.05. 547 BCLC C patients treated with radioembolization with Y-90 had a median OS of 10.7 months (range: 9.5-12.9). 43% (233 of 547) patients classified as BCLC C solely by their ECOG PS had a median OS of 19.4 months (14.7-23.7); 57% (314 of 547) patients with PVT/metastases had a median OS of 7.7 months (6.7-8.7). On multivariate analysis, ECOG PS was not found to be a statistically significant prognostic indicator of OS in BCLC C whereas metastases and PVT exhibited hazards ratios (95%CI) of 0.51 (0.38-0.69) and 0.49 (0.38-0.63), respectively (P < 0.0001). Patients classified as BCLC C due to ECOG PS 1 demonstrated longer survival when compared to those presenting with PVT, metastases and/or ECOG PS 2. Hence, ECOG PS 1, as an isolated variable, may not be a true indicator of advanced disease.

  14. Drug interaction between erlotinib and phenytoin for brain metastases in a patient with nonsmall cell lung cancer.

    Science.gov (United States)

    Ohgami, Masahiro; Kaburagi, Takayuki; Kurosawa, Atsuhiko; Homma, Masato

    2016-11-01

    Erlotinib, a substrate drug metabolized by the CYP3A4 enzyme, is an epidermal growth factor receptor tyrosine kinase inhibitor used to treat nonsmall cell lung cancer (NSCLC). Concomitant use of erlotinib and the antiepileptic drug phenytoin, an inducer of CYP3A4, may result in a drug-drug interaction accompanied by changes in the blood concentrations of both drugs. We determined the blood concentration of each drug to confirm the interaction between phenytoin and erlotinib in a case of NSCLC with brain metastases. The phenytoin blood concentration (8.2-10.0μg/mL) gradually increased 3-fold (to 24.2μg/mL) 7 months after the start of erlotinib (150mg/d) co-administration. The erlotinib blood concentration which was maintained at 0.15-0.37μg/mL under phenytoin co-administration, increased 12-fold (to 1.77μg/mL) after the stoppage of phenytoin co-administration. The present case revealed that blood phenytoin increased and blood erlotinib decreased subsequent to the interaction of the 2 drugs in the CYP3A4 metabolic enzyme system. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Comparison of the molecular profile of brain metastases from colorectal cancer and corresponding primary tumors.

    Science.gov (United States)

    Aprile, Giuseppe; Casagrande, Mariaelena; De Maglio, Giovanna; Fontanella, Caterina; Rihawi, Karim; Bonotto, Marta; Pisa, Federica E; Tuniz, Francesco; Pizzolitto, Stefano; Fasola, Gianpiero

    2017-01-01

    Little is known about molecular biology of brain metastasis (BM) from colorectal cancer and its concordance with matched primary tumors. We identified 56 consecutive colorectal cancer patients who underwent neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and PIK3CA. The molecular profile of the brain lesion was compared with the corresponding primary tumor. The molecular profile concordance rate was 95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median overall survival was 24.0 months (95% CI: 15.6-32.4). In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.

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

    OpenAIRE

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-15

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

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

    Directory of Open Access Journals (Sweden)

    Fabio Ynoe de Moraes

    2016-02-01

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

  19. Incidence of Brain Metastases on Follow-up18F-FDG PET/CT Scans of Non-Small Cell Lung Cancer Patients: Should We Include the Brain?

    Science.gov (United States)

    Nia, Emily S; Garland, Linda L; Eshghi, Naghmehossadat; Nia, Benjamin B; Avery, Ryan J; Kuo, Phillip H

    2017-09-01

    The brain is the most common site of distant metastasis from lung cancer. Thus, MRI of the brain at initial staging is routinely performed, but if this examination is negative a follow-up examination is often not performed. This study evaluates the incidence of asymptomatic brain metastases in non-small cell lung cancer patients detected on follow-up 18 F-FDG PET/CT scans. Methods: In this Institutional Review Board-approved retrospective review, all vertex to thigh 18 F-FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to August 2016 were reviewed. A total of 1,175 18 F-FDG PET/CT examinations in 363 patients were reviewed. Exclusion criteria included brain metastases on initial staging, histologic subtype of small-cell lung cancer, and no follow-up 18 F-FDG PET/CT examinations. After our exclusion criteria were applied, a total of 809 follow-up 18 F-FDG PET/CT scans in 227 patients were included in the final analysis. The original report of each 18 F-FDG PET/CT study was reviewed for the finding of brain metastasis. The finding of a new brain metastasis prompted a brain MRI, which was reviewed to determine the accuracy of the 18 F-FDG PET/CT. Results: Five of 227 patients with 809 follow-up 18 F-FDG PET/CT scans reviewed were found to have incidental brain metastases. The mean age of the patients with incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial diagnosis to time of detection of incidental brain metastasis was 36 mo (range, 15-66 mo). When MRI was used as the gold standard, our false-positive rate was zero. Conclusion: By including the entire head during follow-up 18 F-FDG PET/CT scans of patients with non-small cell lung cancer, brain metastases can be detected earlier while still asymptomatic. But, given the additional scan time, radiation, and low incidence of new brain metastases in asymptomatic patients, the cost-to-benefit ratio should be weighed by each institution. © 2017 by the Society of

