2079 - Treatment Toxicity and Outcomes Following Definitive Radiotherapy for Patients with Early-Stage Non-Small Cell Lung Cancers and Pre-Existing Interstitial Lung Disease - A Systematic Review

G. J. Li¹, M. Sam Soon², H. Chen³, G. Boldt⁴, H. Bahig⁵, P. Cheung¹, D. A. Palma⁶, C. Ryerson⁷, S. Senan⁸, and A. V. Louie¹; ¹Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, ²Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, ³Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, ⁴Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada, ⁵Department of Radiation Oncology, Centre Hospitalier de lUniversité de Montréal, Montreal, QC, Canada, ⁶London Health Sciences Centre, London, ON, Canada, ⁷Department of Medicine, University of British Columbia, Vancouver, BC, Canada, ⁸Amsterdam UMC, Amsterdam, Netherlands

Purpose/Objective(s): Patients with interstitial lung disease (ILD) who develop lung cancer represent a unique challenge, as they are at a higher risk for serious toxicity from surgery, radiotherapy, and many systemic therapies. The aim of this study is to provide an up-to-date analysis on toxicities and outcomes associated with definitive radiotherapy in patients with ILD and early-stage non-small cell lung cancer (ES-NSCLC). Materials/

Methods: We performed a systematic review in accordance with PRISMA guidelines. The PubMed (MEDLINE), EMBASE, and Cochrane Library databases were searched from inception until March 2024. Studies that included patients who underwent definitive radiotherapy alone for ES-NSCLC were included. All forms of radiotherapy, including proton and carbon ion therapy were included. Data including treatment-related toxicity, local control rates, and overall survival were collected and analyzed.
Results: Of the 3096 records reviewed, 24 studies were included for full data abstraction, with a minority (n = 4) being prospective. In total, 705 patients with stage 1-2 NSCLC were included, including both surgical and non-surgical candidates. Seventeen studies utilized photon-based radiotherapy (XRT), 4 carbon ion radiotherapy (CIRT), and 3 proton beam therapy (PBT), with each modality contributing to 81% (n = 574), 13% (n = 90), and 6% (n = 41) of included patients, respectively. Prescribed doses in BED10 ranged from 43 Gy to 180 Gy for XRT, and up to 300 Gy (RBE) for CIRT. Reporting of ILD subtype, severity, and pulmonary function testing were variable. Idiopathic pulmonary fibrosis accounted for 21% (n = 147) of patients, while a specific subtype was not reported for 71% (n = 502) of patients. Within the 11 studies reporting severity data, the majority of patients (65%) had mild ILD as defined by authors, while 26% and 9% had moderate and severe ILD, respectively. Eight studies reported median forced vital capacities ranging from 82-97% of predicted, and 5 reported median diffusing capacities for carbon monoxide ranging from 42-56% of predicted. The prevalence of severe (grade 3-5) treatment-related respiratory toxicity was 16.7% for XRT, 12.2% for CIRT, and 9.7% for PBT, while treatment-related mortality was 9.6% for XRT, 0% for CIRT, and 2.4% for PBT. The most commonly reported risk factor for respiratory toxicity (n = 6) was higher volume of lung receiving at least 5 Gy (V5), with two studies reporting cutoffs of 11.2% and 18%. Estimated local control at 3-years was 75.9%. Estimated overall survival at 3-years was 44.3%, with a median of 30.6 months.
Conclusion: There is a high risk of treatment-related toxicity and mortality for patients with ILD who receive definitive radiotherapy for treatment of ES-NSCLC. All treatment modalities should be carefully considered, including the option of ongoing surveillance without treatment. Future studies would benefit from consistent reporting of ILD details, which may help in risk stratification in this challenging clinical scenario.