Giorgia Mangili

EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT)

From June 1980 through December 1985, 36 high-risk GTT patients received Bagshawes EMA/CO regimen, 22 as first-line, and 14 as second-line treatment, after primary chemotherapy with CHAMOCA, or cyclic regimen, or MTX-CF. All treated patients were metastatic at the start of treatment with EMA/CO; three showed liver metastases and one brain metastasis. Seventeen patients had a high score, greater than 15. Nineteen patients had histologically confirmed diagnosis of choriocarcinoma. The overall response rate was 86% with 81% survival during a median observation time of 32 months. The median number of courses needed to achieve complete remission was 3 (range 3-7). Toxicity was acceptable, and was less than with CHAMOCA and MAC regimens. Only 1 out of 17 high-risk patients developed drug resistance, and 3 needed urgent surgery. The relapse rate of responders was 19% after a median of 5.5 months. The survival rate of high-risk patients was 88%, of which 76% are alive with no evidence of disease, while 12% have still detectable beta-chorionic gonadotrophin. The remission rate in the second-line treatment group was 64%, higher than using other regimens such as MAC or CHAMOCA. In conclusion, we consider EMA/CO to be the best choice for patients with high-risk GTT, because it is effective and well tolerated. In our opinion, the cure rate of high-risk GTT could perhaps be improved by starting trials to establish what salvage treatment to employ after EMA/CO failure and using more aggressive first-line chemotherapy in selected high-risk patients, on the basis of the scoring system.

Familial trophoblastic disease: Case report

Presented is a report of familial trophoblastic disease (repeated hydatidiform mole) which is of interest because of the double familial components. The patients were sisters who were married to two brothers.

The problem of identification of prognostic factors for persistent trophoblastic disease

The role of anamnestic and clinical factors in defining the high group at risk of developing persistent trophoblastic disease (PTD) has been analyzed in 301 cases of hydatidiform mole. Patients age 40 or more years with AB blood, and a previous history of molar pregnancy had an elevated risk of developing PTD. The presence of various risk factors increased the frequency of PTD. However, with discriminant analysis, correct classification of outcome was obtained for only 69% of cases. Despite the magnitude of risk of PTD for women with three or more risk factors, the clinical relevance of prognostic variables in the prediction of outcome was limited by the low proportion of women classified in the low- and high-risk groups, making the identification at diagnosis of the women who could benefit of prophylactic chemotherapy extremely difficult and hence of little clinical importance.

The role of DNA ploidy in postoperative management of stage I endometrial cancer.

BACKGROUNDnDefinition of high-risk stage I endometrial cancer (EC) patients who might benefit from adjuvant therapy (AT) is controversial. Decision is on the basis of traditional prognostic factors. We report our experience in which ploidy has found to play a role in clinical practice since 1999.nnnPATIENTS AND METHODSnTwo hundred and twenty-two patients with stage I EC with a median follow-up of 4.57 years were studied. After primary surgery, patients are chronologically divided in group A, from 1990 to 1998 (n = 141), receiving AT in IC stage and group B, from 1999 to 2003 (n = 81), receiving AT in case of DNA index >1.2 or stage IC grade 3 with unknown lymph node status. We analyzed prognostic factors, survival and relapse rate of the two groups.nnnRESULTSnSince ploidy was introduced as a decision-making factor, only 30.6% (n = 11) of patients with stage IC received AT. Despite this considerable decrease of AT, no tumor-related deaths were reported in the group of patients with diploid IC stage who did not receive AT. Only DNA ploidy and age at diagnosis were independent predictors of overall survival.nnnCONCLUSIONSnOur results indicate the important role of ploidy in order to identify high-risk patients who need AT and avoid overtreatment.

Oral contraceptives and risk of gestational trophoblastic disease.

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD. Cases were 268 women with a histologically confirmed diagnosis of complete or partial mole referred to the participating Trophoblastic Disease Centers. A total of 268 subjects were interviewed; 79 cases were classified as partial and 159 as complete mole. Controls were randomly selected women who gave birth to healthy infants at term on randomly selected days in the same network of hospitals in which cases had been identified. A total of 104 cases and 130 controls reported ever OC use, and the corresponding odds ratio (OR) was 1.5 (95% CI, 1.1-2.1). The risk of GTD increases with duration of OC use: the OR was 1.7 (95% CI 1.2-2.6) for ever-users reporting >or=12 months of use. No consistent pattern of risk was observed with time since last OC use. We have analyzed separately the association between OC use and risk of complete and partial moles: no statistically significant difference emerged, but the OR for partial moles was higher (OR 3.0, 95% CI 1.6-8.4) than for complete mole (OR 1.0, 95% CI 1.8). In conclusion, we observed a weak association between OC use and GTD; such a weak association could be explained by factors other than causality.

