21 June 2022

Cell-free DNA biomarkers can help to identify treatment responders and non-responders of head and neck cancer patients

Bianca-Olivia Nita

Bianca-Olivia Nita

The team of Jeroen de Ridder finalized a Clinical Proof of Concept (CPoC) study in which they tested the feasibility of circulating tumor DNA (ctDNA) analysis in head- and neck cancer patients as treatment response identifier. Their results are promising and more extensive validation in larger patient cohorts is underway.

About the Clinical Proof of Concept Programme

Oncode Institute aims to link fundamental and clinical research to enable efficient translation of promising findings into novel diagnostic methods and clinical treatment strategies. Oncode created the Clinical Proof-of-Concept (CPoC) fund to support the clinical translation of Oncode’s fundamental research.

The unmet clinical need

Each year, head and neck cancers account for 380.000 deaths worldwide. Radiotherapy with or without concurrent chemotherapy is the primary treatment for advanced pharynx and larynx cancer. For the many patients that do not respond to primary curative (chemo) radiotherapy, salvage surgery is the final treatment for residual or recurrent disease. Unfortunately, it turns out that many patients are not fit for this treatment anymore as a consequence of earlier treatment.

This creates an urgent need for patients to identify the response to treatment while treatment is ongoing. This information will aid in making decisions on treatment adaptation, for example dose(de)-escalation or switching to a different treatment such as immunotherapy. Hence, monitoring treatment response, and early detection of recurrences or residual disease is important for increasing the chances of treatment success and improving patient’s quality of life.

What could be the solution?

A solution could be a reliable biomarker to ascertain (individualized) treatment response or disease recurrence. In the blood of cancer patients, tumour DNA (ctDNA) is circulating. However, it remains difficult to detect ctDNA, as many DNA molecules from healthy cells are circulating in the blood plasma.

Oncode Investigator Jeroen de Ridder (UMC Utrecht) and his research group investigated a new and innovative approach - called CyclomicsSeq. With this approach, single ctDNA molecules can be sequenced with high accuracy by a three-step processconsisting of capturing, copying and concatenation of the original double-stranded ctDNA molecules. This approach is unparalleled by any other method in terms of sensitivity, cost-efficiency and speed. Within the CPoC project titled “Point-of-care monitoring of head and neck cancer treatment response and recurrence development using nanopore-based ctDNA consensus sequencing”, the researchers applied the CyclomicsSeq ctDNA test in patients with advanced head and neck cancer squamous cell carcinoma (HNSCC). Prior to and during treatment, they measured the ctDNA levels in the blood of these patients in order to determine whether a patient responds to the primary chemoradiation treatment.

Main results and next steps

Roughly, 50% of the patients responded to the treatment. For these patients, the ctDNA levels in the blood decreased and were even absent 1-3 weeks after treatment initiation.

One patient with recurrent disease initially showed a similar decrease in ctDNA levels, but ctDNA remained present in the blood. These results show that 3-4 weeks after treatment initiation, CyclomicsSeq already identified responders and non-responders correctly. The initial study results have been published here.

Jeroen de Ridder says: “Based on the results obtained in this CPoC project, we were able to confidently set the next steps towards validating our technology in clinical practice. As a next step, we aim to include more patient samples to confirm these results in a larger study group.”

Marlinde Smit

Marlinde Smit

Programme Manager

Marlinde is a programme manager at Lygature. After completing her biomedical studies at the University of Groningen, she did a Phd at the Pediatric Oncology department in the UMCG. Marlinde is passionate about oncology research and loves to bring people together and organize and manage projects. As a programme manager for Oncode, Marlinde supports Oncode researchers to translate their findings into the clinic. By organizing clinical workshops, she brings researchers and clinicians together to explore how fundamental research can address unmet clinical needs. She also focuses on the clinical proof-of-concept programme used to fund pre-clinical and clinical projects. She coordinates a team of experts to support and advice Oncode Researchers and clinicians who together applied for funding.

Programme Manager

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