Xiong Qunli, Zeng Zhu, Yang Yang, Wang Ya, Xu Yongfeng, Zhou Ying, Liu Jinlu, Zhang Zhiwei, Qiu Meng, Zhu Qing
Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China.
Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2022 May 26;12:872630. doi: 10.3389/fonc.2022.872630. eCollection 2022.
Close to one third of colorectal cancer (CRC) patients are diagnosed with metastatic CRC (mCRC). Patients with wild-type RAS and BRAF usually receive anti-EGFR monoclonal antibody therapy containing cetuximab. Overall, 30-50% of mCRC patients are reported to harbor RAS mutations, and RAS mutation status should be assessed when considering EGFR inhibitor treatment according to mCRC biomarker guidelines. Of note, 0.67-2% of patients with CRC harbored a KRAS amplification. Here we reported a case of advanced rectal cancer with wild-type RAS and BRAF in a male patient who harbored a KRAS amplification during anti-EGFR treatment.
A 46-year-old man was diagnosed with rectal adenocarcinoma with liver metastases (cT3NxM1a, stage IVA). After receiving first-line irinotecan- fluorouracil chemotherapy (FOLFIRI) plus cetuximab, second-line capecitabine- oxaliplatin chemotherapy (XELOX) plus bevacizumab, and third-line regorafenib, he rechallenged FOLFIRI and cetuximab for seven cycles, achieving a prolonged survival of at least 5 months. The KRAS copy number of circulating tumor DNA (ctDNA) was assessed during treatment. Notably, apart from serum carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA), the change of plasm Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) copy number appeared to strongly correlate with treatment response.
Our findings suggest that the dynamic change of KRAS copy number on ctDNA during treatment might be a negative predictive biomarker. Additionally, RAS and BRAF wild-type mCRC patients who are resistant to first-line FOLFIRI plus cetuximab therapy may respond well to the FOLFIRI plus cetuximab "rechallenged" strategy.
近三分之一的结直肠癌（CRC）患者被诊断为转移性结直肠癌（mCRC）。RAS和BRAF基因野生型的患者通常接受含西妥昔单抗的抗表皮生长因子受体（EGFR）单克隆抗体治疗。总体而言，据报道30%-50%的mCRC患者存在RAS突变，根据mCRC生物标志物指南，在考虑EGFR抑制剂治疗时应评估RAS突变状态。值得注意的是，0.67%-2%的CRC患者存在KRAS扩增。在此，我们报告了1例男性晚期直肠癌患者，其RAS和BRAF基因野生型，但在接受抗EGFR治疗期间出现KRAS扩增。
一名46岁男性被诊断为直肠腺癌伴肝转移（cT3NxM1a，IVA期）。在接受一线伊立替康-氟尿嘧啶化疗（FOLFIRI）联合西妥昔单抗、二线卡培他滨-奥沙利铂化疗（XELOX）联合贝伐单抗以及三线瑞戈非尼治疗后，他再次接受FOLFIRI和西妥昔单抗治疗7个周期，实现了至少5个月的长期生存。在治疗期间评估了循环肿瘤DNA（ctDNA）的KRAS拷贝数。值得注意的是，除血清糖类抗原199（CA199）和癌胚抗原（CEA）外，血浆 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）拷贝数的变化似乎与治疗反应密切相关。
我们的研究结果表明，治疗期间ctDNA上KRAS拷贝数的动态变化可能是一种阴性预测生物标志物。此外，对一线FOLFIRI联合西妥昔单抗治疗耐药的RAS和BRAF基因野生型mCRC患者可能对FOLFIRI联合西妥昔单抗“再挑战”策略反应良好。
