Next Generation Sequencing (NGS) is increasingly being applied in clinical practice. Credit: Shutterstock / FOTOGRIN

N​​​​​​​ext Generation Sequencing (NGS) is a rapidly evolving field in cancer.  

Around 190 NGS devices are in various stages of development globally, according to GlobalData’s medical device pipeline database, with 127 in active development, including 59 in early and 68 in late stage development. 

Exact Sciences, which launched its OncoExtra NGS device in 2023, is working to ensure physicians understand and have a minimum awareness of guidelines issued on NGS technology by the American Society of Clinical Oncology (ASCO).  

Focal areas of education for the company include spreading awareness around the drugs in associated targeted therapies, and how many genes physicians need to test with NGS to ensure their patients have been adequately assessed for potentially life-changing targeted therapies. 

“We have a medical affairs team that works in the field, delivering talks regarding these next generation sequencing guidelines and best in class practices,” Exact Sciences CMO, precision oncology Rick Baehner tells Medical Device Network. 

The company also works closely with patient advocacy groups. While it is focused on making sure that doctors understand this complicated technology, it also wants to help patients understand their options when they are faced with a life changing diagnosis like cancer. 

To drive adoption of NGS technology, Exact recently partnered with the Mayo Clinic. It will provide the medical centre with OncoExTra and RiskGuard, a test that screens for hereditary risk of cancer in patients that are currently healthy. 

“The partnership enables us to support their 130,000 unique cancer patients across their three cancer sites, a population which reflects the broad tapestry of the colour of American society,” Baehner says. 

ASCO recently issued guidelines on NGS recommending RNA sequencing be used if a gene mutation cannot be found in DNA testing. 

According to Baehner, the growing literature in the field indicates that RNA sequencing can detect upwards of 30% more therapeutically relevant fusions. 

Bahner says RNA sequencing can be understood as the transcript coming off the DNA, the blueprint by which protein – a key therapy target in cancer treatment – is made.  

“RNA can be powerful to detect fusions, where two pieces of two genes come together and form a new transcript, like an on switch, that can be an oncogenic switch that turns a tumour on,” he explains. “RNA can have a significant impact on patients and what therapy they receive.” 

To highlight the importance of RNA sequencing, he relates a recent case study of a 65-year-old man who had noticed a mass in his neck near a thyroid gland. 

A needle biopsy revealed this was a high-grade BRAF mutation in need of immediate surgical treatment. 

A BRAF mutation is a spontaneous change in the BRAF gene, which causes it to work incorrectly. The mutation causes the gene to turn on the protein and keep it on, which means certain cells receive ongoing signals to keep dividing and no instructions on when to stop. In time, this can lead to the development of a tumour.  

Upon this identification, the question became one of which targeted therapy this patient was eligible for. Immunohistochemistry and standard gene tests found that BRAF was negative for all targeted therapies. 

“But with comprehensive testing, the RNA sequencing part of the test identified a Neurotrophic tyrosine receptor kinase (NTRK) gene fusion,” Baehner says. 

This fusion is very rare. According to Baehner, it represents only around 1% of solid tumours. 

“In this patient's case, finding this NTRK fusion meant that, in addition to surgery, this patient was eligible for an NTRK inhibitor,” he says. 

ASCO recently issued two further guidelines, recommending that all women with breast cancer should be offered genetic testing, irrespective of their age or the stage of advancement of their cancer.  

The association now also recommends for all patients with solid cancer to get genetic testing, and they specify the types of tumours that need to be included in a testing panel, beyond the testing of BReast CAncer gene 1 and 2 (BRCA1/BRCA2), the testing of which aims to identify harmful mutations in these genes that predispose individuals, or their relatives, to cancer. 

With its comprehensive testing capabilities, NGS is effectively a universal platform. It can be used for tumour testing, but also has the capability to target other areas based on new guidance as it releases.  

According to Baehner, studies have shown the importance of Poly (ADP-ribose) polymerase (PARP) inhibitor therapies for patients with cancer, if they have germline mutations in BRCA1/2 in other genes.  

"The platform testing of the tumours is important today, but increasingly, the guidelines are also recommending testing germline, in order to assess for BRCA1/2 in Homologous recombination repair (HRR) genes,” says Baehner. 

“Patients with germline mutations have been shown to benefit from PARP inhibitors.” 

Baehner believes we're looking at a future today, particularly in reflecting on the new ASCO guidelines on BRCA1/2, where protein testing through immunohistochemistry, NGS of the tumour with broad tests, of which its OncoExtra device is capable, and notably germline testing are all important aspects of cancer research. 

"We're starting to see how all these pieces fit together to help cancer patients with their therapy, help their families understand the risk that they may or may not have, as a basis of a germline test, and helping inform the development of new targeted therapies," he says. 

An emergent field Exact would like to enter in the future is Molecular Residual Disease (MRD). MRD is a technology that uses NGS and involves sequencing a patient’s tumour, either via a biopsy or once it has been removed, to determine what mutations are unique to that tumour. Following a surgery, the physician can look through a blood sample to see if the patient still has that tumour’s DNA circulating in their blood. If it remains, a patient may then receive chemotherapy, and undergo monitoring to see if the tumour levels in their blood are going down. 

