Prediction of Response to PD-L1 Inhibitor After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer Using Multi-omics-based Liquid Biopsy

Inclusion Criteria:

1. Age 18-75 years, male or female;

2. Histologically or cytologically confirmed limited-stage small cell lung cancer (LS-SCLC) (AJCC, 8th edition);

3. No more than 2 cycles of chemotherapy or no previous systemic therapy;

4. ECOG PS 0-1;

5. Measurable disease, as defined by RECIST v1.1 (tumor lesions long axis≥10mm,lymph nodes short axis ≥15mm);

6. Life expectancy ≥3 months;

7. Adequate pulmonary function;

8. Adequate hematologic and end-organ function, defined by the following criteria:

9. Hematology

• Hemoglobin (HGB) ≥90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L;
• Platelet count (PLT) ≥ 100 x 10^9/L;
• White blood cell count (WBC) ≥ 3.0 x 10^9/L;

2. Serum chemistry

• Serum albumin (ALB) ≥ 30 g/L;

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 xULN;

• Total bilirubin (TBIL) ≤1.5 ULN; Note: Patients diagnosed with Gilbert'ssyndrome (persistent or recurrent hyperbilirubinemia [mainly unconjugatedbilirubin] without evidence of hemolysis or liver pathology) afterconsultation with their physician can be allowed;

• Creatinine ≤ 1.5 ULN;

9. Women of childbearing age must have taken reliable contraceptive measures orundergone a negative pregnancy test (serum or urine) within 7 days prior toenrollment. Both men and women of childbearing age must agree to maintainadequate contraceptive measures throughout the study and for 6 months followingthe completion of treatment;

10. Patients must voluntarily participate in this study, sign the informed consentform, demonstrate good compliance, and actively cooperate with follow-upprocedures.

Exclusion Criteria:

1. Histological mixture of SCLC and NSCLC components;

2. Extensive-stage SCLC;

3. Patients with a history of allogeneic organ transplantation or allogeneichematopoietic stem cell transplantation, or those planned for transplantation;

4. Treatment with immunosuppressive medications (including but not limited toprednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, andanti-tumor necrosis factor agents) within 14 days prior to the first dose ofPD-L1 inhibitor, except for intranasal and inhaled corticosteroids or low-dosesystemic steroids (i.e., ≤10 mg/day prednisolone or equivalent);

5. History of hypersensitivity to etoposide, cisplatin, PD-L1 antibody, orexcipients in the formulation; or history of severe allergic reactions to othermonoclonal antibodies;

6. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation ofstudy treatment, or anticipation of need for such a vaccine during studytreatment;

7. Active or history of autoimmune disease or immune deficiency (including but notlimited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis,hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism);

Note:

• Patients with vitiligo or alopecia are eligible for this study;

• Patients with stable hypothyroidism undergoing hormone replacement therapy (e.g.,Hashimoto's syndrome) are eligible for this study;

8. Poorly controlled asthma despite systemic treatment, such asbronchodilators; Note: Patients with complete remission of asthma duringchildhood and no need for any intervention in adulthood can be allowed;

9. Urinalysis shows proteinuria ≥ ++ or confirmed 24-hour urine protein ≥ 1.0g;

10. Malignancies other than LS-SCLC, with the following exceptions:

• Adequately treated basal or squamous cell skin cancer or carcinoma in situ of thecervix;

• Malignancy that has been treated with curative intent, with no known active diseasefor ≥5 years prior to the first dose of the study treatment, and with a lowpotential risk of recurrence;

11. Human immunodeficiency virus (HIV) infection or known to have acquiredimmunodeficiency syndrome (AIDS);

12. Significant cardiovascular disease within 6 months prior to enrollment,such as myocardial infarction, severe/unstable angina, New York HeartAssociation cardiac disease (class II or greater), poorly controlledarrhythmias (including QTcF interval >450 ms for males and >470 ms forfemales, with QTcF interval calculated using the Fridericia formula), andsymptomatic congestive heart failure;

13. Severe infections within 4 weeks prior to first dose of study treatment,including but not limited to infections requiring intravenous antibiotics,antifungal, or antiviral agents , or unexplained fever ≥38.5°C occurringduring the screening period or before the first dose of the studytreatment;

14. Active tuberculosis, hepatitis B (HBV-DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit ofdetection of the assay), or co-infection with both hepatitis B and C;

15. Treatment with any other investigational agent with therapeutic intentwithin 4 weeks prior to the first dose of the study treatment;

16. History of abuse of psychotropic drugs or drug addiction;

17. Patients with other severe physical or mental illnesses or abnormallaboratory test results that may increase the risk of participating in thestudy, or interfere with the study results, as well as those whom theinvestigator deems unsuitable for participation in the study for otherreasons.