Tumorbank@uza: A Collection of Tissue, Fluid Samples and Associated Data of Oncology Patients for the Use in Translational Research

Tumorbank@UZA is an academic hospital integrated biobank that collects tissue, blood and urine samples from oncology patients. We work according to a quality management system and have established SOPs for all work procedures in the biobank. Tumorbank@UZA is funded by the National Cancer Plan, an initiative from the Belgian government since 2009. Samples from our biobank are available for both academic as well as commercial researchers, through a well-established access procedure. Currently the collection consists of more than 85.000 samples of more than 8000 patients.

The aims of Tumorbank@UZA is the collection, processing and distribution of different sample types and the associated data for the use in research projects. Sample types include fresh frozen and FFPE tissue, whole blood and blood derivates such as serum, plasma, buffy coat and red blood cells and recently also urine samples are being collected. All biobank processes are well documented in a quality management system which we continually strive to improve. Tissue material and serum samples are residual (left-over) material, which is collected within the opt-out system as stated in the Belgian law of 19 th of December 2008. Residual material that is not needed for diagnosis of the patient may be used for translational research, upon approval by the hospital research ethics committee (REC). For human material that is specifically collected for the biobank, a broad consent is used which explicitly asks to the patient for an extra blood sample that will be stored in the biobank. These blood samples are stored as whole blood or processed into serum or plasma, buffy coat and red blood cell fractions.
All material transfers are covered by a human material transfer agreement and every research project has to be approved by the local REC.

Classification (2)
Biological samples and associated data, clinical data.
From 2010 onwards, it started to actively collect residual tissue samples. In 2012 the residual serumbank was added to Tumorbank@UZA.
In 2013 the broad informed consent of the biobank was approved and the collection of blood and blood derivates such as plasma and buffy coat started.
In September 2016 Tumorbank@UZA started with the collection of residual urine samples of oncology patients.
All collections described above are still ongoing as long as governmental funding from the National Cancer Plan continues.

Temporal coverage for accessibility:
N/A. Tumorbank@UZA has no indicated date when it must be destroyed.

Steps
All processes in the biobank including: All materials such as tissue, residual serum and blood taken with informed consent are all delivered to the biobank, as fast as possible and with the necessary request forms containing information such as patient identification, material collected, collection date and time, … If necessary, the informed consent will also be delivered to the biobank. All steps (collection/excision, reception by biobank, centrifugation, fractionation and snap freezing) are timestamp documented in the LIMS system of the biobank.
Dedicated biobank technicians check the received material and handle it according to the different SOPs. All material is registered within a single sample management database (Slims -Genohm) which is connected to other databases in the hospital to retrieve clinical data, associated with the patient. Only trained biobank staff has access to this database and the physical collections.

Type of long-term preservation
All material is stored in access restricted areas where only biobank personnel can enter.
• FFPE tissue: stored in cabinets at room temperature • Fresh frozen tissue: stored in manual -80°C freezers. Plasma, buffy coat, red blood cells, serum: stored in manual -80°C freezers.
Tissue samples and dedicated blood derivates will be stored in fully automated freezers in the vapour phase of liquid nitrogen (Hermetic storage system from Askion with internal and external automation) from May 2017 onwards. Samples in this system are automatically processed at at least -100°C and are stored between -150°C till -190°C to maintain a continuous cold chain.

Storage temperature
Room temperature, -80°C, -150°C, vapour phase of liquid nitrogen (< -150°C). If requested so by the researcher, samples can also be stored at 4°C and -20°C.

Shipping temperature from patient/source to preservation or research use
Shipping of samples from the clinic to the biobank, is done immediately after collection at room temperature. The biobank is notified when samples are taken and follows up actively on fast delivery. Timestamps are documented in the LIMS.

Shipping temperature from storage to research use
Frozen material is shipped on dry ice (-80°C). FFPE material is shipped at room temperature. Deviations can occur when requested by the client.

