治疗分层的病理完全缓解与可切除局限期小细胞肺癌生存的关联：一项具有探索性空间免疫特征的多中心回顾性研究
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.
作者
作者单位
- Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
- Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
- State Key Laboratory of Trauma and Chemical Poisoning, Department of Trauma Medical Center, Daping Hospital, Army Medical University, Chongqing, China.
- Department of Thoracic Surgery, Southwest Hospital, Army Medical University, Chongqing, China.
- Department of Respiratory Medicine, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
- Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
- Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: yangzz@cqmu.edu.cn.
- Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: yxia@zju.edu.cn.
- Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China. Electronic address: dpyyhxlili@tmmu.edu.cn.
摘要
中文
新辅助免疫化疗在局限期小细胞肺癌（LS-SCLC）中比单纯化疗获得更高的病理完全缓解（pCR）率，但pCR是否在不同治疗方式中携带相似的预后信息尚不确定。这项多中心回顾性队列研究包括85名在新辅助免疫化疗（NIC，n = 28）或化疗（NC，n = 57）后接受根治性切除术的I-III期LS-SCLC患者。比较了不同方案之间的pCR率，并评估了治疗分层的pCR与无事件生存期（EFS）和总生存期（OS）的关联。使用Firth惩罚Cox模型检查了治疗与pCR的交互作用。在9个有目的选择的标本中进行了七重多重免疫荧光（mIF），两个公共转录组队列提供了探索性免疫背景。NIC的pCR率为35.7%，NC为14.0%（P = 0.022）。在中位NIC随访21.1个月时，pCR与更长的EFS相关（NR vs 20.3个月，P = 0.007）。在NC组未检测到相应的关联（18.0 vs 19.8个月，P = 0.892）。治疗与pCR的交互作用显著（Firth惩罚Cox，P = 0.004），表明pCR与EFS之间的关联在不同治疗组间存在差异。在描述性mIF分析中，两个选定的NIC pCR标本均显示免疫热表型，其特征在于所检查标本中最高的CD8+ T细胞浸润和低于NIC非pCR标本的PD-1耗竭。较高的抗肿瘤免疫评分与GSE60052中的较长OS相关。在这个选定的手术队列中，NIC后的pCR比NC更常见，并且在探索性分析中显示出跨治疗组的差异EFS关联。两个检查的NIC pCR标本均为免疫热，但这些mIF观察结果是假设生成的，不能确定机制。这些发现需要前瞻性验证。
English
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. 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. 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. 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.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区