Survivors of childhood cancer

Approximately 500,000 adult survivors of childhood cancer in the US.

Approximately 14,500 new cases of cancer diagnosed in children from birth to 19 years annually, and approximately 1800-1900 will die.

About 1 in every 640 adults is a survivor of childhood cancer.

Presently, more than 85% of children with cancer become long-term survivors.

The most common adverse effects in individuals who survive childhood cancer are endocrine disorders, subsequent neoplasm, and cardiovascular disease.

Long-term survivors of childhood cancer have an elevated risk of morbidity and early mortality due to the late effects of the prior cancer therapy.

In people who survive childhood cancer, complications that develop may be related to chemotherapy and radiation therapy that were used to treat the cancer during childhood.

Survivors of childhood cancer mortality rates elevated for many years beyond 5 year survival compared to the general population.

Survivors of childhood cancer have recurrent or progressive disease as the leading cause of death following 5 year survival of the original disease, followed by second primary cancers and nonneoplastic conditions.

Mortality of adult long-term survivors of childhood cancer are at a substantially elevated risk of mortality, with a life expectancy shortened by a mean of 10 years compared with the general population.

Radiation related adverse effects usually develop within the radiation field and are related to dose  and they are more likely to occur if radiation therapy is administered at a younger age.

The most common neoplasms after radiation treatment for childhood cancers, include:  basal cell, carcinoma, breast, cancer, and thyroid cancer.

Radiation fields, including the chest with risk of breast, cancer in females and lung cancer in both sexes, brain with risk of CNS neoplasm, and neck with the risk of thyroid, cancer, and abdomen and pelvis with the risk of colorectal cancer.

There is a high risk for the development of secondary basal cell carcinoma, especially in treatment fields.

Chemotherapy related risks are also dose and age related and may affect multiple organs due to systemic nature of the exposure.

Premature heart disease is a major long-term complication in adult survivors of childhood cancer.


Adult survivors are eight times more likely to die of heart disease than other people, and more than half of children treated for cancer develop some type of cardiac abnormality.

Premature aging is most evident in survivors of childhood cancers, and the majority of whom have coexisting medical conditions, which may be life-threatening by the age of 45 years.

Survivors of childhood cancer are also at risk of developing adverse effects on the kidneys and the liver.


Hearing impairment is associated with platinum base chemotherapy or radiotherapy directly to the cochlear, and is typically bilateral, permanent and progressive.


Severe hearing impairment after ototoxic therapy is associated with neurocognitive deficits in childhood cancer survivors.

There is a significant inverse association between exercise and all-cause mortality in adult survivors of childhood cancer.

Childhood and young adult cancer survivors have a substantially higher risk of cardiovascular disease when compared with the general population, largely attributable to exposure to cardiotoxic drugs, radiation at a young age and emergence of new cardiovascular risk factors later in life.

Commonly observed cardiovascular complications among childhood cancer survivors include: congestive heart, failure, valvular abnormalities, pericardial disease, and coronary artery disease.

Prior radiation and anthracycline chemotherapy are associated with cardiovascular complications.

Stroke incidence after cranial radiation in childhood is increased.

Survivors of childhood cancer, have a greater incidence of hypertension and dyslipidemia.

Survivors of childhood cancer have a higher prevalence of sensory neuropathy, and motor neuropathy, particularly if exposed to vinca alkaloids.

Adolescent and young adult cancer survivors have a 73% higher risk for endocrine diseases than the cancer-free population.

childhood cancer, survivors, exposed to radiation before age of five years are found to have an association with higher rates of musculoskeletal growth problems, including muscular atrophy, skeletal hypoplasia, scoliosis and osteoporosis.

Osteonecrosis is seen in patients with prolong steroid therapy, and most commonly and children with a cute lymphoblastic leukemia.

Childhood survivors of cancer have a higher rate of restrictive pulmonary disease, that is interstitial, lung disease, with previous radiation to the chest and chemotherapy with bleomycin , busulfan, and nitorureas.

People treated for childhood cancer, have a higher prevalence of abnormal levels of growth, hormone, thyroid hormone, adrenocorticotropin, and gonoadotropin hormones.

Patients exposed to neck radiation have a 6.6 fold risk of developing hypothyroidism compared with absence of such exposure.

People exposed to cranial radiation have a greater risk for obesity, and adrenal insufficiency.

