MODERN STRATEGIES FOR TREATMENT OF PATIENTS WITH BRAIN METASTASES

2017 ◽  
Vol 63 (4) ◽  
pp. 523-535
Author(s):  
Sergey Banov ◽  
Andrey Golanov ◽  
Sergey Ilyalov ◽  
Yelena Vetlova ◽  
Natalya Antipina ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Standard Of Care ◽  
Current Treatment ◽  
Management Options ◽  
Brain Radiotherapy ◽  
Tumor Pathology ◽  
Treatment Paradigm ◽  
Overall Health Status

Brain metastases are the most common intracranial malignancy accounting for significant morbidity and mortality in cancer patients. The current treatment paradigm for brain metastasis depends on patient’s overall health status, the primary tumor pathology and the number and location of brain lesions. Treatment of brain metastases should be individualized for each patient: in case of single brain metastasis surgery or radiosurgery should be considered as first options of treatment; in case of multiple lesions whole-brain radiotherapy is the standard of care in association with systemic therapy or surgery/radiosurgery. Herein, we review the modern management options for these tumors including surgical resection, radiotherapy. In the last decades TKIs or monoclonal antibodies have showed an increase in overall response rate and overall survival in Phase II-III trials. The aim of this paper is to make an overview of the current approaches in management of patients with brain metastases.

Prognostic factors and survival after whole-brain radiotherapy for initial brain metastases arising from non-small cell lung cancer

2021 ◽  
pp. 1-6
Author(s):  
Yukinori Okada ◽  
Mariko Kobayashi ◽  
Mio Shinozaki ◽  
Tatsuyuki Abe ◽  
Naoki Nakamura
Keyword(s):  
Prognostic Factors ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Gene Mutation ◽  
Stage Iv ◽  
Whole Brain Radiotherapy ◽  
Hazard Ratio ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Brain Radiotherapy

Abstract Aim: To identify prognostic factors and investigate patient survival after whole-brain radiotherapy (WBRT) for initial brain metastases arising from non-small cell lung cancer (NSCLC). Methods: Patients diagnosed with NSCLC between 1 January 2010 and 30 September 2019, and who received WBRT upon first developing a brain metastasis, were investigated. Overall survival was determined as related to age, sex, duration between initial examination and brain metastasis detection, stage at the first examination, presence of metastases outside the brain, blood analysis findings, brain metastasis symptoms, radiotherapy dose and completion, imaging findings, therapeutic course of chemotherapy and/or radiation therapy, histological type, and gene mutation status. Results: Thirty-one consecutive patients (20 men and 11 women) with a mean age of 63·8 years and median survival of 129 days were included. Multivariate analysis with stepwise testing was performed to investigate differences in survival according to gene mutation status, lactate dehydrogenase (LDH) level, irradiation dose, WBRT completion and Stage status. Of these, a statistically significant difference in survival was observed in patients with gene mutation status (hazard ratio: 0·31, 95% CI: 0·11–0·86, p = 0·025), LDH levels <230 vs. ≥230 IU/L (hazard ratio: 4·08, 95% CI: 1·45–11·5, p < 0·01) received 30 Gy, 30 Gy/10 fractions to 35 Gy/14 fractions, and 37·5 Gy/15 fractions (hazard ratio: 0·26, 95% CI: 0·09–0·71, p < 0·01), and stage IV versus non-stage IV (hazard ratio: 0·13, 95 CI:0·02–0·64, p < 0·01) Findings: Gene mutation, LDH, radiation dose and Stage are prognostic factors for patients with initial brain metastases who are treated with WBRT.

scholarly journals Current treatment of patients with multiple brain metastases

2000 ◽  
Vol 9 (2) ◽  
pp. 1-5 ◽  
Author(s):  
Steven D. Chang ◽  
John R. Adler
Keyword(s):  
Brain Metastases ◽  
Treatment Options ◽  
Whole Brain Radiotherapy ◽  
Mass Effect ◽  
Current Treatment ◽  
Rapid Reduction ◽  
Multiple Brain Metastases ◽  
Brain Radiotherapy ◽  
Multiple Metastases ◽  
Difficult Challenge

