The BIOPAC study
Since its initiation, the BIOPAC study has undertaken several projects in a multidisciplinary setting (see list of published studies using material from the BIOPAC study). The BIOPAC study promotes the advance of translational research and precision medicine within the pancreatic cancer landscape.
In line with increasing demand for precision medicine, the need to bridge patients and high-quality clinical data to molecular and genetic research is self-evident. New biomarkers for early diagnosis, prediction of treatment effects and better evaluation of prognosis and monitoring of patients with pancreatic cancer are urgently needed to reduce pancreatic-cancer mortality rates. The focus of our study (BIOPAC- “BIOmarkers in patients with PAncreatic Cancer) is to identify a panel of biomarkers in blood and tissue for early detection of pancreatic cancer. The study will select patients who may benefit from neoadjuvant chemotherapy, and it will prognosticate and predict the effect of different types of systemic therapies. The project will include many translational biomarker studies of gene profiles, DNA, RNAs, microRNAs, SNPs, proteins and metabolites in patients of all ages and at all stages of pancreatic cancer.
The BIOPAC study protocol has been prepared and implemented according to the REMARK guidelines. To increase awareness of the BIOPAC study, and to facilitate dissemination of methods to the scientific community, the standard operating procedures used, current progress as well as completed and ongoing studies are constantly being updated on the BIOPAC Biobank website.
Study design and setting
In July 2008, the Danish BIOPAC Study (BIOmarkers in patients with PAncreatic Cancer – can they provide new information about the disease and improve diagnosis and prognosis of the patients?), was initiated at the Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark with the aim to conduct translational research. It is a prospective multicentre biomarker study in which biological samples (blood and cancer tissue) and clinical data are collected prospectively from Danish patients with localised, locally advanced or metastatic pancreatic cancer being treated at seven oncological expert centres in Denmark. Samples are also from patients who have undergone surgery in whom pancreatic cancer was suspected but not histologically confirmed.
All patients included in the study are >18 years of age, have histologically verified pancreatic cancer or ampullary adenocarcinoma in a resected specimen, or histopathological confirmation of carcinoma if surgery has not been performed. Futhermore all patients have signed an informed consent form. The patients are undergoing treatment with different types of chemotherapy according to national guidelines - www.gicancer.dk. One group consists of patients who have undergone surgery for pancreatic cancer, and a subgroup of patients consists of patients who have undergone surgery due to suspected pancreatic cancer but in whom no cancer was found on histologic examination after resection.
Clinical data and outcomes are registered in the BIOPAC database, and biological samples are collected via the Danish nationwide BIOPAC biobank.
The patients included in the BIOPAC study are followed from time of diagnosis and during treatment and follow-up until death. Relevant clinical characteristics of the patients are included in the BIOPAC and the database and includes a large number of parameters.
The BIOPAC study is a nationwide collaboration between surgical gastro-enterology, oncology, pathology and clinical biochemistry departments in Denmark. As of February 2019, eight hospitals from all regions of Denmark (Rigshospitalet, North Denmark Regional Hospital, Copenhagen University Hospital in Herlev, Zealand University Hospital in Roskilde and Næstved, Odense University Hospital, Aalborg University Hospital, Aarhus University Hospital and Hospital Lillebaelt in Vejle) have agreed to participate in the BIOPAC study. The BIOPAC biobank is located at Copenhagen University Hospital in Herlev, and it is the first comprehensive pancreatic cancer biobank in Denmark.
Patient inclusion started in July 2008 and will continue until July 2028 (or until 5,000 patients have been included), with follow-up until July 2035. The inclusion period can be extended if deemed appropriate after assessment by the investigators.
As of February 2019, blood samples from 2,210 patients had been collected. Approximately 200 patients are included each year in the BIOPAC study..
Different types of biological material, i.e. blood and cancer tissue, are collected, handled and stored according to nationally approved Standard Operating Procedures (SOPs).
The BIOPAC study is an open cohort study. Patients are eligible for inclusion if they are in routine clinical follow-up after a diagnosis of pancreatic cancer. A subgroup of patients operated on due to suspicion, but without evidence, of pancreatic cancer is also included, since blood samples were taken before surgery. Patient inclusion and follow-up are carried out by nurses and physicians when the patients meet for scheduled routine clinical visits.
At the time of inclusion, the following clinical data are collected in the BIOPAC database:
- Patient demographics: e.g. age, gender, diagnosis, weight and weight loss, height, BMI, performance status, family history of pancreatic cancer, medications, histological/cytological characteristics, TNM stage, site of metastasis, as well as lifestyle factors like smoking and alcohol intake.
- Comorbidities including Charlson comorbidity index: e.g. other types of cancer, diabetes, hypertension and hypercholesterolemia.
- Paraclinical information: e.g. routine blood tests (haematology, liver enzymes, bilirubin, creatinine) including serum CA 19-9 and serum C-reactive protein and information on CT and/or positron emission tomography and computed tomography (PET/CT).
- Exposures: e.g. date of operation and treatment with one or more of the following types of chemotherapy: gemcitabine, nab-paclitaxel + gemcitabine, FOLFIRINOX, capecitabine + gemcitabine, or oxaliplatin + capecitabine. Start and stop date and reason for treatment cessation as well as number of cycles in each line of treatment and adverse events.
- Outcomes: e.g. resectability status and date of disease recurrence (in patients operated on), date of disease progression after each line of treatment and date of death.
- Any oncological, surgical and/or medical treatment undertaken, and monitoring of disease status (CT, PET/CT) are done as part of routine care according to international and national guidelines.
Ethics and dissemination
The BIOPAC study protocol has been approved by the Danish Ethics Committee (VEK, j.nr. KA-20060113) and the Danish Data Protection Agency (j.nr. 2012-58-0004; HGH-2015-027; I-Suite j.nr. 03960). All patients receive verbal and written information before enrolment and they give their written consent at baseline according to the guidelines from the Danish Ethics Committee. All patients are informed that they can withdraw from the study at any time without any consequences for their treatment. If a patient withdraws, all blood and tissue samples are discarded, and all patient-related information is deleted from the BIOPAC study.
Recruitment started on 3 July 2008 and is expected to continue until 1 July 2028, with follow-up until 2 July 2035. Currently (12 February 2019), 2,210 patients (out of planned 5,000) have been enrolled on the study.
The BIOPAC study is the first comprehensive study with prospective collection of biological materials and clinical data for researchers and clinicians wishing to conduct basic, clinical and translational research in pancreatic cancer in Denmark and abroad. Since its initiation, the BIOPAC study has undertaken several projects in a multidisciplinary setting (see list of published studies using material from the BIOPAC study) and constantly promotes the advance of translational research and precision medicine within the pancreatic cancer landscape.