Multi-institutional Retrospective Analysis of the Outcomes of Proton Beam Therapy for Patients with 1–3 Pulmonary Oligometastases from Various Primary Cancers

Abstract Purpose: To evaluate the efficacy of proton beam therapy (PBT) in patients with 1–3 pulmonary oligometastases from various primary cancers in Japan. Methods and Materials: This multi-institutional retrospective survey included 118 patients with 141 metastatic lung tumors from miscellaneous primary cancers, across six Japanese institutions, and involved the analyses of local progression-free rate (LPF), distant progression-free rate (DPF), progression-free survival rate (PFS), cause-specific survival rate (CSS), and overall survival rate (OS). Treatment-induced adverse effects of grade ≥2 were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0). Cox proportional hazards regression models were used in univariable analysis and multivariable analysis (MVA) for the identification of the prognostic factors, LPF and OS. Results: The median follow-up duration from the time of PBT was 25.5 months. The major primary disease sites included colorectal cancer (CRC; 42.4%), lung cancer (11.9%), head and neck cancer (8.5%), and kidney cancer (8.5%). For years 1, 2, and 3, LPF were 92.2%, 86.3%, and 78.4%; DPF were 59.1%, 44.1%, and 34.0%; PFS were 49.6%, 31.7%, and 24.2%; CSS were 83.4%, 72.5%, and 64.8%; and OS were 79.0%, 67.8%, and 59.6%, respectively. Eight patients developed acute adverse effects (grade ≥2). Ten patients developed radiation pneumonitis (grade 2) as a late adverse effect. None of the patients developed severe late toxicity (grade ≥3). CRC as the primary disease was the only prognostic factor associated with LPF that remained independently significant in the MVAs performed using three sets of parameters (hazard ratio [HR] = 3.31–4.76 in three MVA sets). In the MVA, the significant prognostic factors for OS were performance status (HR = 2.78 [95% CI = 1.01–7.67]) and total tumor volume (HR = 1.01 [95% CI = 1.00–1.02]). Conclusion: PBT provided promising outcomes for pulmonary oligometastasis with acceptable toxicities.