Abstract

Simple SummaryUnderlying lung disease can affect the pulmonary toxicity after radiotherapy for lung cancer, but treatment outcomes after proton beam therapy (PBT) for lung cancer patients with underlying lung disease have been limited to small retrospective studies. In this prospective study, we aimed to assess pulmonary toxicity following PBT for lung cancer with poor lung function or pulmonary fibrosis. We found that idiopathic pulmonary fibrosis (IPF) was associated with severe pulmonary toxicity and poor survival even after PBT, while PBT seems to be a safe treatment modality for lung cancer patients with chronic obstructive pulmonary disease.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.

Highlights

  • Surgical resection is the treatment of choice for patients with early-stage non-small cell lung cancer (NSCLC), definitive radiation therapy (RT) is recommended as an alternative to surgery for patients unable to undergo resection, including older patients and those with a poor performance status, impaired cardiopulmonary function, or comorbidities [1,2]

  • Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are well-known pulmonary comorbidities that are associated with an increased risk of lung cancer [7–9], but the impact of COPD and IPF on treatment outcomes after RT has not been fully examined [4]

  • Eligible patients were older than 20 years of age, had pathologically or clinically diagnosed NSCLC that was unsuitable for surgical resection as evaluated by thoracic surgeons, and one of the following: forced expiratory volume in 1 s (FEV1) ≤ 1.0 L, FEV1 ≤ 50% predicted or diffusing capacity of lungs for carbon monoxide (DLco) ≤ 50%, or pulmonary fibrosis

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Summary

Introduction

Surgical resection is the treatment of choice for patients with early-stage non-small cell lung cancer (NSCLC), definitive radiation therapy (RT) is recommended as an alternative to surgery for patients unable to undergo resection, including older patients and those with a poor performance status, impaired cardiopulmonary function, or comorbidities [1,2]. Pulmonary toxicity, including radiation pneumonitis (RP), is one of the most common treatment-related complications following RT, and underlying lung disease can affect pulmonary toxicity [4–6]. An increased risk of severe radiation-related pulmonary toxicity was demonstrated in patients with IPF [4,6,10]. Because baseline pulmonary function of forced expiratory volume in one second (FEV1) ≥ 1.0 L is one of the eligibility criteria in randomized trials of passive scattering PBT and intensity-modulated radiation therapy (IMRT) [16], the role of PBT in patients with poor pulmonary function could not be assessed

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