||5R01CA268143-02 Interpret this number
||Sloan-Kettering Inst Can Research
||International Study of Subsequent Colorectal Cancer Among Survivors of Childhood, Adolescent, and Young Adult Cancers (I-Scry)
PROJECT SUMMARY / ABSTRACT
Survivors of childhood, adolescent, and young adult (AYA) cancer have an elevated risk of subsequent
malignant neoplasms which are associated with morbidity and premature mortality. Emerging evidence
suggests that colorectal cancer (CRC), associated with abdominal or pelvic radiotherapy used to treat the
childhood or AYA cancer, is one such neoplasm. Early studies indicate other treatment exposures, including
cisplatin and alkylator therapy, may also be associated with CRC risk and may interact with the radiotherapy to
confer a markedly elevated risk. Knowledge of whether age at exposure to these therapies might modify risk is
limited. Further, prognosis after a treatment-related CRC is not well-understood. These gaps in knowledge are
due to the limited number of CRCs in any single cohort, lack of detailed information on primary cancer
treatments for some cohorts, the relatively young age of cohorts, and the focus of existing cohorts on either
childhood cancer survivors or on survivors of specific young adult cancers.
We propose to leverage the unique resources of eight international childhood and AYA cancer survivor
cohorts. We will pool individual participant data on 51,309 survivors, 298 with CRC, and with median follow-up
across studies ranging from 13 to 26 years after primary cancer diagnosis, to comprehensively examine risk
factors of, and mortality after, subsequent CRCs. This is almost four-fold the number of CRCs in any known
childhood or AYA cohort with detailed treatment data available. Thus, the combination of childhood and AYA
cancer survivors into a single cohort is novel and given common treatment approaches to pediatric and AYA
cancer, will enable us to address these questions with the ability to assess the role of age at exposure.
The primary aim of this project is to evaluate the association of childhood and AYA cancer therapy
(abdominal and/or pelvic radiation fields and dose, as well as chemotherapy exposures including cumulative
doses of alkylating agents, anthracyclines, platinating agents) on CRC risk in a large, multi-cohort, international
survivor population. Secondary aims will focus on conducting an expanded assessment of the burden of CRC
in childhood and AYA cancer survivors. This includes estimating and comparing the incidence of CRC in
childhood and AYA cancer survivors to the incidence of CRC in the general population, as well as
characterizing mortality following a CRC diagnosis in childhood and AYA cancer survivors and comparing it to
that observed following a de novo CRC diagnosis in the general population.
The results from this work have the potential to help refine screening guidelines and strategies for
preventing CRC. In addition, in achieving our aims, we will establish a resource that may be leveraged for
future investigator-initiated research.