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Objective: Mucinous ovarian carcinomas account for 3% of all epithelial ovarian carcinomas and are categorized into expansile or infiltrative subtypes. Nevertheless, the prognostic impact of these subtypes in stage I disease remains unclear., Methods: This retrospective study included patients with mucinous ovarian cancer who were referred to or treated at our institution between 1976 and 2022. Pathologic review was performed by 2 expert pathologists. Only patients with stage I disease were included in this study. Tumors were characterized as expansile or infiltrative, and oncologic features were analyzed., Results: A total of 80 cases met the inclusion criteria, with 36 and 44 patients having expansile and infiltrative subtypes, respectively. The disease stages were as follows: expansile subtype in 14 patients, stage IC in 22 patients, infiltrative subtype stage IA in 26 patients, and stage IC in 18 patients. The characteristics of the 2 groups of patients were comparable, except for the use of lymphadenectomy (more frequent in the infiltrative subtype: 28/44 [63%] vs 8/36 [22%] in expansile disease, p < .05). After a median follow-up of 79 months (range; 27.7-119.2), 10 (12.5%) recurrences occurred (3 expansile and 7 infiltrative). A total of 2 cases of expansile recurrence with pelvic recurrence were cured after secondary surgery and chemotherapy, and 1 patient died of the disease. A total of 5 patients with infiltrative recurrence had extra-pelvic spread and died of the disease, 1 patient was still alive with progressive disease, and the last was still alive and disease-free. A total of 2 cases of recurrence were observed after conservative surgery (1 of each subtype)., Conclusions: In this series, the overall and disease-free survival rates were not significantly different between patients with expansile and infiltrative stage I mucinous ovarian carcinoma. However, the prognosis of recurrent infiltrative cases is poorer than expansile cases., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2025 European Society of Gynaecological Oncology and the International Gynecologic Cancer Society. Published by Elsevier Inc. All rights reserved.)