  20. Raman spectroscopic imaging for in vivo detection of cerebral brain metastases.

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    Kirsch, Matthias; Schackert, Gabriele; Salzer, Reiner; Krafft, Christoph

    2010-10-01

    We report for the first time a proof-of-concept experiment employing Raman spectroscopy to detect intracerebral tumors in vivo by brain surface mapping. Raman spectroscopy is a non-destructive biophotonic method which probes molecular vibrations. It provides a specific fingerprint of the biochemical composition and structure of tissue without using any labels. Here, the Raman system was coupled to a fiber-optic probe. Metastatic brain tumors were induced by injection of murine melanoma cells into the carotid artery of mice, which led to subcortical and cortical tumor growth within 14 days. Before data acquisition, the cortex was exposed by creating a bony window covered by a calcium fluoride window. Spectral contributions were assigned to proteins, lipids, blood, water, bone, and melanin. Based on the spectral information, Raman images enabled the localization of cortical and subcortical tumor cell aggregates with accuracy of roughly 250 μm. This study demonstrates the prospects of Raman spectroscopy as an intravital tool to detect cerebral pathologies and opens the field for biophotonic imaging of the living brain. Future investigations aim to reduce the exposure time from minutes to seconds and improve the lateral resolution.

  1. 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

  2. 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.)

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

    Science.gov (United States)

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

    2014-11-01

    Normal brain tissue doses have been shown to be strongly apparatus dependent for multi-target stereotactic radiosurgery. In this study, we investigated whether inter-target dose interplay effects across contemporary radiosurgical treatment platforms are responsible for such an observation. For the study, subsets ([Formula: see text] and 12) of a total of 12 targets were planned at six institutions. Treatment platforms included the (1) Gamma Knife Perfexion (PFX), (2) CyberKnife, (3) Novalis linear accelerator equipped with a 3.0-mm multi-leaf collimator (MLC), and the (4) Varian Truebeam flattening-filter-free (FFF) linear accelerator also equipped with a 2.5 mm MLC. Identical dose-volume constraints for the targets and critical structures were applied for each apparatus. All treatment plans were developed at individual centers, and the results were centrally analyzed. We found that dose-volume constraints were satisfied by each apparatus with some differences noted in certain structures such as the lens. The peripheral normal brain tissue doses were lowest for the PFX and highest for TrueBeam FFF and CyberKnife treatment plans. Comparing the volumes of normal brain receiving 12 Gy, TrueBeam FFF, Novalis, and CyberKnife were 180-290% higher than PFX. The mean volume of normal brain-per target receiving 4-Gy increased by approximately 3.0 cc per target for TrueBeam, 2.7 cc per target for CyberKnife, 2.0 cc per target for Novalis, and 0.82 cc per target for PFX. The beam-on time was shortest with the TrueBeam FFF (e.g., 6-9 min at a machine output rate of 1,200 MU/min) and longest for the PFX (e.g., 50-150 mins at a machine output rate of 350 cGy/min). The volumes of normal brain receiving 4 and 12 Gy were higher, and increased more swiftly per target, for Linac-based SRS platforms than for PFX. Treatment times were shortest with TrueBeam FFF.

  4. 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.

