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Vo TN, Nguyen PN. SEVERE DISEASE PROGRESSION OF POSTMOLAR GESTATIONAL NEOPLASM IN A VIETNAMESE YOUNG FEMALE PATIENT AFTER TREATMENT REFUSAL: INSIGHTS FROM A CASE REPORT AND LITERATURE REVIEW. Exp Oncol 2024; 46:154-164. [PMID: 39396168 DOI: 10.15407/exp-oncology.2024.02.154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Indexed: 10/14/2024]
Abstract
Choriocarcinoma is characterized as the most aggressive malignant alternation of gestational trophoblastic neoplasm; however, this illness is a curable malignancy. Although a rarity, this disease affects a female patient's life and causes a fatal condition. Choriocarcinoma is a life-threatening disease since it is initially insidious and can rapidly lead to masive hemorrhage, even death. Choriocarcinoma should be suspected in childbearing-age women with the high-risk scores according to FIGO. The study aims to report a severe case of widespread metastatic choriocarcinoma to optimize the treatment with multiagent chemotherapy and a multidisciplinary cooperation at our center. A G1P0 20-year-old woman was referred to the hospital for suspicion of metastatic choriocarcinoma after self-stopping chemotherapy because of the COVID-19 pandemic. During hospitalization, the tumor metastasized and presented profuse intraabdominal hemorrhage. The patient underwent immediate surgical intervention to control bleeding, and a definitive diagnosis was accurately established by the histopathological examination. After surgery, the EMA/CO regimen was administered as the first line of treatment, despite the patient being in a coma and requiring a ventilator machine. After 6 cycles of the EMA/CO regimen, her serum β-hCG level decreased to 8 mUI/mL, however, her β-hCG concentration was not down to a negative value. Thus, the patient received paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE regimen) for complete remission following 2 cycles. The delays in choriocarcinoma treatment are prognostic factors for worse outcomes, whereas chemotherapy may be considered a suitable treatment even in a patient's coma, thus improving a prognosis substantially.
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Affiliation(s)
- Thanh Nhan Vo
- Department of Gynecologic Oncology, Tu Du Hospital, Ho Chi Minh City, Vietnam
| | - Phuc Nhon Nguyen
- Tu Du Clinical Research Unit, Tu Du Hospital, Ho Chi Minh City, Vietnam
- Department of High-risk Pregnancy, Tu Du Hospital, Ho Chi Minh City, Vietnam
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Deleuze A, Massard C, Le Du F, You B, Lefeuvre-Plesse C, Bolze PA, de la Motte Rouge T. Management of trophoblastic tumors : review of evidence, current practice, and future directions. Expert Rev Anticancer Ther 2023; 23:699-708. [PMID: 37198729 DOI: 10.1080/14737140.2023.2215438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 05/15/2023] [Indexed: 05/19/2023]
Abstract
INTRODUCTION Gestational trophoblastic neoplasia (GTN) is a group of rare tumors characterized by abnormal trophoblastic proliferation following pregnancy including invasive moles, choriocarcinomas, and intermediate trophoblastic tumors (ITT). Although the treatment and follow-up of GTN has been heterogeneous, globally the emergence of expert networks has helped to harmonize its management. AREAS COVERED We provide an overview of the current knowledge, diagnosis, and management strategies in GTN and discuss innovative therapeutic options under investigation. While chemotherapy has been the historical backbone of GTN treatment, promising drugs such as immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway and anti-angiogenic tyrosine kinase inhibitors are currently being investigated remodeling the therapeutical landscape of trophoblastic tumors. EXPERT OPINION Chemotherapy regimens for GTN have potential long-term effects on fertility and quality of life, making innovative and less toxic therapeutic approaches necessary. Immune checkpoint inhibitors have shown promise in reversing immune tolerance in GTN and have been evaluated in several trials. However, immunotherapy is associated with rare but life-threatening adverse events and evidence of immune-related infertility in mice, highlighting the need for further research and careful consideration of its use. Innovative biomarkers could help personalize GTN treatments and reduce chemotherapy burden in some patients.
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Affiliation(s)
- Antoine Deleuze
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | | | - Fanny Le Du
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Benoit You
- Department of Gynecological Oncological, and Obstetrics Department, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France
- French Reference Center for Trophoblastic Diseases, University Hospital Lyon Sud, Lyon, France
- Institute of Cancerology, Hospices Civils de Lyon, CITOHL, Lyon, UR, France
| | | | - Pierre-Adrien Bolze
- Department of Gynecological Oncological, and Obstetrics Department, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France
- Institute of Cancerology, Hospices Civils de Lyon, CITOHL, Lyon, UR, France
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Frasik C, Luong E, Chang M, Sandhu S, Shah AC. Severe Thyrotoxicosis Caused by Molar Pregnancy: A Case Report and Review of the Literature. Cureus 2023; 15:e37582. [PMID: 37197102 PMCID: PMC10184734 DOI: 10.7759/cureus.37582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2023] [Indexed: 05/19/2023] Open
Abstract
Severe thyrotoxicosis is an acute and life-threatening state of hyperthyroidism. While it is a rare presentation of hyperthyroidism, it is clinically significant because of its high mortality and necessitates early identification and treatment to reduce the incidence of poor outcomes. The most common causes of this hypermetabolic state are Graves' disease, toxic thyroid adenoma or multinodular goiter, thyroiditis, iodine-induced hyperthyroidism, and excessive intake of levothyroxine. The less common causes include trauma, medications (i.e., amiodarone), discontinuation of anti-thyroid medications, and interactions with sympathomimetic medications such as ketamine that may be administered during general anesthesia. Regardless of etiology, thyrotoxicosis management should be coordinated using an interdisciplinary team-based approach to optimize outcomes. We discuss a molar pregnancy requiring emergency surgery as an uncommon cause of thyrotoxicosis and highlight appropriate management steps. The patient's symptoms resolved post-operatively, and her post-operative laboratory results (thyroid function and beta-human chorionic gonadotropin {β-hCG}) were followed until they normalized. The patient's preoperative presentation and preparation with a multidisciplinary team discussion, intraoperative anesthetic considerations and course, and post-operative management and follow-up are described.
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Affiliation(s)
- Christina Frasik
- Obstetrics and Gynecology, University of California, Irvine School of Medicine, Irvine, USA
| | - Eli Luong
- Anesthesiology and Perioperative Medicine, University of California, Irvine School of Medicine, Irvine, USA
| | - Melissa Chang
- Anesthesiology and Perioperative Medicine, University of California, Irvine School of Medicine, Irvine, USA
| | - Sareen Sandhu
- Endocrinology, University of California, Irvine School of Medicine, Irvine, USA
| | - Aalap C Shah
- Anesthesiology and Perioperative Medicine, University of California, Irvine School of Medicine, Irvine, USA
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Parker VL, Winter MC, Tidy JA, Hancock BW, Palmer JE, Sarwar N, Kaur B, McDonald K, Aguiar X, Singh K, Unsworth N, Jabbar I, Pacey AA, Harrison RF, Seckl MJ. PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia? Int J Cancer 2023; 152:986-997. [PMID: 36346113 PMCID: PMC10108153 DOI: 10.1002/ijc.34352] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 10/13/2022] [Accepted: 10/17/2022] [Indexed: 11/10/2022]
Abstract
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.