Objective: Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values., Methods: We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival., Results: BRCA -mutated (BRCA m) patients had higher standardized KELIM than BRCA -wild type ( BRCA wt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCA wt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCA m and unfavorable KELIM, or BRCA wt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCA m and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001)., Conclusions: The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCA m or BRCA wt patients. Patients with both BRCA wt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies., Competing Interests: Competing interests: J-MC: reports personal fees from AstraZeneca, Roche, Vifor, Clovis, GlaxoSmithKline, and Merck Sharp and Dohme, outside the submitted work. LC: reports non-financial support from Pharmamar and GSK, outside the submitted work. P-EC: reports personal fees from Merck Sharp and Dohme, AstraZeneca, and GlaxoSmithKline, outside the submitted work. AD: reports non-financial support from Monaco Age Oncologie, outside the submitted work. TMR: reports personal fees from Pfizer, AstraZeneca, GlaxoSmithKline, Clovis Oncology, Roche, Merck Sharp and Dohme, Mylan, Tesaro, and Norvartis; grants from Pfizer, Merck Sharp and Dohme, and Seagen; a non-financial advisory role for the French National Cancer Institute, Arcagy, and Unicancer, outside the submitted work. LG: reports personal fees from Viatris, Roche, Merck Sharp and Dohme, Clovis, GlaxoSmithKline, and AstraZeneca, outside the submitted work. FJ: reports personal fees from Amgen, Astellas, AstraZeneca, Byaer, EISAI, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp and Dohme, Novartis, Novocure, Pfizer, Seagen, and Viatris; non-financial support from Astellas, AstraZeneca, Bristol-Meyer Squibb, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Ipsen, EISAI, and Chugai, outside the submitted work. EL: reports personal fees from Strycker, outside the submitted work. PP: reports personal fees from GlaxoSmithKline, Merck Sharp and Dohme, PharmaMar, and Roche, outside the submitted work. CP: reports personal fees from Roche, GlaxoSmithKline, Pharmamar, and Merck Sharp and Dohme, outside the submitted work. RS: reports grants from AstraZeneca; personal fees from GlaxoSmithKline, EISAI, Seagen, and Novartis; non-financial support from Merck Sharp and Dohme, GlaxoSmithKline, and Novartis, outside the submitted work. IR-C: reports personal fees from Agenus, Amgen, AstraZeneca, Clovis, Deciphera, GlaxoSmithKline, Macrogenics, Merck Sereno, Mersena, Novartis, Oxnea, Roche, Bristol-Meyer Squibb, and Merck Sharp and Dohme, outside the submitted work. MR: reports non-financial support from AstraZeneca; grants from Merck Sharp and Dohme, Daiichi Sankyo, and Bristol-Meyer Squibb; personal fees from AstraZeneca, Immunocore, Merck Sharp and Dohme, and GlaxoSmithKline, outside the submitted work. BY: reports personal fees from Merck Sharp and Dohme, AstraZeneca, GSK-TESARO, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, Bristol-Meyer Squibb, Seagen, Myriad, Menarini, Gilead, and EISAI, outside the submitted work. EB, OB, LB, MCa, MCh, OC, HC, CG, FM, TP, BS, and A-MS have nothing to disclose., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: IR-C has reported advisory boards for Abbvie, Agenus, Advaxis, Blueprint, BMS, ESAÏ, Daichi Sankyo, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Macrogenics, Novartis, Amgen, Tesaro and Clovis, and grants for traveling from Roche, MSD, AstraZeneca, Chugai and GSK; PG-C has reported Institution research grants from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Ther Inc, Glaxo, Hutchinson MediPharam Lt, Inhibrx Inc, Karyopharm Pharmaceuticals, PTC Ther, Novartis, Pfizer, PharmaMar, Rain Oncology, and SpringWorks Ther; RJ has reported advisory boards for Adaptimmune, Astex, Athenex, Bayer, Borhringer Ingelheim, Blueprint, Clinigen, Eisai, Epizume, Daichii, Deciphera, Immunedesign, Immunicum, Karma Oncology, Lilly, Merck, Mundipharma, PharmaMar, Springworks, SynOx, Tracon, and Upto Date; RS has reported grants for traveling from ParmaMar; FA has reported advisory boards for MiMark; J-YB has reported advisory boards for Deciphera, Bayer and Roche, and grants for traveling from OSE Pharma (unrelated); JM-B has reported advisory boards for Asofarma, Tecnofarma, FarmaMar, GSK, Novartis, Amgen, Bayer, Roche, Lilly and Boehringer Ingelheim, and grants for traveling from PharmaMar; AC has reported advisory boards for AstraZeneca and EISAI, and grants for traveling from PharmaMar, Merck and AstraZeneca; APDT has reported advisory boards for GSK, Boehringer and Novartis Oncology, and grants for traveling from PharmaMar; MLH has reported advisory boards for Aadi; PH has reported advisory boards for Boehringer Ingelheim and PharmaMar, and grants for traveling from Boehringer Ingelheim, PharmaMar, and Lighthouse PTC; PP has reported advisory boards for PharmaMar and MSD, and grants for traveling from Amgen, PharmaMar, AstraZeneca, and MSD; ARAR has reported research support (institutional) from 23&Me, Abbisko, AbbVie, Adaptimmune, Amgen, AstraZeneca, Bayer, Biontech, Blueprint Medicine, Boehringer Ingleheim, Bristol Myers Squibb, Cogent Biosciences, Daiichi Sankyo, Deciphera, Frontier Biopharma, Gilead, GSK, Iterion Therapeutics, Karyopharm Therapeutics, MedImmune, Medison, Merck, Neoleukin, Novartis, Pfizer, Polaris, Roche/Genentech, Rain Therapeutics, and Symphogen, expert testimony/advisory boards for Boehringer Ingelheim and Medison, DSMB (self) for Inhibrx, and honorarium (self) from Journal of Clinical Oncology, Medison and UpToDate; JS has reported advisory boards for AstraZeneca, Eisai, MSD, GSK, Novocure, Intuitive Surgical Deutschland GmbH, Seagan, Bayer Vital, GmbH, Mundipharma GmbH, PharmaMar, Sanofi-Aventis Deutschland GmbH, Immunogen, Tubulis GmbH, and Daiichi Sankyo, and grants for traveling from AstraZeneca, Eisai, MSD, GSK, Novocure, Intuitive Surgical Deutschland GmbH, Seagan, Bayer Vital, GmbH, Mundipharma GmbH; PharmaMar, Sanofi-Aventis Deutschland GmbH, Immunogen, Tubulis GmbH, Daiichi Sankyo; WvH has reported advisory boards for Sanofi, Belpharma, Boehringer Ingelheim, MSD, and Novartis, and grants for traveling from Sanofi; MF has reported consulting fees from AstraZeneca, Novartis, GSK, and Incyclix, payment for honoraria for lectures, presentations, spearkers bureaus, manuscript writing or educational events from AstraZeneca, GSK, MSD, and Limbic, participation on a data safety monitoring board or advisory board for AGITG IDSMB, and ENDO-3, and research grants (institution) from AstraZeneca, Beigene and Novartis; SCr, FMF, DF, IZ, SCh, RH, J-WK, SIK, MMM, and FP have reported no conflicts of interest.