The management of patients with multiple brain metastases remains a difficult challenge for neurosurgeons. This patient population has a poor prognosis when compared with those harboring a solitary brain metastasis, and historically treatment has generally consisted of administering whole-brain radiotherapy once the diagnosis of multiple brain metastases is made. Resection can be useful in a subset of patients with multiple metastases in whom one or two of the lesions are symptomatic, as this may provide rapid reduction of mass effect and edema. Furthermore, the authors of recent studies have shown that stereotactic radiosurgery can be used in certain patients with multiple brain metastases as part of the treatment regimen. In this review the authors outline the treatment options and indications as well as a management strategy for the treatment of patients with multiple brain metastases.

Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies

2013 ◽  
pp. 393-398 ◽  
Author(s):  
Georgina V. Long ◽  
Kim A. Margolin
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
First Line Therapy ◽  
Melanoma Brain Metastases

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

Low protracted dose of temozolomide (TMZ) and concurrent radiotherapy for brain metastasis of solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12525-12525
Author(s):  
R. Addeo ◽  
V. Faiola ◽  
G. Cennamo ◽  
R. Guarrasi ◽  
L. Montella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Overall Response Rate ◽  
Response Rate ◽  
Whole Brain Radiotherapy ◽  
Primary Brain Tumours ◽  
Brain Radiotherapy ◽  
Dna Alkyltransferase ◽  
Grade 3

12525 Background. Whole brain radiotherapy (WBRT) remains the mainstay of therapy for brain metastasis of solid tumours not amenable to surgical resection. Chemotherapy with temozolomide (TMZ) has emerged as an alterative approach for recurrent brain metastases. It has been already used alone or in combination with radiotherapy in the treatment of primary brain tumours. Protracted administration of TMZ, even at relatively low daily doses, leads to significant and prolonged depletion of enzyme O6-alkylguaninae-DNA alkyltransferase (AGAT) activity, with may enhance the antitumor activity of the agent. Methods. Patients with histologically or cytologically confirmed breast cancer and NSCLC and inoperable brain metastasis were eligible for the study .We have treated 29 consecutive patients (16 F and 13 M, mean age: 55, range 46–76) affected by brain metastases ( 16 non-small-cell lung cancer and 13 breast cancer) with WBRT at 3 Gy/day administered over a two-week period (on wks 1–2), total dose 30 Gy, and an induction with TMZ 50 mg/m2/day during this period, following TMZ 50mg/m2 fractionated in 21 days every 28 days, for up to 12 cycles. Pts who received at least one cycle of TMZ were assessable for response. Results. Twenty-four patients were subjected to the induction therapy and 124 cycles were performed. TMZ was generally well tolerated, and the main toxicities seen were hematologic. The toxicities were generally between grade 1 or 2 in severity although two patients had grade 3 events. Two CR, in patients with breast cancer and NSCLC. Nine partial responses were recorded in 5/11 patients with breast cancer, 4/13 patients with NSCLC, while a stable disease was achieved in other 5 patients. Eight patients showed progressive BM growth during the treatment. The overall response rate was 45.5% (C.I. 38.7–56.9%), while the disease control rate was 77% (C.I. 61.7–82.4%). At the present, the overall survival at 12 months was 64%. Conclusions. We developed a new regimen based on a different strategy: the utilization of a more intensive TMZ dosing schedule that would permit the concomitant use of a second cytotoxic agent on the primary cancer. Final data analysis will be presented. The schedule was safe and well tolerated and has suggested an encouraging activity in brain metastases. No significant financial relationships to disclose.

scholarly journals Is local radiotherapy a viable option for patients with an opening of the ventricles during surgical resection of brain metastases?

