Clinical and Dosimetric Risk Factors Associated With Radiation-Induced Lung Toxicities After Multiple Courses of Lung Stereotactic Body Radiation Therapy
Xingzhe Li, Ellen Yorke, Andrew Jackson, Yujuan Yue, Charles B. Simone, Aditya Apte, Andreas Rimner, Daniel R. Gomez, Narek Shaverdian, Daphna Y. Gelblum, Abraham J. Wu, Annemarie F. Shepherd
Abstract
IntroductionData is limited on radiation induced lung toxicities (RILT) after multiple courses of lung stereotactic body radiation therapy (SBRT). We herein analyze a large cohort of patients to explore the clinical and dosimetric risk factors associated with RILT in such settings.MethodsA single institutional database of patients treated with multiple courses of lung SBRT between January 2014 and December 2019 was analyzed. Grade 2 or higher RILT (G2+RILT) after the last course of SBRT was the primary endpoint. Composite plans were generated with advanced algorithms including deformable registration and EQD adjustment. Logistic regression analyses were performed to examine correlations between patient or treatment factors including dosimetry and G2+RILT. Risk stratification of patients and lung constraints based on acceptable normal tissue complication probability (NTCP) were calculated based on risk factors identified.ResultsAmong 110 eligible patients (56 female and 54 male), there were 64 (58.2%) synchronous (defined as 2 courses of SBRT delivered within 30 days) and 46 (41.8%) metachronous courses of SBRT. The composite median lung V20, lung V5 and MLD were 9.9% (IQR: 7.3-12.4%), 32.2% (IQR: 25.5-40.1%) and 7.0 Gy (IQR: 5.5-8.6Gy), respectively.With a median follow-up of 21.1 months, 30 (27.3%) patients experienced G2+RILT. Five (4.5%) patients developed grade 3 RILT and one (0.9%) patient developed grade 4 RILT, with no grade 5 RILT.On multivariable regression analysis, female gender (Odds Ratio [OR]=4.35; 95% CI, 1.49-14.3; P=0.01), synchronous SBRT (OR=8.78; 95% CI 2.27-47.8; P=0.004), prior G2+RILT (OR=29.8; 95% CI, 2.93, 437; P=0.007) and higher composite lung V20 (OR=1.18; 95% CI, 1.02-1.38; P=0.030) were associated with significantly higher likelihood of G2+ RILT.ConclusionOur data suggest an acceptable incidence of G2+RILT after multiple courses of lung SBRT. Female gender, synchronous SBRT, prior G2+RILT and higher composite lung V20 may be risk factors for G2+RILT.