{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:42:11Z","timestamp":1787625731296,"version":"build-2736575974"},"reference-count":19,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018430","name":"Fondazione Istituto Europeo di Oncologia e Centro Cardiologico Monzino","doi-asserted-by":"publisher","award":["FIEORDT-U144 grant"],"award-info":[{"award-number":["FIEORDT-U144 grant"]}],"id":[{"id":"10.13039\/100018430","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF\u2009&gt;\u20090 and 23 had negative ctDNA (VAF\u2009=\u20090). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10\u20131.26), p\u2009=\u20090.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02\u20131.07), p\u2009=\u20090.058]. The presence of a baseline VAF\u2009&gt;\u20090 was associated with a trend toward a lower EFS compared with VAF\u2009=\u20090 patients [hazard ratio (HR)\u2009=\u20092.30, 95% CI: 0.63\u20138.36, p\u2009=\u20090.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR\u2009=\u20091.18, 95% CI: 0.35\u20134.06, p\u2009=\u20090.79).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359241249602","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T18:00:28Z","timestamp":1718301628000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-8527","authenticated-orcid":false,"given":"Lorenzo","family":"Gervaso","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy"},{"name":"Molecular Medicine Department, University of Pavia, Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-0305","authenticated-orcid":false,"given":"Davide","family":"Ciardiello","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Gregato","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology\u2013Oncology, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Guidi","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy"},{"name":"Department of Oncology and Haemato\u2013Oncology, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1150-0345","authenticated-orcid":false,"given":"Carmine","family":"Valenza","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy"},{"name":"Department of Oncology and Haemato\u2013Oncology, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Ascione","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy"},{"name":"Department of Oncology and Haemato\u2013Oncology, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boldrini","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy"},{"name":"Department of Oncology and Haemato\u2013Oncology, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Frassoni","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Methods, University of Milan\u2013Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Alessandra","family":"Cella","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Spada","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Funicelli","sequence":"additional","affiliation":[{"name":"Division of Radiology, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"De Roberto","sequence":"additional","affiliation":[{"name":"Division of Endoscopy, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Petz","sequence":"additional","affiliation":[{"name":"Digestive Surgery Division, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Borin","sequence":"additional","affiliation":[{"name":"Digestive Surgery Division, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna Alessandra","family":"Gerardi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Division of Pathology, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darina","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Bertani","sequence":"additional","affiliation":[{"name":"Digestive Surgery Division, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Fumagalli 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