GESTATIONAL TROPHOBLASTIC DISEASE METASTATIC TO THE CENTRAL-NERVOUS-SYSTEM

Objective: To evaluate characteristics of patients with central nervou s system (CNS) lesions of gestational trophoblastic disease (GTD) and determine prognostic and therapeutic implications applicable to manage ment. Methods: We retrospectively reviewed the records of 454 patients treated at the Southeastern Regional Trophoblastic Disease Center bet ween 1966 and 1992 with at least 2 years of follow-up, and identified 42 (9.3%) with CNS metastases. Sixteen patients presented for primary therapy and 27 patients had received significant therapy prior to pres entation. Three heavily treated moribund patients died before their fi rst cycle of chemotherapy and were excluded from analysis. Brain metas tases were documented by physical exam and radionuclide imaging (befor e 1976), computed tomography scan (after 1976), or magnetic resonance imaging (after 1986). Patients received multiagent chemotherapy with m ethotrexate, actinomycin D, and chlorambucil (MAC)- or etoposide-based regimens. All patients received radiation therapy. No intrathecal che motherapy was given. Craniotomy was employed in seven cases. Remission was defined as three weekly hCG levels below assay sensitivity (<5 mI U/ml). Results: Overall survival was 44%. Twelve of 16 patients (75%) who presented with CNS metastases with no prior therapy (Group A), 5 o f 13 (38%) patients who had prior treatment (Group B), and none of 10 patients who developed CNS metastases during therapy (Group C) survive d (P < 0.05), Two of four patients who failed in the CNS after treatme nt for CNS lesions were salvaged. Demographic characteristics of Group s A and B were similar. No significant differences with respect to WHO score, interval from pregnancy to onset of disease, or age among thes e groups were found. Group B patients had a four-fold higher incidence of liver metastases. Survival of Group A patients was not related to conventional clinical prognostic factors. Inverse (nonsignificant) cor relations were found for Group B patients between survival and WHO sco re, hCG level, size and number of metastatic lesions, but not type of prior therapy. Survival was higher in those with prior molar pregnanci es (56%) as contrasted with aborted (50%) or term (27%) gestations. Se lective use of craniotomy helped alleviate intracranial pressure and r esect refractory foci. Conclusions: Chemotherapy combined with radiati on therapy in GTD patients with CNS metastases yields survival rates c omparable to those reported for intrathecal methotrexate regimens. Tum or burden as indicated by hCG level and size/number of metastases in p reviously treated patients may correlate with survival. Patients who d evelop CNS metastases during active therapy have a very poor outcome. (C) 1995 Academic Press, Inc.