Qun Zhang1,2, Duojie Li1,2,3, Hongmei Yin1, Chaomang Zhu1, Jie Huang1, Shixiang Zhou1,*
1Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233030, Anhui, China.
2Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Bengbu 233000, Anhui, China.
3Joint Research Center for Regional Diseases of IHM, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233030, Anhui, China.
*Corresponding author: Shixiang Zhou
This work was supported by the University Research Projects of the Anhui Provincial Department of Education (No. 2025AHGXZK40692) and the Anhui Province Key Laboratory Open Projects (Bengbu Medical College, No. KFDX202204).
Abstract
Background: Acute radiation pneumonitis (ARP) remains one of the most important dose-limiting toxicities associated with thoracic radiotherapy. This study evaluated clinical and dosimetric factors of grade ≥2 ARP in patients with locally advanced esophageal cancer receiving definitive radiotherapy and explored the value of routine peripheral blood inflammatory markers. Methods: In this single-center retrospective study, 115 patients with locally advanced esophageal cancer treated with definitive radiotherapy were analyzed. Data on clinical characteristics, treatment-related variables, lung dose–volume parameters, and baseline peripheral blood inflammatory markers were collected for analysis. The primary endpoint was grade ≥2 ARP occurring from the start of radiotherapy until 3 months after completion of radiotherapy. Logistic regression and receiver operat-ing characteristic (ROC) analyses were performed, with attention to multicollinearity among dosimetric variables. Results: Grade ≥2 ARP was observed in 31 patients (27.0%), including 24 cases of grade 2 and 7 cases of grade 3. Patients who developed ARP exhibited significantly higher bilateral lung V20, mean lung dose (MLD), as well as V10, V5, and V30, compared with those without ARP. ROC analysis indicated that V20 (AUC=0.730), MLD (AUC=0.727), V10 (AUC=0.715), V5 (AUC=0.717), and V30 (AUC=0.704) demonstrated moderate predictive performance. An exploratory analysis suggested an optimal cutoff value of 21.23% for V20. COPD was more prevalent in the ARP group than in the non-ARP group (19.4% vs. 2.4%, P=0.0047). After adjustment for COPD, V20, and clinical stage in the multivariable model, both COPD (OR=11.67, 95% CI: 2.04-66.75, P=0.0058) and V20 per 5% increase (OR=1.97, 95% CI: 1.31-2.96, P=0.0011) remained independently associated with ARP, with a model AUC of 0.783. No significant differences were observed between groups in baseline NLR, PLR, MLR, or SII. Conclusions: Among patients with locally advanced esophageal cancer undergoing definitive radiotherapy, COPD and higher lung dose exposure, particularly bilateral lung V20, were associated with a higher risk of grade ≥2 ARP. Routine peripheral blood inflammatory markers appeared to have limited predictive utility in this cohort. These results highlight the importance of individualized pulmonary risk assessment and careful management of lung dose prior to radiotherapy.
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