This application is being submitted in response to theNotice of Special Interest (NOSI) identified as NOT- CA-20-038. Childhood cancer survivors are at high risk of adverse events and roughly a third of survivors of common childhood cancers will experience a serious or lethal late event by age 40. The risk of these events are almost twice as likely to occur in women, and can include several serious chronic health. However, despite the known increased relative risks, particularly in females, we are currently unable to provide primary care physicians and patients with more specific guidance as to the risk of having a specific event within a specified period of time. There is therefore a critical need for practical risk prediction tools for these patients and their providers that can be used to help guide and encourage optimal survivorship care. In this study, we will use data from all adult female survivors in the Childhood Cancer Survivors Study (CCSS) cohort to investigate the ability of an existing risk calculator developed in the United Kingdom (UK) to predict the 5-year rate of serious events. To predict risk, we will use the UK calculator, which provides simplified risk stratification for childhood cancer survivors as a function of their treatment. Patients will be assigned either a risk of low, intermediate, and high based on the treatment they received in accordance with the UK risk model. We will then test the model?s ability to predict the rate of serious events within specified 5-year windows.
Aim 1 : To predict long-term overall survival in females within the CCSS cohort using the UK risk categorization. Using the UK calculator we will place females in low, intermediate, or high risk categories and compare long- term overall survival by risk category. We will conduct our study with survival being defined at A) 10 years after initial diagnosis, B) 15 years after diagnosis, C) 25 years of age, and D) 30 years of age to assess to what extent these risks can be consistently assessed over time.
Aim 2 : To predict the incidence of serious chronic health conditions (grade 3-5) within the CCSS cohort using the UK risk categorization. We will examine the incidence of serious chronic health conditions including cardiovascular, pulmonary, renal conditions, depression, and development of secondary malignancies. We will assess these events both at A) 10 years after initial diagnosis, B) 15 years after diagnosis, C) 25 years of age, and D) 30 years of age. Women will be limited to those without any evidence of chronic health conditions at each time point, with the focus being to identify incident late events in previously healthy women. This study is an important women?s health initiative which will provide patients and providers with individualized, intermediate-term risk profiles to encourage appropriate and optimal survivorship care.
Secondary to the therapies that cured childhood cancer survivors, most will develop a chronic disease early in life. For example, women treated with chest radiation are at significantly elevated risk of breast cancer at a young age. In EMPOWER-II, we are currently testing an intervention aimed at promoting early breast cancer detection by screening with breast MRI and mammography and thus reduce the morbidity and mortality faced by these young women. In this study, we propose to develop a breast imaging repository including mammograms and breast MRIs completed by women enrolled in the EMPOWER-I and EMPOWER-II Studies. We will then look at how often women treated for a childhood cancer have dense breast tissue or abnormal breast MRIs.
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