Definitive treatment for patients with early-stage non-small cell lung cancer (ES-NSCLC) is usually well tolerated. Patients with ES-NSCLC and coexisting interstitial lung disease (ILD) are at increased risk of severe treatment-related toxicity after definitive therapy. The main objective of this systematic review is to provide a pooled estimation of treatment-related mortality and ILD-specific toxicity in this population of patients and to identify trends for further study.

The MEDLINE and Embase databases were queried from respective dates of inception to January 2016. Studies that included patients who underwent definitive treatment for ES-NSCLC not combined with other treatments were included. Patients with oligometastases who were treated with aggressive palliation were included if it did not constitute the majority of patients in a specific study. The results were summarized with weighted proportions according to the sample size of individual studies.

Overall, 3056 records were reviewed and 50 journal articles were included in the abstraction. The weighted proportion of treatment-related mortality (and ILD-specific toxicity) in primarily medically inoperable patients was as follows: stereotactic ablative radiation therapy (SABR) 15.6% (25%), particle beam therapy 4.3% (18.2%) and radiofrequency ablation (RFA) 8.7% (25%). The data for medically operable patients who underwent surgery were extracted for reference. Treatment-related mortality and ILD-specific toxicity were 2.2% and 12%, respectively, in the surgical population. On analysis of reported SABR dose parameters, V20 ≤ 6.5% and mean lung dose ≤4.5 Gy were found to be metrics associated with reduced mortality.

A consistently high level of treatment-related mortality and ILD-specific toxicity was observed in primarily medically inoperable patients treated with SABR, particle beam therapy, and RFA. For these patients, curative treatment should be considered in the context of the high toxicity rates and overall poor prognosis. Stringent radiation dosimetric parameters may result in reduced toxicity.