Table 9. Treatment Complications Observed in Hodgkin Lymphoma Survivors continued...
Female Gonadal Toxicity
Because ovarian hormone production is linked to the maturation of primordial follicles, depletion of follicles by alkylating agent chemotherapy can potentially affect both fertility and ovarian hormone production.
Because of their greater complement of primordial follicles, the ovaries of young and adolescent girls are less sensitive to the effects of alkylating agents than are the ovaries of older women. In general, girls maintain ovarian function at higher cumulative alkylating agent doses compared with the germ cell function maintained in boys.
Most females treated with contemporary risk-adapted therapy will attain menses (if prepubertal at treatment) or regain normal menses (if pubertal at treatment) unless pelvic radiation therapy is given without oophoropexy.
Ovarian transposition to a lateral or medial region from the planned radiation volume may preserve ovarian function in young and adolescent girls who require pelvic radiation therapy for lymphoma.
The risk of acute ovarian failure and premature menopause is substantial if treatment includes combined-modality therapy with alkylating agent chemotherapy and abdominal or pelvic radiation or dose-intensive alkylating agents for myeloablative conditioning before hematopoietic cell transplantation.[12,13]
In the Childhood Cancer Survivor Study (CCSS), investigators observed that Hodgkin lymphoma survivors were among the highest risk groups for acute ovarian failure and early menopause. In this cohort, the cumulative incidence of nonsurgical premature menopause among survivors treated with alkylating agents and abdominal or pelvic radiation approached 30%.[12,13]
In a large study of 1,700 women treated between the ages of 15 and 40 years, there was a high incidence (60%) of premature ovarian failure after alkylating chemotherapy with no excess risk of premature ovarian failure following nonalkylating chemotherapy. Among women who developed premature ovarian failure, 22% had previously had one or more children.
Abnormalities of the thyroid gland, including hypothyroidism, hyperthyroidism, and thyroid neoplasms have been reported to occur at a higher rate among survivors of Hodgkin lymphoma compared with the general population.
Risk factors for hypothyroidism include increasing dose of radiation, female gender, and older age at diagnosis.[15,16,17] CCSS investigators reported a 20-year actuarial risk of 30% of developing hypothyroidism in Hodgkin survivors treated with 3,500 cGy to 4,499 cGy and 50% for subjects whose thyroid received 4,500 cGy or more.
Hypothyroidism develops most often in the first 5 years after treatment, but new cases have been reported to emerge more than 20 years after the diagnosis.
Hyperthyroidism has been observed after treatment for Hodgkin lymphoma with a clinical picture similar to that of Graves disease. Higher radiation dose has been associated with greater risk of hyperthyroidism.
Thyroid neoplasms, both benign and malignant, have been reported with increased frequency following neck irradiation. The incidence of nodules varies substantially across studies (2%-65%) depending on the length of follow-up and detection methods used.[15,16,17] Risk factors for the development of thyroid nodules in Hodgkin lymphoma survivors reported by CCSS include time since diagnosis greater than 10 years (relative risk [RR], 4.8; 95% confidence interval [CI], 3.0-7.8), female gender (RR, 4.0; 95% CI, 2.5- 6.7), and radiation dose to thyroid greater than 25 Gy (RR, 2.9; 95% CI, 1.4-6.9).