This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-038. Cardiovascular complications have emerged as the leading cause of death among long-term childhood cancer survivors. It has been well-studied that these survivors have 15- and 7-fold of increased risk of developing congestive heart failure and premature death due to cardiac events compared to the general population. Since a long latency period often occurs before the clinically evident disease, the ability to predict is critical to expand the impact of survivor-based research to inform the future design and treatment regimes. To provide proper follow-up care for survivors, it is imperative to conduct patient-centered risk predictions that incorporate patient heterogeneity in a personalized and dynamic manner. While there is a growing body of literature on risk-stratification methods, most models only utilize baseline factors associated with the disease outcome. Cardiovascular burden is well-documented among childhood cancer survivor with cardiac risk factors increasing over time. In addition, a range of neighborhood and socioeconomic factors can affect risk for specific outcomes such as obesity. Leveraging the resources of the St. Jude Lifetime Cohort study (SJLIFE), we aim to develop a novel statistical model for personalized dynamic cancer risk prediction to improve the current cancer risk classification paradigm. Given that longitudinal information is routinely measured and documented for SJLIFE survivors, it is optimal to make full use of available longitudinal data to improve risk classification and guide timely risk-based prevention interventions to reduce the burden of cardiac diseases. The proposed method is appealing for its conceptual simplicity and efficiency for conducting dynamic prediction incorporating comprehensive longitudinal information, where risk prediction/ stratification can be updated as new observations are gathered to reflect the patient's latest health and behavior status. The proposed solutions will be accessible through open-source R software that we will make publicly available, and will be applied to data from childhood cancer survivors participating in SJLIFE.

Public Health Relevance

The goal of this project is to develop a novel statistical model for personalized dynamic cancer risk prediction integrating comprehensive longitudinal information. Successful completion of the proposed study will serve as a promising tool to improve risk stratification among cancer survivors to guide cancer survivorship care.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01CA195547-06S1
Application #
10166232
Study Section
Program Officer
Shelburne, Nonniekaye F
Project Start
2020-08-10
Project End
2021-06-30
Budget Start
2020-08-10
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
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Varedi, Mitra; Lu, Lu; Howell, Carrie R et al. (2018) Peripheral Neuropathy, Sensory Processing, and Balance in Survivors of Acute Lymphoblastic Leukemia. J Clin Oncol 36:2315-2322
Green, Daniel M; Wang, Mingjuan; Krasin, Matthew J et al. (2018) Serum ALT elevations in survivors of childhood cancer. A report from the St. Jude Lifetime Cohort Study. Hepatology :
Huang, I-Chan; Klosky, James L; Young, Chelsea M et al. (2018) Misclassification of self-reported smoking in adult survivors of childhood cancer. Pediatr Blood Cancer 65:e27240
Monahan, Ken; Lenihan, Daniel; Brittain, Evan L et al. (2018) The relationship between pulmonary artery wedge pressure and pulmonary blood volume derived from contrast echocardiography: A proof-of-concept study. Echocardiography 35:1266-1270
Fernandez-Pineda, Israel; Davidoff, Andrew M; Lu, Lu et al. (2018) Impact of ovarian transposition before pelvic irradiation on ovarian function among long-term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study. Pediatr Blood Cancer 65:e27232
Chow, Eric J; Chen, Yan; Hudson, Melissa M et al. (2018) Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer. J Clin Oncol 36:44-52
Im, Cindy; Ness, Kirsten K; Kaste, Sue C et al. (2018) Genome-wide search for higher order epistasis as modifiers of treatment effects on bone mineral density in childhood cancer survivors. Eur J Hum Genet 26:275-286
Huang, I-Chan; Bhakta, Nickhill; Brinkman, Tara M et al. (2018) Determinants and Consequences of Financial Hardship Among Adult Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort Study. J Natl Cancer Inst :

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