Relevance between patients' clinical factors and 4D-CT lung ventilation heterogeneity for evaluating the adoption of functional avoidance thoracic radiotherapy with a large patient database.
- 1Key Laboratory of Radiation Oncology of Taizhou, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
- 2Department of Thoracic Surgery, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
Abstract
Objective
Four-dimensional computed tomography (4D-CT)-guided functional-avoidance radiotherapy reduces radiation pneumonitis, but the lack of patient selection criteria limits its adoption. This study aimed to identify clinical predictors of lung ventilation heterogeneity and determine which patients derive the greatest dosimetric benefit from functional-avoidance planning.Methods
We retrospectively analyzed 274 lung cancer patients. 4D-CT ventilation imaging was generated via deformable registration and a density-change algorithm, and the coefficient of variation (CoV) across six lung zones quantified heterogeneity. Clinical factors were assessed using Mann-Whitney U, Spearman, and multivariable logistic regression for three ventilation outcomes. Thirty-two patients were selected from CoV quartiles and re-planned with functional-avoidance plans; dosimetric parameters were compared using the Wilcoxon signed-rank test, with False Discovery Rate (FDR) correction applied to address multiple comparisons.Results
Univariate analysis showed chronic obstructive pulmonary disease (COPD) and airway obstruction reduced bilateral mean ventilation, while central tumors impaired ipsilateral ventilation. Higher CoV was observed in stage III-IV versus I-II, central versus peripheral tumors, and patients with airway obstruction. Multivariable analysis identified airway obstruction as an independent predictor of elevated CoV (adjusted OR = 2.914, 95% CI: 1.315-6.454, P<0.05). Central location and advanced stage showed borderline significance, while COPD trended toward lower CoV. Dosimetrically, functional-avoidance plans reduced functional lung metrics in a heterogeneity-dependent manner. After FDR correction, key metrics (fMLD, fV10, fV20, fV30) remained significant in Group 1 (highest CoV; Q = 0.040-0.049), while significance diminished in lower CoV groups. Leave-one-out (LOO) sensitivity analysis confirmed fMLD and fV20 as robust endpoints. Furthermore, beam arrangement modifications were most frequent in Group 1 (5/8 patients) and absent in Group 4 (0/8), reflecting clinical optimization needs rather than confounding.Conclusions
Ventilation heterogeneity is driven by tumor burden and airway patency. Patients with advanced stage, central tumors, or airway obstruction exhibit the strongest heterogeneity and may represent appropriate candidates for functional-avoidance radiotherapy in future prospective trials. However, as this replanning study lacked clinical follow-up for radiation pneumonitis, these findings reflect dosimetric rather than confirmed clinical patient-level benefit. Notably, CoV quartiles were derived from internal median splits within this cohort and require external validation. This study provides a dosimetric basis for hypothesis-generating patient selection.
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BibTeX
@article{deng2026relevance,
title = {{Relevance between patients' clinical factors and 4D-CT lung ventilation heterogeneity for evaluating the adoption of functional avoidance thoracic radiotherapy with a large patient database.}},
author = {Guozhong Deng and Yongquan Ying and Xiaomei Wang and Xingni Tang and Shi Su and Changhui Yu and Pingjun Gu and Haihua Yang},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1955295},
url = {https://europepmc.org/article/MED/42908534},
note = {CC BY},
}
RIS
TY - JOUR
TI - Relevance between patients' clinical factors and 4D-CT lung ventilation heterogeneity for evaluating the adoption of functional avoidance thoracic radiotherapy with a large patient database.
AU - Guozhong Deng
AU - Yongquan Ying
AU - Xiaomei Wang
AU - Xingni Tang
AU - Shi Su
AU - Changhui Yu
AU - Pingjun Gu
AU - Haihua Yang
PY - 2026
DA - 2026/10/07
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1955295
UR - https://europepmc.org/article/MED/42908534
AB - Objective Four-dimensional computed tomography (4D-CT)-guided functional-avoidance radiotherapy reduces radiation pneumonitis, but the lack of patient selection criteria limits its adoption. This study aimed to identify clinical predictors of lung ventilation heterogeneity and determine which patients derive the greatest dosimetric benefit from functional-avoidance planning.Methods We retrospectively analyzed 274 lung cancer patients. 4D-CT ventilation imaging was generated via deformable registration and a density-change algorithm, and the coefficient of variation (CoV) across six lung zones quantified heterogeneity. Clinical factors were assessed using Mann-Whitney U, Spearman, and multivariable logistic regression for three ventilation outcomes. Thirty-two patients were selected from CoV quartiles and re-planned with functional-avoidance plans; dosimetric parameters were compared using the Wilcoxon signed-rank test, with False Discovery Rate (FDR) correction applied to address multiple comparisons.Results Univariate analysis showed chronic obstructive pulmonary disease (COPD) and airway obstruction reduced bilateral mean ventilation, while central tumors impaired ipsilateral ventilation. Higher CoV was observed in stage III-IV versus I-II, central versus peripheral tumors, and patients with airway obstruction. Multivariable analysis identified airway obstruction as an independent predictor of elevated CoV (adjusted OR = 2.914, 95% CI: 1.315-6.454, P<0.05). Central location and advanced stage showed borderline significance, while COPD trended toward lower CoV. Dosimetrically, functional-avoidance plans reduced functional lung metrics in a heterogeneity-dependent manner. After FDR correction, key metrics (fMLD, fV10, fV20, fV30) remained significant in Group 1 (highest CoV; Q = 0.040-0.049), while significance diminished in lower CoV groups. Leave-one-out (LOO) sensitivity analysis confirmed fMLD and fV20 as robust endpoints. Furthermore, beam arrangement modifications were most frequent in Group 1 (5/8 patients) and absent in Group 4 (0/8), reflecting clinical optimization needs rather than confounding.Conclusions Ventilation heterogeneity is driven by tumor burden and airway patency. Patients with advanced stage, central tumors, or airway obstruction exhibit the strongest heterogeneity and may represent appropriate candidates for functional-avoidance radiotherapy in future prospective trials. However, as this replanning study lacked clinical follow-up for radiation pneumonitis, these findings reflect dosimetric rather than confirmed clinical patient-level benefit. Notably, CoV quartiles were derived from internal median splits within this cohort and require external validation. This study provides a dosimetric basis for hypothesis-generating patient selection.
SN - 2234-943X
ER -