Prospective Evaluation of Stereotactic Body Radiotherapy and Immunotherapy for Mediastinal and Hilar Lymph Node Metastases

Abstract

Stereotactic body radiotherapy (SBRT) is associated with high rates of metastasis control. However, given the adjacent organs-at-risk (OAR) and observed high rates of airway toxicity in the past, SBRT has historically not been routinely utilized for metastatic mediastinal and hilar lymphadenopathy (MHL). Immunotherapy is increasingly being used in metastatic patients and can cause clinically significant pneumonitis. In order to evaluate the feasibility, safety and efficacy of SBRT to MHL in the setting of immunotherapy, clinical outcomes of patients treated with immune-oncology (IO) agents and SBRT to MHL on three consecutive phase 1 clinical trials at a single institution were reviewed.A total of 213 patients with widely metastatic solid tumors were treated with combination multisite SBRT and IO on three consecutive phase 1 trials between 2016 and 2020. All metastases in each patient were not irradiated and metastases > 65 mL were partially irradiated. Those with mediastinal and hilar nodes targeted met eligibility criteria. MHL were prescribed 50 Gy in 5 fractions, but under coverage was allowed in order to prioritize meeting OAR constraints formulated from NRG protocols. IO was administered sequentially (within 7 days after completion of SBRT) or concurrently (before or at the start of SBRT). IO treatments included: pembrolizumab, ipilimumab with nivolumab, urelumab with nivolumab, and cabiralizumab with nivolumab. Endpoints included irradiated tumor control per Response Evaluation Criteria in Solid Tumors version 1.1, overall survival (OS), dosimetric coverage and toxicity per Common Terminology Criteria for Adverse Events version 4.0. The Kaplan-Meier method was used to estimate tumor control and OS.A total of 55 patients were treated to 89 MHL nodes with 18 patients receiving concurrent IO and 37 patients receiving sequential IO. The most common histologies included non-small cell lung cancer (49%), ovarian cancer (7%) and colon adenocarcinoma (5%). Median follow up was 15 months. Irradiated tumor control was excellent with 0 local failures (# of living patients) at 12 (n = 32), 18 (n = 19) and 24 (n = 13) months. Median OS was 18 months (95% confidence interval, 11-33). Even after prioritizing OAR sparing, dosimetric parameters for the gross tumor volume (GTV) were: mean dose 50.9 Gy, V95 82% and V100 75%. Regarding toxicity, 6 patients (11%) experienced grade 3 pneumonitis and 1 patient (2%) experienced grade 3 esophagitis with no grade 4 or 5 toxicity events.In the largest series of SBRT and immunotherapy for MHL, irradiated tumor control was excellent with acceptable toxicity. By prioritizing OARs during SBRT planning, 50 Gy/5 fraction SBRT to mediastinal and hilar nodes is feasible in the setting of immunotherapy.