Application of 4DCT-Based Pulmonary Ventilation Imaging in Lung Cancer Radiotherapy (FLAR-4DCT)

Clinical Study on 4DCT-Based Pulmonary Ventilation Imaging for Functional Lung Avoidance in Radiotherapy of Lung Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Neoplasms; Radiation Pneumonitis

Detailed Description

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 (Actual): 202

Contacts and Locations

Study Locations

• China
  • Chongqing, China, 400000
    • Cancer Center, Second Affiliated Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Single-center retrospective cohort of consecutive adults (≥18 years) with primary lung cancer treated with thoracic radiotherapy planned with IMRT, with adequate 4DCT scans for ventilation mapping (2022-01-01 to 2025-09-09).

Description

Inclusion Criteria:

• Histologically confirmed primary lung cancer (adenocarcinoma, squamous cell carcinoma, or small-cell carcinoma) treated with thoracic radiotherapy.
• High-quality 4DCT scans performed before radiotherapy, enabling generation of ventilation or perfusion maps.
• Radiotherapy plans designed using IMRT.
• Availability of both functional lung avoidance plans and conventional anatomical radiotherapy plans for paired analysis.
• Complete treatment and follow-up records, including radiation-induced lung injury (e.g., radiation pneumonitis) and pulmonary function tests.

Exclusion Criteria:

• Incomplete or poor-quality imaging data preventing accurate ventilation/perfusion map generation.
• Radiotherapy interrupted or incomplete for any reason.
• Severe underlying lung diseases (e.g., extensive emphysema, pulmonary fibrosis, active tuberculosis) that may confound treatment outcomes or toxicity assessment.
• Presence of other untreated primary malignancies during the study period.
• Prior lung surgery or local therapies (e.g., ablation) that may affect evaluation of radiation-induced lung injury.
• Missing follow-up data, making assessment of radiation-induced lung injury or long-term lung function changes impossible.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

4DCT-IMRT Lung Cancer Cohort; Single-center retrospective cohort of consecutive lung cancer patients with high-quality 4DCT planned with IMRT (2022-01-01-2025-09-09; actual enrollment = 202). 4DCT-based ventilation maps delineate high-function lung. Paired-plan comparison of functional-lung-avoidance versus conventional plans; primary outcomes: dose to high-function lung and radiation pneumonitis. Secondary outcomes: doses to heart, spinal cord, and esophagus, and plan-quality metrics (e.g., MLD, V20, DVH). No additional procedures or treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessed at 3 months, 6 months, and 12 months after completion of radiotherapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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 = VRI / VT). The score ranges from 1.0 to >2.0, where a value closer to 1.0 indicates better conformity and thus higher plan quality.	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 (D2% - D98%) / D50%. The score typically ranges from 0 to 1.0, where lower values indicate more homogeneous dose distribution and better plan quality.	At treatment planning (baseline, pre-radiotherapy delivery).

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Publications and helpful links

General Publications

• Mattila S, Sovijarvi AR, Harjula A, Viljanen A, Takkunen O, Takkunen H, Mattila I, Mattila P, Merikallio E. Effects of mitral valve replacement on ventilation, volumes, diffusing capacity and regional perfusion of lungs in patients with mitral valve disease. Ann Chir Gynaecol. 1985;74(2):82-5.
• Henshaw SK. Induced abortion: a world review, 1990. Fam Plann Perspect. 1990 Mar-Apr;22(2):76-89.
• Lombardo J, Castillo E, Castillo R, Miller R, Jones B, Miften M, Kavanagh B, Dicker A, Boyle C, Leiby B, Banks J, Simone NL, Movsas B, Grills I, Guerrero T, Rusthoven CG, Vinogradskiy Y. Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report. Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):593-602. doi: 10.1016/j.ijrobp.2024.03.046. Epub 2024 Apr 12.

Helpful Links

• National Clinical Research Registration and Filing Information System (China) record for this study(ID：MR-50-25-001899).

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Actual): September 9, 2025
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: September 9, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 31, 2025

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: IMRT; Radiation Pneumonitis; 4DCT; Functional Lung Imaging; Lung Ventilation Imaging; Functional-Lung-Avoidance Radiotherapy (FLAR); Organs at Risk (OARs); Radiation-Induced Lung Injury
• Additional Relevant MeSH Terms: Wounds and Injuries; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases, Interstitial; Radiation Injuries; Lung Injury; Lung Neoplasms; Radiation Pneumonitis
• Other Study ID Numbers: IRB-2024-394

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the primary results will be available to qualified researchers upon reasonable request after publication. Available data include demographics, key clinical outcomes (e.g., radiation-induced lung injury), 4DCT-derived ventilation maps, radiotherapy dose/plan files and DVH metrics. Direct identifiers will be removed; data will be shared in compliance with ethics approval and local regulations.
• IPD Sharing Time Frame: De-identified IPD and supporting documents will be available from publication of the primary results until 2035-08-31. Requests will be reviewed within 30 days of receipt and, if approved, data will be shared within 60 days after execution of a Data Use Agreement.
• IPD Sharing Access Criteria: Qualified researchers with a methodologically sound proposal and evidence of IRB/ethics approval may request access. A Data Use Agreement with the sponsor institution is required. Only de-identified data will be shared; no re-identification, redistribution, or commercial use is permitted. Data will be transferred via secure, access-controlled methods. Please contact Zhi Chen (2023440076@stu.cqmu.edu.cn).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No