D B Y Fontein1, M Klinten Grand2, J W R Nortier3, C Seynaeve4, E Meershoek-Klein Kranenbarg1, L Y Dirix5, C J H van de Velde1, H Putter6. 1. Department of Surgery. 2. Department of Medical Statistics. 3. Department of Medical Oncology, Leiden University Medical Center, Leiden. 4. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 5. Department of Medical Oncology, Academisch Ziekenhuis Sint-Augustinus Antwerp, Antwerp, Belgium. 6. Department of Medical Statistics. Electronic address: h.putter@lumc.nl.
Abstract
BACKGROUND: Predictive models are an integral part of current clinical practice and help determine optimal treatment strategies for individual patients. A drawback is that covariates are assumed to have constant effects on overall survival (OS), when in fact, these effects may change during follow-up (FU). Furthermore, breast cancer (BC) patients may experience events that alter their prognosis from that time onwards. We investigated the 'dynamic' effects of different covariates on OS and developed a nomogram to calculate 5-year dynamic OS (DOS) probability at different prediction timepoints (tP) during FU. METHODS:Dutch and Belgian postmenopausal, endocrine-sensitive, early BC patients enrolled in the TEAM trial were included. We assessed time-varying effects of specific covariates and obtained 5-year DOS predictions using a proportional baselines landmark supermodel. Covariates included age, histological grade, hormone receptor and HER2 status, T- and N-stage, locoregional recurrence (LRR), distant recurrence, and treatment compliance. A nomogram was designed to calculate 5-year DOS based on individual characteristics. RESULTS:A total of 2602 patients were included (mean FU 6.2 years). N-stage, LRR, and HER2 status demonstrated time-varying effects on 5-year DOS. Hazard ratio (HR) functions for LRR, high-risk N-stage (N2/3), and HER2 positivity were HR = (8.427 × 0.583[Formula: see text], HR = (3.621 × 0.816[Formula: see text], and HR = (1.235 × 0.851[Formula: see text], respectively. Treatment discontinuation was associated with a higher mortality risk, but without a time-varying effect [HR 1.263 (0.867-1.841)]. All other covariates were time-constant. DISCUSSION: The current nomogram accounts for elapsed time since starting adjuvant endocrine treatment and optimizes prediction of individual 5-year DOS during FU for postmenopausal, endocrine-sensitive BC patients. The nomogram can facilitate in determining whether further therapy will benefit an individual patient, although validation in an independent dataset is still needed.
RCT Entities:
BACKGROUND: Predictive models are an integral part of current clinical practice and help determine optimal treatment strategies for individual patients. A drawback is that covariates are assumed to have constant effects on overall survival (OS), when in fact, these effects may change during follow-up (FU). Furthermore, breast cancer (BC) patients may experience events that alter their prognosis from that time onwards. We investigated the 'dynamic' effects of different covariates on OS and developed a nomogram to calculate 5-year dynamic OS (DOS) probability at different prediction timepoints (tP) during FU. METHODS: Dutch and Belgian postmenopausal, endocrine-sensitive, early BC patients enrolled in the TEAM trial were included. We assessed time-varying effects of specific covariates and obtained 5-year DOS predictions using a proportional baselines landmark supermodel. Covariates included age, histological grade, hormone receptor and HER2 status, T- and N-stage, locoregional recurrence (LRR), distant recurrence, and treatment compliance. A nomogram was designed to calculate 5-year DOS based on individual characteristics. RESULTS: A total of 2602 patients were included (mean FU 6.2 years). N-stage, LRR, and HER2 status demonstrated time-varying effects on 5-year DOS. Hazard ratio (HR) functions for LRR, high-risk N-stage (N2/3), and HER2 positivity were HR = (8.427 × 0.583[Formula: see text], HR = (3.621 × 0.816[Formula: see text], and HR = (1.235 × 0.851[Formula: see text], respectively. Treatment discontinuation was associated with a higher mortality risk, but without a time-varying effect [HR 1.263 (0.867-1.841)]. All other covariates were time-constant. DISCUSSION: The current nomogram accounts for elapsed time since starting adjuvant endocrine treatment and optimizes prediction of individual 5-year DOS during FU for postmenopausal, endocrine-sensitive BC patients. The nomogram can facilitate in determining whether further therapy will benefit an individual patient, although validation in an independent dataset is still needed.
Authors: Esther Paredes-Aracil; Antonio Palazón-Bru; David Manuel Folgado-de la Rosa; José Ramón Ots-Gutiérrez; Antonio Fernando Compañ-Rosique; Vicente Francisco Gil-Guillén Journal: Sci Rep Date: 2017-03-24 Impact factor: 4.379
Authors: Susanna F Fustolo-Gunnink; Karin Fijnvandraat; Hein Putter; Isabelle M Ree; Camila Caram-Deelder; Peter Andriessen; Esther J d'Haens; Christian V Hulzebos; Wes Onland; André A Kroon; Daniël C Vijlbrief; Enrico Lopriore; Johanna G van der Bom Journal: Haematologica Date: 2019-02-28 Impact factor: 9.941
Authors: Dario Callegaro; Rosalba Miceli; Sylvie Bonvalot; Peter C Ferguson; Dirk C Strauss; Veroniek V M van Praag; Antonin Levy; Anthony M Griffin; Andrew J Hayes; Silvia Stacchiotti; Cecile Le Pèchoux; Myles J Smith; Marco Fiore; Angelo Paolo Dei Tos; Henry G Smith; Charles Catton; Joanna Szkandera; Andreas Leithner; Michiel A J van de Sande; Paolo G Casali; Jay S Wunder; Alessandro Gronchi Journal: EClinicalMedicine Date: 2019-11-22