Functional Lung Avoidance Radiotherapy Guided by 4DCT Pulmonary Ventilation Function Imaging: A Prospective Single-arm Clinical Study

NCT07339644 | Recruiting

• 1 other identifier: IRB-2025-243
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-center, single-arm study will evaluate the feasibility and safety of 4DCT ventilation functional imaging-guided functional lung avoidance radiotherapy (FLAR) in patients with lung malignancies receiving IMRT radiotherapy. All participants will undergo 4DCT simulation as part of routine radiotherapy preparation. A ventilation map will be generated from 4DCT data, and the top 80% ventilation region will be defined as the high-function lung. This structure will be imported into the treatment planning system to create an FLAR plan that prioritizes sparing of high-function lung while maintaining target coverage (PTV D95%) and meeting standard dose constraints for organs at risk. A conventional anatomic plan (without functional guidance) will also be created for paired, within-patient dosimetric comparison. The primary outcome is improvement in dosimetric sparing of the high-function lung (V10, V20, V30, and mean lung dose). Secondary outcomes include the incidence of grade ≥2 radiation pneumonitis (CTCAE v5.0), changes in pulmonary function (e.g., FEV1 and DLCO), and lung-related quality-of-life scores. Assessments will be performed mid-treatment (after 15 fractions), at the end of radiotherapy (after 30 fractions), and at 1, 3, 6, and 12 months after radiotherapy. The study plans to enroll 100 participants and follow each participant for 12 months.

Conditions

Radiation Pneumonitis; Radiation-induced Lung Injury; Lung Cancer (Including Metastatic Cancer)

Keywords

Functional lung avoidance radiotherapy; 4DCT ventilation imaging; Functional lung imaging (FLI); Dose-volume histogram (DVH); High-function lung; Radiotherapy planning optimization; Radiation pneumonitis; Pulmonary function

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (14)

• Mean Dose to High-Function Lung (Gy)

  At baseline treatment planning (prior to radiotherapy delivery).]

• MLD for Whole Lung (Gy)

  At baseline treatment planning (prior to radiotherapy delivery).

• V5 of High-Function Lung (%)

  At baseline treatment planning (prior to radiotherapy delivery).

• V20 of High-Function Lung（%）

  At baseline treatment planning (prior to radiotherapy delivery).

• Mean Dose to Heart (Gy)

  At treatment planning (baseline, pre-radiotherapy delivery).

Study Arms (1)

4DCT-FLI-Guided Functional Lung Avoidance Radiotherapy (FLAR)

EXPERIMENTAL

Participants receive IMRT planned with 4DCT ventilation functional imaging guidance. A ventilation map is generated from 4DCT, high-function lung (top 80% ventilation) is contoured, and the treatment plan is optimized to spare high-function lung while maintaining target coverage and meeting standard OAR constraints. A conventional anatomic plan is also generated for within-patient dosimetric comparison.

Procedure: 4DCT Ventilation Imaging-Guided Functional Lung Avoidance Radiotherapy (FLAR)

Interventions

4DCT Ventilation Imaging-Guided Functional Lung Avoidance Radiotherapy (FLAR) PROCEDURE

All participants undergo 4DCT simulation. A ventilation map is generated from 4DCT data, and the high-function lung is defined as the top 80% ventilation region. This structure is imported into the treatment planning system, and an IMRT plan is optimized to preferentially spare high-function lung while maintaining target (PTV) coverage and meeting standard organ-at-risk constraints. A conventional anatomic plan (without functional guidance) is also created for within-patient paired dosimetric comparison.

Also known as: Functional Lung Avoidance Radiotherapy, 4DCT-FLAR, 4DCT Ventilation Functional Imaging (4DCT-FLI)-Guided Radiotherapy

4DCT-FLI-Guided Functional Lung Avoidance Radiotherapy (FLAR)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 85 years (inclusive); any sex.
• Diagnosed lung malignancy requiring thoracic radiotherapy (e.g., non-small cell lung cancer, small cell lung cancer, or pulmonary metastases).
• Planned to receive thoracic radiotherapy using either conventionally fractionated IMRT/VMAT or stereotactic body radiotherapy (SBRT), and able to complete pre-treatment 4DCT simulation suitable for generating a ventilation map.
• Adequate baseline organ function and clinically judged able to tolerate radiotherapy; ECOG performance status 0-1.
• No absolute contraindication to pulmonary function testing; patients with moderate COPD or impaired lung function may be included if the treating team judges radiotherapy to be tolerable.
• Able to comply with treatment and follow-up assessments.
• Written informed consent provided.

You may not qualify if:

• Pregnant or breastfeeding women. Women of childbearing potential must have pregnancy excluded prior to radiotherapy per institutional practice.
• Age \<18 or \>85 years.
• Uncontrolled severe cardiopulmonary disease or other severe comorbidities that make radiotherapy excessively high risk (e.g., decompensated heart failure, unstable cardiopulmonary status, active severe pulmonary infection).
• Prior high-dose thoracic radiotherapy to the same region such that safe re-irradiation is not feasible.
• Concurrent other active/advanced malignancy requiring priority treatment that would confound study outcomes.
• Recent participation in another interventional clinical trial or concurrent investigational therapy judged likely to interfere with this study's endpoints.
• Severe psychiatric, cognitive, or other conditions that prevent cooperation with radiotherapy and/or scheduled follow-up.
• Inadequate 4DCT image quality or inability to generate/validate the 4DCT ventilation map required for functional-lung-guided planning.
• Any other condition deemed unsuitable by the investigators in the interest of participant safety.

Sponsors & Collaborators

• The Second Affiliated Hospital of Chongqing Medical University: lead

Study Sites (1)

Cancer Center, Second Affiliated Hospital of Chongqing Medical University

Chongqing, 400000, China

RECRUITING

Related Publications (1)

• Vinogradskiy Y, Castillo R, Castillo E, Tucker SL, Liao Z, Guerrero T, Martel MK. Use of 4-dimensional computed tomography-based ventilation imaging to correlate lung dose and function with clinical outcomes. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):366-71. doi: 10.1016/j.ijrobp.2013.01.004. Epub 2013 Mar 6.

  PMID: 23474113 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Radiation Pneumonitis

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Interstitial; Lung Injury; Radiation Injuries; Wounds and Injuries

Study Officials

• zhengjun Guo, MD.

  The Second Clinical College of Chongqing Medical University: The Second Affiliated Hospital of Chongqing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhi chen, MD.

CONTACT

+86 18982928222; 2023440076@stu.cqmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Radiation Oncology, Cancer Center, Second Affiliated Hospital of Chongqing Medical University

Model Details: Single-arm, single-center prospective study. All participants receive 4DCT ventilation imaging-guided functional lung avoidance radiotherapy (FLAR). For within-patient paired dosimetric comparison, a conventional anatomic plan (non-functional plan) is also generated for each participant.

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 14, 2026
• Study Start: October 24, 2025
• Primary Completion (Estimated): December 24, 2026
• Study Completion (Estimated): December 24, 2027
• Last Updated: February 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)