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Cioffi R, Fruscio R, Sabetta G, Bergamini A, Dell'Oro C, Scarfone G, Danese S, Cormio G, Ferrandina G, Pignata S, Mangili G. Consolidation courses in low-risk gestational trophoblastic neoplasia and relapse rate: A MITO-9 retrospective study. Gynecol Oncol 2025; 196:54-58. [PMID: 40179516 DOI: 10.1016/j.ygyno.2025.03.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 03/13/2025] [Accepted: 03/23/2025] [Indexed: 04/05/2025]
Abstract
OBJECTIVE Methotrexate (MTX) is the gold standard treatment for gestational trophoblastic neoplasia (GTN). It is administered until negative human chorionic gonadotropin (hCG) levels, after which consolidation courses are recommended. Aim of this study was to evaluate the relationship between number of consolidation courses and relapse rate. METHODS Patients with low-risk GTN treated with first-line MTX between 1981 and 2022 in Italy were retrospectively identified. Exclusion criteria were exclusive surgical treatment, missing data on number of courses or non-standardized definitions of chemoresistance. RESULTS Among 435 low-risk GTN patients, 333 were eligible. A total of 224 (67.2 %) patients achieved remission after treatment with first-line MTX. Forty-one patients (17.4 %) underwent 2 consolidation courses and had no relapse; 132 (56.1 %) received 3 consolidation courses with a relapse rate of 2.2 %; 39 patients (16.5 %) received more than 3 consolidation courses with a relapse rate of 10.2 %. Ninety-five percent of patients undergoing 2 consolidation courses had a FIGO score ≤ 4. Multivariate analysis showed that number of consolidation courses is not related to disease relapse in patients scoring 0-2. CONCLUSIONS Number of consolidation courses in low-risk GTN does not impact relapse rate. Our study demonstrates that patients with FIGO scores of 0,1 and 2 can safely receive 2 consolidation courses. Further studies should investigate the appropriate number of consolidation courses in patients with higher scores.
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Affiliation(s)
- Raffaella Cioffi
- Department of Gynecological Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
| | - Robert Fruscio
- Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy; UO Gynecology, IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Giulia Sabetta
- Department of Gynecological Oncology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Alice Bergamini
- Department of Gynecological Oncology, IRCCS San Raffaele Hospital, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Cristina Dell'Oro
- Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy; UO Gynecology, IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Giovanna Scarfone
- Obstetrics and Gynecology Unit, IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Saverio Danese
- Obstetrics and Gynecology Unit, Ospedale S. Anna, Turin, Italy
| | - Gennaro Cormio
- Gynecologic Oncology Unit, Istituto Tumori "Giovanni Paolo II" and University of Bari, Italy
| | - Gabriella Ferrandina
- Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS -Università Cattolica del Sacro Cuore, Rome, Italy
| | - Sandro Pignata
- Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples, Italy
| | - Giorgia Mangili
- Department of Gynecological Oncology, IRCCS San Raffaele Hospital, Milan, Italy
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Zhong L, Yin R, Li Q, Wang D, Song L. The clinical characteristics and prognostic analysis of 35 postterm choriocarcinomas. BMC Cancer 2025; 25:255. [PMID: 39948554 PMCID: PMC11827171 DOI: 10.1186/s12885-025-13645-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
OBJECTIVE Postterm choriocarcinoma is rare and seldom reported. Patients with postterm choriocarcinoma have unfavorable outcomes. Thus, we conducted a retrospective study to better understand this disease. METHODS Thirty-five patients with postterm choriocarcinoma who received treatment at West China Second University Hospital from January 2011 to August 2022 were enrolled. RESULTS The most common symptom in our cohort was abnormal uterine bleeding (25/35, 71.4%). Interval to diagnosis, serum β-hCG, and FIGO score or FIGO stage were not related to recurrence (P = 0.523, P = 0.812, P = 0.343, P = 0.440). However, the number of chemotherapy courses before achieving normal β-hCG (crude hazard ratio [HR] [95% confidence interval [CI]: 1.15 [1.04-1.26], P = 0.007) was positively related to recurrence, while the number of consolidation chemotherapy courses was negatively related to recurrence (crude HR [95% CI]: 0.51 [0.30-0.88], P = 0.015). Patients who received EMA-CO had a lower risk of recurrence, but the difference was not statistically significant (crude HR [95% CI]: 0.41 [0.08-2.06], P = 0.281). Patients who received other regimens (other than EMA-CO or 5-FU + Act-D) had a significantly higher risk of recurrence (crude HR [95% CI]: 8.30 [1.61-42.78], P = 0.011). CONCLUSIONS The complete remission rate of postterm choriocarcinoma was 88.6% in our study. Serum β-hCG surveillance and/or pathological examination of curettage might lead to an earlier diagnosis. The number of consolidation chemotherapy courses was negatively related to recurrence. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Lan Zhong
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20 The third section of South Renmin Road, Chengdu, 610041, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Rutie Yin
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20 The third section of South Renmin Road, Chengdu, 610041, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Qingli Li
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20 The third section of South Renmin Road, Chengdu, 610041, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Danqing Wang
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20 The third section of South Renmin Road, Chengdu, 610041, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Liang Song
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20 The third section of South Renmin Road, Chengdu, 610041, Sichuan, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
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Mandava A, Koppula V, Kandati M, Reddy AK, Rajappa SJ, Rao TS. Multimodality Imaging in the Diagnosis and Staging of Gestational Choriocarcinoma. Indian J Radiol Imaging 2025; 35:148-158. [PMID: 39697498 PMCID: PMC11651844 DOI: 10.1055/s-0044-1788590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024] Open
Abstract
Choriocarcinoma is an uncommon, highly invasive malignancy arising from the placental trophoblastic tissue. Though staging is clinical, imaging has significant role in the diagnosis, staging, prognostic risk scoring, and management of choriocarcinomas. The purpose of this article is to review the role of multimodality imaging in the diagnosis, staging, and management of choriocarcinomas in correlation with clinicopathologic findings.
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Affiliation(s)
- Anitha Mandava
- Department of Radiodiagnosis, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
| | - Veeraiah Koppula
- Department of Radiodiagnosis, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
| | - Meghana Kandati
- Department of Radiodiagnosis, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
| | - Arvind K. Reddy
- Department of Radiodiagnosis, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
| | - Senthil J. Rajappa
- Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
| | - T. S. Rao
- Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
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Brawley A, Moffitt C, Bruce SF, Farabaugh CS, Podczaski E, Sorosky J. Use of a PD-1 checkpoint inhibitor in a patient with ultra-high-risk gestational trophoblastic neoplasia and gastrointestinal metastases. Gynecol Oncol Rep 2024; 56:101530. [PMID: 39494392 PMCID: PMC11530858 DOI: 10.1016/j.gore.2024.101530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 10/07/2024] [Accepted: 10/10/2024] [Indexed: 11/05/2024] Open
Abstract
Gestational trophoblastic neoplasia (GTN) are rare diseases that are typically chemo-responsive. While the majority of patients are cured with chemotherapy alone, a small portion of cases are fatal due to chemotherapy resistance. Risk factors for treatment failure are liver and brain metastases, extensive disease, and chemo-refractory disease. Gastrointestinal (GI) metastases are extremely rare and indicate a poor prognosis. Treatment with immunotherapy has been studied and included in treatment guidelines for high-risk and chemotherapy-resistant GTN. This case reports on the early use of programmed cell death protein 1 (PD-1) inhibitor in combination with systemic chemotherapy in a patient with ultra-high risk GTN with GI metastases.
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Affiliation(s)
- Amalia Brawley
- Department of Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H103 Hershey, PA, United States
| | - Casey Moffitt
- Department of Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H103 Hershey, PA, United States
| | - Shaina Feldman Bruce
- Department of Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H103 Hershey, PA, United States
| | - Caitlin Stashwick Farabaugh
- Department of Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H103 Hershey, PA, United States
| | - Edward Podczaski
- Department of Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H103 Hershey, PA, United States
| | - Joel Sorosky
- Department of Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H103 Hershey, PA, United States
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Akhavan S, Hoorshad N, Mousavi AS, Sheikhhasani S, Rezayof E, Zamani N. The role of single-dose prophylactic methotrexate in the prevention of post-molar gestational trophoblastic neoplasia in patients with high-risk molar pregnancy. BMC Cancer 2024; 24:1400. [PMID: 39538177 PMCID: PMC11562075 DOI: 10.1186/s12885-024-13162-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
INTRODUCTION Prophylactic chemotherapy (PC) has been suggested to be effective in prevention of post molar gestational trophoblastic neoplasia (PGTN) in patients with high-risk molar pregnancies. The goal of this study is to assess the efficacy of single dose methotrexate as PC in terms of spontaneous remission, time to remission, and progression to PGTN. MATERIALS AND METHODS Patients with molar pregnancy were recruited to the study and underwent cervical dilation and suction curettage. Patients who had pathologically proven complete hydatidiform mole were evaluated with abdominal ultrasonography to confirm complete evacuation and absence of remnants. These patients were allocated to two groups: group one received Methotrexate 50 mg/m2 via intramuscular injection, while group two did not. PGTN was defined according to the 2018 FIGO criteria. For patients with confirmed PGTN, the following variables were recorded: occurrence of metastasis, resistance to first-line chemotherapy and time to βHCG level normalization. RESULTS Eighty patients were enrolled to the study, of which 22 cases (27.5%) received PC. It was found that PC with MTX did not significantly influence spontaneous remission (18 (81.8%) Vs 37 (63.7%), p value: 0.12) or time to remission (57 ± 22.5 Vs 61.24 ± 21.78 days, p value: 0.46) in high-risk molar pregnancies. Moreover, among patients in PC group and control group, 4 cases (18.2%) and 21 patients (36.3%) progressed to PGNT, respectively (p value: 0.12). Although patients in PC group tended to be diagnosed in lower stages compared to patients in control group, this difference was insignificance (p value: 0.95). Among patients who developed to PGTN, PC did not reduce the frequency of metastatic disease, resistance to first-line chemotherapy, or the time interval to serum βHCG level normalization (all p values > 0.05). CONCLUSION This study suggests that a single-dose MTX as PC may not be an effective therapeutic option for preventing PGTN in patients with high-risk molar pregnancy.
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Affiliation(s)
- Setareh Akhavan
- Department of Gynecologic Oncology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloufar Hoorshad
- Department of Obstetrics and Gynecology, Tehran University of Medical Sciences, Tehran, Iran
| | - Azam Sadat Mousavi
- Department of Gynecologic Oncology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahrzad Sheikhhasani
- Department of Gynecologic Oncology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Elahe Rezayof
- Vali-E-Asr Reproductive Health Research Center,Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Narges Zamani
- Department of Gynecologic Oncology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
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Mitric C, Yang K, Bhat G, Lheureux S, Laframboise S, Li X, Bouchard-Fortier G. Gestational trophoblastic neoplasia: does centralization of care impact clinical management? Int J Gynecol Cancer 2023; 33:1724-1732. [PMID: 37723102 DOI: 10.1136/ijgc-2023-004526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2023] Open
Abstract
OBJECTIVE International societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of trophoblastic care on clinical outcomes. METHODS A centralized program was implemented in 2018 at two affiliated academic hospitals, Princess Margaret Cancer Center and Mount Sinai Hospital. A retrospective analysis of patients treated between 2000 and 2022 was performed and the clinical outcomes were compared before (2000-2017) and after (2018-2022) centralization. Statistical analyses were performed with significance set as p<0.05. RESULTS A total of 94 patients with trophoblastic neoplasia were included: 60 pre-centralization and 34 post-centralization, 79.8% low-risk and 18.1% high-risk. Centralization led to significant improvement for: (1) accurate score documentation (from 37.9% to 89.3%,); (2) contraception counseling (from 67.2% to 96.7%); (3) median time from diagnosis to chemotherapy (from 9 days to 1 day); and (4) incomplete follow-up (from 20.7% to 3.3%) (all p<0.05). First-line chemotherapy for low-risk neoplasia was dactinomycin in 47.9% and 87.0% pre- and post-centralization, respectively (p=0.005). The median number of chemotherapy cycles decreased from seven to four (p=0.01), and the median number of consolidation cycles increased from two to three (p<0.001). Serum human chorionic gonadotropin (hCG) levels of 10 000-100 000 IU/L were significantly associated with longer time to hCG normalization and higher risk of resistance to first-line chemotherapy compared with hCG levels <1000 IU/L. CONCLUSION Centralization of trophoblastic neoplasia care leads to greater guideline compliance, faster chemotherapy initiation, fewer chemotherapy cycles with optimized consolidation, and enhanced surveillance completion. This supports the establishment of trophoblastic neoplasia expert centers.
