Pierre-Adrien Bolze1, Cécilia Riedl2, Jérôme Massardier3, Jean-Pierre Lotz4, Benoit You5, Anne-Marie Schott6, Touria Hajri7, François Golfier8. 1. French Reference Center for Trophoblastic Diseases, Lyon, France; Department of Gynecological Surgery and Oncology, Obstetrics, University of Lyon 1, University Hospital Lyon Sud, Pierre Bénite, France; French Center for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite, France. 2. French Reference Center for Trophoblastic Diseases, Lyon, France; Department of Gynecology and Obstetrics, University of Limoges, University Hospital Mère Enfant, Limoges, France. 3. French Reference Center for Trophoblastic Diseases, Lyon, France; Department of Gynecological Surgery and Oncology, Obstetrics, University of Lyon 1, University Hospital Lyon Sud, Pierre Bénite, France; French Center for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite, France; Department of Prenatal Diagnosis, University Hospital Femme Mere Enfant, Bron, France. 4. French Reference Center for Trophoblastic Diseases, Lyon, France; Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris, France. 5. French Reference Center for Trophoblastic Diseases, Lyon, France; Medical Oncology, Investigational Center for Treatments in Oncology and Hematology of Lyon, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France. 6. French Reference Center for Trophoblastic Diseases, Lyon, France; Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France. 7. French Reference Center for Trophoblastic Diseases, Lyon, France; French Center for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite, France; Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France. 8. French Reference Center for Trophoblastic Diseases, Lyon, France; Department of Gynecological Surgery and Oncology, Obstetrics, University of Lyon 1, University Hospital Lyon Sud, Pierre Bénite, France; French Center for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite, France. Electronic address: francois.golfier@chu-lyon.fr.
Abstract
BACKGROUND: Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is encouraged in cases of gestational trophoblastic neoplasia to predict the potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score of ≥7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk gestational trophoblastic neoplasia. There is a crucial need for the early identification of high-risk patients with gestational trophoblastic neoplasia who have an increased death risk to organize their treatment in highly specialized centers. OBJECTIVES: The purpose of this study was to describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with an International Federation of Gynecology and Obstetrics prognostic score of ≥13, for whom low-dose etoposide and cisplatin induction chemotherapy recently was shown to reduce early death rate. STUDY DESIGN: We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of gestational trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who were at high risk of resistance to single-agent chemotherapy (International Federation of Gynecology and Obstetrics score, ≥7), 29 patients (21%) had a score of ≥13. Mortality rate was estimated with the use of the Kaplan-Meier method. RESULTS: The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25-3.13%). High-risk patients had a 5-year mortality rate of 12% (95% confidence interval, 7.49-18.9%). Patients with an International Federation of Gynecology and Obstetrics score of ≥13 had a higher 5-year mortality rate (38.4%; 95% confidence interval, 23.4-58.6%) and accounted for 52% of the deaths in the entire cohort. Early deaths, defined as those that occur within 4 weeks after treatment initiation, occurred in 8 patients of the entire cohort. Six of them had an International Federation of Gynecology and Obstetrics score of ≥13 at presentation, of whom 5 patients had brain and/or liver metastases. CONCLUSION: Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of ≥13 have an increased risk of early death. We suggest that an International Federation of Gynecology and Obstetrics score of ≥13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia with increased risk of death, particularly early death. These patients justify treatment in highly specialized gestational trophoblastic disease centers and may benefit from the use of induction low-dose etoposide and cisplatin.
BACKGROUND:Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is encouraged in cases of gestational trophoblastic neoplasia to predict the potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score of ≥7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk gestational trophoblastic neoplasia. There is a crucial need for the early identification of high-risk patients with gestational trophoblastic neoplasia who have an increased death risk to organize their treatment in highly specialized centers. OBJECTIVES: The purpose of this study was to describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with an International Federation of Gynecology and Obstetrics prognostic score of ≥13, for whom low-dose etoposide and cisplatin induction chemotherapy recently was shown to reduce early death rate. STUDY DESIGN: We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of gestational trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who were at high risk of resistance to single-agent chemotherapy (International Federation of Gynecology and Obstetrics score, ≥7), 29 patients (21%) had a score of ≥13. Mortality rate was estimated with the use of the Kaplan-Meier method. RESULTS: The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25-3.13%). High-risk patients had a 5-year mortality rate of 12% (95% confidence interval, 7.49-18.9%). Patients with an International Federation of Gynecology and Obstetrics score of ≥13 had a higher 5-year mortality rate (38.4%; 95% confidence interval, 23.4-58.6%) and accounted for 52% of the deaths in the entire cohort. Early deaths, defined as those that occur within 4 weeks after treatment initiation, occurred in 8 patients of the entire cohort. Six of them had an International Federation of Gynecology and Obstetrics score of ≥13 at presentation, of whom 5 patients had brain and/or liver metastases. CONCLUSION:Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of ≥13 have an increased risk of early death. We suggest that an International Federation of Gynecology and Obstetrics score of ≥13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia with increased risk of death, particularly early death. These patients justify treatment in highly specialized gestational trophoblastic disease centers and may benefit from the use of induction low-dose etoposide and cisplatin.
Authors: Hextan Y S Ngan; Michael J Seckl; Ross S Berkowitz; Yang Xiang; François Golfier; Paradan K Sekharan; John R Lurain; Leon Massuger Journal: Int J Gynaecol Obstet Date: 2021-10 Impact factor: 4.447