P14.25 Melanoma brain metastases in the era of novel therapies: a single-center, Dutch cohort study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii43-ii43
Author(s):  
S H A E Derks ◽  
J L M Jongen ◽  
C Slagter ◽  
A Joosse ◽  
J W Schouten ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Braf Mutation ◽  
Checkpoint Inhibitors ◽  
Whole Brain Radiotherapy ◽  
Novel Therapies ◽  
Single Center ◽  
Male Predominance ◽  
Brain Radiotherapy ◽  
Melanoma Brain Metastases ◽  
Before And After

Abstract BACKGROUND Until recently, patients with melanoma brain metastases (MBMs) had limited therapeutic options. With the arrival of immune checkpoint inhibitors (ICIs), targeted therapy (TT) and advances in stereotactic radiotherapy (SRT), treatment has improved. We evaluated treatments and patient outcome before and after the introduction of these novel therapies. MATERIAL AND METHODS In this retrospective, single-center study, patients presenting with MBMs at the Erasmus MC between November 2005 and January 2021 with sufficient follow-up were included. Overall survival (OS), measured from date of MBM diagnosis, was calculated using the Kaplan-Meier method. Patients were stratified according to MBM diagnosis before and after January 1, 2016, since novel therapies were mostly prescribed in our clinic after this date. Results were significant (p<0.05), unless otherwise stated. RESULTS Overall, 413 patients were included. Median [IQR] age was 56.6 years [52–71] with a 60% male predominance. A BRAF mutation was present in 46.7% of patients. A single MBM was found in 29.3% and ≥4 MBMs were found in 49.0% of patients. Before January 1, 2016, 191 patients were treated, and 222 patients after that date. Chemotherapy was more frequently used before 2016, both prior to (3.9% pre-2016 vs. 0.9% post-2016) and after (7.0% vs. 0.0%) the diagnosis of MBMs. In contrast, treatment with TT was more frequent after 2016, both prior to (3.7% vs. 16.2%) and after (7.9% vs. 41.4%) the diagnosis of MBMs. Comparable changes were observed for treatment with ICIs (prior to MBM diagnosis: 0.5% vs. 25.2%; after MBM diagnosis: 18.3% vs 39.2%). The application of SRT did not differ significantly before and after 2016 (12.0% vs. 19.4%, p=0.89), while the application of whole brain radiotherapy (WBRT) decreased (52.4% vs. 13.5%). Surgical resection was not significantly different between those periods (15.7% vs. 16.7%, p=0.90). Before 2016, median OS [IQR] was shorter than after 2016 (4.6 [1.9–10.9] vs. 6.6 [1.8–24.5] months). The effect of novel therapies on OS was further analysed in patients diagnosed after 2016; treatment vs. no treatment was compared. ICI treatment prior to MBM diagnosis was associated with worse OS (median OS 4.0 vs. 7.5 months). ICI treatment after MBM diagnosis was associated with better OS (median OS 24.5 vs. 3.0 months). In patients with a BRAF mutation, TT before MBM diagnosis was associated with worse OS (median OS 1.8 vs. 9.4 months). TT after MBM diagnosis in those patients was not significantly associated with improved OS (median OS 7.6 vs. 5.2 months, p=0.96). CONCLUSION Recent therapeutic advances for MBM replaced WBRT and chemotherapy with SRT, TT and ICIs. In that period, prognosis of MBM patients increased significantly. OS in patients treated with ICIs or TT prior to MBM diagnosis is still poor, but OS is improved in patients treated with ICIs after the diagnosis of MBM.

