Lung cancer (Amsterdam, Netherlands) · 2026
Treatment-stratified associations of pathological complete response with survival in resected limited-stage small cell lung cancer: A multicenter retrospective study with exploratory spatial immune profiling.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Liu Zhulin, Zhu Yin, Bi Wanda, Han Zhaojie, Xing Xiangju, Lu Conghua, Liu Ying, Yang Zhenzhou, Xia Yang, Li Li
Аннотация
BACKGROUND: Neoadjuvant immunochemotherapy achieves higher pathological complete response (pCR) rates than chemotherapy alone in limited-stage small cell lung cancer (LS-SCLC), but whether pCR carries similar prognostic information across treatment modalities is uncertain.
PATIENTS AND METHODS: This multicenter retrospective cohort study included 85 patients with stage I-III LS-SCLC who underwent radical resection after neoadjuvant immunochemotherapy (NIC, n = 28) or chemotherapy (NC, n = 57). pCR rates were compared between regimens, and treatment-stratified associations of pCR with event-free survival (EFS) and overall survival (OS) were assessed. Treatment-by-pCR interactions were examined using Firth-penalized Cox models. Seven-plex multiplex immunofluorescence (mIF) in nine purposively selected specimens and two public transcriptomic cohorts provided exploratory immune context.
RESULTS: The pCR rate was 35.7% for NIC and 14.0% for NC (P = 0.022). At a median NIC follow-up of 21.1 months, pCR was associated with longer EFS (NR vs 20.3 months, P = 0.007). No corresponding association was detected in the NC group (18.0 vs 19.8 months, P = 0.892). The treatment-by-pCR interaction was significant (Firth-penalized Cox, P = 0.004), indicating that the association between pCR and EFS differed between treatment groups. In the descriptive mIF analysis, both selected NIC pCR specimens showed an immune-hot phenotype, characterized by the highest CD8 + T cell infiltration among the specimens examined and lower PD-1 exhaustion than the NIC non-pCR specimens. Higher antitumor immune scores were associated with longer OS in GSE60052.
CONCLUSIONS: In this selected surgical cohort, pCR was more frequent after NIC than NC and showed different EFS associations across treatment groups in exploratory analyses. Both examined NIC pCR specimens were immune-hot, but these mIF observations are hypothesis-generating and cannot establish a mechanism. These findings require prospective validation.
PATIENTS AND METHODS: This multicenter retrospective cohort study included 85 patients with stage I-III LS-SCLC who underwent radical resection after neoadjuvant immunochemotherapy (NIC, n = 28) or chemotherapy (NC, n = 57). pCR rates were compared between regimens, and treatment-stratified associations of pCR with event-free survival (EFS) and overall survival (OS) were assessed. Treatment-by-pCR interactions were examined using Firth-penalized Cox models. Seven-plex multiplex immunofluorescence (mIF) in nine purposively selected specimens and two public transcriptomic cohorts provided exploratory immune context.
RESULTS: The pCR rate was 35.7% for NIC and 14.0% for NC (P = 0.022). At a median NIC follow-up of 21.1 months, pCR was associated with longer EFS (NR vs 20.3 months, P = 0.007). No corresponding association was detected in the NC group (18.0 vs 19.8 months, P = 0.892). The treatment-by-pCR interaction was significant (Firth-penalized Cox, P = 0.004), indicating that the association between pCR and EFS differed between treatment groups. In the descriptive mIF analysis, both selected NIC pCR specimens showed an immune-hot phenotype, characterized by the highest CD8 + T cell infiltration among the specimens examined and lower PD-1 exhaustion than the NIC non-pCR specimens. Higher antitumor immune scores were associated with longer OS in GSE60052.
CONCLUSIONS: In this selected surgical cohort, pCR was more frequent after NIC than NC and showed different EFS associations across treatment groups in exploratory analyses. Both examined NIC pCR specimens were immune-hot, but these mIF observations are hypothesis-generating and cannot establish a mechanism. These findings require prospective validation.