Quality assurance measures
Tissue material will be processed to a control slide, stained with hematoxilin-eosin and checked by a certified pathologist before transfer of tissue material to a researcher. Diagnosis will be confirmed and, if applicable, tumour cell percentage will be estimated. DNA and RNA extractions performed by biobank will be quality controlled by spectophotometry based methods (Nanodrop -Thermo Scientific). For RNA the RNA integrity will be assessed (Bioanalyzer -Agilent).
Freeze-thaw cycles are avoided but, in case they emerge, documented in the LIMS system and will be provided to the requesting researcher.

Source of associated data
The demographical information (gender, birth date, postal code) of patients is extracted automatically from the patient administration database from UZA.
• Tissue: pathology diagnosis and description of localisation (CODAP code and ICD-O coding system) are automatically imported in SLims, from the LIMS of the pathology department. • Serum: clinical results of the serum is automatically imported in SLims through database connectivity with the LIMS system of the clinical chemistry lab of the hospital.
Quality parameters such as SPREC [1] is calculated automatically from sample data entered in SLims.
All clinical data of the patient is recorded in an electronic patient database (EPD) which can be accessed by authorized biobank personnel. All databases, including SLims, are embedded in a datawarehouse which is maintained by the hospital IT department. The researcher can request additional clinical information which is processed and procured by MOCA data management.

Ethics Statement
The procedures used by Tumorbank@UZA for the residual material collections, were approved by the REC of the hospital (Comité voor Medische Ethiek van het Universitair Ziekenhuis Antwerpen en de Universiteit Antwerpen) at 30/4/2012. The broad consent used by Tumorbank@UZA was approved at 04/03/2013 and an updated version was approved at 18/11/2014. Every research project needs to be approved by the REC of the hospital as well, before samples can be exchanged.

Constraints
All material stored in Tumorbank@UZA is collected within the University Hospital of Antwerp. Residual material from patients processed at the laboratories of the University Hospital of Antwerp but not seen in this hospital will be excluded from the biobank.  Tumorbank@UZA is a clinical biobank with main focus on samples from oncology patients.

Type of sampling
Disease-based biobank, sampled in clinical care.

Anatomical site
Because Tumorbank@UZA is a clinical biobank, tissue from various tumour types and anatomical sites are available.

Clinical characteristics of patients/source
Tumorbank@UZA is a clinical biobank. We have no specific inclusion criteria, except for some quality criteria. Patients within the oncological care program of the hospital might be included in the biobank on the condition that residual material is available and that the patient did not opt-out and/or that an informed consent of the biobank is signed by the patient.
All clinical data registered in the electronic patient database, or other in-house databases, can be linked to the biobank material.

Size of the bioresource
Tumorbank@UZA is a hospital embedded biobank, not a project with a fixed end date. It contains more than 75.000 samples of more than 8000 patients.

Vital state of patients/source
Patients are alive at the moment of sample collection.

Clinical diagnosis of patients/source
Any oncological diagnosis. Besides malignant tumours we also have a large collection of benign tumours.

Control samples
For tissue samples both tumour and macroscopically assessed tumour-free (uninvolved) tissue material of the same organ. Clients (both academic and commercial researchers can be granted access to our collection) will submit the Material Request Form in which they describe their project. This is reviewed by the BAB (i.e. a multidisciplinary board consisting of surgeons, clinicians and scientists) in terms of study design, sample availability, project funding and scientific relevance within 10 working days.
Depending on the request, costs will be agreed upon before finalization of the contract. Costs will cover the consumables needed for collection, handling and storage of the samples as well as the additional services asked for such as DNA/RNA isolation, making tissue slides, look-up of extra clinical data, … Finally, every project will also be evaluated by the local REC.
Samples, and if requested, associated coded data are released following approval by REC and after positive evaluation by the BAB. According to the terms of the HMTA researchers are committed to give feedback on sample quality and results obtained with the samples from Tumorbank@UZA. Researchers should also acknowledge Tumorbank@UZA in any scientific communication according to the terms in the HMTA.
(4) Reuse potential Fluid samples are stored in small aliquots of 500µl/vial, with multiple aliquots per collection per patient. Hence, these samples can be used for multiple projects.
Tissue samples are always processed (eg. cutting slides) by dedicated and trained biobank staff only. In this way these samples can be used for multiple projects as well. We do not take back remains of samples as we cannot guarantee the quality of that material anymore.