  5. 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

  6. Brain metastases in patients with epithelial ovarian cancer: report of two cases and literature review

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    Vieira, Leonardo Jose; Alves, Christiane Maria Meurer [Servico de Cirurgia Oncologica do Hospital ASCOMCER, Juiz de Fora, MG (Brazil); Oliveira, Alexandre Ferreira; Nascimento, Antonio Carlos Rodrigues do, E-mail: ljvieira@terra.com.br [Universidade Federal de Juiz de Fora, MG (Brazil)

    2011-07-01

    Brain metastasis from primary ovarian cancer is rare. We report two patients diagnosed with FIGO stage IIIc ovarian carcinoma. After primary diagnosis, the two patients underwent six cycles of neoadjuvant paclitaxel plus carboplatin chemotherapy, followed by optimum debulking surgery and three additional cycles of adjuvant chemotherapy. Patient 1 developed several supratentorial lesions twenty months after initial diagnosis and subsequently was treated with intrathecal chemotherapy, cranial radiotherapy and intravenous chemotherapy. Patient 2 developed an isolated cerebellar metastasis ten months after initial diagnosis and subsequently was treated with surgical resection, cranial radiotherapy and intravenous chemotherapy. (author)

  7. Clinical effect of systemic chemotherapy combined with transcatheter arterial chemoembolization in treatment of breast cancer with liver metastases

    Directory of Open Access Journals (Sweden)

    LI Liye

    2016-01-01

    Full Text Available ObjectiveTo investigate the clinical effect of systemic chemotherapy combined with transcatheter arterial chemoembolization (TACE in the treatment of breast cancer with liver metastases. MethodsA total of 86 female breast cancer patients with liver metastases who were treated in the Affiliated Hospital of Shandong Academy of Medical Sciences from December 2012 to December 2014 were selected and equally divided into experimental group and control group. The patients in the control group received systemic chemotherapy, and those in the experimental group received systemic chemotherapy combined with TACE. The clinical effect, changes in lesions, and patients′ quality of life (QOL scores after treatment were compared between two groups. The t-test was applied for comparison of continuous data between the two groups, and the chi-square test was applied for comparison of categorical data between the two groups. ResultsThe experimental group had a significantly higher overall response rate than the control group (90.70% vs 58.14%, χ2=13.07, P=0.001. Compared with the control group, the experimental group had significantly smaller diameters of tumors and lymph nodes after treatment (t=4.26 and 4.63, both P<0.001, as well as significantly higher QOL scores at 3 and 6 months after treatment (t=6.30 and 3.89, both P<0001. ConclusionSystemic chemotherapy combined with TACE has a significant therapeutic effect in breast cancer patients with liver metastases, and can improve patients′ symptoms, reduce adverse drug reactions, and improve QOL. As a safe and reliable therapeutic method, it is worthy of clinical application.

  8. ADRENALECTOMY FOR ISOLATED METASTASES

    Directory of Open Access Journals (Sweden)

    Svetlana Shumarova

    2017-08-01

    Full Text Available Background: Isolated adrenal gland metastases are not frequently finding. The aim of the present retrospective study was to estimate clinical and pathological parameters that could be used to predict survival after adrenalectomy. Material and methods: A total of 34 patients with adrenal gland masses suspected to be metastases was included in this study. The group of patients with isolated metastases was19 (56% and a group of patients with adrenal adenomas -15 (44%. Results: The sample of patients consisted of 18 (53% men and 16 (47% women from 40 to 81 years old with a mean (±SD age of 61.6±10.3 years, presented with adrenal mass suspected to be metastases. Nineteen (56% of them had demonstrated metastases and 16 (84% metachronous with median overall survival (OS 54.6 (range 43-66 months. Median OS in the group with metastases was 22.6 months. Lung carcinoma was the most common primary tumour metastasizing in the adrenal gland – 58% of all metastases with a disease-free interval (DFI of 13 months. It was presented by shorter median survival than the rest primary tumour types (37.8 vs. 96.7months; log-rank test, p=0.028. In the multivariate Cox’s hazard analysis of the surgical technique was found to be an independent prognostic factor (p=0.047, together with lung carcinoma vs. renal cell carcinoma (p=0.045. Conclusion: Adrenalectomy due to isolated metastases in the adrenal glands showed the median overall survival of 22.6 months. Shorter survival periods were associated with lung carcinoma, DFI<12months, conversion to open surgery, synchronous metastases, but not with age, tumour size or resection status.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Andratschke, Nicolaus; Parys, Alan; Stadtfeld, Susanne; Wurster, Stefan; Huttenlocher, Stefan; Imhoff, Detlef; Yildirim, Müjdat; Rades, Dirk; Rödel, Claus Michael; Dunst, Jürgen; Hildebrandt, Guido; Blanck, Oliver