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Affiliation(s)
- Victoria L Parker
- Department of Oncology and Metabolism, The Medical School, The University of Sheffield, Sheffield, UK
| | - Matthew C Winter
- Department of Oncology and Metabolism, The Medical School, The University of Sheffield, Sheffield, UK.,Sheffield Centre for Trophoblastic Disease, Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John A Tidy
- Sheffield Centre for Trophoblastic Disease, Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Barry W Hancock
- Department of Oncology and Metabolism, The Medical School, The University of Sheffield, Sheffield, UK
| | - Julia E Palmer
- Sheffield Centre for Trophoblastic Disease, Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Naveed Sarwar
- Gestational Trophoblastic Disease Centre, Department of Medical Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Baljeet Kaur
- Gestational Trophoblastic Disease Centre, Department of Medical Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Katie McDonald
- Sheffield Centre for Trophoblastic Disease, Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Xianne Aguiar
- Gestational Trophoblastic Disease Centre, Department of Medical Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Kamaljit Singh
- Sheffield Centre for Trophoblastic Disease, Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Nick Unsworth
- Gestational Trophoblastic Disease Centre, Department of Medical Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Imran Jabbar
- Sheffield Centre for Trophoblastic Disease, Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Allan A Pacey
- Department of Oncology and Metabolism, The Medical School, The University of Sheffield, Sheffield, UK
| | - Robert F Harrison
- Department of Automatic Control and Systems Engineering, The University of Sheffield, Sheffield, UK
| | - Michael J Seckl
- Gestational Trophoblastic Disease Centre, Department of Medical Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
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You B, Bolze PA, Lotz JP, Massardier J, Gladieff L, Floquet A, Hajri T, Descargues P, Langlois-Jacques C, Bin S, Villeneuve L, Roux A, Alves-Ferreira M, Grazziotin-Soares D, Dherret G, Gerentet C, Rousset P, Freyer G, Golfier F. Avelumab in patients with gestational trophoblastic tumors with resistance to polychemotherapy: Cohort B of the TROPHIMMUN phase 2 trial. Gynecol Oncol 2023; 168:62-67. [PMID: 36401942 DOI: 10.1016/j.ygyno.2022.11.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/02/2022] [Accepted: 11/04/2022] [Indexed: 11/17/2022]
Abstract
PURPOSE There is a need for innovative treatments in women with gestational trophoblastic tumors (GTT) resistant to chemotherapy. The TROPHIMMUN trial assessed the efficacy of avelumab in patients with resistance to single-agent chemotherapy (cohort A), or to polychemotherapy (cohort B). Cohort B outcomes are reported here. METHODS In the cohort B of this phase 2 multicenter trial (NCT03135769), women with GTT progressing after polychemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. The primary endpoint was the rate of hCG normalization enabling treatment discontinuation (2-stage Simon design). RESULTS Between February 2017 and August 2020, 7 patients were enrolled. Median age was 37 years (range: 29-47); disease stage was I or III in 42.9% and 57.1%; FIGO score was 9-10 in 28.6%, 11 in 28.6%, and 16 in 14.3%, respectively. Median follow-up was 18.2 months. One patient (14.3%) experienced hCG normalization enabling treatment discontinuation. However, resistance to avelumab was observed in the remaining 6 patients (85.7%). The cohort B was stopped for futility. Grade 1-2 treatment-related adverse events occurred in 57.1%, most commonly fatigue (42.9%), nausea, diarrhea, infusion-related reaction, muscle pains, dry eyes (each 14.3%). The median resistance-free survival was 1.4 months (95% CI 0.7-5.3). CONCLUSIONS Although avelumab is active in patients with single-agent chemotherapy-resistant GTT (cohort A), it was associated with limited efficacy in patients with resistance to polychemotherapy (cohort B). The prognosis of patients with polychemotherapy resistance remains poor, and innovative immunotherapy-based therapeutic combinations are needed.
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Affiliation(s)
- Benoit You
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud, EA 3738 CICLY, Lyon, France; Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France.
| | - Pierre-Adrien Bolze
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud, EA 3738 CICLY, Lyon, France; Service de Chirurgie Gynécologique et Oncologique, Obstétrique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
| | - Jean-Pierre Lotz
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Hôpital Tenon, Pôle Onco-Hématologie Hôpitaux Universitaires de l'Est Parisien, APHP, Université Pierre et Marie Curie, Paris, France
| | - Jérome Massardier
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Service de Gynécologie, Obstétrique, Unité de Diagnostic Anténatal, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
| | - Laurence Gladieff
- Département d'oncologie médicale, Institut Claudius Regaud, IUCT-ONCOPOLE, Toulouse, France
| | | | - Touria Hajri
- Centre de Référence des Maladies Trophoblastiques, Lyon, France
| | - Pierre Descargues
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud, EA 3738 CICLY, Lyon, France; Service de Chirurgie Gynécologique et Oncologique, Obstétrique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
| | - Carole Langlois-Jacques
- Service de Biostatistique, Hospices Civils de Lyon, Lyon, France; CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Sylvie Bin
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Laurent Villeneuve
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Adeline Roux
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Marine Alves-Ferreira
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Daniele Grazziotin-Soares
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Hôpital Tenon, Pôle Onco-Hématologie Hôpitaux Universitaires de l'Est Parisien, APHP, Université Pierre et Marie Curie, Paris, France
| | - Guillemine Dherret
- Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France
| | - Christine Gerentet
- Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France
| | - Pascal Rousset
- Univ Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud, EA 3738 CICLY, Lyon, France; Radiologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Gilles Freyer
- Univ Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud, EA 3738 CICLY, Lyon, France; Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France
| | - Francois Golfier
- Centre de Référence des Maladies Trophoblastiques, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Sud, EA 3738 CICLY, Lyon, France; Service de Chirurgie Gynécologique et Oncologique, Obstétrique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
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Dataset for the Reporting of Gestational Trophoblastic Neoplasia: Recommendations From the International Collaboration on Cancer Reporting (ICCR). Int J Gynecol Pathol 2022; 41:S34-S43. [DOI: 10.1097/pgp.0000000000000876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Horowitz NS, Eskander RN, Adelman MR, Burke W. Epidemiology, diagnosis, and treatment of gestational trophoblastic disease: A Society of Gynecologic Oncology evidenced-based review and recommendation. Gynecol Oncol 2021; 163:605-613. [PMID: 34686354 DOI: 10.1016/j.ygyno.2021.10.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/28/2021] [Accepted: 10/04/2021] [Indexed: 12/22/2022]
Affiliation(s)
- N S Horowitz
- Brigham & Women's Hospital/Dana Farber Cancer Institute, Boston, MA, USA.
| | - R N Eskander
- University of California, San Diego, Moores Cancer Center, La Jolla, CA, USA
| | | | - W Burke
- Stony Brook Medicine, Long Island, NY, USA
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Tantengco OAG, De Jesus FCC, Gampoy EFS, Ornos EDB, Vidal MS, Cagayan MSFS. Molar pregnancy in the last 50 years: A bibliometric analysis of global research output. Placenta 2021; 112:54-61. [PMID: 34274613 DOI: 10.1016/j.placenta.2021.07.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/01/2021] [Accepted: 07/06/2021] [Indexed: 11/18/2022]
Abstract
Molar pregnancy is a gestational trophoblastic disease characterized by an abnormal growth of placental tissues because of a nonviable pregnancy. The understanding of the pathophysiology and management of molar pregnancy has significantly increased in the recent years. This study aims to determine the characteristics and trends of published articles in the field of molar pregnancy through a bibliometric analysis. Using the Scopus database, we identified all original research articles on molar pregnancy from 1970 to 2020. Bibliographic and citation information were obtained, and visualization of collaboration networks of countries and keywords related to molar pregnancy was conducted using VOSviewer software. We obtained a total of 2009 relevant papers published between 1970 and 2020 from 80 different countries. The number of publications continued to increase through the years. However, the number of publications in molar pregnancy is still low compared to the other research fields in obstetrics and gynecology. The USA (n = 421, 32.1%), Japan (n = 199, 15.2%), and the UK (n = 191, 14.6%) contributed the greatest number of publications in this field. The top journals which contributed to the field of molar pregnancy include AJOG (n = 91), Obstetrics and Gynecology (n = 81), and the Gynecologic Oncology (n = 57). The most cited articles in molar pregnancy include papers on the genetics and chromosomal abnormalities in molar pregnancies. The focus of current research in this field was on elucidating the molecular mechanism of hydatidiform moles. Our bibliometric analysis showed the global research landscape, trends and development, scientific impact, and collaboration among researchers in the field of molar pregnancy.
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Affiliation(s)
| | | | - Eloina Faye S Gampoy
- College of Medicine, University of the Philippines Manila, Ermita, Manila, Philippines
| | - Eric David B Ornos
- College of Medicine, University of the Philippines Manila, Ermita, Manila, Philippines
| | - Manuel S Vidal
- College of Medicine, University of the Philippines Manila, Ermita, Manila, Philippines
| | - Maria Stephanie Fay S Cagayan
- Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila, Manila, Philippines; Division of Trophoblast Diseases, Department of Obstetrics and Gynecology, University of the Philippines - Philippine General Hospital, Taft Avenue, Manila, Philippines
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Eiriksson L, Dean E, Sebastianelli A, Salvador S, Comeau R, Jang JH, Bouchard-Fortier G, Osborne R, Sauthier P. Guideline No. 408: Management of Gestational Trophoblastic Diseases. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2021; 43:91-105.e1. [PMID: 33384141 DOI: 10.1016/j.jogc.2020.03.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 03/02/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVE This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. INTENDED USERS General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. TARGET POPULATION Women of reproductive age with gestational trophoblastic diseases. OPTIONS Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. EVIDENCE Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. VALIDATION METHODS The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. BENEFITS These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES) RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).