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Affiliation(s)
- Cristina Mitric
- Sinai Health, Toronto, Ontario, Canada
- Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
- Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
| | - Kelsey Yang
- Sinai Health, Toronto, Ontario, Canada
- Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
- Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
| | - Gita Bhat
- Medical Oncology, Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
| | - Stephanie Lheureux
- Medical Oncology, Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
| | - Stephane Laframboise
- Sinai Health, Toronto, Ontario, Canada
- Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
- Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
| | - Xuan Li
- Department of Biostatistics, Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
| | - Geneviève Bouchard-Fortier
- Sinai Health, Toronto, Ontario, Canada
- Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
- Princess Margaret Cancer Centre/ University Health Network, Toronto, Ontario, Canada
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Bogani G, Ray-Coquard I, Mutch D, Vergote I, Ramirez PT, Prat J, Concin N, Ngoi NYL, Coleman RL, Enomoto T, Takehara K, Denys H, Lorusso D, Takano M, Sagae S, Wimberger P, Segev Y, Kim SI, Kim JW, Herrera F, Mariani A, Brooks RA, Tan D, Paolini B, Chiappa V, Longo M, Raspagliesi F, Benedetti Panici P, Di Donato V, Caruso G, Colombo N, Pignata S, Zannoni G, Scambia G, Monk BJ. Gestational choriocarcinoma. Int J Gynecol Cancer 2023; 33:1504-1514. [PMID: 37758451 DOI: 10.1136/ijgc-2023-004704] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.
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Affiliation(s)
- Giorgio Bogani
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Isabelle Ray-Coquard
- Centre Leon Berard, LYON CEDEX 08, France
- Hesper lab, Université Claude Bernard Lyon 1, Villeurbanne, France
| | - David Mutch
- Washington University in Saint Louis, St Louis, Missouri, USA
| | - Ignace Vergote
- Department of Gynecology and Obstetrics, Gynecologic Oncology, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium
| | - Pedro T Ramirez
- Department of Obstetrics and Gynecology, Houston Methodist Hospital, Houston, Texas, USA
| | - Jaime Prat
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Nicole Concin
- Department of Gynecology and Obstetrics; Innsbruck Medical Univeristy, Innsbruck, Austria
| | | | | | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Belgium
| | - Kazuhiro Takehara
- Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | | | | | - Masashi Takano
- Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Japan
| | - Satoru Sagae
- Gynecologic Oncology, Tokeidai Kinen Byoin, Sapporo, Japan
| | - Pauline Wimberger
- Gyncology and Obstetrics, Technische Universitat Dresden Medizinische Fakultat Carl Gustav Carus, Dresden, Germany
| | - Yakir Segev
- Obstetrics and Gynecology, Carmel Hospital, Haifa, Israel
| | - Se Ik Kim
- Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea (the Republic of)
| | - Jae-Weon Kim
- Obstetrics and gynecology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | - Fernanda Herrera
- Centre Hospitalier Universitaire Vaudois Departement doncologie CHUV-UNIL, Lausanne, Switzerland
| | - Andrea Mariani
- Gynecologic Surgery, Mayo Clinic Rochester, Rochester, Minnesota, USA
| | - Rebecca A Brooks
- Section of Gynecologic Oncology, University of Chicago Medicine, Chicago, Illinois, USA
| | - David Tan
- National University Cancer Institute, Singapore
| | - Biagio Paolini
- Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy
| | - Valentina Chiappa
- Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy
| | | | | | | | | | | | - Nicoletta Colombo
- Medical Gynecologic Oncology Unit; University of Milan Bicocca; Milan; Italy, European Institute of Oncology, Milano, Italy
| | - Sandro Pignata
- Gynaecological Oncology, National Cancer Institute Napels, Naples, Italy
| | - Gianfranco Zannoni
- Dipartimento Scienze della Salute della Donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giovanni Scambia
- Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Bradley J Monk
- Virginia G Piper Cancer Center - Biltmore Cancer Center, Phoenix, Arizona, USA
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Paydas S. Immune checkpoint inhibitor using in cases with gestational trophoblastic diseases. Med Oncol 2023; 40:106. [PMID: 36823367 DOI: 10.1007/s12032-022-01941-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 12/24/2022] [Indexed: 02/25/2023]
Abstract
Gestational trophoblastic neoplasias (GTNs) are chemosensitive disorders with very high cure rates. However, individuals with chemoresistant diseases pass away as a result of their illness, necessitating the use of innovative medications. Immune checkpoint inhibitors (ICIs) are a critical component of the strategy for the management of drug-resistant GTD due to the high rate of PD-1 expression and the paternal genetic inheritance in GTNs. Immunotherapy is mentioned as a potential therapeutic approach for chemotherapy-resistant GTD in the most recent worldwide recommendations. However, multicenter worldwide collaborative studies are required to give additional evidence to detect and identify prognostic markers due to the rarity of GTDs and the dearth of data in the literature.
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Affiliation(s)
- Semra Paydas
- Dept of Medical Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey.
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Gestational trophoblastic disease: an update. ABDOMINAL RADIOLOGY (NEW YORK) 2023; 48:1793-1815. [PMID: 36763119 DOI: 10.1007/s00261-023-03820-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 02/11/2023]
Abstract
Gestational trophoblastic diseases (GTD) encompass a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue. This updated review will highlight important radiological features, pathology and classification, and provide insight into the clinical management of these uncommon disorders. There is a wide geographic variation with the incidence of hydatidiform mole varying between 0.57 and 2 per 1000 pregnancies. The use of ultrasound (US) in the management of early pregnancy symptoms and complications has positively impacted the earlier detection of these diseases and resulted in diminished morbidity. Additional imaging modalities are reserved for problem solving or assessment of pulmonary manifestations of molar pregnancy. Having an awareness of their pleomorphic sonographic presentation and additional pathology that can mimic GTD is critical to avoiding pitfalls. Histologic and molecular analysis further aids in differential diagnosis. Gestational trophoblastic neoplasia (GTN) is inclusive of all malignant GTDs, and arises after 20% of molar pregnancies but can also be seen with non-molar gestations. Biochemical monitoring with human chorionic gonadotrophin is imperative for ongoing monitoring and surveillance and allows early detection of this entity. Doppler US is used for confirmation of diagnosis with magnetic resonance imaging (MRI) reserved for problem solving or assessment of myometrial invasion. This is of heightened relevance in patients undergoing surgical management. Cross sectional imaging is reserved for patients in the setting of GTN for the purposes of staging, prognostication and in the setting of recurrent disease. This may require a combination of computed tomography, MRI and positron emission tomography. Doppler US can provide insight into chemotherapeutic response/predict resistance in patients with GTN. As our understanding of these disorders evolves, there has been maturation in management options with a shift from traditional chemotherapy to innovative immunotherapy, particularly in the setting of resistant or high-risk disease.
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Liu Y, Ye Y, Cheng X, Lu W, Xie X, Wang X, Li X. The effect of prophylactic chemotherapy on treatment outcome of postmolar gestational trophoblastic neoplasia. BMC Womens Health 2023; 23:1. [PMID: 36593459 PMCID: PMC9806869 DOI: 10.1186/s12905-022-02134-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/16/2022] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE To evaluate whether prophylactic chemotherapy (P-chem) increased the drug resistance rate of postmolar GTN and whether the first-line chemotherapy should be different from P-chem. METHODS Postmolar GTN received P-Chem was defined as P-Chem group. Postmolar GTN without P-chem was randomly selected as control group according to the ratio of 1:3 (P-chem:control) and matched by age for low risk and high risk GTN separately. RESULTS Totally 455 low-risk and 32 high-risk postmolar GTN patients were included. WHO risk score, chemotherapy cycles to achieve hCG normalization and resistant rate were similar between P-chem (27 cases) and control (81 cases) group. Among low-risk GTN patients, interval from hydatidiform mole to GTN was significantly longer in P-chem group than control (44 vs 69 days, P = 0.001). Total chemotherapy cycles and resistant rate were similar between low-risk GTN treated with same agent as P-chem (group A) and alternative agent (group B). But group A needed more chemotherapy cycles to achieve hCG normalization than group B. CONCLUSIONS P-chem delayed the time to GTN diagnosis, but didn't increase risk score or lead to drug resistance of postmolar GTN. Alternative agent different from P-chem had the potential of enhancing chemotherapy response in low- risk postmolar GTN.
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Affiliation(s)
- Yuanyuan Liu
- grid.13402.340000 0004 1759 700XDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang China ,grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,grid.13402.340000 0004 1759 700XCancer Research Institute of Zhejiang University, Hangzhou, Zhejiang China
| | - Yaqiong Ye
- grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,Ninghai Second People’s Hospital, Ninghai, 315600 Zhejiang China
| | - Xiaodong Cheng
- grid.13402.340000 0004 1759 700XDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang China ,grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,grid.13402.340000 0004 1759 700XCancer Research Institute of Zhejiang University, Hangzhou, Zhejiang China
| | - Weiguo Lu
- grid.13402.340000 0004 1759 700XDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang China ,grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,grid.13402.340000 0004 1759 700XCancer Research Institute of Zhejiang University, Hangzhou, Zhejiang China ,Center for Uterine Cancer Diagnosis and Therapy Research of Zhejiang Province, Hangzhou, 310006 Zhejiang China
| | - Xing Xie
- grid.13402.340000 0004 1759 700XDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang China ,grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,grid.13402.340000 0004 1759 700XCancer Research Institute of Zhejiang University, Hangzhou, Zhejiang China
| | - Xinyu Wang
- grid.13402.340000 0004 1759 700XDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang China ,grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,grid.13402.340000 0004 1759 700XCancer Research Institute of Zhejiang University, Hangzhou, Zhejiang China
| | - Xiao Li
- grid.13402.340000 0004 1759 700XDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang China ,grid.13402.340000 0004 1759 700XZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China ,grid.13402.340000 0004 1759 700XCancer Research Institute of Zhejiang University, Hangzhou, Zhejiang China
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11
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Weikel K, Watkins E. Gestational Trophoblastic Disease and Neoplasia. PHYSICIAN ASSISTANT CLINICS 2022. [DOI: 10.1016/j.cpha.2022.02.008] [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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12
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Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN). Cancers (Basel) 2022; 14:cancers14112782. [PMID: 35681761 PMCID: PMC9179472 DOI: 10.3390/cancers14112782] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/26/2022] [Accepted: 06/01/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Gestational trophoblastic neoplasia (GTN) is a rare tumor group that arises from the malignant transformation of placental tissue. Based on the evaluation of International Federation of Gynecology and Obstetrics (FIGO) anatomic staging and FIGO prognostic score, GTN is divided into low-, high-, and ultra-high-risk groups if the score obtained is less than or equal to 6, greater than 6 or greater than 12, respectively. The standard treatment is chemotherapy, using a single agent in low-risk disease and multiagent chemotherapy in high- and ultra-high-risk GTN. In chemoresistant forms of GTN, the use of immune checkpoint inhibitors, such as anti-PD-1 or anti-PD-L1/2, could represent a new therapeutic strategy. In this study, we evaluate the available evidence on immune checkpoint inhibitors for GTN treatment. Abstract Background: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. Methods: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. Results: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. Conclusions: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.
