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Michael J. Seckl - One of the best experts on this subject based on the ideXlab platform.
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fertility and pregnancy outcome in Gestational Trophoblastic Disease
International Journal of Gynecological Cancer, 2021Co-Authors: Michael J. Seckl, Nienke E Van Trommel, Ulrika Joneborg, Leonoor Coopmans, Christianne A R LokAbstract:The aim of this review is to provide an overview of existing literature and current knowledge on fertility rates and reproductive outcomes after Gestational Trophoblastic Disease. A systematic literature search was performed to retrieve all available studies on fertility rates and reproductive outcomes after hydatidiform mole pregnancy, low-risk Gestational Trophoblastic neoplasia, high- and ultra-high-risk Gestational Trophoblastic neoplasia, and the rare placental site Trophoblastic tumor and epithelioid Trophoblastic tumor forms of Gestational Trophoblastic neoplasia. The effects of single-agent chemotherapy, multi-agent including high-dose chemotherapy, and immunotherapy on fertility, pregnancy wish, and pregnancy outcomes were evaluated and summarized. After treatment for Gestational Trophoblastic neoplasia, most, but not all, women want to achieve another pregnancy. Age and extent of therapy determine if there is a risk of loss of fertility. Single-agent treatment does not affect fertility and subsequent pregnancy outcome. Miscarriage occurs more often in women who conceive within 6 months of follow-up after chemotherapy. Multi-agent chemotherapy hastens the natural menopause by three years and commonly induces a temporary amenorrhea, but in young women rarely causes permanent ovarian failure or infertility. Subsequent pregnancies have a high chance of ending with live healthy babies. In contrast, high-dose chemotherapy typically induces permanent amenorrhea, and no pregnancies have been reported after high-dose chemotherapy for Gestational Trophoblastic neoplasia. Immunotherapy is promising and may give better outcomes than multiple schedules of chemotherapy or even high-dose chemotherapy. The first pregnancy after immunotherapy has recently been described. Data on fertility-sparing treatment in placental site Trophoblastic tumor and epithelioid Trophoblastic tumor are still scarce, and this option should be offered with caution. In general, patients with Gestational Trophoblastic neoplasia may be reassured about their future fertility and pregnancy outcome. Detailed registration of high-risk Gestational Trophoblastic neoplasia is still indispensable to obtain more complete data to better inform patients in the future.
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practical clinical guidelines of the eottd for treatment and referral of Gestational Trophoblastic Disease
European Journal of Cancer, 2020Co-Authors: Christianne A R Lok, Michael J. Seckl, Alice Bergamini, Nienke E Van Trommel, Francois Golfier, Leon F A G Massuger, Miguel Henriques Abreu, Jocelyne Attia, Kirsty Balanchandran, Pierre Adrien BolzeAbstract:Abstract Background and aim Gestational Trophoblastic Disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of Trophoblastic tissue. Since GTD and its malignant sequel Gestational Trophoblastic neoplasia (GTN) are rare Diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the ‘European Organisation for Treatment of Trophoblastic Diseases’ (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD. Methods Members from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid Trophoblastic tumours and follow-up. Results Between 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated. Conclusions Despite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks.
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a pictorial ultrasound essay of Gestational Trophoblastic Disease
Journal of Ultrasound in Medicine, 2020Co-Authors: Paolo Cavoretto, Giorgia Mangili, Alice Bergamini, Massimo Candiani, Raffaella Cioffi, M C Petrone, Emanuela Rabaiotti, Luca Valsecchi, Michael J. SecklAbstract:Gestational Trophoblastic Disease (GTD) includes a wide variety of clinical and histopathologic entities that require prompt identification and definition by the integration of clinical, laboratory, and imaging data. Recently, the role of grayscale ultrasound and spectral and power/color Doppler techniques has become pivotal in the diagnosis, staging, and management of GTD, thanks to both technical improvements and the growing expertise of dedicated operators. The aim of this essay is to summarize the most recent data on the ultrasound and Doppler findings of GTD and to provide a pictorial overview, including useful prognostic and therapeutic implications for clinical practice.