    2016-05-28

    We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean-dose-optimized and real-time motion-compensated robotic stereotactic body radiation therapy (SBRT) in the treatment of liver metastases. Between March 2011 and July 2015, 52 patients were treated with SBRT for a total of 91 liver metastases (one to four metastases per patient) with a median GTV volume of 12 cc (min 1 cc, max 372 cc). The optimization of mean GTV dose was prioritized during treatment planning at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The delivered median GTV biological effective dose (BED10) was 142.1 Gy10 (range, 60.2 Gy10 -165.3 Gy10) and the prescribed PTV BED10 ranged from 40.6 Gy10 to 112.5 Gy10 (median, 86.1 Gy10). We analyzed local control (LC), progression-free interval (PFI), overall survival (OS), and toxicity. Median follow-up was 17 months (range, 2-49 months). The 2-year actuarial LC, PFI, and OS rates were 82.1, 17.7, and 45.0 %, and the median PFI and OS were 9 and 23 months, respectively. In univariate analysis histology (p Robotic real-time motion-compensated SBRT is a safe and effective treatment for one to four liver metastases. Reducing the PTV prescription dose and keeping a high mean GTV dose allowed the reduction of toxicity while maintaining a high local control probability for the treated lesions.

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

    Science.gov (United States)

    Jung, Jinhong; Song, Si Yeol; Kim, Jong Hoon; Yu, Chang Sik; Kim, Jin Cheon; Kim, Tae Won; Jeong, Seong-Yun; Kim, Su Ssan; Choi, Eun Kyung

    2015-11-21

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

  12. Estimating prognosis at the time of repeat whole brain radiation therapy for multiple brain metastases: The reirradiation score

    Directory of Open Access Journals (Sweden)

    Natalie Logie, MD

    2017-07-01

    Conclusions: In the largest reported cohort to receive repeat WBRT, application of the RPA score was not predictive of MS. The new ReRT score is a simple tool based on readily available clinical information.

  13. 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.

  14. Breast cancer subtype as a predictor for outcomes and control in the setting of brain metastases treated with stereotactic radiosurgery.

    Science.gov (United States)

    Grubb, Christopher S; Jani, Ashish; Wu, Cheng-Chia; Saad, Shumaila; Qureshi, Yasir H; Nanda, Tavish; Yaeh, Andrew; Rozenblat, Tzlil; Sisti, Michael B; Bruce, Jeffrey N; McKhann, Guy M; Sheth, Sameer A; Lesser, Jeraldine; Cheng, Simon K; Isaacson, Steven R; Lassman, Andrew B; Connolly, Eileen P; Wang, Tony J C

    2016-03-01

    We investigated effects of breast cancer subtype on overall survival (OS), local and distant control, and time from initial diagnosis to brain metastases (BM). We also investigated advances in graded prognostic assessment (GPA) scores. A cohort of 72 patients treated for BM from breast cancer with Gamma Knife stereotactic radiosurgery at our institution from 2000 to 2014 had subtyping available and were used for this study. Median follow up for OS was 12 months and for control was 6 months. OS for luminal, HER2, and triple negative subtypes were 26, 20, and 22 months. OS when stratified by Sperduto et al. (J Clin Oncol 30(4):419-425, 2012) and Subbiah et al. (J Clin Oncol 33(20):2239-2245, 2015) GPAs were similar (p = 0.087 and p = 0.063). KPS and treatment modality were significant for OS (p = 0.002; p = 0.034). On univariate analysis, triple negative subtype and >3 BM were trending and significant for decreased OS (p = 0.084; p = 0.047). On multivariable analysis HER2, triple negative, and >3 BM were significant for OS (p = 0.022; p = 0.040; p = 0.009). Subtype was significant for response on a per lesion basis (p = 0.007). Subtype was trending towards significance when analyzing time from initial diagnosis to BM treatment (p = 0.064). Breast cancer subtype is an important prognostic factor when stratifying breast cancer patients with BM. The addition of number of BM to the GPA is a useful addition and should be further investigated. Subtype has an effect on lesion response, and also on rate of development BM after initial diagnosis.

  15. The influence of lung metastases on the clinical course of gestational trophoblastic neoplasia: a historical cohort study

    NARCIS (Netherlands)

    Vree, M. de; Trommel, N. van; Kenter, G.; Sweep, F.C.; Kate-Booij, M. Ten; Massuger, L.F.; Lok, C.

    2016-01-01

    OBJECTIVE: To evaluate whether gestational trophoblastic neoplasia (GTN) patients with lung metastases have more adverse outcomes such as resistance to chemotherapy, recurrence or death of disease compared with patients without lung metastases. DESIGN: Historical observational cohort study. SETTING:

  16. Sites of Distant Relapse and Clinical Outcomes in Patients with Metastatic Triple-Negative Breast Cancer: High Incidence of Central Nervous System Metastases

    Science.gov (United States)

    Claus, Elizabeth; Sohl, Jessica; Razzak, Abdul R.; Arnaout, Amal; Winer, Eric P.

    2008-01-01

    Purpose To characterize the outcomes of patients with metastatic triple negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) relapse. Patients and Methods Using pharmacy and pathology records, a study group of 116 patients treated for metastatic triple negative breast cancer at Dana-Farber Cancer Institute from January 2000 to June 2006 was identified. Results The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases prior to death. Median survival after a diagnosis of CNS metastasis was 4.9 months. The age and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95%CI:1.9, 6.1) that of patients without a CNS lesion at first metastatic presentation. Of 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow up prior to death. Conclusion Triple negative breast cancer is associated with poor survival after recurrence. CNS relapse is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is due to a sanctuary effect, but rather to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed. PMID:18833576

  17. Validation of the new graded prognostic assessment scale for brain metastases: a multicenter prospective study

    Directory of Open Access Journals (Sweden)

    Cuadras Patricia

    2011-03-01

    Full Text Available Abstract Background Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM. We evaluated the new Graded Prognostic Assessment (GPA scale in a prospective validation study to compare it with two published prognostic indexes. Methods A total of 285 newly diagnosed BM (n = 85 with synchronous BM patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100 and 3 (range, 1-50, respectively. The majority of primary tumours were lung (53%, or breast (17% cancers. Treatment was administered to 255 (89.5% patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA 1, 8.4% and Basic Score for BM (BSBM 3, 9.1%. Mean follow-up (FU time was 5.2 ± 4.7 months. Results During the period of FU, 225 (78.9% patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P P P = 0.007, RPA (P = 0.02 and GPA (P = 0.03 were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. Conclusions Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

  19. Evaluation of a composite Gel-Alanine phantom on an end-to-end test to treat multiple brain metastases by a single isocenter VMAT technique.

    Science.gov (United States)

    Pavoni, Juliana Fernandes; Neves-Junior, Wellington Furtado Pimenta; da Silveira, Matheus Antonio; Haddad, Cecília Maria Kalil; Baffa, Oswaldo

    2017-09-01

    This work aims to evaluate the application of a cylindrical phantom made of dosimetric gel containing alanine pellets distributed inside the gel volume during an end-to-end test of a single isocenter VMAT for simultaneous treatment of multiple brain metastases. The evaluation is based on the comparison of the results obtained with the composite phantom with the treatment planning system (TPS) dose distribution validated by using the clinical conventional quality control with point and planar dose measurements. A cylindrical MAGIC-f gel phantom containing alanine dosimeters (composite phantom) was used to design the VMAT plan in the treatment planning system (TPS). The alanine dosimeters were pellets with radius of 2.5 mm and height of 3 mm, and played the role of brain metastasis inside the gel cylinder, which simulated the cerebral tissue. Five of the alanine dosimeters were selected to simulate five lesions; five planning target volumes (PTVs) were created including the dosimeters and irradiated with different doses. Conventional quality assurance (QA) was performed on the TPS plan and on the composite phantom; a phantom containing only gel (Gel 1 phantom) was also irradiated. One day after irradiation, magnetic resonance images were acquired for both phantoms on a 3T scanner. An electron spin resonance spectrometer was used to evaluate alanine doses. Calibration curves were constructed for the alanine and the gel dosimeters. All the gel only measurement was repeated (Gel 2 phantom) in order to confirm the previous gel measurement. The VMAT treatment plan was approved by the conventional QA. The doses measured by alanine dosimeters on the composite gel phantom agreed to the TPS on average within 3.3%. The alanine dose for each lesion was used to calibrate the gel dosimeter measurements of the concerned PTV. Both gel dose volume histograms (DVH) achieved for each PTV were in agreement with the expected TPS DVH, except for a small discrepancy observed for the Gel 2

  20. 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 ini...... in the initial phase in a clinical setting with emphasis on pathway criteria....

  1. Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuchcinski, Gregory; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine [University of Lille, CHU Lille, Department of Neuroradiology, Lille (France); Le Rhun, Emilie [University of Lille, CHU Lille, Department of Neurosurgery, Lille (France); Oscar Lambret Center, Department of Medical Oncology, Lille (France); Inserm U1192-PRISM-Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse, Lille (France); Cortot, Alexis B. [University of Lille, CHU Lille, Department of Thoracic Oncology, Lille (France); Drumez, Elodie [University of Lille, CHU Lille, Department of Biostatistics, Lille (France)

    2017-09-15

    To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K{sup trans}, k{sub ep}, v{sub e}, v{sub p}) and their early variation (∇K{sup trans}, ∇k{sub ep}, ∇v{sub e}, ∇v{sub p}). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∇K{sup trans}, ∇v{sub e} and ∇v{sub p} were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∇v{sub e} with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∇v{sub e} may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. (orig.)

  2. Breast carcinoma with an Oncotype Dx recurrence score metastases in a large series with clinical follow-up.

    Science.gov (United States)

    Wen, Hannah Y; Krystel-Whittemore, Melissa; Patil, Sujata; Pareja, Fresia; Bowser, Zenica L; Dickler, Maura N; Norton, Larry; Morrow, Monica; Hudis, Clifford A; Brogi, Edi

    2017-01-01

    A 21-gene expression assay (Oncotype DX recurrence score [RS]) that uses reverse transcriptase-polymerase chain reaction is used clinically in patients with early-stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast carcinoma (ER+/HER2- BC) to determine both prognosis with tamoxifen therapy and the usefulness of adding adjuvant chemotherapy. Use of the assay is associated with reductions in overall chemotherapy use. The current study examined the treatments and outcomes in patients with low RS. The authors reviewed the institutional database to identify patients with lymph node-negative, ER+/HER2- BC who were treated at the study institution between September 2008 and August 2013 and their 21-gene RS results. A total of 1406 consecutive patients with lymph node-negative ER+/HER2- BC and a low RS were identified (510 patients had an RS of 0-10 and 896 patients had an RS of 11-17). The median age at the time of diagnosis of BC was 56 years; 63 patients (4%) were aged metastases (1 patient with an RS of 5 and 5 patients with an RS of 11-17). In the cohorts of patients with an RS of 11 to 17, the absolute rate of distant metastasis among patients aged metastases. Analysis of data from other studies is necessary to validate this observation further. Cancer 2017;131-137. © 2016 American Cancer Society. © 2016 American Cancer Society.

  3. A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

    Science.gov (United States)

    Salamanna, Francesca; Contartese, Deyanira; Maglio, Melania; Fini, Milena

    2016-07-12

    While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients' quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.

  4. N-Telopeptide of Type I Collagen Long-Term Dynamics in Breast Cancer Patients With Bone Metastases: Clinical Outcomes and Influence of Extraskeletal Metastases.

    Science.gov (United States)

    Ferreira, Arlindo R; Alho, Irina; Shan, Ning; Matias, Margarida; Faria, Mariana; Casimiro, Sandra; Leitzel, Kim; Ali, Suhail; Lipton, Allan; Costa, Luís

    2016-12-01

    Markers of bone metabolism, such as N-telopeptide of type I collagen (NTX), have been demonstrated to be prognostic in previous trials of breast cancer (BC) patients with bone metastases (BMs). In the present study, we tested the survival effect of the NTX response to zoledronic acid (ZA) at 3 and 12 months in a contemporaneous cohort of BC patients with BMs and evaluated the influence of extraskeletal metastatic disease on NTX variation. The present study was a prospective cohort study of consecutive BC patients diagnosed and treated at a single center. Patients presenting with de novo radiological evidence of BMs who started monthly intravenous ZA were included. Urinary NTX was measured at baseline and 1, 3, 6, 9, and 12 months after ZA introduction. Overall, 71 patients were enrolled, 32 with BMs and 39 with BMs plus extraskeletal metastases. The proportion of patients with elevated NTX at baseline and 3 and 12 months was 49.3%, 26.6%, and 34.2%, respectively. The variables associated with survival included age at diagnosis, tumor estrogen receptor status, and NTX at 3 and 12 months. Multivariate analysis showed that, in addition to age at diagnosis, only the 3-month NTX level was significantly associated with survival. Patients with BMs plus extraskeletal metastases had an erratic NTX variation pattern, unrelated to survival. In the present contemporaneous cohort of BC patients with BMs, the NTX response at 3 months was strongly associated with survival. Furthermore, an early response to ZA was strongly associated with long-term NTX control. Finally, patients with BMs plus extraskeletal metastases had an erratic NTX variation. The present study showed that when accommodating recent therapy innovations and longer patient survival, the N-telopeptide (NTX) variation at 3 months is strongly associated with survival. In this setting, in addition to a few other clinicopathological features, NTX is a powerful prognostic marker. Moreover, early NTX correction

  5. Whole brain radiotherapy with hippocampal avoidance and simultaneous integrated boost for brain metastases: a dosimetric volumetric-modulated arc therapy study.

