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

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 ag...

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Detalles Bibliográficos
Autores: Martelli, Valentino, Vidal, Joana, Gibert Fernández, Joan, Fernández-Rodríguez, Maria Concepción, Linares, Jenniffer, García-Alfonso, Pilar, Páez López-Bravo, David, Alonso Orduña, Vicente, Gomez-España, Maria Auxiliadora, Guix, Marta, Santos Vivas, Cristina, Duran, G., Élez, Elena, Garcia Carbonero, Rocio, Ferreiro Monteagudo, Reyes, Pineda Losada, Estela, Sastre, Javier, Cano, M.T., Manzano, Jose Luis, Losa Gaspà, Ferran, Aranda, Enrique, Rivera Herrero, Fernando, Sibilio, Annarita, Toledo, Rodrigo, Tabernero Caturla, Josep, Salazar Soler, Ramón, Bellosillo Paricio, Beatriz, Montagut Viladot, Clara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/223530
Acceso en línea:https://hdl.handle.net/2445/223530
Access Level:acceso abierto
Palabra clave:Tumors
Biòpsia
Càncer colorectal
Marcadors bioquímics
Biopsy
Colorectal cancer
Biochemical markers
Descripción
Sumario: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: ctDNA results were available for 106 patients at baseline and 90 patients at week 8 of treatment. Single timepoint aggVAFWEEK8 >0% showed significantly worse survival outcomes compared to aggVAFWEEK8 = 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; mOS 41.1 months; mPFS NR). Conversely, patients with ctDNA partial response (CPR) and ctDNA progressive disease (CPD) had the worst clinical outcomes (mOS 16.4 and 25.5 months, and mPFS 12.7 and 11.9 months, respectively). Conclusions: LB-RECIST is prognostic and predictive of clinical outcomes in frontline mCRC. The clinical utility of LB-RECIST to guide early treatment decisions is warranted through interventional trials.

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