Nonmetastatic Gestational Trophoblastic Neoplasia Research Articles

Fertility-sparing, surgical interventions for low-risk, non-metastatic gestational trophoblastic neoplasia

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To measure efficacy and safety of fertility‐sparing surgical interventions, with or without adjuvant chemotherapy, for the treatment of women with low‐risk, non‐metastatic gestational trophoblastic neoplasia (LR‐NMGTN).

Prognosis of Gestational Trophoblastic Neoplasia in Women at 40 Years Old and Above: A Multicentre Retrospective Study

Purpose: To investigate the outcome of different treatment strategies in patients with gestational trophoblastic neoplasia (GTN) in women at 40 years old and above. Patients and Methods: We analysed a historical cohort from 5 referral centres from 5 countries, including all women with GTN treated between 2012 and 2017, who were 40 years old and older. Baseline characteristics and outcome of different treatment strategies were recorded and evaluated. The patients were categorized into low-risk non-metastatic, low-risk metastatic and high-risk, based on the FIGO classification. Results: A total of 141 cases were identified, of which 112 cases fulfilled the inclusion criteria. Mean age was 45.4 years ± 4.2SD. Of 80 patients with LR non-metastatic GTN, 46 women received single agent chemotherapy and 34 a hysterectomy with or without (n = 4) chemotherapy. Higher remission rate and shorter treatment duration (P=0.001) was seen in the group that underwent hysterectomy. Seven of the 14 patients with low-risk, metastatic GTN were cured with methotrexate. Two of the 18 high risk patients died before treatment, four were treated with polychemotherapy; two of them needed second line chemotherapy for incomplete response. Two cases received induction with methotrexate followed by EMA/CO. Ten highrisk patients were treated with hysterectomy and chemotherapy, of these six achieved complete remission, three needed second line chemotherapy, and one patient died during chemotherapy treatment. Conclusion: In this cohort of women with GTN at 40 years old or above, we found high proportions of metastatic and high-risk cases, of methotrexate resistance, and of need for multiple treatment lines. In all groups, hysterectomy was performed, but its role remains controversial in metastatic low-risk and high-risk disease.

Cost-effectiveness of second curettage for treatment of low-risk non-metastatic gestational trophoblastic neoplasia

ObjectiveLow-risk non-metastatic gestational trophoblastic neoplasia (GTN) has been treated with single agent chemotherapy, but second curettage is emerging as an alternative strategy with reported cure rates of 40%. We sought to estimate the cost-effectiveness of second curettage as the first line treatment of low-risk GTN. MethodsA decision-analytic model was created using TreeAge software to compare costs and outcomes for women with WHO staged low-risk GTN undergoing treatment with 5-day methotrexate (MTX), biweekly pulsed actinomycin-D, or second curettage. Probabilities were derived from the literature. Outcomes of interest included side effects from chemotherapy, need for additional agents, hemorrhage, uterine perforation, and cure rates. Utilities were applied to discounted life expectancy at a rate of 3% to generate quality adjusted life years (QALYs). Sensitivity analyses were then performed in order to assess the robustness of our assumptions. ResultsOf the three treatment arms, MTX was associated with the lowest cost and had similar QALYs to the other studied modalities. Second curettage was associated with 49 additional cures when applied to a theoretic cohort of 1000 women, as well as an additional 83 hemorrhages and 17 uterine perforations. Sensitivity analysis on the cure rate of second curettage revealed that second curettage was not cost-effective over MTX unless its probability of cure was 98%. ConclusionOur study found 5-day MTX was the cost-effective strategy for treatment of women with low-risk, non-metastatic GTN when compared to second curettage and actinomycin-D. In a carefully selected patient population, second curettage may be an additional treatment strategy.

Second Curettage for Treatment of Low-Risk Gestational Trophoblastic Neoplasia: A Cost-Effectiveness Analysis

OBJECTIVES: Low risk non-metastatic gestational trophoblastic neoplasia (GTN) is typically treated with methotrexate (MTX) or actinomycin D with second curettage emerging as an alternative treatment modality; we sought to estimate the cost-effectiveness of second curettage for the treatment of low-risk GTN.

Second curettage for treatment of low-risk gestational trophoblastic neoplasia: A cost-effectiveness analysis

Objective: Low-risk nonmetastatic gestational trophoblastic neoplasia (GTN) is typically treated with methotrexate (MTX) or actinomycin D with second curettage emerging as an alternative treatment modality. We sought to estimate the cost-effectiveness of second curettage for the treatment of low-risk GTN.