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13
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Wang Y, Wang Z, Zhu X, Wan Q, Han P, Ying J, Qian J. Intestinal metastasis from choriocarcinoma: a case series and literature review. World J Surg Oncol 2022; 20:173. [PMID: 35650620 PMCID: PMC9158317 DOI: 10.1186/s12957-022-02623-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 04/04/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Gestational choriocarcinoma is a rare trophoblastic tumor that spreads mainly to the lung, liver, and central nervous system. Fewer than 5% of patients present with metastasis to the gastrointestinal system and have a poor prognosis CASE PRESENTATION: We describe four cases of patients with intestinal metastasis from choriocarcinoma who visited the First Affiliated Hospital of Zhejiang University School of Medicine and the First People's Hospital of Hangzhou between April 2012 and October 2019. Four patients presented with gastrointestinal symptoms or developed gastrointestinal symptoms during treatment for choriocarcinoma. Three patients had these intestinal lesions surgically removed, and the postoperative pathology results suggested choriocarcinoma. All patients received multiple chemotherapy regimens during treatment for suboptimal human chorionic gonadotropin (hCG) levels; one patient died 22 months after a definitive diagnosis was made, and the other three patients are still undergoing regular follow-up. CONCLUSION Given the low incidence of intestinal metastases from choriocarcinoma, the metastatic route of intestinal metastases from choriocarcinoma remains to be elucidated, and diagnosis mainly depends on pathology findings. An effective treatment has not been determined, and surgical excision with chemotherapy is generally accepted.
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Affiliation(s)
- Yuting Wang
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhe Wang
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaoxu Zhu
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qihong Wan
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Peilin Han
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jun Ying
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jianhua Qian
- Department of Gynaecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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14
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Bezzi C, Monaco L, Ghezzo S, Mathoux G, Bergamini A, Zambella E, Fallanca F, Samanes Gajate AM, Presotto L, Sabetta G, Mangili G, Cioffi R, Bettinardi V, Gianolli L, Mapelli P, Picchio M. 18F-FDG PET/CT May Predict Tumor Type and Risk Score in Gestational Trophoblastic Disease. Clin Nucl Med 2022; 47:525-531. [PMID: 35353763 DOI: 10.1097/rlu.0000000000004135] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
PURPOSE The aim of this study was to investigate the role of 18F-FDG PET/CT in predicting pathological prognostic factors, including tumor type and International Federation of Gynecology and Obstetrics (FIGO) score, in gestational trophoblastic disease (GTD). METHODS Retrospective monocentric study including 24 consecutive patients who underwent to 18F-FDG PET/CT from May 2005 to March 2021 for GTD staging purpose. The following semiquantitative PET parameters were measured from the primary tumor and used for the analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolisis (TLG). Statistical analysis included Spearman correlation coefficient to evaluate the correlations between imaging parameters and tumor type (nonmolar trophoblastic vs postmolar trophoblastic tumors) and risk groups (high vs low, defined according to the FIGO score), whereas area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive value of the PET parameters. Mann-Whitney U test was used to further describe the parameter's potential in differentiating the populations. RESULTS SUVmax and SUVmean resulted fair (AUC, 0.783; 95% confidence interval [CI], 0.56-0.95) and good (AUC, 0.811; 95% CI, 0.59-0.97) predictors of tumor type, respectively, showing a low (ρ = 0.489, adjusted P = 0.030) and moderate (ρ = 0.538, adjusted P = 0.027) correlation. According to FIGO score, TLG was instead a fair predictor (AUC, 0.770; 95% CI, 0.50-0.99) for patient risk stratification. CONCLUSIONS 18F-FDG PET parameters have a role in predicting GTD pathological prognostic factors, with SUVmax and SUVmean being predictive for tumor type and TLG for risk stratification.
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Affiliation(s)
| | | | | | | | | | | | - Federico Fallanca
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
| | | | - Luca Presotto
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
| | - Giulia Sabetta
- Unit of Obstetrics and Gynaecology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giorgia Mangili
- Unit of Obstetrics and Gynaecology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Raffaella Cioffi
- Unit of Obstetrics and Gynaecology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Luigi Gianolli
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
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15
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Georgiou M, Ntavelou P, Stokes W, Roy R, Maher GJ, Stoilova T, Rakhit CP, Martins M, Ajuh P, Horowitz N, Berkowitz RS, Elias K, Seckl MJ, Pardo OE. ATR and CDK4/6 inhibition target the growth of methotrexate-resistant choriocarcinoma. Oncogene 2022; 41:2540-2554. [PMID: 35301407 PMCID: PMC9054653 DOI: 10.1038/s41388-022-02251-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 11/12/2021] [Accepted: 02/15/2022] [Indexed: 11/10/2022]
Abstract
Low-risk gestational trophoblastic neoplasia including choriocarcinoma is often effectively treated with Methotrexate (MTX) as a first line therapy. However, MTX resistance (MTX-R) occurs in at least ≈33% of cases. This can sometimes be salvaged with actinomycin-D but often requires more toxic combination chemotherapy. Moreover, additional therapy may be needed and, for high-risk patients, 5% still die from the multidrug-resistant disease. Consequently, new treatments that are less toxic and could reverse MTX-R are needed. Here, we compared the proteome/phosphoproteome of MTX-resistant and sensitive choriocarcinoma cells using quantitative mass-spectrometry to identify therapeutically actionable molecular changes associated with MTX-R. Bioinformatics analysis of the proteomic data identified cell cycle and DNA damage repair as major pathways associated with MTX-R. MTX-R choriocarcinoma cells undergo cell cycle delay in G1 phase that enables them to repair DNA damage more efficiently through non-homologous end joining in an ATR-dependent manner. Increased expression of cyclin-dependent kinase 4 (CDK4) and loss of p16Ink4a in resistant cells suggested that CDK4 inhibition may be a strategy to treat MTX-R choriocarcinoma. Indeed, inhibition of CDK4/6 using genetic silencing or the clinically relevant inhibitor, Palbociclib, induced growth inhibition both in vitro and in an orthotopic in vivo mouse model. Finally, targeting the ATR pathway, genetically or pharmacologically, re-sensitised resistant cells to MTX in vitro and potently prevented the growth of MTX-R tumours in vivo. In short, we identified two novel therapeutic strategies to tackle MTX-R choriocarcinoma that could rapidly be translated into the clinic.
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Affiliation(s)
- Marina Georgiou
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
| | - Panagiota Ntavelou
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
| | - William Stokes
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
| | - Rajat Roy
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
| | - Geoffrey J Maher
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
| | - Tsvetana Stoilova
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
| | | | - Miguel Martins
- MRC Toxicology Unit, University of Cambridge, Cambridge, UK
| | | | - Neil Horowitz
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Ross S Berkowitz
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Kevin Elias
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Michael J Seckl
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK.
| | - Olivier E Pardo
- Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK.
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16
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Phianpiset R, Ruengkhachorn I, Kuljarusnont S, Jareemit N, Udompunturak S. Predictive factors associated with resistance to initial methotrexate treatment in women with low-risk gestational trophoblastic neoplasia. Asia Pac J Clin Oncol 2022; 18:e495-e506. [PMID: 35253996 DOI: 10.1111/ajco.13774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 01/31/2022] [Indexed: 11/30/2022]
Abstract
AIM To compare clinical characteristics and identify factors predictive of resistance to initial treatment with methotrexate-folinic acid (MTX-FA) in women with low-risk gestational trophoblastic neoplasia (GTN). METHODS Retrospective chart reviews were conducted in patients diagnosed with low-risk GTN who were treated with MTX-FA at Siriraj Hospital between 2002 and 2018. Demographic data, disease characteristics, treatment response, toxicity, and data of the subsequent pregnancy were collected and analyzed. Groups of patients who were responsive or resistant to treatment were compared. Stepwise logistic regression analysis was used to identify factors predictive of resistance to methotrexate chemotherapy. RESULTS Totally, 113 patients were eligible for analysis. The primary remission rate was 55.8% with first-line MTX-FA. All other patients achieved remission by subsequent treatment with actinomycin D or multiple-agent chemotherapy. Relapse of disease occurred in 4.4% and the overall survival rate was 99.1%. Univariate analysis showed that pretreatment serum hCG, neutrophil-to-lymphocyte ratio at baseline, and serum hCG ratio of the first three consecutive cycles (C) were significantly associated with resistance to MTX-FA. Independent factors that predict failure to respond to first-line MTX-FA were pretreatment serum hCG ≥15,000 IU/L, a less than 4.8-fold reduction of serum hCG between cycle 1 and cycle 2 (C1/C2), and a less than seven-fold reduction of serum hCG from cycle 2 to cycle 3 (C2/C3). CONCLUSIONS First-line MTX-FA treatment is effective in 55.8% of patients. Pretreatment serum hCG, and serum hCG ratio between consecutive treatment cycles can predict initial treatment failure.
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Affiliation(s)
- Rattiya Phianpiset
- Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.,Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Irene Ruengkhachorn
- Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sompop Kuljarusnont
- Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nida Jareemit
- Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Suthipol Udompunturak
- Clinical Epidemiology Clinic, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Wallin E, Niemann I, Faaborg L, Fokdal L, Joneborg U. Differences in Administration of Methotrexate and Impact on Outcome in Low-Risk Gestational Trophoblastic Neoplasia. Cancers (Basel) 2022; 14:cancers14030852. [PMID: 35159119 PMCID: PMC8834333 DOI: 10.3390/cancers14030852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 12/10/2022] Open
Abstract
Simple Summary Low-risk gestational trophoblastic neoplasia is a rare but highly curable malignancy. The most common first line treatment is methotrexate, which can be administered in different forms. In order to investigate the impact of route of administration on methotrexate resistance, toxicity demanding treatment switch, complete remission and relapse, we performed an observational study including women with low-risk gestational trophoblastic neoplasia in a population-based setting in Sweden and Denmark. We found that oral compared to intra-muscular administration of methotrexate gives a higher rate of drug resistance, but does not affect rates of complete remission, recurrence or overall survival. Intra-muscular treatment was associated with more toxicity leading to switch of treatment. We conclude that, although a larger proportion of women develop drug resistance, oral methotrexate, which is easy to administer and highly tolerable, could be an option for well-informed and motivated women. Abstract Methotrexate (MTX) is frequently used as first-line treatment for low-risk gestational trophoblastic neoplasia (GTN). Intravenous and intramuscular (im) routes of administration are the most common methods, although oral administration is used by some Scandinavian centers. The primary aim of this study was to assess the impact of form of administration (im/oral) on resistance to methotrexate (MTX-R) treatment in low-risk GTN. Secondary aims were time to hCG normalization, rates of toxicity-induced treatment switch, and rates of complete remission and recurrence. In total, 170 women treated at Karolinska University Hospital in Sweden and Aarhus University Hospital in Denmark between 1994 and 2018 were included, of whom 107 were given im and 63 oral MTX. MTX-R developed in 35% and 54% in the im and oral groups, respectively (p = 0.01). There was no difference in days to hCG normalization (42 vs. 41 days, p = 0.50) for MTX-sensitive women. Toxicity-induced treatment switch was only seen in the im group. Complete remission was obtained in 99.1% and 100% (p = 0.44), and recurrence rate within one year was 2.8% and 1.6% (p = 0.29). The form of administration of MTX had a significant impact on development of MTX-R and treatment-associated toxicity, but does not affect rates of complete remission, recurrence or survival.
