Xia Gan, Zhengzheng Yu, Lin Zhang, Wenji Xie, Xiaowen Sun, Yue Li, Jianing Fang, Yanxian Li, Yating Liu, Zhongjie Liu, Yaning Tang, Can Zhou, Zhuolong Xie, Wen Yao, Shuyu Ouyang, Jing Zhang, Pan Chen, Hui Wang, Huai Liu
iICIs was associated with longer PFS, substantial pre-radiotherapy downstaging and tumor-volume reduction. Post-induction volumetrics provided independent prognostic stratification and may inform individualized decisions within the iICIs strategy.
BACKGROUND: Induction chemoimmunotherapy combined with definitive chemoradiotherapy (CRT) represents a promising approach for unresectable stage III non-small cell lung cancer (NSCLC). Nevertheless, the safety, efficacy, and prognostic markers for this treatment regimen remain to be established.
METHODS: This single-center retrospective cohort included unresectable stage III NSCLC treated with definitive thoracic radiotherapy plus immune checkpoint inhibitors (ICIs) from January 2020 to October 2022. Patients receiving chemo-immunotherapy before radiotherapy were classified as induction ICIs (iICIs), and those receiving immunotherapy after thoracic CRT as consolidation ICIs (cICIs). The primary endpoint was progression-free survival (PFS). Propensity score matching (1:1) was performed. TNM restaging and CT-based tumor volume were assessed before radiotherapy in the iICIs group.
RESULTS: Among 168 patients treated with definitive radiotherapy (iICIs, n = 111; cICIs, n = 57), with a median follow-up of 48.2 months, median PFS was longer with iICIs (35.6 vs 23.7 months; p = 0.035) and remained longer after matching (36.1 vs 22.9 months; p = 0.019), while overall survival was similar. Grade ≥ 3 pneumonitis occurred 3.6% and 5.2% in the iICIs and cICIs groups, respectively. In the iICIs group, downstaging after induction therapy was observed (T4: 56.3%→14.6%; stage IIIC: 22.2%→2.9%), with median gross tumor volume reduced from 101.3 to 32.3 cm3 (median relative reduction: 60.9%). Larger post-induction residual tumor volume independently predicted shorter PFS (HR = 2.12; p = 0.032), whereas greater tumor-volume reduction independently predicted longer PFS (HR = 0.38; p = 0.002) and OS (HR = 0.26; p = 0.001).
CONCLUSIONS: iICIs was associated with longer PFS, substantial pre-radiotherapy downstaging and tumor-volume reduction. Post-induction volumetrics provided independent prognostic stratification and may inform individualized decisions within the iICIs strategy.