ABO blood-groups and the risk of gestational trophoblastic disease.

The relation between ABO blood group, mating patterns of patient/husband blood group, and the risk of gestational trophoblastic disease was investigated in a case-control study conducted in Milan on 286 women with histologically confirmed trophoblastic disease (245 benign hydatidiform moles and 41 persistent trophoblastic disease) and 433 control subjects admitted for normal delivery to the same hospitals where cases had been identified. ABO blood groups were associated with the risk of gestational trophoblastic disease (x26 for heterogeneity = 14.46, p = 0.02). Compared to women of group O or B, women of group A and AB had an elevated relative risk (RR) of benign mole (RR = 1.4 and 2.3, respectively). The risk estimates were higher for persistent trophoblastic disease, i.e., 2.2 for women of group A and 4.8 of group AB. The tests for linear trend in risk from benign to persistent disease were statistically significant in both A and AB groups. There was a significant interaction between blood group and age, since the ABO-related risk was elevated only for women over the age of 35. When mating combinations of maternal/paternal blood groups were considered, women of group A married to males of group O had a risk estimate not substantially different than those married to group A males.

Analysis of 309 cases after hydatidiform mole: Different follow-up program according to biologic behavior

Between 1976 and 1985, at the Obstetrics and Gynecology Department of Milan University, a total of 309 cases of hydatidiform mole, 223 complete moles and 86 partial moles, were monitored with the assay of beta-human chorionic gonadotropin, following a postmolar biochemical surveillance program. Spontaneous remission of the disease occurred in 287 (92.9%) patients. Marker levels were undetectable in 80.4 % of cases within 60 days after evacuation of the mole and in 19.6% between 61 and 140 days. There were 22 (7.1%) patients diagnosed as having gestational trophoblastic tumors (GTT) and treated with chemotherapy: 20 were complete moles and 2 partial moles. Considering these data, the authors suggest different follow-up times for partial and complete moles and confirm the necessity of selection criteria in a diagnosis of GTT.

Methotrexate with citrovorum factor in low-risk gestational trophoblastic tumor

From January 1976 through December 1985, methotrexate (MTX) with citrovorum factor (CF) was administered as primary treatment to 57 patients with low-risk gestational trophoblastic tumor (GTT); 51 patients were non-metastatic and 6 were metastatic GTT. The median number of courses needed to achieve biochemical remission was two (range, 1–7). Complete remission was attained in 95% of non-metastatic GTT patients with postmolar persistent trophoblastic disease, but when choriocarcinoma was histologically confirmed, this fell to 60%. The cure rate of metastatic GTT patients was only 50%. The overall remission rate with the MTX-CF combination was 84.2%. Toxicity was mild, consisting of myelosuppression and mucositis. Fifteen patients were resistant to MTX-CF, or relapsed subsequently, but they all achieved remission with chemotherapy rescue treatment (VP 16 alone, EMA/CO, CHAMOCA). Two patients required a pulmonary lobectomy. They are all still alive in biochemical remission with a median survival of 54 months. Our experience suggests that drug resistance and relapse rate seem related to a β-HCG value higher than 104, an enlarged uterus with myometrial deep involvement, and a histologically confirmed diagnosis of choriocarcinoma. In conclusion, the MTX-CF combination is effective in postmolar GTT, whereas a different therapeutic approach may be considered for a « special » low-risk group of patients, on the basis of prognostic factors.

Prognostic effect of DNA content depends on the amount of the residual disease in ovarian tumours

SummaryA retrospective study was conducted on 47 patients with ovarian malignancies (1986–1991). DNA content analysis, surgical stage, residual tumor and histological grade were correlated to prognosis. In our experience, 36 months survival rate shows a more favourable outcome in diploid forms 166·7%), compared with 34·5% in aneuploid ovarian cancer patients. The results of flow cytometry may be used in conjunction with other prognostic factors. such as stage, residual tumor after primary surgery, grade and histological type, to tailor treatment protocols based on risk assessment. The importance of RT after primary debulking surgery is emphasised in our study. In fact RT was the only independent prognostic factor. The magnitude of the prognostic effect of DNA ploidy is dependent on the ability of the surgeon to reach an optimal debulking surgery.