2017版美国国立综合癌症网络结直肠癌指南更新解读

Interpretation of the updates of NCCN 2017 version 1.0 guideline for colorectal cancer

2017版美国国立综合癌症网络（NCCN）结直肠癌指南更新了数点内容．其中4个方面的内容是有可能改变临床实践的：（1）早期结直肠癌根治术后建议服用低剂量阿司匹林作为“癌症二级预防”措施。（2）可切除肝／肺转移瘤的新辅助化疗方案中删除靶向药物。这也许是由于西妥昔单抗和贝伐珠单抗在该领域的阳性研究数据的缺乏所致．但对于NCCN的这次更新，应该谨慎对待，要从技术难度和预后信息两个角度权衡治疗策略，对于预后不好的可切除转移性结直肠癌（mCRC），新辅助治疗中也不应该排除靶向药物。（3）RAS野生型mCRC的一线靶向治疗：表皮生长因子受体（EGFR）单抗仅限于左侧结肠癌患者。原发瘤部位是mCRC靶向治疗的疗效预测标志物，EGFR单抗在右侧mCRC中的获益很小．但在左侧mCRC，EGFR单抗的获益则显著大于单纯化疗或血管内皮生存因子受体（VEGF）靶向治疗。（4）首次推荐错配修复缺陷（dMMR）／高度微卫星不稳定（MSI—H）的mCRC在标准治疗失败后接受免疫检查点抑制剂的免疫治疗。具有dMMR／MSI—H表型的mCRC．由于MMR基因突变。产生大量新抗原而成为高免疫源性肿瘤，从而对免疫治疗变得敏感。

The NCCN has recently released its 2017 version 1.0 guideline for eolorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with eolorectal cancer after colectomy for secondary chemoprevention. Update two,biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer （mCRC）. This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting. Both technical criteria and prognostic information should be considered for decision-making. Currently biological agents may not be excluded from the neoadjuvant setting for patients with resectable but poor prognostic disease. Update three, panitumumab and cetuximab combination therapy is only recommended for left-sided tumors in the first line therapy. The location of the primary tumor can be both prognostic and predictive in response to EGFR inhibitors in metastatic colorectal cancer. Cetuximab and panitumumab confer little benefit to patients with metastatic colorectal cancer in the primary tumor originated on the fight side. On the other hand, EGFR inhibitors provide significant benefit compared with bevacizumab-containing therapy or chemotherapy alone for patients with left primary tumor. Update four, PD-1 immune checkpoint inhibitors including pembrolizumab or nivolumab are recommended as treatment options in patients with metastatic deficient mismatch repair （dMMR） eolorectal cancer in second- or third-line therapy. dMMR tumors contain thousands of mutations, which can encode mutant proteins with the potential to be recognized and targeted by the immune system. It has therefore been hypothesized that dMMR tumors may be sensitive to PD-1 inhibitors.