Circulating tumor DNA (ctDNA) dynamics in liver-limited metastatic colorectal cancer (mCRC) patients resected after first-line systemic treatment.
Year: 2025
Type: conference-abstract
Abstract: 3544 Background: Liver-limited disease (LLD) occurs in 20-30% of metastatic colorectal cancer (mCRC) patients. Although 20-30% of patients who undergo resection can achieve a long-term overall survival benefit from liver surgery, most patients relapse during the first two years after hepatectomy. ctDNA is a promising tool in detecting the presence of minimal residual disease (MRD) after resection of colorectal liver metastases and a reliable prognostic tool for recurrence. ctDNA and its dynamics may also serve as a prognostic tool in patients candidate to liver resection following upfront chemotherapy. Methods: mCRC patients (N = 116) with initially unresectable LLD and R0/R1 resected after upfront chemotherapy were selected from 3 Italian academic centers. Blood samples were collected prospectively at baseline (T0), pre-surgery (TPrS) and post-surgery (TPoS). T0 samples were evaluable for 82 patients, TPrS for 116 and TPoS for 60. Biobanked plasma samples were analyzed with the Tempus xM MRD assay (xM), a tumor-naïve ctDNA MRD assay that integrates methylation and genomic variant classifiers to deliver a binary MRD call blinded to clinical outcomes. The methylation classifier detects fragments with CRC methylation signatures in differentially methylated regions trained by sequencing CRC and presumed-healthy samples on a 6 Mbp panel. The variant classifier detects highly prevalent CRC variants. Results: Methylation results were available for 60 TPoS patients with a clinical sensitivity of 56.4% and specificity of 100%. TPoS ctDNA status was associated with relapse-free survival (RFS) with the ctDNA- group experiencing longer median RFS (mRFS) than ctDNA+ (HR = 6.7, mRFS > 24 mos vs. 5.5 mos, p < 0.001). Patients who were persistently ctDNA- by methylation calls (n = 20) or converted to negative (n = 13) from TPrS to TPoS experienced longer RFS (mRFS 16.3 mos and > 24 mos respectively). Those who remained persistently ctDNA+ (n = 9) or converted to ctDNA+ (n = 12) had a mRFS of 5.3 and 5.9 mos respectively. Patients with variant allele fraction (VAF) reduction of ≥50% from T0 to TPrS (N = 53) experienced longer RFS than those who had < 50% reduction or increase in VAF (N = 18) (HR 2.21, mRFS 18.8 mos vs. 9.8 mos, p = 0.012). Lastly, patients that remained positive from T0 to TPrS (N = 23) experienced a numerically shorter RFS compared to those who converted to negative (N = 47) (median RFS 10.4 and 15.1 mos, HR 1.65, p = 0.10). Conclusions: xM demonstrates remarkable performance in predicting clinical recurrence and correlation to RFS at TPoS in LLD mCRC patients resected after upfront systemic therapy. Interestingly, patients with a VAF reduction ≥ 50% experience longer RFS following surgery, suggesting a potential role for this tool in multidisciplinary decision making in this setting.
Source: Journal of Clinical Oncology
Authors: Vittorio Studiale, Kristiyana Kaneva, Roberto Moretto, Farahnaz Islam, Guglielmo Vetere, Daniel Neems, Christine Lo, Robert Tell, Seung Won Hyun, Veronica Conca, Chithra Sangli, Ada Taravella, Matteo Landi, Filippo Ghelardi, Kate Sasser, Sabina Murgioni, Michele Prisciandaro, Riccardo Cerantola, Halla Nimeiri, Chiara Cremolini
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4410804713