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Late Effects of Treatment for Childhood Cancer (PDQ®)     
Last Modified: 03/26/2008
Health Professional Version
General Information

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. Late effects include organ dysfunction, second malignant neoplasms, and adverse psychosocial sequelae.

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.[2-9] This summary will discuss some of these late effects in detail by organ system and will address issues of second malignant neoplasms, mortality, and monitoring.

Table 1. Common Agents Associated With Therapy Late Effects
Agent/Agent Class/Modality  Affected Body System 
Anthracyclines Circulatory (Cardiac 2)
Respiratory 3 (Pulmonary)
Alkylating agents Reproductive (Gonadal 4)
Second malignant neoplasms 5
Topoisomerase II inhibitors Second malignant neoplasms 5
Platinums Urinary (Renal 6)
Special senses (Hearing 7)
Second malignant neoplasms 5
Corticosteroids Central nervous system 8
Musculoskeletal (Bone and body composition 9)
Musculoskeletal (Obesity 10)
Intrathecal chemotherapy Central nervous system 8
Bleomycin Respiratory (Pulmonary 11)
Methotrexate Central nervous system 8
Vincristine Digestive (Dental 12)
Thioguanine Digestive (Hepatic 13)

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.[5]

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. 14 Last accessed April 19, 2007. 

  2. 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]

  3. Meister LA, Meadows AT: Late effects of childhood cancer therapy. Curr Probl Pediatr 23 (3): 102-31, 1993.  [PUBMED Abstract]

  4. Schwartz CL: Long-term survivors of childhood cancer: the late effects of therapy. Oncologist 4 (1): 45-54, 1999.  [PUBMED Abstract]

  5. Schwartz C L, Hobbie WL, Constine LS, et al., eds.: Survivors of Childhood Cancer: Assessment and Management. St. Louis, Mo: Mosby, 1994. 

  6. 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. 

  7. Green DM, D'Angio GJ, eds.: Late Effects of Treatment for Childhood Cancer. New York, NY: Wiley-Liss, Inc., 1992. 

  8. Friedman DL, Meadows AT: Late effects of childhood cancer therapy. Pediatr Clin North Am 49 (5): 1083-106, x, 2002.  [PUBMED Abstract]

  9. 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]



Table of Links

1http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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2http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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3http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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4http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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5http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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6http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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7http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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8http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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9http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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10http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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11http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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12http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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13http://www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional
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14http://seer.cancer.gov/publications/childhood