PDF(Pubmed)
Abstract：
UNASSIGNED: Colorectal cancer (CRC) with the Raf murine sarcoma viral oncogene homolog B (BRAF) V600E had a relatively poor prognosis. Anaplastic lymphoma kinase (ALK) fusion and the mesenchymal-to-epithelial transition factor (MET) amplification have been recognized as potentially important therapeutic targets in non-small cell lung cancer (NSCLC). However, both of them are of extremely lower frequencies (<2%) in metastatic CRC, and few studies have mentioned the real application of their inhibitors in CRC treatment.
UNASSIGNED: A 49-year-old Chinese male was diagnosed with ascending colon adenocarcinoma (cT3N+?M1) with liver metastases. The patient performed next-generation sequencing (NGS) using tissue and circulating tumor DNA (ctDNA), and the results showed a BRAF V600E mutation. He received an initial combination treatment with cetuximab, dabrafenib, and trametinib with a partial response (PR) assessment. We changed the therapy regimen on this patient several times because of the patient\'s intolerance to the drugs or the inefficacy of the treatment. During this period, we detected the c-MET amplification and tropomyosin 4 (TPM4)-ALK fusion by NGS after triplet targeted therapy (tislelizumab, dabrafenib, and trametinib), thus he was finally treated with programmed cell death protein 1 (PD-1) inhibitor (tislelizumab), MET/ALK inhibitor (crizotinib) plus multikinase inhibitor (regorafenib). Imageological examinations showed that PR was achieved and ctDNA sequencing results indicated a significantly reduced BRAF mutation frequency, MET amplification and TPM4-ALK fusion were undetectable. NGS analysis of peripheral blood showed a recurrence of the MET acquired resistant amplification mutation over 2 months of ongoing treatment. but the patient was assessed as PR and still under treatment of crizotinib, tislelizumab and regorafenib within good physical condition. At the last follow-up on October 2021, the patient died of symptomatic treatment fail for obstructive jaundice. The patient finally achieved 11 months overall survival.
UNASSIGNED: This study reported a co-existence of a BRAF V600E mutation, c-MET amplification and TPM4-ALK fusion in a CRC patient. Administration of crizotinib combined with regorafenib and tislelizumab obtained an obvious response. Furthermore, continuous ctDNA detection appears to be a promising technique to monitor tumor burden, which may provide better clinical decision support during the disease course.
UNASSIGNED: A 49-year-old Chinese male was diagnosed with ascending colon adenocarcinoma (cT3N+?M1) with liver metastases. The patient performed next-generation sequencing (NGS) using tissue and circulating tumor DNA (ctDNA), and the results showed a BRAF V600E mutation. He received an initial combination treatment with cetuximab, dabrafenib, and trametinib with a partial response (PR) assessment. We changed the therapy regimen on this patient several times because of the patient\'s intolerance to the drugs or the inefficacy of the treatment. During this period, we detected the c-MET amplification and tropomyosin 4 (TPM4)-ALK fusion by NGS after triplet targeted therapy (tislelizumab, dabrafenib, and trametinib), thus he was finally treated with programmed cell death protein 1 (PD-1) inhibitor (tislelizumab), MET/ALK inhibitor (crizotinib) plus multikinase inhibitor (regorafenib). Imageological examinations showed that PR was achieved and ctDNA sequencing results indicated a significantly reduced BRAF mutation frequency, MET amplification and TPM4-ALK fusion were undetectable. NGS analysis of peripheral blood showed a recurrence of the MET acquired resistant amplification mutation over 2 months of ongoing treatment. but the patient was assessed as PR and still under treatment of crizotinib, tislelizumab and regorafenib within good physical condition. At the last follow-up on October 2021, the patient died of symptomatic treatment fail for obstructive jaundice. The patient finally achieved 11 months overall survival.
UNASSIGNED: This study reported a co-existence of a BRAF V600E mutation, c-MET amplification and TPM4-ALK fusion in a CRC patient. Administration of crizotinib combined with regorafenib and tislelizumab obtained an obvious response. Furthermore, continuous ctDNA detection appears to be a promising technique to monitor tumor burden, which may provide better clinical decision support during the disease course.