First-line hysterectomy for women with low-risk non-metastatic gestational trophoblastic neoplasia no longer wishing to conceive

BackgroundLow-risk gestational trophoblastic neoplasia (GTN) patients (FIGO score ≤6) are generally treated with single agent chemotherapy (methotrexate or dactinomycin) resulting in a 5-year mortality rate of 0.3%. However, despite these encouraging survival rates, chemotherapy is associated with significant adverse events in most patients. Although it is generally accepted that patients who no longer wish to conceive may be treated by hysterectomy for a hydatidiform mole, the evidence to support this strategy in low-risk GTN patients is lacking. ObjectivesTo describe the survival, efficacy, and tolerance associated with first-line hysterectomy in low-risk non-metastatic GTN patients.Study design.Seventy-four of 1072 low-risk GTN patients treated in the French Center underwent first-line hysterectomy. Patients data with successful first-line hysterectomy were retrospectively compared to those requiring further salvage chemotherapy. ResultsFirst-line hysterectomy was followed by hCG normalization in 61 patients (82.4%, 95% confidence interval [CI] 71.8–90.3) without any further salvage chemotherapy, whereas 13 patients required salvage chemotherapy. After multivariate analysis, a FIGO score of 5–6 (exact OR 8.961, 95%CI 1.60–64.96), and the presence of choriocarcinoma (exact OR 14.295, 95%CI 1.78–138.13) were associated with the risk of requiring salvage chemotherapy. ConclusionHysterectomy as a first-line treatment is effective without salvage chemotherapy in 82.4% of women with low-risk non-metastatic GTN and can be presented as an alternative to single-agent chemotherapy when childbearing considerations have been fulfilled. In young patients, this therapeutic option should not be considered because single-agent chemotherapies are curative in nearly 100% of patients while maintaining fertility.

Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?

ObjectiveTo evaluate expectant management versus immediate chemotherapy following pathological diagnosis of gestational choriocarcinoma (GCC) in patients with nonmetastatic disease. MethodsMulticenter retrospective cohort that included patients with histological diagnosis of GCC with nonmetastatic disease followed at one of thirteen Brazilian referral centers for gestational trophoblastic disease from January 2000 to December 2016. ResultsAmong 3191 patients with gestational trophoblastic neoplasia, 199 patients with nonmetastatic GCC were identified. Chemotherapy was initiated immediately in 152 (76.4%) patients per FIGO 2000 guideline, while 47 (23.6%) were managed expectantly. Both groups presented with similar characteristics and outcomes. All patients (n=12) who had normal human chorionic gonadotropin (hCG) in the first 2–3weeks of expectant management achieved complete sustained remission with no chemotherapy. Only 44.7% (21 patients) of patients who were expectantly managed needed to receive chemotherapy due to plateauing or rising hCG level in the first 2–3weeks of follow up. The outcome of patients receiving chemotherapy after initial expectant management was similar to those who received chemotherapy immediately after the diagnosis in terms of need for multi-agent chemotherapy or number of cycles of chemotherapy. There was no case of relapse or death in either group. Logistic regression analysis showed that age≥40years and hCG≥92,428IU/L at GCC diagnosis were risk factors for needing chemotherapy after initial expectant management of nonmetastatic GCC. ConclusionIn order to avoid exposing patients unnecessarily to chemotherapy, close surveillance of women with pathological diagnosis of nonmetastatic GCC seems to be a safe practice, particularly for those who have a normal hCG at the time of diagnosis. If confirmed by other studies, the FIGO guidelines may need to be revised.

Etoposide-Actinomycin as Salvage Regimen for the Treatment of Nonmetastatic and Low-Risk Metastatic Gestational Trophoblastic Neoplasia: Experience at the Philippine General Hospital.