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Braga A, Paiva G, Ghorani E, Freitas F, Velarde LGC, Kaur B, Unsworth N, Lozano-Kuehne J, Dos Santos Esteves APV, Rezende Filho J, Amim J, Aguiar X, Sarwar N, Elias KM, Horowitz NS, Berkowitz RS, Seckl MJ. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study. Lancet Oncol 2021; 22:1188-1198. [PMID: 34181884 DOI: 10.1016/s1470-2045(21)00262-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 11/15/2022]
Abstract
BACKGROUND Patients with gestational trophoblastic neoplasia who have an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6 usually receive non-toxic single-agent chemotherapy as a first-line treatment. Previous studies suggest that only a third of patients have complete remission, with the remaining patients requiring toxic multiagent chemotherapy to attain remission. As stratification factors are unknown, some centres offer multiagent therapy upfront, resulting in overtreatment of many patients. We aimed to identify predictive factors for resistance to single-agent therapy to inform clinicians on which patients presenting with a FIGO score of 5 or 6 are likely to benefit from upfront multiagent chemotherapy. METHODS We did a multicentre, retrospective, cohort study of patients with gestational trophoblastic neoplasia presenting with a FIGO score of 5 or 6, who received treatment at three gestational trophoblastic neoplasia reference centres in the UK, Brazil, and the USA between Jan 1, 1964, and Dec 31, 2018. All patients who had been followed up for at least 12 months after remission were included. Patients were excluded if they had received a non-standard single-agent treatment (eg, etoposide); had been given a previously established first-line multiagent chemotherapy regimen; or had incomplete data for our analyses. Patient data were retrieved from medical records. The primary outcome was the incidence of chemoresistance after first-line or second-line single-agent chemotherapy. Variables associated with chemoresistance to single-agent therapies were identified by logistic regression analysis. In patient subgroups defined by choriocarcinoma histology and metastatic disease status, we did bootstrap modelling to define thresholds of pretreatment human chorionic gonadotropin concentrations and identify groups of patients with a greater than 80% risk (ie, a positive predictive value [PPV] of 0·8) of resistance to single-agent chemotherapy. FINDINGS Of 5025 patients with low-risk gestational trophoblastic neoplasia, we identified 431 patients with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6. All patients were followed up for a minimum of 2 years. 141 (40%) of 351 patients developed resistance to single-agent treatments and required multiagent chemotherapy to achieve remission. Univariable and multivariable logistic regression revealed metastatic disease status (multivariable logistic regression analysis, odds ratio [OR] 1·9 [95% CI 1·1-3·2], p=0·018), choriocarcinoma histology (3·7 [1·9-7·4], p=0·0002), and pretreatment human chorionic gonadotropin concentration (2·8 [1·9-4·1], p<0·0001) as significant predictors of resistance to single-agent therapies. In patients with no metastatic disease and without choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 411 000 IU/L or higher yielded a PPV of 0·8, whereas in patients with either metastases or choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 149 000 IU/L or higher yielded the same PPV for resistance to single-agent therapy. INTERPRETATION Approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors. FUNDING None. TRANSLATION For the Portuguese translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Antonio Braga
- Rio de Janeiro Trophoblastic Disease Centre, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Postgraduate Programme in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, Brazil; Postgraduate Programme in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Young Leadership Physicians Programme, National Academy of Medicine, Rio de Janeiro, Brazil
| | - Gabriela Paiva
- Rio de Janeiro Trophoblastic Disease Centre, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Postgraduate Programme in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Ehsan Ghorani
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Fernanda Freitas
- Rio de Janeiro Trophoblastic Disease Centre, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Postgraduate Programme in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | | | - Baljeet Kaur
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Nick Unsworth
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Jingky Lozano-Kuehne
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Ana Paula Vieira Dos Santos Esteves
- Rio de Janeiro Trophoblastic Disease Centre, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
| | - Jorge Rezende Filho
- Rio de Janeiro Trophoblastic Disease Centre, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Postgraduate Programme in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Joffre Amim
- Rio de Janeiro Trophoblastic Disease Centre, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Postgraduate Programme in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Xianne Aguiar
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Naveed Sarwar
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Kevin M Elias
- Department of Obstetrics, Gynecology and Reproductive Biology, Division of Gynecologic Oncology, New England Trophoblastic Disease Centre, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Neil S Horowitz
- Department of Obstetrics, Gynecology and Reproductive Biology, Division of Gynecologic Oncology, New England Trophoblastic Disease Centre, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Ross S Berkowitz
- Department of Obstetrics, Gynecology and Reproductive Biology, Division of Gynecologic Oncology, New England Trophoblastic Disease Centre, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Michael J Seckl
- Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK.
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Ismail N, Zainudin AM, Hua GS. Normalisation of human chorionic gonadotrophin (hCG) levels in a patient with partial molar pregnancy with a uterine mass without chemotherapy: impact of using herbal remedies. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2021; 18:859-863. [PMID: 33818024 DOI: 10.1515/jcim-2019-0091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 10/28/2020] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Level of βhCG and the presence of any uterine mass of hydatidiform mole need a careful review or monitoring in order to prevent metastasis, provide an early treatment and avoid unnecessary chemotherapy. CASE PRESENTATION A 36-year old fifth gravida patient who had a missed abortion was diagnosed as having a molar pregnancy with beta human chorionic gonadotrophin (βhCG) level of 509,921 IU/L. Her lung field was clear and she underwent suction and curettage (S & C) procedure. However, after six weeks, AA presented to the emergency department with a massive bleeding, although her βhCG level had decreased to 65,770 IU/L. A trans-abdominal ultrasound indicated the presence of an intra-uterine mass (3.0 × 4.4 cm). Nevertheless, her βhCG continued to show a declining trend (8,426 IU/L). AA was advised to undergo a chemotherapy but she refused, citing preference for alternative medicine like herbs instead. She opted for an "at own risk" (AOR) discharge with scheduled follow up. Subsequently, her condition improved with her βhCG showing a downward trend. Surprisingly, at six months post S & C, her βhCG ameliorated to 0 IU/L with no mass detected by ultrasound. CONCLUSIONS Brucea javanica fruits, Pereskia bleo and Annona muricata leaves can potentially be useful alternatives to chemotherapy and need further studies.
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Affiliation(s)
- Norzila Ismail
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Aida Maziha Zainudin
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Gan Siew Hua
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
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Winter MC. Treatment of low-risk gestational trophoblastic neoplasia. Best Pract Res Clin Obstet Gynaecol 2021; 74:67-80. [PMID: 33741258 DOI: 10.1016/j.bpobgyn.2021.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/08/2021] [Indexed: 12/20/2022]
Abstract
Low-risk gestational trophoblastic neoplasia (GTN), defined as FIGO/WHO score 0-6, is highly curable with an overall survival rate, which is approximately 100%. For most low-risk GTN patients, first-line single-agent chemotherapy with either methotrexate or actinomycin-D is recommended with overall complete human chorionic gonadotrophin (hCG) response rates of 60%-90% in mostly retrospective, non-randomised studies. The few randomised trials that exist are not appropriately powered or designed to define the optimal first-line treatment. Approximately 25%-30% of low-risk patients will develop resistance to initial single-agent chemotherapy with an increase in the FIGO score, a diagnosis of choriocarcinoma, higher pre-treatment hCG and the presence of metastatic disease being associated with an increase in the risk of resistance. The optimal treatment of patients scoring WHO 5 and 6 remains poorly defined given that approximately 70%-80% of these patients develop resistance to first-line single-agent chemotherapy, and there is an urgent need to refine the FIGO/WHO scoring system so that these patients can be identified for more intensive therapy from the outset. Despite this, almost all low-risk patients who experience treatment failure with first-line monotherapy will be cured with either sequential single-agent chemotherapy or multiagent chemotherapy with or without surgery. Given the associated increased short and longer-term toxicities associated with multi-agent chemotherapy, promising strategies to reduce the exposure of women to combination chemotherapy in low-risk disease have been investigated, including the use of carboplatin and immune check-point inhibitors. Further evaluation is required to define optimal patient selection, particularly with the use of immunotherapeutic agents given their significant increased costs and lack of longer-term safety data. Although there is a clear need to revise the FIGO/WHO (2000) scoring system, consistent international use of this is recommended to facilitate the comparison of data along with future focus in the development of international collaborative translational and clinical research, including randomised controlled trials.
