Tumor-informed ctDNA assay to predict recurrence in locally advanced squamous-cell carcinoma of the head and neck (SCCHN).
Background: Despite multimodal treatment, locally advanced (LA) squamous-cell carcinoma of the head and neck (SCCHN) has a recurrence rate of ∼50%. Circulating tumor DNA (ctDNA) has emerged as a potential biomarker for minimal residual disease detection after curative-intent treatment. This strategy could be used to identify the patients at greater risk of recurrence, for whom extended or intensified therapy and/or surveillance imaging may be considered.
Methods: A personalized, tumor-informed 16-plex multiplex PCR-next-generation sequencing assay was used for the detection of ctDNA in banked plasma samples collected pre-treatment (baseline time point) and within 12 weeks from the end of curative-intent treatment (post-treatment time point). The primary and secondary endpoints were recurrence-free-survival (RFS) and overall survival (OS) of post-treatment ctDNA-positive and -negative patients, respectively.
Results: Out of a cohort of 50 patients with LA SCCHN, personalized ctDNA assays were successfully designed for 43 patients. Among these 43 patients, ctDNA was detected in 42 of 43 (97.6%) patients at baseline. At the post-treatment time point, ctDNA was detected in 4 of 42 (9.5%) patients, 3 of whom relapsed. Of the 43 patients, 11 (26%) experienced disease recurrence within 2 years of follow-up. Patients with post-treatment ctDNA positivity demonstrated a significantly inferior RFS and OS (P ≤ 0.05), compared with ctDNA-negative patients. The median lead time for ctDNA positivity over clinical recurrence was 7.0 months (range 3.6-7.1 months).
Conclusions: The personalized, tumor-informed assay detected pre-treatment ctDNA in the majority of the patients with LA SCCHN. ctDNA positivity within 12 weeks of completing curative-intent treatment was predictive of worse RFS and OS. These results support studies to assess the value of longitudinal testing for surveillance and may open the path to initiating treatment upon molecular recurrence in patients with LA SCCHN.