F. Golfier

Cytoreductive Surgery and Intraperitoneal Chemohyperthermia for Chemoresistant and Recurrent Advanced Epithelial Ovarian Cancer: Prospective Study of 81 Patients

PurposeThere is no standardized treatment for patients with chemoresistant or recurrent advanced ovarian cancer. Locoregional treatments combining cytoreductive surgery and intraperitoneal chemohyperthermia (HIPEC) may improve survival for locoregional disease.Patients and methodsA prospective single center study of 81 patients with recurrent or chemoresistant peritoneal carcinomatosis from ovarian cancer was performed. Patients were treated by maximal cytoreductive surgery combined with HIPEC (with cisplatinum at 20 mg/m²/L). A total of 47 patients were included for their third, fourth, fifth, sixth, or seventh surgical look. Altogether, 54 patients presented with extensive carcinomatosis (malignant nodules of >5 mm).ResultsComplete macroscopic resection (CCR-0) was achieved in 45 patients. Mortality and morbidity rates were 2.5% and 13.6%, respectively. With a median follow-up of 47.1 months, the overall and disease-free median survivals were 28.4 and 19.2 months, respectively. Carcinomatosis extent and completeness of cytoreduction (p = 0.02 and p <0.001, respectively) were identified as independent prognostic factors. For CCR-0 patients, overall and disease-free survivals were 54.9 and 26.9 months, respectively.ConclusionSalvage therapy combining optimal cytoreductive surgery and HIPEC may achieve long-term survival in selected patients with recurrent or chemoresistant ovarian cancer. This strategy may be most effective in patients with limited carcinomatosis or when cytoreductive surgery provides sufficient downstaging.

Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

M. J. Seckl1, N. J. Sebire2, R. A. Fisher1, F. Golfier3, L. Massuger4 & C. Sessa5, on behalf of the ESMO Guidelines Working Group* Department of Cancer Medicine; Department of Histopathology, Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College London, London, UK; Centre de Référence des Maladie Trophoblastiques, Hospices Civils de Lyon, Lyon, France; Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland;

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Persistent and Recurrent Advanced Ovarian Carcinoma: A Multicenter, Prospective Study of 246 Patients

BackgroundEpithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed.ResultsAn optimal cytoreductive surgery was possible in 92.2xa0% of patients. Mortality and morbidity rates were 0.37xa0% and 11.6xa0%, respectively. The overall median survival was 48.9xa0months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10).ConclusionsSalvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.

Twin pregnancy with complete hydatidiform mole and coexistent fetus Obstetrical and oncological outcomes in a series of 14 cases

OBJECTIVEnTwin pregnancy with complete hydatidiform mole and coexistent fetus (CHM&CF) is a rare situation and a challenge for diagnosis. Results related to fetal outcome and maternal risk of subsequent gestational trophoblastic neoplasia (GTN) are controversial. We here display a series from the French Trophoblastic Disease Reference Center, which is to date the third in number of cases registered by the same center.nnnSTUDY DESIGNnBy retrospective method based on patients from the French Trophoblastic Disease Reference Center data base between November 1999 and December 2006, 17 assumed cases were reviewed. In 14 cases the diagnosis of CHM&CF was ascertained. All files were reviewed to confirm diagnosis. Methods of initial diagnosis, outcome of pregnancy and evolution to GTN were studied.nnnRESULTSnIn 10 cases (71%) diagnosis was made by ultrasonography. Differential diagnoses were partial hydatidiform mole and mesenchymal dysplasia. Three patients in 14 (21%) delivered a healthy child. In only one case, delivery occurred after 37 weeks of gestation. Seven patients (50%) had a diagnosis of GTN. No patient had fatal evolution. Clinical events, such as vaginal bleeding, pre-eclampsia or hyperthyroidism, had no effect on the evolution to GTN. Continuation of the pregnancy did not increase the risk of GTN.nnnCONCLUSIONnIn case of prenatal diagnosis of CHM&CF, and even if delivery of a healthy child is possible, patients should be aware of a possibly higher risk of GTN than in CHM.

Trophoblastic disease review for diagnosis and management: a joint report from the International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup.

Objective The objective of this study was to provide a consensus review on gestational trophoblastic disease diagnosis and management from the combined International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup. Methods A joint committee representing various groups reviewed the literature obtained from PubMed searches. Results and Conclusions Guidelines were constructed on the basis of literature review. After initial diagnosis in local centers, centralization of pathology review and ongoing care is recommended to achieve the best outcomes.

