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Late Effects of Treatment for Childhood Cancer (PDQ®)

Changes to This Summary (01/29/2015)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Late Effects of Treatment for Childhood Cancer

Added text to state that the even higher prevalence of late effects among clinically ascertained cohorts is related to the subclinical and undiagnosed conditions detected by screening and surveillance measures.

Subsequent Neoplasms

Added text about a report on 2,492 female participants in the National Wilms Tumor Studies 1 through 4; 16 of 369 women who received chest irradiation for metastatic Wilms tumor developed invasive breast cancer (cited Lange et al. as reference 33).

Added Daniëls et al. as reference 53.

Late Effects of the Cardiovascular System

This section was comprehensively reviewed and extensively revised.

Late Effects of the Central Nervous System

Added text to state that while there is considerable evidence published about late effects of the central nervous system (CNS), its quality is often limited by small sample size, cohort selection and participation bias, cross-sectional versus prospective evaluations, and variable time of assessment from treatment exposures.

Added Khong et al. as reference 10.

Added text to state that cavernomas have also been observed in acute lymphoblastic leukemia (ALL) survivors treated with cranial radiation; they have been speculated to result from angiogenic processes as opposed to tumorigenesis (cited Faraci et al. as reference 13).

Revised text to state that in a study that involved long-term neurocognitive testing in 92 children with a history of standard-risk ALL who had received either dexamethasone or prednisone during treatment, no meaningful differences in mean neurocognitive and academic performance scores were observed.

Added text to state that numerous reports describe abnormalities of CNS integrity and function, but such studies are typically limited by small sample size, cohort selection and participation bias, cross-sectional ascertainment of outcomes, and variable time of assessment from treatment exposures. In contrast, relatively few studies comprehensively or systematically ascertain outcomes related to peripheral nervous system function.

Added text to state that evidence for adverse psychosocial adjustment after childhood cancer has been derived from a spectrum of sources, ranging from patient-reported or proxy-reported outcomes to data from population-based registries. The former may be limited by small sample size, cohort selection and participation bias, and variable methods and venues of assessments. The latter is often not well correlated with clinical and treatment characteristics that permit the identification of survivors at high risk of psychosocial deficits.

Added text to state that survivors with neurocognitive deficits are particularly vulnerable to adverse psychosocial outcomes that affect achievement of expected social competence during adulthood.

Late Effects of the Digestive System

Added Fromm et al. as reference 10.

Added text to state that the most significant degree of tooth aplasia or delayed eruption occurs in younger children who are exposed to radiation doses of 20 Gy or higher (cited Thompson et al. as reference 11).

Late Effects of the Endocrine System

Added text to state that there is considerable evidence linking radiation exposure to thyroid abnormalities, but the prevalence of specific conditions varies widely because studies are limited by cohort selection and participation bias, heterogeneity in radiation treatment approach, time since radiation exposure, and method of ascertainment.

Added text to state that although the quality of the literature regarding pituitary endocrinopathy among childhood cancer survivors is often limited by retrospective data collection, small sample size, cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment, the evidence linking this outcome with radiation, surgery, and tumor infiltration is quite compelling because affected individuals typically present with metabolic and developmental abnormalities early in follow-up.

Added text to state that the evidence for metabolic syndrome ranges from clinically manifested conditions that are self-reported by survivors to retrospectively assessed data in medical records and hospital registries to systematic clinical evaluations of clinically well-characterized cohorts. Studies have been limited by cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment.

Late Effects of the Immune System

Added text to state that late effects of the immune system have not been well studied, especially in survivors treated with contemporary therapies. Reports published about long-term immune system outcomes are limited by retrospective data collection, small sample size, cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment.

Added text about the the recommended reimmunization schedule for children who have undergone intensive treatments (cited Ruggiero et al and Patel et al. as references 12 and 13, respectively).

Late Effects of the Reproductive System

Added text to state that evidence for this outcome in childhood cancer survivors is limited by studies characterized by small sample size, cohort selection and participation bias, cross-sectional assessment, heterogeneity in treatment approach, time since treatment, and method of ascertainment. In particular, the literature is deficient regarding hard outcomes of reproductive potential and outcomes after contemporary risk-adapted treatment approaches.

Added text to state that although available data suggest that Leydig cells are more vulnerable when exposed to radiation before puberty, confounding factors, such as the age at testing and the effects of both orchiectomy and chemotherapy, limit the reliability of this observation.

Late Effects of the Respiratory System

Added text to state that evidence for this outcome in childhood cancer survivors is limited by studies characterized by small sample size, cohort selection and participation bias, cross-sectional assessment, heterogeneity in treatment approach, time since treatment, and method of ascertainment.

Late Effects of the Special Senses

Added Lewis et al. as reference 6.

Revised text to state that high-frequency sensorineural hearing loss is uncommon at cumulative radiation doses below 35 Gy, and is rarely severe below doses of 45 Gy (cited Bhandare et al. as reference 13). Also added Merchant et al. as reference 14.

Late Effects of the Urinary System

Added text to state that the evidence for long-term renal injury in childhood cancer survivors is limited by studies characterized by small sample size, cohort selection and participation bias, cross-sectional assessment, heterogeneity in time since treatment, and method of ascertainment. In particular, the inaccuracies of diagnosing chronic kidney dysfunction by estimating equations of glomerular dysfunction should be considered (cited Jaworek et al. as reference 2).

Added text to state that specific quantitative data are sparse, but a study of 108 children treated for Wilms tumor who had undergone unilateral nephrectomy showed that 41% of children who received less than 12 Gy to the contralateral remaining kidney, 56% of children who received 12 Gy to 24 Gy, and 91% of children who received more than 24 Gy had a decreased creatinine clearance, defined as less than 63 mL/min/m2 (cited Mitus et al. as reference 18).

Added text about how the age at time of radiation exposure and unilateral versus bilateral radiation affect renal toxicity (cited Peschel et al., Ritchey et al., Paulino et al., and Cheng et al. as references 20, 21, 22, and 23, respectively).

Added text to state that in a study of 6,119 children treated between 1986 and 2010, 1.6% developed hemorrhagic cystitis, most of whom had severity scores of II or III. Older age, previous bone marrow or peripheral stem cell transplantation, and BK virus in the urine were risk factors for hemorrhagic cystitis and were associated with a higher severity score (cited Riachy et al. as reference 32).

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

  • Updated: January 29, 2015