title: Estimating 12-week death probability in patients with refractory metastatic colorectal cancer: the Colon Life nomogram.
abstract: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC.
  
  
  
  Four hundred eleven refractory mCRC patients with ECOG performance status (PS) ≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets.
  
  
  
  Four variables were selected and included in the nomogram: PS (P < 0.0001), primary tumor resection (P = 0.027), LDH value (P = 0.0001) and peritoneal involvement (P = 0.081). In the developing set, the nomogram discriminative ability was high (C = 0.778), and was confirmed in the validating set (C = 0.778), where the overall outcome was better as a consequence of the enrichment in patients receiving regorafenib or TAS-102 (46% versus 34%; P < 0.0001).
  
  
  
  Our nomogram may be a useful tool to predict the probability of death within 12 weeks in patients with refractory mCRC. Based on four easy-to-collect variables, the 'Colon Life' nomogram and free app for smartphones may improve mCRC patients' selection for later-line therapies and assist researchers for the enrollment in clinical trials in this setting.
authors.affiliation: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1,Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Trial Office and Biomedical Statistics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: R
authors.initials: R
authors.lastname: Miceli
authors.affiliation: Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan.
authors.forename: L
authors.initials: L
authors.lastname: Rimassa
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Istituto Oncologico Veneto - IRCCS, Padova.
authors.forename: S
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Department of Oncology, University and General Hospital, Udine.
authors.forename: G
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1,Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mennitto
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa.
authors.forename: F
authors.initials: F
authors.lastname: Marmorino
authors.affiliation: Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan.
authors.forename: S
authors.initials: S
authors.lastname: Bozzarelli
authors.affiliation: S.C. Oncologia Medica 1, Azienda Ospedaliero Universitaria Careggi, Firenze.|Department of Medical Biotechnologies, University of Siena, Siena.
authors.forename: L
authors.initials: L
authors.lastname: Antonuzzo
authors.affiliation: Medical Oncology Unit, Rimini Hospital, Rimini.
authors.forename: E
authors.initials: E
authors.lastname: Tamburini
authors.affiliation: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1,Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Morano
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa.
authors.forename: D
authors.initials: D
authors.lastname: Rossini
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Istituto Oncologico Veneto - IRCCS, Padova.
authors.forename: F
authors.initials: F
authors.lastname: Battaglin
authors.affiliation: Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan.
authors.forename: M
authors.initials: M
authors.lastname: Baretti
authors.affiliation: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1,Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Berenato
authors.affiliation: Medical Oncology Unit, Policlinico Tor Vergata University Hospital, Roma.
authors.forename: V
authors.initials: V
authors.lastname: Formica
authors.affiliation: Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo.
authors.forename: S
authors.initials: S
authors.lastname: Mosconi
authors.affiliation: Department of Oncology, ASST Bergamo Ovest, Treviglio, Bergamo.
authors.forename: F
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: Division of Medicine and Medical Oncology, Azienda Istituti Ospitalieri, Cremona.
authors.forename: M
authors.initials: M
authors.lastname: Ghidini
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Istituto Oncologico Veneto - IRCCS, Padova.
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: ASL Lecce-Presidio Ospedaliero Vito Fazzi, UOC Oncologia Medica, Lecce.
authors.forename: D
authors.initials: D
authors.lastname: Spada
authors.affiliation: Medical Oncology, Hospital A. Perrino, Brindisi.
authors.forename: S
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: Medical Oncology Unit, Humanitas Gavazzeni, Bergamo.
authors.forename: G
authors.initials: G
authors.lastname: Beretta
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa.
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.affiliation: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1,Milan, Italy.|Oncology and Hemato-Oncology Department, University of Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa.
authors.forename: C
authors.initials: C
authors.lastname: Cremolini
mesh_terms: D000368:Aged; D003106:Colon / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003362:Cost-Benefit Analysis; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049451:Nomograms; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D011725:Pyridines / Q000008:administration & dosage; D011759:Pyrrolidines; D013941:Thymine; D014271:Trifluridine / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D004338:Drug Combinations; D010671:Phenylurea Compounds; D011725:Pyridines; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; C559147:regorafenib; D014498:Uracil; D013941:Thymine; D014271:Trifluridine
keywords: TAS-102; colorectal cancer; nomogram; prognosis; refractory; regorafenib