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is there uniformity in definitions and treatment of Gestational Trophoblastic Disease in europe
International Journal of Gynecological Cancer, 2019Co-Authors: Minke Frijstein, Michael J. Seckl, Christianne A R Lok, John Coulter, Nienke E Van Trommel, Marianne Ten J Katebooij, Francois Golfier, Leon F A G MassugerAbstract:Objectives Because Gestational Trophoblastic Disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in Gestational Trophoblastic Disease, we evaluated differences and similarities between protocols in EOTTD countries. Methods Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of Gestational Trophoblastic Disease and Gestational Trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up. Results Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Federation Internationale de Gynecologie et d9Obstetrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar Gestational Trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk Gestational Trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar Gestational Trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk Disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements. Conclusions This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several GestationalTrophoblastic Disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe.
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update on the diagnosis and management of Gestational Trophoblastic Disease
International Journal of Gynecology & Obstetrics, 2015Co-Authors: Hextan Y.s. Ngan, Michael J. Seckl, Ross S. Berkowitz, Francois Golfier, Yang Xiang, P K Sekharan, John R. LurainAbstract:Gestational Trophoblastic Disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of Gestational Trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score 7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of Disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.
John T. Soper - One of the best experts on this subject based on the ideXlab platform.
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Gestational Trophoblastic Disease current evaluation and management
Obstetrics & Gynecology, 2021Co-Authors: John T. SoperAbstract:This review summarizes the current evaluation and management of Gestational Trophoblastic Disease, including evacuation of hydatidiform moles, surveillance after evacuation of hydatidiform mole and the diagnosis and management of Gestational Trophoblastic neoplasia. Most women with Gestational Trophoblastic Disease can be successfully managed with preservation of reproductive function. It is important to manage molar pregnancies properly to minimize acute complications and to identify Gestational Trophoblastic neoplasia promptly. Current International Federation of Gynecology and Obstetrics guidelines for making the diagnosis and staging of Gestational Trophoblastic neoplasia allow uniformity for reporting results of treatment. It is important to individualize treatment based on their risk factors, using less toxic therapy for patients with low-risk Disease and aggressive multiagent therapy for patients with high-risk Disease. Patients with Gestational Trophoblastic neoplasia should be managed in consultation with an individual experienced in the complex, multimodality treatment of these patients.
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Gestational Trophoblastic Disease
Obstetrics & Gynecology, 2006Co-Authors: John T. SoperAbstract:This review summarizes the primary management of molar pregnancies, surveillance after evacuation, and the evaluation and management of malignant Gestational Trophoblastic neoplasia (GTN). Most women with Gestational Trophoblastic Disease can be successfully managed with preservation of their normal reproductive function. It is important to manage molar pregnancies properly to minimize acute complications and identify malignant sequelae promptly. Current International Federation of Gynecology and Obstetrics (FIGO) guidelines for making the diagnosis and staging of GTN allow uniformity for reporting results of treatment. It is important to individualize treatment for women with malignant GTN based upon risk factors, using less toxic therapy for patients with low-risk Disease and aggressive multiagent therapy for those with high-risk Disease. Patients with malignant GTN should be managed in consultation with an individual experienced in the complex, multimodality treatment of these patients.
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diagnosis and treatment of Gestational Trophoblastic Disease acog practice bulletin no 53
Gynecologic Oncology, 2004Co-Authors: John T. Soper, David G. Mutch, Julian C. SchinkAbstract:Gestational Trophoblastic Disease comprises a spectrum of interrelated conditions originating from the placenta. Other terms often used to refer to these conditions include Gestational Trophoblastic neoplasia and Gestational Trophoblastic tumor. Histologically distinct Disease entities encompassed by this general terminology include complete and partial hydatidiform moles, invasive moles, Gestational choriocarcinomas, and placental site Trophoblastic tumors. Before the advent of sensitive assays for human chorionic gonadotropin (hCG) and efficacious chemotherapy, the morbidity and mortality from Gestational Trophoblastic Disease were substantial. At present, with sensitive quantitative assays for beta-hCG and current approaches to chemotherapy, most women with malignant Gestational Trophoblastic Disease can be cured and their reproductive function preserved. The purpose of this document is to address current evidence regarding the diagnosis, staging, and management of Gestational Trophoblastic Disease.
