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Purpose: Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype., Methods: A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m 2 given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population., Results: Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months ( P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B ( P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy., Conclusion: Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.

Background: Malignant ovarian germ cell tumors usually occur in young women. The standard of care is fertility sparing surgery and comprehensive surgical staging followed by adjuvant chemotherapy with BEP (bleomycin, etoposide, cisplatin) if needed. The aim of this study was to analyze the reproductive outcomes after conservative treatment in patients diagnosed, treated and followed up in MITO (Multicenter Italian Trials in Ovarian Cancer) centers., Methods: A questionnaire concerning gynecological symptoms, reproductive outcomes and fertility treatment was administered to 164 MOGCTs survivors. Data regarding patients deceased were collected from MITO-9 database. There were 114 patients diagnosed at reproductive age between 1983 and 2019 included., Results: 109 patients answered the questionnaire and 5 patients decesased were included (median age 24.9 years). 78.1% were stage I,4.4% stage II, 14.9% stage III and 2.6% stage IV. 57.9% received chemotherapy, the mean number of cycles was 4.1. Median time to menstrual recovery after BEP was of 5.6 months range, only 1 case of premature ovarian failure was reported. Among the 114 patients 38 (33.3%) attempted to become pregnant, 29/38 (76.3%) got pregnant with a total of 44 conceptions. 40.9% received chemotherapy and 22.9% did not (p 0.048). Pregnancy desire was the only predictive factor associated with live births among women who attempted pregnancy after treatment., Conclusions: As MOGCTs affect women of child-bearing age, fertility preservation represents a major treatment issue. Our results are consistent with the available evidence, confirming that adjuvant chemotherapy for MOGCT does not impact the reproductive function and fertility., Competing Interests: Conflicts of interest Alice Bergamini, Giorgia Mangili and Gabriella Ferrandina declare honoraria and research funding from MSD, GSK, Clovis and Astrazeneca. Sandro Pignata declares honoraria from Roche, MSD, Astrazeneca, GSK and research funding from Pfizer, Roche, Astrazeneca, MSD and GSK., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity., Methods: In this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs)., Results: Activated T cells showing features of partial exhaustion with a CD137 + CD39 + PD-1 + TIM-3 + CD45RA - CD62L - CD95 + surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137 + CD39 + PD-1 + TIM-3 + CD45RA - CD62L - CD95 + signature., Conclusion: These data demonstrate that EOC is enriched in CD137 + CD39 + PD-1 + TIM-3 + CD45RA - CD62L - CD95 + T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches., Competing Interests: CBo: received research support from Intellia Therapeutics and is member of advisory boards/consultant/speaker for Molmed, Intellia, TxCell, Novartis, GSK, Allogene, Kite/Gilead, Miltenyi, Kiadis, QuellTX, Janssen. BS is an employee and shareholder of Intellia Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tassi, Bergamini, Wignall, Sant’Angelo, Brunetto, Balestrieri, Redegalli, Potenza, Abbati, Manfredi, Cangi, Magliacane, Scalisi, Ruggiero, Maffia, Trippitelli, Rabaiotti, Cioffi, Bocciolone, Candotti, Candiani, Taccagni, Schultes, Doglioni, Mangili and Bonini.)

Introduction: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer. The aim of this survey was to better understand prescription patterns of anticoagulants, in particular of DOACs, especially in gynecological cancers (GCs)., Methods: Our survey was made up of 21 questions, the last four questions addressed to medical doctors (MDs) involved in GCs. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members., Results: Overall, 113 MDs completed the questionnaire, 69 involved in GCs. Most respondents (46, 41%) were aged 30-40 years old, worked in public hospitals (59, 52.2%), were medical oncologists (86, 76.1%). LMWH was the preferred choice for the treatment of CAT (104, 92%). However, 89 respondents (78.8%) prescribed or asked to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty in verifying the therapeutic effect and the absence of antidotes in case of bleeding (37.9%). In patients with GCs, DOACs were used with niraparib, olaparib, rucaparib and immune checkpoint inhibitors (ICIs) in less than 10 patients by 23%, 20%, 9% and 10.2% of respondents, respectively., Conclusion: The responders are aware of the Direct-acting oral anticoagulants option and would like to use them.

Malignant ovarian sex cord-stromal tumors are rare neoplasms that account for approximately 5-7% of all ovarian malignancies, and they are primarily treated with surgery. The prognosis of patients with different surgical extents remains controversial. Therefore, the effects of different surgical extents on the prognosis of patients were explored in this retrospective cohort study. Patients with malignant ovarian sex cord-stromal tumors who underwent surgical treatment from January 2000 to December 2019 were selected. Disease-free survival and overall survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. Prognosis factors were identified by Cox regression analysis. P < 0.05 was considered a statistically significant difference. A total of 278 patients with an average age at onset of 42 (8-78) years old were enrolled. The median follow-up time was 73 months. There was no significant difference in disease-free survival and overall survival rates between patients who underwent fertility-sparing surgery and those who underwent Non-fertility-sparing surgery, and between patients underwent staging surgery and those underwent Non-staging surgery. Age < 40 years (P = 0.024), stage II-III (P = 0.038), a high CA125 level (P = 0.035) and WT-1 (+) (P = 0.016) were independent risk factors for recurrence. In conclusion, different surgical extents have no significant influence on recurrence and survival status of patients with malignant ovarian sex cord-stromal tumors., (© 2024. The Author(s).)

