MA06.01 Death From Intercurrent Disease After Proton- Versus Photon-Based Chemoradiotherapy for Non-Small Cell Lung Cancer

Abstract

Patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) often have cardiopulmonary comorbidities and receive significant radiation dose to normal structures. One way to reduce normal tissue exposure is with proton beam therapy (PBT). We sought to determine if PBT was associated with a reduced risk of death from intercurrent disease in this patient population. We retrospectively reviewed the records of 187 patients with LA-NSCLC who received definitive CRT with either PBT (n=98) or photon therapy (n=89) between December 2008 and November 2016 at a single academic center. No patient received consolidation immunotherapy as this cohort predated the results of the PACIFIC trial. Baseline patient-, tumor-, and treatment-related parameters were collected. Primary endpoint was death from intercurrent disease (DID), defined as death in the absence of disease progression. DID was compared between PBT and photon therapy groups using the cumulative incidence function and Gray’s test and modelled using the Fine-Gray method. Disease progression was considered a competing event. Secondary endpoint was overall survival (OS), assessed using the Kaplan-Meier method and Cox regression. The PBT group was older (median 69 years vs 62 years, p<0.001), had a more extensive smoking history (median 40 pack-years vs 30 pack-years, p=0.043), and had a greater burden of pre-CRT cardiovascular events (54.1% vs 34.8%, p=0.008). Median radiotherapy dose in both groups was 66.6Gy (range, 52.2-74Gy). The PBT group experienced lower mean heart dose (MHD) (median 6.7Gy vs 15Gy, p<0.001), total lung V5Gy (median 35.9% vs 48.2%, p<0.001), contralateral mean lung dose (median 0.97Gy vs 5.9Gy, p<0.001), and mean esophageal dose (MED) (median 22.1Gy vs 26.5Gy, p=0.003). Median follow-up was 28.8 months (range, 3.6-131.6 months). Following CRT, 25 patients (13.4%) experienced DID. Presumed causes of DID included: respiratory failure due to congestive heart failure, COPD, pneumonia, or aspiration (n=10), out-of-hospital cardiopulmonary arrest of unclear etiology (n=4), undifferentiated sepsis (n=2), probable radiation pneumonitis (n=1), esophagopleural fistula (n=1), and unknown (n=7). 3-year cumulative incidence of DID was 7.1% in the PBT group versus 14.6% in the photon therapy group (p=0.098). PBT (subdistribution hazard ratio [sHR] 0.25, p=0.0042), MHD (sHR 1.06/Gy, p=0.0018), and MED (sHR 1.05/Gy, p=0.019) were associated with a reduced, increased, and increased risk of DID, respectively, after controlling for age and ECOG performance status in three separate 3-variable regression models. OS was similar between the PBT and photon therapy groups (median 29 months vs 28.8 months, p=0.6; HR 1.09, p=0.6). MHD (HR 1.02/Gy, p=0.013) was associated with worse OS after controlling for age, ECOG performance status, baseline pulmonary comorbidity, and internal gross tumor volume. Patients receiving MHD >10Gy vs ≤10Gy experienced higher 3-year cumulative incidence of DID (15.6% vs 6.7%, p=0.049) and inferior OS (median 22.9 months vs 34.1 months, p<0.001). In this cohort of patients treated with definitive CRT for LA-NSCLC, PBT was associated with reduced cardiac, pulmonary, and esophageal dose and reduced risk of DID on multivariable analysis. These results suggest PBT may have a clinically meaningful benefit in this population.