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Affiliation(s)
- Matthew C Winter
- Trophoblastic Disease Centre, Weston Park Cancer Centre, Sheffield, S10 2SJ, United Kingdom.
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Eiriksson L, Dean E, Sebastianelli A, Salvador S, Comeau R, Jang JH, Bouchard-Fortier G, Osborne R, Sauthier P. Directive clinique n o 408 : Prise en charge des maladies gestationnelles trophoblastiques. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2021; 43:106-123.e1. [PMID: 33384137 DOI: 10.1016/j.jogc.2020.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIF Cette directive passe en revue l'évaluation clinique et la prise en charge des maladies gestationnelles trophoblastiques, notamment les traitements chirurgicaux et médicamenteux des tumeurs bénignes, prémalignes et malignes. L'objectif de la présente directive clinique est d'aider les fournisseurs de soins de santé à rapidement diagnostiquer les maladies gestationnelles trophoblastiques, à normaliser les traitements et le suivi et à assurer des soins spécialisés précoces aux patientes dont l'atteinte est maligne ou métastatique. PROFESSIONNELS CONCERNéS: Gynécologues généralistes, obstétriciens, médecins de famille, sages-femmes, urgentologues, anesthésistes, radiologistes, anatomopathologistes, infirmières autorisées, infirmières praticiennes, résidents, gynécologues-oncologues, oncologues médicaux, radio-oncologues, chirurgiens, omnipraticiens en oncologie, infirmières en oncologie, pharmaciens, auxiliaires médicaux et autres professionnels de la santé qui traitent des patientes atteintes d'une maladie gestationnelle trophoblastique. La présente directive vise également à fournir des renseignements aux parties intéressées qui prodiguent des soins de suivi à ces patientes après le traitement. POPULATION CIBLE Femmes en âge de procréer atteintes d'une maladie gestationnelle trophoblastique. OPTIONS Les femmes ayant reçu un diagnostic de maladie gestationnelle trophoblastique doivent être orientées vers un gynécologue afin qu'il réalise une évaluation initiale, envisage une intervention chirurgicale primaire (évacuation ou hystérectomie) et effectue un suivi. Il y a lieu d'orienter les femmes ayant reçu un diagnostic de tumeur trophoblastique gestationnelle vers un gynécologue-oncologue afin qu'il effectue la stadification tumorale, établisse le score de risque et envisage l'intervention chirurgicale primaire ou un traitement systémique (mono- ou polychimiothérapie) et la nécessité d'éventuels traitements supplémentaires. Il est recommandé de discuter de chaque cas de néoplasie gestationnelle trophoblastique lors d'une réunion multidisciplinaire de cas oncologiques et de l'inscrire dans une base de données centralisée (régionale et/ou nationale). DONNéES PROBANTES: Des recherches ont été effectuées au moyen des bases de données Embase et MEDLINE, du Cochrane Central Register of Controlled Trials et de la Cochrane Database of Systematic Reviews afin de trouver les études publiées depuis 2002 utilisant un ou plusieurs des mots clés suivants : trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome et remission. La recherche initiale a été effectuée en avril 2017; une mise à jour a été faite en mai 2019. Les données probantes pertinentes ont été sélectionnées aux fins d'inclusion selon l'ordre suivant : méta-analyses, revues systématiques, directives cliniques, essais cliniques randomisés, études de cohortes prospectives, études observationnelles, revues non systématiques, études de séries de cas et rapports. D'autres articles pertinents ont été trouvés en recoupant les revues répertoriées. Le nombre total d'études relevées était de 673, dont 79 études sont citées dans la présente revue. MéTHODES DE VALIDATION: Le contenu et les recommandations ont été rédigés et acceptés par les auteurs. La direction et le conseil d'administration de la Société de gynéco-oncologie du Canada ont passé en revue le contenu de la version préliminaire et ont soumis des commentaires à prendre en considération. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation). Consulter les tableaux dans l'annexe en ligne pour connaître les critères de notation et d'interprétation des recommandations. BéNéFICES, RISQUES, COûTS: Les présentes recommandations aideront les médecins à diagnostiquer rapidement les maladies gestationnelles trophoblastiques et à orienter de façon urgente les patientes ayant reçu un diagnostic de maladie gestationnelle trophoblastique en gynécologie oncologique pour une prise en charge spécialisée. Le traitement des néoplasies gestationnelles trophoblastiques en centre spécialisé combiné à l'utilisation de bases de données centralisées permet de recueillir et de comparer des données sur les résultats thérapeutiques des patientes atteintes de ces tumeurs rares et d'optimiser les soins aux patientes. DÉCLARATIONS SOMMAIRES (CLASSEMENT GRADE ENTRE PARENTHèSES): RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES).
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14
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You B, Bolze PA, Lotz JP, Massardier J, Gladieff L, Joly F, Hajri T, Maucort-Boulch D, Bin S, Rousset P, Devouassoux-Shisheboran M, Roux A, Alves-Ferreira M, Grazziotin-Soares D, Langlois-Jacques C, Mercier C, Villeneuve L, Freyer G, Golfier F. Avelumab in Patients With Gestational Trophoblastic Tumors With Resistance to Single-Agent Chemotherapy: Cohort A of the TROPHIMMUN Phase II Trial. J Clin Oncol 2020; 38:3129-3137. [PMID: 32716740 PMCID: PMC7499607 DOI: 10.1200/jco.20.00803] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All GTT subtypes express programmed death-ligand 1 (PD-L1), and natural killer (NK) cells are involved in trophoblast immunosurveillance. Avelumab (anti-PD-L1) induces NK cell-mediated cytotoxicity. The TROPHIMMUN trial assessed avelumab in women with chemotherapy-resistant GTT. METHODS In this phase II multicenter trial (ClinicalTrials.gov identifier: NCT03135769), women with GTT who experienced disease progression after single-agent chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. Rate of hCG normalization was the primary endpoint (2-step Simon design). RESULTS Between December 2016 and September 2018, 15 patients were treated. Median age was 34 years; disease stage was I or III in 53.3% and 46.7% of women, respectively; and International Federation of Gynecology and Obstetrics (FIGO) score was 0-4 in 33.3%, 5-6 in 46.7%, and ≥ 7 in 20% of patients. Prior treatment included methotrexate (100%) and actinomycin D (7%). Median follow-up was 25 months, and median number of avelumab cycles was 8 (range, 2-11). Grade 1-2 treatment-related adverse events occurred in 93% of patients, most commonly (≥ 25%) fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reaction (26.7%). One patient had grade 3 uterine bleeding (treatment unrelated). Eight patients (53.3%) had hCG normalization after a median of 9 avelumab cycles; none subsequently relapsed. Probability of normalization was not associated with disease stage, FIGO score, or baseline hCG. One patient subsequently had a healthy pregnancy. In avelumab-resistant patients (46.7%), hCG was normalized with actinomycin D (42.3%) or combination chemotherapy/surgery (57.1%). CONCLUSION In patients with single-agent chemotherapy-resistant GTT, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.
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Affiliation(s)
- Benoit You
- Centre de Référence des Maladies Trophoblastiques, Lyon, France.,Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, CICLY, Lyon, France.,Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon, Centre d'Investigation de Thérapeutiques en Oncologie et Hématologie de Lyon, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France
| | - Pierre-Adrien Bolze
- Centre de Référence des Maladies Trophoblastiques, Lyon, France.,Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, CICLY, Lyon, France.,Service de Chirurgie Gynécologique et Oncologique, Obstétrique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Jean-Pierre Lotz
- Centre de Référence des Maladies Trophoblastiques, Lyon, France.,Hôpital Tenon, Pôle Onco-Hématologie Hôpitaux Universitaires de l'Est Parisien, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France
| | - Jérome Massardier
- Centre de Référence des Maladies Trophoblastiques, Lyon, France.,Service de Gynécologie Obstétrique, Unité de Diagnostic Anténatal, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
| | - Laurence Gladieff
- Département d'Oncologie Médicale, Institut Claudius Regaud, IUCT-ONCOPOLE, Toulouse, France
| | - Florence Joly
- Clinical Research Department, Centre François Baclesse, Caen Cedex, France
| | - Touria Hajri
- Centre de Référence des Maladies Trophoblastiques, Lyon, France
| | - Delphine Maucort-Boulch
- Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, CICLY, Lyon, France.,Service de Biostatistique, Hospices Civils de Lyon, Lyon; and CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Sylvie Bin
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Pascal Rousset
- Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, CICLY, Lyon, France.,Radiologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | | | - Adeline Roux
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Marine Alves-Ferreira
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Daniele Grazziotin-Soares
- Centre de Référence des Maladies Trophoblastiques, Lyon, France.,Hôpital Tenon, Pôle Onco-Hématologie Hôpitaux Universitaires de l'Est Parisien, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France
| | - Carole Langlois-Jacques
- Service de Biostatistique, Hospices Civils de Lyon, Lyon; and CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Catherine Mercier
- Service de Biostatistique, Hospices Civils de Lyon, Lyon; and CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Laurent Villeneuve
- Unité Recherche et Epidémiologie Cliniques - Pôle de Santé Publique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Gilles Freyer
- Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, CICLY, Lyon, France.,Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon, Centre d'Investigation de Thérapeutiques en Oncologie et Hématologie de Lyon, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France
| | - Francois Golfier
- Centre de Référence des Maladies Trophoblastiques, Lyon, France.,Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, CICLY, Lyon, France.,Service de Chirurgie Gynécologique et Oncologique, Obstétrique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
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Delivery of Euthyroid Baby following Hyperthyroidism in Twin Gestation with Coexisting Complete Hydatidiform Mole. Case Rep Endocrinol 2019; 2019:2941501. [PMID: 31949957 PMCID: PMC6944968 DOI: 10.1155/2019/2941501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 12/13/2019] [Indexed: 01/22/2023] Open
Abstract
Context Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Twin pregnancies with GTD and coexisting normal fetus are extremely rare with an estimated incidence of 1 case per 22,000–100,000 pregnancies. Molecular mimicry between human chorionic gonadotrophin (hCG) and thyroid-stimulating hormone (TSH) leads to gestational trophoblastic hyperthyroidism (GTH) which is further associated with increased maternal and fetal complications. This is the first reported case in literature describing the delivery of a baby with biochemical euthyroid status following a twin pregnancy with hydatidiform mole (HM) associated with gestational trophoblastic hyperthyroidism (GTH). Case Description A 24-year-old G4 P3 Caucasian female with twin gestation was admitted to hospital for gestation trophoblastic hyperthyroidism. She was later diagnosed to have twin pregnancy with complete mole and coexisting normal fetus complicated by gestational trophoblastic hyperthyroidism (GTH). Despite the risk associated with the continuation of molar pregnancy, per patient request, pregnancy was continued till viability of the fetus. The patient underwent cesarean section due to worsening preeclampsia and delivered a euthyroid baby at the 24th week of gestation. Conclusions Twin pregnancy with gestational trophoblastic disease and coexisting normal fetus is associated with high risk of hyperthyroidism, and careful monitoring of the thyroid function test along with dose titration of thionamides is of utmost importance throughout the gestation. If normal thyroid hormone levels are maintained during the pregnancy, euthyroidism could be successfully achieved in the baby.
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Comparison between vacuum aspiration and forceps plus blunt curettage for the evacuation of complete hydatidiform moles. Taiwan J Obstet Gynecol 2019; 58:650-655. [DOI: 10.1016/j.tjog.2019.07.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/03/2019] [Indexed: 11/17/2022] Open
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Okada Y, Miyamoto S, Mimura T, Ishikawa T, Sekizawa A, Matsumoto K. Spontaneous regression of quiescent gestational trophoblastic disease after pregnancy: a case report. BMC WOMENS HEALTH 2019; 19:101. [PMID: 31337386 PMCID: PMC6651975 DOI: 10.1186/s12905-019-0794-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 07/02/2019] [Indexed: 11/10/2022]
Abstract
Background A persistent low-level elevation of serum human chorionic gonadotropin (hCG) without clinical or radiological evidence of pregnancy or tumors was recently defined as quiescent gestational trophoblastic disease (Q-GTD). Whether patients with Q-GTD should be treated or allowed to become pregnant remains unclear. We herein report a rare case of Q-GTD in which the hCG level spontaneously returned to normal after a successful pregnancy. Case presentation The patient was a 37-year-old primigravida who presented with a persistent low-level elevation of hCG after uterine evacuation of a hydatidiform mole. There was no evidence of neoplasia in the uterus or distant metastasis. The low-level elevation of hCG persisted for at least 2 years but never exceeded 200 mIU/mL. The patient had a successful pregnancy at the age of 40 years. Conclusions Interestingly, her hCG level subsequently normalized without chemotherapy. The present case may imply the safety and therapeutic effect of pregnancy in women with Q-GTD.
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Affiliation(s)
- Yoshiyuki Okada
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Shingo Miyamoto
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
| | - Takashi Mimura
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Tetsuya Ishikawa
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Akihiko Sekizawa
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Koji Matsumoto
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
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Braga A, Mora P, de Melo AC, Nogueira-Rodrigues A, Amim-Junior J, Rezende-Filho J, Seckl MJ. Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide. World J Clin Oncol 2019; 10:28-37. [PMID: 30815369 PMCID: PMC6390119 DOI: 10.5306/wjco.v10.i2.28] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 11/12/2018] [Accepted: 01/01/2019] [Indexed: 02/06/2023] Open
Abstract
Gestational trophoblastic neoplasia (GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma (CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor (PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases. The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria: four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However, the latter reason for treatment is no longer used by many centers. In addition, GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1 cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate (MTX) or Actinomycin-D (Act-D), can cure about 70% of patients with FIGO/World Health Organization (WHO) prognosis risk score ≤ 6 (low risk), reserving multiple agent chemotherapy, such as EMA/CO (Etoposide, MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7 (high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death, allow the healing and maintenance of the reproductive potential of these women.
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Affiliation(s)
- Antonio Braga
- Postgraduate Program of Medical Sciences, Fluminense Federal University, Niterói 24033-900, Brazil
- Department of Gynecology and Obstetrics, Faculty of Medicine, Rio de Janeiro Federal University, Postgraduate Program of Perinatal Health, Maternity School, Rio de Janeiro 22240-000, Brazil
| | - Paulo Mora
- Postgraduate Program of Medical Sciences, Fluminense Federal University, Niterói 24033-900, Brazil
- Brazilian National Cancer, Hospital do Câncer 2, Rio de Janeiro 20220-410, Brazil
| | | | - Angélica Nogueira-Rodrigues
- Department of Internal Medicine, Faculty of Medicine, Minas Gerais Federal University, Belo Horizonte 30130-100, Brazil
| | - Joffre Amim-Junior
- Department of Gynecology and Obstetrics, Faculty of Medicine, Rio de Janeiro Federal University, Postgraduate Program of Perinatal Health, Maternity School, Rio de Janeiro 22240-000, Brazil
| | - Jorge Rezende-Filho
- Department of Gynecology and Obstetrics, Faculty of Medicine, Rio de Janeiro Federal University, Postgraduate Program of Perinatal Health, Maternity School, Rio de Janeiro 22240-000, Brazil
| | - Michael J Seckl
- Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College London, London W6 8RF, United Kingdom
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Braga A, Biscaro A, do Amaral Giordani JM, Viggiano M, Elias KM, Berkowitz RS, Seckl MJ. Does a human chorionic gonadotropin level of over 20,000 IU/L four weeks after uterine evacuation for complete hydatidiform mole constitute an indication for chemotherapy for gestational trophoblastic neoplasia? Eur J Obstet Gynecol Reprod Biol 2018; 223:50-55. [PMID: 29477553 DOI: 10.1016/j.ejogrb.2018.02.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Revised: 01/22/2018] [Accepted: 02/01/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate whether a human chorionic gonadotropin (hCG) level ≥20,000 IU/L four weeks after uterine evacuation for complete hydatidiform mole (CHM) is an appropriate indicator for initiating chemotherapy for the treatment of gestational trophoblastic neoplasia (GTN). STUDY DESIGN Historical database review of 1228 women with CHM who received treatment and follow-up between January 2000 and June 2013 at four Brazilian trophoblastic disease centers. The primary outcome measure was the progression from CHM to GTN. The secondary outcomes were the occurrence of uterine perforation, staging of GTN, WHO/FIGO risk score, and treatment (use of single- or multiagent chemotherapy). RESULTS An hCG level ≥20,000 IU/L four weeks after uterine evacuation for CHM, while occurring in only 6.1% of women, was the most important risk factor for the development of postmolar GTN (adjusted RR = 5.83; p < 0.01; CI: 3.47-9.79), with a sensitivity of 36.8%, a specificity of 98.6%, a positive predictive value of 80%, and a negative predictive value of 91.1%. On the other hand, there were no differences in postmolar GTN stage, prognostic score, or need for multiagent chemotherapy relative to hCG level ≥20,000 IU/L versus <20,000 IU/L. CONCLUSIONS Although hCG level ≥20,000 IU/L four weeks after uterine evacuation for CHM was very predictive of development of post-molar GTN, delay in treatment until hCG plateau or increase did not affect outcomes, with no uterine perforations or treatment failures.
