Clinical Outcomes of Pencil Beam Scanning Proton Therapy in Locally Advanced Non-Small Cell Lung Cancer: Propensity Score Analysis

SIMPLE SUMMARY: We analyzed the oncologic outcomes and toxicities after intensity-modulated radiation therapy (IMRT) or pencil beam scanning proton therapy (PBSPT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation therapy. Due to an imbalance in baseline characteristics between IMRT and PBSPT, we used propensity score-based statistical analysis. Regarding radiation therapy planning, PBSPT exhibited superior sparing of the lung, heart, and spinal cord compared to intensity-modulated (photon) radiotherapy in patients with advanced NSCLC. However, PBSPT resulted in higher incidence of grade 3 or more dermatitis and esophagitis compared to IMRT. Despite declined baseline lung function, PBSPT demonstrated a comparable rate of symptomatic radiation pneumonitis compared to IMRT. PBSPT could be an effective and safe treatment technique with comparable locoregional control. ABSTRACT: This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8–26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.