scholarly journals Survival in Melanoma Brain Metastases in the era of novel systemic therapies

2020 ◽  
Author(s):  
Joseph P Merola ◽  
Joanita Ocen ◽  
Satish Kumar ◽  
James Powell ◽  
Caroline Hayhurst
Keyword(s):  
Brain Metastases ◽  
Demographic Data ◽  
Systemic Disease ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Aggressive Approach ◽  
Brain Radiotherapy ◽  
Melanoma Brain Metastases ◽  
Receive Treatment

Abstract Background Melanoma brain metastases (MBM) have historically poor overall survival (OS). Recently introduced systemic anticancer therapies (SACT), namely targeted therapies (TT) such as BRAF inhibitors and immunotherapy (IO), to control advanced disease have shown improved survival. Today, increasingly aggressive strategies are sought for MBM. We review outcomes in MBM after surgery or stereotactic radiosurgery (SRS) and the survival impact in advanced systemic disease when combined with novel anticancer therapies. Methods Retrospective cohort study of patients referred to a regional neuro-oncology multidisciplinary (MDT) meeting with MBM. Demographic data, extent of systemic disease and data on surgical and oncological management were collected, plus use of SACT. The primary outcomes were median OS, 12 and 24 month survival and progression-free survival. Results Between 2010 – 2018 142 patients with MBM were referred. Following the introduction of SACT the rate of referrals to MDT more than doubled from 11.6 to 25.7 patients per year. A focal brain metastasis was treated surgically in 23 (16.2%) patients, and by SRS in 29 (20.4%). 56 (39.4%) patients underwent palliative whole brain radiotherapy (WBRT) and 34 (23.9%) did not receive treatment. Median OS was 11 months for the surgical cohort, 9 months for the SRS cohort and increased when treatment with or without SACT was considered to 23 months and 12 months respectively. Conclusion In the setting of SACTs, survival in MBM is significantly improved after surgery or SRS even in patients with advanced and uncontrolled systemic disease at the time of presentation, supporting an aggressive approach to MBM management.

scholarly journals THER-02. PARP Inhibitor Tolerability and Impact on Progression-Free Survival in Patients with High-Grade, Ovarian Carcinoma with Brain Metastasis: A Case-Series

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii12-iii13
Author(s):  
Alexander Mohler ◽  
Belkys Salinas ◽  
Karissa Nazur ◽  
Yazmin Odia ◽  
Nicholas Lambrou
Keyword(s):  
Brain Metastases ◽  
Ovarian Carcinoma ◽  
Parp Inhibitor ◽  
Systemic Disease ◽  
Case Series ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Adjunctive Treatment ◽  
Brain Radiotherapy

Abstract Brain metastases secondary to ovarian carcinoma is an uncommon but increasing phenomenon. PARP inhibitors (PARPi) are increasingly used as an adjunctive treatment in patients with central nervous system metastases (CNS). Historically brain metastases has a historically poor prognosis. Five women with a mean age of 60.4 ± 7.6 years were included. All had stage IIIC/IV ovarian cancer and diagnosed with brain metastases at recurrence. Three underwent resection for oligometastatic disease followed by post-operative stereotactic radiosurgery (SRS), one had SRS without surgery, and one patient underwent whole brain radiotherapy for multiple metastases. Pathology was confirmed in those who were resected. Two patients had evidence of systemic disease in addition to CNS spread. Three women were BRCA1/2 Positive. Following initial radiotherapy, one patient received adjuvant chemotherapy followed by olaparib maintenance, one received 13 cycles of bevacizumab/olaparib, followed by olaparib maintenance. A third patient was treated with olaparib/bevacizumab and two patients received olaparib monotherapy, both of whom continued on therapy. All received olaparib therapy during their treatment and all had minor dose modifications due to side effects. Mean survival from initial cancer diagnosis was 62.4 ± 20.4 months. Mean duration of PARPi therapy was 27.6 ± 16.8 months. Mean survival following CNS recurrence was 22.8 ± 12 months. One patient is disease-free, two patients are alive with stable disease, one patient is alive but off treatment secondary to progression, and one patient is deceased secondary to progression of her brain metastases after being on PARP therapy for 18 months. The cohort remained highly functional across the trajectory of their disease with ECOG scores of 1 (n=4) or 0 (n=1). The results of this single institution retrospective evaluation suggest olaparib in combination with radiotherapy +/- bevacizumab is well tolerated and can provide additional benefit in patients with brain metastases secondary to ovarian carcinoma.

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.

