Establishment of a Prospective Clinical Cohort of Small Cell Lung Cancer Patients Receiving Radiotherapy-Involved Comprehensive Treatment

Establishment of a Prospective Clinical Cohort of Small Cell Lung Cancer Patients Receiving Radiotherapy-Involved Comprehensive Treatment

By establishing a prospective clinical cohort for small cell lung cancer (SCLC) and systematically collecting high-quality real-world data integrating clinical, imaging, pathological, and molecular dimensions, this study aims to enable personalized treatment for distinct SCLC subtypes. Furthermore, by evaluating the influence of radiotherapy timing, dose and fractionation, and target selection on efficacy and toxicity, we aim to identify the optimal radio-immunotherapy combination regimen that maximizes the synergistic effect in SCLC patients.

Inclusion Criteria:

Inclusion Criteria for Limited-Stage Small Cell Lung Cancer (LS-SCLC):

1. Voluntary signed informed consent according to clinical routine practice. 2. Histologically and radiologically confirmed, previously untreated limited-stage SCLC (according to the Veterans Administration Lung Study Group staging system).

3. Age ≥ 18 years. 4. Life expectancy ≥ 8 weeks. 5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. 6. At least one documented efficacy assessment. 7. At least one measurable lesion as confirmed by the investigator according to RECIST (iRECIST 2017) criteria.

8. Adequate organ and bone marrow function, with laboratory tests performed within 7 days prior to the first dose meeting the following criteria (without receiving any blood components, hematopoietic growth factors, albumin, or other corrective therapies considered by the investigator within 14 days prior to laboratory assessments):

1. Hematology: Hemoglobin (Hb) ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 90 × 10⁹/L.
2. Biochemistry: Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN); serum total bilirubin (TBIL) ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN in patients without liver metastases, or ≤ 5.0 × ULN in patients with liver metastases; serum albumin (ALB) ≥ 25 g/L.
3. Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN; prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (for patients receiving prophylactic anticoagulation, the INR and APTT values should be judged by the treating physician or investigator to be within a safe and effective therapeutic range).

9. Pulmonary function test showing FEV₁ > 0.75 L. 10. No evidence of severe interstitial lung disease confirmed by CT or PET/CT prior to treatment.

11. No prior or concurrent primary malignancy at other sites. 12. No requirement for PD-L1 expression level.

Inclusion Criteria for Extensive-Stage Small Cell Lung Cancer (ES-SCLC):

1. Voluntary signed informed consent according to clinical routine practice. 2. Histologically confirmed SCLC with complete staging workup showing extensive-stage disease (according to the Veterans Administration Lung Study Group staging system).

3. Age ≥ 18 years. 4. Life expectancy ≥ 8 weeks. 5. At least one documented efficacy assessment. 6. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. 7. Adequate organ and bone marrow function, with laboratory tests performed within 7 days prior to the first dose meeting the following criteria (without receiving any blood components, hematopoietic growth factors, albumin, or other corrective therapies considered by the investigator within 14 days prior to laboratory assessments):

1. Hematology: Hemoglobin (Hb) ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 90 × 10⁹/L.
2. Biochemistry: Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN); serum total bilirubin (TBIL) ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN in patients without liver metastases, or ≤ 5.0 × ULN in patients with liver metastases; serum albumin (ALB) ≥ 25 g/L.
3. Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN; prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (for patients receiving prophylactic anticoagulation, the INR and APTT values should be judged by the treating physician or investigator to be within a safe and effective therapeutic range).

8. No severe concurrent medical illness. 9. Forced expiratory volume in one second (FEV₁) > 0.75 L. 10. For patients with prior radiotherapy to the primary lesion, the current radiotherapy target is limited to metastatic lesions.

11. No prior or concurrent primary malignancy at other sites. 12. No requirement for PD-L1 expression level. 13. For patients with limited-stage SCLC who previously received curative-intent treatment, upon recurrence or metastasis, if complete staging workup is available and this is their first use of immunotherapy, they may still be considered for inclusion in the extensive-stage cohort.

Exclusion Criteria:

Exclusion Criteria for Limited-Stage Small Cell Lung Cancer (LS-SCLC):

1. Histologically confirmed non-small cell lung cancer (NSCLC).
2. No efficacy assessment record, or missing efficacy assessment data.
3. Presence of other primary malignancies; history of allogeneic organ transplantation.
4. Major surgery (excluding diagnostic biopsy) within 4 weeks prior to the first dose.
5. History of substance abuse (e.g., drug addiction), long-term alcoholism, or AIDS or HIV carrier.
6. Active autoimmune disease, or history of autoimmune disease with potential for relapse.
7. Current systemic corticosteroid therapy (e.g., equivalent to >10 mg prednisone daily) or use of any other form of immunosuppressive therapy within 14 days prior to the first dose.
8. Prior treatment with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints), including but not limited to PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3.
9. Interstitial lung disease (ILD) or history of ILD requiring corticosteroid therapy.
10. History of idiopathic pulmonary fibrosis (IPF), drug-induced pneumonitis, organizing pneumonia (e.g., bronchiolitis obliterans), idiopathic pneumonia, or evidence of active pneumonitis on screening chest CT.
11. Receipt of live vaccine within 28 days prior to the first dose of study drug.
12. Any other disease or condition that contraindicates chemoradiotherapy, including but not limited to active infection, within 6 months post-myocardial infarction, symptomatic heart disease (including unstable angina, congestive heart failure, or uncontrolled arrhythmias), and immunosuppressive therapy.
13. Unresolved toxicity of Grade 2 or higher (according to CTCAE version 5.0).
14. Pregnant or breastfeeding women; men or women of childbearing potential who are unwilling to use adequate contraceptive measures.
15. Evidence of inherited bleeding diathesis or coagulation disorders.
16. Prior history of malignancy (excluding skin cancer, or in situ breast cancer, oral cancer, or cervical cancer with life expectancy >3 years).

Exclusion Criteria for Extensive-Stage Small Cell Lung Cancer (ES-SCLC):

1. Pulmonary carcinoid or non-small cell lung cancer, unless transformed SCLC is ruled out.
2. No efficacy assessment record, or missing efficacy assessment data.
3. History of severe anaphylactic/allergic reaction to humanized antibodies or fusion proteins.
4. Acute exacerbation of chronic obstructive pulmonary disease (COPD) or other pulmonary diseases requiring hospitalization.
5. Active or prior autoimmune disease (within the past 2 years) or history of primary immunodeficiency.
6. Progression after immunotherapy; prior or concurrent diagnosis of any other malignancy, excluding non-melanoma skin cancer or carcinoma in situ of the cervix.
7. Any other disease or condition that contraindicates chemoradiotherapy, including but not limited to active infection, within 6 months post-myocardial infarction, symptomatic heart disease (including unstable angina, congestive heart failure, or uncontrolled arrhythmias), or immunosuppressive therapy.
8. Unresolved toxicity of Grade 2 or higher (according to CTCAE version 5.0).
9. Current or prior history of autoimmune disease or immunodeficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, and rheumatoid arthritis.
10. History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonia; or evidence of active pneumonitis on chest CT scan. Patients with a history of radiation pneumonitis (fibrosis) within the radiation field may be enrolled.
11. Pregnant or breastfeeding women; men or women of childbearing potential who are unwilling to use adequate contraceptive measures.