title: Effects of single-agent and combination chemotherapy for gestational trophoblastic tumors on risks of second malignancy and early menopause.
abstract: OBJECTIVE
  To assess the risks of second malignancy and early menopause in a large cohort of patients with gestational trophoblastic tumor who were treated with chemotherapy.
  
  
  METHODS
  A survey of patients treated at Charing Cross Hospital between 1958 and 2000 was performed in 2006 to assemble incidence data for subsequent malignancies and the age at menopause. Treatment records were reviewed for the regimens and durations, and the incidence of subsequent malignancies was compared with that in the national age-matched population.
  
  
  RESULTS
  Data were obtained for 1,903 patients, with a mean follow-up of 16.9 years. Eighty-six patients developed a subsequent malignancy compared with an expected number of 79 (standardized incidence ratio [SIR], 1.1; 95% CI, 0.9 to 1.3). The overall risk was low for patients treated with single-agent methotrexate and folinic acid (MTX-FA; SIR, 0.7; 95% CI, 0.5 to 1.1) and also for patients treated with etoposide, methotrexate, and dactinomycin followed by cyclophosphamide and vincristine on alternating weeks (EMA-CO) with an SIR of 0.9 (95% CI, 0.4 to 2.2), but there were significantly increased risks of oral cancer, melanoma, meningioma, and leukemia. The cumulative risk of early menopause was low after MTX-FA but was substantial after EMA-CO, reaching 13% by age 40 years and 36% by age 45 years.
  
  
  CONCLUSIONS
  Subsequent cancer risks for patients cured of gestational trophoblastic tumors with modern chemotherapy appear similar to those of the normal population with no overall increased risk of malignancy after MTX-FA or EMA-CO. However, there was evidence of an increased risk of leukemia after EMA-CO and some evidence of other site-specific increased risks based on small patient numbers. All major treatments except MTX-FA increased the risk of early menopause.
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom. savage13561@msn.com.
authors.forename: Philip
authors.initials: P
authors.lastname: Savage
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Rosie
authors.initials: R
authors.lastname: Cooke
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: O'Nions
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Jon
authors.initials: J
authors.lastname: Krell
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Kwan
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Camarata
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Gairin
authors.initials: G
authors.lastname: Dancy
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Dee
authors.initials: D
authors.lastname: Short
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
authors.affiliation: Philip Savage, Jenny O'Nions, Jon Krell, Amy Kwan, Michelle Camarata, Gairin Dancy, Dee Short, and Michael J. Seckl, Charing Cross Hospital, Imperial Hospitals National Health Service Trust, London; and Rosie Cooke and Anthony Swerdlow, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Swerdlow
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008594:Menopause, Premature / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D016017:Odds Ratio; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000188:drug therapy*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C036539:fluoresceinated methotrexate; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D008727:Methotrexate