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

Abstract

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.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…51 AYA patients receiving RT to testes or ovaries are at risk of developing infertility later in life. 52 Women with HL who receive chest RT between 10 and 30 years of age are at increased risk of developing breast cancer.…”

The Role of Exercise in Pediatric and Adolescent Cancers: A Review of Assessments and Suggestions for Clinical Implementation

“…The functional changes after external beam radiation usually occur by six months but may become evident up to 20 years later, and comprise clinical or subclinical hypothyroidism, with a combined incidence of 20-30% [6,7,16]. The morphological changes consist of benign lesions, primarily adenomas, and malignant lesions, with an average 6-fold increased risk compared to the normal population.…”

“…As normal growth occurs, the deformity becomes progressively more pronounced. However, the most evident effect on linear growth is seen when radiotherapy is given before skeletal maturation has occurred [7]. Bone irradiation >20 Gy, especially near long-bone growth plates, leads to reduced bone growth and potentially asymmetric limb growth.…”

“…In children treated for cancer, LAE include impaired growth [6], cognitive dysfunction [7,8], diminished neurological function [9], cardiopulmonary compromise [10,11], musculoskeletal disturbances [10], and secondary malignancy [12,13]. As a result, adult survivors of childhood cancer may suffer from cardiomyopathy, heart valve and conduction disorders [14,15], increased cardiovascular risk factors including hypertension, dyslipidemia [16][17][18], and obesity [19,20], pulmonary disorders [21,22], endocrine disorders [23] including hypothalamic-pituitary-adrenal disorders [24], diabetes mellitus [25], ovarian and Leydig cell dysfunction [26], and hypothyroidism [27].…”

Acute effects on the thyroid gland after non-directed radiation therapy in children and adolescents

“…2 However, cancer therapy carries a high morbidity rate, and may affect organs not targeted during treatment. 3 During radiation therapy, the highest radiation doses are directed to the tumour or target tissues, but radiation may scatter to nearby healthy tissue. 4 Children are more sensitive to radiation injury, perhaps because of higher cell replication rates and their longer life expectancy.…”