Single-agent chemotherapy has been the standard of treatment for nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia (GTN). However, it is estimated that approximately 12% to 32% of patients given single-agent therapy will require a change of chemotherapy regimen because of drug resistance and/or intolerable toxicity. The Section of Trophoblastic Diseases of the Philippine General Hospital started using the combination of etoposide-actinomycin (EA) as salvage chemotherapy in the early 2000s. This study was carried out to describe the local experience with this salvage chemotherapy. This is a retrospective descriptive study aimed to analyze the efficacy and safety of the EA regimen as salvage treatment for the management of nonmetastatic and low-risk metastatic GTN. Records of the Section of Trophoblastic Diseases of the Philippine General Hospital from January 1, 2002 to June 30, 2014 were reviewed to identify all patients who had a diagnosis of nonmetastatic and metastatic low-risk GTN. Primary remission rate and toxicity profile of all patients who received the EA regimen as salvage treatment were determined. During the study period, a total of 67 cycles of the EA regimen were administered to 15 patients as salvage chemotherapy. Patients received a median of 4 cycles of EA, attaining normal serum beta human chorionic gonadotropin after 2 to 3 cycles. Thirteen of the 15 patients achieved complete remission with the EA regimen, giving a remission rate of 87%. The major toxicity that the patients experienced was myelosuppression. Grade 1/2 anemia was addressed by blood transfusion. Grade 3 neutropenia/myelosuppression was addressed by the administration of granulocyte colony-stimulating factor. Alopecia was seen in all of the patients. One patient experienced dermatitis with accompanying myelosuppression. The EA regimen was efficacious and well tolerated for the treatment of refractory nonmetastatic and low- risk metastatic GTN.

Outcomes of Non-Metastatic Gestational Trophoblastic Neoplasia: Twelve Year Experience from a Northern Thailand Tertiary Care Center.

Gestational trophoblastic neoplasia (GTN) is the malignant form of gestational trophoblastic disease. In non-metastatic GTN, the outcomes of treatment are impressive with methotrexate (MTX) or actinomycin D. We retrospectively reviewed the outcomes of non-metastatic GTN treated at our center from January, 1999 to December, 2013. One hundred and nine patients were recruited to the study. The median age was 33.1 years and over 90% were referral cases. Abnormal vaginal symptoms developed in 37.6% while 56.4% were asymptomatic. The most common antecedent pregnancy was a complete mole (92.7%) with the median interval time from antecedent pregnancy to GTN development being 2.0 months. The median pretreatment B-hCG was 5,624 mIu/ ml. The most common first line treatment was methotrexate (MTX) and folinic acid (91.7%) followed by weekly MTX (4.6%), etoposide+ MTX+actinomycin D (EMA) (2.8%), and actinomycin D (0.9%), with the median number of cycles at 5.0. The positive response to first line chemotherapy was 73.8%. The patients were given subsequent chemotherapeutic regimens after resistance to the first line therapy and showed a final remission rate of 89.9%.The significant factor that was frequently found in patients who were non-responders to the first line treatment was a hysterectomy procedure. Two patients developed lung metastasis and brain metastasis at one and four years after the first treatment, respectively. In conclusion, the outcomes of non-metastatic GTN were excellent. However, the patients need long term follow up due to the possibility of developing multiple organ metastases.

2A phase II study to determine the response to second curettage as initial management for persistent “low-risk” non-metastatic gestational trophoblastic neoplasia: A Gynecologic Oncology Group study

2A phase II study to determine the response to second curettage as initial management for persistent “low-risk” non-metastatic gestational trophoblastic neoplasia: A Gynecologic Oncology Group study

Differentiating Squamous Cell Carcinoma of the Cervix and Epithelioid Trophoblastic Tumor

Epithelioid trophoblastic tumor (ETT) is a recently described subtype of gestational trophoblastic neoplasia (GTN). Its diagnosis requires a high level of suspicion because it is often mistaken for more common cervical or uterine corpus epithelial neoplasms. This is a 39-year-old woman who presented with a cervical mass and positive human chorionic gonadotropin and was diagnosed with both locally advanced squamous cell cervical carcinoma and nonmetastatic GTN. She was treated unsuccessfully with concurrent intravenous cisplatin plus pelvic radiation and single-agent intravenous methotrexate. A retrospective review of the cervical biopsy using immunohistochemistry as well as genotyping of the tumor changed the original diagnosis to ETT. It is known that ETT is relatively unresponsive to chemotherapy compared with most other types of GTN; therefore, surgery would have been the optimal treatment. She died despite multiple salvage chemotherapies. Malignant GTN is one of the most curable gynecologic malignancies; however, its correct diagnosis is critical for the appropriate treatment. It can be easily misdiagnosed as a carcinoma because of their morphologic similarity. Genetic fingerprinting and immunohistochemistry are potentially valuable tools to confirm the diagnosis of ETT.