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role of surgery and radiation therapy in the management of Gestational Trophoblastic Disease
Best Practice & Research in Clinical Obstetrics & Gynaecology, 2003Co-Authors: John T. SoperAbstract:Although sensitive human chorionic gonadotrophin (hCG) assays and advances in chemotherapy have assumed primary importance in the management of Gestational Trophoblastic Disease (GTD), surgery and radiation therapy remain important in the overall management of patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy may decrease the risk of post-molar Trophoblastic Disease. When incorporated into the primary management of malignant GTD, hysterectomy decreases chemotherapy requirements for patients with low-risk Disease. Surgical intervention is frequently required to control complications of Disease or as therapy to stabilize patients during chemotherapy. Salvage hysterectomy or other extirpative procedures may be integrated into the management of patients with chemorefractory Disease. Interventional radiographical techniques are useful adjuncts to control haemorrhage from vaginal or pelvic metastases. Radiation therapy may also be combined with chemotherapy for the management of patients with brain metastases or, rarely, isolated metastases at other sites.
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5 day methotrexate for women with metastatic Gestational Trophoblastic Disease
ACOG Current Journal Review, 1995Co-Authors: John T. Soper, Daniel L Clarkepearson, Andrew Berchuck, Gustavo C Rodriguez, C HammondAbstract:The objective of this study was to analyze the toxicity and the efficacy of single-agent 5-day methotrexate for women with metastatic Gestational Trophoblastic Disease. The study is a retrospective analysis of 52 patients who received repetitive 5-day cycles of intramuscular methotrexate as primary therapy for metastatic Trophoblastic Disease between 1975 and 1990. The majority of patients were low-risk by both clinical and World Health Organization prognostic index score criteria. Sixty percent achieved primary remission with a median of 3 cycles of single-agent methotrexate. Therapy was changed because of toxicity and drug-resistance by hCG criteria in 11 (21%) and 10 (19%) patients, respectively. Pretherapy hCG > 10,000 mIU/ml was associated with the development of drug-resistance. Remission was achieved in all patients, with only 2 (4%) requiring multiagent therapy. The use of repetitive 5-day cycles of methotrexate is efficacious therapy of low-risk metastatic Trophoblastic Disease. Future studies are needed to define a cost-effective and minimally toxic therapy that retains a high primary remission rate in these patients.
E S Newlands - One of the best experts on this subject based on the ideXlab platform.
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low risk persistent Gestational Trophoblastic Disease outcome after initial treatment with low dose methotrexate and folinic acid from 1992 to 2000
Journal of Clinical Oncology, 2002Co-Authors: Iain A Mcneish, Michael J. Seckl, L Holden, S Strickland, G J S Rustin, M Foskett, E S NewlandsAbstract:PURPOSE: We have simplified the treatment of Gestational Trophoblastic Disease (GTD) in order to reduce the number of patients exposed to potentially carcinogenic chemotherapy. Patients who score 0 to 8 on the Charing Cross scoring system are classified as low-risk and receive methotrexate (MTX) and folinic acid (FA), whereas those who score higher than 8 are classified as high-risk and receive the etoposide, methotrexate, and dactinomycin (EMA)/cyclophosphamide and vincristine (CO) regimen. PATIENTS AND METHODS: Between 1992 and 2000, 485 women with GTD were commenced on MTX/FA at Charing Cross Hospital, London, United Kingdom. If patients developed MTX resistance or toxicity, treatment was altered according to the level of beta human chorionic gonadotropin (hCG). If serum hCG was ≤ 100 IU/L, patients received dactinomycin; if hCG was greater than 100 IU/L, patients received EMA/CO. RESULTS: The median duration of follow-up was 4.7 years. Overall survival was 100% and the relapse rate was 3.3% (16 of 485...