“This is a powerful new technology,” Baehner says. “Today it's reimbursed in colorectal cancer, but I think this is a technology that will be broadly applicable across solid cancers.” 

President Biden and First Lady Jill Biden’s Cancer Moonshot was outlined in 2022 with the aim to drive down the cancer mortality rate and prevent four million deaths by 2047. The drive advocates for expanding the availability of cancer screening in the US and for earlier cancer detection. 

Baehner believes we can now see the future of cancer in the use of techniques facilitated by NGS. He states the ongoing approach to cancer will centre on several areas, including broad sequencing of patients’ germline DNA, with a priority on understanding patients’ hereditary risk to help prevent cancer in the first place.  

According to Baehner, the modality of Multi-Cancer Detection – using NGS to look in the blood of healthy or at-risk patients to see if they may be harbouring an early cancer – will become a key focus. 

For patients with cancer, the ongoing evolution of approaches to diagnosis will centre on a combination of germline testing and tumour testing to help guide what therapy a patient will need.  

He adds that MRD tests as an outgoing solution, to be able to dynamically show whether patients were cured by therapy alone, are another piece in this puzzle. If chemotherapy or other targeted therapies are needed, the final stages will be in determining whether patients’ circulating tumour DNA levels are staying negative when they return to their oncology team for follow ups. 

Along with NGS technology, Baehner says the pharmaceutical industry has a large hand in helping drive this revolution by its ability to now target personalised therapies to mutations, checkpoint inhibitors, or PARP inhibitors.  

On the future of treatment, he concludes: “There'll definitely be a combination of advanced diagnostics and therapeutics, to help eradicate cancer for those unfortunate enough to have it.” 

The MedTech Forum 2024 took place in Vienna 22-24 May. Credit: Joshua Silverwood/GlobalData

A​​​​​​​ct now or lose out, was one of the major themes running through proceedings at the Medtech Forum 2024 event in Vienna Austria, with talks calling on stakeholders to be wary of geopolitical events including upcoming elections, climate change and the threat of cyber-attacks. 

The three-day conference, taking place between 22 and 24 May, saw stakeholders from medtech firms from across Europe and the world for discussions on the impending geopolitical shift awaiting the continent’s healthcare scene as regional and European Union (EU) elections threaten to shake up proceedings over the next year. 

The impending EU elections took central focus with MedTech Europe CEO Oliver Bisazza calling on stakeholders not to count out the upcoming elections across the continent for the sake of some of the more publicly observed and exciting national elections taking place throughout the year. A general election is set to hit the UK in July, and Austria is expecting its elections in September. 

Addressing the anxious crowd at the top of the summit, Bisazza said: “EU elections are not the trendiest or sexiest of elections when compared with national elections, but they are of critical importance. 

“So where is Europe going next? In terms of politics, it could be going in a very fresh new direction very soon. Both at a national level and at the European level. How can medtech companies work with governments to help us all get to where we need to be? To answer that question and inspire a new generation of policymakers who will take power in a few weeks or months, MedTech Europe has released a manifesto.” 

The MedTech 2024 Forum came alongside the group’s newly published MedTech Manifesto, published as a guide for the industry leading to 2029, calling on stakeholders and governments to ensure their various national healthcare systems are robust enough to face a series of problems with the same level of impact as the Covid-19 pandemic. Iterating that lessons of resilience learned during the pandemic are upheld in the face of political instability, economic downturns, and hostile actors. 

At the same time, the manifesto calls on governments across Europe to make smaller changes to European-wide healthcare systems for the benefit of the industry, with calls to overhaul the current European standard CE marking system for medical devices by creating a singular and more available European-wide entity to provide oversight for the entire regional industry. 

At the same time, it also urges nations across the continent to shore up access to medical staff in hopes of staving off a collapse in staffing as many medtech corporations inversely axe hundreds of worldwide. The manifesto also argues that the EU needs to remain a competitive and attractive place for medical technology and pharmaceutical firms to do business, in part, by ensuring its administrative and legislative systems can stay on top of an increasingly unstable political and ecological environment. 

Concluding his remarks, Bisazza added: “Europe went through much in the previous five years, it has had to manage a historic pandemic, as well as wars in Ukraine and Gaza, massive supply chain disruptions, energy inflation and the rise of protectionism and the rise in various austerity programmes. 

“Let me be clear, like many others, we too have become concerned from time to time that Europe is trending towards over-regulation. We have expressed many concerns to the EU and policymakers that their very valid leaning indication to regulate, if taken too far, risks ruining Europe’s historic leadership space as the global epicentre of MedTech innovation. 

“Despite this, we have reached the conclusion that the EU remains unequivocally attractive, thanks to its vibrant healthcare systems.” 