    Science.gov (United States)

    Giaj Levra, Niccolò; Sicignano, Gianluisa; Fiorentino, Alba; Fersino, Sergio; Ricchetti, Francesco; Mazzola, Rosario; Naccarato, Stefania; Ruggieri, Ruggero; Alongi, Filippo

    2016-01-01

    To develop a feasible volumetric modulated arc therapy (VMAT) treatment in whole brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) and hippocampal (HP) sparing in 1-5 brain metastases (BMs). Ten patients with 20 BMs received a WBRT prescription of 20 Gy, SIB dose on BMs of 40 Gy/5 fractions. PTVWBRT was generated from brain minus BMs-PTVs (PTVSIB) and planning organ at risk volume to HP. All plans were evaluated in: homogeneity index (HI), target coverage (TC), maximum dose to prescription dose ratio (MDPD), prescription isodose to target volume ratio (PITV) and paddick conformity index (CI). We also evaluate D100%, mean and maximum doses to HP. Planning objectives were for PTVWBRT, D2% = 25 Gy with acceptable deviation of 26.7 Gy and D98% ≥ 16.7 Gy; for PTVSIB D95% ≥ 38 Gy; for HP, D100% = 6 Gy with acceptable deviation of 6.7 Gy, Dmax = 10.7 Gy with acceptable deviation of 11.3 Gy, a mean dose of 8 Gy. Mean number of BMs was 2 (range 1-5). Mean values for BMs were volume of PTVSIB = 5.1 ± 4.9 cc, dose to 95% of PTVSIB 39.3 ± 0.9 Gy, HI 0.083 ± 0.03, TC 0.96 ± 0.24, CI 0.78 ± 0.17. Mean MDPD was 1.06 ± 0.02 and PITV 0.96 ± 0.24. For WBRT, mean target volume was (13.46 ± 2)*10(2) cc, mean dose to 90% of PTVWBRT 19.8 ± 0.2 Gy, mean HI 0.42 ± 0.12 and TC 0.78 ± 0.11. Mean and maximum HP doses were 7.7 ± 0.3 Gy and 10.5 ± 0.5 Gy. Mean dose to 100% of HP volume (D100%) was 6.7 ± 0.3 Gy. WBRT plus SIB with HP avoidance with VMAT was feasible. All dosimetric parameters were satisfied for PTVWBRT and PTVSIB.

  6. 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

  7. Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

    Science.gov (United States)

    Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

    2014-04-14

    Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

  8. Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

    Science.gov (United States)

    Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

    2014-01-01

    Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. PMID:24744570

  9. Comprehensive Clinical Staging for Resectable Lung Cancer: Clinicopathological Correlations and the Role of Brain MRI.

    Science.gov (United States)

    Vernon, Jordyn; Andruszkiewicz, Nicole; Schneider, Laura; Schieman, Colin; Finley, Christian J; Shargall, Yaron; Fahim, Christine; Farrokhyar, Forough; Hanna, Waël C

    2016-11-01

    In our model of comprehensive clinical staging (CCS) for lung cancer, patients with a computerized tomography scan of the chest and upper abdomen not showing distant metastases will then routinely undergo whole body positron emission tomography/computerized tomography and magnetic resonance imaging (MRI) of the brain before any therapeutic decision. Our aim was to determine the accuracy of CCS and the value of brain MRI in this population. A retrospective analysis of a prospectively entered database was performed for all patients who underwent lung cancer resection from January 2012 to June 2014. Demographics, clinical and pathological stage (seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, and metastasis staging manual), and costs of staging were collected. Correlation between clinical and pathological stage was determined. Of 315 patients with primary lung cancer, 55.6% were female and the mean age was 70 ± 9.6 years. When correlation was analyzed without consideration for substages A and B, 49.8% of patients (158 of 315) were staged accurately, 39.7% (125 of 315) were overstaged, and 10.5% (32 of 315) were understaged. Only 4.7% of patients (15 of 315) underwent surgery without appropriate neoadjuvant treatment. Preoperative brain MRI detected asymptomatic metastases in four of 315 patients (1.3%). At a median postoperative follow-up of 19 months (range 6-43), symptomatic brain metastases developed in seven additional patients. The total cost of CCS in Canadian dollars was $367,292 over the study period, with $117,272 (31.9%) going toward brain MRI. CCS is effective for patients with resectable lung cancer, with less than 5% of patients being denied appropriate systemic treatment before surgery. Brain MRI is a low-yield and high-cost intervention in this population, and its routine use should be questioned. Copyright © 2016 International Association for the Study of Lung Cancer. Published by

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

    Directory of Open Access Journals (Sweden)

    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

  11. Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis.

