title: Ovarian function in survivors of childhood medulloblastoma: Impact of reduced dose craniospinal irradiation and high-dose chemotherapy with autologous stem cell rescue.
abstract: Data on ovarian function (OvF) in medulloblastoma (MB) survivors is limited, with most studies describing outcomes in survivors treated with craniospinal irradiation (CSI) doses >24 Gy ± standard chemotherapy. The objective of the current study is to report on OvF: (i) across a range of CSI doses; and (ii) following high-dose chemotherapy with autologous stem cell rescue (ASCR).
  
  
  
  Retrospective review of female MB survivors who were diagnosed in childhood and followed at Memorial Sloan Kettering Cancer Center. Patients were divided into three groups: (i) CSI ≤24 Gy +/- standard chemotherapy; (ii) CSI ≥35 Gy +/- standard chemotherapy; and (iii) high-dose chemotherapy with ASCR +/- CSI.
  
  
  
  Primary ovarian dysfunction (POD) occurred in 2/17 subjects in group 1, 3/9 subjects in group 2 and 5/5 subjects in group 3 (P < 0.01). Normalization of function was noted in four subjects with POD. Persistent POD requiring hormone replacement (POF) was observed in 1/17 subjects in group 1, 2/9 in group 2, and 3/5 in group 3 (P = 0.02). Neither age at treatment nor type of standard chemotherapy correlated with risk of POD or POF.
  
  
  
  Both POD and POF appear to occur in a small proportion of patients who are treated with contemporary doses of CSI +/- standard chemotherapy. However, ovarian dysfunction requiring hormone replacement therapy is common following high-dose chemotherapy associated with ASCR. These findings will assist clinicians in counseling patients regarding fertility preservation and risk of impaired ovarian function/future fertility. Pediatr Blood Cancer 2015;62:317-321. © 2014 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: Sadana
authors.initials: S
authors.lastname: Balachandar
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pediatrics, Weill Cornell Medical College, New York, NY.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Dunkel
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pediatrics, Weill Cornell Medical College, New York, NY.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Khakoo
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wolden
authors.affiliation: Department of Pediatrics, NYU Langone Medical Center, New York, NY.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Allen
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pediatrics, Weill Cornell Medical College, New York, NY.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000379:methods; D061888:Craniospinal Irradiation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D059247:Fertility Preservation; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D007223:Infant; D008527:Medulloblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D010053:Ovary / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000517:prevention & control*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods; D055815:Young Adult
keywords: autologous stem cell rescue; craniospinal irradiation; medulloblastoma; ovarian function; premature ovarian failure; primary ovarian dysfunction