Role of dynamic ctDNA monitoring in cervical and anal epidermoid carcinomas under curative chemoradiation.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker to predict recurrence in solid tumors such as colorectal and breast cancer. Defining complete response after chemoradiation remains challenging, as post-treatment inflammatory and tissue changes limit clinical and imaging evaluation.

METHODS: The authors conducted a prospective longitudinal study of patients with localized cervical and anal cancer treated with curative-intent chemoradiation with the aim of evaluating the role of ctDNA as a predictor of recurrence. Blood specimens were collected at D1, D29, immediately post-treatment, 8-weeks, 24-weeks, and every 6-months up to 5-years. ctDNA testing (Signatera™) was provided by Natera as an in-kind donation. The primary endpoint was correlation between 8-week ctDNA and recurrence.

RESULTS: 28 patients were evaluable. Ten recurrences occurred, all in patients with positive ctDNA after chemoradiation and before radiologic progression. The median interval between ctDNA positivity and radiologic progression was 3.0-months (range 0.5-21.3). All patients with radiologic complete response at 6 months had negative 8-week ctDNA. Among those without complete response, 8-week ctDNA identified most who later progressed (6/8), while all without complete response who did not progress had negative ctDNA. Eight-week ctDNA positivity was strongly associated with inferior progression-free survival: median 6.7-months in ctDNA-positive versus not reached in ctDNA-negative patients (HR = 40.09, p = 0.001).

CONCLUSION: Among patients with cervical and anal cancer, ctDNA monitoring after definitive chemoradiation identifies individuals without complete response and predicts recurrence. ctDNA positivity at 8-weeks identifies a very high-risk group for whom treatment intensification trials are warranted.