How are advanced diagnostics benefitting patients? Our recent webinar discussed the use of next-generation molecular analysis in precision oncology, focusing on improved treatment decision-making using these new tools. Here, we summarise the key insights from the session.
Access the ‘Unlocking Precision Oncology’s Full Potential through Next-Gen Molecular Analysis’ webinar series here.
Highlights:
- Sanjay Popat highlighted the implementation of ctDNA in the NHS for lung cancer, noting an estimated cost-effective benefit of £53 million.
- Eric Christenson emphasised the use of ctDNA testing in colorectal cancer, particularly in minimal residual disease and EGFR targeting therapies.
- Umberto Malapelle stressed the importance of integrating molecular pathology with next-generation sequencing to improve diagnostic accuracy and treatment efficacy.
- The discussion also covered the challenges and potential of using ctDNA and RNA-based NGS for cancer diagnostics and therapeutic decisions.
Implementing ctDNA testing in clinical practice
One important focus of the webinar was the challenges and potential of implementing ctDNA testing in routine clinical practice. In particular, Sanjay Popat explored recent pilot studies undertaken within NHS England to assess the effectiveness of ctDNA testing for individuals with suspected stage 3 or 4 non-small cell lung cancer. This method has the potential to improve patient outcomes by decreasing the length, and increasing the accuracy, of the current diagnostic process.
Below, we outline some of the key challenges identified before and during the pilot studies, the potential solutions and the benefits that ctDNA testing could bring.
Next-generation sequencing and ctDNA testing
Umberto Malapelle’s talk highlighted the technical advantages of using next-generation sequencing (NGS) in ctDNA testing. Notably, NGS has significant potential due to the limitations of single-gene testing strategies, including limited coverage, tissue constraints, incomplete mutational profiling and a reduced ability to identify rare mutations. NGS offers a more comprehensive overview, providing a more complex molecular profile.
While there might be a perception that NGS is more expensive, Umberto argues that it can be more cost-effective in the long run. By enabling the analysis of more genes and more patients with the same resources, NGS can optimise resource utilisation. Principally, optimised NGS strategies can double the number of patients assessed for the same cost as single-gene testing. Moreover, in terms of personnel hours, over three times as many patients can be assessed using the same resources.
Which innovation will have the greatest impact on the future of cancer care?
During the webinar, we asked the audience which innovation they think will have the greatest impact on the future of cancer care over the next 5 years? Check out the answers below.
ctDNA analysis and minimal residual disease
Eric Christenson’s talk described the use of ctDNA in the setting of minimal residual disease and the determination of EGFR targeting therapies in metastatic disease, specifically in the context of colorectal cancer.
Ongoing trials have shown that ctDNA analysis holds promise for identifying patients who may benefit from adjuvant therapy and for monitoring treatment response. Additionally, ctDNA positivity after surgery is strongly associated with a higher risk of relapse in colorectal cancer patients, whilst clearance of ctDNA during adjuvant therapy is associated with better outcomes. In light of these findings, studies are ongoing to determine the best strategies for the use of ctDNA, particularly to guide adjuvant therapy in colorectal cancer. The clinical utility of ctDNA for minimal residual disease is still being investigated, and challenges remain, such as the need for improved sensitivity and a need for standardised approaches.
Q&A Highlights:
“Q: Were there combined tissue and ctDNA testing at any stage [in the NHS England pilot studies], and how did they correlate?
Sanjay Popat: We’ve actually done this in a separate project. As you can see, we didn’t just turn up to the government and say ‘give us several million pounds to run this project.’ We had a lot of discussion, and parts of our dataset for combined ctDNA with tissue NGS testing was actually published in the European Journal of Cancer. We did a joint project where we did routine standard of care tissue NGS with ctDNA at the point of knowing the patient had cancer. And in fact, they correlated very well. But we saw 25% of cases had a tier one actual variant in ctDNA that was not picked up by tissue for a variety of reasons: coverage, lack of tumour, cellularity, all sorts of reasons. And 25% of cases where ctDNA didn’t pick up the variant, but tissue did so.
The way we’ve set the thing up in the UK, we very much hope that ctDNA will be the primary catch all. There’ll be a group of patients in whom we envisage that you may not need the tissue genomics, because you’ve got all the information you need to make your therapy decisions. Because lung cancer, genomically, is pretty straightforward, I would suggest, from the ctDNA. But there will be some in whom actually the ctDNA is non informative, and actually you do need to wait for the tissue moving forward.”
“Q: Do you think the results seen in colorectal cancer could be reflected in other cancers too?
Eric Christensen: Absolutely, I do. Obviously these tests are going to have slightly different characteristics depending on the tumour type that you’re talking about. But I do believe that even in things like lung cancer, there may be a role in the future to help guide adjuvant treatment decision making, after definitive treatments. I think colorectal cancer was the first one targeted because it’s a very common disease, and it’s really a situation where there is a kind of discrepancy, where a lot of patients are cured with surgery, but we end up giving pretty much all of them adjuvant treatment, at least in the US, to cure a minority of patients. There’s ongoing trials in pancreatic cancer, lung cancer and breast cancer as well, so I think we’ll get that data with more time.”
“Q: How is the shift from phenotype based approaches to personalised, biomarker driven treatment changing the landscape of diagnostics and therapeutic choices in solid tumours?
Umberto Malapelle: This is a really relevant point. By using the type of the advancement that we have discussed [in this talk], when we are able to fully integrate methylation information, RNA information and DNA information, this means that we will be able also to decodify the shift in morphological view. Also, by analysing the molecular counterpart.
Right now, to see this type of shift, for example, the phenotype shift in some resistant patients after the first-line treatment, you need to have tissue. You need to collect tissue, to re-analyse the tissue, and to define if there is a morphological shift or not.”
Access the ‘Unlocking Precision Oncology’s Full Potential through Next-Gen Molecular Analysis’ webinar series here.
