Findings from two studies authored by Tara Henderson, MD, MPH, Chair of Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago, are advancing the understanding of early colorectal cancer and risk factors in childhood cancer survivors. 

Mortality After Colorectal Cancer Among Survivors of Childhood Cancer 

Survivors of childhood cancer face substantial long-term risks from their cancer treatments, including  subsequent malignant neoplasms, which are a leading cause of premature death after recurrence of the primary cancer. Subsequent colorectal cancer is notable for its elevated incidence in this population, with survivors experiencing roughly a fourfold higher risk than the general population. Some are diagnosed within a decade of their childhood cancer. This study published in the Journal of the National Cancer Institute analyzed data from 25,656 long-term survivors in the Childhood Cancer Survivor Study to examine subsequent colorectal cancer and associated mortality.  

Overall Findings 

  • 96 survivors developed subsequent colorectal cancer. 
  • Half of these survivors were diagnosed before age 40, and nearly 20 percent before age 30.  
  • Thirty-five percent of those diagnosed before age 40 had never received abdominal, pelvic, or spine radiation, a key criterion for high-risk screening. 
  • There were 31 deaths following colorectal cancer diagnosis, representing a mortality rate approximately three times higher than in survivors without colorectal cancer. 

Key Takeaways 

  • Many survivors developing subsequent colorectal cancer would not have been captured by current Children’s Oncology Group surveillance guidelines, which recommend screening starting at age 30 or 5 years after abdomen, pelvic, spine, or total-body irradiation, which occurs last.  
  • Subsequent colorectal cancer may develop earlier than previously thought, including in survivors not currently considered high-risk. 
  • Current risk stratification may under-identify survivors at elevated risk for subsequent colorectal cancer. 

Colorectal-Specific Radiation Dose and Chemotherapy Risk for Subsequent Colorectal Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study (CCSS) Report 

Radiation therapy and chemotherapy are established risk factors for subsequent colorectal cancer in childhood cancer survivors. However, earlier studies evaluating chemotherapy were limited by small sample sizes, and prior radiation exposure studies lacked detailed information on radiation dose distribution across the colorectum. This study published in the Journal of Clinical Oncology analyzed data from 25,723 participants in the Childhood Cancer Survivor Study to examine the association between subsequent colorectal cancer incidence and colorectal-specific radiation doses, and between subsequent colorectal cancer incidence and cumulative chemotherapy exposure.  

Overall Findings 

  • 104 cases of subsequent colorectal cancer were identified. 
  • Subsequent colorectal cancer risk increased substantially when the colon and rectum received greater than or equal to 10 grays of radiation: incidence rates were nearly fourfold higher for doses of 10 to less than 20 grays and eightfold higher for doses greater than or equal to 20 grays compared with the general population.  
  • Risk also rose with increasing irradiated volume: approximately fourfold higher when 20 percent to less than 40 percent of the colorectum was exposed, and up to ninefold higher when greater than or equal to 80 percent was exposed compared to the general population.  
  • Among survivors who did not receive radiation therapy, subsequent colorectal cancer rates increased with higher cumulative doses of platinum-based agents, alkylating agents, anthracyclines, and procarbazine.  

Key Takeaways

  • These dose-response relationships highlight opportunities to refine childhood cancer treatment planning to minimize long-term colorectal cancer risk. 
  • The findings support risk-stratified surveillance strategies for long-term survivors, informed by both colorectal-specific radiation dose metrics and cumulative chemotherapy exposures. 

Next Steps for the Henderson Survivorship Research Laboratory

A key goal of long-term survivorship is the early detection and prevention of treatment-related health complications. Yet many childhood cancer survivors do not fully engage in recommended risk-based follow-up, often due to limited knowledge and understanding of the risks they face. At the same time, primary care providers, who may see only a few childhood cancer survivors in their practice, often lack familiarity with survivorship-specific guidelines and screening recommendations. Addressing these dual gaps in survivor engagement and provider awareness is essential to improving long-term outcomes for this population. 

The Henderson Survivorship Laboratory is developing innovative approaches to strengthen survivorship care and improve long-term outcomes of this population, including proposals to: 

  • Test a bundled screening approach that coordinates multiple cancer screenings (breast, colorectal, and skin) in a single visit. This study also proposes using an AI-powered chatbot to address survivors’ information needs and remote patient navigation to bridge communication and care coordination gaps between survivors and medical providers. 
  • Evaluate an adaptive chatbot-based genetic service delivery intervention to increase uptake of genetic testing. Currently, only about 15 percent of adult childhood cancer survivors have access to genetic services, even though up to 20 percent carry a germline mutation in a cancer susceptibility gene. 
  • Investigate biological age acceleration and chronic health conditions among childhood cancer survivors—a relationship that remains largely unexplored. The geroscience framework views aging as a measurable and potentially modifiable process, offering a strong rationale for studying accelerated aging in this population. 

Dr. Henderson is an attending physician in the Division of Hematology, Oncology, Neuro-oncology, and Stem Cell Transplantation at Lurie Children’s and a professor of pediatrics at Northwestern University Feinberg School of Medicine. She holds the Founder’s Board Centennial Professorship in Pediatrics at Lurie Children’s. 

Pediatric research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute.