AACR 2025: In Colorectal Cancer a ctDNA based Liquid Biopsy may Detect Recurrence Prior to Imaging

Interim results from the VICTORI study presented at the American Association for Cancer Research (AACR) Annual Meeting 2025, held April 25-30, in Chicago, Illinois, shows that  an ultra-sensitive circulating tumor DNA (ctDNA)-based liquid biopsy assay (NeXT Personal®; Personalis) detected signs of recurrence prior to imaging and provided prognostic value within one month after surgery in patients with colorectal cancer (CRC).[1]

NeXT Personal, which is uses whole-genome sequencing paired with advanced analytics, is designed to help detect minimal residual disease (MRD), monitor therapy response, and identify recurrence with high analytical sensitivity and accuracy, enhancing the decision-making process and ultimately improving patient outcomes in the ongoing battle against cancer.[2]

Recurrence
Detection of ctDNA after treatment is a strong indicator of recurrence in CRC, “but it often goes undetected because traces of ctDNA in the blood can be very low,” said Emma Titmuss, MSc, a bioinformatician at BC Cancer in Vancouver, BC, Canada, and the study presenter.

“If captured early enough, blood-based biomarkers could provide valuable information that can be incorporated into clinical decision-making,” Titmuss explained.

“After surgery, ctDNA-based liquid biopsies may help identify patients who would benefit most from additional treatment,” added Jonathan Loree, MD, MS, a medical oncologist at BC Cancer and the senior investigator of the study.

“Alternatively, this may help patients with good prognosis avoid toxicities from unnecessary chemotherapy. By monitoring patients for recurrences, liquid biopsies can continue to support clinical care and allow more patients to undergo second curative intent surgeries to remove early recurrences,” Loree added.

VICTORI study
VICTORI is a prospective study of colorectal cancer patients designed to identify the optimal timepoint post-surgery at which detecting ctDNA can predict recurrence following surgery. The interim analysis included 71 patients with resectable CRC, 52 with stage 1-3 disease and 19 with stage 4 disease.

The investigators created a personalized, tumor tissue-derived panel of up to 1,800 somatic variants for MRD detection for each patient, enabling detection of ctDNA down to ~1 part per million (PPM). [1]

Liquid biopsies were taken prior to surgery, every two weeks for eight weeks post-surgery, and every three months for a potential three years, and analyzed with the NeXT Personal assay.

All 33 participating patients with treatment-naïve disease greater than stage 1 had detectable ctDNA prior to surgery.

Of 65 patients evaluable for clinical outcome, 23 experienced clinical recurrence, the vast majority (87%) were ctDNA-positive within the landmark eight-week post-surgical period during which adjuvant chemotherapy is typically administered. All patients with clinical recurrence were ctDNA-positive before recurrence was detected via reflex imaging, by a median of 198 days earlier, including difficult-to-detect metastatic sites such as the lung. One patient had ctDNA recurrence 416 days prior to clinical recurrence.

According to Titmuss, ctDNA was detected as low as 2 parts per million (ppm). The median ctDNA level at first detection was 24.4 ppm, and the highest was 111,120 ppm. Higher ctDNA levels at first detection were linked to shorter times to clinical relapse.

“The results from our study help to clarify the ideal timepoint for ctDNA testing following a surgical procedure, showing that we can detect residual cancer as early as two weeks following surgery,” said Titmuss.

“However, with ctDNA assessments this close to surgery, there is the potential for normal cell-free DNA to dilute ctDNA, and four weeks appears to be a better time point clinically to sample for ctDNA to inform clinical decision-making,” she added.

Improving precision
The study continues to enroll more patients, which the authors hope will improve the precision of the results and guide future prospective studies that incorporate ctDNA as a decision point for clinical management and care.

One limitation of the study is the lack of intervention after ctDNA detection as this was an observational study. The authors note the need for randomized trials to determine the most effective use of this technology in clinical management.

The study was funded by Personalis, and BC Cancer Foundation.

Reference
[1] Titmuss E, Solar Vasconcelos JP, Navarro FCP, Ravi N, Abbott C, Chia B, Topham JT, Ladua G, Hegebarth D, Chuang SC, Lim HJ, Gill K, Gill S, Brown CJ, Ghuman A, Meneghetti A, Schaeffer DF, Chen RO, Boyle SM, Loree JM. Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study. In: Proceedings of the 116th Annual Meeting of the American Association for Cancer Research; 2025 April 25-30; Chicago, IL.: AACR; 2025. Abstract nr 3774.
[2] Northcott J, Bartha G, Harris J, Li C, Navarro FCP, Pyke RM, Hong M, Zhang Q, Ma S, Chen TX, Lai J, Udar N, Saldivar JS, Ayash E, Anderson J, Li J, Cui T, Le T, Chow R, Velasco RJ, Mallo C, Santiago R, Bruce RC, Goodman LJ, Chen Y, Norton D, Chen RO, Lyle JM. Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay. Oncotarget. 2024 Mar 14;15:200-218. doi: 10.18632/oncotarget.28565. PMID: 38484152; PMCID: PMC10939476.

Featured image © 2024 – 2025 Allison Saeng. Licensed under the Unsplash+ License

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