Kaira Kyoichi, Ichiki Yoshinobu, Imai Hisao, Kawasaki Tomonori, Hashimoto Kosuke, Kuji Ichiei, Kagamu Hiroshi
Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.
Department of General Thoracic Surgery, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.
Transl Lung Cancer Res. 2024 May 31;13(5):1137-1149. doi: 10.21037/tlcr-24-142. Epub 2024 May 24.
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.
Recently, several studies have explored potential biomarkers for the pathological response after NACI. For example, F-fluorodeoxyglucose positron emission tomography (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) 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 CD4PD-1 cells or natural killer cells and a decrease in CD3CD56CTLA4 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 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.
新辅助化疗免疫疗法（NACI）是可切除非小细胞肺癌（NSCLC）患者的标准治疗方案。尽管据报道NACI后的病理完全缓解（pCR）率超过20%，但尚未确立pCR的最佳预测指标。本综述旨在探讨NACI后pCR的可能预测指标。
我们通过PubMed数据库检索了2018年至2022年间发表的英文研究文章。50项研究被视为相关文章，并对其进行审查以编辑本叙述性综述的信息。
最近，多项研究探索了NACI后病理反应的潜在生物标志物。例如，对可切除NSCLC患者评估了F-氟脱氧葡萄糖正电子发射断层扫描（F-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，以预测NACI后的病理反应。根据PET反应标准，完全代谢缓解（CMR）对预测pCR的阳性预测值（PPV）为71.4%，NACI后治疗后最大标准化摄取值（SUV）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，表现为CD8 T细胞增加，CD3 T细胞或Foxp3 T细胞减少。就血液样本而言，TME表现为CD4PD-1细胞或自然杀伤细胞增加，CD3CD56CTLA4细胞、总T细胞、Th细胞、髓源性抑制细胞（MDSC）或调节性T细胞减少。尽管NACI前ctDNA水平较低以及NACI后ctDNA水平检测不到与生存率显著相关，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。
NACI后F-FDG摄取率降低以及淋巴细胞上与TME相关的表面标志物可能是pCR的最佳预测指标。然而，这些pCR预测指标在NACI中的作用仍未得到充分验证，需要进一步研究。本综述重点关注可切除NSCLC患者NACI后病理反应的预测生物标志物。
