The Pathology-Oncology Connection: Labs in Action

Episode 8 of the 'Better Testing, Better Treatment' podcast welcomes our special guests, Dr. Chandler Park, co-director of GU cancer clinical trials at Norton Cancer Institute, and Dr. Sameer Talwalkar, board-certified Hematopathologist and Molecular Pathologist at CPA Lab, Norton Healthcare.

Dr. Park and Dr. Talwalkar to discuss how tailored testing and clear communication have led to better diagnostic and treatment decisions. The conversation also explores how the relationship between the lab and oncologist was built and how they navigate this through advancing treatment options.

The Better Testing, Better Treatment Podcast series

We are excited to announce that our eighth episode is now available!

This series of digital engagements highlights how targeting pathogenic gene fusions can improve patient outcomes:

The clinical utility of NRG1 fusions as a poor prognostic factor across tumor types, exploring NRG1+ tumors’ metastatic potential and histological features

Testing for NRG1 fusions in cancer patients, focusing on the importance of targeted NGS approaches and RNA-based NGS

As we conclude this series, catch-up on various activities so far:

 into the molecular biology of NRG1 fusions and explore its clinical relevance

to Dr Pranil Chandra discuss the clinical utility of NRG1 fusions and how to test for them using targeted NGS approaches and RNA-based NGS during the Lab Talk "Testing for NRG1 fusions: The new kid on the block of actionable pathogenic gene fusions"

key insights about RNA-NGS (RNA-based Next-Generation Sequencing) and its importance in detecting pathogenic NRG1 fusions

 the FAQs from the series and the slides from the Lab Talk. These can be printed for ease of reference.

 shed light on pathogenic gene fusions and the significant clinical utility of NRG1 fusions as key actionable pathogenic gene fusions which have been identified across many tumor types. The message highlighted the importance of comprehensive testing with RNA-based NGS being the optimal methodology to capture pathogenic gene fusions.

(Senior Vice President, Chief Genomics Officer, PathGroup), exploring NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions. To further support labs in NRG1 fusions testing Dr Chandra discussed how to properly test for NRG1 fusions in cancer patients, focusing on targeted NGS approaches and RNA-based NGS.

, and detecting them can improve patient outcomes.

RNA-NGS (RNA-based Next-Generation Sequencing)

 is more effective than DNA-only NGS in identifying actionable gene fusions.

Clinical guidelines (e.g., ESMO, ASCO) recommend RNA-NGS

 for detecting gene fusions, including NTRK fusions, due to its superior sensitivity.

 are emerging as actionable targets linked to poor prognosis, highlighting the importance of comprehensive RNA and DNA profiling.

RNA-NGS and DNA-NGS together enhances the detection of structural variants

, providing expanded therapeutic opportunities for patients.

Thank you for joining us throughout the series!

If you have any questions on this series or would like to learn more about the DXRX Network, contact help@dxrx.io.

Over the past few months, Diaceutics have delivered a series of digital activities focusing on testing of NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions.


Spain got its first Notified Body (NB) in February when the Centro Nacional de Certificatión de Productos Sanitarios (CNCps) received its designation. The Irish NB The National Standards Authority of Ireland (NSAI) had its designation temporarily suspended in December 2024 but was reinstated on 18 March 2025 after process improvements identified in an audit were put in place. There are, therefore, currently 14 NB listed as active and able to take on certification work. There is likely still not enough NB to provide conformity assessment to all devices that require it, especially given the time taken for the process. Estimates of the time taken for certification vary: one survey found that 75% of devices received certification in 13-18 months with 17% taking 19-24 months with the chief limitations being the tightened regulatory requirements and limited time and capacity of notified bodies. These problems are exacerbated by the fact that many manufacturers may be interacting with a NB for the first time and are unfamiliar with several of the processes involved. Also, in order to maintain impartiality, NB are not allowed to act as consultants to clients for whom they are undertaking conformity assessments – they can’t “coach” a client through the process.
NB may refuse or return applications and the most common reasons are: outside of the scope of the NB, wrong classification of the device, wrong conformity assessment procedure or incomplete application.
The structure and quality of the technical documentation supporting the application can also be problematic, again made worse by an applicant’s unfamiliarity with the process and the documentation required. Here, the role of consultancies with expertise in the field, but not acting as NB, may be vital to help manufacturers get the certification they need for their products but will likely add considerably to the costs and possibly be in short supply.
Certification costs vary considerably among NB with flat fees for application of the order of several thousand € and separate fees for certification audits and assessment of technical documentation running several hundred € per hour or several thousand € per day depending on the NB.Overall, certification costs could be a minimum of €50k with the potential to go much higher, an even higher if consultancy is required.The EU mandates that all NB publish their fees for the sake of transparency and this information is available 


So, a lot of the issues with NB are still present and it remains to be seen how many low margin products become economically unsustainable because of regulatory costs and are, therefore, pulled from the market.

EUDAMED – the plot thickens…or does it?


So far just 3 out of 6 EUDAMED modules are operational and that only on a voluntary basis. These are:
- Actor Registration: Information on manufacturers, importers, distributors, and other relevant parties.
- UDI/Device Registration: Details on unique device identifiers (UDIs), device classification, and registration.
- Notified Bodies and Certificates: Information about notified bodies and the certificates they issue.
The other 3 modules are:
- Vigilance: Reporting of adverse incidents and recalls.
- Market Surveillance: Oversight of medical devices on the market.
- Clinical Investigations and Performance Studies: Data on clinical trials and performance studies.