Objective: The aim of this study was to investigate the relation between the peritoneal cancer index, overall survival, and recurrence free survival, in patients with epithelial ovarian cancer., Methods: Patients treated at the Gustave-Roussy Institute between December 2004 and November 2017 for advanced epithelial ovarian cancer in complete resection were included. The correlation between the peritoneal cancer index and survival was studied using statistical modeling. Multivariate analysis was performed with a logistic regression model., Results: Of the 351 patients included, 94 (27%) had initial surgery and 257 (73%) had interval surgery. Median follow-up was 52.7 months (range 47.6-63.9). Median peritoneal cancer index was 10 (range 0-32). The linear model best represented the relationship between peritoneal cancer index and overall survival. Patients with neoadjuvant chemotherapy had a greater instantaneous risk of baseline death than those with initial surgery, as well as a more rapid increase in this risk as the peritoneal cancer index increased. Overall survival and recurrence free survival were better in the initial surgery group (103.4 months (79.1-not reached (NR)) vs 66.5 months (59.1-95.3) and 31.8 months (23.7-48.7) vs 25.9 months (23.2-29), respectively). Risk factors for death were body mass index, peritoneal cancer index, and need for neoadjuvant chemotherapy., Conclusion: The peritoneal cancer index is a prognostic indicator, but its linear relationship with survival precluded setting a unique peritoneal cancer index cut-off. Moreover, the prognostic impact of peritoneal cancer index was stronger in the setting of neoadjuvant chemotherapy., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies., Methods: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials. All G2 healthcare providers were invited to participate in monthly multidisciplinary meetings. Patient data were collected using a standardized form and case summaries were distributed before each meeting. After each tumor board, a meeting summary with treatment recommendations was sent to all participants and the project manager at the coordinating center. The multidisciplinary tumor board format and outcomes were regularly discussed at G2 domain meetings. Anonymized clinical data and treatment recommendations were registered in a prospective database. For this report, clinical data were collected between November 2017 and December 2020 and follow-up data retrieved until May 2021., Results: During the 3-year period, 31 multidisciplinary tumor boards were held with participants from 10 countries and 20 centers. 91 individual patients were discussed between one and six times for a total of 109 case discussions. Follow-up data were retrieved from 64 patients and 80 case discussions. Adherence to treatment recommendations was 99%. Multidisciplinary tumor board recommendations resulted in 11 patients getting access to off-label treatment and one patient being enrolled in a clinical trial in another European country. 14/91 patients were recommended for surveillance only when additional treatment had been considered locally., Conclusion: Cross-border multidisciplinary tumor boards enable networking and clinical collaboration between healthcare professionals in different countries. Surveillance strategies, off-label drug use, and increased participation in clinical trials are possible benefits to patients with rare gynecological tumors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: Chemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According to in vitro data, BRCA mutated patients are sensitive to replicative stress agents but BRCA status is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according to BRCA status in first platinum-sensitive relapse., Methods: The ESME ovarian cancer database comprises a multicenter retrospective cohort of patients with ovarian cancer treated in French cancer centers between January 2011 and December 2017. Patients with high-grade serous ovarian cancers at first platinum-sensitive relapse who received one of these doublets were included. The objective was to compare progression-free survival of each chemotherapy doublet according to BRCA status., Results: Among the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825 BRCA wild type patients (53.6%) and 304 BRCA mutated patients (19.8%) (7 patients had a homologous recombination mutation and BRCA status was unkown for 403 patients). Median progression-free survival was longer in BRCA mutated patients than in BRCA wild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; p<0.001). In contrast, we observed no difference in patients treated with carboplatin/paclitaxel (14.6 vs 14.3 months, respectively; p=0.70) or in those treated with carboplatin/gemcitabine (12.0 vs 9.8 months, respectively; p=0.18). In BRCA wild type patients without maintenance, better progression-free survival occurred with carboplatin/paclitaxel (median progression-free survival 14.3 months) than with carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin (9.8 and 11.8 months, respectively; p=0.017). In BRCA mutated patients without maintenance, there was no difference between the three doublets (median progression-free survival of 14.6, 12.0, and 15.8 months with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin, respectively; p=0.40)., Conclusion: While treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy in BRCA mutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin in BRCA wild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse., Competing Interests: Competing interests: MR received honoraria from AstraZeneca, MSD, GSK, Immunocore and grant support from Bristol-Myers Squibb and Merck. RS received honoraria from GSK, EISAI, and Novartis and declares research grants from AstraZeneca. TD declares advisory boards from Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, MSD, Mylan, and Tesaro, research grants from Novartis, Pfizer, MSD, abd Seagen and local PI from Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma, and Seagen. The other authors have no conflicts of interest to declare., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: Improvement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment., Primary Objective: To test if the activity of non-platinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab., Study Hypothesis: The addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months., Trial Design: Patients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PD-L1) status., Major Inclusion/exclusion Criteria: Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatment-free interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria., Primary Endpoint: Overall survival and progression-free survival are co-primary endpoints., Sample Size: It is planned to randomize 664 patients., Trial Registration: NCT03353831., Competing Interests: Competing interests: PH reports grants and personal fees from Astra Zeneca, grants and personal fees from Roche, personal fees from Sotio, grants and personal fees from Tesaro, personal fees from Stryker, personal fees from Zai Lab, personal fees from MSD, grants and personal fees from public funding (ASCO, DKH, DFG), personal fees from Clovis, personal fees from Immunogen, grants from GSK, grants from Boehringer Ingelheim, grants from Medac, grants from Genmab, outside the submitted work. PP reports personal fees from Roche Laboratory, other personal fees from MSD laboratory, other from Clovis Oncology, outside the submitted work. AR reports grants and personal fees from Pharmamar, personal fees from Lilly, personal fees from Novartis, personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Tesaro, grants and personal fees from Roche, grants from Eisai, outside the submitted work. KL reports other personal fees from Astra Zeneca, other from GSK, outside the submitted work. CK reports personal fees and non-financial support from Roche, personal fees and non-financial support from Tessaro, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Pharmamar, personal fees from Lilly, personal fees from Genomic Health, outside the submitted work. EP reports personal fees from AGEA, personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Angelini, personal fees from Celgene, personal fees from Eisai, personal fees from Eli Lilly, personal fees from GSK, personal fees from MSD, personal fees from Novartis, personal fees from Pharmamar, personal fees from Pfizer, personal fees from Roche, personal fees from Tesaro, personal fees from Clovis, personal fees from Daiichi Sankyo, outside the submitted work. FH reports non-financial support from NewOncology; personal fees from Roche, personal fees from AstraZeneca, from Clovis, personal fees from Tesaro, from PharmaMar, outside the submitted work. JS reports grants, non-financial support and other from Roche, grants, non-financial support, and other perdonal fees from PharmaMar, grants, non-financial support and other peredonal fees from Teasaro, grants, non-financial support and other personal fees from Clovis, grants, non-financial support and other peersonal fees from Astra Zeneca, grants and non-financial support from MSD, grants, non-financial support and other personal fees from Novocure, outside the submitted work. ND: Dr. de Gregorio reports personal fees from Roche, personal fees from GSK, personal fees from Pharmamar, personal fees from Astra Zeneca, personal fees from Clovis, personal fees from Ingress, from null, outside the submitted work. PW reports grants and personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Clovis, personal fees from MSD, grants and personal fees from Novartis, personal fees from Pfizer, grants and personal fees from Roche, personal fees from Tesaro, personal fees from Eisai, personal fees from Pharmamar, personal fees from Teva, outside the submitted work. JL reports personal fees and other from Pfizer, grants and other from Merck/MSD, personal fees from Eisai, personal fees from Tesaro/GSK, grants and personal fees from AstraZeneca, personal fees from Artios, personal fees from Regeneron, outside the submitted work. DL reports grants, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from Tesaro, grants and personal fees from Clovis, grants and personal fees from Merck, grants, personal fees and non-financial support from Pharmamar, personal fees from Immunogen, personal fees from Genmab, personal fees from Amgen, personal fees and non-financial support from Astra Zeneca, outside the submitted work. FM reports personal fees from Roche, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Tesaro, personal fees from Novartis, personal fees from Amgen, personal fees from PharmaMar, personal fees from GenomicHealth, personal fees from CureVac, personal fees from EISAI, outside the submitted work., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: High grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear., Methods: A retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I-III) treated in 10 French Sarcoma Group centers was conducted., Results: 39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6-112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3-49.1) and 23 (4.4-41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I-II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival., Conclusions: The standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to report our institutional experience of a multimodal approach for treatment of locally advanced high-grade neuroendocrine cervical cancer., Methods and Materials: Patients with primary locally advanced neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The scheduled treatment sequence was as follows: pelvic +/- para-aortic radiotherapy (according to tumor stage), associated with chemotherapy based on platine-derivate and etoposide regimen, followed with a brachytherapy boost, then completion surgery if there was no progression +/- consolidation etoposide chemotherapy (for a total of 5-6 cycles). Disease-free survival (DFS) and overall survival (OS) were reported and prognostic factors were searched., Results: A total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22-77 years). Fourteen patients (58%) had pelvic lymph node metastases. After chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of 24 patients (75%). Histologically complete resection was achieved in 14 (78%) of 18 patients. Complete pathological response was reported in 7 (39%) of 18. With median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor relapse, all associated with distant failure, including one local failure. The DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022, respectively). Complete resection was associated with a lower incidence of relapses, as compared with microscopically incomplete resection (P = 0.04). A total of 12 (86%) of 14 patients with histologically complete resection were in complete remission at last follow-up. Apart from manageable acute hematological toxicities, most treatment complications were mild to moderate., Conclusions: This series based on a multimodal management compares favorably with previously published data. Most patients could be eligible to surgery, and complete remission was achieved in 85% of those amenable to complete resection.

