ORIGINAL RESEARCH article
Front. Public Health
Sec. Radiation and Health
Volume 13 - 2025 | doi: 10.3389/fpubh.2025.1656120
This article is part of the Research TopicAdvances in Radiation Research and Applications: Biology, Environment and MedicineView all 15 articles
Development and Validation of NTCP Models for Predicting Acute Esophagitis in Carbon Ion Radiotherapy for Thoracic Malignancies
Provisionally accepted
- Shanghai Proton and Heavy Ion Center (SPHIC), Shanghai, China
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Objective: By utilizing observed acute esophagitis (AE) data from thoracic malignancy (TM) patients undergoing carbon ion radiotherapy (CIRT), this study develops Normal Tissue Complication Probability (NTCP) models to identify key risk factors, enabling personalized treatment planning for esophageal toxicity reduction.To develop Normal Tissue Complication Probability (NTCP) models for acute esophagitis (AE) in thoracic malignancies (TM) treated with carbon ion radiotherapy (CIRT), identifying key risk factors to optimize treatment planning. Methods: 168 patients with TM (non-small cell lung cancer (NSCLC): 95, tracheobronchial adenoid cystic carcinoma (TACC): 43, thoracic bone and soft tissue sarcomas (TBSTS): 30) treated with CIRT (59.5-80 GyGy(RBE) in 16-23 fractions) were analyzed. AE was graded per Common Terminology Criteria for Adverse Events v4.03. Dosimetric parameters and clinical variables were evaluated using logistic regression. The Lyman-Kutcher-Burman NTCP model was optimized via maximum likelihood estimation to establish volume effect (n), slope (m), and tolerance dose for 50% complication probability (TD50) parameters. Model performance was assessed by the area under curve (AUC) of the receiver operating characteristic (ROC) curve and validated internally. Results: No grade ≥ 3 AE was observed. TACC showed highest rates (G1:88.4%; G2:20.9%), followed by TBSTS (G1:50.0%; G2:16.7%) and NSCLC (G1:35.8%; G2:1.1%). Females had higher G1 (63.0% vs 47.5%) but doubled G2 risk (13.0% vs 7.4%) versus males. Toxicity peaked in patients < 60 years (G1:64.4%; G2:16.4%), declining with age. Paradoxically, non-drinkers had 9-fold higher G2 risk (14.0% vs 1.5%), while smoking showed protection (non-smokers vs smokers, G2:1.2% vs 17.1%). Notably, multivariate analysis identified V44GyGy(RBE) as the independent predictor for G1 AE (OR: 1.06, 95% CI: 1.013-1.115; p<0.001) with AUC 0.83. While G2 toxicity was driven by D9cc (1.07, 1.02-1.13; p=0.004), age years (0.94, 0.895-0.986; p=0.012), and smoking status (0.12, 0.013-1.04; p=0.05) with AUC 0.936.The LKB models demonstrated for G1 AE: n=0.23 (95%CI:0.05-0.45), m=0.81 (0.2-1.0), TD50=62.8 Gy (35.5-75.5) with AUC=0.792, and for Grade 2 AE: n=0.06 (0.01-0.20), m=0.16 (0.01-0.25), TD50=80 GyGy(RBE) (50.0-95.0) with AUC=0.764.The first validated NTCP models for CIRT-induced AE highlight V44GyGy(RBE), D9cc, age, and smoking as critical predictors. Derived LKB parameters enable personalized planning to reduce esophageal toxicity, advancing particle therapy optimization.
Keywords: Carbon ion radiotherapy, Thoracic tumors, Acute esophagitis, Normal Tissue Complication Probability models, Dose constraints
Received: 29 Jun 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Li, Zhang, Liu, Wu, Mao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jian Chen, Shanghai Proton and Heavy Ion Center (SPHIC), Shanghai, China
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