Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity

Diao, Kevin; Bian, Shelly X.; Routman, David M.; Yu, Changhong; Ye, Jason C.; Wagle, Naveed; Wong, Michael K.; Zada, Gabriel; Chang, Eric L.

doi:10.1007/s11060-018-2880-y

Cited by 74 publications

(68 citation statements)

References 37 publications

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“…Previously published studies have also investigated the association of immunotherapy combined with RT and chemotherapy with outcomes. 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 Most previous studies only included patients with metastatic melanoma who received a single drug (ie, ipilimumab). 28 , 35 , 36 , 37 The findings of the current study are consistent with the earlier studies that were focused on patients with melanoma.…”

Section: Discussionmentioning

confidence: 99%

Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor

et al. 2020

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Key Points Question Is combining immunotherapy with other cancer treatments associated with improved overall survival in patients with brain metastases? Findings In this comparative effectiveness study of 3112 adult patients who received definitive surgery of the primary cancer site, those who received any treatment plus immunotherapy had better overall survival than those who received no immunotherapy. Results varied with other combined therapies; immunotherapy plus radiation therapy was associated with improved overall survival compared with radiation therapy alone, but immunotherapy plus chemotherapy was not associated with improved overall survival compared with chemotherapy alone. Meaning In this study, immunotherapy plus radiotherapy was associated with improved overall survival compared with radiotherapy alone.

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Section: Discussionmentioning

confidence: 99%

Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor

et al. 2020

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“…MBM are generally known to have a high disposition for intralesional hemorrhage, with rates of up to 50% even before the first specific treatment 18,31,32 . Recent studies reporting on the combined treatment of anti‐PD1 or anti‐CTLA‐4 and stereotactic radiosurgery (SRS), did not show an increased hemorrhage rate 21,28,33,34 . Other studies described an increased hemorrhage rate in patients treated with SRS and BRAF inhibitors despite the reported improvement in local control 35 .…”

Section: Discussionmentioning

confidence: 99%

Toxicity and efficacy of Gamma Knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy—A retrospective cohort study

et al. 2020

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Background: Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT. Methods: We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era. Results: The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7-1.2 years). Patients treated with anti-PD-1 or a combination of anti-CTLA-4/PD-1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti-PD-1, anti-CTLA-4, or a combination of anti-CTLA-4/PD-1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT. Conclusion: In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted. K E Y W O R D S brain metastases, gamma knife radiosurgery, immunotherapy, melanoma, targeted therapy | 4027 GATTERBAUER ET Al.

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“…Treatment regimens were classified as “RT alone” or “ICI-RT” (for combinations). “ICI-RT” treatment was further classified as “concurrent ICI-RT” if ICI treatment was administered within 4 weeks of the start or end of RT, otherwise it was classified as “sequential ICI-RT”; the threshold was selected based on the half-lives of ICI drugs ( 20 , 21 ). If information on such timing was not reported or alternative cut-offs were used, the regimen was classified as “unknown ICI-RT.” ICI therapy was classified as “PD-(L)1” or “CTLA-4” targeted; if both ICI classes or their combination were considered, the therapy was defined as “unknown ICI-RT.” If only stereotactic RT regimens such as SRS or stereotactic radiotherapy (SRT) were used in the study, they were classified as “stereotactic”; if other conventional RT regimens such as whole-brain radiotherapy (WBRT), partial brain irradiation (PBI) were also considered, the RT regimen was classified as “WBRT-PBI.” Patient characteristics were collected, including age, histology, initial tumor volume, Karnofsky performance status (KPS) or ECOG performance status, previous chemotherapy (CT) or targeted therapy with BRAF inhibitors, combination of BRAF and MEK inhibitors, EGFR or ALK inhibitors or other agents (TT).…”

Section: Methodsmentioning

confidence: 99%

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

Voronova¹,

Sekacheva

Helmlinger³

et al. 2020

Front. Oncol.

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Objectives: The goal of this quantitative research was to evaluate the impact of various factors (e.g., scheduling or radiotherapy (RT) type) on outcomes for RT vs. RT in combination with immune checkpoint inhibitors (ICI), in the treatment of brain metastases, via a meta-analysis. Methods: Clinical studies with at least one ICI+RT treatment combination arm with brain metastasis patients were identified via a systematic literature search. Data on 1-year overall survival (OS), 1-year local control (LC) and radionecrosis rate (RNR) were extracted; for combination studies which included an RT monotherapy arm, odds ratios (OR) for the aforementioned endpoints were additionally calculated and analyzed. Mixed-effects meta-analysis models were tested to evaluate impact on outcome, for different factors such as combination treatment scheduling and the type of ICI or RT used. Results: 40 studies representing a total of 4,359 patients were identified. Higher 1-year OS was observed in ICI and RT combination vs. RT alone, with corresponding incidence rates of 59% [95% CI: 54-63%] vs. 32% [95% CI: 25-39%] ( P < 0.001). Concurrent ICI and RT treatment was associated with significantly higher 1-year OS vs. sequential combinations: 68% [95% CI: 60-75%] vs. 54% [95% CI: 47-61%]. No statistically significant differences were observed in 1-year LC and RNR, when comparing combinations vs. RT monotherapies, with 1-year LC rates of 68% [95% CI: 40-90%] vs. 72% [95% CI: 63-80%] ( P = 0.73) and RNR rates of 6% [95% CI: 2-13%] vs. 9% [95% CI: 5-14%] ( P = 0.37). Conclusions: A comprehensive, study-level meta-analysis of brain metastasis disease treatments suggest that combinations of RT and ICI result in higher OS, yet comparable neurotoxicity profiles vs. RT alone, with a superiority of concurrent vs. sequential combination regimens. A similar meta-analysis using patient-level data from past trials, as well as future prospective randomized trials would help confirming these findings.

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Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity

Cited by 74 publications

References 37 publications

Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor

Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor

Toxicity and efficacy of Gamma Knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy—A retrospective cohort study

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

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