Background: The present study retrospectively determined the outcomes and prognoses in stage I mucinous ovarian carcinoma according to histological type (ie, expansile or infiltrative)., Methods: A centralized pathologic review of tumors in patients treated from 1976 to 2016 for ovarian mucinous carcinoma was performed by 2 expert pathologists according to the 2014 World Health Organization classification. Only patients with stage I disease were analyzed. Tumors were typed as expansile or infiltrative and oncological issues analyzed., Results: A total of 114 cases were reviewed. Fifty were excluded (stage > I in 30 cases and no accessibility to a pathological review for 20 cases). Thus, 64 patients fulfilled the inclusion criteria: 29 had expansile-type and 35 infiltrative-type disease. The characteristics of both groups of patients were comparable, except the use of nodal staging surgery, which was more frequent in patients with infiltrative type. The International Federation of Gynecology and Obstetrics stages in expansile and infiltrative types were as follows: IA in 13 (45%) and 20 (57%), and IC in 16 (55%) and 15 (43%), respectively. Recurrence occurred in 3 patients with expansile type and 6 patients with infiltrative type. Two cases of expansile recurrence had pelvic recurrence and were salvaged after secondary surgery and chemotherapy, whereas 5 cases of infiltrative recurrence had extrapelvic spread and died from disease or were alive with progressive disease., Conclusions: Recurrence occurred in both types of stage I mucinous ovarian cancer. However, lethal recurrences were observed mainly in infiltrative type.

