555P - Association between copy number aberration and ctDNA MRD in colorectal cancer: CIRCULATE-Japan GALAXY

Background

Colorectal cancer (CRC) progression is associated with increased genetic diversity, which can be influenced by the duplication of the entire chromosome set. The relationship between copy number (CN) aberration and circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) in CRC remains poorly understood.

Methods

The GALAXY, a large-scale prospective observational study, monitored ctDNA MRD status in patients with clinical stage II to IV or relapsed CRC postsurgery (UMIN000039205). Tumor tissue and matched normal DNA were processed for whole-exome sequencing (WES) to identify up to 16 patients-specific somatic single nucleotide variants (SNVs), and a personalized, tumor-informed assay using these SNVs (Signatera^TM, Natera, Inc.) was employed for ctDNA detection in plasma samples. To identify average CN (ACN), WES data was analyzed utilizing the PureCN software and KASHIWARP, a supercomputer to extract data from BAM files and calculate tumor purity. High ACN was defined as 3.5 or higher.

Results

Of 5,549 patients with CRC analyzed, high ACN was identified in 1650 (29.7%). Among them, 75 (1.35%) patients had high ACN of 5.5 or higher. In clinicopathological factors, female (P=0.05), the left-sided colon(P=0.03) and rectum (P<0.01), non-microsatellite instability (MSI) high (P<0.01) and RAS wild type (P<0.01) were significantly associated with high ACN. Patients with high ACN were more likely to have positive ctDNA compared to those with low ACN (33.1% [218/658] vs. 28.6% [1094/3824], P=0.02) at MRD window (2 to 10 weeks after surgery). While there was no significant difference in disease-free survival (DFS) between patients with high and low ACN, patients with an ACN of ≥5.5 demonstrated significantly shorter DFS compared to those with low ACN (hazard ratio 0.50, 95% CI 0.31 to 0.85, P=0.01).

Conclusions

High ACN significantly correlates with ctDNA MRD as well as specific clinicopathological characteristics in CRC, suggesting a potential role in on development and aggressiveness of CRC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Kotani: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eli lilly, MSD, MerckBiopharma, Ono pharma, Pfizer, Taiho pharma, Takeda, Sysmex, Nihonkayaku, Novartis, Guardant Health; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Local PI: Ono pharma, MSD, Servier, Novartis, Janssen pharma, IQVIA, Syneos health, CIMIC shiftzero, CIMIC; Financial Interests, Institutional, Funding: Ono pharma. H. Taniguchi: Financial Interests, Personal, Invited Speaker: Ono, Takeda, Eli Lilly, Chugai, Taiho, Merck Biopharma, Amgen, MSD K.K, Bristol-Myers Squibb Japan, Roche Diagnostics; Financial Interests, Institutional, Coordinating PI: Takeda, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Ono. J. Watanabe: Financial Interests, Personal, Invited Speaker: Medtronic, Johnson and Johnson, Eli Lilly, Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Funding: Medtronic, Terumo, Amco, Stryker Japan. T. Kato: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Eli Lilly and Company, ONO Pharmaceutical Co, Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Coordinating PI: ASAHIKASEI. E. Oki: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly, Bristol Myers Squibb, MSD, Takeda Pham; Financial Interests, Institutional, Research Grant: Guardant Health. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd., Merus N.V., Bristol-Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.