Granulosa cell tumors of the ovary have an indolent behavior and a good prognosis, but a high incidence of local recurrence after surgery. The best treatment in the recurrent setting is unclear and randomized clinical trials on the management in the recurrent setting are lacking. The role of radiotherapy is controversial in adjuvant settings and unknown in case of relapse after surgery. This review aims to summarize the level of evidence of the role of radiation treatments for granulosa cell tumors of the ovary., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This open-label phase II clinical trial evaluated the antitumor activity and safety of trabectedin in patients with advanced ovarian (OC) or uterine carcinosarcomas (UC)., Methods: Eligible patients were adults (≥18 years) with histologically proven recurrent OC/UC not amenable to surgery or radiotherapy who received up to two prior chemotherapy lines. Trabectedin 1.3 mg/m 2 was administered as a 3-h infusion every three weeks. The primary endpoint was objective response rate (ORR) as per RECIST v.1.1. If at least 8 of 43 patients (18.6%) achieve an objective response, trabectedin would be declared worthy for further investigations., Results: Forty-five patients with either OC (n = 32) or UC (n = 13) from seven MITO centers across Italy were enrolled. The ORR was 11.9% (90% CI: 6-23) and included two patients with a complete response and three with a partial response. Eight patients (19.0%) had disease stabilization for a disease control rate of 31.0% (90% CI: 20-44). Median progression-free survival was 2.01 months (95% CI: 1.78-2.30) and median overall survival was 4.64 months (95% CI: 3.19-8.29). Neutrophil count decreases (n = 8, 18.2%) and transaminase increases (n = 6, 13.6%) were the most common grade 3-5 adverse events related with trabectedin. Two patients died due to trabectedin-related grade 5 hematological toxicity., Conclusion: Although trabectedin did not meet the prespecified activity criteria, it confers modest but clinically meaningful benefit to patients with advanced OC/UC as being as effective as any other available treatment for this indication. The toxicity profile appears in line with that previously reported for the drug., Competing Interests: Declaration of Competing Interest DL reports personal fees, travel support and institutional grants and founding from PharmaMar. SP reports personal fees from MSD, AstraZeneca, Roche, PharmaMar, Clovis and GSK; research funding from AstraZeneca, MSD, Roche and Pfizer. VS reports personal fees from MSD, GSK, Roche, PharmaMar, Clovis, Eisai and AstraZeneca; travel support from Roche, PharmaMar and AstraZeneca; funding from MSD, GSK, Roche and AstraZeneca. AB (Alice Bergamini) reports personal fees from GSK, PharmaMar, Clovis, Eisai and AstraZeneca/MSD; funding from GSK and AstraZeneca/MSD. All remaining authors have declared no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Endometrioid borderline ovarian tumor (EBOT) is a rare subtype of borderline ovarian malignancies. This study was designed to determine the prognosis of a series of EBOT., Methods: This is a retrospective review of patients with EBOT treated in or referred to our institutions and a centralized, histological review by a reference pathologist. Data on the clinical characteristics, management (surgical and medical), and oncologic outcomes of patients were required for inclusion., Results: Forty-eight patients were identified. Median age was 52 years (range 14-89). Fourteen patients underwent a conservative surgery and 32 a bilateral salpingo-oophorectomy (unknown in 2 cases). Two patients had bilateral tumors. Forty-three patients had stage I disease, and five patients had stage II disease (10%). Stromal microinvasion and intraepithelial carcinoma was observed in 6 (12%) and 13 (27%) patients respectively. Endometriosis was histologically associated in 12 patients (25%). Synchronous endometrial disease was found in 7 (24%) of 29 patients with endometrial histological evaluation. The median follow-up was 72 months (range 6-146). Two patients developed a recurrence after cystectomy in form of borderline disease (5%). No death related to EBOT occurred., Conclusions: Peritoneal restaging surgery should be performed if not realized initially, because 5% of EBOTS are diagnosed at stage II-III. Fertility-sparing surgery seems a safe option in selected patients. Because synchronous endometrial diseases, including endometrial carcinoma are frequent, systematic hysterectomy (or endometrial sampling in case of fertility-sparing surgery) is mandatory. Prognosis is generally excellent. Recurrence is a rare event (6%), but it can occur in the form of invasive disease., (© 2022. Society of Surgical Oncology.)

