In addition, second malignant neoplasms occur in 3% to 6% at 20 years following diagnosis.41 Irradiation and alkylating agents are primary risk factors for these secondary tumors. The risk increases over time, with 12% of WT survivors developing second PS-341 molecular weight malignancies at 50 years. The secondary malignancies include bone cancer, breast cancer, thyroid cancer, central nervous system (CNS) tumors often occurring 10 or more years later, as well as leukemia, following treatment with

alkylating agents or topoisomerase II inhibitors.42 Inhibitors,research,lifescience,medical Renal cell carcinoma has occurred in survivors of neuroblastoma and WT.41,43 Post-treatment fertility problems can occur due to surgical injury to genital structures, neurologic impairment, cranial or gonadal irradiation, and chemotherapy.

Although the ovary is relatively Inhibitors,research,lifescience,medical radioresistant to chemotherapy, ovarian failure can develop after abdominal irradiation. It is dose related and can result in delayed puberty and premature menopause.44 Inhibitors,research,lifescience,medical Premature menopause can also occur after chemotherapy. In males, hypogonadism and temporary azoospermia can result following gonadal radiation.45 Although Leydig cells are more radioresistant than germ cells, high-dose radiotherapy can lead to inadequate testosterone production and delayed sexual maturity. Alkylating agents can also result in testicular

dysfunction.46 Semen preservation should be considered in the pubertal male, and testicular cryopreservation has recently been reported.47 In women who undergo abdominal/pelvic irradiation, pregnancy Inhibitors,research,lifescience,medical outcomes may be affected, with increased rates of miscarriage and prematurity and lower birth weight infants reported.48 Chemotherapy alone does not appear to adversely affect pregnancy. Bladder dysfunction can result from pelvic or CNS surgery, pelvic irradiation, or alkylating agent chemotherapy such as cyclophosphamide. It is usually seen Inhibitors,research,lifescience,medical in patients with bladder/prostate RMS. Yeung and Tryptophan synthase colleagues studied the effects of irradiation in 11 patients with pelvic RMS who had bladder preservation followed for a mean of 6.6 years.49 Seven of these children received radiation therapy and all had reduced bladder capacity (11%–48%) and enuresis, whereas four children who did not receive radiation had normal bladder function. A later study by Raney and coworkers reported continence outcomes in 164 patients over age 6 years of age with bladder/prostate RMS followed for a median of 8 years.50 Of the 62 patients who did not undergo cystectomy, 31% were incontinent. Of the 44 patients who underwent partial cystectomy, 27% were incontinent. Only 11 patients underwent urodynamics and 8 of the studies were abnormal.