2742 - Dosimetric Predictors and Clinical Risk Factors for Radiation Pneumonitis In Lung Cancer Patients Receiving Intensity-Modulated Proton Re-Irradiation: A Retrospective Cohort Study
Presenter(s)
Y. Guo1, H. Zhu2, W. Jia3, S. Lu4, Z. Sun1, J. Yu5, and J. Li6; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 3Department of Radiation Oncology, Shandong Cancer Hospital & Institute Affiliated to Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China., Jinan, Shandong, China, 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China, 5Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 6Department of Radiation Oncology, Shandong Cancer Hospital & Institute Affiliated to Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China., Jinan, China
Purpose/Objective(s): Locoregional recurrence lung cancers following definitive radiotherapy represents a significant clinical challenge. Conventional photon-based re-irradiation, typically utilizing IMRT, is frequently constrained by cumulative damage to surrounding healthy lung parenchyma, leading to a high risk of severe radiation pneumonitis (RP). Intensity-modulated proton therapy (IMPT), leveraging the physical precision of the Bragg peak, theoretically provides a safer and more reliable therapeutic alternative by optimizing the dose distribution between target coverage and organ sparing. This study aimed to evaluate the safety and preliminary clinical efficacy of IMPT for thoracic re-irradiation and to identify independent risk factors for treatment-related toxicity.
Materials/Methods:
We conducted a retrospective analysis of 68 consecutive lung cancer patients (28 squamous cell, 18 adenocarcinoma, and 22 small cell) who received IMPT re-irradiation between November 2023 and June 2025. The primary endpoint was the incidence of symptomatic (Grade = 2) RP within 3 months post-treatment. Secondary outcomes evaluated included objective response rate (ORR), disease control rate (DCR), additional radiotherapy-related adverse events, and hematological toxicity.Results:
Following an initial photon dose of 51.0 Gy and a median interval of 18.5 months, patients received a median IMPT dose of 52.5 Gy. Symptomatic Grade = 2 RP was observed in 30 patients (44.1%), comprising Grade 2 (27.9%), Grade 3 (14.7%), and Grade 4 (1.5%) cases, with no treatment-related fatalities recorded. Subgroup analysis demonstrated a higher RP risk in patients with short treatment intervals (= 1 year, 50.0%) and in-field recurrences (50.0%) compared to their counterparts. Multivariate analysis identified smoking index > 400, elevated baseline C-reactive protein (CRP), and specific dosimetric parameters (V25, V30, and MLD) as independent risk factors for Grade = 2 RP (all P < 0.05). ROC curve analysis confirmed that Mean Lung Dose (MLD) was the most robust predictor (AUC=0.848, 95% CI: 0.752–0.944), with an optimal cutoff of 4.83 Gy. Regarding clinical efficacy, the ORR and DCR were 13.2% and 79.4%, respectively. Notable secondary toxicities included Grade = 2 radiation esophagitis in 25.0% and Grade = 3 lymphopenia in 35.3% of the cohort.Conclusion:
IMPT is a viable and effective salvage modality for recurrent lung cancer, offering a high rate of disease control with manageable toxicity. To mitigate the risk of severe RP, clinicians should prioritize stringent lung sparing (target MLD < 4.83 Gy) and implement vigilant monitoring for high-risk individuals characterized by heavy smoking history and systemic pro-inflammatory states.