Ass/Prof Ben Tran, WEHI
Germ cell tumours (GCTs) are rare compared to other cancers, but are still the most common type of cancer in young men, formed from reproductive cells and mostly occurring in the testicles. These cancers are highly treatable, but determining the most appropriate treatment for each patient relies on a good foundation of clinical data.
At its core, the treatment of GCT has remained the same over many years. However, there are many nuances associated with its treatment that may not be known to clinicians who don’t see these cancers regularly or frequently. These include simple things such as chemotherapy dosing, dose intensity, use of imaging, and surgical techniques, and understanding the impacts of these variables can make a difference to treatment outcomes.
In addition to the difficulty accessing information about treatments and subsequent outcomes, the rarity of GCTs makes it difficult to enrol sufficient numbers of patients onto clinical trials that address important clinical questions.
This situation is made more difficult by the decentralisation of cancer treatment in Australia, as no single Australian centre can accumulate sufficient numbers of patients with GCT to generate any meaningful research, whether that be clinical, retrospective or translational.
As a result, clinicians treating GCTs often look to data from retrospective studies undertaken by large international centres to answer these questions.
A team at the Walter and Eliza Hall Institute of Medical Research (WEHI) has developed iTestis to fill the gap in detailed national clinical data to help clinicians to assess treatment options and resulting outcomes for their GCT patients.
iTestis is a detailed database with a user-friendly web-based interface that facilitates prospective collection of high quality clinical data and record tissue location data from GCT patients treated in Australia.
Data captured includes presentation and disease characteristics, patient characteristics, local and systemic therapies, surveillance methods, recurrence data and treatment outcomes. These data will be collected for up to 4 years and will be updated regularly by study personnel throughout the patient’s treatment and follow-up from their medical record.
iTestis aims to demonstrate that organised data and tissue collection from GCT patients across multiple sites, using a registry and biobank, can generate quality data and translational research.
iTestis helps to describe the current care and treatment patterns for GCT patients and identify any deficiencies or abnormalities to ensure that Australian GCT patients receive the best care possible.
iTestis provides valuable insight for clinicians by:
Initially, iTestis was rolled out to selected high volume centres with interested and engaged investigators. The vision is to have data collected from 70% of Australia’s GCT patient population within iTestis, and then to consider rolling out to interested international parties.
The Global Germ Cell Collaborative Group (G3) is an international consortium committed to the management of GCT, and part of this commitment includes conducting multiple retrospective data research projects. It has always been difficult for Australia to contribute meaningfully to these projects, as patient numbers from individual centres have always been relatively small compared to international centres. iTestis will enable Australia to make large contributions to these projects and potentially lead some of the projects.
Translational research involves combining biological specimens with corresponding clinical data to answer biological research questions. Tumour specimens are stored in pathology labs for many years and can be accessed if there is an appropriate, ethics-approved protocol and if the patient has provided consent. However, the challenge is matching these specimens to reliable patient data, which is difficult to collect retrospectively.
“The ideal situation is that patient data is collected prospectively, and this is essential for facilitating translational research," says Dr Tran. “Outside of clinical trials, the most successful translational research cohorts involve the use of prospectively collected data within registries.”
Selected centres participating in iTestis will gain patient consent for archival tissue collection and analysis, and blood collection and analysis. The availability of tissue or blood will be indicated within iTestis, so that at a later date, when there is a relevant research project, a query can be made to identify eligible patients with available specimens for translational studies (with approval of the investigators involved).
Many clinically-relevant questions can be answered using such a resource. Additionally, the resource can be used to join international collaborations such as the Craig Nichols led miR371 biomarker for stage 1 disease protocol or the Movember GAP5 biomarkers for platinum resistance protocol.
Randomised-controlled trials (RCT) are the current gold standard for comparative studies. However, few are currently conducted and many important clinical questions remain unaddressed. RCTs are typically conducted at high-volume centres, have narrow inclusion criteria that create uncertainty regarding applicability into clinical practice, are expensive and, where industry-funded, frequently align with study sponsor interests.
“Registry-based RCTs are a novel and promising alternative that address these concerns. They have the additional advantages of providing comprehensive data across multiple lines of treatment at no additional cost, with the in-built capacity to compare study eligible and ineligible patients enrolled on the registry for a real-world comparison,” says Dr Tran.
Following the establishment of iTestis as a robust and reliable registry, there will be capabilities to conduct registry-based RCTs. iTestis will become a valuable resource to the wider GCT community.
BioGrid’s secure platform underpins the iTestis database, and BioGrid’s experience over 15 years with building and managing registries provides the perfect skill-set for supporting iTestis’ future objectives.
An important recent feature of the iTestis registry is the ability for patients to complete online questionnaires that assist treating clinicians to better manage patient care and quality of life due to feedback received. This capability was developed by BioGrid as an improvement upgrade to the iTestis software.
Dynamic reporting of iTestis registry data provided by BioGrid enables A/Prof Tran and his colleagues to review data they have each collected which can assist with cohort identification and analyses.
BioGrid’s solution means that a significant data set can be provided for participation in global initiatives like G3 projects, and enables iTestis to be expanded to include international sites.
Published 13 October, 2023