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a retrospective comparison of current and proposed staging and scoring systems for persistent Gestational Trophoblastic Disease
International Journal of Gynecological Cancer, 2000Co-Authors: B W Hancock, E M Welch, A M Gillespie, E S NewlandsAbstract:. Hancock BW, Welch EM, Gillespie AM, Newlands ES. A retrospective comparison of current and proposed staging and scoring systems for persistent Gestational Trophoblastic Disease. It is widely accepted that patients with persistent Gestational Trophoblastic Disease (GTD) are best managed by stratifying their treatment according to recognized adverse prognostic features. We retrospectively evaluated 201 patients who had received chemotherapy for persistent low or high risk GTD at the Sheffield Center according to criteria used in established and proposed WHO scoring and FIGO staging systems to identify the numbers of patients in each risk category, the treatment they would receive, chemotherapy resistance patterns, and eventual outcome. The systems were broadly comparable and chemotherapy resistance was always greater in the high-risk groups (at least 33%), particularly when patients were divided into just two risk categories. Such a categorization led to fewer patients (less than 15%) falling into high-risk groupings, but outcome was not compromised. Mortality (3 deaths) was associated with high risk categorization in all systems evaluated. A proposal to combine revised FIGO staging and modified WHO scoring systems, with two risk groupings, is realistic and practicable.
B W Hancock - One of the best experts on this subject based on the ideXlab platform.
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ectopic Gestational Trophoblastic Disease a case series review
Journal of Reproductive Medicine, 2012Co-Authors: Ayman Hassadia, John Anthony Tidy, Fiona M Kew, Michael Wells, B W HancockAbstract:OBJECTIVE: To highlight the clinical presentation, treatment, histological review and outcome of patients referred to the Sheffield Centre with possible ectopic Gestational Trophoblastic Disease (GTD). STUDY DESIGN: A retrospective case note review of patients with possible ectopic GTD referred to the Sheffield Centre between 1997 and 2010 was performed. RESULTS: During the 13 years of this retrospective study 6,708 patients were registered at the Centre with GTD, of whom 42 had possible ectopic GTD. Most patients presented with abdominal pain and/or vaginal bleeding (67%). Ectopic pregnancy was diagnosed by ultrasound scan in 19%. Laparoscopic removal of ectopic pregnancy was carried out in 50% of cases; the rest underwent laparotomy for removal of ectopic conceptus. Histological review of slides was performed in 19 cases for whom there was clinical concern. This resulted in 12 confirmed cases of ectopic GTD: 4 choriocarcinomas, 5 partial moles and 3 complete moles. No evidence of metastasis was recorded in any of the cases. Three patients diagnosed with ectopic choriocarcinoma needed chemotherapy. Two responded to methotrexate and 1 needed second-line chemotherapy. All patients are alive and free of Disease. CONCLUSION: Ectopic GTD is rare and still overdiagnosed. Presentation is the same as for conventional ectopic pregnancy. Central review of the histology should be undertaken, especially in cases where there is clinical, hCG level or histopathologic concern. Conventional chemotherapy for Gestational Trophoblastic neoplasia is effective. Prognosis remains excellent.
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role of hysterectomy in managing persistent Gestational Trophoblastic Disease
Journal of Reproductive Medicine, 2008Co-Authors: Moiad Alazzam, B W Hancock, John Anthony TidyAbstract:OBJECTIVE: To evaluate incidence, indications and outcomes of hysterectomy for Gestational Trophoblastic Disease (GTD) and compare outcomes for patients who underwent primary hysterectomy with outcomes for those who underwent adjuvant hysterectomy. STUDY DESIGN: Using the Sheffield Trophoblastic Tumour Centre database (January 1, 1986, until June 30, 2007), patients who underwent hysterectomy were identified, along with age, antecedent pregnancy, diagnosis date, hysterectomy date and chemotherapy and pathologic findings. RESULTS: A total of 8,860 patients were registered at Weston Park Hospital, Sheffield. Of them, 627 (7.1%) needed chemotherapy and 62 (0.71%) underwent hysterectomy. The most frequent indication was resistance to chemotherapy in 22 of 62 (35.5%), followed by major hemorrhage in 21 of 62 (33.9%). Emergent hysterectomy was performed in 22 (35.5%). Mean International Federation of Gynecology and Obstetrics risk score was 6.5. Choriocarcinoma was the most frequent pathology (23), followed by invasive mole (10) and placental site Trophoblastic tumor (9). Thirty-one patients needed chemotherapy after hysterectomy, 93.5% are in remission, 7 relapsed, 3 were cured and 4 died of Disease. CONCLUSION: Incidence of hysterectomy for GTD was 1 in 140. Patients who underwent hysterectomy represent a high-risk group, often having more aggressive pathology. Hysterectomy is valuable as primary and adjuvant treatments.
