title: Development of a risk stratification system to guide treatment for female germ cell tumors.
abstract: OBJECTIVE
  Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer.
  
  
  METHODS
  Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome.
  
  
  RESULTS
  Of 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76-92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12).
  
  
  CONCLUSIONS
  Modified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT.
authors.affiliation: Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Meisel
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Woo
authors.affiliation: Department of Medicine, St. Luke's Roosevelt Hospital Center, Continuum Cancer Centers, New York, NY, United States.
authors.forename: Nora
authors.initials: N
authors.lastname: Sudarsan
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Jana
authors.initials: J
authors.lastname: Eng
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Erin P
authors.initials: EP
authors.lastname: Jacobsen
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Rajmohan
authors.initials: R
authors.lastname: Murali
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Ginger J
authors.initials: GJ
authors.lastname: Gardner
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: George J
authors.initials: GJ
authors.lastname: Bosl
authors.affiliation: Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States. Electronic address: feldmand@mskcc.org.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000145:classification* / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000145:classification* / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D055815:Young Adult
keywords: Autologous stem cell transplant; Germ cell tumors; Histology; IGCCCG; Ovarian cancer; Salvage chemotherapy