title: High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients.
abstract: OBJECTIVE
  To report our recent experience managing four patients with brain metastases of gestational trophoblastic neoplasia (GTN), coordinating systemic chemotherapy with early neurosurgical intervention or stereotactic radiosurgery and intensive supportive care during initial therapy to prevent early mortality.
  
  
  METHODS
  A series of four consecutive patients with brain metastases from high-risk Stage IV GTN managed at our institution in 2003 and 2005. Patients were assigned FIGO stage and risk score prospectively. Because of concern for chronic toxicity resulting from concurrent moderate dose methotrexate and whole brain radiation, an individualized multidisciplinary approach was used to manage patients.
  
  
  RESULTS
  All four women presented with brain and pulmonary metastases; one had multiple liver metastases. Neurological symptoms at presentation included grand mal seizures in 2 patients, left upper extremity hemiparesis and headache each in 1 patient, while 1 patient was asymptomatic. Index pregnancies were term pregnancies in all patients with interval from prior delivery ranging from 2 weeks to 4 years. Two had received prior chemotherapy for postmolar GTN prior to the index pregnancy with incomplete follow-up. Initial hCG values ranged from 26,400 to 137,751 mIU/ml; FIGO risk scores were > or =16 for all patients. Systemic combination chemotherapy was initiated with etoposide and cisplatin followed by moderate/high-dose (500-1000 mg/m(2)) methotrexate combinations. Craniotomy was used before or during the first chemotherapy cycle to extirpate solitary lesions in 3 patients, while stereotactic radiosurgery was administered after the first cycle to treat two brain lesions in the remaining patient. None received whole brain radiation or intrathecal methotrexate. In one patient, selective angiographic embolization was used to control hemorrhage from multiple liver metastases. Two patients required ventilator support early in treatment to allow stabilization from intrathoracic hemorrhage and neutropenic sepsis with respiratory distress syndrome, respectively. Hysterectomy was performed in one patient after completion of salvage chemotherapy. All have completed maintenance chemotherapy and are in prolonged remission (12-24 months). Neurologic sequelae include persistent left upper extremity dyskinesia and weakness in one patient, and episodic grand mal seizures and pseudoseizures in a second patient with a pre-existing seizure disorder.
  
  
  CONCLUSIONS
  This case series documents the utility for a multidisciplinary approach to the treatment of brain metastases from GTN. Using early craniotomy or stereotactic radiosurgery combined with etoposide-cisplatin and moderate/high-dose methotrexate combination chemotherapy, we were able to stabilize patients early in their treatment and avoid whole brain radiation therapy or intrathecal chemotherapy.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. jsoper@med.unc.edu
authors.forename: J T
authors.initials: JT
authors.lastname: Soper
authors.forename: M
authors.initials: M
authors.lastname: Spillman
authors.forename: J H
authors.initials: JH
authors.lastname: Sampson
authors.forename: J P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.forename: J K
authors.initials: JK
authors.lastname: Wolf
authors.forename: D L
authors.initials: DL
authors.lastname: Clarke-Pearson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D002822:Choriocarcinoma / Q000473:pathology / Q000556:secondary / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003399:Craniotomy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D031901:Gestational Trophoblastic Disease / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D011247:Pregnancy; D016634:Radiosurgery; D012307:Risk Factors; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D005492:Folic Acid; D002945:Cisplatin; D008727:Methotrexate