Molecular Subtyping of Extensive Stage Small Cell Lung Cancer and Relevent Clinical Significance

Study Overview
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Brief Summary
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To validate the predictive value of transcriptome-based molecular subtyping of extensive stage small cell lung cancer (SCLC) for the efficacy of programmed death-1(PD-1)/programmed death-ligand1(PD-L1) inhibitor in the first line setting; to explore the differences of immune microenvironment between different SCLC subtypes to reveal the mechanisms of immunotherapy resistance of SCLC

Detailed Description
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This retrospective observational study examines the predictive value of transcriptome-based molecular subtyping of extensive stage SCLC for PD-1/PD-L1 inhibitor efficacy and explores immune microenvironment differences between subtypes to uncover immunotherapy resistance mechanisms. Patients with extensive stage SCLC receiving first-line standard treatment are enrolled, and baseline tumor tissue and peripheral blood samples are collected for transcriptome sequencing and immunohistochemistry (IHC). Based on results, patients are classified into four molecular subtypes, and treatment efficacy and safety are recorded. The study compares the efficacy between SCLC subtypes to determine if molecular typing predicts immunotherapy efficacy and investigates immune microenvironment differences between subtypes to uncover resistance mechanisms. Treatment regimens follow first-line extensive stage SCLC guidelines, including cisplatin+etoposide or carboplatin+etoposide and PD-(L)1 inhibitors, with options determined by the supervising physician.

Official Title
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Molecular Subtyping of Extensive Stage Small Cell Lung Cancer and Relevent Clinical Significance

Conditions
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SCLC,Extensive Stage

Intervention / Treatment
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* Drug: PD-(L)1 antibody immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The enrolled subjects shall meet all the following conditions at the same time. Male or female, aged 18 to 100 years Patients with untreated advanced small cell lung cancer clearly diagnosed by histopathology Be able to provide tumor biopsy tissue sample for molecular analysis Eastern Cooperative oncology Group (ECOG) score: 0 2 Expected survival of more than 3 months. Has at least 1 measurable or evaluable tumor lesion with a longest diameter ≥ 10 mm at baseline (in case of lymph nodes, a shortest diameter ≥ 15 mm is required) according to RECIST v1.1 Received first-line chemotherapy or chemotherapy＋PD-(L)1 inhibitor and be able to provide complete treatment information and efficacy evaluation results. Voluntary signed informed consent and expected good compliance. Exclusion Criteria: Those meeting any of the following conditions may not be included. Patient unable to tolerate chemotherapy. Patients unable to provide tumor tissue samples for testing Patients with other malignant tumors or a history of other malignant tumors Patients have any other reason to be unfit to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| immunotherapy cohort<br>Extensive stage SCLC patients receiving first-line chemotherapy plus PD-(L)1 antibody treatment will be enrolled in this cohort. Baseline tumor tissue samples and peripheral blood samples will be collected for transcriptome and immunohistochemistry analysis etc. | Drug: PD-(L)1 antibody immunotherapy<br>* The treatment regimen involved in this study follows guidelines for the first-line treatment of extensive stage SCLC: cisplatin+etoposide or carboplatin+etoposide and PD-(L)1 inhibitor.<br>|
| chemotherapy cohort<br>Extensive stage SCLC patients receiving only first-line etoposide plus platinum chemotherapy will be enrolled in this cohort. Baseline tumor tissue samples and peripheral blood samples will be collected for transcriptome and immunohistochemistry analysis etc. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | From the start of first-line treatment until disease progression or death due to any cause | 2022.4.1-2023.12.31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the start of first-line treatment until death due to any cause | 2022.4.10-2024.12.31 | 
| Objective response rate | The tumor size was calculated by computed tomography or magnetic resonance Imaging scan, the best response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECISTVersion1.1) | 2022.4.10-2023.12.31 | 
| molecular subtyping and tumor microenvironment biomarkers | The molecular subtyping was carried out based on transcripsome sequencing following the method in published article PMID: 33482121, the tumor microenvironment biomarkers include tumor infiltrated immune cells and specific gene expression evaluated by transcripsome and Multiplex immunohistochemical analysis etc. | 2022.4.10-2023.12.31 |