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Affiliation(s)
- Emelie Wallin
- Department of Women’s and Children’s Health, Karolinska Institutet, 171 21 Stockholm, Sweden;
- Department of Pelvic Cancer, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Isa Niemann
- Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark;
- Department of Obstetrics and Gynecology, Aarhus University Hospital, 8200 Aarhus, Denmark
| | - Louise Faaborg
- Department of Oncology, Vejle Hospital, 7100 Vejle, Denmark;
| | - Lars Fokdal
- Department of Oncology, Aarhus University Hospital, 8200 Aarhus, Denmark;
| | - Ulrika Joneborg
- Department of Women’s and Children’s Health, Karolinska Institutet, 171 21 Stockholm, Sweden;
- Correspondence:
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Tsai J, Vellayappan B, Venur V, McGranahan T, Gray H, Urban RR, Tseng YD, Palmer J, Foote M, Mayr NA, Combs SE, Sahgal A, Chang EL, Lo SS. The optimal management of brain metastases from gestational trophoblastic neoplasia. Expert Rev Anticancer Ther 2022; 22:307-315. [PMID: 35114862 DOI: 10.1080/14737140.2022.2038566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Gestational trophoblastic diseases and neoplasias (GTDs and GTNs) comprise a spectrum of diseases arising from abnormally proliferating placental/trophoblastic tissue following an antecedent molar or non-molar pregnancy. These can spread to the brain hematogenously in about 10% of patients, mostly in high-risk disease. The optimal management of patients with brain metastases from GTN is unclear, with multiple systemic regimens under use and an uncertain role for radiotherapy. AREAS COVERED Here, we review the epidemiology, workup, and treatment of GTN with central nervous system (CNS) involvement. Literature searches in PubMed and Google Scholar were conducted using combinations of keywords such as "gestational trophoblastic disease," "gestational trophoblastic neoplasia," "choriocarcinoma," and "brain metastases." EXPERT OPINION Systemic therapy is the frontline treatment for GTN with brain metastases, and radiotherapy should only be considered in the context of a clinical trial or for resistant/recurrent disease. Surgery has a limited role in palliating symptoms or relieving intracranial pressure/bleeding. Given the highly specialized care these patients require, treatment at a high-volume referral center with multidisciplinary collaboration likely leads to better outcomes. Randomized trials should be conducted to determine the best systemic therapy option for GTN.
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Affiliation(s)
- Joseph Tsai
- Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195, USA
| | | | - Vyshak Venur
- Alvord Brain Tumor Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Tresa McGranahan
- Alvord Brain Tumor Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Heidi Gray
- Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA, USA
| | - Renata R Urban
- Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA, USA
| | - Yolanda D Tseng
- Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195, USA
| | - Joshua Palmer
- Department of Radiation Oncology, Arthur G. James Cancer Hospital, The Ohio State University, Columbus, OH, USA
| | - Matthew Foote
- Princess Alexandra Hospital, University of Queensland, ICON Cancer Care, Brisbane 4072, Australia
| | - Nina A Mayr
- Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195, USA
| | - Stephanie E Combs
- Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), 81675 Munich, Germany
| | - Arjun Sahgal
- Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON M4N 3M5, Canada
| | - Eric L Chang
- Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
| | - Simon S Lo
- Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195, USA
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Hoeijmakers YM, Eysbouts YK, Massuger LFAG, Dandis R, Inthout J, van Trommel NE, Ottevanger PB, Thomas CMG, Sweep FCGJ. Early prediction of post-molar gestational trophoblastic neoplasia and resistance to methotrexate, based on a single serum human chorionic gonadotropin measurement. Gynecol Oncol 2021; 163:531-537. [PMID: 34602288 DOI: 10.1016/j.ygyno.2021.09.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 09/11/2021] [Accepted: 09/21/2021] [Indexed: 01/26/2023]
Abstract
BACKGROUND Clinicians are unable to provide individualized counseling regarding risk of progression for patients with a complete hydatidiform mole (CHM). We developed nomograms enabling early prediction of post-molar gestational trophoblastic neoplasia (GTN) and resistance to methotrexate (MTX) based on a single serum human chorion gonadotropin (hCG) measurement. METHODS We generated two nomograms with logistic regression: to predict post-molar GTN, and MTX resistance. For patients with high probability to progress to post-molar GTN or MTX resistance, we determined hCG cut-offs at 97.5% specificity to select patients for additional- or adjustments in current treatment. RESULTS The nomograms had a good to excellent ability to distinguish either between patients with uneventful hCG regression versus progression to post molar GTN, or between patients cured by MTX versus patients in whom resistance would occur. At 97.5% specificity, we identified 66% (95%CI 56-75) of the 149 patients who would progress to post-molar GTN, four weeks after initial curettage. For patients treated with MTX, we identified 55% (95%CI 23-83) of the 43 patients who would become resistant, preceding their third course at 97.5% specificity. CONCLUSION The nomograms and cut-off levels can be used to assist in counseling for patients diagnosed with CHM.
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Affiliation(s)
- Yvonne M Hoeijmakers
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
| | - Yalck K Eysbouts
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, Netherlands
| | | | - Rana Dandis
- Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Joanna Inthout
- Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - N E van Trommel
- Center for Gynecologic Oncology Amsterdam, location Antoni van Leeuwenhoek- the Netherlands Cancer Institute, Amsterdam, Netherlands
| | | | - Chris M G Thomas
- Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands
| | - Fred C G J Sweep
- Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands
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Liu X, Pan X, Liu H, Ma X. Gut Microbial Diversity in Female Patients With Invasive Mole and Choriocarcinoma and Its Differences Versus Healthy Controls. Front Cell Infect Microbiol 2021; 11:704100. [PMID: 34513727 PMCID: PMC8428518 DOI: 10.3389/fcimb.2021.704100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/09/2021] [Indexed: 12/12/2022] Open
Abstract
Objective To investigate variation in gut microbiome in female patients with invasive mole (IM) and choriocarcinoma (CC) and compare it with healthy controls. Methods Fecal microbiome of 12 female patients with IM, 9 female patients with CC, and 24 healthy females were analyzed based on 16s rDNA sequencing. Alpha (α) diversity was evaluated using Shannon diversity index and Pielou evenness index, while beta (β) diversity was assessed using principle coordinate analysis (PCoA) of unweighted Unifrac distances. The potential functional changes of microbiomes were predicted using Tax4Fun. The relative abundance of microbial taxa was compared using Welch’s t test. The role of varied gut microbiota was analyzed via receiver operating characteristic (ROC) curve. Results The α diversity and β diversity were significantly different between IM patients and controls, but not between CC patients and controls. In addition, the abundance of cancer-related genes was significantly increased in IM and CC patients. Notably, a total of 19 families and 39 genera were found to have significant differences in bacterial abundance. ROC analysis indicated that Prevotella_7 may be a potential biomarker among IM, CC, and controls. Conclusion Our study demonstrated that the diversity and composition of gut microbiota among IM patients, CC patients, and healthy females were significantly different, which provides rationale for using gut microbiota as diagnostic markers and treatment targets, as well as for further study of gut microbiota in gestational trophoblastic neoplasia (GTN).
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Affiliation(s)
- Xiaomei Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xue Pan
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hao Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoxin Ma
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
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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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Jiang TY, Ren JJ, Zhang Y, Zhao Y, Feng XL. A comparative study of the efficiency and safety of chemotherapy as a therapeutic method for recurrent or resistant gestational trophoblastic neoplasia: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e26263. [PMID: 34128856 PMCID: PMC8213289 DOI: 10.1097/md.0000000000026263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Gestational trophoblastic neoplasia (GTN) is an infrequent spectrum of placental malignant cases. Generally, single-agent or multiple-agent chemotherapy is used to treat the condition. The condition has a significant impact on women in the childbearing age, which makes post-chemo fertility and obstetrical results a significant contemplation. Nearly 25% of GTN tumors are recurrent, or have a likelihood of relapsing after, the first round of chemotherapy. Therefore, these resistive and recurring lesions require salvage chemotherapy with or without surgical treatment. Therefore, the current meta-analysis and systematic review will assess the effectiveness and level of safety when using chemotherapy to treat women with resistive or recurring GTN. METHODS The current study will perform a comprehensive systematic search for randomized controlled trials (RCTs) that have assessed the efficacy and safeness of chemo as a line of treatment for women with resistive or recurring GTN. To this end, a search will be conducted on the following electronic databases: Web of Science, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), EMBASE, WanFang database, and the Cochrane Library. The search will cover the period from the inception of databases to May 2021. In order to identify additional related studies, we will manually search the reference lists of suitable research articles and related systematic reviews. A pair of independent authors will review the titles/abstracts of the studies to check if the studies are eligible, which is proceeded by screening the full texts. This study will employ a uniform data extraction table for data extraction. Moreover, based on the Cochrane Risk of Bias Tool, this protocol review also assesses the bias risk in the studies involved. RESULTS A comprehensive synthesis of existing indication on chemo treatment for women with resistive or recurring GTN. CONCLUSION The results offer fresh references for evaluating the effectiveness and safeness of chemo-based treatment for women with resistive or recurring GTN. ETHICS AND DISSEMINATION An ethical approval is not needed as all data are published. REVIEW REGISTRATION NUMBER May 17, 2021.osf.io/uwky7. (https://osf.io/uwky7/).
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Seckl MJ, Ghorani E. Progress to international harmonisation of care and future developments. Best Pract Res Clin Obstet Gynaecol 2021; 74:159-167. [PMID: 34119435 DOI: 10.1016/j.bpobgyn.2021.05.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 05/18/2021] [Indexed: 01/01/2023]
Abstract
Considerable differences exist in the management of gestational trophoblastic disease (GTD) both nationally and internationally despite numerous efforts to harmonise patient care. This partly reflects differences in healthcare systems and availability of resources. However, even in first world equivalent economies with similar healthcare systems differences remain, which appear to impact survival. Recently, new international guidelines have been established in Europe through a series of consensus meetings. Improvement of outcomes will depend on the establishment of dedicated centres with appropriate patient pathways according to these guidelines. This review will highlight some of the differences and efforts to unify the management of GTD across the globe and discuss areas for future development.
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Affiliation(s)
- Michael J Seckl
- Dept Medical Oncology, Gestational Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College London, Fulham Palace Rd, London W68RF, UK.
| | - Ehsan Ghorani
- Dept Medical Oncology, Gestational Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College London, Fulham Palace Rd, London W68RF, UK
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The many faces of ectopic pregnancies: demystifying the common and less common entities. Abdom Radiol (NY) 2021; 46:1104-1114. [PMID: 32889610 DOI: 10.1007/s00261-020-02681-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/16/2020] [Accepted: 07/21/2020] [Indexed: 12/11/2022]
Abstract
Ectopic pregnancy is a major cause of 1st trimester pregnancy deaths. It occurs in various locations in the abdominopelvic cavity. Ultrasonography is a first-line, rapid, and noninvasive modality for ectopic pregnancy evaluation. MRI can help clarify equivocal cases. When in doubt about the location, one should give an intrauterine pregnancy the benefit of the doubt with close ultrasound and hCG follow-up. Here, we will review the imaging findings and mimickers of ectopic pregnancies.
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Silva ALMD, Monteiro KDN, Sun SY, Borbely AU. Gestational trophoblastic neoplasia: Novelties and challenges. Placenta 2021; 116:38-42. [PMID: 33685753 DOI: 10.1016/j.placenta.2021.02.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 02/18/2021] [Accepted: 02/19/2021] [Indexed: 12/22/2022]
Abstract
Gestational trophoblastic diseases are a group of pregnancy-related disorders, originated from trophoblast cells. They include benign and aggressive tumors, such as the invasive mole, the choriocarcinoma, the placental site trophoblastic tumor (PSTT), and the epithelioid trophoblastic tumor (ETT). These malignancies are characterized as gestational trophoblastic neoplasm (GTN), rarer, although more dangerous. The diagnosis of GTN is made in most cases by monitoring serum chorionic gonadotropin (hCG) with histological confirmation. The use of specific tissue biomarkers has been increasingly employed as a differential diagnosis, leading to more accurate results and different therapy protocols and prognosis for each GTN. The treatment is based on the International Federation of Gynecology and Obstetrics anatomical staging system and the World Health Organization prognostic score system. If an accurate diagnosis is made and the guidelines followed, the cure for choriocarcinoma and invasive mole cases can reach 98%, whereas PSTT and ETT still present mild success rates. The improved knowledge about GTN and its peculiarities allows physicians to efficiently achieve the differential diagnosis and choose the best available therapy protocol, thus increasing the overall survival of affected women. Nevertheless, obtaining epidemiological data and improving knowledge through basic and translational research are essential to answer open questions on GTN physiopathology, their causes, and cellular behavior.
