Gestational trophoblastic disease: does central nervous system chemoprophylaxis have a role?

Abstract

Follow-up takes the form of serial urinary and serum human chorionic gonadotrophin (hCG) measurements. Standardized surveillance procedures are adopted nationwide. Patient compliance with the follow-up programme is very high, which allows the two treatment centres (in Sheffield and London) to adopt stringent treatment criteria and a conservative treatment philosophy. The UK treatment centres report high cure rates while exposing the minimal number of patients possible to cytotoxic chemotherapy (Sheridan et al, 1993).As standardized surveillance procedures are adopted nationwide, there are several differences in practice between the two treatment centres in terms of definition of persistent GTD, initial prognostic risk assessment and chemotherapeutic regimens. One difference is the use of prophylactic chemotherapy for possible occult central nervous system (CNS) metastases. It is well recognized that choriocarcinoma can metastasize to the brain. Charing Cross Hospital has previously reported that patients with persistent GTD and multiple pulmonary metastases or other high-risk features are at increased risk of CNS metastases. Since 1973 their patients without evidence of CNS metastases, but with pulmonary metastases, have been given CNS chemoprophylaxis in the form of intrathecal (i.t.) methotrexate (12.5 mg) with their first three cycles of systemic chemotherapy (Althanassiou et al, 1983;Newlands, 1997). At Weston Park Hospital, however, our management differs in that only patients with proven CNS involvement are treated with CNS chemotherapy. Our policy is to perform a computerized tomographic (CT) scan of the head and a lumbar puncture (providing there is no clinical evidence of raised intracranial pressure) to obtain cerebrospinal fluid (CSF) for βhCG levels in all patients who: (1) are classified Ôhigh riskÕ at initial prognostic risk assessment by the Sheffield modification of the Charing Cross Hospital prognostic scoring system (³ 8 points Ð Sheridan et al, 1993); (2) have βhCG levels of 50 000 iu l Ð1 or greater, and/or (3) have five or more metastases visible on chest radiographs/eight or more nodules visible on CT scan of thorax. Confirmation of CNS involvement is established by imaging and/or a high (> 1:60) CSFÐserum hCG ratio (Bagshawe and Harland, 1976).The cure rates for patients with GTD are now high, and so the focus of patient care has shifted from defining active chemotherapeutic agents to optimizing therapeutic regimens and minimizing risk to patients diagnosed with this condition. Our objective in this study was to evaluate the results of our conservative treatment approach to putative occult CNS disease in patients with GTD and pulmonary metastases. METHODS SubjectsAll patients with GTD registered between 1987 and 1996 were included in this retrospective analysis. Of 195 patients with persistent GTD who were treated in this time period, 69 had pulmonary metastases at initial presentation detected by chest radiography and/or CT of the thorax. The median age of patients in this group was 27 ye...

Choriocarcinoma with brain, lung and vaginal metastases successfully treated without brain radiation or intrathecal chemotherapy: A case report

“…Initial concerns regarding subtherapeutic CNS methotrexate levels originally led the Charing Cross group to recommend intrathecal methotrexate during EMA-CO treatment, however, most treating physicians do not routinely use intrathecal methotrexate for treatment of brain metastases or prophylaxis (Soper et al, 1994, Gillespie et al, 1999). Therapeutic CSF methotrexate levels have also been documented when > 600 mg/m 2 of intravenous moderate/high-dose methotrexate was used to treat CNS metastases (Tetef et al, 2000).…”