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ctDNA May Offer Clues to Prognosis in Patients With Rectal Cancer

By: Celeste L. Dixon
Posted: Thursday, August 8, 2019

In which patients with locally advanced rectal cancer would a “watch and wait” approach be most appropriate after neoadjuvant chemoradiation and surgery? Steps toward an answer may be found in the results of a pilot study of circulating tumor DNA (ctDNA) as a potential prognostic marker, which were presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 3544).  

Clinical complete response is the treatment goal, noted Lifeng Yang, MD, PhD, of Fudan University Shanghai Cancer Center, Shanghai, China, and colleagues. However, there is “growing interest [in] organ preservation…to improve quality of life.”

The team recruited 119 patients with locally advanced rectal cancer who were receiving neoadjuvant chemoradiation. Then they collected 595 serial plasma samples on days 0, 15, and 25 of radiotherapy as well before and 7 days after surgery. They calculated ctDNA levels by dynamic monitoring of the mutant allele frequency of somatic mutations in plasma.

The dynamic monitoring process may predict tumor recession grade (TRG) and prognosis in such patients, concluded the researchers. Specifically, “detected mutation of TP53 and APC genes in pretreatment samples was negatively correlated with patients’ response to neoadjuvant chemoradiation,” noted Dr. Yang and co-investigators. “Alterations in homologous recombination and adherens junction pathways were associated with a better response (P < .05). Detection of pretreatment mutations [at any time] during neoadjuvant chemoradiation was significantly (P = .03) decreased from TRG3 to TRG0 group (33%, 29%, 22%, and 4%, respectively), whereas detection of acquired mutations showed an opposite trend (P = .04). Further, detection of pretreatment mutations after completion of neoadjuvant chemoradiation was significantly associated with worse disease-free survival (P < .05).”

Disclosure: The study authors’ disclosure information may be found at coi.asco.org.



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