Patients exposed to total body radiation, radiation to the pancreas, have an associated increased risk of diabetes and primary ovarian insufficiency.

Males exposed to alkylating chemotherapy, and radiation therapy have increased risk of gonadal insufficiency.

Premature ovarian failure is more common in patients who have received the alkylating agents/abdomino/pelvic radiation.

In a British Childhood Cancer Survivor Study 17981 5 year survivors of childhood cancer: excess mortality from second primary cancers and circulatory and pulmonary diseases continue to occur beyond 25 years from diagnosis (Reuln RC).

Current estimates on 81% of childhood cancers associated with a 5 year survival.

More than two thirds develop a long-term complication or a chronic condition as a complication of their disease or its therapy.

Damage from chemotherapy and radiation treatments may not become clinically evident for many years.

Experience excess deaths from cardiac, pulmonary diseases and malignancies.

Survivors of childhood leukemia and brain tumors have a higher risk of chronic complications including second malignancies, neurocognitive deficits, hormone deficiencies, cardiac impairment, short stature and obesity.

In the Childhood Cancer Survivor Study (CCSS) of more than 17,000 survivors of childhood cancer treated between 1970-1986, 27.5% of adult survivors report at least one severe, life-threatening, or disabling condition compared with 5.2% of siblings, by 25 years after treatment.

Childhood cancer survivors are predisposed to obesity, diabetes, dyslipidemia, and hypertension: Survivors are 70% more likely than very siblings to be diagnosed with diabetes, 60% will likely have to take a cholesterol lowering medication and 90% as likely to have to take blood pressure medications.

Of 108 secondary sarcomas in children surviving childhood malignancies osteosarcoma was the second most common cancer occurring in 31 of 100 tumors ( Henderson TO et al).

Subsequent neoplasms incancers survivors include skin cancers, breast cancer, thyroid cancer, CNS tumors and bone tumors, and soft tissue sarcomas.

Half of childhood cancers survivors have received anthracyclines, and approximately 5% of children in previously treated with such agents will develop congestive heart failure and 40% will develop arrhythmias (Ginsberg JP et al).

Childhood cancer survivors have a six fold likelihood of developing CHF, five times more likely to have myocardial infarction, five times more likely to have heart valve disease than their cancer free siblings.

Cardio-pulmonary diseases, are the third leading cause of early mortality in survivors of childhood cancer behind cancer recurrence and second malignancies ( Shankar SM et al).

Risk factors for the development of anthracycline related cardiac toxicity in survivors of childhood cancer include: less than five years of age at the time of treatment, female gender, Blacks, cumulative dose of greater than 300 mg a meter squared if less than 18 years of age, and greater than 500 mg 2 m² if greater than 18 years at the time of treatment, treatment in infancy, and exposure to chest radiation at about 30 Gy.

Long-term survivors are at risk for growth and pubertal disorders related to hypothalamic-pituitary dysfunction, gonadal deficiency and failure, thyroid deficiency and metabolic bone disorders.

Survivors of childhood leukemia and brain tumors have an excess risk of stroke as a late occurrence.

Survivors of childhood leukemia and brain tumors are at an increased risk of late stroke particularly if treated with cranial radiotherapy at doses of greater than 30 Gy.

Survivors of childhood acute lymphoblastic leukemia are at risk for late effects of cancer therapy compared to the general population with a cumulative mortality of 5760 year survivors 13% at 25 years from diagnosis: Recurrent ALL and secondary neoplasms were the major causes of death (Mody R).

In a study of 5760 year ALL survivors 199 had secondary neoplasms with 53% in the central nervous system, and survivors reported more adverse general and mental health, functional impairment, and activity limitations (Mody R).

Late effects of treatment generally associated with individuals at a younger age and is associated with higher risk of radiation related injuries to musculoskeletal tissues and adverse effects on growth.

In older age at diagnosis there is an associated with increased risk of osteonecrosis predisposed by glucocorticoid use.

Survivors who have received cranial radiotherapy for CNS malignant neoplasms experience the highest risk for neurocognitive dysfunction.

Girls have more cognitive deficits after CNS radiation, and boys are more sensitive to effects of alkylating agents on gonadal function.

Children with CNS tumors are vulnerable to treatment effects on intellectual function and emotional and social development.

