Abstract
Background
Patients with unresectable stage IIIB/C-IV non-squamous non-small cell lung cancer (NSCLC) lacking driver mutations (EGFR/ALK/ROS1/RET/BRAF/MET) face limited treatment options. This single-center prospective exploratory pilot case series, limited to a small pre-selected cohort, aims to descriptively characterize real-world efficacy, survival signals and safety profiles of sequential platinum-doublet chemotherapy followed by individualized stereotactic body radiotherapy (SBRT) combined with tislelizumab; this work cannot draw definitive therapeutic conclusions and only generates preliminary hypothesis-building observations.
Methods
This exploratory pilot case series enrolled only patients who maintained disease control after 4-cycle platinum-based chemotherapy (introducing notable selection bias favoring chemo-sensitive tumors). Individualized SBRT with heterogeneous dose/fractionation schemes (3–10 Gy/fx) was delivered to metastatic lesions, with tislelizumab 200 mg q3w initiated within five SBRT fractions and maintained until progression or intolerable toxicity. We added standardized multi-modal toxicity surveillance and grading-based intervention protocols for differentiating radiation versus immune pneumonitis. Endpoints were analyzed purely for descriptive purposes, including 1-year PFS rate, median PFS, OS, ORR, DCR, and treatment-related adverse events (TRAEs).
Results
The 1-year PFS rate was 25%. The median PFS was 10.14 months (95%CI: 3.65–17.38). Median OS was 26.89 months (95%CI: 17.68–30.19), with 1-year and 2-year OS rates of 100% and 62.5%, respectively. The best overall response rate (BOR), defined as the best response recorded from the start of treatment until disease progression or initiation of new anticancer therapy, was 87.5%, with 7 patients achieving partial response (PR) and 1 patient achieving stable disease (SD) as best response. At the fixed 1-year time point, the ORR was 12.5% (1/8 patients in PR) and the DCR was 100% (1 patient in PR and 7 patients in SD). Treatment-related adverse events (TRAEs) were observed in all patients (100%). The incidence of grade ≥3 TRAEs was 62.5%.
Conclusion
This small exploratory case series provides only preliminary, hypothesis-generating signals regarding the feasibility of sequential SBRT and tislelizumab after chemotherapy in selected patients with advanced nsNSCLC. The observed efficacy and safety data are insufficient to establish definitive conclusions or clinical recommendations. These findings require rigorous validation in larger, controlled trials before any therapeutic inference can be drawn.