Monitoring of circulating tumor DNA (ctDNA) shows promise as a tool for early response assessment in patients with anal cancer receiving chemoradiation, according to a presentation at the 2023 ASCO Gastrointestinal Cancers Symposium.

In a retrospective analysis, researchers evaluated patients with anal squamous cell carcinoma who were treated with definitive-intent chemoradiation. The researchers examined several outcomes in conjunction with ctDNA analyses in these patients.

The analysis of ctDNA involved a commercially available, multiplex PCR-based assay (Signatera) that targeted clonal mutations found in tumors. ctDNA was analyzed at baseline and as a component of post-treatment surveillance.

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The study included 31 patients who had a median age of 61 years (range, 46-79). Most patients (65%) had stage III disease. Patients received a median radiotherapy dose of 54 Gy over a median of 27 fractions, and the median radiotherapy duration was 38 days. For chemotherapy, patients received mitomycin plus capecitabine (68%), mitomycin plus 5-fluorouracil (16%), or capecitabine alone (16%). The median follow-up was 32 weeks.

One patient was excluded from the analysis due to insufficient tissue, corresponding to a technical failure rate of 3%. From a total of 27 patients who successfully completed baseline testing, detectable ctDNA was found in 23 patients, giving an 85% baseline ctDNA detectability rate.

Average baseline ctDNA values differed between patients with stage I/II disease and those with stage III disease. Patients with stage III disease had an average baseline ctDNA level of 34 mean tumor molecules (MTM)/mL, compared with 3.2 MTM/mL in patients with stage I/II disease.

Mid-treatment analysis showed that 57% of patients cleared ctDNA in a median of 21 days. Mid-treatment clearance of ctDNA was seen in 73% of patients with stage I/II disease at a median of 30 days and in 50% of patients with stage III disease at a median of 31 days.

Baseline median ctDNA values were lower in patients who cleared ctDNA mid-treatment, compared with patients who cleared it post-treatment (0.59 MTM/mL and 34 MTM/mL, respectively). By the end of treatment, the rate of ctDNA clearance in the overall population was 96%.

The clinical complete response rate at 3 months post-treatment was 96%. The 1-year locoregional recurrence rate was 4%, the 1-year disease-free survival rate was 96%, and the 1-year overall survival rate was 100%. The median time to ctDNA clearance was 30 days, and the median time to clinical complete response was 136 days.

“With a high baseline detectability rate and low technical failure rate, ctDNA has been very useful in tracking response throughout treatment, as our patients cleared ctDNA by a median of 100 days before clinical response assessment,” said study presenter Janet Alvarez, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“I do want to acknowledge that, given the retrospective nature of this report, our ctDNA draws did not correlate with clinical reassessment, so we are unable to state definitively if ctDNA clearance preceded clinical response. But, based on prior studies suggesting a delayed clinical response, we hypothesize this is likely the case.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Alvarez J, Cercek A, Mohan N, et al. Circulating tumor DNA (ctDNA) for response assessment in patients with anal cancer treated with definitive chemoradiation. ASCO GI 2023. January 19-21, 2023. Abstract 1.