Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients.Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC).Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P = .006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment.Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with intensified treatment. (C) 2013 Elsevier Inc.

Study objectives:To determine the efficacy and toxicity of high-dose hypofractionated proton beam radiotherapy for patients with clinical stage I lung cancer.Design:A prospective phase 2 clinical trial.Setting:Loma Linda University Medical Center.Patients:Subjects with clinical stage I non-small cell lung cancer who were medically inoperable or refused surgery.Interventions:All patients were treated with proton beam radiotherapy. The target included the gross tumor volume as seen on CT scan, with additional margin to allow for respiratory motion. A multibeam treatment plan was generated. Delivered treatment was 51 cobalt Gray equivalent (CGE) in 10 fractions over 2 weeks to the initial 22 patients; the subsequent 46 patients received 60 CGE in 10 fractions over 2 weeks.Results:Sixty-eight patients were analyzed for this report, with a median follow-up time of 30 months. No cases of symptomatic radiation pneumonitis or late esophageal or cardiac toxicity were seen. The 3-year local control and disease-specific survival rates were 74%, and 72%, respectively. There was significant improvement in local tumor control in T1 vs T2 tumors (87% vs 49%), with a trend toward improved survival. Cox regression analysis revealed that patients with higher performance status, female gender, and smaller tumor sizes had significantly improved survival.Conclusion:High-dose hypofractionated proton beam radiotherapy can be administered safely, with minimal toxicity, to patients with stage I lung cancer. Local tumor control appears to be improved when compared to historical results utilizing conventional radiotherapy, with a good expectation of disease-specific survival 3 years following treatment.