MRD continues to reliably predict disease progression in CRC

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Of the 79 patients with UICC stage II/III colorectal cancer (CRC) who participated in the Molecular Signatures in Colorectal Cancer study, screening tests for minimal residual disease (MRD) in 8 d ‘among them revealed positive results for circulating tumor DNA (ctDNA) after R0 resection for patients with non-metastasized solid tumors. Four of these patients also showed disease progression within 2 years.

These study results and others were presented recently at the 2022 American Society of Clinical Oncology Symposium on Gastrointestinal Cancers by researchers who compared the results of using MRD versus ultra-deep cell-free DNA sequencing (cfDNA ) for the potential for disease progression.

“The detection of primary tumor mutations in the cDNA of postoperative plasma from patients with non-metastasized solid tumors resected by R0 is a strong indicator of disease recurrence,” they explained. “We explored whether ultra-deep cfDNA sequencing could improve sensitivity and specificity with respect to time to progression.”

Eight-four patients were recruited for the study, but samples from only 79 patients passed all quality controls and could be included in the final analysis of matched tumor tissue samples, plasma-depleted blood cells, and cfDNA taken on average 7 days after surgery. The researchers used Roche AVENIO Tumor Tissue and ctDNA surveillance kits for next-generation sequencing, and they used AVENIO Oncology Analysis 2.0 software to identify somatic variants.

Following ultra-deep cfDNA sequencing at a median of 180 million reads per sample, the 8 patients identified as ctDNA positive (ctDNA+) were found to have 28 variants and an allele frequency (AF) of 0.15%. The results also identified a sensitivity of 44% (95% CI, 0.137-0.788), a specificity of 94% (95% CI, 0.86-0.984), a positive predictive value of 50% (95% CI, %, 0.157-0.843) and a negative predictive value. predictive value of 93% (95% CI, 0.843-0.977).

When the results were compared between ctDNA+ and ctDNA-negative (ctDNA–) patients, P values ​​of 0.0058 and 0.0333 were observed for the comparison of disease progression time and survival times, respectively. Multivariate analysis of time to progression determined ctDNA status (HR, 7.098; P = 0.0022) and neoadjuvant treatment (HR, 6.618; P = .0010) as significant parameters. Additionally, “multivariate analyzes of survival times resulted in ctDNA status (HR, 4.082; P = 0.0508) as the only significant parameter at the limit of the 9 parameters tested,” the authors wrote.

Non-significant parameters were gender, rectal tumor, right colon tumor, lymph node metastases, lymphatic invasion, venous invasion or positive perineural invasion, Eastern Cooperative Oncology Group status of 0, treatment neoadjuvant and adjuvant therapy.

For this study, patients were considered positive or negative for MRD (MRD+ and MRD–, respectively) whether or not there was disease progression within 2 years of surgery. The patients were followed for more than 2 years. For ctDNA+ status, a variant had to have an AF of at least 5% in tissues or at least 0.5% in postoperative plasma and a patient had to have at least 1 ctDNA+ variant.

“Even in this small cohort of CRC UICC stage II/III patients, detection of MRD in postoperative plasma is the strongest predictor of a shorter time to progression,” the authors concluded. “Ultra-deep sequencing of cfDNA samples did not influence MRD detection at the patient level.”

Reference

McNamara S, Patel RD, Adams HP, et al. Detection of minimal residual disease (MRD) in UICC stage II/III colorectal cancer (CRC) patients by ultra-deep sequencing of cfDNA from postoperative plasma. Presented at the American Society of Clinical Oncology Symposium on Gastrointestinal Cancers; January 20-22, 2022; San Francisco, California and virtual; Poster 26. Accessed 24 January 2022. https://meetinglibrary.asco.org/record/204647/poster

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