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Affiliation(s)
- Ana Lucia Mendes da Silva
- Cell Biology Laboratory, Institute of Health and Biological Sciences, Federal University of Alagoas, Av. Lourival Melo Mota S/n, 57072-970, Maceio, Brazil
| | | | - Sue Yazaki Sun
- Department of Obstetrics, Universidade Federal de Sao Paulo - UNIFESP, Escola Paulista de Mediina, Sao Paulo, Brazil
| | - Alexandre Urban Borbely
- Cell Biology Laboratory, Institute of Health and Biological Sciences, Federal University of Alagoas, Av. Lourival Melo Mota S/n, 57072-970, Maceio, Brazil.
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Braga A, Elias KM, Horowitz NS, Berkowitz RS. Treatment of high-risk gestational trophoblastic neoplasia and chemoresistance/relapsed disease. Best Pract Res Clin Obstet Gynaecol 2021; 74:81-96. [PMID: 33622563 DOI: 10.1016/j.bpobgyn.2021.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/05/2020] [Accepted: 01/08/2021] [Indexed: 01/01/2023]
Abstract
High-risk gestational trophoblastic neoplasia (GTN) has an increased risk of developing chemoresistance to single-agent chemotherapy; therefore, the primary treatment should be a multiagent etoposide-based regimen, preferably EMA/CO. After remission (normalization of human chorionic gonadotropin - hCG), at least three consolidation courses of EMA-CO are needed to reduce the risk of relapse. Chemoresistance is diagnosed during treatment if hCG levels plateau/increase, in two consecutive values over a two-week period. When this occurs after remission, in the absence of a new pregnancy, there is a relapse. In both cases, after re-assessment of the extent of disease, EMA-EP is the most common chemotherapy choice. Even in these cases, remission rates are high. After remission is achieved, hCG should be measured monthly for a year. Pregnancy can be allowed after 12 months from remission. The follow-up of these patients in referral centers minimizes the chance of death from this disease and should be encouraged.
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Affiliation(s)
- Antonio Braga
- Rio de Janeiro Trophoblastic Disease Center (Maternity School of Rio de Janeiro Federal University and Antonio Pedro University Hospital of Fluminense Federal University), Brazil; Postgraduate Program in Perinatal Health, Faculty of Medicine, Rio de Janeiro, RJ, Brazil; Postgraduate Program in Medical Sciences, Fluminense Federal University, Niterói, RJ, Brazil.
| | - Kevin M Elias
- New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Neil S Horowitz
- New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, 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, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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27
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Di Mattei V, Mazzetti M, Perego G, Cugnata F, Brombin C, Bergamini A, Cioffi R, Vasta F, Pella F, Rabaiotti E, Mangili G, Candiani M. Psychological factors influencing emotional reactions to gestational trophoblastic disease: The role of coping mechanisms and illness perception. Eur J Cancer Care (Engl) 2021; 30:e13404. [PMID: 33459425 DOI: 10.1111/ecc.13404] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 09/30/2020] [Accepted: 12/23/2020] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Referring to Leventhal's common-sense model, this observational cross-sectional study aimed at investigating the relationship between illness mental representations, coping mechanisms and psychological distress in a sample of women with gestational trophoblastic disease (GTD). METHODS Thirty-eight women diagnosed with GTD (18 with hydatidiform mole; 20 with gestational trophoblastic neoplasia) were asked to complete the Illness Perception Questionnaire-Revised, the Coping Orientation to the Problems Experienced, the State-Trait Anxiety Inventory-Form Y and the Beck Depression Inventory-Short Form. Demographic and clinical information was collected through a self-report questionnaire. RESULTS The sample did not report significant symptomatic distress in relation to GTD. Correlation analysis showed that the Emotional representations subscale of the Illness Perception Questionnaire-Revised was significantly associated with both state anxiety and depression; avoidant coping significantly and positively correlated with anxiety and depression, as well as with illness emotional representations. Mediation analysis revealed significant indirect effects of avoidant coping on both anxiety and depression through the mediation of emotional representations. CONCLUSION Avoidant coping could lead women to develop emotional representations of illness characterised by negative affects, which in turn enhance distress levels. Results underline the importance to promote adaptive coping strategies, along with accurate illness perceptions, to foster better psychological adjustment to GTD.
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Affiliation(s)
- Valentina Di Mattei
- Clinical and Health Psychology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,School of Psychology, Vita-Salute San Raffaele University, Milan, Italy
| | - Martina Mazzetti
- Clinical and Health Psychology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gaia Perego
- Department of Psychology, University of Milano-Bicocca, Milan, Italy
| | - Federica Cugnata
- School of Psychology, Vita-Salute San Raffaele University, Milan, Italy.,University Centre for Statistics in the Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, Milan, Italy
| | - Chiara Brombin
- School of Psychology, Vita-Salute San Raffaele University, Milan, Italy.,University Centre for Statistics in the Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, Milan, Italy
| | - Alice Bergamini
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Raffaella Cioffi
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Vasta
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Pella
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuela Rabaiotti
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giorgia Mangili
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Candiani
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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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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Vandewal A, Delbecque K, Van Rompuy AS, Noel JC, Marbaix E, Delvenne P, Nisolle M, Van Nieuwenhuysen E, Kridelka F, Vergote I, Goffin F, Han SN. Curative effect of second curettage for treatment of gestational trophoblastic disease - Results of the Belgian registry for gestational trophoblastic disease. Eur J Obstet Gynecol Reprod Biol 2020; 257:95-99. [PMID: 33383413 DOI: 10.1016/j.ejogrb.2020.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 11/30/2020] [Accepted: 12/03/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVE We assessed the curative effect of a second curettage in patients with persistent hCG serum levels after first curettage for a gestational trophoblastic disease (GTD). STUDY DESIGN This prospective observational study used the data of the Belgian register for GTD between July 2012 and January 2017. We analysed the data of patients who underwent a second curettage. We included 313 patients in the database. Primary endpoints were need for second curettage and chemotherapy. RESULTS Thirty-seven patients of the study population (12 %) underwent a second curettage. 20 had persistent human chorionic gonadotropin hormone (hCG) elevation before second curettage. Of them, 9 patients (45 %) needed no further treatment afterwards. Eleven patients (55 %) needed further chemotherapy. Nine (82 %) were cured with single-agent chemotherapy and 2 patients (18 %) needed multi-agent chemotherapy. Of the 37 patients, patients with hCG levels below 5000 IU/L undergoing a second curettage were cured without chemotherapy in 65 % versus 45 % of patients with hCG level more than 5000 IU/L. Of the ten patients with a hCG level below 1000 IU/L, eight were cured without chemotherapy. CONCLUSIONS Patients with post-mole gestational trophoblastic neoplasia can benefit from a second curettage to avoid chemotherapy, especially when the hCG level is lower than 5000 IU/L.
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Affiliation(s)
- A Vandewal
- Department of Obstetrics and Gynaecology, Gynecologic Oncology, Leuven Cancer Institute University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - K Delbecque
- Department of Pathologic Anatomy, University Hospital of Liège, Liège, Belgium
| | - A S Van Rompuy
- Department of Pathologic Anatomy, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - J-Ch Noel
- Department of Pathologic Anatomy, Erasmus Hospital, Brussels, Belgium
| | - E Marbaix
- Department of Pathologic Anatomy, University Hospital Saint-Luc, Brussels, Belgium
| | - P Delvenne
- Department of Pathologic Anatomy, University Hospital of Liège, Liège, Belgium
| | - M Nisolle
- Department of Obstetrics and Gynaecology, University Hospital of Liège, Liège, Belgium
| | - E Van Nieuwenhuysen
- Department of Obstetrics and Gynaecology, Gynecologic Oncology, Leuven Cancer Institute University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - F Kridelka
- Department of Obstetrics and Gynaecology, University Hospital of Liège, Liège, Belgium
| | - I Vergote
- Department of Obstetrics and Gynaecology, Gynecologic Oncology, Leuven Cancer Institute University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - F Goffin
- Department of Obstetrics and Gynaecology, University Hospital of Liège, Liège, Belgium
| | - S N Han
- Department of Obstetrics and Gynaecology, Gynecologic Oncology, Leuven Cancer Institute University Hospitals Leuven, KU Leuven, Leuven, Belgium.
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Di Mattei V, Mazzetti M, Perego G, Rottoli S, Mangili G, Bergamini A, Cioffi R, Candiani M. Psychological aspects and fertility issues of GTD. Best Pract Res Clin Obstet Gynaecol 2020; 74:53-66. [PMID: 33176992 DOI: 10.1016/j.bpobgyn.2020.10.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 12/31/2022]
Abstract
Gestational trophoblastic disease (GTD) represents a spectrum of rare pregnancy-related disorders, including both premalignant and malignant entities. Although GTD's medical outcomes have been widely explored, limited data are available regarding the related psychological, sexual, and fertility issues. The present chapter aims to enhance comprehension of the psychosocial impact of GTD by discussing the main quantitative and qualitative evidence available in this field. Although patients globally report a good quality of life, clinically significant levels of anxiety and depression have been consistently found across studies. Similarly, despite the quality of couple relationships being generally satisfactory, they often complain of a lack of sexual desire. Moreover, pregnancy loss may raise significant and long-term fertility-related concerns. Specific socio-demographic and clinical factors have been identified as predictors of psychosocial outcomes. At the clinical level, research suggests that there is a need to provide multidisciplinary care to patients.