Objective: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL)., Methods: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28)., Results: This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS., Conclusions: Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL., Competing Interests: Declaration of Competing Interest DMC reports personal fees from GSK; has received honoraria from Roche; been a consultant to Mateon Therapeutics and AstraZeneca, and her institution has received research grants from Genentech. Margarita RM reports grants from GSK, Clovis, and Pfizer; consulting fees from Merck & Co., Inc. and GSK; has received honoraria and travel support from AstraZeneca. FB has served on advisory boards from Merck, Eisai, Agenus, AstraZeneca, and GSK. WG reports personal fees from Tesaro. Mansoor RM reports receiving advisory board fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck & Co., Inc., Roche, and Zailab; travel support from GSK and AstraZeneca; is a member of board of directors and holds shares in Karyopharm; received institutional research grants from Apexigen, AstraZeneca, Ultimovacs, and GSK. BP has received institutional grant support from Tesaro/GSK, AstraZeneca, Merck, Genentech/Roche, Celsion Corporation, Mersana Therapeutics, Inc., and Clovis Oncology, and advisory board compensation from Tesaro/GSK, AstraZeneca, Merck, Toray, Mersana Therapeutics, Inc., Elevar, Arquer Diagnostics, and Eisai. GM reports receiving travel grants from Merck & Co., Inc., GSK, AstraZeneca, and PharmaMar. DOM reports grants and personal fees from Clovis Oncology; has served on advisory boards for Agenus, AstraZeneca, Eisai, Genentech/Roche, ImmunoGen, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Merck, Mersana, Myriad, Novartis Pharmaceuticals, Novocure, Regeneron Pharmaceuticals, Seagen, Tarveda, and Tesaro/GSK; has served on steering committees for Amgen; has served as a consultant to AbbVie, Agenus, Ambry, AstraZeneca, Eisai, Genentech/Roche, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Novartis Pharmaceuticals, Novocure, Seagen, and Tesaro/GSK; and has received research support to his institution from AbbVie, Agenus, Ajinomoto, Amgen, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, Ergomed Clinical Research, Genentech/Roche, Genmab, GOG Foundation, ImmunoGen, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Ludwig Institute for Cancer Research, Merck, Mersana, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron Pharmaceuticals, Seagen, Serono, Stemcentrx, Tesaro/GSK, TRACON Pharmaceuticals, VentiRx, and Yale University. LW reports receiving fees from Genentech, GSK, AstraZeneca, Merck & Co., Inc., and Eisai. RLC reports grants and consulting fees from Agenus, Alkermes, Deciphera, GSK, OncoQuest Inc., Onxeo, Oncxerna, Regeneron, AstraZeneca, Clovis Oncology, Genelux, Genmab, Merck & Co., Inc., ImmunoGen Janssen, Roche/Genentech; served as a board member of VBL Therapeutics. DL reports receiving advisory board fees from AstraZeneca, Clovis Oncology, Genmab, Immunogen, and Amgen; grant support, paid to her institution, and consulting fees from PharmaMar, and grant support, paid to her institution, and advisory board fees from Merck. FMK and TW are employees of GSK. BJM reports receiving honoraria from Agenus, Akeso, Inc., Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, Gynecologic Oncology Group foundation, Gradalis, ImmunoGen, Karyopharm, Iovance, Macrogenics, Merck & Co., Inc., Mersana, Novartis, Novocure, Myriad, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL Therapeutics. AG-M reports receiving consulting fees, lecture fees, and/or travel support from Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Immunogen, MacroGenics, Mersana, MSD, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, and Takeda. SH, DB, KB, TS, V-HS have no conflicts to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Sex cord stromal tumors are rare neoplasms, frequently diagnosed in young women often as early-stage disease. In patients who desire to preserve fertility, when possible, unilateral salpingo-oophorectomy with peritoneal surgical staging is a safe alternative to radical treatment. In this review, we analyze the available literature on the obstetrical outcomes after fertility-sparing surgery in a total of 255 patients with sex cord stromal tumors. We found that the spontaneous conception rate in granulosa cells tumor is encouraging (88.5%). In particular, juvenile granulosa cell tumors are associated with a more successful pregnancy rate than adult granulosa cells tumors (11/26 (42.3%) in juvenile granulosa cells tumors compared with 28.5% in adult granulosa cell tumors, respectively.) On the other hand, the results of obstetrical outcomes in Sertoli-Leydig cells tumors are less promising (7/36 (19.4%)). Unfortunately, no evidence on this topic is available for sex cord tumor with annular tubules due to the low incidence. Regarding the oncological outcomes of 900 cases of sex cord stromal tumors treated conservatively, data are reassuring with comparable outcomes between patients treated with conservative and radical surgery. Given the limited available data on this rare tumor, further studies are needed to evaluate the safety of conservative approaches and to define the obstetrical outcomes in this patient population., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

Background: Clear cell borderline ovarian tumor (CCBOT) is one of the rarest subtypes of borderline ovarian malignancies. The aim of this study was to determine the prognosis of a series of CCBOT., Patients and Methods: A retrospective review of patients with CCBOT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion., Results: Nineteen patients were identified. Median age was 62 (range 36-83) years. Four patients underwent a conservative surgery and 14 a bilateral salpingo-oophorectomy +/- hysterectomy (unknown in 1 case). One patient had bilateral tumor, and all cases were stage-I disease. All CCBOTs showed an adenofibromatous pattern. Stromal microinvasion was observed in seven cases and intraepithelial carcinoma in two cases. Endometriosis was histologically associated in one case. The median follow-up was 76 (range 6-231) months. No recurrence occurred. Two patients died of intercurrent disease., Conclusions: Peritoneal staging procedures should always be associated, but restaging surgery could be omitted if there was no suspicious lesion in the peritoneum during initial surgery, since all patients reported had stage-I disease. Fertility-sparing surgery appears to be a safe alternative in young patients. Synchronous endometrial disorders with atypia are infrequent. Prognosis is generally excellent, and long-term risk of recurrence is low. The two recurrences described in literature occurred in stage-IC diseases, highlighting the importance of avoiding perioperative rupture., (© 2021. Society of Surgical Oncology.)