One of the major themes across the event on day one, taking centre stage as part of its own talk was the need for European-wide healthcare systems, service providers and private entities to adapt and prepare for more record-breaking summers as heatwaves threaten to batter the continent this summer following a slew of summers each of which ends up breaking the previous year’s records in terms of heat. 

The panel discussion entitled “The Climate Crisis – Our Next Health Crisis?” saw representatives from groups such as Siemens Healthineers and Philips joined with representatives from the World Health Organization (WHO) and the European Commission to discuss how manufacturers can be prepared for an incoming climate crisis and some of the things they can do themselves to reduce their own climate impact. Additionally, the same panel sought suggestions from the audience of medical technology stakeholders on what solutions they would want to see when it comes to tackling the overall climate crisis in terms of policy suggestions for EU members of parliament (MPs). 

The talk started off with a grim statistic from the WHO’s Antonius Kolimenakis who reminded attendees of the audience of the heat waves of 2022 in which research published in the journal Nature Medicine detailed how there were approximately 60,000 to 70,000 preventable deaths across the continent that year directly linked to the sharp rise in temperature. 

At the start of the conference, attendees were asked if they felt that the climate crisis was the next big crisis the medical technology industry was set to face in the coming years, event host Sue Savile then confirmed that the vast majority of attendees agreed that it likely was. 

Addressing the troubling stats, deputy director for small and medium enterprises at the European Commission, Hubert Gambs said: “It does not surprise me at all that many people think there will be another health crisis linked to climate change. But also, I think it is an opportunity for an innovative economic sector like MedTech. 

“The number of extreme situations is increasing, that cannot be denied by anybody. In Europe what we can do is look at ways to make ourselves more resilient in this challenge. That starts by developing products and devices that are safe and sustainable. Do you think about sustainability when you design a product?” 

Later in the day a side room at the conference another critical issue that has seen escalation over the past few years in the field of health tech, the rise in cyber warfare and ransomware attacks, primarily coming from hostile ransom groups acting out of countries such as Russia. These attacks primarily target weaker systems provided by private companies in smaller more vulnerable European nations, but these attacks have escalated in recent years since the launch of the Russian invasion of Ukraine, with some attacks taking over whole systems in countries such as the UK or US. 

The talk, entitled “Cyber resilience of European healthcare: the readiness of the sector” played host to a discussion between Martha De Cunha Maluf-Burgman, director of regulatory affairs and digital health at Edwards Lifesciences; and Alina Urs, a senior cyber security coordinator for the National Cyber Security Directorate of Romania. 

Launching the panel and detailing research carried out by the Romanian advisory body, Alina Urs said: “We discovered that many companies we were speaking to as part of our research identified ransomware as one of the biggest threats. What we saw from surveys was over 70%. One of the main issues that we saw was that around 95% of healthcare entities are not fully prepared when it comes to cybersecurity risk management. What we saw in our research was that again over 70% of entities in Romanian healthcare really don’t know about many of the aspects surrounding cyber-risk management. 

“There is a bit of a gap between the public and private sector. When we talk about cyber-risk management it’s not just about having the procedures and doing the paperwork. It’s all about being able to communicate with the clients and the decision-makers and getting them to make the right choices to ensure that your entity is protected from ransomware attacks. So that they invest in having backups but also so that they understand the reason for having a backup.” 

The overall theme of a resilient healthcare sector echoed on into day two of the conference when representatives from Edwards Lifesciences, Flying Health and the UK’s University of Warwick took to the central stage for a discussion on how the MedTech sector can ensure that its supply chains remain strong as outside pressures and sharp declines in available materials threaten to drive up device costs and stretch implementation timelines. At the same time, the panel faced the problems associated with capacity and what hospitals and healthcare facilities can do when they find themselves stretching the limits of their own capacity. 

When discussing the increasing demands on the staff of the current healthcare system, panellists were confronted with a stat taken from the new MedTech Manifesto that found that by the year 2040, one in every four workers will need to be a healthcare worker to prop up the current system without leaving a catastrophic shortfall. 

Commenting on the shocking figure, consultant for the German Healthcare think tank Flying Health, Rabea Stockert, said: “We all know that rough times are coming up for the healthcare system. Critical healthcare staff shortages are one of the main topics that we need to address. At several sessions today you have heard something that I will repeat again. We have a system that is under pressure today. We have demographic changes and rising costs as well as a lack of investment in healthcare and hospital infrastructure. All of these are leading to a healthcare workforce shortage that is actually already present today and will get worse in the upcoming years with a population that is getting older. 

“We see right now, particularly in the inpatient sector purchasing decisions at the moment do not take into account capacity savings. So, we still have a financing model, especially in hospitals, that encourages short-term economic considerations.” 

Panellists urged attendees and MedTech firms to push investors and sponsors to better select staff and equipment to prioritise longevity, sustainability and long-term viability over short-term models of spending high in a short time span so as to receive high returns. 

It follows as many countries across Europe and the UK, especially in the publicly funded sector, have seen an increasing exodus of highly-qualified healthcare staff amid cuts to pay and mass layoffs carried out by healthcare giants disincentivising the very staff healthcare firms claim to be in demand.