Long-Term Effects of Radiation Exposure among Adult Survivors of Childhood Cancer: Results from the Childhood Cancer Survivor Study

Department of Epidemiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Radiation Research (Impact Factor: 2.91). 12/2010; 174(6):840-50. DOI: 10.1667/RR1903.1
Source: PubMed


In the last four decades, advances in therapies for primary cancers have improved overall survival for childhood cancer. Currently, almost 80% of children will survive beyond 5 years from diagnosis of their primary malignancy. These improved outcomes have resulted in a growing population of childhood cancer survivors. Radiation therapy, while an essential component of primary treatment for many childhood malignancies, has been associated with risk of long-term adverse outcomes. The Childhood Cancer Survivor Study (CCSS), a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource to quantify associations between radiation therapy and risk of long-term adverse health and quality of life outcomes. Radiation therapy has been associated with increased risk for late mortality, development of second neoplasms, obesity, and pulmonary, cardiac and thyroid dysfunction as well as an increased overall risk for chronic health conditions. Importantly, the CCSS has provided more precise estimates for a number of dose-response relationships, including those for radiation therapy and development of subsequent malignant neoplasms of the central nervous system, thyroid and breast. Ongoing study of childhood cancer survivors is needed to establish long-term risks and to evaluate the impact of newer techniques such as conformal radiation therapy or proton-beam therapy.

Download full-text


Available from: Marilyn Stovall,
  • Source
    • "It is well known that cranial and total body irradiation result in an increased risk of a broad range of late complications, and efforts to reduce radiotherapy in treatment protocols without compromising survival rates have been successful for ALL patients during the last three decades [22,23]. Nevertheless, Bradley et al. could not find a specific treatment modality to be a risk factor for hospitalization when survivors of all childhood cancers were grouped together [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Previous studies have indicated that survivors of childhood acute lymphoblastic leukemia (ALL) have an increased morbidity measured in terms of health care utilization. However, earlier studies have several potentially important limitations. To overcome some of these, we investigated hospital contact rates, and predictors thereof, among 5-year survivors of ALL in a population-based setting, and compared them to a control cohort regarding outcome measures from a comprehensive nation-wide health register. Methods All individuals diagnosed with ALL before the age of 18 in Southern Sweden during 1970–1999 and alive January 2007 (n = 213; male = 107) were identified through the Swedish Cancer Register. Each subject was matched to fifty controls, identified in the Swedish Population Register. All study subjects were linked to the National Hospital Register and detailed information was obtained on all hospital contacts (hospital admissions and outpatients visits) starting five years after cancer diagnosis, and the corresponding date for the controls, until 2009. Results The median follow-up among the 5-year survivors of ALL was 16 years (range 5–33), accruing a total of 3,527 person-years. Of the 213 5-year survivors, 105 (49.3%) had at least one hospital contact compared to 3,634 (34.1%) of the controls (p < 0.001). Survivors had more hospital contacts (3 [1–6] vs. 2 [1–4] contacts, p < 0.001) and more total days in hospital (6 [2–18] vs. 3 [1–7] days, p < 0.001) than the controls during the study period. Logistic regression analysis showed that survivors treated with cranial irradiation and/or total body irradiation (45% and 7%, respectively) had an increased risk of at least one hospital contact (OR 2.3, 95%CI; 1.5–3.6 and OR 11.0, 95%CI; 3.2–50.7, respectively), while there was no significant difference between the non-irradiated survivors and controls. Conclusions We show that irradiated survivors of childhood ALL have an increased morbidity measured in terms of hospital contacts, in comparison to non-irradiated survivors and controls, while non-irradiated survivors have not. These findings are encouraging regarding the future morbidity of children currently treated for ALL, as radiotherapy is necessary only for a minority of these.
    BMC Cancer 06/2014; 14(1):419. DOI:10.1186/1471-2407-14-419 · 3.36 Impact Factor
  • Source
    • "For example, patients treated with total body irradiation for bone marrow transplants are at high risk of developing cancer (Rizzo et al 2009). Large numbers of survivors of childhood cancer, currently under study, are at higher risk of radiation-induced cancers of the thyroid, breast, bone and brain as well as heart disease (Armstrong et al 2010). Patients treated with radiotherapy for Hodgkin's lymphoma are at higher risk of radiation-induced cancers of the breast and lung (Boice 2007, Gilbert et al 2003, Travis et al 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (<0.75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident.
    Journal of Radiological Protection 04/2014; 34(2):R25-R52. DOI:10.1088/0952-4746/34/2/R25 · 1.70 Impact Factor
  • Source
    • "As of 2005, there were over 328,000 childhood cancer survivors in the USA, a number that will continue to grow with emerging treatment procedures [1]. Unfortunately, survival from childhood cancer is often accompanied by an increased risk for adverse late effects from treatment [2] [3] [4], including cardiovascular risk [5] [6], insulin resistance [7], and neurologic, musculoskeletal, and pulmonary complications [8]. Furthermore, adult survivors of childhood cancer may be particularly prone to weight-related problems as approximately half report low levels of physical activity [9] [10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Population-based studies are needed to estimate the prevalence of underweight or overweight/obese childhood cancer survivors. Procedure. Adult survivors (diagnosed ≤20 years) were identified from the linked Utah Cancer Registry and Utah Population Database. We included survivors currently aged ≥20 years and ≥5 years from diagnosis (N = 1060), and a comparison cohort selected on birth year and sex (N = 5410). BMI was calculated from driver license data available from 2000 to 2010. Multivariable generalized linear regression models were used to calculate prevalence relative risks (RR) and 95% confidence intervals (95% CI) of BMI outcomes for survivors and the comparison cohort. Results. Average time since diagnosis was 18.5 years (SD = 7.8), and mean age at BMI for both groups was 30.5 (survivors SD = 7.7, comparison SD = 8.0). Considering all diagnoses, survivors were not at higher risk for being underweight or overweight/obese than the comparison. Male central nervous system tumor survivors were overweight (RR = 1.12, 95% CI 1.01-1.23) more often than the comparison. Female survivors, who were diagnosed at age 10 and under, had a 10% higher risk of being obese than survivors diagnosed at ages 16-20 (P < 0.05). Conclusion. While certain groups of childhood cancer survivors are at risk for being overweight/obese, in general they do not differ from population estimates.
    Journal of Cancer Epidemiology 01/2014; 2014:531958. DOI:10.1155/2014/531958
Show more