This retrospective single-center study investigates whether four-dimensional CT (4DCT)-based lung ventilation imaging can guide functional lung avoidance radiotherapy (FLAR) for patients with primary lung cancer. Ventilation maps generated from planning 4DCT are used to identify well-ventilated lung regions, enabling paired comparison between functional lung avoidance radiotherapy plans and conventional anatomic radiotherapy plans. The study aims to assess whether incorporating functional lung information into radiotherapy planning can reduce radiation exposure to well-ventilated lung while maintaining adequate tumor coverage, and to explore its relationship with radiation-induced lung injury. All analyses are based on existing clinical imaging, treatment planning data, and follow-up records. No additional interventions, imaging, or procedures are performed as part of this study.
This study retrospectively evaluates a functional lung-guided radiotherapy planning workflow based on four-dimensional CT (4DCT) ventilation imaging in patients with primary lung cancer who previously underwent thoracic radiotherapy. High-quality 4DCT datasets acquired during routine simulation are processed to generate voxel-based lung ventilation maps using deformable image registration and Jacobian-based computational methods. These ventilation maps are spatially registered to planning CT images and incorporated into the treatment planning system to delineate high-function lung subregions. For each eligible patient, paired radiotherapy plans are retrospectively generated and analyzed: a conventional anatomic radiotherapy plan and a functional lung avoidance radiotherapy (FLAR) plan that incorporates ventilation-defined avoidance structures. Both plans are optimized to achieve comparable target coverage while differing in lung avoidance strategy. Dosimetric and clinical data are obtained from existing treatment planning records and routine clinical follow-up to support comparative analyses of functional lung sparing and associated pulmonary outcomes. All analyses are conducted retrospectively using data derived from standard clinical care. No prospective enrollment, additional imaging, or study-specific interventions are performed.
Study Type
OBSERVATIONAL
Enrollment
202
Cancer Center, Second Affiliated Hospital of Chongqing Medical University
Chongqing, China
Incidence of Radiation-Induced Lung Injury (Grade ≥2)
Incidence of radiation-induced lung injury (RILI) of Grade ≥ 2, assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. CTCAE grades range from Grade 1 (mild) to Grade 5 (death related to adverse event), with higher grades indicating more severe toxicity. The primary outcome is the proportion of patients experiencing CTCAE Grade ≥ 2 RILI.
Time frame: Assessed at 3 months, 6 months, and 12 months after completion of radiotherapy.
Mean Dose to High-Function Lung (Gy)
DVH-derived mean dose to ventilation-defined high-function lung on paired plans (functional-lung-avoidance vs conventional plans). Lower dose indicates better sparing.
Time frame: At baseline treatment planning (prior to radiotherapy delivery).
MLD for Whole Lung (Gy)
DVH-derived mean lung dose (MLD) for whole lung on paired plans; absolute values reported separately for functional-lung-avoidance vs conventional plans.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
V5 of High-Function Lung (%)
Percentage volume (%) of ventilation-defined high-function lung receiving ≥5 Gy, reported separately for functional-lung-avoidance and conventional radiotherapy plans.
Time frame: At baseline treatment planning (prior to radiotherapy delivery).
V20 of High-Function Lung
DVH-derived V20 of ventilation-defined high-function lung, defined as the percentage of lung volume receiving ≥20 Gy, compared between functional-lung-avoidance and conventional radiotherapy plans.
Time frame: At baseline treatment planning (prior to radiotherapy delivery).
Mean Dose to Heart (Gy)
DVH-derived mean dose (Dmean) to the heart, compared between functional-lung-avoidance and conventional radiotherapy plans.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Maximum Dose to Esophagus (Gy)
DVH-derived maximum dose (Dmax) to the esophagus, compared between functional-lung-avoidance and conventional radiotherapy plans.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Maximum Dose to Spinal Cord (Gy)
DVH-derived maximum dose (Dmax) to the spinal cord, compared between functional-lung-avoidance and conventional radiotherapy plans.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Target Coverage (PTV D95)
Percentage of planning target volume (PTV) receiving at least 95% of prescribed dose, compared between functional-lung-avoidance and conventional plans.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Conformity Index of Radiotherapy Plans
Conformity Index (CI) of paired treatment plans, comparing functional-lung-avoidance and conventional anatomic radiotherapy plans. The Conformity Index is defined as the ratio of the prescription isodose volume to the target volume (CI = V\<sub\>RI\</sub\> / V\<sub\>T\</sub\>). The score ranges from 1.0 to \>2.0, where a value closer to 1.0 indicates better conformity and thus higher plan quality.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Homogeneity Index of Radiotherapy Plans
Homogeneity Index (HI) of paired treatment plans, comparing functional-lung-avoidance and conventional anatomic radiotherapy plans. The Homogeneity Index is defined as (D\<sub\>2%\</sub\> - D\<sub\>98%\</sub\>) / D\<sub\>50%\</sub\>. The score typically ranges from 0 to 1.0, where lower values indicate more homogeneous dose distribution and better plan quality.
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
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