O'Hayer Kevin, Farber John, Yeo Charles J, Sama Ashwin R
Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Case Rep Pancreat Cancer. 2015 Nov 1;1(1):7-10. doi: 10.1089/crpc.2015.29004.koh. eCollection 2015.
Ampullary adenocarcinomas are a rare subset of periampullary tumors with an overall poor prognosis. Treatment decisions are generally extrapolated from pancreatic chemotherapy protocols and consist mainly of traditional chemotherapy drugs. There are no known targets for therapeutic intervention in ampullary adenocarcinoma at this time. Next generation sequencing and other novel molecular profiling of tumors, including circulating tumor DNA (ctDNA), have recently made it possible to better understand tumor biology and elucidate driver mutations which are amenable to targeted therapy. This case describes the use of novel DNA sequencing technology to provide a targeted treatment option, HER-2 inhibition, in a patient with HER-2 overexpressing ampullary adenocarcinoma. This is the first time this has been described in the literature. The patient is a 63-year-old Caucasian man who initially presented with symptoms of obstructive jaundice and was found to have a periampullary tumor. He underwent resection of his tumor and pathology confirmed a stage IIB ampullary adenocarcinoma. He unfortunately developed a recurrence in the liver and lung two years later. Next generation sequencing of his tumor at the time of resection as well as ctDNA analysis demonstrated a HER-2 overexpressing tumor. Following first line therapy with FOLFOX he had progression and was treated with trastuzumab and pertuzumab with stabilization of his disease prior to his ultimate demise from multifocal pneumonia. The use of next generation sequencing as well as ctDNA technology generated a novel therapeutic intervention in our patient. As these techniques become more widespread, it is likely more targeted therapies will be used in these difficult to treat diseases.
壶腹腺癌是壶腹周围肿瘤中罕见的一个亚组，总体预后较差。治疗决策通常从胰腺癌化疗方案推断而来，主要由传统化疗药物组成。目前在壶腹腺癌中尚无已知的治疗干预靶点。肿瘤的新一代测序及其他新型分子分析，包括循环肿瘤DNA（ctDNA），最近使人们能够更好地理解肿瘤生物学并阐明适合靶向治疗的驱动突变。本病例描述了使用新型DNA测序技术为一名HER-2过表达的壶腹腺癌患者提供靶向治疗方案——HER-2抑制。这是文献中首次对此进行描述。患者为一名63岁的白人男性，最初表现为梗阻性黄疸症状，被发现患有壶腹周围肿瘤。他接受了肿瘤切除术，病理证实为IIB期壶腹腺癌。不幸的是，两年后他出现了肝肺转移。切除肿瘤时进行的新一代测序以及ctDNA分析显示肿瘤HER-2过表达。在接受一线FOLFOX治疗后病情进展，随后接受曲妥珠单抗和帕妥珠单抗治疗，病情稳定，最终因多灶性肺炎死亡。新一代测序以及ctDNA技术的应用为我们的患者带来了一种新的治疗干预措施。随着这些技术越来越普及，在这些难以治疗的疾病中可能会使用更多的靶向治疗方法。
