Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer

ESMO Open

article

M. Benavides¹  J. Alcaide-Garcia¹  E. Torres¹  S. Gil-Calle¹  I. Sevilla¹  R. Wolman³  G. Durán¹  M. Álvarez⁵  C. Reyna-Fortes¹  I. Ales¹  T. Pereda⁶  M. Robles²  M. Kushnir⁷  J. Odegaard⁷  I. Faull⁷  E. Alba¹ 

[1] Medical Oncology Intercenter Unit, Hospital Universitario Regional y Virgen de la Victoria;Medical Oncology Department, Hospital Costa del Sol;Medical Oncology Service, Hospital Xanit;Medical Oncology Department, Hospital Universitario San Cecilio;Cancer Molecular Biology Laboratory ,(CIMES), University of Málaga;Pathology Department, Hospital Costa del Sol;Guardant Health Inc

关键词: metastatic colorectal cancer;    circulating tumor DNA;    liquid biopsy;    biomarker;    next-generation sequencing;    genomic profiling;   

DOI  :  10.1016/j.esmoop.2022.100481

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing.Patients and methods Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM.Results Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001).Conclusions Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

【 授权许可】

CC BY|CC BY-NC-ND