Idiopathic Adrenal Hemorrhage in a Patient with Gestational Trophoblastic Neoplasia

BACKGROUND: Idiopathic unilateral adrenal hemorrhage is rare. Described is the first case reported in the setting of nonmetastatic gestational trophoblastic neoplasia. CASE: A primigravida presented with abdominal pain, fever, and a right upper quadrant mass during the workup for gestational trophoblastic neoplasia. She was diagnosed with idiopathic unilateral adrenal hemorrhage. She was treated with surgical resection and single-agent chemotherapy and had complete remission. CONCLUSIONS: Idiopathic unilateral adrenal hemorrhage is a rare condition and must be considered in the presentation of abdominal pain, fever, and an abdominal mass.

Does chest CT matter in the staging of GTN?

Objective The term gestational trophoblastic neoplasia (GTN) encompasses a variety of uncommon neoplastic conditions arising from the placental trophoblast. Staging of GTN using the FIGO 2000 system divides patients into low and high risk groups and treatment of these patients depends on the risk score achieved. Chest x-ray (CXR) is recommended to assess lung metastases; however the significance of lung metastases seen on computed tomography (CT) scan of the chest is uncertain. The aim of this study is to determine whether or not CT scan significantly influences outcome of patients with GTN in terms of a need to change to second line chemotherapy or time to remission. Methods 96 patients with low risk metastatic GTN and 102 patients with low risk non-metastatic GTN who had been staged at Weston Park Hospital, Sheffield were identified. Staging according to the FIGO 2000 system was retrospectively calculated to assess what impact using CT scan would have had on the scores of those patients. Rates of first line treatment failure and time to remission were assessed and comparisons made. Results There was no significant difference in the need to change to second line chemotherapy or in time to remission in those patients with metastatic GTN whose score or risk was changed when CT scan was used in place of CXR. Low risk patients with metastatic disease were, however, significantly more likely to need to change to second line chemotherapy than patients with non-metastatic GTN although there was no significant difference in time to remission between these groups. Conclusions CT scan of the chest used instead of CXR in the staging of GTN does not alter outcome.

Weekly Intravenous Methotrexate with Folinic Acid for Nonmetastatic Gestational Trophoblastic Neoplasia

Objective. The objective of this study was to determine the complete response rate to weekly intravenous methotrexate at 100 mg/m2 with folinic acid for patients with nonmetastatic gestational trophoblastic neoplasia.Methods. From 1988 to 1999, 22 women with nonmetastatic gestational trophoblastic neoplasia were treated with weekly intravenous methotrexate with folinic acid at the Hamilton Regional Cancer Centre. Complete response was defined as the attainment of a serum β-hCG level <5 IU/L for 3 consecutive weeks. Toxicity was graded according to the National Cancer Institute of Canada–Clinical Trials Group criteria for chemotherapy toxicity.Results. There were 10 women who achieved complete response with weekly intravenous methotrexate alone (45.5%). Of the 12 who did not achieve complete response with methotrexate, 10 received actinomycin D and 2 received EMA as second-line chemotherapy. Patients successfully treated with methotrexate required a median of 6.5 cycles (including 2 cycles for consolidation) to achieve complete response. The only significant prognostic factor for failure with methotrexate was pretreatment β-hCG (P = 0.01).Conclusions. Only a select group of patients with low pretreatment β-hCG titers would be expected to achieve complete response with this regimen. Large randomized studies are required to determine the optimal treatment for nonmetastatic gestational trophoblastic neoplasia.

Do imaging techniques, grey scale ultrasound, color doppler flow ultrasound and magnetic resonance imaging provide clinically useful information during the therapy of nonmetastatic gestational trophoblastic neoplasia

Do imaging techniques, grey scale ultrasound, color doppler flow ultrasound and magnetic resonance imaging provide clinically useful information during the therapy of nonmetastatic gestational trophoblastic neoplasia

Is magnetic resonance imaging a useful aid in confirming the diagnosis of nonmetastatic gestational trophoblastic neoplasia?

