Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study

Jeanne Tie ^1,2,3,4, Yuxuan Wang ⁵, Joshua Cohen ⁵

¹The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
²Western Health, Melbourne, Australia.
³Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia.
⁵Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland, United States of America.
⁶Royal Melbourne Hospital, Melbourne, Australia.
⁷Eastern Health, Melbourne, Australia.
⁸Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
⁹Royal Brisbane and Women's Hospital, Brisbane, Australia.
¹⁰Nepean Cancer Care Centre, Sydney, Australia.
¹¹Icon Cancer Centre, Adelaide, Australia.
¹²Olivia Newton-John Cancer and Wellness Centre, Melbourne, Australia.
¹³Flinders Medical Centre, Flinders University, Adelaide, Australia.
¹⁴Border Medical Oncology, Albury, Australia.
¹⁵The Alfred Hospital, Melbourne, Australia.
¹⁶Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

⁰The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

Plos Medicine +

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May 3, 2021

View abstract on PubMed

Summary

Postoperative circulating tumor DNA (ctDNA) detection in colorectal liver metastases (CRLM) patients indicates a higher risk of recurrence and poorer survival. Serial ctDNA analysis during adjuvant chemotherapy may predict treatment efficacy, guiding future therapy decisions.

Area Of Science

Oncology
Molecular Diagnostics
Surgical Oncology

Background

The role of perioperative systemic therapy in resectable colorectal liver metastases (CRLM) remains debated.
Circulating tumor DNA (ctDNA) is a prognostic marker for minimal residual disease in colorectal cancer (CRC).
Serial ctDNA analysis may optimize perioperative chemotherapy for resectable CRLM.

Purpose Of The Study

To validate the prognostic significance of postoperative ctDNA in patients with resectable CRLM.
To assess the utility of serial ctDNA monitoring during adjuvant chemotherapy.

Main Methods

Prospective collection of plasma samples from 54 patients with resectable CRLM.
Personalized ctDNA detection using Safe-SeqS assay targeting 15 common CRC mutations.
Analysis of ctDNA levels pre- and post-surgery, during chemotherapy, and in follow-up.

Main Results

ctDNA was detectable in 85% of patients pre-treatment and 24% post-surgery.
Detectable postoperative ctDNA significantly correlated with lower recurrence-free survival (RFS) and overall survival.
ctDNA clearance during adjuvant chemotherapy was associated with disease-free status in 2/3 patients; persistent ctDNA indicated recurrence.

Conclusions

Post-surgery and post-treatment ctDNA levels are confirmed prognostic markers in resected CRLM.
Serial ctDNA analysis shows potential as an early indicator of adjuvant chemotherapy efficacy.
Further research is needed to integrate ctDNA analysis into treatment decisions for resectable CRLM.