Joana Vidal; Laura Muinelo; Alba Dalmases; Frederick S. Jones; Daniel L. Edelstein; Mar Iglesias; Mayra Orrillo; Alicia Abalo; Carmela Rodríguez; E. Brozos; Yoanis Socarras Vidal; Sonia Candamio; Francisca Vázquez; J. Ruiz; Marta Guix; Laura Visa; V. Sikri; Joan Albanell; Beatríz Bellosillo; R. López; Clara Montagut · 2017 · Annals of Oncology
Paper
BACKGROUND: RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. PATIENTS AND METHODS: RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. RESULTS: Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. CONCLUSION: The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.
Analysis
This study evaluates plasma ctDNA RAS mutation analysis using the OncoBEAM™ assay as a minimally invasive alternative to tissue biopsy for metastatic colorectal cancer (mCRC) patients, showing high concordance and utility in monitoring treatment response and resistance.
Discovery
Hyukjung Kwon; Sun Hye Shin; Hyun Ho Kim; Na Young Min; Yugyeong Lim; T. Joo; Kyoung Joo Lee; Minseon Jeong; Hyojung Kim; Seon-young Yun; Yoon-Hee Kim; Dabin Park; Joungsu Joo; Jin‐Sik Bae; Sunghoon Lee; Byeong‐Ho Jeong; Kyungjong Lee; Hayemin Lee; Hong Kwan Kim; Kyongchol Kim; Sang‐Won Um; Changhyeok An; Min Seob Lee
Christopher Abbosh; Alexander M. Frankell; Thomas Harrison; Judit Kisistók; Aaron T. Garnett; Laura Johnson; Selvaraju Veeriah; Mike Moreau; Adrian Chesh; Tafadzwa L. Chaunzwa; Jakob Weiss; Morgan R. Schroeder; Sophia Ward; Kristiana Grigoriadis; Aamir Shahpurwalla; Kevin Litchfield; Clare Puttick; Dhruva Biswas; Takahiro Karasaki; James R. Black; Carlos Martínez‐Ruiz; Maise Al Bakir; Oriol Pich; Thomas B.K. Watkins; Emilia L. Lim; Ariana Huebner; David A. Moore; Nadia Godin-Heymann; Anne L’Hernault; Hannah Bye; Aaron Odell; Paula Kalavakur; Fábio Gomes; Akshay J. Patel; Elizabeth Manzano; Crispin T. Hiley; Nicolas Carey; Joan Riley; Daniel E. Cook; Darren Hodgson; Daniel Stetson; J. Carl Barrett; Roderik M. Kortlever; Gérard I. Evan; Allan Hackshaw; Robert Daber; Jacqui Shaw; Hugo J.W.L. Aerts; Abel Licon; Josh Stahl; Mariam Jamal‐Hanjani; J.F. Lester; Amrita Bajaj; Apostolos Nakas; Azmina Sodha-Ramdeen; Keng Ang; Mohamad Tufail; Mohammed Fiyaz Chowdhry; Molly Scotland; Rebecca Boyles; Sridhar Rathinam; Claire Wilson; Domenic Marrone; Sean Dulloo; Dean A. Fennell; Gurdeep Matharu; Lindsay Primrose; Ekaterini Boleti; Heather Cheyne; Mohammed S. Khalil; Shirley Richardson; Tracey Cruickshank; Gillian Price; Keith M. Kerr; Sarah Benafif; Kayleigh Gilbert; Babu Naidu; Aya Osman; Christer Lacson; Gerald Langman; Helen Shackleford; Madava Djearaman; Salma Kadiri; Gary Middleton; Angela Leek; Jack Davies Hodgkinson; Nicola Totten; Ángeles Montero; Elaine Smith; Eustace Fontaine; Felice Granato; Helen Doran; Juliette Novasio; Kendadai Rammohan; Leena Dennis Joseph; Paul Bishop; Rajesh Shah; Stuart Moss; Vijay Joshi; Philip Crosbie
Siobhan Connal; James M. Cameron; Alexandra Sala; Paul M. Brennan; David Scott Palmer; Joshua D. Palmer; Haley K. Perlow; Matthew J. Baker
Giovanna Maria Stanfoca Casagrande; Marcela de Oliveira Silva; Rui Manuel Reis; Letícia Ferro Leal
Saife N. Lone; Sabah Nisar; Tariq Masoodi; Mayank Singh; Arshi Rizwan; Sheema Hashem; Wael El‐Rifai; Davide Bedognetti; Surinder K. Batra; Mohammad Haris; Ajaz A. Bhat; Muzafar A. Macha
David L. Crosby; Sangeeta N. Bhatia; Kevin M. Brindle; Lisa M. Coussens; Caroline Dive; Mark Emberton; Sadik C. Esener; Rebecca C. Fitzgerald; Sanjiv S. Gambhir; Peter Kühn; Timothy R. Rebbeck; Shankar Balasubramanian
Source record