Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07339644

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Lung Cancer (Including Metastatic Cancer) Lung Diseases Lung Diseases, Interstitial Lung Injury Lung Neoplasms Neoplasms Neoplasms by Site Radiation Injuries Radiation Pneumonitis Radiation-induced Lung Injury Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Wounds and Injuries

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Cancer Center, Second Affiliated Hospital of Chongqing Medical University

Chongqing, 400000, China

Location status: Recruiting

Location contact

Xiongying Fang, MD.

CONTACT

[email protected]

+86 23 62888436

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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.

Other names: Functional Lung Avoidance Radiotherapy, 4DCT-FLAR, 4DCT Ventilation Functional Imaging (4DCT-FLI)-Guided Radiotherapy

Primary outcomes

  1. Incidence of Radiation-Induced Lung Injury (Grade ≥2)

    Time frame: Time Frame: Assessed at 3 months, 6 months, and 12 months after completion of radiotherapy.

    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.

Secondary outcomes

  1. Mean Dose to High-Function Lung (Gy)

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

    DVH-derived mean dose to ventilation-defined high-function lung on paired plans (functional-lung-avoidance vs conventional plans). Lower dose indicates better sparing.

  2. MLD for Whole Lung (Gy)

    Time frame: At baseline treatment planning (prior to radiotherapy delivery).

    Percentage volume (%) of ventilation-defined high-function lung receiving ≥5 Gy, reported separately for functional-lung-avoidance and conventional radiotherapy plans.

  3. V5 of High-Function Lung (%)

    Time frame: At baseline treatment planning (prior to radiotherapy delivery).

    Percentage volume (%) of ventilation-defined high-function lung receiving ≥5 Gy, reported separately for functional-lung-avoidance and conventional radiotherapy plans.

  4. V20 of High-Function Lung（%）

    Time frame: At baseline treatment planning (prior to radiotherapy delivery).

    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.

  5. Mean Dose to Heart (Gy)

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

    DVH-derived mean dose (Dmean) to the heart, compared between functional-lung-avoidance and conventional radiotherapy plans.

  6. Maximum Dose to Esophagus (Gy)

    Time frame: At treatment planning (baseline, pre-radiotherapy delivery).]

    DVH-derived maximum dose (Dmax) to the esophagus, compared between functional-lung-avoidance and conventional radiotherapy plans.

  7. Maximum Dose to Spinal Cord (Gy)

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

    DVH-derived maximum dose (Dmax) to the spinal cord, compared between functional-lung-avoidance and conventional radiotherapy plans.

  8. Target Coverage (PTV D95)

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

    Percentage of planning target volume (PTV) receiving at least 95% of prescribed dose, compared between functional-lung-avoidance and conventional plans.

  9. Conformity Index of Radiotherapy Plans

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

    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.

  10. Homogeneity Index of Radiotherapy Plans

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

    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.

  11. Gradient Measure (GM) of Radiotherapy Plans

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

    Gradient Measure (cm) of paired radiotherapy plans, comparing 4DCT-FLI-guided functional lung avoidance plans and conventional anatomic plans. GM is defined as the difference between the equivalent sphere radii of the 50% and 100% prescription isodose volumes (GM = R50% - R100%); lower values indicate steeper dose fall-off and better plan quality.

  12. Forced Expiratory Volume in 1 Second (FEV1)

    Time frame: Baseline and 1, 3, 6, and 12 months after radiotherapy.

    FEV1 measured by standardized spirometry (L and % predicted). Outcome is change from baseline.

  13. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

    Time frame: Baseline and 1, 3, 6, and 12 months after radiotherapy.

    DLCO measured using a standardized single-breath method (mL/min/mmHg and % predicted). Outcome is change from baseline.

  14. Forced Vital Capacity (FVC)

    Time frame: Baseline and 1, 3, 6, and 12 months after radiotherapy.

    FVC measured by standardized spirometry (L and % predicted). Outcome is change from baseline.

Study contacts

Contact information is provided by the study sponsor or research team.

Zhi chen, MD.

CONTACT

[email protected]

+86 18982928222

Sponsors and collaborators

Lead sponsor

The Second Affiliated Hospital of Chongqing Medical University

Other

Registry information

Acronym: 4DCT-FLAR

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Jan 14, 2026
Registry last updated
Feb 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.