EMA vs EMACO in the treatment of gestational trophoblastic neoplasia.

OBJECTIVE: To compare experiences with EMA versus EMACO in the treatment of gestational trophoblastic neoplasia. METHODS: The medical records of women diagnosed with GTN at the New England Trophoblastic Disease Center from 1986 to 2019 were reviewed, and women receiving EMA or EMACO as their first multiagent regimen were eligible. Clinical characteristics, treatment, outcomes, and adverse events were compared between the two groups. RESULTS: We identified 44 and 39 patients who received EMA and EMACO, respectively. The complete remission rate was significantly higher in the EMA group (97.7%) than in the EMACO group (71.8%) (p = 0.001). However, patients receiving EMACO were more likely to have adverse prognostic factors such as higher median prognostic risk score (8 vs 4, p < 0.001), non-molar antecedent pregnancy (59 vs 27.3%, p = 0.014) and distant metastasis (64.1 vs 47.7%, p = 0.017). Time to complete remission was also similar (p = 0.947) with a median of 12 weeks with EMA and 13.1 weeks with EMACO. There was no significant difference in treatment delays or use of adjuvant surgery. After multivariate analysis, chemotherapy regimen (EMA or EMACO) did not retain prognostic significance for remission. Overall toxicities were more frequent in EMA (60.2 vs 32.7%, p < 0.001), especially neutropenia, but this did not delay treatment and likely resulted from less growth factor support (18.2 vs 48.7%, p = 0.003). CONCLUSIONS: When controlling for other prognostic factors, outcomes with EMA appear similar to EMACO. It may be worthwhile to investigate whether EMA, a simpler and less costly regimen, may be as effective as EMACO in the treatment of GTN.

Is chemotherapy necessary for patients with molar pregnancy and human chorionic gonadotropin serum levels raised but falling at 6months after uterine evacuation?

OBJECTIVE: To compare the outcomes of Brazilian patients with molar pregnancy who continue human chorionic gonadotropin (hCG) surveillance with those treated with chemotherapy when hCG was still positive, but falling at 6months after uterine evacuation. METHODS: Retrospective chart review of 12,526 patients with hydatidiform mole treated at one of nine Brazilian reference centers from January 1990 to May 2016. RESULTS: At 6months from uterine evacuation, 96 (0.8%) patients had hCG levels raised but falling. In 15/96 (15.6%) patients, chemotherapy was initiated immediately per FIGO 2000 criteria, while 81/96 (84.4%) patients were managed expectantly. Among the latter, 65/81 (80.2%) achieved spontaneous remission and 16 (19.8%) developed postmolar gestational trophoblastic neoplasia (GTN). Patients who received chemotherapy following expectant management required more time for remission (11 versus 8months; p=0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6months; p<0.001), and presented with a median WHO/FIGO risk score higher than women treated according to FIGO 2000 criteria (4 versus 2, p=0.04), but there were no significant differences in the need for multiagent treatment regimens (1/15 versus 3/16 patients, p=0.60). None of the women relapsed, and no deaths occurred in either group. CONCLUSION: In order to avoid unnecessary exposure of women to chemotherapy, we no longer follow the FIGO 2000 recommendation to treat all patients with molar pregnancy and hCG raised but falling at 6months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.

Clinical epidemiology and management of gestational trophoblastic neoplasia in Hungary in the past 34 years.

OBJECTIVE: To review our clinical experience in the treatment of patients with gestational trophoblastic neoplasia (GTN) over the past 34 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2010, 331 patients with low-risk GTN and 174 patients with high-risk GTN (altogether 505) were treated. The patients were directed to the national trophoblastic disease center from all parts of Hungary. The patients were between 14 and 54 years of age, with an average age of 28.7 years. Primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 237 low-risk patients, 228 (96.2%) achieved remission as a result of primary methotrexate (MTX) therapy. Out of 94 low-risk patients 90 (95.7%) achieved remission as a result of primary actinomycin-D (Act-D) therapy. MTX, Act-D and cyclophosphamide (MAC) as a primary therapy was used in 118 high-risk cases, and 110 (93.2%) patients achieved complete remission. A total of 32 high-risk patients were treated with the etoposide, high-dose MTX/folinic acid, Act-D, cyclophosphamide and vincristine (EMA-CO) regimen, and of 26 primary therapies complete remission was achieved in 21 (80.8%) cases. Primary cisplatin, etoposide and bleomycin (CEB) therapy was successful in 16 of 17 high-risk cases (94.1%). Metastases were found in 47.3% (239/505) of the patients. Hysterectomy was performed in 68 of 505 (13.5%) cases. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of nonmetastatic and metastatic low-risk disease. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO, and MAC and EMA-CO. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Patients with high-risk metastatic GTN should be treated primarily with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens. Results also show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.