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Affiliation(s)
- Valentina Di Mattei
- Division of Neuroscience, Clinical and Health Psychology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Psychology, Vita-Salute San Raffaele University, Milan, Italy
| | - Martina Mazzetti
- Division of Neuroscience, Clinical and Health Psychology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Gaia Perego
- Department of Psychology, University of Milano-Bicocca, Milan, Italy
| | - Sara Rottoli
- Division of Neuroscience, Clinical and Health Psychology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giorgia Mangili
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alice Bergamini
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Raffaella Cioffi
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Candiani
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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Dudiak KM, Maturen KE, Akin EA, Bell M, Bhosale PR, Kang SK, Kilcoyne A, Lakhman Y, Nicola R, Pandharipande PV, Paspulati R, Reinhold C, Ricci S, Shinagare AB, Vargas HA, Whitcomb BP, Glanc P. ACR Appropriateness Criteria® Gestational Trophoblastic Disease. J Am Coll Radiol 2020; 16:S348-S363. [PMID: 31685103 DOI: 10.1016/j.jacr.2019.05.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 05/14/2019] [Indexed: 11/30/2022]
Abstract
Gestational trophoblastic disease (GTD), a rare complication of pregnancy, includes both benign and malignant forms, the latter collectively referred to as gestational trophoblastic neoplasia (GTN). When metastatic, the lungs are the most common site of initial spread. Beta-human chorionic gonadotropin, elaborated to some extent by all forms of GTD, is useful in facilitating disease detection, diagnosis, monitoring treatment response, and follow-up. Imaging evaluation depends on whether GTD manifests in one of its benign forms or whether it has progressed to GTN. Transabdominal and transvaginal ultrasound with duplex Doppler evaluation of the pelvis are usually appropriate diagnostic procedures in either of these circumstances, and in posttreatment surveillance. The appropriateness of more extensive imaging remains dependent on a diagnosis of GTN and on other factors. The use of imaging to assess complications, typically hemorrhagic, should be guided by the location of clinical signs and symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Affiliation(s)
| | | | - Esma A Akin
- George Washington University Hospital, Washington, District of Columbia
| | - Maria Bell
- Sanford Health, Sioux Falls, South Dakota, American College of Obstetricians and Gynecologists
| | | | - Stella K Kang
- New York University Medical Center, New York, New York
| | | | - Yulia Lakhman
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Refky Nicola
- State University of New York Upstate Medical University, Syracuse, New York
| | | | | | | | - Stephanie Ricci
- Cleveland Clinic, Cleveland, Ohio, American College of Obstetricians and Gynecologists
| | - Atul B Shinagare
- Brigham & Women's Hospital Dana-Farber Cancer Institute, Boston, Massachusetts
| | | | - Bradford P Whitcomb
- University of Connecticut, Farmington, Connecticut, Society of Gynecologic Oncology
| | - Phyllis Glanc
- Specialty Chair, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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Hoeijmakers YM, Sweep FCGJ, Lok CAR, Ottevanger PB. Risk factors for second-line dactinomycin failure after methotrexate treatment for low-risk gestational trophoblastic neoplasia: a retrospective study. BJOG 2020; 127:1139-1145. [PMID: 32141676 PMCID: PMC7383780 DOI: 10.1111/1471-0528.16198] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2020] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To find risk factors for second-line dactinomycin failure in patients with low-risk gestational trophoblastic neoplasia (GTN). DESIGN Retrospective multicentre study. SETTING Tertiary reference centre. POPULATION Patients with low-risk GTN, treated with dactinomycin after methotrexate (MTX) failure. METHODS Retrospective analysis of 45 patients with low-risk GTN treated with dactinomycin after MTX failure, registered between 2006 and 2018. MAIN OUTCOME MEASURES Treatment outcome and risk factors for second-line dactinomycin failure. RESULTS Thirty patients (66.7%) were cured and 15 patients (33.3%) required third-line therapy. Type of antecedent pregnancy and hCG levels pre-dactinomycin were risk factors for failure in univariate analysis (odds ratio [OR] 19.30, 95% CI 2.04-182.60, P = 0.01 and OR 2.77, 95% CI 1.18-6.50, P = 0.02, respectively). Level of hCG pre-dactinomycin remained a significant risk factor in multivariate analysis (OR 2.93, 95% CI 1.02-8.40, P = 0.045). Complete remission (CR) was achieved in 83.3% of patients with pre-dactinomycin hCG levels <10 ng/ml, in 75% with hCG levels between 10 and 20 ng/ml, in 66.7% with hCG levels between 20 and 30 ng/ml, and in 50% with hCG levels between 30 and 40 ng/ml. No patients with hCG levels >40 ng/ml achieved CR. Patients with dactinomycin failure were treated surgically and/or with multi-chemotherapy; all except one achieved CR. CONCLUSIONS Treatment with dactinomycin after MTX failure in patients with low-risk GTN resulted in CR in 66.7%. Chance of curative treatment with dactinomycin is strongly related to the hCG level. TWEETABLE ABSTRACT Chance of curative treatment with dactinomycin after MTX failure in GTN patients is strongly related to the level of hCG pre-dactinomycin.
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Affiliation(s)
- YM Hoeijmakers
- Department of Obstetrics and GynaecologyRadboud University Medical CentreNijmegenthe Netherlands
| | - FCGJ Sweep
- Department of Laboratory MedicineRadboud University Medical CentreNijmegenthe Netherlands
| | - CAR Lok
- Department of Gynaecologic OncologyAntoni van LeeuwenhoekAmsterdamthe Netherlands
- Cancer Institute AmsterdamAmsterdamthe Netherlands
| | - PB Ottevanger
- Department of Medical OncologyRadboud University Medical CentreNijmegenthe Netherlands
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Cavoretto P, Cioffi R, Mangili G, Petrone M, Bergamini A, Rabaiotti E, Valsecchi L, Candiani M, Seckl MJ. A Pictorial Ultrasound Essay of Gestational Trophoblastic Disease. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2020; 39:597-613. [PMID: 31468566 DOI: 10.1002/jum.15119] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 07/30/2019] [Accepted: 08/03/2019] [Indexed: 06/10/2023]
Abstract
Gestational trophoblastic disease (GTD) includes a wide variety of clinical and histopathologic entities that require prompt identification and definition by the integration of clinical, laboratory, and imaging data. Recently, the role of grayscale ultrasound and spectral and power/color Doppler techniques has become pivotal in the diagnosis, staging, and management of GTD, thanks to both technical improvements and the growing expertise of dedicated operators. The aim of this essay is to summarize the most recent data on the ultrasound and Doppler findings of GTD and to provide a pictorial overview, including useful prognostic and therapeutic implications for clinical practice.
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Affiliation(s)
- Paolo Cavoretto
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Raffaella Cioffi
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Giorgia Mangili
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Micaela Petrone
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Alice Bergamini
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Emanuela Rabaiotti
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Luca Valsecchi
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Massimo Candiani
- Department of Obstetrics and Gynecology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Michael J Seckl
- Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Center, Imperial College National Health Service Healthcare Trust and Imperial College London, London, England
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Zakaria A, Hemida R, Elrefaie W, Refaie E. Incidence and outcome of gestational trophoblastic disease in lower Egypt. Afr Health Sci 2020; 20:73-82. [PMID: 33402895 PMCID: PMC7750079 DOI: 10.4314/ahs.v20i1.12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Gestational trophoblastic disease (GTD) defines a spectrum of proliferative disorders of trophoblastic epithelium of the placenta. Incidence, risk factors, and outcome may differ from one country to another. OBJECTIVE To describe incidence, patient characteristics, treatment modalities, and outcome of GTD at Mansoura University which is a referral center of Lower Egypt. METHODS An observational prospective study was conducted at the GTD Clinic of Mansoura University. The patients were recruited for 12 months from September 2015 to August 2016. The patients' characteristics, management, and outcome were reported. RESULTS We reported 71 clinically diagnosed GTD cases, 62 of them were histologically confirmed, 58 molar (33 CM and 25 PM) in addition to 4 initially presented GTN cases. Mean age of the studied cases was 26.22 years ± 9.30SD. Mean pre-evacuation hCG was 136170 m.i.u/ml ±175880 SD. Most of the cases diagnosed accidentally after abnormal sonographic findings (53.2%). Rate of progression of CM and PM to GTN was 24.2% and 8%, respectively. CONCLUSION The incidence of molar pregnancy and GTN in our locality was estimated to be 13.1 and 3.2 per 1000 live births respectively. We found no significance between CM and PM regarding hCG level, time to hCG normalization, and progression rate to GTN.
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Abu-Rustum NR, Yashar CM, Bean S, Bradley K, Campos SM, Chon HS, Chu C, Cohn D, Crispens MA, Damast S, Dorigo O, Eifel PJ, Fisher CM, Frederick P, Gaffney DK, Han E, Huh WK, Lurain JR, Mariani A, Mutch D, Nagel C, Nekhlyudov L, Fader AN, Remmenga SW, Reynolds RK, Sisodia R, Tillmanns T, Ueda S, Wyse E, McMillian NR, Scavone J. Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019; 17:1374-1391. [PMID: 31693991 DOI: 10.6004/jnccn.2019.0053] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.
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Affiliation(s)
| | | | | | | | | | | | | | - David Cohn
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | | | | | | | | | | | | | | | - John R Lurain
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - David Mutch
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | - Christa Nagel
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | | | | | - Todd Tillmanns
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | - Stefanie Ueda
- UCSF Helen Diller Family Comprehensive Cancer Center
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Maisenbacher MK, Merrion K, Kutteh WH. Single-nucleotide polymorphism microarray detects molar pregnancies in 3% of miscarriages. Fertil Steril 2019; 112:700-706. [DOI: 10.1016/j.fertnstert.2019.06.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 05/24/2019] [Accepted: 06/10/2019] [Indexed: 11/16/2022]
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Tranoulis A, Georgiou D, Sayasneh A, Tidy J. Gestational trophoblastic neoplasia: a meta-analysis evaluating reproductive and obstetrical outcomes after administration of chemotherapy. Int J Gynecol Cancer 2019; 29:1021-1031. [PMID: 31253638 DOI: 10.1136/ijgc-2019-000604] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 03/14/2019] [Accepted: 03/25/2019] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION Gestational trophoblastic neoplasia represents a rare placental malignancy spectrum that is treated with single- or multi-agent chemotherapy. This disease often impacts women of childbearing age, making post-chemotherapy fertility and obstetrical outcomes an important consideration. We aimed to ascertain the pregnancy rates and obstetric outcomes in women with gestational trophoblastic neoplasia after undergoing treatment with chemotherapy. METHODS A systematic literature review was conducted to identify studies that reported post-chemotherapy fertility and obstetric outcomes among women with gestational trophoblastic neoplasia. We performed a single-proportion meta-analysis for the outcomes of conception/pregnancy rate, term live birth rate, first and second trimester spontaneous abortions rate, stillbirth rate, premature delivery rate, and fetal/neonatal malformation rate. RESULTS A total of 27 studies were included in the analysis. The median age ranged between 25.5 and 33.1 years. The pregnancy rate among women with a desire to conceive, comprising a total of 1329 women and 1192 pregnancies, was 86.7% (95% CI 80.8% to 91.6%). The term live birth rate in 6752 pregnancies was 75.84% (95% CI 73.4% to 78.2%). The adverse pregnancy outcomes were seemingly comparable to those of the general population apart from a minor increase in the stillbirth rate. The pooled proportion for the outcome of malformation rate was 1.76% (95% CI 1.3% to 2.2%). The repeat mole rate in 6384 pregnancies was 1.28% (95% CI 0.95% to 1.66%). Subsequent sub-group analysis indicated that neither multi-agent chemotherapy nor conception within 12 months post-chemotherapy increased the adverse obstetric events risk or fetal malformations. CONCLUSIONS Nearly 90% of patients desiring future fertility after chemotherapy for gestational trophoblastic disease were able to conceive. In addition, adverse pregnancy outcomes were similar to that in the general population. Multi-agent chemotherapy does not seemingly increase the malformation rate.
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Affiliation(s)
- Anastasios Tranoulis
- Department of Gynaecological Oncology, Guy's and St Thomas' NHS Foundation Trust, King's College, London, UK
| | - Dimitra Georgiou
- Department of Obstetrics and Gynaecology, Chelsea and Westminster NHS Foundation Trust, Imperial College, London, UK
| | - Ahmad Sayasneh
- Department of Gynaecological Oncology, Guy's and St Thomas' NHS Foundation Trust, King's College, London, UK
- School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College, London, UK
| | - John Tidy
- Sheffield Trophoblastic Centre, Weston Park Hospital, Sheffield, UK
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Reproductive outcomes following treatment for a gynecological cancer diagnosis: a systematic review. J Cancer Surviv 2019; 13:269-281. [DOI: 10.1007/s11764-019-00749-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 02/22/2019] [Indexed: 01/06/2023]
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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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Frijstein MM, Lok CAR, Coulter J, van Trommel NE, Ten Kate-Booij MJ, Golfier F, Seckl MJ, Massuger LFAG. Is there uniformity in definitions and treatment of gestational trophoblastic disease in Europe? Int J Gynecol Cancer 2019; 29:108-112. [PMID: 30640691 DOI: 10.1136/ijgc-2018-000028] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/29/2018] [Accepted: 09/06/2018] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES Because gestational trophoblastic disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in gestational trophoblastic disease, we evaluated differences and similarities between protocols in EOTTD countries. METHODS Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of gestational trophoblastic disease and gestational trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up. RESULTS Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar gestational trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk gestational trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar gestational trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements. CONCLUSIONS This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several gestationaltrophoblastic disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe.
