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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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
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spelling Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B studyMartelli, ValentinoVidal, JoanaGibert Fernández, JoanFernández-Rodríguez, Maria ConcepciónLinares, JennifferGarcía-Alfonso, PilarPáez López-Bravo, DavidAlonso Orduña, VicenteGomez-España, Maria AuxiliadoraGuix, MartaSantos Vivas, CristinaDuran, G.Élez, ElenaGarcia Carbonero, RocioFerreiro Monteagudo, ReyesPineda Losada, EstelaSastre, JavierCano, M.T.Manzano, Jose LuisLosa Gaspà, FerranAranda, EnriqueRivera Herrero, FernandoSibilio, AnnaritaToledo, RodrigoTabernero Caturla, JosepSalazar Soler, RamónBellosillo Paricio, BeatrizMontagut Viladot, ClaraTumorsBiòpsiaCàncer colorectalMarcadors bioquímicsTumorsBiopsyColorectal cancerBiochemical markersBackground: 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.Elsevier2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/223530Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.esmoop.2025.105760ESMO Open, 2025, vol. 10, num.9https://doi.org/10.1016/j.esmoop.2025.105760cc-by-nc-nd (c) Martelli, Valentino et al., CH, 2025http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2235302026-05-27T06:46:51Z
dc.title.none.fl_str_mv Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
title Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
spellingShingle Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
Martelli, Valentino
Tumors
Biòpsia
Càncer colorectal
Marcadors bioquímics
Tumors
Biopsy
Colorectal cancer
Biochemical markers
title_short Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
title_full Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
title_fullStr Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
title_full_unstemmed Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
title_sort Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study
dc.creator.none.fl_str_mv 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
author Martelli, Valentino
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tumors
Biòpsia
Càncer colorectal
Marcadors bioquímics
Tumors
Biopsy
Colorectal cancer
Biochemical markers
topic Tumors
Biòpsia
Càncer colorectal
Marcadors bioquímics
Tumors
Biopsy
Colorectal cancer
Biochemical markers
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/223530
url https://hdl.handle.net/2445/223530
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.esmoop.2025.105760
ESMO Open, 2025, vol. 10, num.9
https://doi.org/10.1016/j.esmoop.2025.105760
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Martelli, Valentino et al., CH, 2025
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Martelli, Valentino et al., CH, 2025
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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