PDF(Pubmed)
Abstract：
BACKGROUND: BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment.
METHODS: Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead.
CONCLUSIONS: This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.
METHODS: Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead.
CONCLUSIONS: This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.
摘要：
背景：BRAF突变已被认为是转移性结直肠癌（mCRC）的阴性预后标志物，但这些数据来自常见的BRAFV600E突变的mCRC。BRAF抑制剂和抗表皮生长因子受体（EGFR）抗体的联合治疗已被批准用于BRAFV600E突变的mCRC。然而,BRAF非V600突变是罕见的突变，他们的临床行为不被理解。此外，BRAFK601E突变在mCRC中极为罕见，没有关于其具体治疗的报道。
方法：这里，我们报告了一例59岁女性，患有多发性转移的超侵袭性mCRC，延伸到全身，包括纵隔到腹部淋巴结，骨头,胸膜,还有腹膜.肿瘤组织的伴随诊断显示RAS/BRAF野生型，无微卫星不稳定性。她接受mFOLFOX6（奥沙利铂+输注5-氟尿嘧啶[5-FU]和亚叶酸）+帕尼单抗化疗，遵循FOLFIRI（伊立替康+输注5-FU和亚叶酸）+雷莫单抗。对于下一个方案选择，进行了全面的基因组分析小组，发现了BRAFK601E突变，初始伴随诊断中未涵盖这一点。疾病进展后,恩科拉非尼的组合，比米替尼,选择西妥昔单抗作为三线化疗方案。随着胸腔积液和腹水的改善，血清肿瘤标志物水平立即降低。然而,疾病再次进展，相反，最好的支持性护理被做了。
结论：该病例为BRAF非V600E-mCRC的临床行为提供了新的见解，可能推进罕见和侵袭性病例的个性化治疗。
方法：这里，我们报告了一例59岁女性，患有多发性转移的超侵袭性mCRC，延伸到全身，包括纵隔到腹部淋巴结，骨头,胸膜,还有腹膜.肿瘤组织的伴随诊断显示RAS/BRAF野生型，无微卫星不稳定性。她接受mFOLFOX6（奥沙利铂+输注5-氟尿嘧啶[5-FU]和亚叶酸）+帕尼单抗化疗，遵循FOLFIRI（伊立替康+输注5-FU和亚叶酸）+雷莫单抗。对于下一个方案选择，进行了全面的基因组分析小组，发现了BRAFK601E突变，初始伴随诊断中未涵盖这一点。疾病进展后,恩科拉非尼的组合，比米替尼,选择西妥昔单抗作为三线化疗方案。随着胸腔积液和腹水的改善，血清肿瘤标志物水平立即降低。然而,疾病再次进展，相反，最好的支持性护理被做了。
结论：该病例为BRAF非V600E-mCRC的临床行为提供了新的见解，可能推进罕见和侵袭性病例的个性化治疗。
