Hypofractionated Proton Beam Therapy for Centrally Located Lung Cancer

Abstract

To clarify the efficacy and safety of hypofractionated proton beam therapy (PBT) for centrally located lung cancer. We retrospectively reviewed 39 patients who received hypofractionated (≧3 Gy [relative biological effectiveness: RBE] / fraction) PBT for centrally located cT1-2N0M0 (UICC 8th edition) lung cancer at one institution between 1999 and 2015. A tumor within 2 cm of the proximal bronchial tree (the distal 2 cm of the trachea, carina, main bronchi, and named major lobar bronchi up to their first bifurcation) was defined as a centrally located tumor. The median age of the included patients was 74 years (range: 48-88). Twenty-one patients (54%) had T1 disease. Sixteen patients (41%) had adenocarcinoma, eight (21%) had squamous cell carcinoma, three (8%) were diagnosed with non-small cell carcinoma, and twelve (31%) were clinically diagnosed without pathological confirmation. All patients were treated by passive scattering proton beam therapy with two or three ports. Twenty-four patients (62%) were treated with 80 Gy (RBE) in 20 fractions, whereas eight (21%) were treated with 66 Gy (RBE) in 10 fractions. The median biological equivalent dose was 112 Gy10 (range: 78-127). The median follow-up period for censored patients was 48 months (range: 4-140). The 3- and 5-year overall survival rates were 94 and 85%, respectively. The 3- and 5-year progression-free survival rates were 56 and 42%, respectively. Disease progression was noted in 22 patients (56%). The sites of the first recurrence was local in six patients (27%), regional in seven (32%), distant in seven (32%), and local and distant in two (9%). Of 13 patients who had the first recurrence in the locoregional area, only two patients (15%) received salvage treatment with radical intent. Dyspnea of grade 3 was noted in one patient (3%), and pneumonitis of grade 2 was noted in four patients (10%). No other grade 2 or more severe late adverse events were found. On multivariate analysis, T2 disease was a significant predictor of more frequent disease progression (p = 0.01; odds ratio: 13.7, 95% confidence interval: 1.8-101.6). Hypofractionated PBT for centrally located lung cancer was effective and safe.