Objective: To describe the clinical and ultrasound characteristics of recurrent granulosa cell and Sertoli-Leydig cell tumors., Methods: This was a retrospective observational study performed at Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS, Rome (Gemelli center), Italy. Patients with a histological diagnosis of recurrent granulosa cell tumor or Sertoli-Leydig cell tumor were identified from the database of the Department of Gynecological Oncology. Those who had undergone a preoperative ultrasound examination at the Gemelli center between 2012 and 2020 were included, and the data retrieved from the original ultrasound reports. In all of these reports, the recurrent tumors were described using International Ovarian Tumor Analysis (IOTA) terminology. If a patient had more than one episode of relapse, information from all episodes was collected. If there was more than one recurrent tumor at the same ultrasound examination, all tumors were included. One expert sonographer also reviewed all available ultrasound images to identify typical ultrasound patterns using pattern recognition., Results: We identified 30 patients with a histological diagnosis of recurrent granulosa cell tumor (25 patients, 55 tumors) or Sertoli-Leydig cell tumor (five patients, seven tumors). All 30 had undergone at least one preoperative ultrasound examination at the Gemelli center and were included. These women had a total of 66 episodes of relapse, of which a preoperative ultrasound examination had been performed at the Gemelli center in 34, revealing 62 recurrent lesions: one in 22/34 (64.7%) episodes of relapse, two in 4/34 (11.8%) episodes and three or more in 8/34 (23.5%) episodes. Most recurrent granulosa cell tumors (38/55, 69.1%) and recurrent Sertoli-Leydig tumors (6/7, 85.7%) were classified as solid or multilocular-solid tumors, while 8/55 (14.5%) recurrent granulosa cell tumors and 1/7 (14.3%) recurrent Sertoli-Leydig cell tumors were unilocular cysts and 9/55 (16.4%) recurrent granulosa cell tumors were multilocular cysts. The nine unilocular cysts had contents that were anechoic (n = 2) or had low-level echogenicity (n = 7), had either smooth (n = 4) or irregular (n = 5) internal cyst walls, and ranged in largest diameter from 8 to 38 mm, with three being < 20 mm and five being 20-30 mm. On retrospective review of the images, two typical ultrasound patterns were described: small solid tumor measuring < 2 cm (15/62, 24.2%) and tumor with vascularized echogenic ground-glass-like content (12/62, 19.4%)., Conclusions: Some granulosa cell and Sertoli-Leydig cell recurrences manifest one of two typical ultrasound patterns, while some appear as unilocular cysts. These are usually classified as benign, but in patients being followed up for a granulosa cell tumor or Sertoli-Leydig cell tumor, a unilocular cyst should be considered suspicious of recurrence. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

After more than 30 years of a one-size-fits-all approach in the management of advanced ovarian cancer, in 2018 the SOLO1 trial results have introduced a new era of personalized medicine. A deeper knowledge of ovarian cancer biology and the development of new drugs targeting specific molecular pathways have led to biomarker-driven phase 3 trials with practice changing results. Thereafter, platinum-based combinations are no longer the only therapeutic options available in first line setting and poly-ADP ribose polymerase inhibitors maintenance therapy has become the mainstay in patients with tumor harboring a homologous recombination defect. However, most of the recent therapeutic breakthroughs regard high grade serous carcinoma, the most frequent ovarian cancer subtype, and only few improvements have occurred in the management of less common histotypes. Moving towards the next challenges, we aimed to investigate and review new potential molecular targets in ovarian cancer, according to histotype, starting from promising molecular drivers and matched drugs that have been investigated in early and late-stage clinical trials or conceptualized in preclinical studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity., Material Methods: This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis., Results: Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17-82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9-700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2-995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown., Conclusion: It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might be recommended routine surveillance alone after complete surgical staging., Methods: MITO-9 was a prospective observational study analyzing data collected between January 2013 and December 2019. Three groups were identified: group A included 13 patients stage IA dysgerminoma and IAG1 immature teratoma; group B included 29 patients with stage IB-C dysgerminomas, IA-C G2-G3 immature teratomas and stage IA mixed malignant ovarian germ cell tumors and yolk sac tumors; and group C included five patients (two patients with stage IC1 and one patient with stage IC2 yolk sac tumors and two patients with mixed-stage IC2 malignant ovarian germ cell tumors)., Results: A total of 47 patients with stage I conservatively treated malignant ovarian germ cell tumors were analyzed. Two patients in group B were excluded from the routine surveillance alone group due to positive surgical restaging. Therefore, a total of 45 patients were included in the study. Median follow-up was 46.2 months (range; 6-83). In total, 14 of 45 patients (31.1%) received chemotherapy, while 31 (68.9%%) underwent surveillance alone. One patient in group A, with stage IA dysgerminoma had a relapse, successfully managed with conservative surgery and chemotherapy. None of the patients in group B and C relapsed. All patients were alive at completion of the study. Overall, among 31 patients (68.9%) who underwent surveillance alone, only one patient relapsed but was treated successfully., Conclusions: Our data showed that close surveillance alone could be an alternative option to avoid adjuvant chemotherapy in properly staged IB-C dysgerminomas, IA-IC G2-G3 immature teratomas, and IA mixed malignant ovarian germ cell tumors with yolk sac tumor component., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Juvenile type granulosa cell tumor (JGCTs) are extremely rare, mainly diagnosed in young women and pre-pubertal girls at stage I disease. Literature is scanty and guidelines regarding the optimal management are still controversial. The aim of this study is to add on the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer)., Methods: Clinicopathological data from patients with stage I JGCTs were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse., Results: Seventeen patients were identified. Surgical approach was laparoscopic and open for 7 (41%) and 10 (59%) patients, respectively. Fertility sparing surgery (FSS) was performed in 15 patients (88%): unilateral salpingo-oophorectomy (USO) in 11 patients, cystectomy with subsequent USO in 2 patients and cystectomy alone in the remaining 2. Adjuvant chemotherapy was given in 2 cases. After a median follow up time of 80 months, no recurrences were registered., Conclusions: Given the available data, minimally invasive surgery is safe in stage I JGCTs. Because of the good prognosis and of the young age of patients, FSS can be chosen in most of the cases. The role of cystectomy deserves further validation. The need of adjuvant chemotherapy in stage I disease is still unclear, even if available data does not seem to support treatment over surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs)., Methods: A multi-institutional retrospective study was conducted within the MITO Group., Results: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT., Conclusions: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished., Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice., Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue., Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

