Risk factors for metachronous colorectal cancer in Lynch syndrome patients: a registry-based observational mono-institut
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ORIGINAL ARTICLE
Risk factors for metachronous colorectal cancer in Lynch syndrome patients: a registry‑based observational mono‑institutional study cohort Stefano Signoroni1 · Guglielmo Niccolò Piozzi2 · Maria Teresa Ricci1 · Andrea Mancini3 · Alberto Morabito4 · Lucio Bertario1 · Marco Vitellaro1,2 Received: 8 November 2019 / Accepted: 4 May 2020 © Japan Society of Clinical Oncology 2020
Abstract Background Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection. Methods Patient’s clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. The age-related cumulative risk of mCRC was calculated using the Kaplan–Meier method. Factors significantly associated with mCRC were analyzed with a Cox regression model. Overall and specific competitive risks were also calculated. Results In a total of 1346 CRC patients, 159 (11.8%) developed a mCRC after a mean follow-up of 138 months from the primary tumor. The independent risk factors reported by a multivariate analysis were: pathogenetic variants in MLH1 and MSH2 (HR 2.96 and 1.91, respectively) and history of colorectal adenomas (HR 1.54); whereas female sex and extended surgery were protective (HR 0.59 and 0.79, respectively). Conclusions Among a high-risk population for CRC, in particular LS, an extended surgery may be considered in CRC patients with specific risk factors (MLH1 or MSH2 germline pathogenic variants, history of colorectal adenomas) to reduce the risk of mCRC development. Keywords Metachronous colorectal cancer · Lynch syndrome · Colorectal surgery · Hereditary non-polyposis colorectal cancer · DNA mismatch repair genes Stefano Signoroni and Guglielmo Niccolò Piozzi contributed equally as co-first authors. Alberto Morabito and Lucio Bertario are Retired from July 2014. * Stefano Signoroni [email protected] 1
Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133 Milan, Italy
2
Colorectal Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133 Milan, Italy
3
Diagnostic and Surgical Endoscopy Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133 Milan, Italy
4
Medical Statistics Unit, University of Milan, via Festa del Perdono, 7, 20122 Milan, Italy
Introduction Colorectal cancer (CRC) is the third cause of cancer worldwide and the second for cancer-related death [1]. Surgery is the cornerstone in CRC treatment; however, the extent of surgical resection is still debated. In additi
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