The brain metastasis journey: Experience from patient, caregiver, and physician surveys on diagnosis and treatment of brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14004-e14004
Author(s):  
Albert Eusik Kim ◽  
GI-Ming WANG ◽  
Kristin A Waite ◽  
Scott Elder ◽  
Avery Fine ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Whole Brain Radiotherapy ◽  
Well Being ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Brain Radiotherapy

e14004 Background: Brain metastases (BM) is one of the most feared complications of cancer due to substantial neurologic sequalae, neuro-cognitive morbidity and grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have resulted in meaningfully improved overall survival for a minority of these patients. Accordingly, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been a well-conducted formal study to specifically explore these questions of survivorship and practice standardization for BM patients. Methods: Here, we present results from a cross-sectional survey in which we analyzed responses from 237 BM patients, 209 caregivers, and 239 physicians. Surveys contained questions about BM symptoms, discussion of BM diagnosis by the clinician, psychosocial concerns, available treatment options for BM, BM patient advocacy resources, and BM-specific clinical trials. Results: Our survey revealed compelling findings about current care of BM patients. There were discrepancies in the perceived discussion of the implications of the diagnosis of BM, from the patient/caregiver and physician perspective. Important topics, such as prognosis and worrisome symptoms, were felt to have been discussed more frequently by physicians than by patients or caregivers. In our physician survey, private practice physicians, compared to academic physicians, were significantly more likely to recommend whole brain radiotherapy (61.1 vs 39.7%; p = 0.009). Participation in a clinical trial was one of the least recommended treatment options. Many physicians (59.1% private; 71.9% academic) stated that BM patients in their care are denied participation in a clinical trial, specifically due to the presence of BM. The consensus among physicians, patients and caregivers was that the highest yield area for federal assistance is increased treatment and research funding for BM. Conclusions: Our hope is that these findings will serve as a basis for future quality improvement measures to enhance patient-physician communication and patient well-being, continuing medical education activities detailing latest advances in BM for oncologists, and lobbying efforts to the federal government in prioritizing BM research, clinical trials, and patient survivorship.

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.

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

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

Evaluation of Stereotactic Radiotherapy of the Resection Cavity After Surgery of Brain Metastases Compared to Postoperative Whole-Brain Radiotherapy (ESTRON)—A Single-Center Prospective Randomized Trial

Neurosurgery ◽  
2018 ◽  
Vol 83 (3) ◽  
pp. 566-573 ◽  
Author(s):  
Rami A El Shafie ◽  
Angela Paul ◽  
Denise Bernhardt ◽  
Henrik Hauswald ◽  
Thomas Welzel ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiotherapy ◽  
Randomized Study ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Locoregional Control ◽  
Single Center ◽  
Whole Brain ◽  
Resection Cavity ◽  
Brain Radiotherapy

Abstract BACKGROUND Neurosurgical resection is recommended for symptomatic brain metastases, in oligometastatic patients or for histology acquisition. Without adjuvant radiotherapy, roughly two-thirds of the patients relapse at the resection site within 24 mo, while the risk of new metastases in the untreated brain is around 50%. Adjuvant whole-brain radiotherapy (WBRT) can reduce the risk of both scenarios of recurrence significantly, although the associated neurocognitive toxicity is substantial, while stereotactic radiotherapy (SRT) improves local control at comparably low toxicity. OBJECTIVE To compare locoregional control and treatment-associated toxicity for postoperative SRT and WBRT after the resection of 1 brain metastasis in a single-center prospective randomized study. METHODS Fifty patients will be randomized to receive either hypofractionated SRT of the resection cavity and single- or multisession SRT of all unresected brain metastases (up to 10 lesions) or WBRT. Patients will be followed-up regularly and the primary endpoint of neurological progression-free survival will be assessed by magnetic resonance imaging (MRI). Quality of life and neurocognition will be assessed in 3-mo intervals using standardized tests and EORTC questionnaires. EXPECTED OUTCOMES We expect to show that postoperative SRT of the resection cavity and further unresected brain metastases is a valid means of improving locoregional control over observation at less neurocognitive toxicity than caused by WBRT. DISCUSSION The present study is the first to compare locoregional control as well as neurocognitive toxicity for postoperative SRT and WBRT in patients with up to 10 metastases, while utilizing a highly sensitive and standardized MRI protocol for treatment planning and follow-up.

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