Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Surg Oncol. 2021 Oct;28(11):6189-6198. doi: 10.1245/s10434-021-09975-z. Epub 2021 Apr 19.
Previous studies have reported the utility of systemic inflammatory markers and CD8+ tumor-infiltrating lymphocyte (TIL) separately in predicting response to chemoradiotherapy (CRT) in rectal cancer; however, the efficacy of combining these markers remains unclear.
This study aimed to elucidate the predictive efficacy of systemic inflammatory markers combined with CD8+ TIL density on response to neoadjuvant CRT in locally advanced rectal cancer.
Ten systemic inflammatory markers and CD8+ TIL density were assessed in 267 patients with rectal cancer using pretreatment clinical data and biopsy samples. Response to CRT was determined using the Dworak tumor regression grade (TRG), with good responders classified as TRG3-4.
Receiver operating characteristic curve analysis showed high areas under the curve for the lymphocyte-to-C-reactive protein ratio (LCR) and neutrophil × monocyte (N × M) value (0.58 and 0.62, respectively). In the multivariate analysis, LCR, N × M value, and CD8+ TIL density were independently associated with good responders (p = 0.016, 0.005, and 0.002, respectively). Stratified analysis with these three markers showed a positive correlation between TRG3-4 ratio and the number of positive predictive factors (8.2%, 20.0%, 34.2%, and 59.1% in patients with 0, 1, 2, and 3 predictors, respectively). Overall and disease-free survival were significantly worse in patients with zero factors present compared with those with one to three factors present.
LCR, N × M value, and CD8+ TIL density are independently associated with response to CRT. Assessing local TIL density along with systemic inflammatory markers may be useful for selecting a multimodal neoadjuvant approach in rectal cancer therapy.
先前的研究报告称，全身炎症标志物和 CD8+肿瘤浸润淋巴细胞（TIL）分别可用于预测直肠癌放化疗（CRT）的疗效；然而，联合这些标志物的疗效尚不清楚。
本研究旨在阐明全身炎症标志物联合 CD8+TIL 密度对局部晚期直肠癌新辅助 CRT 反应的预测效果。
使用 267 例直肠癌患者的治疗前临床数据和活检样本，评估了 10 种全身炎症标志物和 CD8+TIL 密度。通过 Dworak 肿瘤消退分级（TRG）来确定 CRT 反应，将良好反应者定义为 TRG3-4。
受试者工作特征曲线分析显示，淋巴细胞与 C 反应蛋白比值（LCR）和中性粒细胞×单核细胞（N×M）值的曲线下面积较高（分别为 0.58 和 0.62）。多变量分析显示，LCR、N×M 值和 CD8+TIL 密度与良好反应者独立相关（p=0.016、0.005 和 0.002）。这三个标志物的分层分析显示，TRG3-4 比例与阳性预测因子的数量之间呈正相关（在患者中分别为 0、1、2 和 3 个预测因子，TRG3-4 比例分别为 8.2%、20.0%、34.2%和 59.1%）。与存在 1 至 3 个因素的患者相比，无因素患者的总生存率和无病生存率明显更差。
LCR、N×M 值和 CD8+TIL 密度与 CRT 反应独立相关。评估局部 TIL 密度与全身炎症标志物一起可能有助于选择直肠癌治疗的多模态新辅助方法。