Background: The role of surveillance after surgery for stage IA-C grade 2 (G2) or grade 3 (G3) immature teratomas (ITs) is controversial with many guidelines advocating adjuvant chemotherapy. Here, we investigate the safety of surveillance in stage IA-C G1-3 ITs., Methods: Clinicopathological data were analysed on postpubertal patients with stage I pure ITs in Multicenter Italian Trials in Ovarian Cancer centres and at Charing Cross Hospital, UK, between January 1985 and January 2018., Results: Of 108 stage I patients, 66 (61.1%), 3 (2.8%) and 39 (36.1%) were International Federation of Gynecology and Obstetrics IA, IB, IC, respectively, with 31 (28.7%), 41 (38%) and 36 (33.3%) having grade 1 (G1), 2 and 3 disease, respectively. After surgery, 27 patients (25%) had adjuvant chemotherapy and 81 (75%) surveillance. There was no significant increase in the risk of malignant (G2-3 IT) relapse (9/81 vs 2/27; p = 0.72) or in disease-free survival (DFS) or overall survival in the surveillance vs chemotherapy groups. The median time to relapse was 17.8 months (range: 3-47) with no significant difference between surveillance or chemotherapy groups. The median follow-up was 64.3 months (Interquartile range (IQR) 22.2-101.7). Chemotherapy induced cures in all except for one patient who did not follow the surveillance protocol due to pregnancy and died of disease. Univariate and multivariate analyses revealed that only tumour grade (hazard ratio [HR] = 3.11; p = 0.02) and complete surgical staging (HR = 0.2; p = 0.01) were independent prognostic factors for decreased DFS., Conclusion: The present study suggests that in the adult setting careful surveillance appears to be an acceptable alternative to adjuvant chemotherapy for stage IA-C ITs of any grade, properly staged and with negative postoperative tumour markers., Competing Interests: Conflict of interest statement All authors declare no potential conflict of interests regarding this manuscript., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Objective: Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS., Materials and Methods: Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes., Results: 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate., Conclusions: Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity., Methods: This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients., Results: 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity., Conclusion: Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown., Methods: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival., Results: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred., Conclusions: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.)., (Copyright © 2019 Massachusetts Medical Society.)

