BACKGROUND

Since the advent of chemotherapy, cure rates for gestational trophoblastic neoplasia (GTN) have improved significantly. With increased survival, patients must cope with long-term sequelae of their treatment, including early menopause. Unlike natural menopause, treatment-induced menopause may cause a sudden and dramatic decline in estrogen, which can lead to more severe symptoms.

OBJECTIVES

This study aimed to evaluate the prevalence of menopausal symptoms among young GTN survivors and to determine the impact of these symptoms on their health-related quality of life (QoL).

METHODOLOGY

Ninety GTN survivors (RESULTS

A total of 90 patients were enrolled in the study with a mean age of 33.06 years. Majority (81.1%) reported at least one menopausal symptom. The most prevalent symptoms were psychological symptoms, followed by somatic, then urogenital problems. Among those with an intact uterus, 8.2% reported permanent amenorrhea. Only Stage III/IV and the presence of total hysterectomy were significantly associated with menopausal symptoms. The presence of menopausal symptoms was significantly associated with poorer health-related QoL among the respondents.

CONCLUSION

Menopausal symptoms are prevalent among young GTN survivors, and these negatively affect their health-related QoL. Emphasis should be placed on recognizing and addressing these symptoms. Adjunctive procedures, especially hysterectomy, should be carefully considered because these are significantly associated with menopausal symptoms.

Human ; Chemotherapy ; Drug Therapy ; Gestational Trophoblastic Neoplasia ; Gestational Trophoblastic Disease ; Menopause

OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN. METHODS: The clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system. RESULTS: Among the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination. CONCLUSIONS Pretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.
Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Multivariate Analysis ; Pregnancy ; Retrospective Studies ; Risk Factors

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Objective: To investigate the impact of lung metastases on the prognosis of patients with gestational trophoblastic neoplasia (GTN). Methods: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage Ⅰ-Ⅲ GTN receiving primary chemotherapy in Peking Union Medical College Hospital between July 2014 and December 2018 were retrospectively analyzed and divided into group 1 with lung metastasis and group 2 without lung metastasis. The baseline characteristics and treatment outcomes of the two groups were compared. The optimal cut-off values of the diameter of largest lung nodule associated with recurrence were identified by receiver operating characteristic (ROC) curves. Logistic regression analyses were performed to identify risk factors for prognosis. Survival analysis was performed by Kaplan-Meier method and Log rank test. Results: Of the 381 GTN patients enrolled (216 with lung metastases and 165 without lung metastases), the pretreatment β human chorionic gonadotrophin [median: 12 572 IU/L (1 832-51 594 IU/L) vs. 5 614 IU/L (559-26 140 IU/L), P=0.001] and FIGO score [median: 3 (1-6) vs. 2 (1-4), P=0.038] were significantly higher in patients with lung metastases than those without lung metastases. In patients with FIGO score≥5, the emergence of resistance (26.76% vs. 10.26%, P=0.036) and median number of chemotherapy courses to achieve complete remission [6 (6-8) vs. 5 (4-6), P<0.001] were significantly higher than patients with lung metastases. In patients with FIGO score 0-4, no significant difference was found in the treatment outcomes between the two groups(P=0.833). Among all patients with lung metastases, the ROC curve showed a sensitivity and specificity of 62.5% and 78.8%, respectively, for predicting recurrence when the length of the largest lung nodule was 1.6 cm, with an area under the curve (AUC) of 0.711 (95% CI: 0.550, 0.871, P=0.044). Multivariate logistic regression analysis suggested a significantly higher recurrence rate when the largest lung nodule was ≥1.6 cm (OR=7.394, 95% CI: 1.003, 54.520, P=0.049). The 1-year disease-free survival rate was significantly lower in patients with the largest lung nodule ≥1.6 cm than in patients with the nodule <1.6 cm (98.2% vs. 82.4%, P=0.001). Conclusions: Lung metastasis is associated with increased first-line chemotherapy resistance in patients with FIGO scores≥5. The diameter of the largest lung metastatic nodule ≥1.6 cm is an effective factor for predicting recurrence.
Pregnancy ; Female ; Humans ; Retrospective Studies ; Gestational Trophoblastic Disease/pathology* ; Prognosis ; Lung Neoplasms/drug therapy* ; Disease-Free Survival ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Ovarian vein thrombosis (OVT) is a rare disease with complications that can be life-threatening. An ovarian vein thrombus in a gestational trophoblastic neoplasia (GTN) is an extremely rare condition that has not been previously reported in the literature. We report the case of a 23-year-old woman who presented with symptoms of amenorrhea for 15 weeks and 6 days along with intermittent lower abdominal pain. She was diagnosed with a hydatidiform mole, and a metastatic workup was scheduled. Abdominal computed tomography showed a right ovarian vein thrombus. She received methotrexate chemotherapy combined with oral anticoagulants. Complete radiological remission was obtained. During the 12-month follow-up period, no disease progression or recurrence was noted. Early recognition and detection of the condition are of the utmost importance. The differential diagnosis of OVT must be considered when there is unexplained abdominal pain, fever, and leukocytosis during the diagnosis and treatment of GTN. A high level of suspicion is required for prompt diagnosis of OVT.
Abdominal Pain ; Amenorrhea ; Anticoagulants ; Diagnosis ; Diagnosis, Differential ; Disease Progression ; Drug Therapy ; Female ; Fever ; Follow-Up Studies ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole ; Leukocytosis ; Methotrexate ; Pregnancy ; Rare Diseases ; Recurrence ; Thrombosis ; Veins ; Venous Thrombosis ; Young Adult