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Gestational Trophoblastic Disease is intensive follow up essential in all women
British Journal of Obstetrics and Gynaecology, 2004Co-Authors: Narendra Pisal, John Anthony Tidy, B W HancockAbstract:Objective To determine the timescale of the registration process for Gestational Trophoblastic Disease and its impact on hCG level at registration and subsequent need for chemotherapy. Design A prospective observational study using a standardised protocol for registration, assessment and treatment for molar pregnancy. Setting A supra-regional tertiary referral centre for Gestational Trophoblastic Disease. Participants A total of 2046 consecutive women registered between January 1994 and December 1998 with a diagnosis of molar pregnancy. Methods Data at and after registration, collected prospectively on a computerised database, were statistically analysed (by multiple logistic regression and ANOVA). Main outcome measures Relationship between length of time to and hCG value at registration; also the subsequent need for chemotherapy. Results A total of 2046 women with a diagnosis of molar pregnancy were registered in the study period. The mean time interval between first evacuation and registration at the referral centre was 47 days (median 37, range 0–594). One hundred and five out of 2046 (5.1%) women needed chemotherapy. Sixty-three precent of the women (1296 out of 2046) had a normal level of urinary hCG (less than 40 IU/24 hours) at the time of registration and only one (0.08%) needed chemotherapy. Binary logistic regression analysis showed a statistically significant relationship between time to registration, hCG value, histology, pretreatment risk score and decision to administer chemotherapy. Conclusion Women with Gestational Trophoblastic Disease who were registered late were significantly more likely to have normal levels of hCG and were less likely to need chemotherapy. A less intensive follow up may be justified in women with Gestational Trophoblastic Disease who are registered with a normal hCG level.
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low risk persistent Gestational Trophoblastic Disease treated with low dose methotrexate efficacy acute and long term effects
British Journal of Cancer, 2003Co-Authors: Faisal Khan, J Everard, Robert E Coleman, S Ahmed, M Aitken, B W HancockAbstract:The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent Gestational Trophoblastic Disease. Between January 1987 and December 2000, 250 patients were treated with intramuscular methotrexate (50 mg on alternate days 1, 3, 5, 7) with folinic acid (7.5 mg orally on alternate days 2, 4, 6, 8) rescue. The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy. Eight women (3.2%) had recurrence following remission and two (0.8%) had new moles. Two women (0.8%) died of their Disease giving an overall cure of 99%. Only 10 women (4%) experienced grade III/IV toxicity during the first course of treatment and 13 women (5.2%) subsequently. Toxicity included mucositis and stomatitis, pleuritic chest pain, thrombocytopenia, uterine bleeding, abdominal pain, liver function changes, rash and pericardial effusion. A total of 59 women (23.6%) required second-line chemotherapy; 48 women had methotrexate resistance, eight had methotrexate toxicity and an empirical decision to change therapy was made in three. In all, 11 women (4.4%) had a hysterectomy before, during or after treatment; 141 women (56.4%) became pregnant following treatment: in 128 (90.7%), the outcome was successful. Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent Trophoblastic Disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility.
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a retrospective comparison of current and proposed staging and scoring systems for persistent Gestational Trophoblastic Disease
International Journal of Gynecological Cancer, 2000Co-Authors: B W Hancock, E M Welch, A M Gillespie, E S NewlandsAbstract:. Hancock BW, Welch EM, Gillespie AM, Newlands ES. A retrospective comparison of current and proposed staging and scoring systems for persistent Gestational Trophoblastic Disease. It is widely accepted that patients with persistent Gestational Trophoblastic Disease (GTD) are best managed by stratifying their treatment according to recognized adverse prognostic features. We retrospectively evaluated 201 patients who had received chemotherapy for persistent low or high risk GTD at the Sheffield Center according to criteria used in established and proposed WHO scoring and FIGO staging systems to identify the numbers of patients in each risk category, the treatment they would receive, chemotherapy resistance patterns, and eventual outcome. The systems were broadly comparable and chemotherapy resistance was always greater in the high-risk groups (at least 33%), particularly when patients were divided into just two risk categories. Such a categorization led to fewer patients (less than 15%) falling into high-risk groupings, but outcome was not compromised. Mortality (3 deaths) was associated with high risk categorization in all systems evaluated. A proposal to combine revised FIGO staging and modified WHO scoring systems, with two risk groupings, is realistic and practicable.