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Affiliation(s)
- Antonio Braga
- Postgraduate Program in Perinatal Health, Rio de Janeiro Trophoblastic Disease Center, Maternity School, Federal University of Rio de Janeiro and Antonio Pedro University Hospital at Fluminense Federal University, Rio de Janeiro, Brazil; Postgraduate Program in Maternal and Child Health, Fluminense Federal University, Niterói, Brazil.
| | - Andressa Biscaro
- Postgraduate Program in Maternal and Child Health, Fluminense Federal University, Niterói, Brazil
| | | | - Maurício Viggiano
- Goiás Trophoblastic Disease Center, Goiás Federal University, Goiânia, Brazil
| | - Kevin M Elias
- New England Trophoblastic Disease Center, Donald P. Goldstein, MD. Trophoblastic Tumor Registry, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Brigham and Women's Hospital, Dana Farber Cancer Institute/Harvard Cancer Center, Harvard Medical School, Boston, United States
| | - Ross S Berkowitz
- New England Trophoblastic Disease Center, Donald P. Goldstein, MD. Trophoblastic Tumor Registry, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Brigham and Women's Hospital, Dana Farber Cancer Institute/Harvard Cancer Center, Harvard Medical School, Boston, United States
| | - Michael J Seckl
- Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College of London, London, UK
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Pantoja Garrido M, Frías Sánchez Z, Gómiz Rodríguez G, Vico de Miguel F, Pantoja Rosso F. Gestación ectópica molar abscesificada sobre cicatriz de cesárea anterior, a propósito de un caso. CLINICA E INVESTIGACION EN GINECOLOGIA Y OBSTETRICIA 2017. [DOI: 10.1016/j.gine.2016.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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21
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Virmani S, Srinivas SB, Bhat R, Rao R, Kudva R. Transient Thyrotoxicosis in Molar Pregnancy. J Clin Diagn Res 2017; 11:QD01-QD02. [PMID: 28892983 DOI: 10.7860/jcdr/2017/28561.10133] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 05/03/2017] [Indexed: 12/31/2022]
Abstract
Molar pregnancy is one of the components of a broader spectrum of diseases known as Gestational Trophoblastic Disease (GTD), presenting with amenorrhoea and irregular bleeding which may be rarely associated with passage of vesicles per vagina. However, it can rarely be associated with hyperthyroidism, which may be associated with clinical features of hyperthyroidism. The following is a report of a 20-year-old woman who presented with amenorrhea followed by irregular bleeding per vagina, thyromegaly and abnormal levels of thyroid hormones. Transvaginal ultrasound revealed features consistent with molar pregnancy. A suction evacuation was done following which serum levels of β-hCG reduced and the levels of thyroid hormones also reduced. On follow up, six weeks later, β-hCG and thyroid hormones were within normal limits. The case and relevant literature are presented here.
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Affiliation(s)
- Samarth Virmani
- Medical Student, Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - Sujatha B Srinivas
- Assistant Professor, Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - Rama Bhat
- Professor, Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - Raghavendra Rao
- Assistant Professor, Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - Ranjini Kudva
- Professor, Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
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Braga A, Torres B, Burlá M, Maestá I, Sun SY, Lin L, Madi JM, Uberti E, Viggiano M, Elias KM, Berkowitz RS. Is chemotherapy necessary for patients with molar pregnancy and human chorionic gonadotropin serum levels raised but falling at 6months after uterine evacuation? Gynecol Oncol 2017; 143:558-564. [PMID: 27640962 DOI: 10.1016/j.ygyno.2016.09.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Revised: 09/06/2016] [Accepted: 09/10/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To compare the outcomes of Brazilian patients with molar pregnancy who continue human chorionic gonadotropin (hCG) surveillance with those treated with chemotherapy when hCG was still positive, but falling at 6months after uterine evacuation. METHODS Retrospective chart review of 12,526 patients with hydatidiform mole treated at one of nine Brazilian reference centers from January 1990 to May 2016. RESULTS At 6months from uterine evacuation, 96 (0.8%) patients had hCG levels raised but falling. In 15/96 (15.6%) patients, chemotherapy was initiated immediately per FIGO 2000 criteria, while 81/96 (84.4%) patients were managed expectantly. Among the latter, 65/81 (80.2%) achieved spontaneous remission and 16 (19.8%) developed postmolar gestational trophoblastic neoplasia (GTN). Patients who received chemotherapy following expectant management required more time for remission (11 versus 8months; p=0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6months; p<0.001), and presented with a median WHO/FIGO risk score higher than women treated according to FIGO 2000 criteria (4 versus 2, p=0.04), but there were no significant differences in the need for multiagent treatment regimens (1/15 versus 3/16 patients, p=0.60). None of the women relapsed, and no deaths occurred in either group. CONCLUSION In order to avoid unnecessary exposure of women to chemotherapy, we no longer follow the FIGO 2000 recommendation to treat all patients with molar pregnancy and hCG raised but falling at 6months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.
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Affiliation(s)
- Antonio Braga
- Rio de Janeiro Trophoblastic Disease Center (Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Maternity Ward of Santa Casa da Misericórdia do Rio de Janeiro), Rio de Janeiro, Rio de Janeiro, Brazil; Postgraduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Postgraduate Program in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Brazil.
| | - Berenice Torres
- Rio de Janeiro Trophoblastic Disease Center (Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Maternity Ward of Santa Casa da Misericórdia do Rio de Janeiro), Rio de Janeiro, Rio de Janeiro, Brazil; Postgraduate Program in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Brazil
| | - Marcelo Burlá
- Rio de Janeiro Trophoblastic Disease Center (Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Maternity Ward of Santa Casa da Misericórdia do Rio de Janeiro), Rio de Janeiro, Rio de Janeiro, Brazil; Postgraduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
| | - Izildinha Maestá
- Trophoblastic Diseases Center of the Clinical Hospital of Botucatu Medical School, Department of Gynecology and Obstetrics, São Paulo State University, Botucatu, São Paulo, Brazil
| | - Sue Yazaki Sun
- São Paulo Hospital Trophoblastic Disease Center, Paulista School of Medicine, São Paulo Federal University, São Paulo, São Paulo, Brazil
| | - Lawrence Lin
- São Paulo Clinics Hospital Trophoblastic Disease Center, University of São Paulo, São Paulo, São Paulo, Brazil
| | - José Mauro Madi
- Caxias do Sul Trophoblastic Disease Center, General Hospital of Caxias do Sul, School of Medicine, Center for Biological and Health Sciences, Caxias do Sul University, Caxias do Sul, Rio Grande do Sul, Brazil
| | - Elza Uberti
- Porto Alegre Trophoblastic Disease Center, Mario Totta Maternity Ward, Irmandade da Santa Casa de Misericórdia Hospital, Porto Alegre, Rio Grande do Sul, Brazil
| | - Maurício Viggiano
- Goiás Trophoblastic Disease Center, Clinical Hospital of Goiás, Goiás Federal University, Goiânia, Goiás, Brazil
| | - Kevin M Elias
- New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ross S Berkowitz
- New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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23
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Brown J, Naumann RW, Seckl MJ, Schink J. 15years of progress in gestational trophoblastic disease: Scoring, standardization, and salvage. Gynecol Oncol 2016; 144:200-207. [PMID: 27743739 DOI: 10.1016/j.ygyno.2016.08.330] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 08/15/2016] [Accepted: 08/22/2016] [Indexed: 01/03/2023]
Abstract
Significant improvements in treatment and the understanding of gestational trophoblastic neoplasia have occurred in the last 15years. These diseases are almost always curable, and refractory patients have more options for salvage therapy. Recent improvements in the understanding of epidemiology, diagnosis, and cell biology have resulted in changes in staging, advances in treatment options, and opportunities for fertility preservation.
