This randomized controlled trial investigated the efficacy and safety of argon-helium cryoablation combined with PD-1 inhibitors compared to PD-1 inhibitors plus chemotherapy for treating non-small cell lung cancer (NSCLC). The study aimed to evaluate differences in survival, tumor response, immune function, and adverse events.

This was a single-center, open-label, randomized controlled trial conducted at the First Hospital of Hebei Medical University, China. Sixty patients with advanced non-small cell lung cancer (NSCLC) were enrolled between December 2020 and December 2023. Patients were randomly assigned (1:1) to either a study group (argon-helium cryoablation combined with PD-1 inhibitor, Camrelizumab) or a control group (PD-1 inhibitor, Camrelizumab, combined with platinum-based doublet chemotherapy). Argon-helium cryoablation was performed prior to PD-1 inhibitor administration in the study group. Both groups received 4 cycles of systemic therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), changes in immune function markers (CD4+, CD8+, CD4+/CD8+ ratio), and adverse reactions. Patients were followed for up to 1 year. The study aimed to determine if combining cryoablation with PD-1 inhibition offers superior outcomes compared to standard chemo-immunotherapy in NSCLC.

Inclusion Criteria:

• Pathologically confirmed NSCLC, stage IIIB, IIIC, or IV (AJCC 8th Edition);
• At least one measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);
• Estimated survival time ≥6 months;
• Receiving argon-helium cryoablation combined with PD-1 inhibitor for the first time at our institution (for study group) or standard chemo-immunotherapy (for control group);
• Unable or unwilling to undergo surgical resection for various reasons;
• Karnofsky Performance Status (KPS) score ≥60;
• Conscious and capable of effective communication;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

Exclusion Criteria:

• Presence of other active malignant tumors;
• Significant uncontrolled hepatic (total bilirubin >1.5 × upper limit of normal [ULN], AST/ALT >2.5 × ULN or >5 × ULN if liver metastases present) or renal dysfunction (creatinine clearance <50 mL/min);
• Non-primary NSCLC (i.e., metastatic from another site);
• Known allergy or contraindication to study drugs or inability to comply with the treatment plan;
• Coexisting active tuberculosis, uncontrolled systemic infections, or other significant pulmonary diseases that would interfere with treatment or outcome assessment;
• Pregnancy or lactation;
• Severe psychiatric disorders;
• Uncorrected coagulation disorders (e.g., INR >1.5 or platelet count <75 × 109/L);
• Known immunodeficiency syndromes (e.g., HIV infection);
• Symptomatic hemorrhagic pleural effusion requiring urgent intervention;
• Patients who withdrew consent before randomization or were deemed non-compliant by investigators.