OBJECTIVE: Highly effective chemotherapy for patients with low-risk gestational trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate. However, 20%–30% of patients treated with chemotherapy need to change their regimens due to severe adverse events (SAEs) or drug resistance. We examined the treatment outcomes of second-line chemotherapy for patients with low-risk GTN. METHODS: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of these 281 patients, 178 patients were primarily treated with 5-day intramuscular methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We examined the remission rates, the drug change rates, and the outcomes of second-line chemotherapy. RESULTS: The primary remission rates and drug resistant rates of 5-day ETP were significantly higher (p < 0.001) and significantly lower (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%) required a change in their chemotherapy regimen due to the SAEs (n=16) and drug resistance (n=31), respectively. Of these 47 patients failed the first-line regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients failed second-line, single-agent chemotherapy and eight patients (17.0%) who failed first-line regimens were treated with combined or multi-agent chemotherapy and achieved remission. CONCLUSIONS: Patients with low-risk GTN were usually treated with single-agent chemotherapy, while 20%–30% patients had to change their chemotherapy regimen due to SAEs or drug resistance. The second-line regimens of single-agent chemotherapy were effective; however, there were several patients who needed multiple agents and combined chemotherapy to achieve remission.
Drug Resistance ; Drug Therapy* ; Etoposide* ; Gestational Trophoblastic Disease* ; Humans ; Infusions, Intravenous ; Methotrexate*

OBJECTIVE: The aim of this study was to compare responses to single-agent chemotherapies and evaluate the predictive factors of resistance in low risk (LR) gestational trophoblastic disease (GTD). The chemotherapy agents included methotrexate (MTX) and actinomycin D (ACT-D). METHODS: We conducted a retrospective study of 126 patients with GTD who were treated between 2000 and 2013. A total of 71 patients with LR GTD were treated with MTX (8-day regimen or weekly regimen, n=53) or ACT-D (bi-weekly pulsed regimen or 5-day regimen, n=18). The successful treatment group and the failed treatment group were compared and analyzed to identify prognostic factors. RESULTS: The complete response rates were 83.3% for ACT-D and 62.2% for MTX, with no statistically significant difference. There was no severe adverse effect reported for either group. Longer interval durations from the index pregnancy (>2 months, p=0.040) and larger tumor size (>3 cm, p=0.020) were more common in non-responders than in responders; these results were statistically significant. CONCLUSION: Based on our results, ACT-D may be a better option than MTX as a first-line single chemotherapy agent for LR GTD. The bi-weekly pulsed ACT-D regimen had minimal, or at least the same, toxicities compared with MTX. However, due to the lack of strong supporting evidence, it cannot be conclusively stated that this is the best single agent for first-line chemotherapy in LR GTD patients. Further larger controlled trials will be necessary to establish the best guidelines for GTD treatment.
Dactinomycin* ; Drug Therapy* ; Gestational Trophoblastic Disease* ; Humans ; Methotrexate* ; Pregnancy ; Retrospective Studies