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Affiliation(s)
- Jubilee Brown
- Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, United States.
| | - R Wendel Naumann
- Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, United States
| | - Michael J Seckl
- Charing Cross Trophoblastic Disease Centre, Department of Medical Oncology, Charing Cross Campus of Imperial College London, London, United Kingdom
| | - Julian Schink
- Spectrum Health Medical Group, Department of Obstetrics, Gynecology, and Womens Health Group, Grand Rapids, MI, United States
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24
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Chen J, Samson SL, Bentley J, Chen Y. Persistent mild increase of human chorionic gonadotropin levels in a 31-year-old woman after spontaneous abortion. CMAJ 2016; 188:E504-E508. [PMID: 27698202 DOI: 10.1503/cmaj.151481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Affiliation(s)
- Jianing Chen
- Department of Laboratory Medicine (J. Chen, Y. Chen), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; School of Medicine (J. Chen), University College Cork, Cork, Ireland; Department of Obstetrics and Gynecology (Samson), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; Departments of Obstetrics and Gynaecology (Samson, Bentley) and Pathology (Y. Chen), Dalhousie University, Halifax, NS
| | - Sheri-Lee Samson
- Department of Laboratory Medicine (J. Chen, Y. Chen), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; School of Medicine (J. Chen), University College Cork, Cork, Ireland; Department of Obstetrics and Gynecology (Samson), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; Departments of Obstetrics and Gynaecology (Samson, Bentley) and Pathology (Y. Chen), Dalhousie University, Halifax, NS
| | - James Bentley
- Department of Laboratory Medicine (J. Chen, Y. Chen), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; School of Medicine (J. Chen), University College Cork, Cork, Ireland; Department of Obstetrics and Gynecology (Samson), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; Departments of Obstetrics and Gynaecology (Samson, Bentley) and Pathology (Y. Chen), Dalhousie University, Halifax, NS
| | - Yu Chen
- Department of Laboratory Medicine (J. Chen, Y. Chen), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; School of Medicine (J. Chen), University College Cork, Cork, Ireland; Department of Obstetrics and Gynecology (Samson), Dr. Everett Chalmers Regional Hospital, Horizon Health Network, Fredericton, NB; Departments of Obstetrics and Gynaecology (Samson, Bentley) and Pathology (Y. Chen), Dalhousie University, Halifax, NS
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25
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Qian XQ, Chen LL, Li BH, Cheng XD, Wan XY. Long-term outcome of patients with persistent low-level elevation of human chorionic gonadotrophin. J Obstet Gynaecol Res 2016; 42:694-700. [PMID: 26916449 DOI: 10.1111/jog.12953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 12/02/2015] [Accepted: 12/23/2015] [Indexed: 11/30/2022]
Affiliation(s)
- Xue-qian Qian
- Department of Gynecologic Oncology, Women's Hospital, School of Medicine; Zhejiang University; Hangzhou China
| | - Li-li Chen
- Department of Gynecologic Oncology, Women's Hospital, School of Medicine; Zhejiang University; Hangzhou China
| | - Bao-hua Li
- Department of Gynecologic Oncology, Women's Hospital, School of Medicine; Zhejiang University; Hangzhou China
| | - Xiao-dong Cheng
- Department of Gynecologic Oncology, Women's Hospital, School of Medicine; Zhejiang University; Hangzhou China
| | - Xiao-yun Wan
- Department of Gynecologic Oncology, Women's Hospital, School of Medicine; Zhejiang University; Hangzhou China
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26
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Taylor F, Short D, Harvey R, Winter MC, Tidy J, Hancock BW, Savage PM, Sarwar N, Seckl MJ, Coleman RE. Late spontaneous resolution of persistent molar pregnancy. BJOG 2016; 123:1175-81. [DOI: 10.1111/1471-0528.13867] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/17/2015] [Indexed: 11/30/2022]
Affiliation(s)
- F Taylor
- Sheffield Centre for Trophoblastic Disease Sheffield Cancer Research Centre Weston Park Hospital Sheffield UK
| | - D Short
- Charing Cross Gestational Trophoblastic Disease Centre Department of Medical Oncology Charing Cross Hospital Campus of Imperial College London London UK
| | - R Harvey
- Charing Cross Gestational Trophoblastic Disease Centre Department of Medical Oncology Charing Cross Hospital Campus of Imperial College London London UK
| | - MC Winter
- Sheffield Centre for Trophoblastic Disease Sheffield Cancer Research Centre Weston Park Hospital Sheffield UK
| | - J Tidy
- Sheffield Centre for Trophoblastic Disease Sheffield Cancer Research Centre Weston Park Hospital Sheffield UK
| | - BW Hancock
- Sheffield Centre for Trophoblastic Disease Sheffield Cancer Research Centre Weston Park Hospital Sheffield UK
| | - PM Savage
- Charing Cross Gestational Trophoblastic Disease Centre Department of Medical Oncology Charing Cross Hospital Campus of Imperial College London London UK
| | - N Sarwar
- Charing Cross Gestational Trophoblastic Disease Centre Department of Medical Oncology Charing Cross Hospital Campus of Imperial College London London UK
| | - MJ Seckl
- Charing Cross Gestational Trophoblastic Disease Centre Department of Medical Oncology Charing Cross Hospital Campus of Imperial College London London UK
| | - RE Coleman
- Sheffield Centre for Trophoblastic Disease Sheffield Cancer Research Centre Weston Park Hospital Sheffield UK
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27
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Goldstein DP, Berkowitz RS, Horowitz NS. Optimal management of low-risk gestational trophoblastic neoplasia. Expert Rev Anticancer Ther 2015; 15:1293-304. [PMID: 26517533 DOI: 10.1586/14737140.2015.1088786] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Low-risk gestational trophoblastic neoplasia is a highly curable form of gestational trophoblastic neoplasia that arises largely from molar pregnancy and, on rare occasions, from other types of gestations. Risk is defined as the risk of developing drug resistance as determined by the WHO Prognostic Scoring System. All patients with non-metastatic disease and patients with risk scores <7 are considered to have low-risk disease. The sequential use of methotrexate and actinomycin D is associated with a complete remission rate of 80%. The most commonly utilized regimen for the treatment of patients resistant to single-agent chemotherapy is a multiagent regimen consisting of etoposide, methotrexate, actinomycin D, vincristine and cyclophosphamide. The measurement of human chorionic gonadotropin provides an accurate and reliable tumor marker for diagnosis, monitoring the effects of chemotherapy and follow-up to determine recurrence. Pregnancy is allowed after 12 months of normal serum tumor marker. Pregnancy outcomes are similar to those of normal population.
