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.

Study Overview

• Status: Recruiting
• Conditions: Radiotherapy; Immunotherapy; Small Cell Lung Cancer ( SCLC ); Personalized Cancer Treatment
• Intervention / Treatment: Radiation: radiatherapy, and chemotherapy with or without immunotherapy as clinical practice

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Xuwei Cai, Ph.D; Phone Number: 02122200000; Email: birdhome2000@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Xuwei Cai, Ph.D; Phone Number: 86+021-22200000; Email: chestgcp@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with small-cell lung cancer

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SCLC Clinical Cohort	Radiation: radiatherapy, and chemotherapy with or without immunotherapy as clinical practice; This is an observation study. This study adopted different timing of radio-immunotherapy combination, fractionation schedules, radiation doses, irradiation sites, PCI, and various types of immune checkpoint inhibitors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The time from the start of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first.	up to 12 months after the last participant entry
Overall Survival (OS)	The time from the start of study treatment to death from any cause or the data cut-off date.	up to 12 months after the last participant entry

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant Metastasis-Free Survival	the time from the date of diagnosis to the first occurrence of distant metastasis. For patients with extensive-stage small cell lung cancer (ES-SCLC) who already have distant metastasis at baseline, DMFS is defined as the time to new distant organ metastasis or new distant lesions. Patients who have not developed distant metastasis by the last follow-up are censored.	up to 12 months after the last participant entry
Locoregional Recurrence-Free Survival (LRFS)	The time from the date of diagnosis to the first locoregional disease progression. Patients who have not experienced locoregional events by the last follow-up are censored.	up to 12 months after the last participant entry
Objective Response Rate (ORR)	The percentage of patients achieving a best overall response of complete response (CR) or partial response (PR) during the study period. The evaluable population includes patients with baseline imaging and at least one response assessment (or documented record).	up to 12 months after the last participant entry
Disease Control Rate (DCR)	The percentage of patients achieving a best overall response of CR, PR, or stable disease (SD). The evaluable population includes patients with baseline imaging and at least one response assessment (or documented record).	up to 12 months after the last participant entry
Local Control Rate (LCR)	The start of radiotherapy to the first objective progression within the irradiated target volume, or death, or the last follow-up date.	up to 12 months after the last participant entry

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoint	Correlation of tumor biomarkers (PD-L1, TMB, ctDNA) and peripheral blood inflammatory/immune indices (NLR, PLR, LMR, CRP, LDH, lymphocyte subsets) with antitumor activity (ORR/DCR) and survival (OS, PFS, DMFS, LRFS).	up to 12 months after the last participant entry

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Radiotherapy; Small Cell Lung Cancer (SCLC); Personalized Cancer Treatment
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Therapeutics; Biological Therapy; Immunomodulation; Drug Therapy; Immunotherapy
• Other Study ID Numbers: IS26056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No