PDF(Pubmed)
Abstract：
\"Liquid biopsy\" is an established technique for examining circulating tumor DNA (ctDNA) from a routine blood draw and detecting actionable biomarkers. Nonetheless, ctDNA testing is rarely utilized for patients with newly diagnosed metastatic colorectal cancer (CRC). We report a case in which ctDNA testing uncovered an actionable biomarker that was not detected by comprehensive genomic profiling of tumor tissue. An 81-year-old woman with a remote history of non-Hodgkin\'s lymphoma presented with primary masses in the ascending colon and sigmoid colon. The ascending colon and sigmoid colon tumors were classified as microsatellite stable (MSS) and mismatch repair proficient (pMMR), and both ctDNA and tissue next-generation sequencing (NGS) from the ascending colon mass were ordered. Because tissue NGS results indicated that the ascending colon tumor was MSS, palliative 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy was started. However, the ctDNA NGS results that arrived after the start of FOLFOX found high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR) disease with a serine/threonine-protein kinase B-Raf (BRAF V600E ) mutation. To treat both her MSS/pMMR ascending colon and sigmoid colon tumors and MSI-H/dMMR metastatic disease, the immunotherapy nivolumab was added to FOLFOX. After 8 months of combined nivolumab and chemotherapy, the patient\'s metastatic disease had a complete clinical response. This case highlights the complementary role of ctDNA testing for biomarker identification. By performing simultaneous ctDNA testing at the time of diagnosis, an actionable biomarker was discovered that significantly altered this patient\'s prognosis and treatment options. Orthogonal testing of key molecular alterations offers significant advantages for identifying actionable biomarkers and improving management of metastatic CRC.
摘要：
“液体活检”是一种已建立的技术，用于从常规抽血中检查循环肿瘤DNA（ctDNA）并检测可操作的生物标志物。尽管如此，ctDNA检测很少用于新诊断的转移性结直肠癌（CRC）患者。我们报告了一个案例，其中ctDNA测试发现了一种可行的生物标志物，该生物标志物未通过肿瘤组织的全面基因组分析检测到。一名81岁女性，有远隔非霍奇金淋巴瘤病史，在升结肠和乙状结肠表现为原发性肿块。升结肠和乙状结肠肿瘤分为微卫星稳定(MSS)和错配修复(pMMR),并从升结肠肿块中订购ctDNA和组织下一代测序（NGS）。因为组织NGS结果显示升结肠肿瘤为MSS,姑息性5-氟尿嘧啶,亚叶酸,并开始奥沙利铂（FOLFOX）化疗。然而,在FOLFOX开始后得出的ctDNANGS结果发现,具有丝氨酸/苏氨酸蛋白激酶B-Raf(BRAFV600E)突变的高度微卫星不稳定性(MSI-H)和错配修复缺陷(dMMR)疾病.为了治疗她的MSS/pMMR升结肠和乙状结肠肿瘤以及MSI-H/dMMR转移性疾病，免疫疗法nivolumab被添加到FOLFOX中.联合纳武单抗和化疗8个月后，患者的转移性疾病有完全的临床反应。这个案例强调了ctDNA测试对生物标志物鉴定的补充作用。通过在诊断时同时进行ctDNA检测，一个可行的生物标志物被发现显著改变了该患者的预后和治疗选择。关键分子改变的正交测试为识别可操作的生物标志物和改善转移性CRC的管理提供了显着优势。