30 years' experience in the treatment of low-risk gestational trophoblastic neoplasia in Hungary.

OBJECTIVE: To review the clinical experience in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) over the past 30 years in a national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2007, 302 patients with low-risk GTN were treated. The patients were directed to our institution from all parts of Hungary. The patients were 14 to 53 years of age with an average age of 28.3 years. Methotrexate (MTX)/folinic acid or actinomycin-D (Act-D) primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 218 low-risk patients, 210 (96.3%) achieved remission as a result of MTX therapy. In 8 patients (3.7%), MTX-Act-D-cyclophosphamide (MAC) combination chemotherapy was needed to achieve complete remission, in some cases assisted by operation. Among 84 patients, 81 (96.4%) achieved remission as a result of Act-D therapy. In 3 cases (3.6%) complete remission was achieved by MAC combination chemotherapy. We detected metastases in 22.8% (69/302) of our low-risk patients. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of low-risk nonmetastatic and metastatic disease. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Importantly, patients with resistance to single-agent chemotherapy regularly achieve complete remission with MAC combination chemotherapy. Results show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.

Selenium binding protein 1 in ovarian cancer.

Selenium binding protein 1 (SELENBP1) was identified to be the most significantly down-regulated protein in ovarian cancer cells by a membrane proteome profiling analysis. SELENBP1 expression levels in 4 normal ovaries, 8 benign ovarian tumors, 12 borderline ovarian tumors and 141 invasive ovarian cancers were analyzed with immunohistochemical assay. SELENBP1 expression was reduced in 87% cases of invasive ovarian cancer (122/141) and was significantly reduced in borderline tumors and invasive cancers (p<0.001). Cox multivariate analysis within the 141 invasive cancer tissues showed that SELENBP1 expression score was a potential prognostic indicator for unfavorable prognosis of ovarian cancer (hazard ratio [HR], 2.18; 95% CI=1.22-3.90; p=0.009). Selenium can disrupt the androgen pathway, which has been implicated in modulating SELENBP1 expression. We investigated the effects of selenium and androgen on normal human ovarian surface epithelial (HOSE) cells and cancer cells. Interestingly, SELENBP1 mRNA and protein levels were reduced by androgen and elevated by selenium treatment in the normal HOSE cells, whereas reversed responses were observed in the ovarian cancer cell lines. These results suggest that changes of SELENBP1 expression in malignant ovarian cancer are an indicator of aberration of selenium/androgen pathways and may reveal prognostic information of ovarian cancer.

Predictors of quality of life among long-term survivors of gestational trophoblastic disease.

OBJECTIVE: To identify predictors of quality of life (QOL) among women diagnosed with gestational trophoblastic tumor (GTT) 5-10 years earlier. STUDY DESIGN: Utilizing a cross-sectional, descriptive design, 111 survivors completed a comprehensive QOL interview. RESULTS: Univariate analyses revealed that numerous psychosocial variables correlated highly with overall QOL. However, multivariate analysis indicated that the significant predictors of long-term QOL were cancer-specific distress, social support, spiritual well-being, reproductive concerns, gynecologic pain and sexual functioning. These 6 variables accounted for 77% of the variance in the overall QOL score. Post hoc analyses demonstrated that each of the predictors had unique effects on the QOL score. CONCLUSION: The variables identified in this model can guide future research and clinical care to reduce short- and long-term burdens associated with GTT.

Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry.

PURPOSE: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. EXPERIMENTAL DESIGN: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens. RESULTS: Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was