PD-L1 Expression Level of Primary Tumor as a Predictor of Local Control and Symptomatic Radiation Necrosis in Patients With Brain Metastases Undergoing SRS/fSRT With Concurrent Immunotherapy

Abstract

PD-L1 is often overexpressed in the tumor microenvironment to dampen host immune response and allow tumor proliferation. Radiation works partially through the immune system, but the correlation between PD-L1 expression in primary tumors and oncologic outcomes for metastatic lesions treated with SRS with concurrent immunotherapy (ICI) is unknown. We seek to evaluate the association of PD-L1 expression level of the primary tumor in patients undergoing SRS/fSRT with local control and symptomatic radiation necrosis.A total of 282 patients with 616 metastatic brain lesions which were treated with SRS or fSRT from 2014-2020 were retrospectively reviewed at a single institution. PD-L1 expression level in the primary tumor was available for 43 patients with 147 metastatic brain lesions, of whom 33 patients with 103 lesions received concurrent ICI. Concurrent ICI was defined as having received ICI within 3 months before, during, or after SRS. PD-L1 expression was categorized as negative (PDn) (< 1%), or positive (PDp) (≥1% - 100%). Patients were excluded if a one month post-treatment MRI was not available or if > 15 lesions were treated. The lesion level endpoint of local failure (LF) and symptomatic radiation necrosis (RN) were analyzed using Kaplan Meyer method with salvage WBRT used as a censoring event. Univariate and multivariate analysis were performed with competing risk adjustment.One-hundred and four lesions (range 1-10) from 33 unique patients were included in the analysis. Ten patients with PDn primary tumors with 31 lesions and 23 patients with PDp primary tumors with 73 lesions were analyzed. After competing risk adjustment, the LF rate at 12 months were rare for both patient cohorts: PDn vs PDp was 3.5% and 1.5% (P = 0.99), respectively. For RN, the event rate at 12 months for PDn vs PDp was 4% vs 14% (HR 0.648; 95% CI 0.05-9.03; P = 0.747). On MVA for local control, factors such as metastasis size (< 2cm vs ≥2 cm; P = 0.181), histology (NSCLC vs other; P = 0.997), or lesion location (supratentorial vs other; P = 0.392) were not found to have a statistically significant association. On MVA for RN, only metastasis size reached statistical significance (HR 32.8; 95% CI 3.56-301.81; P < 0.002).Patients receiving concurrent ICI and SRS for management of brain metastases have an excellent local control, irrespective of PD-L1 status. PD-L1 positive patients may be at an increased risk for RN. These findings require further evaluation in a larger patient cohort.G.S. Alexander: None. B.Savla: None. L.J. Berg: None. K. Sun: None. J.S.Remick: None. E.S. Kowalski: None. S. Chen: None. N.Lamichhane: None. W.F. Regine: None. M.V. Mishra: Employee; Orthofix. Research Grant; ASTRO, Keep Punching. Advisory Board; Patient Centers Outcomes Research Institute (PCORI. Travel Expenses; Patient Centers Outcomes Research Institute (PCORI.