F Pietrantonio1, R Miceli2, L Rimassa3, S Lonardi4, G Aprile5, A Mennitto1, F Marmorino6, S Bozzarelli3, L Antonuzzo7,8, E Tamburini9, F Morano1, D Rossini6, F Battaglin4, M Baretti3, R Berenato1, V Formica10, S Mosconi11, F Petrelli12, M Ghidini13, F Loupakis4, D Spada14, S Cinieri15, G Beretta16, A Falcone6, F de Braud1,17, C Cremolini6. 1. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1,Milan, Italy. 2. Trial Office and Biomedical Statistics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. 3. Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan. 4. Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Istituto Oncologico Veneto - IRCCS, Padova. 5. Department of Oncology, University and General Hospital, Udine. 6. Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa. 7. S.C. Oncologia Medica 1, Azienda Ospedaliero Universitaria Careggi, Firenze. 8. Department of Medical Biotechnologies, University of Siena, Siena. 9. Medical Oncology Unit, Rimini Hospital, Rimini. 10. Medical Oncology Unit, Policlinico Tor Vergata University Hospital, Roma. 11. Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo. 12. Department of Oncology, ASST Bergamo Ovest, Treviglio, Bergamo. 13. Division of Medicine and Medical Oncology, Azienda Istituti Ospitalieri, Cremona. 14. ASL Lecce-Presidio Ospedaliero Vito Fazzi, UOC Oncologia Medica, Lecce. 15. Medical Oncology, Hospital A. Perrino, Brindisi. 16. Medical Oncology Unit, Humanitas Gavazzeni, Bergamo. 17. Oncology and Hemato-Oncology Department, University of Milan, Italy.
Abstract
Background: 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. Patients and methods: 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. Results: 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). Conclusions: 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.
Background: 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. Patients and methods: 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. Results: 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). Conclusions: 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: Katrin M Sjoquist; Lindsay A Renfro; R John Simes; Niall C Tebbutt; Stephen Clarke; Matthew T Seymour; Richard Adams; Timothy S Maughan; Leonard Saltz; Richard M Goldberg; Hans-Joachim Schmoll; Eric Van Cutsem; Jean-Yves Douillard; Paulo M Hoff; Joel Randolph Hecht; Christophe Tournigand; Cornelis J A Punt; Miriam Koopman; Herbert Hurwitz; Volker Heinemann; Alfredo Falcone; Rainer Porschen; Charles Fuchs; Eduardo Diaz-Rubio; Enrique Aranda; Carsten Bokemeyer; Ioannis Souglakos; Fairooz F Kabbinavar; Benoist Chibaudel; Jeffrey P Meyers; Daniel J Sargent; Aimery de Gramont; John R Zalcberg Journal: J Natl Cancer Inst Date: 2018-06-01 Impact factor: 13.506
Authors: Alena Novakova-Jiresova; Katerina Kopeckova; Ludmila Boublikova; Renata Chloupkova; Bohuslav Melichar; Lubos Petruzelka; Jindrich Finek; Ondrej Fiala; Peter Grell; Stanislav Batko; Zdenek Linke; Igor Kiss; Jana Prausova; Tomas Buchler Journal: Cancer Manag Res Date: 2020-07-03 Impact factor: 3.989
Authors: Johannes J M Kwakman; G Vink; J H Vestjens; L V Beerepoot; J W de Groot; R L Jansen; F L Opdam; H Boot; G J Creemers; J M van Rooijen; M Los; A J E Vulink; H Schut; E van Meerten; A Baars; P Hamberg; E Kapiteijn; D W Sommeijer; C J A Punt; M Koopman Journal: Int J Clin Oncol Date: 2017-12-04 Impact factor: 3.402