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

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.