Abstract 458P
Background
Detection of ctDNA after surgery of stage I-III colorectal cancer (CRC) may identify patients with minimal residual disease (MRD) and help inform adjuvant treatment decisions. However, which ctDNA sequencing panel is suitable for monitoring MRD needs more technical research and clinical validation.
Methods
FFPE tumor tissues were collected from the surgical specimen of 40 CRC patients (stage I to III: 10%, 45%, 45%) between 2017 and 2018. Tissues and paired white blood cells were analyzed with a 733-gene NGS panel in a CLIA-certified laboratory. Blood samples were obtained before and 7-10 days after surgery. CtDNA was analyzed in a 127-gene panel with maximal coverage of recurrently mutated genes in CRC using Super-Seq technology-based assay, with median depth of 38678 X.
Results
Totally, the median age was 61 (range, 29-75) and 30% were female. Median follow-up was 31 months (range, 6-42 months). At least one somatic mutation was identified in the tumor tissue of 39 patients (one exclusion without eligible tissue DNA). For presurgical samples, ctDNA was detected in 78% (14/18) evaluable samples (stage I to III: 0 (0/1), 80% (8/10), 86% (6/7)). For postsurgical samples, ctDNA was detected in 16% (4/25) evaluable samples (stage I to III: 25% (1/4), 10% (1/10), 18% (2/11)) and 75% (3/4) ctDNA detectable patients recurred (stage I to III: 100% (1/1), 100% (1/1), 50% (2/2)). Detectable ctDNA after surgery was associated with inferior recurrence-free survival (RFS, HR 8.2; 95%CI, 1.8-38.0; p=0.0016) and inferior disease-free survival (HR 10.4; 95%CI, 2.5-43.1; p<0.0001). Notably, one patient recurred even with super-low frequency mutations (FBXW7 and KRAS, 0.07%) detected in postsurgical ctDNA. Patients with undetectable ctDNA after surgery had a trend of inferior RFS when receiving adjuvant chemotherapy (HR 57.2. 95%CI 0-184853.6; p=0.0629). There was no significant difference in RFS of patients with postsurgical detectable ctDNA receiving adjuvant chemotherapy or not.
Conclusions
CtDNA analysis based on Super-Seq technology assay could predict recurrence risk in stage I-III CRC. Patients with undetectable ctDNA after surgery might benefit little from adjuvant treatment. These findings need to be validated in a larger prospective trial.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.