Objective: Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer., Methods: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor-positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety., Results: Seventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0-31.4) versus 40 weeks (90% confidence interval, 16.3-64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2., Conclusions: Although irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.

Objective: The aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer., Patients and Methods: In this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator's choice of 175 mg/m q3w or 80 mg/m weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety., Results: Between December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1-50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7-27.6 months)., Conclusion: Extended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety.

Objective: In platinum-resistant ovarian cancer, adding pertuzumab to gemcitabine improved progression-free survival in the subgroup with low tumor HER3 messenger RNA expression. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating pertuzumab plus chemotherapy in this population., Patients and Methods: Part 1 evaluated pertuzumab plus either topotecan or paclitaxel. Patients with platinum-refractory or platinum-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer and low HER3 messenger RNA expression (concentration ratio ≤2.81 by central quantitative reverse transcriptase-polymerase chain reaction testing on Cobas z480) received intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks) with the investigator's choice of topotecan (1.25 mg/m days 1-5 every 3 weeks) or weekly paclitaxel (80 mg/m) until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability., Results: Fifty patients were treated in part 1 (22 topotecan; 28 paclitaxel). In both cohorts, disease progression was the most common primary reason for discontinuing pertuzumab, and the most common all-grade adverse events (AEs) were fatigue/asthenia, anemia, and diarrhea. The most common grade ≥3 AEs were anemia (36%), neutropenia (27%), and fatigue/asthenia (18%) for topotecan, and peripheral sensory neuropathy (14%) and anemia (11%) for paclitaxel. Two patients receiving paclitaxel-pertuzumab died from AEs (abdominal infection; unexplained death). Median progression-free survival was 4.1 months (95% confidence interval, 1.9-6.1) with topotecan-pertuzumab and 4.2 months (95% confidence interval, 3.5-6.0) with paclitaxel-pertuzumab., Conclusions: Based on part 1 tolerability, the Independent Data Monitoring Committee had no objection to PENELOPE proceeding to part 2, a double-blind randomized comparison of chemotherapy (topotecan, paclitaxel, or gemcitabine) plus pertuzumab or placebo.

Objective: Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy with doxorubicin or ifosfamide or both is associated with a 10% to 30% objective response rate. We report a monocentric experience with doxorubicin, cisplatin, and ifosfamide (API) combination in the setting of multimodal treatment of advanced or metastatic ULMS., Patients and Methods: This monocentric retrospective study included patients with metastatic or locally advanced ULMS with a physiological age younger than 65 years treated in first line with a multimodal aggressive approach with API chemotherapy. Treatment consisted of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2 per day d1d2 plus mesna, cisplatin 75 mg/m2 d3, plus G-CSF; every 3 weeks up to 6 cycles. Surgery, radiation therapy, or radiofrequency ablation therapy of metastatic sites was associated whenever possible., Results: Thirty-eight patients received API for metastatic or locally advanced ULMS. Median age was 51 years (40-64 years); 4 (11%) patients were treated for a locally advanced disease and 34 (89%) for metastatic disease. Sixteen patients responded (4 complete responses+12 partial responses) among 33 evaluable patients (objective response rate, 48%); 8 and 9 patients had, respectively, stable and progressive disease. Twelve patients had surgeries with 9 surgical complete responses and 3 surgical partial responses. Median progression-free and overall survival in the whole population were 9.8 and 27 months, respectively. Main grade 3-4 toxicities in 38 patients were neutropenia (74%), thrombocytopenia (60%), anemia (55%), fatigue (18%), and vomiting (13%). Febrile neutropenia was observed in 37% of patients., Conclusions: Despite the toxicity observed, API is an effective treatment which compares favorably with other first-line therapies for patients with metastatic or advanced ULMS.

High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive behavior and poor prognosis. Cyclin D1 has been reported as a diagnostic immunomarker for high-grade endometrial stromal sarcoma with an YWHAE-FAM22 rearrangement. YWHAE-FAM22 endometrial stromal sarcomas (ESS) represent a clinically aggressive subtype of ESS classified as high-grade endometrial sarcomas, and its distinction from the usual low-grade ESS with JAZF1 rearrangement and from HGUS with no identifiable molecular aberration may be important in guiding clinical management. Median age of the patients is between 55 and 60 years. The most common symptoms are vaginal bleeding, abdominal pain, and increasing abdominal girth.Disease is usually advanced with approximately 70% of the patients staged III to IV according to the International Federation of Gynecology and Obstetrics classification. Preferential metastatic locations include peritoneum, lungs, intra-abdominal lymph nodes, and bone. Median progression-free survival ranged from 7 to 10 months, and median overall survival ranged from 11 to 23 months. There is no clear prognostic factor identified for HGUS, not even stage. The standard management for HGUS consists of total hysterectomy and bilateral salpingo-oophorectomy. Systematic lymphadenectomy is not recommended. Adjuvant therapies, such as chemotherapy and radiotherapy, have to be discussed in multidisciplinary staff meetings.

