Abstract

BackgroundThe evaluation of response for brain metastases (BM) may be challenging in the context of treatment by stereotactic radiotherapy (SRT) or immunotherapy or both, which represent major therapeutic options for melanoma BM. MethodsWe reviewed clinical and neuroimaging data of 62 melanoma patients with newly diagnosed BM treated by the combination of immunotherapy and SRT (n=33, group A), immunotherapy alone (n=10, group B) or SRT alone or in combination with other systemic therapies (BRAF inhibitors, n=7; alkylating agents, n=6; no systemic treatment, n=6), (n=19, group C). Response was assessed using RECIST 1.1, RANO or iRANO criteria. ResultsBRAF mutations were noted in 26 patients. Until BM diagnosis, a median of 1 (range 1-4) line of systemic treatment was given. At BM diagnosis, median age was 58 years (range 23-85.5). Fifty-four patients (87%) had 1-3 metastases. The median maximum diameter was 18.5mm (range, 9-49). The median DS-GPA was 3 (1-4). After a median follow-up of 30.5 months for surviving patients, 39 patients have experienced CNS progression, 16 (48.5%) in group A, 9 (90%) in group B, 14 (73.5%) in group C. Median PFS was 129.5 days (range 82-532) in group A, 75 days (range 35-203) in group B, 136 days (range 59-514) in group C. Forty-seven patients (76%) had died at the time of the analysis, 22 (66.5%) in group A, 7 (70%) in group B, 18 (94.5%) in group C. Median OS was 345 days (range 65-1824) in group A, 174.5 days (range 50-1361) in group B, 409 days (range 102-1244) in group C. 52 MRI scans were available for central review: pseudoprogression was documented in 9 patients (29%) in group A, 0 (0%) in group B, and 5 (29.5%) in group C. Response rates were similar with all three sets of response criteria. Progressive disease was less often called when applying iRANO to assess SRT target lesions. ConclusionsWhile the retrospective nature and small sample size for subgroups are major limitations of this study, these data may indicate that the omission of SRT from first-line treatment may compromise outcome. Pseudoprogression is uncommon with immunotherapy alone; pseudoprogression rates were similar after SRT alone or in combination with immunotherapy or other systemic treatment. Legal entity responsible for the studyUniversity Hospital of Zurich. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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