Primary chemotherapy, stereotactic radiosurgery, or whole brain radiotherapy in non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19063-e19063
Author(s):  
K. Kim ◽  
J. Lee ◽  
M. Chang ◽  
J. Uhm ◽  
J. A. Yun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Primary Chemotherapy ◽  
Treatment Modalities ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Nsclc Patients

e19063 Background: Approximately 25 to 30% of patients with lung cancer develop brain metastases at some stage and 12∼18% at the time of initial presentation. Whole brain radiotherapy (WBRT) has long been a mainstay of treatment of brain metastases. Another treatment approach, Stereotactic radiosurgery (SRS) is a method of delivering high doses of focal irradiation to a tumor while minimizing the irradiation to the adjacent normal tissue. However, the prognosis of NSCLC patients with asymptomatic brain metastases, who are not treated with SRS or WBRT, has not been fully investigated yet. This study aimed to analyze the outcome for various treatment modalities in NSCLC patients with asymptomatic brain metastases. Methods: We reviewed the medical records of 129 patients with a histopathologically proven NSCLC and a synchronous brain metastases between January 2003 and December 2007. The patients were categorized as primary chemotherapy, primary SRS, and primary WBRT group: primary chemotherapy (78 patients), primary SRS (24 patients), and primary WBRT (27 patients). Results: With median follow-up of 30.0 months (7.2 -70.7), the median overall survival (OS) for the entire patients was 15.6 months (0.5–50.7) and the progression free survival (PFS) was 6.1 months (0.3- 53.0). The OS was 22.4m for primary SRS group, 13.9m for primary chemotherapy group, and 17.7m for primary WBRT group; p=0.86). However, patients treated with primary SRS showed trend toward prolonged survival compared to those of primary WBRT p=0.06). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with primary SRS was longer than those of primary WRBT (29.3m vs 17.7m p=0.01) or primary chemotherapy (29.3m vs 14.6m p=0.04). Conclusions: These results suggest that for NSCLC patients with asymptomatic brain metastases at first diagnosis, SRS rather than primary chemotherapy or WBRT might be considered as initial treatment, especially for patients with adenocarcinoma. No significant financial relationships to disclose.

A new option in brain-metastases: Hippocampal-sparing whole-brain radiotherapy with simultaneous integrated boost VMAT-IGRT.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13589-e13589
Author(s):  
Alicia Marin ◽  
Margarita Martin ◽  
Emma Gonzalez ◽  
Lisselott Torres ◽  
David Hernandez ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Simultaneous Integrated Boost ◽  
Rank Test ◽  
Whole Brain ◽  
Free Survival ◽  
Brain Radiotherapy ◽  
Integrated Boost ◽  
Hippocampal Sparing

e13589 Background: We report our experience with volumetric modulated arc therapy (VMAT-IGRT) use to plan and deliver whole brain radiotherapy whit a simultaneous integrated boost in patients with brain metastases, using hippocampal sparing. Methods: In this retrospective study 57 patients with brain metastases were treated with radiotherapy VMAT-IGRT were administered in 12 daily fractions of 2.7Gy for a total of 32.4Gy (EBD 40Gy) to whole-brain and simultaneous integrated boost to brain metastases, multiple targets, in 12 fractions to 3.4Gy for a total dose of 40.8Gy (EBD 60Gy). The primary endpoint was intracranial progression-free survival (PFS) and secondary endpoints were preserves neurocognitive function and overall survival (OS). Survival rates were determined by Kaplan-Meier method. Differences between survival curves were analyzed by the log-rank test. Results: From January 2015 to December 2018, 57 patients were enrolled. The median follow-up time was 7 months. PFS6, PFS12 and PFS18 were 91.3%, 70.8% and 70.8% respectively. mOS, OS6, OS12 and OS18 were 10 months (95% IC 4.2-15.7 months), 67.2%, 48.6% and 35.3% respectively. Response rates were as follows: 29RC (50.9%), 21RP (36.8%), 7SD (12.3%) and 0PD (0%). Long progression-free survival patients: PFS > 12, 15 and 18 months for initial diagnosis 70%, 70% and 70% respectively. Conclusions: Whole-brain radiotherapy with simultaneous integrated boost to brain-metastases: VMAT-IGRT is safe and promising and possibly produces survival and tolerance benefits. Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning.

scholarly journals Accrual to a randomised trial of adjuvant whole brain radiotherapy for treatment of melanoma brain metastases is feasible