Christianne A R Lok - One of the best experts on this subject based on the ideXlab platform.
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fertility and pregnancy outcome in Gestational Trophoblastic Disease
International Journal of Gynecological Cancer, 2021Co-Authors: Michael J. Seckl, Nienke E Van Trommel, Ulrika Joneborg, Leonoor Coopmans, Christianne A R LokAbstract:The aim of this review is to provide an overview of existing literature and current knowledge on fertility rates and reproductive outcomes after Gestational Trophoblastic Disease. A systematic literature search was performed to retrieve all available studies on fertility rates and reproductive outcomes after hydatidiform mole pregnancy, low-risk Gestational Trophoblastic neoplasia, high- and ultra-high-risk Gestational Trophoblastic neoplasia, and the rare placental site Trophoblastic tumor and epithelioid Trophoblastic tumor forms of Gestational Trophoblastic neoplasia. The effects of single-agent chemotherapy, multi-agent including high-dose chemotherapy, and immunotherapy on fertility, pregnancy wish, and pregnancy outcomes were evaluated and summarized. After treatment for Gestational Trophoblastic neoplasia, most, but not all, women want to achieve another pregnancy. Age and extent of therapy determine if there is a risk of loss of fertility. Single-agent treatment does not affect fertility and subsequent pregnancy outcome. Miscarriage occurs more often in women who conceive within 6 months of follow-up after chemotherapy. Multi-agent chemotherapy hastens the natural menopause by three years and commonly induces a temporary amenorrhea, but in young women rarely causes permanent ovarian failure or infertility. Subsequent pregnancies have a high chance of ending with live healthy babies. In contrast, high-dose chemotherapy typically induces permanent amenorrhea, and no pregnancies have been reported after high-dose chemotherapy for Gestational Trophoblastic neoplasia. Immunotherapy is promising and may give better outcomes than multiple schedules of chemotherapy or even high-dose chemotherapy. The first pregnancy after immunotherapy has recently been described. Data on fertility-sparing treatment in placental site Trophoblastic tumor and epithelioid Trophoblastic tumor are still scarce, and this option should be offered with caution. In general, patients with Gestational Trophoblastic neoplasia may be reassured about their future fertility and pregnancy outcome. Detailed registration of high-risk Gestational Trophoblastic neoplasia is still indispensable to obtain more complete data to better inform patients in the future.
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practical clinical guidelines of the eottd for treatment and referral of Gestational Trophoblastic Disease
European Journal of Cancer, 2020Co-Authors: Christianne A R Lok, Michael J. Seckl, Alice Bergamini, Nienke E Van Trommel, Francois Golfier, Leon F A G Massuger, Miguel Henriques Abreu, Jocelyne Attia, Kirsty Balanchandran, Pierre Adrien BolzeAbstract:Abstract Background and aim Gestational Trophoblastic Disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of Trophoblastic tissue. Since GTD and its malignant sequel Gestational Trophoblastic neoplasia (GTN) are rare Diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the ‘European Organisation for Treatment of Trophoblastic Diseases’ (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD. Methods Members from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid Trophoblastic tumours and follow-up. Results Between 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated. Conclusions Despite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks.
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is there uniformity in definitions and treatment of Gestational Trophoblastic Disease in europe
International Journal of Gynecological Cancer, 2019Co-Authors: Minke Frijstein, Michael J. Seckl, Christianne A R Lok, John Coulter, Nienke E Van Trommel, Marianne Ten J Katebooij, Francois Golfier, Leon F A G MassugerAbstract:Objectives Because Gestational Trophoblastic Disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in Gestational Trophoblastic Disease, we evaluated differences and similarities between protocols in EOTTD countries. Methods Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of Gestational Trophoblastic Disease and Gestational Trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up. Results Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Federation Internationale de Gynecologie et d9Obstetrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar Gestational Trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk Gestational Trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar Gestational Trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk Disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements. Conclusions This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several GestationalTrophoblastic Disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe.