Outcomes Of Stereotactic Radiosurgery And Immunotherapy In Renal Cell Carcinoma With Brain Metastases

Abstract

To investigate the impact of immunotherapy (IT) on outcomes of stereotactic radiosurgery (SRS) in treatment of brain metastases from renal cell carcinoma (RCC). We retrospectively reviewed 48 patients with RCC who were treated with SRS for brain metastases in our institution between 2006 and 2018. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Kaplan-Meier curve was used to estimate survival and log-rank test was used to compare survival between groups. Median age and KPS at initial SRS for IT group (19 patients) vs non-IT group (29 patients) were 55 vs 61 years (p = 0.024) and 100 vs 90 (p = 0.11). Median DS-GPA for both groups was 3 (range 1-4). The number of patients with extracranial metastases at the time of SRS was not statistically different between the groups. Nine patients received IT concurrently with SRS. A total of 372 lesions were treated with Gamma Knife based SRS with a median radiation dose of 20 Gy (range 12-30 Gy) and 22 Gy (range 12-27 Gy) for IT group and non-IT group, respectively. Median tumor volume for IT group and non-IT group was 56.2 mm3 (range, 2.1-14610 mm3) and 88.6 mm3 (range, 2.6-23383 mm3) (p = 0.046). Median total number of lesions treated in IT group and non-IT group were 9 (range, 1-54) and 4 (range, 1-18) (p = 0.40). Median total number of treatment sessions was 2 (range, 1-6) in both groups. Median overall survival (OS) following first SRS was 23.1 months (range, 6.0-93.8 months) for entire cohort. Median OS for IT group and non-IT group were 32.2 months and 18.4 months (p = 0.02). No patient in the IT group had intracranial progression at 2 years. Two-year local progression free survival (PFS) for the non-IT group was 89%. One- and two-year distant intracranial PFS rate for IT group vs non-IT group were 57% vs 50% and 46% vs 34% (p = 0.59), respectively. Eleven patients (22.9%) developed radiation necrosis requiring treatment at a median period of 1 month (range, 0-7 months) following SRS. Cumulative incidence of radiation necrosis requiring intervention at 1 year, censoring for death, for IT group vs non-IT group were 32% vs 18% (p = 0.24). There were no incidences of radiation necrosis after 1 year that required intervention. RCC patients with brain metastases treated with SRS and IT had significantly longer OS than those without immunotherapy. Regardless of systemic therapy options, intracranial disease control offered by SRS remains excellent for RCC brain metastases. No significant difference was found between the two groups for distant PFS or rate of radiation necrosis requiring intervention despite a 2 Gy decrease in the median radiation dose delivered in the IT group. Larger studies are required to validate these findings.