Update on the diagnosis and management of gestational trophoblastic disease

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score 7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

Predictive values of hCG clearance for risk of methotrexate resistance in low-risk gestational trophoblastic neoplasias

BACKGROUNDnEarly identification of patients at high risk for chemoresistance among those treated with methotrexate (MTX) for low-risk gestational trophoblastic neoplasia (GTN) is needed. We modeled human chorionic gonadotropin (hCG) decline during MTX therapy using a kinetic population approach to calculate individual hCG clearance (CL(hCG)) and assessed the predictive value of CL(hCG) for MTX resistance.nnnPATIENTS AND METHODSnA total of 154 patients with low-risk GTN treated with 8-day MTX regimen were retrospectively studied. NONMEM was used to model hCG decrease equations between day 0 and day 40 of chemotherapy. Receiver operating characteristic curve analysis defined the best CL(hCG) threshold. Univariate/multivariate survival analyses determined the predictive value of CL(hCG) and compared it with published predictive factors.nnnRESULTSnA monoexponential equation best modeled hCG decrease: hCG(t) = 3900 x e(-0.149 x t). Median CL(hCG) was 0.57 l/day (quartiles: 0.37-0.74). Only choriocarcinoma pathology [yes versus no: hazard ratio (HR) = 6.01; 95% confidence interval (CI) 2.2-16.6; P < 0.001] and unfavorable CL(hCG) quartile (< or =0.37 versus >0.37 l/day: HR = 6.75; 95% CI 2.7-16.8; P < 0.001) were significant independent predictive factors of MTX resistance risk.nnnCONCLUSIONnIn the second largest cohort of low-risk GTN patients reported to date, choriocarcinoma pathology and CL(hCG) < or =0.37 l/day were major independent predictive factors for MTX resistance risk.

The spectrum of NLRP7 mutations in French patients with recurrent hydatidiform mole

OBJECTIVESnThe NLRP7 gene (19q13.42) is associated with recurrent and/or familial hydatidiform moles. Several mutations, histopathological types and reproductive outcomes have been described. We studied our recurrent hydatidiform mole cases recorded since 1999 in order to identify links between clinic, histology and genetics.nnnSTUDYnWe present here the gestational history and the spectrum of NLRP7 mutations in our French series.nnnDESIGNnWe performed a retrospective study from clinical forms received for genetic diagnosis. Cases declaration was based on a voluntary initiative coming from French practitioners, subjected to patients agreement.nnnRESULTSnAmong 12 recurrent hydatidiform moles investigated, we identified 3 cases of confirmed homozygous NLRP7 mutation and 3 cases of heterozygous NLRP7 mutation. One patient bore a novel mutation p.Leu880Ser in a homozygous state.nnnCONCLUSIONSnWe here identified a new homozygous NLRP7 mutation. Unfortunately, no modern therapeutic option has proven effective to obtain evolutive pregnancies. Then, fundamental and clinical researches seem to be necessary. Moreover, collecting RHM cases is essential.

Formalised consensus of the European Organisation for Treatment of Trophoblastic Diseases on management of gestational trophoblastic diseases

Gestational trophoblastic disease (GTD) is a spectrum of cellular proliferations arising from trophoblast. Their invasive and metastatic potential sometimes requires chemotherapy and/or surgery. Current management is generally associated with favourable prognosis. Therefore, treatments must be chosen according to the desire for further childbearing of each patient. The European Organisation for Treatment of Trophoblastic Diseases (EOTTD) is dedicated to optimise diagnosis, treatment, follow-up and research in GTD by bringing together knowledge of clinicians and researchers from 29 countries working in the field of GTD in Europe. This study assessed the level of agreement among an expert panel of the EOTTD in order to rationalise the management of patients in Europe. The RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgment of experts to yield a statement regarding the appropriateness of performing a procedure at the level of patient-specific symptoms, medical history and test results. There was an agreement for 54 statements while the experts showed a disagreement for two statements. As there is little evidence from randomised trials on which to base recommendations about management of GTD, many of these recommendations are based on expert opinion derived from changes in management fact that have improved outcomes from nearly 100% fatality to nearly 100% cure rates. However, a large agreement among experts is invaluable to the individual clinician who is struggling to decide whether a fertility-sparing treatment of hydatidiform mole or a low-risk GTN can be chosen and how it must be conducted.

Mortality rate of gestational trophoblastic neoplasia with a FIGO score of ≥13.

BACKGROUNDnGestational 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.nnnOBJECTIVESnThe 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.nnnSTUDY DESIGNnWe 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.nnnRESULTSnThe 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.nnnCONCLUSIONnGestational 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.