Low-risk Gestational Trophoblastic Tumor Research Articles

Major clinical research advances in gynecologic cancer 2008.

In this review, we summarized 14 major clinical advances in gynecology which occurred in 2008. For cervical cancer, clinical impact of HPV vaccine, prognostic value of imaging during radiotherapy, and oncologic/obstetric outcomes of fertility-sparing surgery were chosen. For uterine cancer, optimal method of adjuvant radiotherapy in intermediate-risk patients, extent of lymph node dissection, outcome of robot-assisted staging surgery, new standard chemotherapy regimen for leiomyosarcoma were selected. For ovarian cancer, recent changes in adjuvant therapy, feasibility of neoadjuvant chemotherapy, prediction of optimal secondary cytoreduction, studies on new biomarkers, advances in screening and treatment of women with BRCA mutations were included. For other cancers, the safety of sentinel lymph node dissection in vulvar cancer and chemotherapy regimens for low-risk gestational trophoblastic tumors were reviewed.

Relapse Rate of Patients with Low-Risk Gestational Trophoblastic Tumor Initially Treated With Single-Agent Chemotherapy

The authors studied all patients with low-risk gestational trophoblastic tumor who were treated with single-agent chemotherapy at their institution between 1974 and 2000. Their aim was to compare remission rates among these 272 patients and to identify risk factors for development of drug resistance or disease relapse. Chemotherapy agents included conventional methotrexate (MTX), MTX with folinic acid (MTZ-CF), actinomycin D (Act-D), or etoposide. Primary remission according to chemotherapy regimen was 91 of 133 (68.4%) among those receiving MTX, 14 of 24 (58.3%) in those treated with MTX-CF, 20 of 24 (58.3%) for Act-D, and 81 of 89 (91%) in the etoposide group. The primary remission rate was significantly higher in patients who received etoposide compared to MTX (P < 0.0001) or MTX-CF (P = 0.0005). Overall, 24 patients (8.8%) developed drug resistance, including 10 (7.5%) MTX patients, 6 (25%) in the MTX-CF group, 4 (15.4%) Act-D patients, and 4 (4.5%) etoposide patients. Drug resistance was significantly higher for MTX-CF patients compared with etoposide patients (P =.006). Twenty (83.3%) of these 24 patients achieved remission with the second-line chemotherapy. The remaining 4 developed resistance to the second-line drug and required combination chemotherapy to achieve remission. Forty-two patients (15.4%) required a change of chemotherapy as a result of drug toxicity. Toxicity developed in 32 (24.1%) MTX patients, 4 (16.7%) MTX-CF patients, 2 (7.7%) Act-D patients, and 4 (4.5%) etoposide patients. The toxicity rate was significantly higher for MTX compared with etoposide (P < 0.0001). Only one of these 42 patients failed to achieve remission with second-line single-agent chemotherapy and required third-line treatment for successful remission. In an analysis of risk factors for drug resistance, including pretreatment hCG titers, chemotherapy with hysterectomy, disease metastasis, patient age, and initial FIGO scores, only higher FIGO scores were significantly associated with drug resistance (P = 0.026). Of the 230 patients who achieved primary remission, 6 (2.6%) developed a recurrence of disease. Relapse was not associated with chemotherapy agent, hCG titers, hysterectomy with treatment, metastases, or maternal age. However, relapse rates were higher among the patients who became drug-resistant (P = 0.016). Also, higher FIGO scores were significantly associated with relapse (P = 0.016).

Relapse rate of patients with low-risk gestational trophoblastic tumor initially treated with single-agent chemotherapy

