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
Naveed Shuja
Dr. Erhan OKTAY
Michaela Kuhlen; Maximilian Schmut; Markus Metzle; R. Claus
Noriyoshi Sawabata
Aarchi Singh Thakur; Abhijoy Sarkar
Faeze Shahraki; Azadeh Meshkini; Elham Nazari
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