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Affiliation(s)
- Minke M Frijstein
- Department of Gynaecologic Oncology, Centre of Gynaecologic Oncology Amsterdam, Amsterdam, The Netherlands
- Department of Gynaecologic Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Christianne A R Lok
- Department of Gynaecologic Oncology, Centre of Gynaecologic Oncology Amsterdam, Amsterdam, The Netherlands
| | - John Coulter
- Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland
| | - Nienke E van Trommel
- Department of Gynaecologic Oncology, Centre of Gynaecologic Oncology Amsterdam, Amsterdam, The Netherlands
| | | | - Francois Golfier
- Department of Gynaecological Surgery and Oncology, Obstetrics, University of Lyon 1, University Hospital Lyon Sud, Pierre Bénite, France
- French Centre for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite, France
| | - Michael J Seckl
- Department of Medical Oncology, Charing Cross Hospital Campus of Imperial College London, London, UK
| | - Leon F A G Massuger
- Department of Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands
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Venturini M, Bergamini A, Colarieti A, Petrone M, Marra P, Rabaiotti E, Mangili G, Candiani M, Del Maschio A, De Cobelli F. A rare case of a giant arterio-venous fistula (AVF) following metastatic choriocarcinoma conditioning pulmonary embolism: multimodal transcatheter embolization using a simultaneous transarterial and transvenous approach. CVIR Endovasc 2018; 1:30. [PMID: 30652161 PMCID: PMC6319539 DOI: 10.1186/s42155-018-0039-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 11/05/2018] [Indexed: 01/26/2023] Open
Abstract
Background Choriocarcinoma is a highly malignant tumor but with a good prognosis due to the valid response to systemic chemotherapy. We present a case of a young woman affected by a giant pelvic arterio-venous fistula following a metastatic gestational choriocarcinoma, conditioning metrorrhagia and pulmonary embolism, successfully treated by multimodal transcatheter embolization, using a simultaneous transarterial and transvenous approach. Case presentation In a young patient affected by choriocarcinoma and metrorrhagia, a computed tomography showed a giant arterio-venous fistula, pulmonary metastases and embolism. A transfemoral diagnostic arteriography showed a giant arterio-venous fistula sustained by right and left hypogastric arteries with early opacification of the right gonadal vein and of the inferior vena cava. A transarterial embolization of the distal branches of hypogastric arteries with poly-vinyl-alcohol particles, coils and Squid was performed. A transfemoral phlebography of the right gonadal vein showed multiple thrombi, responsible of the pulmonary embolism. An Amplatzer plug via trans-jugular was finally placed at the confluence of the gonadal vein in the vena cava, to reduce arterio-venous fistula out-flow and to occlude the vein, preventing further episodes of pulmonary embolism. Metrorrhagia progressively disappeared. A second transarterial embolization combined with a complete response to systemic chemotherapy determined arterio-venous fistula resolution. Conclusions This was a very rare case of a giant pelvic arterio-venous fistula following choriocarcinoma in a patient symptomatic for metrorrhagia with an accidental finding of pulmonary embolism at computed tomography. A transcatheter embolization was successfully performed with different embolic materials, using a simultaneous transarterial and transvenous approach: the goal was not only to obtain metrorrhagia resolution but also to avoid a massive pulmonary embolism, a potential life threatening condition, in a young woman affected by a highly malignant tumor but with a good prognosis.
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Outcome of First-Line Hysterectomy for Gestational Trophoblastic Neoplasia in Patients No Longer Wishing to Conceive and Considered With Isolated Lung Metastases: A Series of 30 Patients. Int J Gynecol Cancer 2018; 28:1766-1771. [DOI: 10.1097/igc.0000000000001367] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
ObjectiveThis study aimed to assess the outcome of first-line hysterectomy in patients diagnosed as having gestational trophoblastic neoplasia (GTN) whose postoperative imaging showed lung images considered as metastases.MethodsFrom 1999 to 2016, patients no longer wishing to conceive, treated by their initial physician by hysterectomy, and whose postoperative imaging workup showed lung images considered as metastasis were identified in the French Trophoblastic Disease Reference Center database. We sought to identify significant predictive factors of requiring salvage chemotherapy.ResultsThirty patients were identified with a maximum number of 2 visible lung nodules and a median largest size of 14 mm on chest x-ray. Nine of these patients had an International Federation of Gynecology and Obstetrics score of higher than 6, and there were no postterm GTN. Twenty-two patients (73.33%; 95% confidence interval, 54.11–87.72; P = 0.0053) normalized their human chorionic gonadotropin (hCG) without salvage chemotherapy, whereas 7 received 1 line of salvage monochemotherapy (8-day methotrexate) and 1 required 2 lines of monochemotherapy (5-day actinomycin D after failure of methotrexate). After a 12.45-month median follow-up (range, 3–48.4 months) since the first normalized hCG, none of these patients died. The median interval between successful hysterectomy and hCG normalization was 3.15 months (range, 1.6–8.7 months). Patients who required salvage chemotherapy had a median size of the largest lung metastasis on chest computed tomography of 4 mm larger than those cured by hysterectomy (P = 0.0455).ConclusionsFor GTN patients no longer wishing to conceive with lung metastases discovered postoperatively, treated by hysterectomy, and whose hCG is decreasing, it is reasonable to expect and to inform patients that approximately 27% will require salvage chemotherapy. However, in patients with lung metastases discovered preoperatively, evidence to recommend first-line hysterectomy is insufficient and these patients should receive first-line chemotherapy.
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De Nola R, Schönauer LM, Fiore MG, Loverro M, Carriero C, Di Naro E. Management of placental site trophoblastic tumor: Two case reports. Medicine (Baltimore) 2018; 97:e13439. [PMID: 30508960 PMCID: PMC6283185 DOI: 10.1097/md.0000000000013439] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 11/05/2018] [Indexed: 11/27/2022] Open
Abstract
RATIONALE Placental site trophoblastic tumor (PSTT) is a very rare malignant tumor, belonging to a family of pregnancy-related illnesses, called gestational trophoblastic diseases (GTD). Less than 300 cases of PSTT have been reported in literature, with an incidence of ≈ 1/50,000-100,000 pregnancies representing only 0.23% to 3.00% of all GTDs. PATIENT CONCERNS Our report describes 2 additional cases of PSTT outlining their main diagnostic features and the subsequent management. The first case presented contemporary to a persistent hydatidiform mole in a 37-year-old woman, para 2042; whereas the second one originated 5 years after a miscarriage in 43-year-old woman, para 1031 with a previous diagnosis of breast cancer, and shared some features with placental site nodule (PSN), a benign condition. DIAGNOSIS The first case had a difficult diagnosis because there was an amenorrhea of 11th week with high serum beta-human chorionic gonadotropin (beta-HCG) and an initial ultrasound image of vesicular mole. After the Dilatation and Curettage, histology confirmed the previous hypothesis. However, the final histology of PSTT was obtained after major surgery. On the contrary, the diagnosis of the second case was less challenging but surprising, thanks to a routine trans-vaginal ultrasound showing a suspicious endometrial thickness positive for PSTT at a subsequent hysteroscopic guided biopsy. INTERVENTIONS The treatment consisted of hysterectomy and subsequent follow up. Lymphadenectomy or lymph node sampling were not performed due to the initial stage of the disease. OUTCOMES In the first case, there were high values of serum beta-HCG that plummeted after the surgery, whereas in the second one they had been always negative. Hereafter, both went through a follow up with periodic serum oncological markers, imaging studies and clinical evaluation, which have showed negative result for 3 years and 15 months, respectively. LESSONS A detailed gynecological ultrasound examination could be extremely helpful to understand the next diagnostic step of echo-guided D&C or hysteroscopic biopsy and for a pre-operative staging assessment. On the contrary, determining the serum beta-HCG's curve is crucial just in case of an initial positive value to pursue clinical evaluation and follow-up. In case of good prognostic factors, the main therapy remains hysterectomy.
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Affiliation(s)
- Rosalba De Nola
- Interdisciplinary Department of Medicine, Gynecology and Obstetrics Clinic, University of Bari
| | - Luca Maria Schönauer
- Interdisciplinary Department of Medicine, Gynecology and Obstetrics Clinic, University of Bari
| | - Maria Grazia Fiore
- Department of Emergency and Organ Transplantation, Pathology Unit, University of Bari, Bari, Italy
| | - Matteo Loverro
- Interdisciplinary Department of Medicine, Gynecology and Obstetrics Clinic, University of Bari
| | - Carmine Carriero
- Interdisciplinary Department of Medicine, Gynecology and Obstetrics Clinic, University of Bari
| | - Edoardo Di Naro
- Interdisciplinary Department of Medicine, Gynecology and Obstetrics Clinic, University of Bari
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Essel KG, Shafer A, Bruegl A, Gershenson DM, Drury LK, Ramondetta LM, Naumann RW, Brown J. Complete Resection Is Essential in the Surgical Treatment of Gestational Trophoblastic Neoplasia. Int J Gynecol Cancer 2018; 28:1453-1460. [PMID: 30157165 DOI: 10.1097/igc.0000000000001348] [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: 11/26/2022] Open
Abstract
OBJECTIVE The aim of this study was to determine the utility of surgery in patients with gestational trophoblastic neoplasia (GTN). MATERIALS AND METHODS We performed a retrospective institutional review board-approved analysis of all patients with GTN at a single institution from 1985 to 2015 and compared all patients who underwent surgery as definitive management for their disease to a matched cohort of those who did not. Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS). RESULTS Sixty-nine patients underwent a total of 94 surgeries as definitive treatment for GTN. Nineteen patients had multiple surgeries. Progression-free survival and OS were improved in patients with complete macroscopic surgical resection (n = 61) compared with patients with gross residual disease (n = 33) (median PFS 91.2 months vs 3.3 months, and median OS not reached at 108.8 months vs 66.3 months, respectively; P < 0.05). The nature of the surgery (emergent vs planned) and site of metastatic disease did not influence PFS or OS. Of the 61 patients with no visible residual disease, 17 received adjuvant chemotherapy and 44 did not; there were no observed differences in PFS or OS. Patients who underwent surgery as part of definitive treatment (n = 69 patients) were compared with patients with GTN over the same period who received chemotherapy alone (n = 33 patients). Median PFS was improved in the surgical group (5.9 vs 5.1 months, P < 0.01), but OS was not significantly different (P = 0.37). CONCLUSIONS Complete resection results in improved outcomes in patients who undergo surgery for GTN, whether emergent or planned, independent of disease site, and should be considered as an important component of treatment in some situations.