    Science.gov (United States)

    Patel, Kirtesh R; Burri, Stuart H; Boselli, Danielle; Symanowski, James T; Asher, Anthony L; Sumrall, Ashley; Fraser, Robert W; Press, Robert H; Zhong, Jim; Cassidy, Richard J; Olson, Jeffrey J; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

    2017-02-01

    Pre-operative stereotactic radiosurgery (pre-SRS) has been shown as a viable treatment option for resectable brain metastases (BM). The aim of this study is to compare oncologic outcomes and toxicities for pre-SRS and post-operative WBRT (post-WBRT) for resectable BM. We reviewed records of consecutive patients who underwent resection of BM and either pre-SRS or post-WBRT between 2005 and 2013 at two institutions. Overall survival (OS) was calculated using the Kaplan-Meier method. Cumulative incidence was used for intracranial outcomes. Multivariate analysis (MVA) was performed using the Cox and Fine and Gray models, respectively. Overall, 102 patients underwent surgical resection of BM; 66 patients with 71 lesions received pre-SRS while 36 patients with 42 cavities received post-WBRT. Baseline characteristics were similar except for the pre-SRS cohort having more single lesions (65.2% vs. 38.9%, p = 0.001) and smaller median lesion volume (8.3 cc vs. 15.3 cc, p = 0.006). 1-year OS was similar between cohorts (58% vs. 56%, respectively) (p = 0.43). Intracranial outcomes were also similar (2-year outcomes, pre-SRS vs. post-WBRT): local recurrence: 24.5% vs. 25% (p = 0.81), distant brain failure (DBF): 53.2% vs. 45% (p = 0.66), and leptomeningeal disease (LMD) recurrence: 3.5% vs. 9.0% (p = 0.66). On MVA, radiation cohort was not independently associated with OS or any intracranial outcome. Crude rates of symptomatic radiation necrosis were 5.6 and 0%, respectively. OS and intracranial outcomes were similar for patients treated with pre-SRS or post-WBRT for resected BM. Pre-SRS is a viable alternative to post-WBRT for resected BM. Further confirmatory studies with neuro-cognitive outcomes comparing these two treatment paradigms are needed.

  12. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial.

    Science.gov (United States)

    Mehta, Minesh P; Shapiro, William R; Phan, See C; Gervais, Radj; Carrie, Christian; Chabot, Pierre; Patchell, Roy A; Glantz, Michael J; Recht, Lawrence; Langer, Corey; Sur, Ranjan K; Roa, Wilson H; Mahe, Marc A; Fortin, Andre; Nieder, Carsten; Meyers, Christina A; Smith, Jennifer A; Miller, Richard A; Renschler, Markus F

    2009-03-15

    To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-01

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

  14. Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Furtner, Julia; Prayer, Daniela [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Berghoff, Anna S.; Zielinski, Christoph C.; Preusser, Matthias [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Albtoush, Omar M. [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); University of Jordan, Department of Radiology and Nuclear Medicine, Amman (Jordan); Woitek, Ramona; Asenbaum, Ulrika [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Widhalm, Georg; Gatterbauer, Brigitte [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, Karin [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Birner, Peter [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Medical University of Vienna, Department of Pathology, Vienna (Austria); Aretin, Bernadette [General Hospital Vienna, Pharmacy Department, Vienna (Austria); Bartsch, Rupert [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Schoepf, Veronika [University of Graz, Institute of Psychology, Graz (Austria); BioTechMed, Graz (Austria)

    2017-08-15

    To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. (orig.)

  15. 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

  16. The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

    Science.gov (United States)

    Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

    2017-06-01

    To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and

  17. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  19. 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

  20. Intracranial metastases: spectrum of MR imaging findings

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

    2012-12-15

    Intracranial metastatic lesions arise through a number of routes. Therefore, they can involve any part of the central nervous system and their imaging appearances vary. Magnetic resonance imaging (MRI) plays a key role in lesion detection, lesion delineation, and differentiation of metastases from othe