OBJECTIVE: To evaluate the role of adjuvant surgical procedures in the management of gestational trophoblastic neoplasia (GTN). METHODS: In a retrospective review of medical records at the Severance Hospital, we identified 174 patients diagnosed with GTN between 1986 and 2006. Of the 174 patients, 129 (74%) were assigned to the nonmetastatic group, and 45 (26%) to the metastatic group; of the metastatic group patients, 6 were in the low-risk group and 39 were in the high-risk group. Thirty-two patients underwent 35 surgical procedures as part of the GTN treatment. The procedures included hysterectomy, lung resection, craniotomy, uterine wedge resection, uterine suturing for bleeding, salpingo-oophorectomy, pretherapy dilatation and curettage, adrenalectomy, nephrectomy, and uterine artery embolization. RESULTS: Of the 32 patients who underwent surgical procedures, 28 (87%) survived. Eleven patients underwent surgery for chemoresistant disease after receiving one or more chemotherapy regimens. Twelve patients underwent procedures to control tumor hemorrhage. Nine (81%) of 11 patients with chemoresistant disease survived, and 8 patients who underwent salvage surgery for chemoresistant disease received further chemotherapy. Of 21 patients who underwent hysterectomy, 19 (90%) achieved remission. All of three patients who had resistant foci of choriocarcinoma in the lung achieved remission through pulmonary resection. CONCLUSION: Adjuvant surgical procedures, especially hysterectomy and pulmonary resection for chemoresistant disease, as well as procedures to control hemorrhage, are pivotal in the management of GTN.
Adrenalectomy ; Choriocarcinoma ; Craniotomy ; Dilatation and Curettage ; Drug Therapy ; Female ; Gestational Trophoblastic Disease* ; Hemorrhage ; Humans ; Hysterectomy ; Lung ; Medical Records ; Nephrectomy ; Pregnancy ; Retrospective Studies ; Uterine Artery Embolization

Gestational trophoblastic disease (GTD) is a condition of uncertain etiology, choriocarcioma, or placental-site hydatidiform moles, invasive moles, choriocarcinoma, and placental-site trophoblastic tumors. It arises from the abnormal proliferation of trophoblastic tissue and spreads beyond the uterus hematogenously. The early diagnosis of GTD is important to ensure timely and successful management and the preservation of fertility. We report the unusual case of a metastatic choriocarcinoma that formed bullae on the lung surface and presented as recurrent pneumothorax in a 38-year-old woman with elevated beta-human chorionic gonadotropin (hCG) levels. She underwent thoracoscopic wedge resection of the involved lung and four subsequent cycles of consolidation chemotherapy. No other evidence of metastatic disease or recurrent pneumothorax was noted during 22 months of follow-up. GTD should be considered in the differential diagnosis of spontaneous pneumothorax in reproductive-age women with an antecedent pregnancy and abnormal beta-hCG levels.
Adult ; Choriocarcinoma* ; Chorionic Gonadotropin ; Consolidation Chemotherapy ; Diagnosis, Differential ; Drug Therapy ; Early Diagnosis ; Female ; Fertility ; Follow-Up Studies ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole, Invasive ; Lung ; Neoplasm Metastasis* ; Pneumothorax* ; Pregnancy ; Trophoblastic Tumor, Placental Site ; Trophoblasts ; Uterus

OBJECTIVETo evaluate the combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) as primary treatment for gestational trophoblastic neoplasia (GTN).

METHODSClinical data and outcome of the patients with GTN from 1 January 2004 to 31 December 2009 were retrospectively reviewed. Totally 38 eligible patients had received at least one cycle of FAEV chemotherapy as primary treatment. The primary end points were response rate and toxicity of FAEV regimen.

RESULTSTotally 38 patients and 205 cycles of FAEV chemotherapy were included. Twenty-eight of these patients (73.6%) achieved serologic complete remission (SCR). Regimens were changed in 10 patients because of 5 with no response and 5 with intolerable toxicity. The most serious adverse events were greater than or equal to grade 3 neutropenia (31.6%), febrile neutropenia (7.9%), and greater than or equal to grade 3 thrombocytopenia (5.3%). During the follow-up, none relapsed.

CONCLUSIONFAEV is an effective regimen with manageable toxicity for patients with GTN as primary treatment, especially for patients with non-metastatic low or high risk GTN.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Dactinomycin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Floxuridine ; administration & dosage ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Middle Aged ; Pregnancy ; Retrospective Studies ; Treatment Outcome ; Vincristine ; administration & dosage ; Young Adult