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可切除非小细胞肺癌新辅助化免疫治疗后病理反应的潜在预测因素:一篇叙述性综述

英文原题:Potential predictors of the pathologic response after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a narrative review.

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Potential predictors of the pathologic response after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a narrative review.

PubMed 2024/05/24(内容时间) Transl Lung Cancer Res Q2 · IF 3.4(JCR 2025)

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研究概要

NACI 后 18F-FDG 摄取率降低以及淋巴细胞上 TME 相关表面标志物可能是 pCR 的最佳预测因子。然而,这些 pCR 预测因子在 NACI 中的作用仍缺乏充分验证,值得进一步研究。本综述聚焦于可切除非小细胞肺癌患者 NACI 后病理反应的预测性生物标志物。

研究思路结论见上方概要

新辅助化疗免疫治疗(NACI)是可切除非小细胞肺癌(NSCLC)患者的标准治疗。尽管据报道NACI后的病理完全缓解(pCR)率超过20%,但pCR的最佳预测因子尚未确立。本综述旨在探讨NACI后pCR的可能预测因子。

我们通过PubMed数据库识别了2018年至2022年间发表的英文研究文章。50项研究被认为是相关文章,并对其进行了审查,以编辑本叙述性综述的信息。关键内容与发现:近期,多项研究探索了NACI后病理反应的潜在生物标志物。例如,18F-氟脱氧葡萄糖正电子发射断层扫描(18F-FDG-PET)成像、肿瘤微环境(TME)、循环肿瘤DNA(ctDNA)等基因改变,以及中性粒细胞与淋巴细胞比值(NLR)和吸烟特征等临床标志物,均在可切除NSCLC患者中进行了评估,以预测NACI后的病理反应。基于PET反应标准,完全代谢反应(CMR)对预测pCR的阳性预测值(PPV)为71.4%,且NACI后治疗后最大标准化摄取值(SUVmax)的下降率与主要病理反应(MPR)显著相关。TME作为肿瘤标本中MPR的重要标志物,被确定为CD8+ T细胞增加以及CD3+ T细胞或Foxp3 T细胞减少。就血液样本而言,TME包括CD4+PD-1+细胞或NK 细胞增加,以及CD3+CD56+CTLA4+细胞、总T细胞、Th细胞、髓源性抑制细胞(MDSCs)或调节性T细胞减少。尽管治疗前ctDNA低水平以及NACI后ctDNA水平不可检测与生存显著相关,但ctDNA水平与pCR之间的关系仍不明确。此外,基线NLR高的患者pCR发生率低。重度吸烟(>40包年)有利于预测病理反应。

展开英文摘要原文

Neoadjuvant chemoimmunotherapy (NACI) is the standard of care for patients with resectable non-small cell lung cancer (NSCLC). Although the pathological complete response (pCR) after NACI reportedly exceeds 20%, an optimal predictor of pCR is yet to be established. This review aims to examine the possible predictors of pCR after NACI.

We identified research article published between 2018 and 2022 in English by the PubMed database. Fifty research studies were considered as relevant article, and were examined to edit information for this narrative review. KEY CONTENT AND FINDINGS: Recently, several studies have explored potential biomarkers for the pathological response after NACI. For example, 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) imaging, tumor microenvironment (TME), genetic alternation such as circulating tumor DNA (ctDNA), and clinical markers such as neutrophil-to-lymphocyte ratio (NLR) and smoking signature were assessed in patients with resectable NSCLC to predict the pathological response after NACI. Based on the PET response criteria, the complete metabolic response (CMR) achieved a positive predictive value (PPV) of 71.4% for predicting pCR, and the decreasing rate of post-therapy maximum standardized uptake value (SUV max ) after NACI substantially correlated with the major pathological response (MPR). TME, as a significant marker for MPR in tumor specimens, was identified as an increase in CD8 + T cells and decrease in CD3 + T cells or Foxp3 T cells. Considering blood samples, TME comprised an increase in CD4 + PD-1 + cells or natural killer cells and a decrease in CD3 + CD56 + CTLA4 + cells, total T cells, Th cells, myeloid-derived suppressor cells (MDSCs), or regulatory T cells. Although low pretreatment levels of ctDNA and undetectable ctDNA levels after NACI were markedly associated with survival, the relationship between ctDNA levels and pCR remains elusive. Moreover, the patients with a high baseline NLR had a low incidence of pCR. Heavy smoking (>40 pack-years) was favorable for predicting pathological response.

A reduced rate of 18 F-FDG uptake post-NACI and TME-related surface markers on lymphocytes could be optimal predictors for pCR. However, the role of these pCR predictors for NACI remains poorly validated, warranting further investigations. This review focuses on predictive biomarkers for pathological response after NACI in patients with resectable NSCLC.

论文信息

作者
Kaira K、Ichiki Y、Imai H、Kawasaki T、Hashimoto K、Kuji I、Kagamu H
单位
Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.Japan
文献类型
综述
期刊
Translational lung cancer research2024 May 31
原文标识
PubMed 38854945 · DOI 10.21037/tlcr-24-142