Predicting the risk of late effects among cancer survivors: moving toward risk-stratified care Sept 7, 2014 Talya Salz, Ph D Health Outcomes Research Group Memorial Sloan-Kettering Cancer Center New York, NY
Caring for cancer survivors Growing population of long-term cancer survivors Late effects Persistent Late-occurring Late effects may require prevention, early detection, or management. Often care is provided by a different person than the treating oncologist.
Tailoring late effects management to individual Need to predict risk of late effects to guide prevention, early detection, and management of late effects Examples: Mammography after chest radiation Cardiac monitoring after anthracyclines
Personalized care based on risk of late effects Genetics Cancer Personalized plan for prevention, surveillance, and management of late effects Therapy Behaviors Comorbidities Risk-based care
Clinical prediction models Present absolute risk for the individual patient Ideally developed among one group and validated in an independent group Validated internally or externally Discrimination, calibration Can be used in medical setting with patient data Parsimonious Does not require too much or inaccessible data Avoids overfit
Example of clinical risk prediction
Predicting risk of late effects among cancer survivors Watson et al., BJC, 2012
Do such prediction models exist for survivors? Goal: Identify and describe all models predicting late effects that could be used by clinicians to guide prevention, early detection, or management of late effects Performed systematic review: Searched Medline through April 2014 All cancers, all late effects present at 1 year Required that data required for the model be accessible to a clinician providing ongoing survivorship care
Study selection for review Records identified through database searching (Medline) (n = 25,111) Full-text articles assessed for eligibility (n = 278) Studies meeting eligibility criteria (n = 13) Titles and abstracts screened ineligible (n = 24,824) Full-text articles excluded (n = 265) Not English 8 Not original data 23 Not cancer in humans 23 Not late effects 137 Not prediction model 32 Not clinically useful 42 Study identified in reference review (n = 1) Studies included in the final review (n = 14)
Summary of 14 existing models 7 models for prostate cancer survivors Erectile dysfunction, urinary incontinence 4 models for breast cancer survivors Arm lymphedema, psychosocial morbidity, cardiac event, heart failure or cardiomyopathy 1 model for head and neck cancer Swallowing dysfunction 1 model for Hodgkin lymphoma Breast cancer 1 model for childhood cancer Thyroid cancer
Overview of existing models Models predicted risk up to 30 years after treatment. Most models (8/14) predicted risk within 3 years Models used data from trials, cohort studies, institutional cohorts. Only 2 models were externally validated. Of 12 remaining models, 10 were internally validated Most models (8/14) designed to assist with treatment decisions. The clinical presentation varied widely.
Freedom from urinary incontinence, sexual dysfunction, and recurrence after prostate cancer Eastham et al., J Urol, 2008
Erectile function after prostate cancer Alemozzafar et al., JAMA, 2011
Cardiomyopathy or heart failure after breast cancer 4 Ezaz et al., J Am Heart Assoc, 2014
Cardiomyopathy or heart failure after breast cancer Ezaz et al., J Am Heart Assoc, 2014
Breast cancer after Hodgkin lymphoma Travis et al., JNCI, 2005
Breast cancer after Hodgkin lymphoma Travis et al., JNCI, 2005
Thyroid cancer after childhood cancer Kovalchik et al., JCO, 2013
Conclusions: Prediction models Few useful models exist to predict risk of late effects. 14 models of varying quality for 5 cancers Only 2 validated externally Most models were created for treatment decisions, not to help guide prevention, early detection, and management of late effects. Models buried in the literature
Conclusions: late effects Persistent effects no latent period, but worth predicting whether they will diminish Erectile and urinary function after prostatectomy Swallowing function after radiation for head and neck cancer Some models predict events that cannot be modified much Arm lymphedema after breast cancer Late-occurring with preventable, detectable, or modifiable outcomes Heart failure, cardiomyopathy, or other cardiac event after trastuzumab Breast cancer after Hodgkin lymphoma Thyroid cancer after childhood cancer
Work in progress: predicting cardiovascular events after lymphoma diagnosis Funding from LLS to predict CVD after lymphoma Important group to study: Aggressive lymphoma has multiple cardiotoxic treatments. Excess risks of heart failure, stroke, and heart attack are known. There is a latent period between treatment and appearance of cardiovascular disease. Cardiovascular risk can be managed medically.
Study population Danish population registries National patient register and Cause of death register (cardiovascular late effects) Lymphoma register (treatment) Pharmacy register and Diabetes register (comorbidities) 4028 survivors of aggressive lymphoma Diagnosed between 2000 and 2012 Followed through 2012 Age range: 16-95, median 59
Study methods Outcomes : Myocardial infarction (N=108) Stroke (N=95) Heart failure (N=178) Potential predictors Patient characteristics Age, sex, tumor stage Pre-existing cardiovascular risk factors Hypertension, dyslipidemia, diabetes Smoking Treatment Anthracycline use, chest radiation, neck radiation Cox proportional hazards model
Acknowledgements Shrujal Baxi Nirupa Raghunathan Erin Onstad Andrew Freedman Chaya Moskowitz Karyn Goodman Matthew Matasar Kevin Oeffinger Andrew Vickers Susanne Dalton Christoffer Johansen Peter de Nully Brown
Late effects prediction models First Author Year Late Effect Prostate Cancer Alemozaffar 2011 Erectile Dysfunction Briganti 2010 Erectile Dysfunction Gallina 2008 Erectile Dysfunction Kilminster 2011 Erectile Dysfunction Eastham 2008 Erectile Dysfunction, Biochemical Recurrence, and Urinary Incontinence Mathieu 2013 Urinary Dysfunction Chipman 2014 Sexual Dysfunction Breast Cancer Bevilacqua 2012 Arm Lymphedema Ezaz 2014 Heart Failure or Cardiomyopathy Ganz 1993 Psychosocial Morbidity Romond 2012 Cardiac Event Head and Neck Cancer Langendijk 2009 Swallowing Dysfunction Hodgkin Lymphoma Travis 2005 Breast Cancer Childhood Cancer Kovalchik 2013 Thyroid Cancer