Objectives: The Gynecologic Cancer InterGroup aimed to provide an overview of uterine and ovarian leiomyosarcoma management., Methods: Published articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the Gynecologic Cancer InterGroup for review and comment, and appropriate revisions were made., Results: The approach to management of uterine and ovarian leiomyosarcoma management is reviewed., Conclusions: Uterine and ovarian leiomyosarcomas are rare and aggressive cancers that require specialized expertise for optimal management.

Small cell carcinoma of the cervix (SCCC) is a rare histological entity of uterine cervical cancer. Compared with other common histological types, squamous cell carcinoma or adenocarcinoma, the outcome of SCCC is poor because of the high incidence of nodal or distant metastasis even with early stage. In this review, current consensus of epidemiology, pathology, and initial treatment for SCCC will be discussed.

Small cell carcinomas of the ovary are uncommon and account for less than 1% of ovarian cancers. They were first recognized in 1979, and a number of reports appeared during the next 2 decades. They are highly aggressive tumors and usually carry a poor prognosis, although this may reflect that most are diagnosed at advanced stage; however, those diagnosed as stage 1A have only 30% to 40% of long-term survivors. More reports followed extending our experience in the diagnosis and management of these rare cancers. The classification is described below and shown in Table 1, but a revision is expected to be published from the World Health Organization in 2014.

Objective: Lapatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), also inhibits breast cancer resistance protein (BCRP) involved in resistance to topotecan. The aim of this multicenter study was to assess the efficacy of the combination topotecan-lapatinib in epithelial ovarian cancer relapsing after a first line of chemotherapy., Methods: Patients having relapsed within 6 months (n = 20) or between 6 and 12 months (n = 19) received weekly topotecan (3.2 mg/m given intravenously on days 1, 8, and 15) and daily oral lapatinib (1250 mg). Translational studies were performed on tumor and serum., Results: An objective (partial) response was observed for 5 patients (14%), all with late relapse. The rates of overall benefits, including responses and stabilizations, were 37% and 62% in patients having relapsed within or after 6 months, respectively. Corresponding median time to progression were 58 and 94 days. The most frequent toxicity was hematological, including grade 4 neutropenia (18%) and thrombocytopenia (3%). None of the tumors overexpressed HER2 or EGFR, and no mutation was found. Two Kras mutations were identified. Positive expressions of BCRP and cyclin A (median, 70% and 40%) were not correlated to the response to treatment., Conclusions: This study failed to demonstrate a clinical benefit of lapatinib-topotecan compared to previously described activity with topotecan alone in a context of low levels of EGFR and HER2 expressions, and no biomarkers could be identified. The absence of correlation between BCRP expression and clinical outcomes suggests that other mechanisms of resistance to topotecan could predominate.

Background: Surgical management of primary or recurrent ovarian cancer with extensive upper abdominal disease may require splenectomy to achieve complete cytoreduction. The aims of this series were to correlate the macroscopic exploration with the microscopic analysis of the spleen and to evaluate the morbidity of patients submitted to this procedure for primary and recurrent disease., Methods: Data concerning patients who underwent splenectomy at the time of management of the primary (initial group) or recurrent disease were reviewed. The characteristics and survival of patients were analyzed. The correlation between macroscopic suspected lesion and histological results and morbidity according to the Dindo classification was studied., Results: From 1995 to 2008, 58 patients (42 in the initial group and 16 in the recurrence group) underwent a splenectomy in our institution. Except for 3 cases requiring splenectomy for hemostatic reasons, the macroscopically suspected splenic lesion was confirmed by histology in 32 (80%) of 40 cases in the initial group and in 14 (93%) of 15 cases in the recurrence group. Eighteen patients (26.5%) had a morbidity grade strictly superior to 2, and in all the factors we tested, only pelvic posterior exenteration was a risk factor for high morbidity (P = 0.02)., Conclusions: When splenic lesions are macroscopically suspected during cytoreductive surgery for an ovarian cancer, most of the time the disease is confirmed by histology. When required to accomplish complete cytoreduction, splenectomy seemed to be justified.

Objective: Standard treatment of stage IB2/II cervical carcinoma is chemoradiation therapy. Residual disease is evaluated clinically and by magnetic resonance imaging. The place of surgery after this treatment is debated, except when there is suspicion of residual disease. There is no standard management when surgical resection is incomplete. The aim of this study was to describe the outcome of these patients., Methods: A retrospective review was undertaken of patients fulfilling the following inclusion criteria: (1) stage IB2/II cervical cancer, (2) external radiotherapy (45 Gy) with concomitant chemotherapy followed by uterovaginal brachytherapy (15 Gy), (3) magnetic resonance imaging performed between 3 and 8 weeks after brachytherapy, and (4) completion surgery with incomplete resection of pelvic disease. Patients with distant metastasis or carcinosis were excluded., Results: Ten patients treated between 2003 and 2006 fulfilled all inclusion criteria. The locations of the incomplete resection were (some patients had several locations) the parametrium (n = 4), lateral limit of the cervix (n = 4), anterior (n = 2), posterior (n = 3), and vagina (n = 2). Further surgery had been proposed for 3 patients but only performed once and this patient had rapid disease progression. One patient had received chemotherapy for metastatic para-aortic nodes. Seven patients died with a median period of 11 months after surgery (range, 3-21 months). One patient is alive with recurrent disease, and 2 are free of disease with 23 and 33 months of follow-up., Conclusions: The prognosis is poor when resection is incomplete after chemoradiation therapy in advanced-stage cervical cancer, and further surgery does not seem to improve this outcome.

