Medical Genome Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan.
Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 9518510, Japan.
Clin J Gastroenterol. 2022 Apr;15(2):413-418. doi: 10.1007/s12328-022-01599-4. Epub 2022 Feb 8.
Neuroendocrine neoplasms of the colon and rectum are colorectal epithelial neoplasms with neuroendocrine differentiation. A platinum regimen used for small cell lung cancer is the currently recommended chemotherapy for gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), regardless of the organ. The BRAF V600E mutation has been recently reported as a druggable driver mutation in colorectal NECs. In BRAF V600E mutant colorectal cancer, a combination of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody, with or without a MEK inhibitor, is recommended. Here, we report the case of 77-year-old man who had lymph node recurrence after surgery for primary ascending colonic NEC. Two cytotoxic regimens, cisplatin plus irinotecan and modified FOLFOX6, were administered as first- and second-line chemotherapies with no remarkable response observed. At this point, genetic analysis confirmed the tumor harbored a BRAF V600E mutation. Thus, a regimen of BRAF inhibitor plus anti-EGFR antibody was administered. After commencing this regimen, carcinoembryonic antigen levels decreased within normal range, and there was dramatic shrinkage of the lymph node metastases observed by chest and abdominal computed tomography scans. To our knowledge, this is the first reported case of a colorectal NEC responding to a BRAF inhibitor and anti-EGFR antibody.
结直肠神经内分泌肿瘤是具有神经内分泌分化的结直肠上皮性肿瘤。铂类方案被用于治疗小细胞肺癌,目前被推荐用于胃肠胰神经内分泌癌(GEP-NEC)的化疗,无论肿瘤起源于何处。BRAF V600E 突变最近被报道为结直肠神经内分泌癌的一种可用药驱动突变。在 BRAF V600E 突变型结直肠癌中,推荐使用 BRAF 抑制剂联合抗表皮生长因子受体(EGFR)抗体,联合或不联合 MEK 抑制剂。在此,我们报告了一例 77 岁男性,其原发性升结肠 NEC 手术后出现淋巴结复发。一线和二线化疗分别使用顺铂联合伊立替康和改良 FOLFOX6 两种细胞毒性药物,但无明显缓解。此时,基因分析证实肿瘤存在 BRAF V600E 突变。因此,给予 BRAF 抑制剂联合抗 EGFR 抗体治疗。开始该方案后,癌胚抗原水平降至正常范围内,胸部和腹部 CT 扫描显示淋巴结转移明显缩小。据我们所知,这是首例结直肠 NEC 对 BRAF 抑制剂和抗 EGFR 抗体治疗有反应的报道。