Ovarian cancer relapses have been traditionally classified according to the platinum-free interval, leading to an arbitrary categorization of possible scenarios and treatment options. Its relevance in assessing treatment strategies has been revised in the last several years, as the panorama is constantly changing in the era of personalized medicine and targeted therapies. Factors to be considered while defining the best management of recurrent disease, and, consequently, the available treatment alternatives are increasing. Platinum remains one of the milestones of ovarian cancer treatment, but for some patients it might not be an ideal choice for several reasons other than limited platinum sensitivity. This review aims to analyze the scenarios in which platinum is not considered suitable in the management of patients with recurrent ovarian cancer, and the currently available alternatives., Competing Interests: Competing interests: AB and GM report personal fees and non-financial support from Tesaro, AstraZeneca, Pharmamar and Roche, outside the submitted work; LB reports personal fees and non-financial support from Tesaro, AstraZeneca, and Pharmamar outside the submitted work., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer)., Methods: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression., Results: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival., Conclusions: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: What are the reproductive outcomes of women who had fertility preservation (FP) using either oocyte or embryo vitrification after fertility-sparing surgery (FSS) for a borderline ovarian tumor (BOT)?, Methods: A retrospective, single-center cohort study was conducted between January 2013 and December 2021. Patients with BOT who resorted to FP by vitrifying oocytes or embryos were included. Both clinical and reproductive parameters were reviewed. The primary outcome was live birth., Results: In total, thirteen patients who performed 31 FP cycles were included. Of those, six patients achieved eight live births after a mean follow-up period of 79 months. Three further pregnancies are still ongoing. All pregnancies/live births were obtained without using their cryopreserved oocytes or embryos., Conclusion: Women who had FSS for BOT have favorable prospects of live offspring, even without the need to use their cryopreserved material. Fertility preservation in patients with BOT has to be considered as a tool to mitigate the risk of infertility that may arise in case of BOT recurrence requiring castrating surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Women with a BRCA mutation have an increased risk of developing breast and ovarian cancer. Bilateral salpingo-oophorectomy is the only effective strategy to reduce this risk. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended between the ages of 35 and 40 for women carriers of BRCA1 and between the ages of 40 and 45 for women carriers of BRCA1 and BRCA2 mutations. Most women undergo this procedure prior to their natural menopause subsequently developing an anticipated lack of hormones. This condition affects the quality of life and longevity, while it is more pronounced in women carrying a BRCA1 mutation compared to BRCA2 because they are likely to have surgery earlier. Hormone replacement therapy (HRT) is the only strategy able to significantly compensate for the loss of ovarian hormone production and counteract menopausal symptoms. There is strong evidence that short-term HRT use does not increase the risk of breast cancer among women with a BRCA1 mutation. Few data are available on BRCA2 mutation carriers. Therefore, BRCA mutation carriers require careful counseling about the outcomes of their RRSO, including menopausal symptoms and/or the fear associated with HRT use., (© 2022. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Background: MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome., Patients and Methods: Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat., Results: Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC., Conclusion: MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items., Clinicaltrials.gov: NCT00657878.

About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and present with stage I disease. For this subset of women, the issue of fertility sparing surgery (FSS) has become critical. The aim of this survey was to investigate the management of EOC patients desiring to preserve fertility in Italy. A questionnaire consisting of 30 items was developed to evaluate: patient-selection criteria, rate of FSS, patient's counseling- and pregnancy-timing, fertility preservation, obstetrics, and oncologic outcomes. One expert clinician for each of 50 major gynecologic oncology centers was invited to participate. Data were entered into a database and statistically analyzed. 74% of questionnaires were complete. The proportion of EOC patients treated with FSS was <10%, 10%-20% and >20% in 70.3%, 24.3% and 5.4% of cases, respectively. Age, fertility preservation desire, histotype, and stage were considered relevant to select patients for a conservative treatment for 64.8%, 72.9%, and 78.3% of responders, respectively. Only 17 centers (45.9%) resulted to have an assisted reproductive technique service and Obstetrics Department. Our survey highlights discrepancies among oncologists in the management of patients with early EOC undergoing FSS. More efforts should be made to define and broadcast the best management before and after surgery.

Objective: This study assessed the effect of omentectomy on the prognosis and fertility in patients with clinically early-stage (I, II) malignant ovarian germ cell tumours (MOGCT)., Design: A retrospective multicentre study., Setting: Four university teaching hospitals in China., Population: A total of 268 patients with clinically apparent early-stage (I, II) MOGCT., Methods: Data were obtained from the medical records. Additionally, the propensity score matching (PSM) algorithm was adopted., Main Outcome Measures: Prognostic outcomes were disease-free survival (DFS) and overall survival (OS). Fertility outcomes were pregnancy and live birth rates., Results: A total of 187 (69.8%) patients underwent omentectomy. Kaplan-Meier analysis showed no significant differences in DFS and OS between the omentectomy and non-omentectomy groups before and after PSM (p > 0.05). Additionally, subgroup analysis stratified by age (<18 and ≥18 years) showed similar results. International Federation of Gynecology and Obstetrics (FIGO) stage was the only risk factor associated with DFS (hazard ratio [HR] 14.71, 95% confidence interval [CI] 4.47-48.38, p < 0.001) and OS (HR 37.36, 95% CI 3.87-361.16, p = 0.002). Pregnancy and live birth rates in the total population were 80.3% and 66.7%, respectively. There were no significant differences between the two groups before and after PSM., Conclusions: Omentectomy did not improve survival or affect fertility in patients with clinically apparent early-stage (I, II) MOGCT, regardless of the age. The clinical FIGO stage was an independent risk factor for recurrence and death., (© 2022 John Wiley & Sons Ltd.)

