Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study

作者：Valentino Martelli, Joana Vidal, Joan Gibert, Concepción Fernández‐Rodríguez, Jenniffer Linares, Pilar García Alfonso, David Páez, V. Alonso, Auxiliadora Gómez‐España, Marta García Guix, Cristina Santos, Guadalupe Elizabeth Trejo Duran, Elena Élez, R. Garcia-Carbonero, Reyes Ferreiro, E. Pineda, Javier Sastre, María Teresa Cano, J.L. Manzano, Ferrán Losa, Enrique Aranda, Fernando Rivera, Annarita Sibilio, R. Toledo, J. Tabernero, Ramón Salazar, Beatríz Bellosillo, Clara O. Montagut · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105760 · 被引用次数：6 · 研究领域：Cancer Genomics and Diagnostics、Colorectal Cancer Treatments and Studies、Genetic factors in colorectal cancer

BACKGROUND: Circulating tumor DNA (ctDNA) variations predict tumor response to systemic treatment (so-called molecular response) earlier than radiological assessment. However, a standardized categorization of molecular response is an unmet clinical need. Liquid biopsy-RECIST (LB-RECIST), based on aggregate variant allele frequency (aggVAF; sum of all detected variant allele frequencies in a sample) variations, has been proposed to stratify molecular response. Metastatic colorectal cancer (mCRC) may be an attractive clinical scenario for LB-RECIST clinical implementation; however, specific data on clinical validity is still lacking. PATIENTS AND METHODS: The prospective PLATFORM-B study enrolled 130 mCRC patients who received standard frontline treatment and underwent serial ctDNA analysis at baseline and week 8 of treatment. ctDNA was analyzed by next-generation sequencing (Oncomine Colon cfDNA Assay; Ion Torrent S5). LB-RECIST, both qualitative (changes in ctDNA detection) and quantitative (percentage variations of aggVAF), were used to categorize molecular response, and were correlated with clinical outcomes, including progression-free survival (PFS) and overall survival (OS). RESULTS: = 0% (PFS P < 0.0001; OS P = 0.0069). Complete clearance of ctDNA at week 8 (ctDNA complete response, CCR) demonstrated the best prognostic and predictive values [median (m) OS 41.8 months; mPFS not reached (NR)], similar to persistent undetectable ctDNA (ctDNA non-measurable disease, CND; mO...