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This article is part of a series of case studies on the use of NGS and digital tools to drive precision oncology in the Asia Pacific region. Scroll to the bottom of the article for the full list.
In 2018, the Australian government committed $500 million over 10 years for genomic research. With the vast potential to improve disease diagnosis and drive personalised medicine, next-generation sequencing (NGS) and other genomic tests are now performed nationwide in both private and government-funded laboratories. However, most biomarkers are tested one-by-one and only if relevant, rather than upfront and routinely.
Prof Peter Gibbs, a colorectal cancer specialist at The Walter and Eliza Hall Institute of Medical Research in Victoria, and Prof Svetlana Cherepanoff, an ocular histopathologist at St Vincent’s Hospital and SydPath in New South Wales, both work at the interface between research and diagnostic medicine. They spoke with us about the issues surrounding the clinical integration of NGS in Australia.
NGS and MTBs in clinical practice
Despite growing interest in NGS, the average Australian oncologist has limited experience with the latest tools and methods. Medicare, Australia’s national universal healthcare programme, only reimburses NGS tests for specific cancer stages or types like cutaneous melanoma, lung or non-small cell and colorectal carcinomas. Reimbursement limits on different NGS tests mean that smaller, cheaper and more targeted NGS panels are used more often than larger, more expensive and more comprehensive panels.
For complex cases that use novel diagnostic approaches, molecular tumour boards (MTBs) offer opportunities to share expertise. An MTB may comprise researchers, laboratory technicians, oncologists and pathologists who discuss topics like surveillance guidelines, disease classifications, and array and NGS results. But few Australian clinicians have access to one or the knowledge to participate effectively. “A lot of education is needed to establish MTBs as routine in hospitals,” says Prof Gibbs.
Prof Cherepanoff, whose group runs the sole MTB for ocular oncology in Australia, has firsthand experience with the benefits of multidisciplinary collaboration. An MTB for uveal melanoma, for example, successfully integrated information from clinical images, a SNP array for chromosomal copy number changes, and NGS. This inspired SydPath to apply for grants to turn this MTB model into a self-sustaining one.
Biomarker testing versus NGS
NGS testing could become routine and upfront in oncology if it proved to be more efficient and informative than single-biomarker tests, as has happened with lung cancer. For colorectal cancers, Prof Gibbs searches for just a handful of predictive and prognostic biomarkers that are reimbursable, but notes that this practice is likely to become less cost-effective as more biomarkers are added.
Prof Cherepanoff’s laboratory at SydPath offers a validated and accredited 50-gene hotspot panel which only detects ‘short’, targeted genes in colorectal cancers, cutaneous melanoma and non-small cell lung cancer. While reimbursed, this test is less useful in rare tumours like conjunctival melanoma (for which no NGS panel exists), or in the search for drug targets and tumour-agnostic therapies.
Prof Cherepanoff is also developing a larger 161-gene panel that includes mRNA transcripts, but she knows that doctors with little time to digest vast quantities of information and who only want to identify actionable targets are unlikely to accept the data deluge. Larger panels like these are more likely to be routinely offered by bigger hospitals and laboratories. Also, many see little value in using these tools for all patients, so only young, fit and desperate patients may get it.
As platforms and reports improve in user-friendliness and affordability, and more experienced is gained, small-panel NGS for somatic solid tumours are expected to become routine. Enhanced NGS reports that offer tertiary analyses, such as that offered by Sydney’s Royal Prince Alfred’s pathology service, will be sought after. Prof Cherepanoff’s neuro-oncology molecular profiling work uses it to generate insightful reports and summaries from recent literature and relevant mutations.
Digital tools and the future of MTBs
In the next 5–10 years, Prof Cherepanoff expects rapid development in digital tools for workflow management, information sharing and clinical decision support. Already, new tools are ensuring that geographically diverse teams can collaborate effectively and patients in remote areas can gain access to better care. Prof Cherepanoff notes that digital tools have sped up many processes in her MTBs, increasing their frequency from just 6 per year to 8 in 4 months.
Prof Cherepanoff also notes that digital tools are making large volumes of data easier to view and understand. She hopes that NGS reports can be customised to reduce the data overload that overwhelms users with less expertise, and also help prevent them from missing data or overlooking significant molecular features. She also hopes that they increasingly show prognostic impact, and aims to collect trial data on these tools showing improved clinical workflows.
Both Prof Gibbs and Prof Cherepanoff eagerly await AI-assisted digital analysis tools or algorithms that can process complex mutational genomic data and integrate these into treatment guidelines, literature and trials. They also expect that digital tools will increasingly connect less-experienced clinicians to triage algorithms, surveillance, referrals or trials. Over time, it is likely that more of these tools will be cloud-based, and medical information management platforms will ultimately be app- and subscription-based.
Some of these capabilities and services are already here, but clinicians have been slow to adopt them. “I see the gap between what’s possible and what’s being delivered,” says Prof Gibbs. “It’s getting bigger quickly and that concerns me. I work on different ways to understand the significance of biomarkers, and it’s an urgent need, definitely.”
To learn more about the evolving role of next-generation sequencing, molecular tumour boards and clinical decision support tools in cancer care, check out some of these other case studies:
