Thymus Dosimetric and Morphologic Predictors of Radiation-Induced Lymphopenia in Stage III NSCLC

NCT07564089 | Active Not Recruiting

• 1 other identifier: TRIPLE-NSCLC Study
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to find out whether features of the thymus gland can predict a common side effect of radiation therapy for lung cancer called radiation-induced lymphopenia. We will include adults with stage III non-small cell lung cancer (NSCLC) who are scheduled to receive curative radiation therapy to the chest, with or without chemotherapy. Before, during, and after radiation therapy, we will measure: The dose of radiation that reaches the thymus gland (based on each patient's treatment plan) The size and shape of the thymus gland (using CT scans taken for radiation planning) The number of lymphocytes (a type of immune cell) in routine blood samples The main goal is to see if certain radiation doses to the thymus, or a smaller thymus size, can predict severe lymphopenia. We will also check whether lymphopenia affects patient outcomes such as infections or survival. This is an observational study (no added treatment or drug) - patients will receive their standard radiation therapy as planned by their doctor. The study only collects and analyzes data from standard scans and blood tests. Potential benefits: Findings may help doctors design "immune-sparing" radiation plans in the future to reduce lymphopenia. Potential risks: There are no additional risks beyond standard radiation therapy, as this study does not change your treatment.

Conditions

Thymus Dosimetric; Number of Lymphocytes; Radiation-induced Lymphopenia

Outcome Measures

Primary Outcomes (2)

• Severe radiation-induced lymphopenia (grade ≥3)

  Occurrence and severity of radiation-induced lymphopenia during definitive thoracic radiotherapy for stage III non-small cell lung cancer. Lymphopenia is defined based on absolute lymphocyte count (ALC) measured from peripheral blood samples. Severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0: Grade 1: ALC \< lower limit of normal to 800 cells/μL Grade 2: ALC 500 - \<800 cells/μL Grade 3: ALC 200 - \<500 cells/μL Grade 4: ALC \<200 cells/μL The primary analysis will focus on grade ≥3 lymphopenia as the main endpoint. Absolute lymphocyte count nadir (lowest value during treatment) and relative change from baseline are also captured as continuous secondary measures within this outcome.

  From baseline (within 7 days before radiotherapy initiation) to 6 weeks after completion of radiotherapy.

• radiation-induced lymphopenia

  Occurrence and severity of radiation-induced lymphopenia during definitive thoracic radiotherapy for stage III non-small cell lung cancer. Lymphopenia is defined based on absolute lymphocyte count (ALC) measured from peripheral blood samples. Severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Grade 1: ALC \< lower limit of normal to 800 cells/μL Grade 2: ALC 500 - \<800 cells/μL Grade 3: ALC 200 - \<500 cells/μL Grade 4: ALC \<200 cells/μL The primary analysis will focus on grade ≥3 lymphopenia as the main endpoint. Absolute lymphocyte count nadir (lowest value during treatment) and relative change from baseline are also captured as continuous secondary measures within this outcome.

  From baseline (within 7 days before radiotherapy initiation) to 6 weeks after completion of radiotherapy. ALC is measured at least weekly during radiotherapy, at the end of radiotherapy, and at 4-6 weeks post-radiotherapy.

Study Arms (2)

Cohort 1

Patients whose thymus gland receives a relatively high radiation dose during definitive thoracic radiotherapy for stage III non-small cell lung cancer (NSCLC). High exposure is defined prospectively based on dose-volume histogram parameters - for example, mean thymus dose (Dmean) greater than a pre-specified threshold or V5 (percentage of thymus volume receiving ≥5 Gy) above a predefined cutoff. These patients are also characterized by certain thymus morphologic features (e.g., smaller thymus volume or higher CT density) on pre-treatment planning CT. All patients in this cohort receive standard-of-care radiotherapy (with or without chemotherapy) without any study-specific intervention. The cohort serves as the index group to assess the predictive value of thymus-related parameters for radiation-induced lymphopenia.