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Affiliation(s)
- Donald P Goldstein
- a 1 The New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA.,b 2 Brigham, and Women's Hospital, Division of Gynecologic Oncology, 75 Francis Street, Boston, MA 02115, USA
| | - Ross S Berkowitz
- a 1 The New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA.,b 2 Brigham, and Women's Hospital, Division of Gynecologic Oncology, 75 Francis Street, Boston, MA 02115, USA
| | - Neil S Horowitz
- a 1 The New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA.,b 2 Brigham, and Women's Hospital, Division of Gynecologic Oncology, 75 Francis Street, Boston, MA 02115, USA
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28
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Braga A, Maestá I, Short D, Savage P, Harvey R, Seckl MJ. Hormonal contraceptive use before hCG remission does not increase the risk of gestational trophoblastic neoplasia following complete hydatidiform mole: a historical database review. BJOG 2015; 123:1330-5. [PMID: 26444183 DOI: 10.1111/1471-0528.13617] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2015] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To re-evaluate the safety of hormonal contraceptives (HC) after uterine evacuation of complete hydatidiform mole (CHM). DESIGN Historical database review. SETTING Charing Cross Hospital Gestational Trophoblastic Disease Centre, London, United Kingdom. POPULATION Two thousand four hundred and twenty-three women with CHM of whom 154 commenced HC while their human chorionic gonadotropin (hCG) was still elevated, followed between 2003 and 2012. METHODS We compared time to hCG remission between HC users and nonusers. The relationship between HC use and gestational trophoblastic neoplasia (GTN) development was assessed. The relationship between HC use and a high International Federation of Gynecology and Obstetrics (FIGO) risk score was determined. MAIN OUTCOME MEASURES Time to hCG remission, risk of developing postmolar GTN and proportion of women with high FIGO risk score. RESULTS No relationship was observed between HC use with mean time to hCG remission (HC users versus non-users: 12 weeks in both, P = 0.19), GTN development (HC users versus non-users: 20.1 and 16.7%, P = 0.26) or high-risk FIGO score (HC users versus nonusers: 0% and 8%, P = 0.15). Moreover, no association between HC and GTN development was found, even when an age-adjusted model was used (OR = 1.37, 95% CI 0.91-2.08, P = 0.13). CONCLUSIONS The use of current HC is not associated with development of postmolar GTN or delayed time to hCG remission. Therefore, HC can be safely used to prevent a new conception following CHM regardless of hCG level. TWEETABLE ABSTRACT Non-concurrent cohort study to re-evaluate the safety of low dose HCs after uterine evacuation of CHM.
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Affiliation(s)
- A Braga
- Trophoblastic Disease Center, Maternity School of Rio de Janeiro Federal University and Antonio Pedro University Hospital at Fluminense Federal University, Rio de Janeiro, Brazil.,Postdoctoral Program of Science without Borders (Brazilian Government) - Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College School of Medicine, London, UK.,Postdoctoral Program of Gynecology, Obstetrics and Mastology Postgraduate of Botucatu Medical School, UNESP- São Paulo State University, Botucatu, São Paulo, Brazil.,Trophoblastic Disease Center, Department of Gynecology and Obstetrics, Botucatu Medical School, UNESP - São Paulo State University, Botucatu, São Paulo, Brazil
| | - I Maestá
- Trophoblastic Disease Center, Department of Gynecology and Obstetrics, Botucatu Medical School, UNESP - São Paulo State University, Botucatu, São Paulo, Brazil
| | - D Short
- Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College School of Medicine, London, UK
| | - P Savage
- Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College School of Medicine, London, UK
| | - R Harvey
- Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College School of Medicine, London, UK
| | - M J Seckl
- Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College School of Medicine, London, UK
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29
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A retrospective study to evaluate single agent methotrexate treatment in low risk gestational choriocarcinoma in the United Kingdom. Gynecol Oncol 2014; 136:258-63. [PMID: 25542400 DOI: 10.1016/j.ygyno.2014.12.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 12/14/2014] [Accepted: 12/16/2014] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To determine whether single agent chemotherapy with intramuscular methotrexate 50mg administered on days 1, 3, 5, and 7 and oral folinic acid 15mg administered on days 2, 4, 6, and 8 in 2 weekly cycles (IM MTX/FA) is an effective treatment regimen for patients with low risk gestational choriocarcinoma. METHOD Electronic databases were searched to identify patients with gestational choriocarcinoma at the Sheffield and Charing Cross supra-regional trophoblastic disease centres from January 2000 to December 2011. Clinical notes of low risk patients with FIGO score 0-6 were retrospectively reviewed to assess treatment outcomes and subsequent relapse. RESULTS 65 patients were identified with low risk choriocarcinoma. Serum hCG levels normalised in 24 patients without the requirement of chemotherapy (19 with histological confirmation, 4 highly suspicious histology and 1 clinical diagnosis). Of 23 patients with histologically confirmed choriocarcinoma, 8 (35%) had a sustained complete response to IM MTX/FA and did not relapse. Both patients with FIGO score 6, and 1 patient with FIGO stage III metastatic disease developed resistance to IM MTX/FA and required further treatment. Despite the development of drug resistance or relapse all patients were successfully salvaged by subsequent treatments. CONCLUSIONS Not all patients with low risk choriocarcinoma that have had primary intervention prior to staging, such as surgical resection or uterine evacuation will require chemotherapy, providing hCG levels continue to decline to normal. Low risk (FIGO 0-5) patients should initially receive IM MTX/FA due to its low toxicity, outpatient administration and reasonable efficacy. Patients with FIGO score 6 or FIGO stage III disease should make an informed choice between IM MTX/FA and combination chemotherapy.
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Trophoblastic disease review for diagnosis and management: a joint report from the International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup. Int J Gynecol Cancer 2014; 24:S109-16. [PMID: 25341573 DOI: 10.1097/igc.0000000000000294] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVE The objective of this study was to provide a consensus review on gestational trophoblastic disease diagnosis and management from the combined International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup. METHODS A joint committee representing various groups reviewed the literature obtained from PubMed searches. RESULTS AND CONCLUSIONS Guidelines were constructed on the basis of literature review. After initial diagnosis in local centers, centralization of pathology review and ongoing care is recommended to achieve the best outcomes.
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Ngu SF, Chan KKL. Management of Chemoresistant and Quiescent Gestational Trophoblastic Disease. CURRENT OBSTETRICS AND GYNECOLOGY REPORTS 2014; 3:84-90. [PMID: 24533232 PMCID: PMC3920061 DOI: 10.1007/s13669-013-0071-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Gestational trophoblastic neoplasia (GTN) is highly chemosensitive and has a high cure rate. Since the introduction of chemotherapy, reliable measurement of human chorionic gonadotropin (hCG) levels, and individualised risk-based therapy into the management of GTN, almost all low-risk and more than 80 % of high-risk GTN cases are curable. However, approximately 25 % of high-risk GTN developed resistance to chemotherapy or relapsed after completion of initial therapy, which often necessitate salvage combination chemotherapy. On the other end of the spectrum, a proportion of patients with gestational trophoblastic disease (GTD) have persistently low levels of hCG, without clinical or radiological evidence of disease, a condition called quiescent GTD. Recently, measurement of hyperglycosylated hCG has been proposed for the management of patients with quiescent GTD. Although representing a small proportion of GTD cases, the management of patients with chemoresistant and quiescent GTD often poses challenges to medical practitioners.
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Affiliation(s)
- Siew-Fei Ngu
- Department of Obstetrics and Gynecology, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, Hong Kong SAR
| | - Karen K L Chan
- Department of Obstetrics and Gynecology, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, Hong Kong SAR
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Seckl MJ, Sebire NJ, Fisher RA, Golfier F, Massuger L, Sessa C. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 Suppl 6:vi39-50. [PMID: 23999759 DOI: 10.1093/annonc/mdt345] [Citation(s) in RCA: 215] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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Bagga R, Siwatch S, Srinivasan R, Dhaliwal LK. Surveillance without chemotherapy in a woman with recurrent molar pregnancy. BMJ Case Rep 2013; 2013:bcr2012008128. [PMID: 23429019 PMCID: PMC3603678 DOI: 10.1136/bcr-2012-008128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 27-year-old fouth gravida patient with previous two partial molar pregnancies and one missed abortion underwent a suction evacuation for partial molar pregnancy at 9 weeks of gestation. She was followed up with serum HCG values. Though the HCG level reduced from a pre-evacuation value of 1 40 223-31 157 mIU/ml 1 week post procedure, the levels continued to be positive in low titres 6 months after suction evacuation. The management options were discussed with the patient and a decision was taken to continue surveillance with serial HCG titres. HCG levels normalised after 11 months without the need for chemotherapy.
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Affiliation(s)
- Rashmi Bagga
- Department of Obstetrics & Gynecology, PGIMER, Chandigarh, India
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