Objective To determine the factors for relapse in patients with low-risk gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy. Methods Between 1974 and 2000, 272 consecutive patients with low-risk GTT were initially treated with methotrexate (MTX), actinomycin D (Act-D) or etoposide chemotherapy. The primary remission rate, change of chemotherapy because of drug resistance or toxicity, and relapse rate were compared. Results Overall survival rate and primary remission rate for 272 patients were 100% and 75.7%, respectively. Primary remission rate was significantly higher in patients given etoposide than those given conventional MTX ( P < 0.0001) or MTX- folinic acid (MTX-CF) ( P = 0.0005). Twenty-four (8.8%) patients required a change of chemotherapy because of drug resistance. The frequency of drug resistance was significantly higher in patients treated with MTX-CF than those treated with etoposide ( P = 0.006). Although maternal age, presence of metastasis, high pretreatment hCG titer, and planned hysterectomy did not influence the development of drug resistance, the new FIGO scores were significantly higher in patients who developed drug resistance. Relapse rate increased significantly in patients who had high FIGO scores and who required change of chemotherapy due to drug resistance. Conclusions All patients with low-risk GTT eventually attained complete remission, even though some developed drug resistance to the first-line chemotherapy. The relapse rate was significantly higher in patients with drug resistance than those with primary remission. Chemotherapy regimen that induces little drug resistance is desirable from the viewpoint of long-term prognosis.

Relapse rate of patients with low-risk gestational trophoblastic tumor treated in a single institution

8191 Background: To determine the factors for relapse in patients with low-risk gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy. Methods: Between 1974 and 2000, 272 consecutive patients with low-risk GTT were initially treated with methotrexate (MTX), actinomycin D (Act-D) or etoposide chemotherapy. The primary remission rate, change of chemotherapy because of drug resistance or toxicity, and relapse rate were compared. Results: Overall survival rate and primary remission rate for 272 patients were 100% and 75.7%, respectively. Primary remission rate was significantly higher in patients given etoposide than those given conventional MTX (p<0.0001) or MTX-folic acid (MTX-CF) (p=0.0005). Twenty-four (8.8%) patients required a change of chemotherapy because of drug resistance. The frequency of drug resistance was significantly higher in patients treated with MTX-CF than those treated with etoposide (p=0.006). Although maternal age, presence of metastasis, high pretreatment hCG titer, and planned hysterectomy did not influence the development of drug resistance, the new FIGO scores were significantly higher in patients who developed drug resistance. Relapse rate increased significantly in patients who had high FIGO scores and who required change of chemotherapy due to drug resistance. Conclusions: All patients with low-risk GTT eventually attained complete remission, even though some developed drug resistance to the first-line chemotherapy. The relapse rate was significantly higher in patients with drug resistance than those with primary remission. Chemotherapy regimen that induces little drug resistance is desirable from the viewpoint of long-term prognosis. No significant financial relationships to disclose.

Relapse rate of patients with low-risk gestational trophoblastic tumor treated in a single institution

8191 Background: To determine the factors for relapse in patients with low-risk gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy. Methods: Between 1974 and 2000, 272 con...

Risk of Abnormal Pregnancy Completing Chemotherapy for Gestational Trophoblastic Tumor

Matsui, Hideo; Iitsuka, Yoshinori; Susuka, Kiyomi; Yamazawa, Koji; Tanaka, Naotake; Seki, Katsuyoshi; Sekiya, Souei

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

Objective This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). Methods A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. Results The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) ( P = 0.028). Conclusion Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

Management of Low-Risk Gestational Trophoblastic Tumors in an Indigent Population

Management of Low-Risk Gestational Trophoblastic Tumors in an Indigent Population

Management of low-risk gestational trophoblastic tumors in an indigent population

Management of low-risk gestational trophoblastic tumors in an indigent population

Guidelines for the Stratification of Patients Recruited to Trials of Therapy for Low-Risk Gestational Trophoblastic Tumor

Objective. The aim of the study was to initiate a search for factors which might independently predict the need for salvage therapy in patients with low-risk gestational trophoblastic tumor.Methods. The independent effect of six factors on the need for salvage chemotherapy was assessed in patients with low-risk gestational trophoblastic tumor who were treated with low-dose methotrexate and folinic acid. The accuracies of World Health Organization and Charing Cross Hospital scores were also compared.Results. Age, pretreatment βhCG, antecedent pregnancy–treatment interval, and the presence of chest metastases detected on chest X ray were not significantly predictive. The size of tumor (P = 0.001) and the presence of chest metastases on chest computerized tomography (P = 0.00028) had independent, statistically significant predictive power, and a simple prognostic index was derived from these variables. The World Health Organization score was found to be significantly better than the Charing Cross Hospital score. The accuracy of the simple prognostic index was slightly greater than that of the World Health Organization score, although this was not statistically significant.Conclusions. These results confirm that patients entered into studies of different therapies for low-risk gestational trophoblastic tumor should be stratified and that a simple score, derived from the results of tumor size and chest computerized tomography, is potentially as good as the World Health Organization score for predicting the need for salvage therapy.

