Clinical Outcomes in Non-Small Cell Lung Cancer Patients Treated with Pencil Beam Scanning Proton Reirradiation after Previous Thoracic Radiation

Reirradiation for patients with non-small cell lung cancer (NSCLC) presents a dosimetric challenge due to previous exposure of nearby critical organs. Intensity-modulated proton therapy (IMPT) with pencil beam scanning (PBS) offers a unique dosimetric advantage over passive scattering PT, allowing for dose-escalation while limiting normal tissue irradiation. Given the limited published data, we analyzed treatment patterns, toxicities, and clinical outcomes of NSCLC patients with prior radiation history undergoing IMPT-PBS-based definitive reirradiation. A single-institution retrospective IRB-approved analysis was conducted of all NSCLC patients treated with IMPT-PBS-reirradiation between May 2016 and June 2019. We analyzed patient and tumor characteristics, treatment parameters (dose, CTV, DVH parameters), and toxicities. Toxicities were scored according to CTCAE v4.0. The Kaplan-Meier method was used to estimate overall survival (OS) and freedom from local progression (FFLP) calculated from the start of reirradiation. Cox-proportional hazards models were used for multivariate analysis. SPSS statistical software used for analysis. A total of 43 consecutive NSCLC patients (22 females, 21 males) completed a course of definitive-intent PBS-proton reirradiation; 37 patients had recurrent NSCLC, while 6 patients had a different previous histology. The median age was 70 years (range 47-89). Most patients had an ECOG performance status of 0/1 (79%). Median dose of prior RT was 60.2 Gy EQD2 (range 20-94 Gy EQD2). Median time between initial and reirradiation courses was 31.2 months (range 3.5 – 560 months). Median PBS-proton reirradiation dose was 62.0 Gy (RBE) EQD2 (range 40.1 – 99.7 Gy RBE EQD2). Patients received conventionally fractioned (n = 31, 1.8-2.0 Gy/fx), BID (n = 2, 1.2 Gy/fx), or hypofractionated (n = 10, 2.5-7 Gy/fraction) reirradiation. Concurrent chemotherapy was delivered in 19 patients. Grade 3 acute toxicities were only seen in 3 patients (dyspnea [N = 2], effusion [N = 1]). With a median follow-up from the start of reirradiation of 11.0 months, 4 patients experienced a grade 3 late toxicity (esophageal fistula [N = 2], dyspnea [N = 2]). No grade 4-5 toxicities were observed. Median FFLP was 12.8 months (95% CI, 6.6 – 18.9 months) and median OS was 19.3 months (95% CI, 16.5 – 22.1 months). MVA revealed that increasing mean heart dose (HR = 1.020, 95%CI = 1.001-1.039, p = 0.043) was associated with worse OS. No other explanatory variables (e.g., dose, CTV size, DVH parameters, comorbidities, chemotherapy receipt, etc.) were associated with FFLP or toxicity outcomes. This is the largest series to date reporting outcomes for NSCLC patients treated with PBS-proton reirradiation. Our analysis indicates that PBS-proton reirradiation is well tolerated and offers meaningful rates of durable local control and prolonged survival.