摘要：
■具有Raf鼠肉瘤病毒癌基因同源物B(BRAF)V600E的结直肠癌(CRC)具有相对较差的预后。间变性淋巴瘤激酶（ALK）融合和间充质到上皮转化因子（MET）扩增已被认为是非小细胞肺癌（NSCLC）的潜在重要治疗靶标。然而,两者在转移性CRC中的频率极低（<2%），很少有研究提到其抑制剂在CRC治疗中的实际应用。
■一名49岁的中国男性被诊断为升结肠腺癌（cT3N？M1）伴肝脏转移。患者使用组织和循环肿瘤DNA（ctDNA）进行了下一代测序（NGS），结果显示BRAFV600E突变。他接受了西妥昔单抗的初始联合治疗，Dabrafenib,曲美替尼和部分缓解（PR）评估。由于患者对药物不耐受或治疗无效，我们多次改变了该患者的治疗方案。在此期间,我们在三联体靶向治疗后通过NGS检测到c-MET扩增和原肌球蛋白4（TPM4）-ALK融合（tislelizumab，Dabrafenib,和曲美替尼），因此，他最终用程序性细胞死亡蛋白1（PD-1）抑制剂（tislelizumab）治疗，MET/ALK抑制剂（克唑替尼）加多激酶抑制剂（瑞戈非尼）。影像学检查显示达到PR，ctDNA测序结果表明BRAF突变频率明显降低，MET扩增和TPM4-ALK融合是检测不到的。外周血的NGS分析显示，在持续治疗的2个月内，MET获得性耐药扩增突变复发。但患者被评估为PR，仍在接受克唑替尼治疗，tislelizumab和regorafenib在良好的身体条件下。在2021年10月的最后一次随访中，患者因阻塞性黄疸对症治疗失败而死亡。患者最终获得11个月的总生存期。
■这项研究报告了BRAFV600E突变的共存，CRC患者的c-MET扩增和TPM4-ALK融合。克唑替尼联合雷戈非尼和tislelizumab的给药获得了明显的反应。此外，连续ctDNA检测似乎是一种有前途的技术来监测肿瘤负荷，这可能在疾病过程中提供更好的临床决策支持。
■一名49岁的中国男性被诊断为升结肠腺癌（cT3N？M1）伴肝脏转移。患者使用组织和循环肿瘤DNA（ctDNA）进行了下一代测序（NGS），结果显示BRAFV600E突变。他接受了西妥昔单抗的初始联合治疗，Dabrafenib,曲美替尼和部分缓解（PR）评估。由于患者对药物不耐受或治疗无效，我们多次改变了该患者的治疗方案。在此期间,我们在三联体靶向治疗后通过NGS检测到c-MET扩增和原肌球蛋白4（TPM4）-ALK融合（tislelizumab，Dabrafenib,和曲美替尼），因此，他最终用程序性细胞死亡蛋白1（PD-1）抑制剂（tislelizumab）治疗，MET/ALK抑制剂（克唑替尼）加多激酶抑制剂（瑞戈非尼）。影像学检查显示达到PR，ctDNA测序结果表明BRAF突变频率明显降低，MET扩增和TPM4-ALK融合是检测不到的。外周血的NGS分析显示，在持续治疗的2个月内，MET获得性耐药扩增突变复发。但患者被评估为PR，仍在接受克唑替尼治疗，tislelizumab和regorafenib在良好的身体条件下。在2021年10月的最后一次随访中，患者因阻塞性黄疸对症治疗失败而死亡。患者最终获得11个月的总生存期。
■这项研究报告了BRAFV600E突变的共存，CRC患者的c-MET扩增和TPM4-ALK融合。克唑替尼联合雷戈非尼和tislelizumab的给药获得了明显的反应。此外，连续ctDNA检测似乎是一种有前途的技术来监测肿瘤负荷，这可能在疾病过程中提供更好的临床决策支持。
