Abstract
BackgroundFew 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.MethodsWe evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era.ResultsThe 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.ConclusionIn 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.
Highlights
Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available
Development and utilization of new oncological therapies increased the overall survival of melanoma patients but has further led to discussions about the safety of the concurrent stereotactic radiotherapy (SRT) and TT or immunotherapy
Patients treated with checkpoint inhibitors showed a significantly longer time to new melanoma patients with brain metastases (MBM) after GKRS1 compared to patients treated with other forms and combinations of IT/TT or no IT/TT at all (P = .012; Figure 3A)
Summary
The incidence of melanoma has been rising, representing the third most common cause of brain metastases.[1,2] Survival in advanced disease stages has improved significantly over the last 10 years, following the approval of immunotherapy with check-point inhibitors and targeted therapy with BRAF & MEK inhibitors.[3] Patients with asymptomatic brain metastases seem to benefit from these novel therapeutic standards, especially from the combined immune-checkpoint inhibition with Ipilimumab and Nivolumab.[4,5,6] Local treatment options for melanoma patients with brain metastases (MBM) are surgery, stereotactic radiosurgery, fractionated radiotherapy, and whole brain irradiation (WBRT). In this retrospective cohort study we assessed the radiological and clinical outcome data of patients with MBM, who were treated in the modern radiosurgical and oncological era
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