Reirradiation with Hypofractionated Proton Therapy for Recurrent Lung Cancer

Abstract

Proton therapy has been explored in treating locoregionally recurrent lung cancer to decrease toxicity in previously irradiated tissue given the sharp dose gradient achievable with charged particle therapy. However, experience with proton reirradiation (reRT) is limited, dose fractionation is variable, and fatal radiation-related toxicity has been reported. Here we report our single institution experience with efficacy and safety of patients treated with a moderately hypofractionated proton regimen for lung cancer reRT. Thirty-one patients received hypofractionated proton therapy for recurrent lung cancer from 10/2012 to 06/2019. Prior courses of thoracic radiation were delivered using conventionally fractionated radiation therapy (median 60 Gy/30 fx, BED10 = 72 Gy) in 56% patients and hypofractionated/stereotactic body radiotherapy (median BED10 = 100 Gy) in 28% patients. One patient received two prior courses of thoracic radiation. Median time from prior radiation to proton reRT was 19.4 months. Proton reRT was prescribed to 60 Gy (RBE) in 15 fractions in the majority (73%) of cases with a range of 2.5-4 Gy (RBE) per fraction (BED10 = 53.1-84 Gy). Twenty-five patients (80.1%) received proton reRT with direct dose overlap with initial thoracic radiation. Median tumor volume treated was 36.7 cm3 (range 2.76-270.6 cm3). Median PTV V95% coverage was 96% (range 63-100%). At median follow-up of 6.3 months (range 1.4-49 months), 7 patients (22.6%) developed local recurrence, 4 (12.9%) experienced regional recurrences and 3 (9.7%) developed distant metastasis. Median lung V20 Gy and V5 Gy were 6.6% (0.7-42.9%) and 12.3% (1.2-79.6%), respectively. Median mean heart dose was 0.07 Gy (0.0-57.1 Gy). Median esophageal V40 Gy and Dmax were 0.0% (0.0-31.0%) and 13.0 Gy (0.0-64.0 Gy), respectively. There was 1 episode of grade 3 pneumonitis within 1 month of completion of reirradiation and no grade 3-5 late toxicity. There were no treatment-related deaths; 19 patients died from other causes during follow-up period. Reirradiation with moderately hypofractionated proton therapy for locoregionally recurrent lung cancer is well tolerated with low rates of toxicity in this cohort of patients, the majority of whom had dose overlap with prior thoracic radiation. Disease control rates are comparable to previously published data. These promising results warrant prospective studies to establish the role of moderately hypofractionated proton reRT for treating recurrent lung cancer.