Geddam Aaditya Srivant, Lutfi Areeb, Afghan Maaz Khan, Currie Brian M, Rosenblatt Russell, Ramirez Arturo B, Bayer Erin G, Hissong Erika, Kasi Pashtoon Murtaza
Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY, USA.
Division of Vascular and Interventional Radiology, Weill Cornell Medicine, New York, NY, USA.
J Liq Biopsy. 2023 Sep 26;2:100009. doi: 10.1016/j.jlb.2023.100009. eCollection 2023 Dec.
Hepatocellular Carcinoma (HCC) is the most common primary liver carcinoma, accounting for 75-85% of all cases. For patients with advanced unresectable and/or metastatic HCC, treatment options primarily include immunotherapy combinations and/or oral tyrosine kinase inhibitors. For patients with alpha-fetoprotein (AFP) levels above 400 ng/ml, ramucirumab, an anti-VEGF agent, is also approved in the second-line setting. However, none of these therapies are based on a specific molecular marker and the role of molecular testing is limited. In fact, HCC is unique in the sense that a biopsy may not be pursued if imaging findings are classic for HCC, in the appropriate clinical context. Herein, we report a case of a patient with metastatic HCC and a huge disease burden where a circulating tumor DNA (ctDNA) liquid biopsy done as part of our standard of care serendipitously revealed a very high copy number amplification (>78). This was corroborated by HER2 immunohistochemical staining, which demonstrated strong diffuse membranous HER2 3+ expression; tissue next-generation sequencing also identified an unadjusted copy number gain of 183. Furthermore, we were able to demonstrate the feasibility of using both ctDNA and circulating tumor cells (CTCs) to determine the heterogeneity of HER2 and response to dual HER2 blockade trastuzumab/pertuzumab (MyPathway regimen). In addition to the utility of liquid biopsies increasing opportunities for precision medicine, this n-of-1 precision medicine case illustrates and reiterates the need for comprehensive panel-based NGS testing that employs both DNA/RNA for all patients with advanced or metastatic cancers. It also supports the agnostic potential of /HER2 as an actionable marker.
肝细胞癌（HCC）是最常见的原发性肝癌，占所有病例的75 - 85%。对于晚期不可切除和/或转移性HCC患者，治疗选择主要包括免疫治疗联合方案和/或口服酪氨酸激酶抑制剂。对于甲胎蛋白（AFP）水平高于400 ng/ml的患者，抗血管内皮生长因子（VEGF）药物雷莫西尤单抗在二线治疗中也已获批。然而，这些治疗均未基于特定分子标志物，分子检测的作用有限。事实上，HCC具有独特性，即在适当的临床背景下，如果影像学表现符合典型HCC，可能无需进行活检。在此，我们报告一例转移性HCC患者，其疾病负担巨大，作为我们标准治疗的一部分进行的循环肿瘤DNA（ctDNA）液体活检意外发现了非常高的拷贝数扩增（>78）。HER2免疫组化染色证实了这一点，其显示HER2呈强弥漫性膜性3+表达；组织二代测序也确定未校正的拷贝数增益为183。此外，我们能够证明使用ctDNA和循环肿瘤细胞（CTC）来确定HER2的异质性以及对HER2双靶点阻断剂曲妥珠单抗/帕妥珠单抗（MyPathway方案）反应的可行性。除了液体活检有助于增加精准医学的机会外，这个单病例精准医学案例说明了并再次强调了对所有晚期或转移性癌症患者进行基于全面panel的NGS检测的必要性，该检测同时使用DNA/RNA。它还支持将HER2作为一个可操作标志物的未知潜力。
