Introduction: Immune checkpoint blockade is a treatment option for patients with melanoma brain metastases (MBM). This single institutional analysis attempted to determine the optimal management for patients with MBM undergoing craniotomy for tumor resection and immunotherapy.
Methods: An IRB approved retrospective study identified 142 MBM patients treated with immune checkpoint blockade between 2010 and 2015. Overall survival (OS) was calculated from date of diagnosis of brain metastasis until death from any cause. Model building included a prognostic model of overall survival, the effect of sequencing of immunotherapy and surgery on overall survival, and the effect of treatment sequencing on overall survival. Parallel model-building techniques were used to address the potential for guarantee-time bias.
Results: The 2-year OS for patients treated with CTLA-4, PD-1 or combinatorial blockade were 19%, 54%, and 57%, respectively. Accounting for the time-dependent covariate of surgery, factors associated with increased hazard of death included abnormal LDH, presence of extracranial disease at time of brain metastasis diagnosis, and greater than 3 brain metastases. The sequence of therapy was significantly related to survival with a 2.1-fold increase in the hazard of death when comparing patients undergoing immunotherapy +/- surgery compared to surgery + immunotherapy (HR: 2.1, 95% CI: 1.2 to 3.9, P=0.01). Patients undergoing immunotherapy prior to brain metastases diagnosis +/- surgery had a statistically significant 2.3-fold increase in the hazard of death (HR: 2.29, 95% CI: 1.2 to 4.4).
Conclusions: This single institutional analysis demonstrated that the sequence of surgery and immunotherapy is associated with OS. Surgery followed by immunotherapy resulted in the longest OS for patents with newly diagnosed melanoma brain metastases, suggesting that surgical resection should be considered prior to commencing immunotherapy. A prospective, randomized trial comparing the sequence of surgery and immunotherapy for treatment naïve MBM is warranted.
Patient Care: The findings of this study provide novel clinical insights into the role of neurosurgical intervention for patients undergoing immunotherapy for melanoma brain metastases.
Learning Objectives: -Surgery represents a critical adjunct for patients with MBM undergoing immunotherapy
-The sequencing of surgery and immunotherapy has therapeutic implications
-Upfront surgical resection of intracranial disease represents a bridge towards achieving enhanced efficacy with immunotherapy