Abstract
PURPOSE: The proliferation rates of non-small cell lung cancer (NSCLC) and associated radiation resistance highlight the potential of hypofractionated radiation therapy (hypoRT). However, radiation pneumonitis and esophagitis remain dose-limiting adverse events. This study investigates dosimetric factors influencing the risk of pneumonitis and esophagitis in highly multimorbid patients undergoing moderately hypoRT. METHODS AND MATERIALS: Forty-seven NSCLC patients with poor performance status treated between January 2014 and July 2021 were included. Dosimetric parameters including mean lung dose (MLD), percentage of normal (ipsi-/contralateral) lung volume (Vx) receiving ≥x Gy (x = 20, 18, 10, and 5 Gy); mean heart dose (MHD), percentage of the heart volume (HVx) receiving ≥x Gy (x = 20, 10, and 5 Gy); and mean esophageal dose (MED), percentage of esophagus volume (EVx) receiving ≥x Gy (x = 40, 30, 20, 18, 10, and 5 Gy) were analyzed retrospectively. Acute radiation pneumonitis/esophagitis events were assessed within 6/3 months posttreatment. Statistical analyses included random forests, binary logistic regression, and linear regression. RESULTS: Among the 47 patients with compromised lung function and poor prognostic factors, 8 (17%) and 26 (55%) patients developed all-grade pneumonitis or esophagitis, while 4 (9%) and 10 (21%) patients developed CTCAE grade ≥2 pneumonitis and esophagitis, respectively. Exploratory analyses suggest that V10, V18, and MLD values are associated with an increased risk of pneumonitis. Linear regressions confirmed this for MLD values greater than 9.2 Gy (P = .050). Additionally, higher V5 and V10 values in the contralateral lung were associated with a greater risk of pneumonitis (P = .013/P = .032). Dmax proved to be a significant predictor of esophagitis (P = .020). Moreover, evidence suggests that EV5 and EV40 may portend esophagitis onset. CONCLUSIONS: This study provides insights into dosimetric factors influencing pneumonitis/esophagitis development in NSCLC patients undergoing hypoRT. While MLD and Dmax emerged as significant predictors of pneumonitis and esophagitis, the small sample size limited the depth of conclusions. Further research with larger cohorts is warranted to validate these observations, potentially optimizing treatment planning and outcomes in this challenging patient population.