During the past 3 decades, multimodality therapy for childhood cancer has resulted in markedly improved survival. For the period from 1985 to 1997, the 5-year survival rate for childhood cancer reported by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program is 75%.[1] The therapy responsible for this survival can also produce adverse long-term health-related outcomes that manifest months to years after completion of cancer treatment, and are commonly referred to as late effects. It has been clearly demonstrated that long-term survivors of childhood cancer carry a high burden of morbidity with one-third of the survivors reporting severe or life threatening complications 30 years after diagnosis of their primary cancer.[2] Long-term survivors of childhood cancer are at an 8.4-fold increased risk of premature death when compared with an age-matched and gender-matched general population, with increases in cause-specific mortality seen for deaths due to second cancers, and cardiac and pulmonary causes.[3] Late effects include organ dysfunction, second malignant neoplasms, and adverse psychosocial sequelae. Unfortunately, the majority of childhood cancer survivors do not receive recommended risk-based care. The Childhood Cancer Survivor Study reported that 88.8% of survivors were receiving some form of medical care, but only 31.5% reported care that focused on their prior cancer (survivor-focused care) and 17.8% reported survivor-focused care that included advice about risk reduction and discussion or ordering of screening tests.[4]

Risk factors for late effects include:

• Tumor-related factors
  • Direct tissue effects.
  • Tumor-induced organ dysfunction.
  • Mechanical effects.



• Treatment-related factors
  • Radiation therapy: Total dose and fraction size, organ or tissue volume, and machine energy are the most critical factors.
  • Chemotherapy: Agent type, single and cumulative dose and schedule may modify risk.
  • Surgery: Technique and site are relevant.



• Host-related factors
  • Developmental status.
  • Genetic predisposition.
  • Inherent tissue sensitivities and capacity for normal tissue repair.
  • Function of organs not affected by radiation therapy or chemotherapy.
  • Premorbid state.

Several comprehensive reviews and books that address late effects of childhood cancer and its therapy have been published.[5-12] An example of specific recommendations for surveillance based on therapeutic exposure can be found in the Children's Oncology Group long-term follow-up guidelines.[Survivorship Guidelines]

Information concerning late effects is summarized in tables throughout the summary. Tables in the Common Late Effects of Childhood Cancer by Body System section of the summary have been modified from another review, with author permission.[8]

References

1. Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Also available online. Last accessed April 19, 2007. 
   
   
2. Oeffinger KC, Mertens AC, Sklar CA, et al.: Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355 (15): 1572-82, 2006.  [PUBMED Abstract]
   
   
3. Mertens AC, Liu Q, Neglia JP, et al.: Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 100 (19): 1368-79, 2008.  [PUBMED Abstract]
   
   
4. Nathan PC, Greenberg ML, Ness KK, et al.: Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 26 (27): 4401-9, 2008.  [PUBMED Abstract]
   
   
5. Oeffinger KC, Hudson MM: Long-term complications following childhood and adolescent cancer: foundations for providing risk-based health care for survivors. CA Cancer J Clin 54 (4): 208-36, 2004 Jul-Aug.  [PUBMED Abstract]
   
   
6. Meister LA, Meadows AT: Late effects of childhood cancer therapy. Curr Probl Pediatr 23 (3): 102-31, 1993.  [PUBMED Abstract]
   
   
7. Schwartz CL: Long-term survivors of childhood cancer: the late effects of therapy. Oncologist 4 (1): 45-54, 1999.  [PUBMED Abstract]
   
   
8. Schwartz C L, Hobbie WL, Constine LS, et al., eds.: Survivors of Childhood Cancer: Assessment and Management. St. Louis, Mo: Mosby, 1994. 
   
   
9. Constine LS: Late effects of cancer treatment. In: Halperin EC, Constine LS, Tarbell NJ, et al.: Pediatric Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 1999, pp 457-537. 
   
   
10. Green DM, D'Angio GJ, eds.: Late Effects of Treatment for Childhood Cancer. New York, NY: Wiley-Liss, Inc., 1992. 
    
    
11. Friedman DL, Meadows AT: Late effects of childhood cancer therapy. Pediatr Clin North Am 49 (5): 1083-106, x, 2002.  [PUBMED Abstract]
    
    
12. Smith M, Hare ML: An overview of progress in childhood cancer survival. J Pediatr Oncol Nurs 21 (3): 160-4, 2004 May-Jun.  [PUBMED Abstract]
    
    

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