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局部晚期宫颈癌新辅助化疗病理反应的评估。

Evaluation of pathological response to neoadjuvant chemotherapy in locally advanced cervical cancer.

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Department of Pathology, Sun Yat-sen University Cancer Center, 651# Dong Feng Road East, Guangzhou, 510060, Guangdong, China.

出版信息

J Transl Med. 2024 Jul 14;22(1):655. doi: 10.1186/s12967-024-05482-3.

Abstract

Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.

摘要

新辅助化疗(NACT)是局部晚期宫颈癌(LACC)患者的一种可行的治疗选择。然而,影响病理反应的因素仍存在争议。我们收集了 185 例接受 NACT 前后的 LACC 患者的配对标本,并进行了组织学评估。从整个队列中选择了 8 例治疗前的新鲜组织进行免疫基因表达谱分析。通过综合评估肿瘤床中存活肿瘤、炎症基质、纤维性基质和坏死的百分比,建立了一种新的病理分级系统。然后,根据 NACT 后病理反应的好坏,将 185 例患者分为良好病理反应(GPR)组和不良病理反应(PPR)组,其中 134 例(72.4%,134/185)患者达到 GPR。治疗前肿瘤浸润淋巴细胞(TILs)和肿瘤浸润淋巴细胞体积(TILV)的增加与 GPR 相关,TILV 是 GPR 的独立预测因素。此外,CIBERSORT 分析显示 cPR 和非 cPR 组之间免疫标志物的表达存在显著差异。此外,GPR 组 CD8+T 细胞密度升高,FOXP3+T 细胞密度降低,与 PPR 相比差异有统计学意义。重要的是,表现为 GPR 或炎症型的患者总生存和无病生存均得到改善。值得注意的是,在多因素分析中,基质型是独立的预后因素。我们的研究表明,治疗前标本中 TILV 的升高可能预示着对 NACT 的良好反应,而治疗后标本中基质型是独立的预后因素。此外,我们提出了这种 NACT 患者的病理分级系统,可能为治疗反应和预后提供更全面的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da11/11247755/7a8d7eda7c12/12967_2024_5482_Fig1_HTML.jpg

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