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外周血炎性参数对错配修复基因完整型转移性结直肠癌患者免疫治疗疗效和预后的预测价值

Predictive values of peripheral blood inflammatory parameters in the efficacy of immunotherapy and prognosis in patients with proficient mismatch repair metastatic colorectal cancer

    摘要
  • 摘要:
    目的 探讨外周血炎性参数对错配修复基因完整（proficient mismatch repair, pMMR）型转移性结直肠癌（metastatic colorectal cancer, mCRC）患者免疫治疗疗效和预后的预测价值。
    方法 回顾性分析2019年2月至2024年2月在复旦大学附属中山医院厦门医院接受免疫治疗的无手术指征的44例pMMR型mCRC患者的临床资料。收集患者治疗前中性粒细胞/淋巴细胞比值（neutrophil-to-lymphocyte ratio, NLR）、血小板/淋巴细胞比值（platelet-to-lymphocyte ratio, PLR）、泛免疫炎症值（pan-immune-inflammation value, PIV）、全身免疫炎症指数（systemic immune-inflammation index，SII）等外周血炎性参数。绘制受试者工作特征（receiver operating characteristic, ROC）曲线评估炎性参数对免疫治疗疗效的预测价值。以ROC曲线得出的最佳截断值分组，评估炎性参数对免疫治疗预后的影响。采用单因素和多因素Cox比例风险模型分析影响pMMR型mCRC患者预后的危险因素。
    结果 NLR、PLR、PIV和SII对pMMR型mCRC患者的免疫治疗疗效有一定预测价值，SII优于NLR、PLR及PIV。与NLR≥3.36组、PLR≥223.54组和SII≥769.29组患者相比，NLR＜3.36组、PLR＜223.54组和SII＜769.29组患者免疫治疗后疾病控制率（disease control rate, DCR）更高（P＜0.01），NLR＜3.36组及SII＜769.29组患者无进展生存期（progression-free survival, PFS）更长（P＜0.05），NLR＜3.36组、PLR＜223.54组及SII＜769.29组患者总生存期（overall survival, OS）更长（P＜0.05）。单因素分析显示，美国东部肿瘤协作组体力状况（Eastern Cooperative Oncology Group Performance Status, ECOG PS）评分、NLR及SII是影响免疫治疗后PFS的危险因素，肝转移、骨转移、NLR、PLR及SII是影响免疫治疗后OS的危险因素（P＜0.05）；多因素Cox比例风险模型显示，SII≥769.29是pMMR型mCRC患者免疫治疗后预后不良的独立危险因素（P＜0.001）。
    结论 外周血炎性参数NLR、PLR、PIV和SII对pMMR型mCRC患者免疫治疗疗效有一定预测价值，以SII最优；SII≥769.29可独立预测pMMR型mCRC患者免疫治疗后不良预后。

     

    Abstract:
    Objective To explore the values of peripheral blood inflammatory parameters in predicting the efficacy of immunotherapy and prognosis after immunotherapy in patients with proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC).
    Methods The clinical data of 44 inoperable pMMR mCRC patients who received immunotherapy in Zhongshan Hospital (Xiamen Branch), Fudan University from February 2019 to February 2024 were analyzed retrospectively. The pre-treatment peripheral blood inflammatory parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) were collected. The receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of inflammatory parameters on the efficacy of immunotherapy. The effects of inflammatory parameters on the prognosis after immunotherapy were evaluated according to the optimal cutoff value obtained by ROC curves. Univariate and multivariate Cox proportional hazard models were used to analyze the risk factors affecting the prognosis of patients with pMMR mCRC.
    Results NLR, PLR, PIV and SII had some predictive values on the efficacy of immunotherapy in inoperable pMMR mCRC patients, and SII was superior to NLR, PLR and PIV. Compared with NLR≥3.36 group, PLR≥223.54 group and SII≥769.29 group, the disease control rate (DCR) after immunotherapy was higher in the NLR < 3.36 group, PLR < 223.54 group and SII < 769.29 group (P < 0.01); the progression-free survival (PFS) was longer in the NLR < 3.36 group and SII < 769.29 group (P < 0.05), and the overall survival (OS) was longer in the NLR < 3.36 group, PLR < 223.54 group and SII < 769.29 group (P < 0.05). The univariate analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, NLR and SII were risk factors for the PFS of patients after immunotherapy; the liver metastasis, bone metastasis, NLR, PLR and SII were risk factors for the OS of patients after immunotherapy (P < 0.05). The multivariate Cox proportional risk model analysis showed that SII≥769.29 was an independent risk factor for the prognosis of pMMR mCRC patients after immunotherapy (P < 0.001).
    Conclusions Peripheral blood NLR, PLR, PIV and SII could predict the efficacy of immunotherapy in pMMR mCRC patients and SII is superior to NLR, PLR and PIV, and SII≥769.29 has independent predictive value for poor prognosis in pMMR mCRC patients receiving immunotherapy.

     

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