Women that have received chest radiation for pediatric malignancy have a significant risk of breast cancer at a young age.

Risk of breast cancer after chest radiation increases as early as 8 years after treatment and the median age of breast cancer diagnosis ranges from 32-35 years (Kenney L).

Risk of breast cancer is highest in women treated with radiation for Hodgkin’s disease with high dose mantle radiation.

Estimated that by age 45 12-20% of women treated with moderate to high doses radiation to the chest will be diagnosed with breast cancer (Taylor A).

As of 2006 there was an estimated 50,000 survivors of childhood team in the United States, and they have increased risks of secondary cancers, cardiovascular diseases, and other chronic illnesses.

Treatment of childhood cancers with the alkylating agents – cyclophosphamide, procarbazine, mechloroethamine, or anthracycline chemotherapy are associated with secondary lymphomas, and soft tissue sarcomas and breast cancer.

Elevated risk of morbidity and mortality among survivors  beyond the 4th decade of life is increased (Armstrong GT et al).

In a review of the Childhood Cancer Survivor Study it was noted that greater doses of alkylating agents and cisplatinum was associated with decreased likelihood of siring of pregnancy in male survivors of childhood cancer (Chow E et al).

In the above study reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain as there were few effects of the chemotherapy on reproduction.

Between 7.5 and 10% of survivors of childhood cancer carry a pathogenic or likely pathogenic genetic variant that predisposes them to subsequent neoplasms.
Anxiety and depression, or potential late effects of a cancer experience.
Neurocognitive impairment may be related to cranial, radiation and high dose of intrathecal methotrexate.
Cataracs and ocular toxicity may be related to prior radiation to the eyes andthe use of corticosteroids.
Hearing loss and tinnitus may be related to prior platinum based chemotherapy, high-dose cranial, radiation, or total body radiation.
Endocrine abnormalities, such as growth hormone deficiency, infertility, adrenal insufficiency, hypopituitarism, gonadotropin deficiency, hypothyroidism, and diabetes may be related to prior cranial radiation, total body radiation, neck radiation, abdominal radiation.
Complications of cancer therapy include abnormal sperm production in men, and, higher rates of preeclampsia and other pregnancy delivery abnormalities in survivors of childhood cancer.
Cardiomyopathy and cardiovascular diseases of the valves, pericardium, coronary arteries, and atherosclerosis may be related to anthracycline chemotherapy, and chest radiation.
Restrictive pulmonary disease may be related to chest radiation, bleomycin, busulfan, nitrosureas and pulmonary surgery.
Reduced bone mineral density may be related to the use of corticosteroids, allogeneic hematopoetic stem cell transplant.
Muscular atrophy, skeletal hypoplasia, scoliosis, kyphosis may be related to radiation.
Osteonecrosis may be related to corticosteroids, and allogeneic hematopoietic stem cell transplantation.
Peripheral neuropathy may be related to Pryor, vinca, alkaloids, and platinum base chemotherapy.
Gonadal insufficiency, testicular, or ovarian hormone deficiency, premature ovarian failure may be related to pelvic radiation, testicular radiation, alkylating agents, and total body radiation.
Reduced fertility, infertility, shortened lifetime period of fertility, all may be related to pelvic radiation, testicular, radiation, alkylating agents, and total body radiation.
subsequent neoplasm‘s in childhood cancer survivors include:
basal cell carcinoma with prior radiation,
thyroid, cancer with head and neck, radiation,
breast, cancer, with chest, radiation, anthracycline, and alkylating agent chemotherapy,
colorectal cancer with abdominal radiation, pelvic radiation, and total body irradiation
glioma with cranial radiation,
Meningioma with cranial radiation
Sarcoma with anthracyclines chemotherapy, radiation, involving bones or soft tissues.
Cataracs were found in 0.034% of survivors and radiation and corticosteroids are associated with increased risk.
Higher risk of ototoxicity in patients treated with platinum based chemotherapy, cranial radiation, Coadministration of furosemide, younger, age at diagnosis, history of CSF shunt,
Impaired cognition was identified in a group of 1426 at 20% at 24 years.
Impaired cognition, who is associated with higher incidence of cranial irradiation.
among survivors of childhood cancer, approximately 2.3 to 40.8% reported depression, and approximately 1.2% to 27.6% reported having anxiety.

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