It is anticipated that use of the first 3 modules, and of the market surveillance module, will become mandatory some time in 2026 with the timeline for use of the remaining 2 modules uncertain but possibly late 2026 or 2027.

In addition to huge delays – EUDAMED was intended to be operational in 2021 – there have been allegations, somewhat contentious, that the costs related to development of the databases and systems have spiralled, that the project is over time, over budget and over staffed. Whether these allegations are unfounded or not, there are still many uncertainties over how, and on what timescale, EUDAMED will become fully operational.


The EU Commission called for feedback on both the MDR and IVDR with a consultation period extending from 12th December 2024 to 21st March 2025 and adoption of “fine tuning” of the regulations due in Q4 2025.There are currently 398 responses and, according to Medtech Insight, the Commission has faced a “torrent of criticism” of the regulations. Recurrent themes in the feedback include the complexity of the regulations, the difficulty and cost of their implementation (see comments about consultancy, above) and their potential to stifle innovation.
Once the consultation is closed, we’ll analyse the feedback in terms of the problems labs are having with implementing the regulations for laboratory developed tests (LDT, also called the in-house exemption, Article 5.5 IVDR) and present this as a special review.


In December, the EU provided guidance on “The Information Obligation in Case of Interruption or Discontinuation of Supply of Certain Medical Devices and 

 Diagnostic Medical Devices”. As of 10th January 2025, manufacturers will have to inform the EU if they anticipate an interruption in the supply of a device or intend to discontinue it in the EU if the non-availability of the device carries a risk of serious harm to patients or public health in one or more member states of the EU. Completed notifications will have to be cascaded down through economic operators e.g. distributors to final customers. Notification must be provided at least six months prior to anticipated interruption or intended discontinuation.
Included in the guidance as the phrase “It should be noted that serious harm can also be due to the 

inability of a healthcare professional to deliver a specific medical treatment due to an interruption or discontinuation in the supply of a device

.” (our emphasis).This may have special relevance in the case of companion diagnostics where the non-availability of a specific test may interfere with the use of the therapy which is gatekeepered by the companion diagnostic.
However, the regulation does not apply to “custom-made devices”.While not clear, this, and application of the regulation to manufacturers, suggests that labs who make LDTs covered by the in-house exemption may not have to comply with the notification requirements.

So, problems remain with NBs, EUDAMED is still problematic and well behind schedule and a lot of very unhappy people have told the EU what they think of the regulation.

As we move into 2025, the regulatory landscape for IVDR continues to evolve. In 2024, we shared the updates on the upcoming changes and now we’re providing the latest insights in 2025 to ensure you stay informed and prepared.

The goal of Precision Medicine in oncology is to identify the right patient, for the right therapy, at the right time. 

Patient characteristics drive treatment decisions that are most likely to provide benefit.

Targeting pathogenic gene fusions can improve patient outcomes. 

In an analysis of 79 patients with identified gene fusions, poorer outcomes were observed in patients with pathogenic gene fusions who were not matched to an FDA-approved fusion-targeted therapy.

comprehensive profiling at the DNA and RNA levels (RNA-based NGS)

provide patients with therapeutic opportunities beyond standard treatments.

from PathGroup explored pathogenic gene fusions as oncogenic drivers and actionable biomarkers in precision oncology, focusing on NRG1 fusions. The session covered the 

 as a poor prognostic factor across tumor types, exploring 

 and histological features. Dr. Pranil Chandra from PathGroup also 

discussed how to properly test for NRG1 fusions in cancer patients

, focusing on targeted NGS approaches and RNA-based NGS.

defines cancer according to its genomic profile rather than by the organ or tissue of origin

select treatments most likely to benefit the patient

NRG1 is an important pathogenic gene fusion 

and is reported to be associated with poor outcomes

NRG1+ tumors possess aggressive histological features 

associated with increased tumor growth, invasiveness, 

recurrence, resistance to therapy, metastasis, and worse prognosis

Comprehensive testing with RNA-based NGS, including DNA and RNA sequencing, is recommended to detect NRG1 fusions

 due to its diversity of gene fusion partners and breakpoints and its large intronic region

Concurrent RNA-NGS and DNA-NGS testing should be used clinically to maximize structural variant detection relative to DNA-NGS alone

Click here to watch the Lab Talk recording now.

Thank you for joining us so far! Stay tuned for more insights on NRG1 fusions!

Download the testing for NRG1 fusions FAQs here.

Over the past couple of months, Diaceutics have delivered digital activities focusing on testing of NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions.

Exploring Inherited Cancer: from clinic to lab. 

In episode 7 of the 'Better Testing, Better Treatment' podcast, we are thrilled to welcome our guests Anna Considine, Consultant Cancer Genetic Counsellor and Samantha Butler, Principal Clinical Scientist, from the Birmingham Women and Children’s NHS Foundation Trust and the West Midlands Regional Genetics Service.

Anna Considine and Samantha Butler explore how genetic testing for inherited cancer has evolved over the last 20 years, transforming both clinical practice and patient care.

Don't forget to catch up on previous episodes in the series!

Listen now

We are excited to announce that our seventh episode is available now.

Insights

The Pathology-Oncology Connection: Labs in Action

Testing for NRG1 Fusions - The Series

IVDR Report Update 2025

Testing for NRG1 Fusions Series So Far

Exploring Inherited Cancer: from clinic to lab