Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088)
Igor Monsellato,
Elisabetta Garibaldi,
Elisa Cassinotti,
Ludovica Baldari,
Luigi Boni,
Ugo Elmore,
Roberto Delpini,
Riccardo Rosati,
Roberto Perinotti,
Filippo Alongi,
Elisa Bertocchi,
Stefania Gori,
Giacomo Ruffo,
Graziano Pernazza,
Fabio Pulighe,
Carlo De Nisco,
Emilio Morpurgo,
Tania Contardo,
Enzo Mammano,
Federico Perna,
Benedetta Menegatti,
Andrea Coratti,
Piero Buccianti,
Riccardo Balestri,
Cristina Ceccarelli,
Davide Cavaliere,
Leonardo Solaini,
Giorgio Ercolani,
Elena Traverso,
Vittorio Fusco,
Valter Torri,
Sara Orecchia
Affiliations
Igor Monsellato
Department of Surgery, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo
Elisabetta Garibaldi
Department of Radiation Oncology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo
Elisa Cassinotti
Department of Surgery, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan
Ludovica Baldari
Department of Surgery, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan
Luigi Boni
Department of Surgery, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan
Ugo Elmore
Ospedale San raffaele IRCCS
Roberto Delpini
Ospedale San raffaele IRCCS
Riccardo Rosati
Ospedale San raffaele IRCCS
Roberto Perinotti
Ospedale degli Infermi
Filippo Alongi
Ospedale Sacro Cuore Don Calabria
Elisa Bertocchi
Ospedale Sacro Cuore Don Calabria
Stefania Gori
Ospedale Sacro Cuore Don Calabria
Giacomo Ruffo
Ospedale Sacro Cuore Don Calabria
Graziano Pernazza
Azienda Ospedaliera San Giovanni Addolorata
Fabio Pulighe
Ospedale San Francesco
Carlo De Nisco
Ospedale San Francesco
Emilio Morpurgo
Ospedale Civile Pietro Cosma, Camposampiero/Ospedale Sant’Antonio
Tania Contardo
Ospedale Civile Pietro Cosma, Camposampiero
Enzo Mammano
Ospedale Civile Pietro Cosma, Camposampiero/Ospedale Sant’Antonio
Federico Perna
Azienda Ospedaliero Universitaria Careggi
Benedetta Menegatti
Azienda Ospedaliero Universitaria Careggi
Andrea Coratti
Azienda Ospedaliero Universitaria Careggi
Piero Buccianti
Azienda Ospedaliero Universitaria Pisana
Riccardo Balestri
Azienda Ospedaliero Universitaria Pisana
Cristina Ceccarelli
Azienda Ospedaliero Universitaria Pisana
Davide Cavaliere
Ospedale “G.B. Morgagni L. Pierantoni”
Leonardo Solaini
Ospedale “G.B. Morgagni L. Pierantoni”
Giorgio Ercolani
Ospedale “G.B. Morgagni L. Pierantoni”
Elena Traverso
Department of Oncology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo
Vittorio Fusco
Department of Oncology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo
Valter Torri
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Sara Orecchia
Department of Pathology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo
Abstract Background Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT 03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088). Methods All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated. Discussion TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse. Trial registration Clinicaltrials.gov NCT03962088 . Registered on 23 May 2019.