The well-known impact of ovarian endometriosis on female quality of life and the established role of lncRNA LINC01465 in ovarian cancer pathogenesis have been extensively documented; however, the relationship between LINC01465 and ovarian endometriosis is still not clear. This study seeks to explore the potential involvement of LINC01465 in the disease. The study analyzed a sample of 80 endometriosis patients and 80 healthy women. The expression of LINC01465 was measured in ectopic and eutopic endometrial tissues through RT-qPCR. The diagnostic potential of serum LINC01465 levels was evaluated using ROC curve analysis, and the patients were followed up for 3 years after treatment to monitor recurrence. The results revealed that the expression of LINC01465 was significantly lower in ectopic endometrial tissues in comparison to paired eutopic tissues for most of the patients. No correlation was found between the patient's age or lifestyle and serum LINC01465 levels. After treatment, the serum LINC01465 level increased, and patients who experienced recurrence had significantly lower levels compared to those who did not. In conclusion, the study findings suggest that the downregulation of LINC01465 plays a role in the pathogenesis of ovarian endometriosis and may serve as a diagnostic and prognostic biomarker for the disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: To evaluate the changes in the ultrasound characteristics of decidualized non-ovarian endometriotic lesions that occur during pregnancy and after delivery., Methods: This was a prospective observational cohort study carried out at a single tertiary center between December 2018 and October 2021. Pregnant women with endometriosis underwent a standardized transvaginal ultrasound examination with color Doppler imaging once in every trimester and after delivery. Non-ovarian endometriotic lesions were measured and evaluated by subjective semiquantitative assessment of blood flow. Lesions with moderate-to-marked blood flow were considered decidualized. The size and vascularization of decidualized and non-decidualized lesions were compared between the gravid state and after delivery. Only patients with non-ovarian endometriotic lesion(s) who underwent postpartum examination were included in the final analysis., Results: Overall, 26 pregnant women with a surgical or sonographic diagnosis of endometriosis made prior to conception were invited to participate in the study, of whom 24 were recruited. Of those, 13 women with non-ovarian endometriosis who attended the postpartum examination were included. In 7/13 (54%) cases, the lesion(s) were decidualized. In 4/7 (57%) women with decidualized lesion(s), the size of the largest lesion increased during pregnancy, while in 3/7 (43%), the size was unchanged. The size of non-decidualized lesions did not change during pregnancy. On postpartum examination, only seven lesions were observed, of which three were formerly decidualized and four were formerly non-decidualized. Lesions that were detected after delivery appeared as typical endometriotic nodules and were smaller compared with during pregnancy. The difference in maximum diameter between the gravid and postpartum states was statistically significant in decidualized lesions (P < 0.01), but not in non-decidualized lesions (P = 0.09). The reduction in mean diameter was greater in decidualized compared with non-decidualized lesions (P = 0.03)., Conclusions: Decidualization was observed in 54% of women with non-ovarian endometriotic lesion(s) and resolved after delivery. Our findings suggest that the sonographic features of decidualization, which might mimic malignancy, are pregnancy-related and that expectant management and careful monitoring should be applied in these cases. Clinicians should be aware of the changes observed during pregnancy to avoid misdiagnosing decidualized lesions as malignancy and performing unnecessary surgery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Aim: The aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group., Methods: Out of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease-free survival (DFS), and disease-specific survival., Results: The 5-year DFS of the study cohort was 89%, and the 10-year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS., Conclusion: Adjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions., (© 2023 John Wiley & Sons Australia, Ltd.)

Aims: This study aims to evaluate the efficacy and safety of PARP inhibitor therapy in advanced ovarian cancer and identify the optimal treatment for the survival of patients., Background: The diversity of PARP inhibitors makes clinicians confused about the optimal strategy and the most effective BRCAm mutation-based regimen for the survival of patients with advanced ovarian cancer., Objectives: The objective of this study is to compare the effects of various PARP inhibitors alone or in combination with other agents in advanced ovarian cancer., Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched for relevant studies on PARP inhibitors for ovarian cancer. Bayesian network meta-analysis was performed using Stata 15.0 and R 4.0.4. The primary outcome was the overall PFS, and the secondary outcomes included OS, AE3, DISAE, and TFST., Results: Fifteen studies involving 5,788 participants were included. The Bayesian network metaanalysis results showed that olaparibANDAI was the most beneficial in prolonging overall PFS and non-BRCAm PFS, followed by niraparibANDAI. However, for BRCAm patients, olaparibTR might be the most effective, followed by niraparibANDAI. Olaparib was the most effective for the OS of BRCAm patients. AI, olaparibANDAI, and veliparibTR were more likely to induce grade 3 or higher adverse events. AI and olaparibANDAI were more likely to cause DISAE., Conclusion: PARP inhibitors are beneficial to the survival of patients with advanced ovarian cancer. The olaparibTR is the most effective for BRCAm patients, whereas olaparibANDAI and niraparibANDAI are preferable for non-BRCAm patients. Other: More high-quality studies are desired to investigate the efficacy and safety of PARP inhibitors in patients with other genetic performances., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This study investigated the effect of poly(ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy after first- and second-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer (rHGSOC)., Methods: This study retrospectively analyzed 172 patients with rHGSOC treated at Zhejiang Cancer Hospital and Jiaxing Maternity and Child Health Care Hospital between January 2017 and December 2021. The 1st-PARPi group comprised patients who received a PARPi as maintenance therapy after first-line chemotherapy ( n =23), and the 1st-control group comprised those who did not ( n = 105). Similarly, the 2nd-PARPi group comprised patients not given a PARPi in their first-line treatment ( n = 30), and the 2nd-control group comprised those who were given a PARPi ( n = 89)., Results: Among the 23 patients in the 1st-PARPi group and the 105 patients in the 1st-control group, nine and 99 were platinum-sensitive, and 14 and six were platinum-resistant, respectively (hazard ratio [HR]: 14.46, P < 0.0001). Among the 30 patients in the 2nd-PARPi group and 89 patients in the 2nd-control group, 10 and 71 were platinum-sensitive, and 20 and 18 were platinumresistant, respectively (HR: 4.37, P < 0.0001). Age, stage, residual tumor, the courses of platinumbased chemotherapy, and breast cancer susceptibility gene mutations were not associated with platinum sensitivity when using a PARPi as maintenance therapy after first- and second-line chemotherapy., Conclusion: Patients with rHGSOC using a PARPi were more likely to be platinum-sensitive and develop platinum resistance independent of PARPi duration. Care should be taken when using a PARPi as maintenance therapy after first- and second-line chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose of Review: Sex cord-stromal tumours (SCSTs) are rare ovarian cancers. As in the literature, only small case series or case reports are published, gathering solid evidence about their management is challenging. Surgery plays a pivotal role, and accurate staging is one of the most important prognostic factors. This review focuses on the current evidence for surgical staging in the management of SCSTs., Recent Findings: Staging procedures have been inferred by epithelial ovarian cancers; however, they are often only partially performed, and most SCSTs therefore end up incompletely staged, raising the issue of the need for restaging or further treatments. In addition, some parts of the staging procedure have been questioned over the years, and lymphadenectomy is now considered unnecessary for SCSTs.The generally favourable prognosis of SCSTs, the introduction of minimally invasive surgery and fertility-sparing approaches is empowering the question of which staging procedures are beneficial for these patients. We reviewed the role of each staging procedure proposed by the guidelines in light of new scientific updates., Summary: Surgical staging should always be performed. It includes peritoneal samplings (peritoneal washing, multiple peritoneal biopsies, omental biopsy and biopsy of any suspicious area), whereas lymphadenectomy could be omitted. Laparoscopy may be considered a feasible approach., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.

