The utilization of ctDNA for the detection of minimal residual disease in patients with LA HNSCC

The research of Dr Natasha Honoré, medical oncologist at UC Louvain, Brussels focuses on the utilization of circulating tumour DNA (ctDNA) for the detection of minimal residual disease in patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The methodology was developed to identify ctDNA presence within 12 weeks after curative intent treatment, aiming to predict relapse in these patients. A non-personalized approach was employed, eliminating the need for tumour sequencing and thereby saving time.

When applied to our patient cohort, the ctDNA measurement using this methodology demonstrated the ability to predict relapse with a sensitivity of approximately 78%, which was correlated with progression-free survival (PFS) among patient groups post-treatment. To enhance the sensitivity of this method, the study explored various strategies. Currently, 24 genes, along with E6&E7 HPV16 genome and HPV DNA, were analyzed.

Several potential improvements were proposed, necessitating rigorous testing. While the inclination might be to expand the gene panel, it is crucial to strike a balance, as studies employing extensive gene panels have not consistently yielded superior sensitivity. Therefore, identifying the appropriate number of genes and considering the integration of epigenomic alterations were emphasized. The availability of DNA in plasma was deemed critical during the evaluation of different options.

In cases of HPV-positive tumours, the TTMV-HPV DNA biomarker proved valuable, particularly when HPV served as the primary driver of the tumour. However, in P16-positive patients, who often exhibit heavy smoking and drinking habits, the connection between HPV and tumour progression is less certain.

Among the study cohort, three patients experienced relapse unrelated to the primary tumour. In one instance, a methodological factor, specifically the timing of sample collection, could explain this discrepancy. In other cases, the ctDNA outcomes provided a valuable indication to explore beyond the original tumour site.

Despite the promising findings, it is essential to acknowledge the limitations of the study, including the small sample size and single-centre design. While efforts were made to enhance method sensitivity, validation in larger patient cohorts is imperative. Addressing technical challenges related to sequencing, extraction, and data analysis is crucial for successful implementation. Additionally, the retrospective nature of the data underscores the need for prospective studies to further validate the results. Exciting developments are underway in the field of head and neck cancer research, promising significant advancements in our understanding and management of the disease.

References:

Honoré N. – Minimal residual disease (MRD) diagnosed by a plasma tumor-agnostic circulating tumor DNA (ctDNA) assay after curative therapy in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) predicts disease relapse and survival. ESMO2023 – #858O