Stereotactic Radiosurgery With Concurrent Immunotherapy in Melanoma Brain Metastases Is Feasible and Effective

Abstract

Objective: Stereotactic radiosurgery (SRS) is an established treatment for brain metastases in the management of metastasized melanoma. The increasing use of checkpoint inhibitors in melanoma therapy leads to combined treatment schemes consisting of immunotherapy and SRS that need to be evaluated regarding safety and feasibility. Methods: We retrospectively analyzed 36 patients suffering from cerebral metastasized melanoma. Between November 2011 and May 2016, altogether 66 brain metastases were treated with single-fraction SRS (18-20 Gy prescribed to the 80% isodose) in combination with a checkpoint inhibitor (ipilimumab: 82%, pembrolizumab: 14% or nivolumab: 4%), administered within 3 months before or after SRS. Toxicity was evaluated with focus on the incidence of central nervous system (CNS) radiation necrosis (CRN). Overall survival (OS), freedom from local progression (FFLP), freedom from central nervous system radiation necrosis (FFCRN), and freedom from distant intracranial progression (FFDIP) were analyzed using the Kaplan-Meier method. Results: The median follow-up was 25 months (range: 2-115 months). Two patients (6%) presented with cerebral edema CTCAE • III and another two patients (6%) presented with one-sided muscle weakness CTCAE • III after SRS. One of these four symptomatic cases correlated with an observed CRN, the other three symptomatic cases were related to local tumor progression (n = 2) or related to the performance of additional whole brain radiotherapy (WBRT). No further CTCAE • III or • IV toxicity was seen. During follow-up, seven of the growing contrast-enhanced lesions were resected, revealing two cases of CRN and five cases of local tumor progression. Altogether, the observed CRN rate of the irradiated metastases was 6-17% at the time of analysis, ranging due to the radiologically challenging differentiation between CRN and local tumor Liermann et al. Stereotactic Radiosurgery With Concurrent Immunotherapy progression. The observed ranges of the 1-and 2-years FFLP rates were 82-85% and 73-80%, respectively. The median FFDIP was 6.1 months, the median OS was 22.2 months. Conclusion: In the presented cohort, the combination of SRS and checkpoint inhibitors in the management of cerebral metastasized melanoma was safe and effective. Compared to historic data on SRS only, the observed CRN rate was acceptable. To gain resilient data on the incidence of CRN after combined treatment schemes, prospective trials are needed.

Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes

“…Prior observational studies have demonstrated concurrent SRS-IT associated with more effective local control and OS for melanoma BM (Table 5). [11][12][13][14][15][16][26][27][28][33][34][35] Our analysis reiterates the synergistic response of SRS-IT but also further strengthens this relationship by performing additional multivariate analyses of individual BM, patient, treatment and clinical factors that have been previously lacking in the literature. We also present for the first time, outcomes after SRS in patients with melanoma BM according to RANO-BM criteria which may be useful when comparing to cohorts at other institutions and for future trial planning.…”

Managing Metastatic Melanoma in 2022: A Clinical Review

“…Furthermore, multimodality techniques appear to provide the greatest survival benefits, as retrospective evidence supports the combination of ICI in conjunction with SRS therapy for which clinical trials involving radiation combined with ICI (ClinicalTrials.gov identifier: NCT03340129) and targeted therapies (Clin-icalTrials.gov identifier: NCT02974803) are ongoing. 123,124…”

Immunotherapy: an emerging modality to checkmate brain metastasis

“…SRS in combination with immunotherapy has shown better clinical outcomes versus SRS or IT alone ( Fig. 3 ) [ 8 – 10 , 38 , 50 , 51 ]. A study found that the median OS in patients treated with SRS + IT was 15.77 months, significantly improved from the historical median OS [ 46 ].…”

“…One such field of therapy that has gained widespread attention in the past 10 years has been immunotherapy (IT). IT has shown promising results in improving the overall survival (OS) rate in patients with BrM, both alone and in combination with traditional therapies [ 8 – 10 ].…”