Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2

2019 ◽  
Author(s):  
Keyword(s):  
Colorectal Cancer ◽  
Dna Analysis ◽  
Circulating Tumor Dna ◽  
Postoperative Treatment ◽  
Intervention Trial ◽  
Cancer Intervention ◽  
Tumor Dna

Minimal residual disease by circulating tumor DNA analysis for colorectal cancer patients receiving radical surgery: An initial report from CIRCULATE-Japan.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3608-3608
Author(s):  
Hiroki Yukami ◽  
Yoshiaki Nakamura ◽  
Jun Watanabe ◽  
Masahito Kotaka ◽  
Kentaro Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Analysis ◽  
Residual Disease ◽  
Clinical Stage ◽  
Circulating Tumor Dna ◽  
Patient Specific ◽  
Detection Rates ◽  
Initial Report ◽  
Post Surgery ◽  
Tumor Dna

3608 Background: Circulating tumor DNA (ctDNA) analysis can be used to predict the risk of recurrence by detecting molecular residual disease (MRD) in patients with colorectal cancer (CRC). We are conducting a prospective observational study to monitor MRD status in patients with clinical stage II–IV or relapsed CRC amenable to radical surgical resection (GALAXY study), as part of the CIRCULATE-Japan, a nationwide ctDNA-guided precision adjuvant therapy project. Methods: Analysis of ctDNA is being performed at pre- and post-surgery timepoints and will continue periodically for up to 2 years using Signatera, a personalized, tumor-informed ctDNA assay that is designed to track 16 patient-specific somatic variants based on whole-exome sequencing of tumor tissue. The association of peri-operative ctDNA status with clinicopathological characteristics was investigated. Results: As of January 13, 2021, 941 patients have been enrolled in the GALAXY study, of which 400 patients had their pre-operative ctDNA status evaluated. Of the 400 patients, baseline ctDNA was detected in 92% (367/400) of the patients: consisting of 35 patients with pathological stage (pStage) I, 135 with pStage II, 152 with pStage III, and 78 with pStage IV or relapsed disease (pStage IV/R). Patient-specific Signatera assays targeting 16 variants were designed for 100% of the patients. Out of the 6400 designed variants 99.3% passed quality control in the plasma analysis and produced the final results. Among 4425 genes selected for 400 patients, 3330 genes were selected for only one patient, while TP53 was the most commonly selected in 113 patients (28%). Median ctDNA levels, measured in mean tumor molecules per mL of plasma and ctDNA detection rate, stratified by stage are presented in table. Positive ctDNA status post-surgery was significantly associated with advanced pStage, pT and pN, and lymphovascular invasion. Of the 13 patients with recurrence, 10 were detected with a positive ctDNA at 4-weeks post-surgery, before confirmation of recurrence by the radiological imaging. Conclusions: Preoperative ctDNA detection rates were observed to be in >90% in patients with pStage II–III by personalized ctDNA assay based on unique somatic variants, specific to each patient. ctDNA- based MRD detected post-surgery (4W) was significantly associated with certain known clinicopathological factors for recurrence with ctDNA positivity associated with a very short-term of recurrence. Clinical trial information: 000039205. [Table: see text]

scholarly journals Circulating Tumor DNA Analysis in Colorectal Cancer: From Dream to Reality

2019 ◽  
pp. 1-14 ◽  
Author(s):  
Carlotta Antoniotti ◽  
Filippo Pietrantonio ◽  
Salvatore Corallo ◽  
Filippo De Braud ◽  
Alfredo Falcone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Analysis ◽  
Circulating Tumor Dna ◽  
Tumor Dna

Circulating tumor DNA analysis before and after resection for colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3597-3597
Author(s):  
Erin L. Symonds ◽  
Susanne Kartin Pedersen ◽  
David Murray ◽  
Graeme P Young
Keyword(s):  
Colorectal Cancer ◽  
Dna Analysis ◽  
Tumor Resection ◽  
Circulating Tumor Dna ◽  
High Rate ◽  
Ct Scans ◽  
Post Surgery ◽  
Response To Chemotherapy ◽  
The Impact ◽  
Tumor Dna

3597 Background: Detection of circulating tumor DNA (ctDNA) has broad clinical utility including disease monitoring, prognostication and response to chemotherapy. ctDNA is commonly detected by targeting tumor-specific features including mutations, insertions, deletions or hypermethylation. The two genes, BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC). This study aimed to analyze the impact of tumor resection on ctDNA levels by assaying pre- and postoperative blood samples for methylated BCAT1 and IKZF1. Methods: 91 people (age 32-86 years, 53% male) with invasive CRC, but without neoadjuvant therapy, had blood collected prior to surgery and within 12 months (1-12 months) after resection. Cancers were clinicopathologically staged. DNA extracted from plasma was assayed for methylated BCAT1/ IKZF1 and detection of either marker was deemed positive for ctDNA. Results: 47 (52%) of the 91 CRC patients were ctDNA positive before resection, including 5/30 (17%) stage I, 17/28 (61%) stage II, 23/31 (74%) stage III and 2/2 (100%) stage IV. After resection 75% (35/47) became ctDNA negative (median 2 months after resection), and all had apparent tumour clearance. Of the 35 postoperative ctDNA negative cases 22 had further surveillance CT scans within study timeframe. 86% (20/22) showed no recurrent CRC but 2 of these developed a new cancer (metachronous CRC, prostate). The remaining 2 tested ctDNA positive 14 and 25 months later and recurrence was confirmed. Of the 12 postoperative ctDNA positive cases, two were found to not have complete tumour clearance at surgery (residual disease). Follow-up CT scans were available for a further 8 patients which revealed that 4 later presented with cancer (3 recurrence, 1 thyroid) at a median 15 months after resection. The remaining 4 postoperative positive cases were negative at subsequent blood testing (median 8 months later). Conclusions: Methylated BCAT1/IKZF1 DNA in preoperative blood is dependent on tumor stage, but informs the completeness of resection given the high rate (74.5%) of ctDNA disappearance post-surgery. If cases persistently test ctDNA positive after surgery or become ctDNA positive later, residual or recurrent disease should be suspected, respectively.

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