Idiopathic pulmonary fibrosis (IPF) is associated with fatal complications after radiotherapy (RT) for lung cancer patients; however, the role of proton therapy to reduce the incidence of life-threatening complications is unclear. Herein, we present the preliminary results of early-stage lung cancer patients having IPF and treated with RT, with a focus on the comparison between X-ray and proton therapy. From January 2010 to October 2017, we retrospectively reviewed the medical records of 264 patients with stage I-II non-small cell lung cancer (NSCLC) treated with definitive RT alone. Ultimately, 30 patients (11.4%) who had underlying IPF were analyzed. Among these, X-ray and proton RT were delivered to 22 and 8 patients, respectively. Treatment-related complications and survival outcomes were compared between X-ray and proton therapy. The median follow-up duration was 11 months (range, 2 to 51 months). All living patients were followed-up at least 9 months. Treatment-related death occurred in four patients (18.2%) treated with X-ray but none with proton therapy. Most patients died within one month after the onset of pulmonary symptoms in spite of aggressive treatment. In addition, the 1-year overall survival (OS) rate in patients treated with X-ray and proton was 46.4 and 66.7%, respectively, and patients treated with proton therapy showed a tendency of better survival compared to X-ray (p = 0.081). Especially, in GAP stage II and III subgroups, patients treated with proton therapy showed significantly increased survival outcomes compared to X-ray (1-year OS rate; 50.0% versus 26.4%, p = 0.036) in univariate analysis. RT is associated with serious treatment-related complications in patients with IPF. Proton therapy may be helpful to reduce these acute and fatal complications. retrospectively registered.

This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8–26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.

PBT has a unique depth–dose curve with a Bragg peak that enables one to reduce the dose to normal lung tissue. We prospectively enrolled 54 patients with non-small cell lung cancer treated with definitive PBT. The inclusion criteria were forced expiratory volume in 1 s (FEV1) ≤ 1.0 L or FEV1 ≤ 50% of predicted or diffusing capacity of the lungs for carbon monoxide (DLco) ≤ 50%, or pulmonary fibrosis. The primary endpoint was grade ≥ 3 pulmonary toxicity, and secondary endpoints were changes in pulmonary function and quality of life. The median age was 71.5 years (range, 57–87). Fifteen (27.8%) and fourteen (25.9%) patients had IPF and combined pulmonary fibrosis and emphysema, respectively. The median predicted forced vital capacity (FVC), FEV1, and DLco were 77% (range, 42–104%), 66% (range, 31–117%), and 46% (range, 23–94%), respectively. During the follow-up (median, 14.7 months), seven (13.0%) patients experienced grade ≥ 3 pulmonary toxicity. Seven months after the completion of PBT, patients with IPF or non-IPF interstitial lung disease (ILD) experienced a decrease in the FVC but the decrease in DLco was not significant. Under careful monitoring by pulmonologists, PBT could be a useful treatment modality for lung cancer patients with poor lung function or pulmonary fibrosis.