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

Sofie Olsson Hau, Alexandra Petersson, Björn Nodin, Emelie Karnevi, Karolina Boman, Caroline Williamsson, Jakob Eberhard, Karin Leandersson, David Gisselsson, Margareta Heby, Karin Jirström, Sofie Olsson Hau, Alexandra Petersson, Björn Nodin, Emelie Karnevi, Karolina Boman, Caroline Williamsson, Jakob Eberhard, Karin Leandersson, David Gisselsson, Margareta Heby, Karin Jirström

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.

Keywords: Chemotherapy; Immune response; Pancreatic cancer; Periampullary cancer; ctDNA.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart describing the study inclusion procedure. F and G are abbreviations of FOLFIRINOX and gemcitabine. These are examples of regimens, others such as nab-paclitaxel follow similar schedules. DSS = disease specific survival, EOT = end of treatment, OS = overall survival, QoL = Quality of life, TTP = time to progression, SPTC = single patient tissue chip, ctDNA = circulating tumour DNA, PBMCs = Peripheral blood mononuclear cells
Fig. 2
Fig. 2
Methodological overview of the construction of a “Single patient tissue chip” from a resected tumour. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://creativecommons.org/licenses/by/3.0/

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Source: PubMed

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