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sophia Scharl ◽  
Kerstin A. Kessel ◽  
Christian Diehl ◽  
Jens Gempt ◽  
Bernhard Meyer ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Surgical Resection ◽  
Local Treatment ◽  
Whole Brain Radiotherapy ◽  
Standard Of Care ◽  
Neurological Impairment ◽  
Distant Recurrence ◽  
Tumor Bed ◽  
Resection Cavity ◽  
Brain Radiotherapy

Abstract Background Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases. Methods From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery. Results From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01). Conclusion VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.

Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis

2016 ◽  
Vol 126 (6) ◽  
pp. 1749-1755 ◽  
Author(s):  
David R. Raleigh ◽  
Zachary A. Seymour ◽  
Bryan Tomlin ◽  
Philip V. Theodosopoulos ◽  
Mitchel S. Berger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Local Control ◽  
Whole Brain Radiotherapy ◽  
Cavity Volume ◽  
Term Survival ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Iodine 125

OBJECTIVEStereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases.METHODSA total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models.RESULTSThe median age at surgery was 59 years (range 29.9–81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21–76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4–93), and the median activity was 0.73 mCi (range 0.34–1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0–22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02–13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05).CONCLUSIONSTherapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients.▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

scholarly journals Survival time and prognostic factors after whole-brain radiotherapy of brain metastases from of breast cancer

2020 ◽  
Vol 9 (7) ◽  
pp. 205846012093874
Author(s):  
Yukinori Okada ◽  
Mariko Kobayashi ◽  
Mio Shinozaki ◽  
Tatsuyuki Abe ◽  
Yoshihide Kanemaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Survival Time ◽  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Overall Survival Time ◽  
Brain Radiotherapy ◽  
Contrast Enhanced

Background Breast cancer has a poor prognosis due to the high risk of distant metastasis. Purpose To identify the prognosticators of brain metastasis from breast cancer treated by whole-brain radiotherapy. Material and Methods We evaluated patients diagnosed with primary brain metastasis without carcinomatous meningitis from breast cancer and had undergone whole-brain radiotherapy as initial treatment between 1 January 2010 and 30 September 2019. We investigated associations between overall survival time from diagnosis using cranial contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) and the following parameters: (i) age; (ii) sex; (iii) time to appearance of brain metastasis; (iv) other metastasis at appearance of brain metastasis; (v) blood test; (vi) symptoms at time of brain metastasis; (vii) whole-brain radiotherapy dose; (viii) whether whole-brain radiotherapy was completed; (ix) course of chemo- or radiotherapy; (x) subtype; (xi) additional irradiation after whole-brain radiotherapy; (xii) pathology; and (xiii) imaging findings. Results We evaluated 29 consecutive female patients (mean age 55.2 ± 12.1 years). Median overall survival time after diagnosis on cranial contrast-enhanced MRI/CT was 135 days (range 16–2112 days). Multivariate stepwise analysis of the three parameters of lactate dehydrogenase, dose, and subtype identified the following significant differences: Hazard Ratio (HR) for dose (discontinued, 30 Gy/10 fractions, 31.5 Gy/11 fractions, 32.5 Gy/11 fractions, 37.5 Gy/15 fractions) was 0.08 (95% confidence interval [CI] 0.02–0.30, P < 0.01), and HR for subtype (luminal, HER2, triple-negative) was 2.70 (95% CI 1.16–6.243, P < 0.01). Conclusion HER2-type and 37.5 Gy/15 fractions are good prognostic factor after whole-brain radiotherapy in breast cancer with brain metastases.

scholarly journals Brain Metastases from Endometrial Carcinoma

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Ettie Piura ◽  
Benjamin Piura
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Endometrial Carcinoma ◽  
Primary Source ◽  
Whole Brain Radiotherapy ◽  
Endometrial Biopsy ◽  
The Body ◽  
Unknown Primary ◽  
Brain Radiotherapy ◽  
Disseminated Disease

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.

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