Impact of radiation dose to the immune cells in unresectable or stage III non-small cell lung cancer in the durvalumab era.

BACKGROUND/PURPOSE: Higher estimated radiation doses to immune cells (EDIC) have correlated with worse overall survival (OS) in patients with locally-advanced non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, which established consolidative durvalumab as standard-of-care. Here, we examine the prognostic impact of EDIC in the durvalumab era. MATERIALS/METHODS: This single-institution, multi-center study included patients with unresectable stage II/III NSCLC treated with chemoradiation followed by durvalumab. Associations between EDIC [analyzed continuously and categorically (≤6 Gy vs > 6 Gy)] and OS, progression-free survival (PFS), and locoregional control (LRC) were evaluated by Kaplan-Meier and Cox proportional methods. RESULTS: 100 patients were included with median follow-up of 23.7 months. The EDIC > 6 Gy group had a significantly greater percentage of stage IIIB/IIIC disease (76.0 % vs 32.6 %; p < 0.001) and larger tumor volumes (170 cc vs 42 cc; p < 0.001). There were no differences in early durvalumab discontinuation from toxicity (24.1 % vs 15.2 %; p = 0.27). Median OS was shorter among the EDIC > 6 Gy group (29.6 months vs not reached; p < 0.001). On multivariate analysis, EDIC > 6 Gy correlated with worse OS (HR: 4.15, 95 %CI: 1.52-11.33; p = 0.006), PFS (HR: 3.79; 95 %CI: 1.80-8.0; p < 0.001), and LRC (HR: 2.66, 95 %CI: 1.15-6.18; p = 0.023). Analyzed as a continuous variable, higher EDIC was associated with worse OS (HR: 1.34; 95 %CI: 1.16-1.57; p < 0.001), PFS (HR: 1.52; 95 %CI: 1.29-1.79; p < 0.001), and LRC (HR: 1.34, 95 %CI: 1.13-1.60; p = 0.007). CONCLUSIONS: In the immunotherapy era, EDIC is an independent predictor of OS and disease control in locally advanced NSCLC, warranting investigation into techniques to reduce dose to the immune compartment.

Stereotactic body radiotherapy for synchronous early stage non-small cell lung cancer.

INTRODUCTION: In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions. MATERIAL AND METHODS: Patients with synchronous AJCC 8th Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009-2018 were reviewed. SPLC was defined as patients having received two courses of SBRT within 180 days for treatment of separate early stage tumors. In total, 36 patients with 73 lesions were included. Overall survival (OS), progression-free survival (PFS), cumulative incidence of local failure (LF), and regional/distant failure (R/DF) were estimated and compared with a control cohort of solitary early stage NSCLC patients. RESULTS: Median PFS was 38.8 months (95% CI 14.3-not reached [NR]); 3-year PFS rates were 50.6% (35.6-72.1). Median OS was 45.9 months (95% CI: 35.9-NR); 3-year OS was 63.0% (47.4-83.8). Three-year cumulative incidence of LF and R/DF was 6.6% (3.7-13.9) and 35.7% (19.3-52.1), respectively. Patients with SPLC were compared to a control group (n = 272) of patients treated for a solitary early stage NSCLC. There was no statistically significant difference in PFS (p = .91) or OS (p = .43). Evaluation of the patterns of failure showed a trend for worse cumulative incidence of R/DF in SPLC patients as compared to solitary early stage NSCLC (p = .06). CONCLUSION: SBRT alone to multiple lung tumors with SPLC results in comparable PFS, OS, and LF rates to a cohort of patients treated for solitary early stage NSCLC. Those with SPLC had non-significantly higher R/DF. Patients with SPLC should be followed closely for failure and possible salvage therapy.