Faculty

Margaret Zacharin

VIEW CV

Childhood cancer survivors (CCS)

Long term effects of childhood cancer.

Overall survival after childhood cancer has increased to between 80-90% for some conditions but at a cost of increasing cumulative incidence of endocrine abnormalities across the lifespan, with high risks for thyroid cancer, hypothyroidism, impaired fertility, metabolic syndrome and type 2 diabetes mellitus. Endocrine late effects of irradiation and chemotherapy can be direct, resulting in endocrine gland hypofunction or indirect via metaplasia and malignant transformation of exposed tissues and via altered bone growth. Adequate surveillance and planning strategies are essential, to reduce morbidity and to improve quality of life. Recognition of major global effects on learning, short term memory impairment and memory processing is necessary, to understand complex management needs. One in eight survivors after CSXRT will have a symptomatic stroke by age 45 secondary to radiation induced cerebral arteritis.

Hypothalamic pituitary axis deficits occur after radiation exposure in a dose related fashion with
evolution of losses up to 20+ years. Replacement of losses is essential to optimize growth and to reduce morbidity. Acquisition of optimal peak bone mass and maintenance of bone quality in adulthood is compromised by alterations in pubertal and growth cascades.

Altered timing and tempo of puberty after CXRT or total body irradiation, evolving to hypogonadism, requires in depth understanding, to provide treatment appropriate to current status. Specific losses of gonadal function vary, depending on sex, age, type and amount of gonadotoxin. For boys, loss of germinal epithelium occurs with low dose radiation exposure, with Leydig cell damage at higher doses. Germ cell loss with chemotherapy, particularly alkylating agents, requires semen collection or attempted germ cell salvage before puberty as an experimental option for male fertility preservation. For girls, reduction in the oocyte pool occurs at any age, following both radiation and chemotherapy, late recovery being possible even after alkylators. Ovum salvage is should be offered prior to gonadotoxin exposure.

Thyroid nodularity and differentiated carcinoma is common after scatter or direct radiation. Risk continues for 40 years, requiring mandatory ultrasound surveillance every second year.
Future planning should involve risk-based screening and surveillance, targeted education for risk reduction and healthcare delivered by clinicians familiar with issues and risks.

Return to Faculty List