Background: The aim of this study was to assess the outcomes of patients treated for peritoneal or ovarian psammocarcinoma (PSC)., Materials and Methods: Review of patients with PSC who underwent cytoreductive surgery in our institution with a follow-up of more than 18 months (the ovarian or peritoneal tumor was histologically reviewed by our reference pathologist)., Results: From 1997 to 2006, 15 patients with PSC were histologically reviewed in our institution. Five of these patients fulfilled the inclusion criteria. Four patients had ovarian PSC, and 1 had peritoneal PSC. Four patients were surgically treated during initial management and another patient at the time of recurrence. All of them underwent complete cytoreductive surgery followed by intraperitoneal chemotherapy in 2 patients and by conventional adjuvant chemotherapy in 1. After a median follow-up of 42 months, 4 of them remain disease-free., Conclusions: Peritoneal or ovarian PSC is a rare low-grade carcinoma characterized by a more favorable prognosis than classic carcinoma. The place of debulking surgery at the time of initial or recurrent management is important.

The objective is to investigate the activity and toxicity of bleomycin, etoposide, and cisplatin (BEP) regimen in ovarian granulosa cell tumors (OGCTs). Twenty consecutive patients with initial metastatic (5 patients) or recurrent (15 patients) OGCT were treated; BEP regimen: B: 30 mg intravenously or intramurally on days 1, 8, and 15; E: 100 mg/m2/day on days 1-5; and P: 20 mg/m2/day on days 1-5. Median age: 42 years (range: 17-60); median follow-up: 45 months (range: 3-112). The overall response rate is 90% (nine clinical complete response [CR], nine clinical partial response) with a median duration of 24 months (range: 4-77). A second-look laparotomy performed in 11 patients showed a pathologic CR in 7 cases and microscopic disease in 1 case. Seven patients remain free of disease (at 4-84 months); 11 patients relapsed (median: 24 months, range: 13-58), 12 patients are still alive, and 9 patients are without disease (2 patients in second CR). At 4 years, overall survival and event-free survival are respectively 58% and 30%. Toxicity is evaluable for 19 patients (48 cycles). A grade 4 neutropenia occurred in 15% of cycles (in seven patients) with a febrile neutropenia in four patients. Five patients experienced a low bleomycin pulmonary toxicity. BEP regimen appears to be an active regimen for OGCT in first-line chemotherapy.

Two patients treated using chemoradiation therapy (CRT) (with fetus in utero) for advanced-stage squamous cell cervical carcinoma diagnosed during the first trimester of pregnancy are reported. One patient with a stage IVA disease diagnosed at 12 weeks of gestation was treated by exclusive CRT with the fetus in utero. She recurred 20 months after the end of the treatment. The second patient had a stage IIB disease diagnosed at 12 weeks of gestation and was treated by CRT with the fetus in utero followed by completion surgery (radical hysterectomy and para-aortic lymphadenectomy) due to the presence of a suspicious residual disease. No residual disease was observed during the histologic analysis of hysterectomy and nodes specimens. This patient is alive and free of disease 24 months after surgery. Our observations could suggest that CRT in pregnant patients with fetus in utero is feasible without major short-term toxicity. Such management could be proposed in patients with a bulky cervical cancer diagnosed during the first trimester of the pregnancy. Management of the uterine evacuation depends on the local tumor spread.

Unlabelled: Uterine sarcoma is a poor prognosis disease, with a high risk of metastatic relapse. We conducted a study of adjuvant chemotherapy with cisplatin, ifosfamide, and doxorubicin followed by radiotherapy (n=18). The results were then compared in a matched case-controlled study to radiotherapy alone (n=16) or no therapy at all (n=2). Chemotherapy consisted in three cycles of adriamyein-platinum-ifosfamide (API) (doxorubicin 60 mg /m2 on day 1; cisplatin 100 mg /m2 on day 2; ifosfamide 5 g /m2 on day 1+mesna 5 g /m2 on day 1+granulocyte colony-stimulating factor; q 3 weeks). Drug doses were reduced (20% for ifosfamide and cisplatin) four times (four patients) due to hematologic toxicity. Compared to a case-control study of adjuvant radiotherapy alone, results were not decreased by the addition of a toxic chemotherapy., Conclusion: Adjuvant API chemotherapy followed by radiotherapy is a feasible protocol; a multicenter phase III study comparing radiotherapy alone versus API chemotherapy followed by radiotherapy just began in France.

