The following is a summary of “Clinical validation of a tissue-agnostic genome-wide methylome enrichment MRD assay for head and neck malignancies,” published in the September 2024 issue of Oncology by Liu et al.

Despite advances in treatment, outcomes for patients with locally advanced head and neck cancer (HNC) remain suboptimal, with five-year survival rates at approximately 50%. Most recurrences occur within the first two years following treatment, highlighting the need for early detection of molecular residual disease (MRD). A practical, tissue-agnostic test for MRD detection, suitable for both patients who are HPV-positive and HPV-negative HNC, is crucial, given the limited availability of tissue samples in this population. This study aimed to develop and validate such a test using a genome-wide methylome enrichment platform.

A cohort of 325 patients with stage I-IVB HNC, comprising both HPV-positive and HPV-negative cases, was enrolled. Peripheral blood plasma samples were collected at diagnosis and approximately 3, 12, and 24 months post-treatment. A total of 1,155 samples were analyzed, with distinct subsets used to train and validate a classifier capable of detecting MRD. The primary endpoint was recurrence-free survival (RFS), and the study was conducted with a median follow-up of 60 months.

In the blinded validation set, patients who are MRD-positive experienced significantly worse RFS, with a hazard ratio (HR) of 35.7 (95% CI, 10.8 – 117.8; P < 0.0001). Patients who are HPV-negative had an even higher HR of 42.3 (95% CI, 9.8 – 182.3; P < 0.0001), while for patients with HPV-positive oropharyngeal cancer, the HR was 24.1 (95% CI, 3.0 – 196.87; P < 0.0001). Importantly, MRD positivity predicted clinical recurrence with a lead time of up to 14.9 months and an average lead time of 4.1 months. The assay demonstrated high surveillance sensitivity (91%, 95% CI, 77% – 97%) and specificity (88%, 95% CI, 80% – 93%).

This study validates the clinical performance of a tissue-agnostic genome-wide methylome enrichment assay for detecting MRD in patients with HNC. The test exhibited high sensitivity and specificity across diverse anatomical sites, HPV statuses, and treatment regimens, underscoring its broad applicability in monitoring MRD in HNC. Early detection of MRD through this method offers a valuable opportunity to intervene before clinical recurrence, potentially improving outcomes in this challenging patient population.

Source: sciencedirect.com/science/article/pii/S0923753424039292