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Affiliation(s)
- Kathleen Gong Essel
- Department of Obstetrics and Gynecology, The University of Oklahoma, Oklahoma City, OK
| | - Aaron Shafer
- Department of Gynecologic Oncology and Reproductive Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Amanda Bruegl
- Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR
| | - David M Gershenson
- Department of Gynecologic Oncology and Reproductive Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Lane K Drury
- Division of Gynecologic Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC
| | - Lois M Ramondetta
- Department of Gynecologic Oncology and Reproductive Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - R Wendel Naumann
- Division of Gynecologic Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC
| | - Jubilee Brown
- Division of Gynecologic Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC
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Mangili G, Cioffi R, Danese S, Frigerio L, Ferrandina G, Cormio G, Rabaiotti E, Scarfone G, Gadducci A, Bergamini A, Pisano C, Candiani M. Does methotrexate (MTX) dosing in a 8-day MTX/FA regimen for the treatment of low-risk gestational trophoblastic neoplasia affect outcomes? The MITO-9 study. Gynecol Oncol 2018; 151:449-452. [PMID: 30266260 DOI: 10.1016/j.ygyno.2018.09.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 09/15/2018] [Accepted: 09/21/2018] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To compare clinical outcomes of patients diagnosed with low-risk gestational trophoblastic neoplasia (GTN) receiving intramuscular methotrexate 50 mg total dose/day versus 1 mg/kg/day in a 8-day methotrexate/folinic acid (MTX/FA) regimen. METHODS This retrospective, multicenter study included 176 patients: 99 (56%) receiving methotrexate 50 mg total dose/day on days 1, 3, 5, 7 alternated with FA 7,5 mg on days 2, 4, 6, 8, every 14 days (group A); and 77 patients (44%), receiving methotrexate 1 mg/kg/day on days 1, 3, 5, 7 alternated with FA 7,5 mg on days 2, 4, 6, 8, every 14 days (group B). Patients' characteristics and outcomes were compared by univariate analysis. RESULTS Forty-five patients (25.6%) developed resistance to MTX and received a second-line treatment, 7 (4%) received a third-line treatment and 8 (4.5%) relapsed after initial remission. There was no difference between group A and B patients in the average number of chemotherapy cycles required to achieve remission (5.7 ± 2.6 vs 6.3 ± 2.3, p = 0.106). The 2 treatment groups showed comparable rates of MTX resistance (28.3% vs 22.1%, p = 0.387) and relapse (3% vs 6.5%, p = 0.300). There was no difference in the incidence of treatment toxicity of any CTCAE grade between group A and B patients (16.2% vs 15.2%, p = 0.999). Subgroup analysis stratifying patients by weight (<50 kg, ≥60 kg, ≥70 kg, ≥80 kg) confirmed these results. CONCLUSION The 2 MTX schedules showed comparable efficacy in the treatment of low-risk GTN with an acceptable rate of toxicity.
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Affiliation(s)
- Giorgia Mangili
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Raffaella Cioffi
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Saverio Danese
- Obstetrics and Gynecology Unit, Ospedale S. Anna, Turin, Italy
| | - Luigi Frigerio
- Obstetrics and Gynecology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Gabriella Ferrandina
- Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS -Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gennaro Cormio
- Gynecologic Oncology Unit, Istituto Tumori "Giovanni Paolo II", University of Bari, Italy
| | - Emanuela Rabaiotti
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giovanna Scarfone
- Obstetrics and Gynecology Unit, IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Angiolo Gadducci
- Division of Gynecology and Obstetrics, Department of Clinical and Experimental Medicine, University of Pisa, Italy
| | - Alice Bergamini
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carmela Pisano
- Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples, Italy
| | - Massimo Candiani
- Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Prouvot C, Golfier F, Massardier J, You B, Lotz JP, Patrier S, Devouassoux M, Schott AM, Hajri T, Bolze PA. Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia. Int J Gynecol Cancer 2018; 28:1038-1044. [PMID: 29629964 DOI: 10.1097/igc.0000000000001248] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate. METHODS From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure. RESULTS A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3-83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post-dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98-50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%). CONCLUSION Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.
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Affiliation(s)
- Catherine Prouvot
- Department of Gynecological Surgery and Oncology, Obstetrics, University Hospital Lyon Sud, University of Lyon 1
| | | | | | | | - Jean-Pierre Lotz
- Department of Medical Oncology, Alliance for Cancer Research, Tenon Hospital, Public Assistance Hospitals of Paris, Paris
| | - Sophie Patrier
- Department of Pathology, University Hospital of Rouen, Rouen
| | - Mojgan Devouassoux
- Department of Pathology Croix Rousse Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1
| | | | - Touria Hajri
- French Centre for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite
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Faure NP, Massardier J, Bolze PA, Hajri T, Devouassoux M, Golfier F, Rousset P. Tumeurs trophoblastiques gestationnelles : éléments clés dans notre pratique radiologique. IMAGERIE DE LA FEMME 2018. [DOI: 10.1016/j.femme.2018.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Cioffi R, Bergamini A, Gadducci A, Cormio G, Giorgione V, Petrone M, Rabaiotti E, Pella F, Candiani M, Mangili G. Reproductive Outcomes After Gestational Trophoblastic Neoplasia. A Comparison Between Single-Agent and Multiagent Chemotherapy: Retrospective Analysis From the MITO-9 Group. Int J Gynecol Cancer 2018; 28:332-337. [PMID: 29324534 DOI: 10.1097/igc.0000000000001175] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES Gestational trophoblastic neoplasia affects women of reproductive age and is usually treated by chemotherapy. Major concerns related to chemotherapy in young women are the possible infertility, risk of early menopause, and teratogenic effects on subsequent pregnancies. The study's aim was to analyze menstrual and reproductive outcomes of women treated with single-agent versus multiagent chemotherapy for gestational trophoblastic neoplasia. METHODS One-hundred fifty-one patients were treated. Seventy-six patients older than 45 years, with a placental site or epithelioid trophoblastic tumor, undergoing hysterectomy for patient choice, or undergoing human chorionic gonadotropin follow-up at the time of the analysis were excluded. Seventy-five patients were divided into subgroups according to International Federation of Gynecology and Obstetrics score: patients scoring less than 7, receiving single-agent chemotherapy (group A, n = 42); patients scoring 7 or greater, receiving combination treatment (group B, n = 33). Patients' outcomes were compared by univariate and multivariate analyses. RESULTS Temporary amenorrhea occurred in 33% of group A patients and 66.7% of group B (P = 0.01). Premature menopause occurred in 3 patients in group B (0% vs 9%, P = 0.02). Ten patients in group B underwent salvage hysterectomy. Pregnancy desire did not differ between the 2 groups (P = 0.555). In group A, 57.1% became pregnant; in group B, 36.4% did (P = 0.060). Instead, pregnancy rate was 52.2% among high-risk patients not undergoing hysterectomy (57.1% vs 52.2%, P = 0.449). There was no difference in miscarriage (P = 0.479) and premature birth (P = 0.615) rates. In a multivariate analysis that included age, International Federation of Gynecology and Obstetrics score, chemotherapy type, use of assisted reproductive technologies, previous pregnancies, and pregnancy desire, only age (P = 0.006) and pregnancy desire (P = 0.002) had a significant impact on the probability to have subsequent pregnancies. CONCLUSIONS Except for the risk of premature ovarian failure, a rare adverse effect of combined treatments, both single-agent and multiagent chemotherapy can be safely administered to patients with a desire for childbearing. High-risk patients have worse reproductive outcomes because they undergo hysterectomy more frequently than low-risk patients.
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Role of Surgery in the Management of Hydatidiform Mole in Elderly Patients: A Single-Center Clinical Experience. Int J Gynecol Cancer 2018; 27:550-553. [PMID: 28129241 DOI: 10.1097/igc.0000000000000903] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE Women older than 40 years develop gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) more often than do younger women. Therefore, in elderly women, primary hysterectomy has been advocated as first-line treatment. The aim of the present study was to evaluate whether hysterectomy could reduce the incidence of GTN after a diagnosis of HM. METHODS Seventy-six of 442 patients referred to our unit for an HM between 1994 and 2015 were older than 40 years old. Among these, 12 patients were treated by primary hysterectomy. We compared clinical features, serum human chorionic gonadotrophin (hCG), incidence of GTN, and further treatments in these patients and in those who underwent evacuation and serum hCG monitoring, using univariate and multivariate analyses. RESULTS Patients treated by primary hysterectomy all had a diagnosis of a complete or invasive HM, had more hyperemesis than did control subjects (82% vs 37%, P = 0.008), and had an increased uterine volume (100% vs 41%, P = 0.001). Seven of them developed a subsequent GTN, whereas 5 patients achieved complete remission of disease after surgery (58% vs 30%, P = 0.094). All the patients who developed a GTN after surgery showed lower hCG levels than did control subjects (mean, 671.4 [SD, 1178.4] IU/L vs 23,919.4 [SD, 34,284.9] IU/L; P = 0.005), but there were no significant differences in the amount and type of chemotherapy needed to achieve remission. CONCLUSIONS Primary hysterectomy after 40 years old in women affected by HM does not reduce the incidence of GTN and amount of chemotherapy. Although further studies are needed to confirm these results, a careful hCG monitoring should be recommended in these high-risk patients.
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Ray-Coquard I, Trama A, Seckl MJ, Fotopoulou C, Pautier P, Pignata S, Kristensen G, Mangili G, Falconer H, Massuger L, Sehouli J, Pujade-Lauraine E, Lorusso D, Amant F, Rokkones E, Vergote I, Ledermann JA. Rare ovarian tumours: Epidemiology, treatment challenges in and outside a network setting. Eur J Surg Oncol 2017; 45:67-74. [PMID: 29108961 DOI: 10.1016/j.ejso.2017.09.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 09/26/2017] [Accepted: 09/30/2017] [Indexed: 10/18/2022] Open
Abstract
PURPOSE OF THE REVIEW More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of <6 per 100,000) and such tumours represent an important challenge for clinicians. RECENT FINDINGS Rare cancers account for more than one fifth of all new cancer diagnoses, more than any of the single common cancers alone. Reviewing the RARECAREnet database, some of the tumours occur infrequently, whilst others because of their natural history have a high prevalence, and therefore appear to be more common, although their incidence is also rare. Harmonization of medical practice, guidelines and novel trials are needed to identify rare tumours and facilitate the development of new treatments. Ovarian tumours are the focus of this review, but we comment on other rare gynaecological tumours, as the diagnosis and treatment challenges faced are similar. FUTURE This requires European collaboration, international partnerships, harmonization of treatment and collaboration to overcome the regulatory barriers to conduct international trials. Whilst randomized trials can be done in many tumour types, there are some for which conducting even single arm studies may be challenging. For these tumours alternative study designs, robust collection of data through national registries and audits could lead to improvements in the treatment of rare tumours. In addition, concentring the care of patients with rare tumours into a limited number of centres will help to build expertise, facilitate trials and improve outcomes.
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Affiliation(s)
- I Ray-Coquard
- Dpt of Medical Oncology, Centre Leon Berard, University Claude Bernard LyonI, Lyon, France.
| | - AnnaLisa Trama
- AnnaLisa Trama, Fondazione IRCCS istituto nazionale dei tumori Milan, Italy
| | - M J Seckl
- Charing Cross Hospital, Campus of Imperial College London, Fulham Palace Rd, W68RF London, UK
| | - C Fotopoulou
- Dept of Surgery and Cancer, Imperial College London, UK
| | - P Pautier
- Medical Oncology, Dpt Gustave Roussy Institution, Villejuif, France
| | - S Pignata
- Medical Oncology, Department of Urology and Gynecology, Istituto Nazionale Tumori - IRCSS - Fondazione G. Pascale, Naples Italy
| | - G Kristensen
- Dept of Gynecologic Oncology, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway
| | - G Mangili
- Department of Obstetrics and Gynecology, San Raffaele Scientific Institute, Milan, Italy
| | - H Falconer
- Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/University Hospital, 171 76 Stockholm, Sweden
| | - L Massuger
- Department of Obstetrics and Gynaecology, Radboudumc, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - J Sehouli
- Department of Gynecology with Center for Oncological Surgery, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Medical University of Berlin, Germany
| | | | - D Lorusso
- Gynecologic Oncology Unit, Fondazione IRCCS istituto nazionale dei tumori Milan, Italy
| | - F Amant
- Center Gynaecologic Oncology Amsterdam (CGOA), Netherlands Cancer Institute, University of Amsterdam & Gynaecologic Oncology KU Leuven, The Netherlands
| | - E Rokkones
- Dept. of Gynaecological Oncology, The Norwegian Radium Hospital, Division of Cancer Medicine Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway
| | - I Vergote
- Gynaecological Oncologist, University Hospital Leuven, European Union, Herestraat 49, B-3000 Leuven, Belgium
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