Uterine sarcomas are an extremely rare event. There is no standard therapy for cases of relapse, although chemotherapy is commonly used. We studied the use of a cisplatin-based chemotherapy regimen for uterine sarcomas with an unusually long follow-up. Thirty-nine women with a median age of 50 years (32-71) entered the study. Histologically, leiomyosarcomas (26), carcinosarcomas (8), and stromal sarcomas (5) were represented. Group 1 consisted of patients undergoing adjuvant therapy (for initial disease, eight patients; for pelvic recurrence, two patients); Group 2 consisted of patients with advanced disease (locoregional after initial local therapy, five patients; local recurrence, six patients) or metastatic disease (stage IV, four patients; recurrence, 14 patients). DECAV therapy consisted of doxorubicin 50 mg/m2 d1, dacarbazine (DTIC) 200 mg/m2/d d1-3, vindesine 2 mg/day d1-2, cisplatin 100 mg/m2 d3, and either cyclophosphamide (CPM) 200 mg/m2/d d1-3 (n = 21), or ifosfamide (IFM) 2 g/m2/d d1-3 with mesna every 4 weeks Toxicity included 18 hospital stays for cytopenia (nine patients), including 13 cases of febrile neutropenia. Twenty blood transfusions in 10 patients and 12 platelet transfusions in seven patients were required. One toxicity-related death (hemorrhage) occurred. The overall response rate was 54% (3 complete response, 11 partial response) with a median duration of 13 months (4-36). Median overall survival was 14 month overall, 45 months for Group 1 and 13 months for Group 2. We conclude that the DECAV regimen is clearly active in uterine sarcomas but is too toxic to be recommended routinely.

The risk of tamoxifen-related endometrial adenocarcinoma is well established with daily dose and treatment duration of adjuvant tamoxifen as risk factors. There have also been in the past years, a few descriptions of uterine nonepithelial malignancies occurring after tamoxifen. We describe five recent cases of uterine carcinosarcomas occurring under/after tamoxifen administered in an adjuvant setting. None of these patients had received prior pelvic radiation therapy. Their median age at the diagnosis of breast cancer was 58 years (41-68), and 69 years (50-84) at the diagnosis of uterine carcinosarcoma. The median length of exposure to tamoxifen was 9 years (5-20), and the median time from the initiation of tamoxifen to the diagnosis of the uterine malignancy (latency period) 9 years (7-20). All patients presented with an advanced stage (IIA-IVA). Our data, together with those of the literature, plead for a causal role of a prolonged exposure to tamoxifen on the subsequent development of uterine carcinosarcoma. The long latency period observed even in patients receiving only 5 years of treatment leads us also to consider a prolonged gynecologic follow-up of the patients.

The aim of this study was to evaluate prognostic factors and to study combination radiotherapy-surgery as treatment for patients with bulky stage Ib and II cervical carcinoma. From 1985 to 1994, 187 patients with cervical cancer >/= 4 cm, were treated by combined radiation therapy and radical surgery including systematic para-aortic lymphadenectomy. Complications were observed in 34 (18%) patients. In a multivariate analysis, young age, tumor size less than 5 cm, metastatic nodes with capsular rupture, and bilateral nodes were independent prognostic factors. Overall survival at 3 years was 85%, 56%, and 40% in patients with negative nodes, positive pelvic nodes, and positive para-aortic nodes, respectively (P < 0.001). These results confirm the prognostic significance of young age, tumor size, and nodal involvement. Radical surgery combined with radiotherapy is feasible, with an acceptable rate of complications and yields satisfactory survival results in patients with bulky stage IB and II cervical carcinoma. Recent randomized published studies have demonstrated that concomitant chemotherapy and radiotherapy should be the gold standard in this setting. The role of surgery is questioned.

This study describes 45 cases of adult granulosa-cell tumors seen in our institution between 1976 and 1993. The median age was 46.5 years (12-77) and 18 women were postmenopausal. Vaginal bleeding was present in one-third of cases; other complaints were abdominal pain (28%) and the presence of a pelvic mass (47%). The tumor size was variable (<3 cm to 30 cm, median 11.5 cm). FIGO stages were: stage I: 30 (73%) (19 Ia, seven Ic, four I unknown); stage II: seven (17%) (two IIa, five IIC); stage III: three (7%) (one IIIb, two IIIc). Two adenocarcinomas and 13 cases of hyperplasia were found in 25 endometrial samples available. The initial therapy for all the cases was surgery, consisting in 34 patients of hysterectomy, bilateral salpingo-oophorectomy, +/- tumor resection. Sixteen patients received adjuvant therapy as well: chemotherapy (CT) alone for 12, radiotherapy (RT) alone for two, and CT + RT for two patients. Among the 39 patients who achieved a complete response after initial therapy, 15 patients have relapsed (pelvic recurrences) (38.5%) including six stage Ia (three received only conservative surgery). All the recurrent tumors were resected and 14/15 had CT (13/14 with cisplatin). The overall survival rate was 77.2% at 5 years, 66.5% at 10 years, and 41.2% at 20 years. A statistically significant difference was found between the survival of patients with stage Ia disease (75% at 10 and 15 years) and that of other patients (60% at 10 years, and <50% at 15 years). Serum estradiol and serum inhibin were measured in some patients and the results are described.