Radiation: Definitive Thoracic Radiotherapy

Cohort 2

Patients whose thymus gland receives a relatively low radiation dose during definitive thoracic radiotherapy for stage III non-small cell lung cancer (NSCLC). These patients serve as the control comparison for evaluating the occurrence and severity of radiation-induced lymphopenia. They receive the same standard radiotherapy regimen (with or without chemotherapy) as the high-exposure cohort. No study-specific intervention is applied. This cohort allows determination of whether higher thymus radiation dose is associated with a greater risk of severe lymphopenia after adjusting for other clinical factors.

Radiation: Definitive Thoracic Radiotherapy

Interventions

Definitive Thoracic Radiotherapy RADIATION

Patients with stage III non-small cell lung cancer (NSCLC) receive standard-of-care definitive radiotherapy to the chest, with or without concurrent/sequential chemotherapy. Radiotherapy is delivered using conventional fractionation (typically 1.8-2.0 Gy per fraction, total dose 50-66 Gy) or hypofractionated regimens as per institutional protocols. Treatment planning is performed using intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) For the purposes of this observational study, the radiation dose-volume parameters of the thymus gland (e.g., Dmean, V5Gy, V10Gy, V20Gy) are extracted from each patient's treatment planning system. Morphologic features of the thymus (volume, density, transverse diameter) are measured from planning CT scans.

Also known as: IMRT / VMAT for NSCLC, Chest radiotherapy, Thoracic radiation therapy

Cohort 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This observational study will enroll adult patients with stage III non-small cell lung cancer (NSCLC) who are scheduled to receive definitive thoracic radiotherapy (with or without concurrent/sequential chemotherapy) at participating oncology centers. Patients are identified consecutively from radiation oncology departments during routine pre-radiotherapy planning visits. No experimental treatment or randomization is applied. The study population includes both treatment-naïve patients and those who may have received prior systemic therapy as long as they have not undergone prior thoracic radiotherapy or have persistent grade ≥3 lymphopenia at baseline. The target sample size is determined based on event-per-variable criteria. Both inpatients and outpatients are eligible. Recruitment is performed prospectively over an estimated period of 18-24 months. All enrolled patients must meet the full eligibilit.

You may qualify if:

• Age ≥ 18 years;
• Pathologically or cytologically confirmed primary non-small cell lung cancer (NSCLC) with a clinical stage of III (according to the 8th edition or latest version of the AJCC staging system);
• Eligible for radical radiotherapy or chemoradiotherapy to the chest, with a planned total dose of ≥50 Gy to the chest, using a fractionation schedule of 1.8-2.0 Gy per fraction (conventional fractionation) or a high-dose fractionation regimen permitted by the protocol;
• Planned to undergo periodic blood tests before and after radiotherapy, including absolute lymphocyte count;
• ECOG performance status of 0-2;
• Able to undergo regular follow-up and provide blood samples and imaging evaluations as required by the protocol.

You may not qualify if:

• Previous history of thoracic or whole-body radiation therapy;
• A diagnosis of radiation-induced lymphocytopenia or baseline lymphocytopenia graded ≥ Grade 2 (according to the CTCAE criteria) prior to study enrollment;
• Patients with a history of or known primary immunodeficiency, active autoimmune disease, long-term systemic glucocorticoid therapy (prednisone-equivalent dose \> 10 mg/day), or long-term use of immunosuppressants following organ transplantation;
• History of concurrent malignancy (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that has been treated curatively and has been recurrence-free for at least 5 years);
• Pregnant or lactating women;
• Any other condition deemed by the investigator to render the subject unsuitable for participation in this clinical study, including severe hepatic, renal, hematologic, or other organ dysfunction;
• Irreversible contraindications to the radiotherapy plan or dose delivery.

Sponsors & Collaborators

• You Peimeng: lead

Study Sites (1)

Jiangxi Cancer Hospital

Nanchang, Jiangxi, 330000, China

Location

MeSH Terms

Interventions

Radiotherapy, Intensity-Modulated

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: April 26, 2026
• First Posted: May 4, 2026
• Study Start: April 10, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

CN (1)