Estimating the cure fraction in population‐based cancer studies by using finite mixture models

The cure fraction (the proportion of patients who are cured of disease) is of interest to both patients and clinicians and is a useful measure to monitor trends in survival of curable disease. The paper extends the non-mixture and mixture cure fraction models to estimate the proportion cured of disease in population-based cancer studies by incorporating a finite mixture of two Weibull distributions to provide more flexibility in the shape of the estimated relative survival or excess mortality functions. The methods are illustrated by using public use data from England and Wales on survival following diagnosis of cancer of the colon where interest lies in differences between age and deprivation groups. We show that the finite mixture approach leads to improved model fit and estimates of the cure fraction that are closer to the empirical estimates. This is particularly so in the oldest age group where the cure fraction is notably lower. The cure fraction is broadly similar in each deprivation group, but the median survival of the 'uncured' is lower in the more deprived groups. The finite mixture approach overcomes some of the limitations of the more simplistic cure models and has the potential to model the complex excess hazard functions that are seen in real data. Copyright (c) 2010 Royal Statistical Society.

[1]  T. Hakulinen,et al.  Cancer survival corrected for heterogeneity in patient withdrawal. , 1982, Biometrics.

[2]  M. Abrahamowicz,et al.  Modelling time-dependent hazard ratios in relative survival: application to colon cancer. , 2001, Journal of clinical epidemiology.

[3]  J W Denham,et al.  A generalized F mixture model for cure rate estimation. , 1998, Statistics in medicine.

[4]  G. McLachlan,et al.  On the role of finite mixture models in survival analysis , 1994, Statistical methods in medical research.

[5]  F. Berrino,et al.  The cure for colon cancer: Results from the EUROCARE study , 1998, International journal of cancer.

[6]  Kallappa M. Koti Failure-Time Mixture Models: Yet Another Way to Establish Efficacy , 2001 .

[7]  Paul C Lambert,et al.  Additive and multiplicative covariate regression models for relative survival incorporating fractional polynomials for time‐dependent effects , 2005, Statistics in medicine.

[8]  Ram C Tiwari,et al.  Cure fraction estimation from the mixture cure models for grouped survival data , 2004, Statistics in medicine.

[9]  C. J. F. Ridders,et al.  A new algorithm for computing a single root of a real continuous function , 1979 .

[10]  F. Ederer,et al.  The relative survival rate: a statistical methodology. , 1961, National Cancer Institute monograph.

[11]  J G Ibrahim,et al.  Estimating Cure Rates From Survival Data , 2003, Journal of the American Statistical Association.

[12]  Joseph Berkson,et al.  Survival Curve for Cancer Patients Following Treatment , 1952 .

[13]  T. Hakulinen,et al.  Mixture models for cancer survival analysis: application to population-based data with covariates. , 1999, Statistics in medicine.

[14]  A. Tsodikov,et al.  The shape of the hazard function in breast carcinoma , 1999, Cancer.

[15]  J. Estève,et al.  An overall strategy based on regression models to estimate relative survival and model the effects of prognostic factors in cancer survival studies , 2007, Statistics in medicine.

[16]  Paul W Dickman,et al.  Regression models for relative survival , 2004, Statistics in medicine.

[17]  Paul C. Lambert,et al.  Modeling of the Cure Fraction in Survival Studies , 2007 .

[18]  Paul C Lambert,et al.  Flexible parametric models for relative survival, with application in coronary heart disease , 2007, Statistics in medicine.

[19]  P. Lambert,et al.  Temporal trends in the proportion cured for cancer of the colon and rectum: A population‐based study using data from the Finnish Cancer Registry , 2007, International journal of cancer.

[20]  V. Farewell,et al.  The use of mixture models for the analysis of survival data with long-term survivors. , 1982, Biometrics.

[21]  Catherine Quantin,et al.  A relative survival regression model using B‐spline functions to model non‐proportional hazards , 2003, Statistics in medicine.

[22]  Chin-Shang Li,et al.  Identifiability of cure models , 2001 .

[23]  Malcolm E. Turner,et al.  The Decomposition of Time-Varying Hazard into Phases, Each Incorporating a Separate Stream of Concomitant Information , 1986 .

[24]  Paul W Dickman,et al.  Estimating and modeling the cure fraction in population-based cancer survival analysis. , 2007, Biostatistics.

[25]  J. Boag,et al.  Maximum Likelihood Estimates of the Proportion of Patients Cured by Cancer Therapy , 1949 .

[26]  J W Gamel,et al.  Non-parametric comparison of relative versus cause-specific survival in Surveillance, Epidemiology and End Results (SEER) programme breast cancer patients , 2001, Statistical methods in medical research.

[27]  P. Dickman,et al.  Interpreting trends in cancer patient survival , 2006, Journal of internal medicine.

[28]  Richard Sposto,et al.  Cure model analysis in cancer: an application to data from the Children's Cancer Group , 2002, Statistics in medicine.

[29]  Jorge Alberto Achcar,et al.  Mixture hazard models for lifetime data , 2002 .