Surgical intervention and complications for low-risk gestational trophoblastic tumor

Surgical intervention and complications for low-risk gestational trophoblastic tumor

Pregnancy outcome after treatment with etoposide (VP-16) for low-risk gestational trophoblastic tumor.

The aim of this study was to evaluate subsequent fertility and pregnancy in patients treated for persistent trophoblastic tumors with single-agent VP-16. Records of all patients treated for persistent trophoblastic tumors at the Chiba University Hospital between January 1, 1986 and December 31, 1997 were reviewed. Of these, 85 patients were initially treated with single-agent VP-16. Subsequent pregnancy outcome of these patients was investigated. After remission with VP-16, 36 patients (92.3%) of those who wished for a pregnancy (45.9% of all patients studied) conceived, and 91.7% had at least one live birth. A total of 56 conceptions resulted in 42 (75.0%) term live births, seven (12.5%) first-trimester spontaneous abortions, one (1.8%) second-trimester spontaneous abortion, four (7.1%) therapeutic abortions, and two (3.6%) repeated moles. There were no congenital anomalies, no stillbirths, and the neonates' physical growth was comparable to that of the standard population in Japan. Single VP-16 regimen for patients with low-risk gestational trophoblastic tumor appears to have no adverse effects on fertility potential and pregnancy outcome.

Treatment of low-risk metastatic gestational trophoblastic tumors with single-agent chemotherapy

OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of single-agent chemotherapy and to identify risk factors associated with chemotherapy resistance in the treatment of low-risk metastatic gestational trophoblastic tumors. STUDY DESIGN: We reviewed the records of all patients with gestational trophoblastic tumors treated with single-agent chemotherapy at the John I. Brewer Trophoblastic Disease Center of Northwestern University between 1962 and 1992. A total of 92 patients with low-risk metastatic gestational trophoblastic tumors by National Cancer Institute criteria were identified. Patients received methotrexate ( n = 61), actinomycin D ( n = 4), alternating methotrexate and actinomycin D ( n = 5), or hysterectomy with methotrexate ( n = 20) or actinomycin D ( n = 2). RESULTS: All 92 patients with low-risk metastatic gestational trophoblastic tumors were cured. Primary remission was achieved with initial single-agent therapy in 62 patients (67.4%). A second sequential single agent was used because of drug resistance in 20 patients (21.7%) or drug toxicity in 10 patients (10.9%). Only one patient (1%) needed multiagent chemotherapy to be cured. Adjuvant hysterectomy was performed in 22 patients (23.9%). Surgery was not required to remove resistant tumor foci. Chemotherapy toxicity, most commonly stomatitis, occurred in 36 patients (39.1%), but none of these effects was life threatening. Large vaginal metastasis was the only identifiable factor significantly associated with failure of initial single-agent chemotherapy ( p = 003). CONCLUSION: In this large series of patients with low-risk metastatic gestational trophoblastic tumors, sequential single-agent chemotherapy with methotrexate and actinomycin D provided safe and extremely effective treatment. (Am J Obstet Gynecol 1996;174:1917-24.)

Management of Low-Risk Gestational Trophoblastic Tumors with Etoposide (VP16) in Patients Resistant to Methotrexate

Careful selection and treatment monitoring of patients with gestational trophoblastic tumors (GTT) is critical because 20–50% of patients may develop a resistance and consequently require alternative chemotherapeutic agents. In our study we propose and demonstrate the efficacy of etoposide (VP16) as a second-line drug. An average of 5 courses with VP16 were used to achieve a remission in 12 patients resistant to MTX with low-risk GTT. Toxicity was mild and no resistance to VP16 was observed. A follow-up of 66 months (range, 22–109) has been performed for the patients and all of them are now disease free. Two patients had a pregnancy, respectively, 3 and 4 years after treatment. The others did not desire any pregnancy.

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 beta-HCG value higher than 10(4), 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.