Study on the impact of tumor volume change and radiation dose on 4D-CT-based lung ventilation function at mid-treatment adaptive radiotherapy in stage III non-small cell lung cancer.

[PURPOSE] This study aims to evaluate the impact of tumor volume reduction at mid-treatment on four-dimensional computed tomography (4D-CT) based lung ventilation function for patients with lung cancer undergoing adaptive radiotherapy (ART), and explores the relationship between radiation dose and ventilation loss to inform personalized lung dose optimization in radiotherapy planning.

[MATERIALS AND METHODS] Forty patients with stage III non-small cell lung cancer (NSCLC) who had undergone ART were enrolled. 4D-CT scans were performed at pre- and mid-treatment. Patients were categorized according to the relative volume changes in primary gross tumor volume (GTV) and nodal gross tumor volume (GTV). Each metric was used to divide the cohort into three groups, yielding a total of six comparative groups. Pre-treatment lung ventilation maps, divided into high-, medium-, and low-ventilation regions, were intersected with four dose zones that were categorized by the cumulative lung dose. Ventilation changes at mid-treatment ART in these ventilation regions and dose zones were analyzed for each patient group.

[RESULTS] Negative correlations were observed between relative changes in the overall ventilation and relative volume changes of the two target contours (GTV and GTV), with Spearman correlation coefficients being -0.625 and -0.452, respectively. Ventilation recovery resulting from tumor shrinkage significantly counteracted radiation-induced functional loss. In contrast, patients with minimal tumor volume reduction showed marked declines in pulmonary ventilation. Nearly all patient groups exhibited ventilation reduction in the high-ventilation region and improvement in the low-ventilation region.Ventilation loss showed a clear dose-dependent pattern across all regions, with the high-ventilation region most affected in patients without significant tumor-shrinkage-driven ventilation recovery.

[CONCLUSIONS] Changes in lung ventilation at mid-treatment were strongly influenced by tumor volume reduction. A clear dose-dependent functional loss pattern was confirmed in the high-ventilation region, with high radiation doses inhibiting lung ventilation. These findings underscore the importance of protecting high-ventilation lung in NSCLC radiotherapy and suggest incorporating tumor volume reduction into adaptive re-planning.