Detection of Molecular Residual Disease Using Personalized Circulating Tumor DNA Assay in Patients With Colorectal Cancer Undergoing Resection of Metastases. (2021)

• Record Type: Journal Article
• Authors: Loupakis, Fotios; Sharma, Shruti; Derouazi, Madiha; Murgioni, Sabina; Biason, Paola; Rizzato, Mario Domenico; Rasola, Cosimo; Renner, Derrick; Shchegrova, Svetlana; Koyen Malashevich, Allyson; Malhotra, Meenakshi; Sethi, Himanshu; Zimmermann, Bernhard G.; Aleshin, Alexey; Moshkevich, Solomon; Billings, Paul R.; Sedgwick, Jonathon D.; Schirripa, Marta; Munari, Giada; Cillo, Umberto; Pilati, Pierluigi; Dei Tos, Angelo Paolo; Zagonel, Vittorina; Lonardi, Sara; Fassan, Matteo
• Is Part Of: JCO precision oncology. Volume 5(2021)
• Publication Date: 2021
• Subjects: Precision Medicine; Neoplasms; Pharmacogenetics; Molecular Targeted Therapy; Personalized medicine; Oncology; Pharmacogenomics; Periodical; Periodicals; 616.994
• DOI: 10.1200/PO.21.00101
• Languages: English
• ISSNs: 2473-4284

Abstract

Abstract : PURPOSE: More than 50% of patients with stage IV colorectal cancer (metastatic colorectal cancer [mCRC]) relapse postresection. The efficacy of postoperative systemic treatment is limited in this setting. Thus, these patients would greatly benefit from the use of a reliable prognostic biomarker, such as circulating tumor DNA (ctDNA) to identify minimal or molecular residual disease (MRD). PATIENTS AND METHODS: We analyzed a cohort of 112 patients with mCRC who had undergone metastatic resection with curative intent as part of the PREDATOR clinical trial. The study evaluated the prognostic value of ctDNA, correlating MRD status postsurgery with clinical outcomes by using a personalized and tumor-informed ctDNA assay (bespoke multiple PCR, next-generation sequencing assay). Postresection, systemic therapy was given to 39.2% of the patients at the discretion of the treating physician. RESULTS: Postsurgical, MRD positivity was observed in 54.4% (61 of 112) of patients, of which 96.7% (59 of 61) progressed at the time of data cutoff (hazard ratio [HR]: 5.8; 95% CI, 3.5 to 9.7; P < .001). MRD-positive status was also associated with an inferior overall survival: HR: 16.0; 95% CI, 3.9 to 68.0; P < .001. At the time of analyses, 96% (49 of 51) of patients were alive in the MRD-negative arm compared with 52.4% (32 of 61) in the MRD-positive arm. Patients who did not receive systemic therapy and were MRD-negative in the combined ctDNA analysis at two time points had an overall survival of 100%. In the multivariate analysis, ctDNA-based MRD status was the most significant prognostic factor associated with disease-free survival (HR: 5.78; 95% CI, 3.34 to 10.0; P < .001). CONCLUSION: This study confirms that in mCRC undergoing resection of metastases, postoperative MRD analysis is a strong prognostic biomarker. It holds promises for being implemented in clinical decision making, informing clinical trial design, and further translational research.