Lung NeoplasmsFLAR-4DCTNCT07312682
Application of 4DCT-Based Pulmonary Ventilation Imaging in Lung Cancer Radiotherapy
An observational study of Lung Neoplasms and Radiation Pneumonitis, run by The Second Affiliated Hospital of Chongqing Medical University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Lung Neoplasms, Radiation Pneumonitis
- How many people
- 202 participants
- Where
- 1 siteChina
- Study dates
- 9 Dec 2024to 30 Nov 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Cancer Center, Second Affiliated Hospital of Chongqing Medical University
Chongqing, 400000
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Lung Neoplasms, Radiation Pneumonitis
- Keywords
- 4DCT, Lung Ventilation Imaging, Functional Lung Imaging, Functional-Lung-Avoidance Radiotherapy (FLAR), IMRT, Organs at Risk (OARs), Radiation-Induced Lung Injury, Radiation Pneumonitis
- Medical subject headings
- Lung Neoplasms, Radiation Pneumonitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Assessed at 3 months, 6 months, and 12 months after completion of radiotherapy.
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At treatment planning (baseline, pre-radiotherapy delivery).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2025
- Study start9 Dec 2024
- Primary completion9 Sep 2025
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lung NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Second Affiliated Hospital of Chongqing Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ZhenZhou Yang, The Second Affiliated Hospital of Chongqing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07312682
- Sponsor's protocol ID
- IRB-2024-394
- Acronym
- FLAR-4DCT
- Status last verified
- Dec 2025
- First submitted
- 9 Sep 2025
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 23474113Henshaw SK. Induced abortion: a world review, 1990. Fam Plann Perspect. 1990 Mar-Apr;22(2):76-89.
PubMed 2347411Lombardo 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.
PubMed 38614278
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on 4DCT-Based Pulmonary Ventilation Imaging for Functional Lung Avoidance in Radiotherapy of Lung Cancer
- ClinicalTrials.gov ID
- NCT07312682
- Acronym / sponsor ID
- FLAR-4DCT / IRB-2024-394
- Conditions
- Lung Neoplasms, Radiation Pneumonitis
- Keywords
- 4DCT, Lung Ventilation Imaging, Functional Lung Imaging, Functional-Lung-Avoidance Radiotherapy (FLAR), IMRT, Organs at Risk (OARs), Radiation-Induced Lung Injury, Radiation Pneumonitis
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 202 participants (actual)
- Lead sponsor
- The Second Affiliated Hospital of Chongqing Medical UniversityUniversity, hospital or other
- Study start
- 9 Dec 2024 (actual)
- Primary completion
- 9 Sep 2025 (actual)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 31 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Incidence of Radiation-Induced Lung Injury (Grade ≥2)
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.
10 secondary outcomes
Mean Dose to High-Function Lung (Gy)
Time frame: At baseline treatment planning (prior to radiotherapy delivery).
MLD for Whole Lung (Gy)
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
V5 of High-Function Lung (%)
Time frame: At baseline treatment planning (prior to radiotherapy delivery).
V20 of High-Function Lung
Time frame: At baseline treatment planning (prior to radiotherapy delivery).
Mean Dose to Heart (Gy)
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Maximum Dose to Esophagus (Gy)
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Maximum Dose to Spinal Cord (Gy)
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Target Coverage (PTV D95)
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Conformity Index of Radiotherapy Plans
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Homogeneity Index of Radiotherapy Plans
Time frame: At treatment planning (baseline, pre-radiotherapy delivery).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Background: PubMed 23474113Vinogradskiy 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.
- Background: PubMed 2347411Henshaw SK. Induced abortion: a world review, 1990. Fam Plann Perspect. 1990 Mar-Apr;22(2):76-89.
- Background: PubMed 38614278Lombardo 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.
- National Clinical Research Registration and Filing Information System (China) record for this study(ID：MR-50-25-001899).Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Neoplasms and Radiation Pneumonitis, run by The Second Affiliated Hospital of Chongqing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Radiation-Induced Lung Injury (Grade ≥2) (time frame: Assessed at 3 months, 6 months, and 12 months after completion of radiotherapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07312682, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.