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液体活检和多分析物检测指导的壶腹周围腺癌阳性患者在基于曲妥珠单抗治疗后获得持久完全缓解的治疗

Liquid biopsy and multi-analyte testing guided treatment of positive periampullary adenocarcinoma with durable complete response after trastuzumab based therapy.

作者信息

Nagarkar Rajnish, Patil Darshana, Limaye Sewanti, Devhare Pradip, Ghaisas Ashwini, Srivastava Navin, Apurwa Sachin, Patil Sanket, John Jinumary, Raazi Zarrine, Shreenivas Aditya, Sambath Janani, Srinivasan Ajay, Kumar Prashant, Akolkar Dadasaheb, Datar Rajan

机构信息

HCG Manavata Cancer Centre, Nasik, Maharashtra, India.

Datar Cancer Genetics Limited, Nasik, Maharashtra, India.

出版信息

Oncotarget. 2020 Nov 10;11(45):4195-4200. doi: 10.18632/oncotarget.27793.

DOI:10.18632/oncotarget.27793
PMID:33227091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7665235/
Abstract

Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum. Surgical resection followed by adjuvant therapy is considered as the standard of care treatment for these carcinomas. Despite several advances in diagnostics and therapeutics, only 5% of these patients have an overall survival of five years or more. Currently, there is a dearth of viable therapeutic targets for this disease. The role of HER2 in cancer biology has been studied extensively in several tumour subtypes, and HER2 based targeted therapies have shown to have therapeutic benefits on different cancers. In this case report, we present a case of HER2 positive distal common bile duct carcinoma - a subtype of periampullary carcinoma with multiple relapses where multi-analyte testing with Encyclopedic Tumor Analysis (ETA) (Exacta) identified amplification and over expression of HER2 gene which was used as a potential target to treat the patient with trastuzumab. Synchronous chemosensitivity profiling on Circulating Tumor Asscociated Cells (C-TACs) isolated from blood aided us to design the personalized chemotherapeutic regimen with cyclophosphamide and methotrexate. The combination of trastuzumab with cyclophosphamide and methotrexate yielded excellent treatment response with the patient remaining in complete response till the last follow-up. Our study suggests HER2 directed therapy as a potent pathway for treatment in the subset of HER-2 amplified distal common bile duct carcinomas.

摘要

壶腹周围腺癌是一种罕见的肿瘤,起源于胰头、 Vater壶腹、远端胆管或十二指肠。手术切除后辅助治疗被认为是这些癌症的标准治疗方法。尽管在诊断和治疗方面取得了一些进展,但这些患者中只有5%的总生存期达到五年或更长时间。目前,这种疾病缺乏可行的治疗靶点。HER2在癌症生物学中的作用已在多种肿瘤亚型中得到广泛研究,基于HER2的靶向治疗已显示对不同癌症具有治疗益处。在本病例报告中,我们展示了一例HER2阳性远端胆总管癌——壶腹周围癌的一种亚型,该患者多次复发,通过百科全书式肿瘤分析(ETA)(Exacta)进行的多分析物检测确定了HER2基因的扩增和过表达,这被用作使用曲妥珠单抗治疗该患者的潜在靶点。对从血液中分离出的循环肿瘤相关细胞(C-TACs)进行同步化疗敏感性分析,帮助我们设计了以环磷酰胺和甲氨蝶呤为基础的个性化化疗方案。曲妥珠单抗与环磷酰胺和甲氨蝶呤联合使用产生了优异的治疗反应,患者在最后一次随访时仍处于完全缓解状态。我们的研究表明,HER2导向治疗是HER-2扩增远端胆总管癌亚组中一种有效的治疗途径。

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本文引用的文献

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Int J Cancer. 2020 Jun 15;146(12):3485-3494. doi: 10.1002/ijc.32815. Epub 2019 Dec 16.
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Encyclopedic tumor analysis for guiding treatment of advanced, broadly refractory cancers: results from the RESILIENT trial.用于指导晚期广泛难治性癌症治疗的肿瘤百科分析:RESILIENT试验结果
Oncotarget. 2019 Sep 24;10(54):5605-5621. doi: 10.18632/oncotarget.27188.
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HER2-targeted therapies - a role beyond breast cancer.
壶腹周围癌的辅助治疗及组织病理学分型的意义:一项系统综述
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曲妥珠单抗等 HER2 靶向治疗——超越乳腺癌的应用。
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Trastuzumab and pertuzumab in circulating tumor DNA ERBB2-amplified HER2-positive refractory cholangiocarcinoma.曲妥珠单抗和帕妥珠单抗在循环肿瘤DNA ERBB2扩增的HER2阳性难治性胆管癌中的应用
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Adaptive, Iterative, Long-Term Personalized Therapy Management in a Case of Stage IV Refractory NSCLC.IV期难治性非小细胞肺癌病例中的适应性、迭代式、长期个性化治疗管理
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