Late Effects	Causative Treatment	Signs and Symptoms	Screening and Diagnostic Tests	Management and Intervention
aAdapted from Schwartz et al.[37]
Ovarian failure	Chemotherapy: Mechlorethamine, cyclophosphamide, procarbazine, busulfan, melphalan, dacarbazine (DTIC), carmustine (BCNU), CCNU, ifosfamide	Delayed/ arrested/ absent pubertal development including: breasts, female escutcheon, female habitus, vaginal estrogen effect, development of body odor and acne, changes in duration, frequency, and character of menses (cramping), estrogen deficiency: hot flashes, vaginal dryness, dyspareunia, low libido, infertility	Tanner stage, LH, FSH, estradiol: (1) age 12 yrs, (2) failure of pubertal development, (3) baseline when fully mature, (4) as needed for symptoms, assess basal body temperature (midcycle elevation suggests ovulation), (dehydroepiandrosterone for failure of development)	Hormone replacement (estrogen), anticipatory guidance regarding symptoms of estrogen deficiency and early menopause, referral to reproductive endocrinology, alternate strategies for parenting, early intervention (hormone replacement may prevent osteoporosis, atherosclerosis)
	Radiation: 4–12 Gy tolerance decreases with increasing age
	Surgery: Oophorectomy or oophoropexy
Vagina: fibrosis/diminished growth	Chemotherapy: Actinomycin D and doxorubicin enhance radiation therapy effect)	Dyspareunia, vaginal bleeding, small vaginal vault	Pelvic exam (possibly under anesthesia) baseline, during puberty and as needed for symptoms	Dilations, reconstructive surgery, potential need for cesarean section
	Radiation: >40 Gy
Uterus: fibrosis/decreased growth	Radiation: >20 Gy (prepubertal), >40–50 Gy (postpubertal)	Multiple spontaneous abortions, low birth-weight infants, small uterus	Pelvic: baseline, puberty, then annually	Questionable endometrial biopsy, counsel regarding pregnancy
Ureter: fibrosis	Radiation: >50–60 Gy	Frequent UTIs, pelvic hypoplasia, hydronephrosis	Urinalysis every year (urethrogram)	UTI prophylaxis
Urethra: strictures	Radiation: >50 Gy	Frequent UTIs, dysuria, stream abnormalities	Urinalysis every year, (voiding cystogram)	UTI prophylaxis, surgical intervention
	Surgery: Genitourinary

References

37. Schwartz C L, Hobbie WL, Constine LS, et al., eds.: Survivors of Childhood Cancer: Assessment and Management. St. Louis, Mo: Mosby, 1994.