Survivorship and late effects

1

Describe the goals of survivorship care and the role of the survivorship clinic.

Childhood cancer survivors are at an increased risk for significant adverse health effects and impaired quality of life after disease-related therapy. Multimodal regimens, consisting of chemotherapy, radiation, and surgery, can result in a myriad of severe chronic health conditions, secondary malignancies, physical limitations, psychological and neurocognitive dysfunction, infertility, and premature frailty and death. Many of these therapy-related late effects do not present until years after completion of therapy. With childhood cancer survival rates exceeding 80%, the need for survivorship-focused health care is becoming increasingly recognized. Survivorship clinics provide standardized, comprehensive, risk-based follow-up care to decrease exposure-related health risks and improve quality of life among pediatric cancer survivors. Timely screening and intervention, health education, anticipatory guidance, and promotion of healthy lifestyle are all critical to promoting long-term health in this population. Among adolescents and young adults, the survivorship program plays an important role in facilitating the successful transition from a pediatric to an adult healthcare system.

2

Describe the etiology of cardiac late effects and current screening recommendations for survivors.

Cardiotoxicity is one of the most common late effects seen among childhood cancer survivors and results in increased morbidity and mortality in this population. Chemotherapy agents, namely anthracyclines, and radiotherapy, which includes the heart in the radiation field (chest, abdomen, thoracic/whole spine), both independently and in combination with one another, are the primary causes of cardiac late effects among survivors. Chronic progressive cardiotoxicity may appear early after completion of therapy or decades later. Depending on the type and dose of exposure, potential cardiotoxic late effects are vast and include hypertension, heart failure (notably cardiomyopathy, subclinical left ventricular dysfunction, and congestive heart failure), pericardial disease, valvular disorders, atherosclerosis, coronary artery disease, and arrhythmias. During their yearly survivorship visits, patients who received any dose of anthracyclines and/or less than 15 Gy of radiotherapy should be evaluated for shortness of breath, dyspnea or exertion, orthopnea, chest pain, palpitations, and, if younger than 25 years, abdominal symptoms such as nausea/vomiting. Physical examination should include blood pressure (BP) monitoring and a complete cardiac examination, and other risk factors such as glucose and lipid levels should be monitored. Patients should be counseled on a heart-healthy diet and exercise habits. A baseline electrocardiogram (ECG; including QTc interval) should be obtained for every patient who enters survivorship. Echocardiogram screening should be conducted as per Table 24.1 .

3

Describe the occurrence and risk factors associated with secondary malignancies.

The risk of malignancy among survivors over the age of 40 is at least twice that of adult counterparts in the general population who have not had previous exposures. Secondary malignancies are associated with significant morbidity and are the most common cause of nonrelapse late mortality among 5-year survivors, accounting for nearly half of nonrelapse deaths. The risk of developing a second neoplasm is dependent on patient-related factors such as original cancer diagnosis and age at treatment (younger age is a greater risk), genetic susceptibility, and therapeutic exposures received during primary cancer treatment. Specifically, the risk is greatest for those patients who were exposed to radiation and increased doses of chemotherapeutic agents, including alkylating agents, anthracyclines, and epipodophyllotoxins. Among the most common types of secondary cancers are those of the breast, thyroid, central nervous system, bone, and soft tissues. Other secondary malignancies that are also important to screen for are leukemia, lymphoma, melanoma, and gastrointestinal malignancy.

4

What are the screening recommendations for the most common secondary malignancies?

For the most common second malignant neoplasms and associated screening recommendations, see Table 24.2 .

5

Describe the endocrinopathies that can occur in childhood cancer survivors.

Endocrine complications are extremely common among childhood cancer survivors, and approximately 50% of survivors will contend with a hormonal dysfunction during their lifetime. Most of these disorders can be mitigated with timely screening and intervention, thereby preventing significant physical and psychological burden in this population. Endocrinopathies can primarily be attributed to radiation therapy (RT) and surgical interventions. RT to the head/brain may result in pituitary dysfunction, including altered pubertal timing; growth hormone, thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) deficiency; altered body composition (reduced lean muscle mass and increased fat mass resulting in being overweight or obese); hyperprolactinemia; and metabolic syndrome. Noncentral hypothyroidism or hyperthyroidism can result from radiation exposure to the neck, spine, or thorax. Finally, radiation to the abdomen/pelvis or genitourinary system may result in impaired glucose metabolism/diabetes mellitus and impaired production of male and female sex hormones. Neurosurgical procedures affecting the hypothalamic pituitary axis may also result in altered body composition and overweight/obesity, as well as development of diabetes insipidus. Among females, unilateral oophorectomy results in ovarian hormone deficiencies leading to delayed or arrested puberty, as well as premature ovarian insufficiency/menopause, whereas bilateral oophorectomy may result in the absence of puberty and loss of ovarian follicular pool and infertility. Among males, unilateral or partial orchiectomy can result in testosterone deficiency/insufficiency and delayed/arrested puberty, whereas bilateral orchiectomy results in the absence of puberty and azoospermia (infertility). Lastly, thyroidectomy, radioiodine therapy, and therapeutic doses of systemic MIBG lead to hypothyroidism, and certain chemotherapeutic exposures, such as alkylating agents, corticosteroids, and tyrosine kinase inhibitors, are linked to endocrine dysfunction.

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