2014 ◽  
Vol 7 (1) ◽  
Author(s):  
Gerald B Fogarty ◽  
Angela Hong ◽  
Kari Dolven Jacobsen ◽  
Claudius H Reisse ◽  
Brindha Shivalingam ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Randomised Trial ◽  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Melanoma Brain Metastases

Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery (SRS) in patients with 1-3 newly diagnosed brain metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
David M. Peereboom ◽  
Samuel T. Chao ◽  
John H. Suh ◽  
Ding Wang ◽  
Tom Mikkelsen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Brain Metastases ◽  
Systemic Disease ◽  
Neuropsychological Testing ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Growth Factor Signaling ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Primary Disease

2018 Background: For patients with 1-3 brain metastases, standard therapy after SRS is adjuvant whole brain radiotherapy (WBRT). SRS without WBRT carries a higher rate of brain relapse. Due to concerns about neurologic sequelae of WBRT, however, many patients and physicians opt to defer WBRT until the time of central nervous system (CNS) progression. This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Sunitinib inhibits vascular endothelial growth factor signaling, and we hypothesized that it would prevent growth of microscopic brain metastases presumed to be present. The objective was to use adjuvant sunitinib after SRS to prevent the emergence of new or progressive disease in the brain or at the site of SRS and to preserve neurocognitive function. Methods: Eligible patients had 1-3 newly diagnosed brain metastases, RTOG RPA class 1-2, and started sunitinib < 1 month after SRS and baseline neuropsychological testing (NPT). Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/d days 1-28 every 42 days until CNS progression. NPT and MRIs were obtained every 2 cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Results: Fourteen patients enrolled. The median age was 59 (range 46-80). Main histologies: lung 36%, breast 21%, melanoma 14%. Toxicities: Grade 4: neutropenia [ANC] (1 pt); Grade 3: fatigue (5), ANC (2), rash (1). Dose reduction due to toxicity: 1 pt (to 37.5 mg/d). The CNS PFS6 and PFS12 were 50% + 13% and 43% + 13%, respectively. The median PFS was 6.6 months (95% C.I. 1.5-19). NPT results will be reported at the meeting. Conclusions: Sunitinib after SRS for 1-3 brain metastases was well tolerated with a PFS6 of 50%. The use of novel agents to prevent progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient’s primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of brain metastases after definitive local therapy (surgery or SRS).

Addition of upfront whole-brain radiotherapy to surgery or stereotactic radiosurgery versus surgery or stereotactic radiosurgery alone for treatment of brain metastases: A systematic review and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2016-2016
Author(s):  
Yu Yang Soon ◽  
Ivan Weng Keong Tham ◽  
Keith Hsiu Chin Lim ◽  
Wee Yao Koh ◽  
Jiade Jay Lu
Keyword(s):  
Brain Metastases ◽  
Disease Progression ◽  
Stereotactic Radiosurgery ◽  
Meta Analysis ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Neurological Toxicity ◽  
Brain Radiotherapy ◽  
Intracranial Disease ◽  
One Year

2016 Background: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to determine the efficacy and safety of additional upfront WBRT. Methods: We searched MEDLINE, EMBASE, CENTRAL from date of inception and annual meeting proceedings of ASCO and ASTRO from 1999 to September 2011 for RCTs comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), quality of life (Qol) and neurological toxicity. Hazard ratios (HR), confidence intervals (CI), p values (p) were estimated with random effects models using Revman 5.1. Results: We found five RCTs including 663 patients with one to four brain metastases. Adding upfront WBRT decreased the one-year incidence of any intracranial disease progression from 73-76% to 22 - 47% but did not improve OS (HR 1.11, 95%CI 0.83 - 1.48, p = 0.47) and PFS (HR 0.76, 95%CI 0.53 - 1.10, p = 0.14). Subgroup analyses showed that the effects on overall survival are similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The effects of upfront WBRT on NF, Qol and neurological toxicity were variable. Conclusions: Adding upfront WBRT to surgery or SRS significantly decreased any intracranial disease progression at one year but did not improve overall and progression free survival and produced variable effects on neurocognitive function, quality of life and neurological toxicity when compared with surgery or SRS alone. Future research should focus on developing more effective approaches to characterize and ameliorate the potential neurological toxicity of WBRT.

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

2016 ◽  
Vol 9 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Michelle M. Kim ◽  
Hemant Parmar ◽  
Yue Cao ◽  
Priyanka Pramanik ◽  
Matthew Schipper ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Brain Metastases ◽  
Phase I ◽  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Melanoma Brain Metastases
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