Magnetic Resonance Imaging (MRI) of the pelvis was performed in 25 patients with rising or persistently elevated levels of human chorionic gonadotrophin (hCG) after hydatidiform mole evacuation to determine whether this type of imaging would help confirm a diagnosis of neoplasia based on hCG measurement alone. All patients had low risk disease. The images were assessed for the presence of a myometrial mass, increased uterine vascularity, increased myometrial signal and the integrity of the junctional zone. A myometrial mass was present significantly more frequently in patients with high hCG compared to those with low hCG ( P = 0.017). The junctional zone also was disrupted more frequently in patients with an hCG greater then 1500 mIU/ml although this finding is not specific for trophoblastic neoplasia. There was no correlation of the presence of vascularity or of increased myometrial signal with the level of hCG. Patients with an hCG of less than 700 mIU/ml showed only occasional MRI abnormality. One patient with an abnormal MRI during an hCG plateau achieved spontaneous regression. MRI frequently shows abnormalities of uterine architecture, but provides no superior clinical information than sequential hCG. The MRI appearance may be abnormal with spontaneous hCG remission while at persistent low levels of hCG when chemotherapy is clearly indicated the MRI appearances of the uterus show no abnormality.

High-Dose Methotrexate for Gestational Trophoblastic Disease

Eighty patients with low-risk and 5 patients with intermediate-risk gestational trophoblastic neoplasia (GTN) (WHO classification) were treated with single-agent high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI classification, 65 patients had nonmetastatic GTN, 13 patients had low-risk metastatic GTN, and 7 patients had high-risk metastatic GTN. Seventy-one (84%) patients achieved remission (beta HCG < or = 5 IU/liter) with MTX/FAR, whereas 14 (16%) failed to achieve remission with MTX/FAR alone. All failures were salvaged with second-line therapies. Patients successfully treated with MTX/FAR required a median of 4 courses to achieve remission, and a median of 2 consolidative courses. Factors found predictive of with MTX/FAR were pretreatment beta HCG (P = 0.003), prior history of GTN (P < 0.04), and time from termination of antecedent pregnancy to initiation of treatment (P < 0.05). No significant difference was noted between the success and failure groups with respect to MTX dose or infusion time, the timing and dosage of folinic acid rescue, the number of courses of MTX, or the mean interval between courses. Multivariate analysis revealed that the pretreatment beta HCG (P < 0.01) and short time from termination of antecedent pregnancy to initiation of treatment (P < 0.03) were independently significant for failure. No significant (grade 3/4) hematologic or gastrointestinal toxicity occurred, and no treatment delays or dose reductions were required. This regimen is both effective and well tolerated; however, the theoretical advantages of high-dose methotrexate do not appear to offer any clinical advantage over conventional dose MTX in low- and intermediate-risk GTN.

Evaluation of the Criteria Used to Make the Diagnosis of Nonmetastatic Gestational Trophoblastic Neoplasia

The administration of chemotherapy following hydatidiform mole evacuation implies a diagnosis of trophoblastic neoplasia. A review of the literature and an analysis of a questionnaire sent to physicians treating trophoblastic disease shows that the criteria used to make this decision vary significantly. The factors that make it important to arrive at a consensus are discussed. Alternative investigations other than hCG that may distinguish neoplasia such as doppler flow ultrasound and magnetic resonance imaging are examined critically. A definition of neoplasia is presented that relates tumor load as measured by hCG to the length of hCG plateau. The changing criteria for distinguishing metastasis are discussed.

Gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia (GTN) constitutes a spectrum of benign and malignant diseases that are associated with conception. The majority of patients with a benign GTN (hydatidiform mole) spontaneously enter remission after evacuation; however, 15% to 20% will develop a malignant form of GTN. The malignant GTN are classified as nonmetastatic GTN and metastatic GTN. Chemotherapy is the mainstay of treatment for malignant GTN. Patients require continuous emotional support during intense medical therapy because of issues related to the treatment and future pregnancies.

Failure of single dose methotrexate followed by Citrovorum Factor in nonmetastatic gestational trophoblastic neoplasia

With increasing cost of medical care, newer methods of administering chemotherapy on an outpatient basis are being sought to reduce the need for hospitalization and protracted losses of valuable time for patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN). To achieve this end, two NMGTN patients were treated with a single course of one dose of methotrexate (MTX) followed by multidose Citrovorum Factor (CF) without observing the expected response. Failure to respond appeared to be due to the schedule of administration. Although the dose and plasma concentrations of MTX were considered to be adequate for cell kill, fractionation—as established by conventional schedules of MTX administration—appeared necessary for response by exposing the maximum number of trophoblastic cells to inhibitory levels of MTX during the S-phase of the cell cycle.