Dynamic prediction in breast cancer: proving feasibility in clinical practice using the TEAM trial

TY - JOUR

T1 - Dynamic prediction in breast cancer: proving feasibility in clinical practice using the TEAM trial

AU - Fontein, D B Y

AU - Klinten Grand, M

AU - Nortier, J W R

AU - Seynaeve, C

AU - Meershoek-Klein Kranenbarg, E

AU - Dirix, L Y

AU - van de Velde, C J H

AU - Putter, H

N1 - © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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 × 0.583tP), HR = (3.621 × 0.816tP), and HR = (1.235 × 0.851tP), 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.

AB - 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 × 0.583tP), HR = (3.621 × 0.816tP), and HR = (1.235 × 0.851tP), 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents, Hormonal/adverse effects

KW - Belgium

KW - Biomarkers, Tumor/analysis

KW - Breast Neoplasms/chemistry

KW - Chemotherapy, Adjuvant

KW - Decision Support Techniques

KW - Feasibility Studies

KW - Female

KW - Humans

KW - Mastectomy/adverse effects

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Neoplasm Staging

KW - Netherlands

KW - Nomograms

KW - Patient Selection

KW - Predictive Value of Tests

KW - Receptor, ErbB-2/analysis

KW - Risk Assessment

KW - Risk Factors

KW - Survival Analysis

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1093/annonc/mdv146

DO - 10.1093/annonc/mdv146

M3 - Journal article

C2 - 25862439

SN - 0923-7534

VL - 26

SP - 1254

EP - 1262

JO - Annals of Oncology

JF - Annals of Oncology

IS - 6

ER -