胆胰管交界部癌的化疗、宿主反应和分子动力学：CHAMP 研究。

Chemotherapy, host response and molecular dynamics in periampullary cancer: the CHAMP study.

机构信息

Division of Oncology and Therapeutic Pathology, Department of Clinical Sciences, Lund University, SE-221 85, Lund, Sweden.

Division of Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden.

出版信息

BMC Cancer. 2020 Apr 15;20(1):308. doi: 10.1186/s12885-020-06807-3.

DOI:10.1186/s12885-020-06807-3

PMID:32293352

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7161011/

Abstract

BACKGROUND

Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease.

METHODS

The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time.

DISCUSSION

Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory.

TRIAL REGISTRATION

This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

摘要

背景

胰腺癌是一种具有破坏性的疾病，预后不良。尽管近年来在其他侵袭性肿瘤的系统治疗方面取得了重大医学进展，但胰腺癌的诊断通常仍然等同于致命结局。壶腹周围癌这一术语包括胰腺癌，并适用于在 Vater 壶腹附近发现的一组肿瘤。在这组肿瘤中，宿主在化疗期间的分子事件和免疫反应在很大程度上仍未得到探索。因此，“壶腹周围癌的化疗、宿主反应和分子动力学（CHAMP）”研究旨在监测这些过程，以深入了解这一棘手的疾病。

方法

CHAMP 研究是一项前瞻性、单臂观察性研究。邀请在斯科讷大学医院肿瘤学系接受辅助或姑息化疗治疗的所有诊断为胰腺或其他壶腹周围腺癌的患者参加。在研究入组时将汇编临床和病理数据。为每位接受手术切除肿瘤的患者构建一个组织微阵列（TMA）块，并在化疗前后抽取血液样本，以采集外周血单核细胞（PBMC）、细胞因子和循环肿瘤 DNA（ctDNA）。将对肿瘤组织和 ctDNA 进行下一代测序，以检测空间和时间上克隆景观的变化。

讨论

尽管最近出现了一些有前途的壶腹周围癌生物标志物，但在临床实施方面一直没有成功。癌细胞在化疗过程中不断适应并对治疗产生耐药性。为了能够跟上并希望超越这种快速演变，我们必须借助新的诊断工具，随时准备适应并相应地改变治疗方法。在我们看来，前进的唯一途径是在治疗过程中更好地了解疾病的动态。通过 CHAMP 研究获得的见解，我们希望找到在这一大部分未探索领域的关键问题的答案。