Introduction: The objective of this study was to assess the effectiveness and potential benefits of the use of long-acting recombinant follicle-stimulating hormone (FSH) in a random-start protocol for fertility preservation in women with cancer., Material and Methods: This is a retrospective before-and-after study performed between February 2013 and December 2015 in women who underwent ovarian hyperstimulation for oocyte cryobanking using a random-start approach. In the first part of the study period, the women were treated with daily recombinant FSH whereas in the second part the stimulation was initiated with long-acting recombinant FSH. The primary aim of the study was to compare the number of oocytes stored in the two study periods. In all, 140 women were ultimately selected., Results: Compared with daily recombinant FSH, the use of the long-acting compound was associated with a reduced number of injections (12.5 ± 3.5 vs. 16.4 ± 0.3; p < 0.001) and a longer duration of stimulation (11.4 ± 1.9 vs. 10.6 ± 1.9, p = 0.01). Conversely, the number of oocytes collected (13.7 ± 9.5 vs. 11.3 ± 7.0, p = 0.10) as well as those cryopreserved (11.0 ± 8.0 vs. 9.5 ± 5.8, p = 0.21) did not differ., Conclusions: The use of long-acting recombinant FSH in random-start protocols for fertility preservation appears to be a valuable option., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

The MITO 15 was a prospective, single-arm trial, evaluating trabectedin monotherapy in patients with recurrent ovarian cancer (OC) who were BRCA mutation-carriers or had a BRCAness phenotype. It is largely reported that trabectedin may induce nausea and vomiting but the real emetogenic potential of the drug, in the different schedules, has never been fully described; furthermore, OC patients are known to have an enhanced risk of developing nausea and vomiting due to female gender, abdominal spreading of the disease, and major surgery experienced by most of them. We thought to carry on a sub-study in the MITO 15 context focused on chemotherapy-induced nausea and vomiting (CINV) associated with trabectedin single agent. For all patients enrolled in the trial, we evaluated the antiemetic regimen at the first cycle, acute and delayed CINV, any rescue therapy, any change in the prophylactic antiemetic regimen, and the potential relationship between dexamethasone dosage and incidence of CINV. Overall, our findings were consistent with literature and confirmed that trabectedin can be classified as moderately emetogenic. We observed slightly higher rates of both nausea and vomiting compared to previous experiences with trabectedin monotherapy, probably due to intrinsic features of our population: all females and suffering from ovarian cancer. It seems that in preventing acute CINV, the combination of three drugs was more effective than the doublet; however, the difference did not reach statistical significance; further studies are required to verify such hypothesis. Given the extreme heterogeneity of the antiemetic regimens used, it appears that a standard antiemetic protocol does not exist and more specific guidelines for clinicians are needed.

Background: Surgery followed by platinum-based chemotherapy is the standard of care for MOGCTs, except for stage IA dysgerminoma and stage IA grade 1 immature teratoma where surveillance only is recommended. The role of adjuvant chemotherapy and surgical staging is debated., Patients and Methods: Data from 144 patients with stage I MOGTs were collected among MITO centers (Multicenter Italian Trials in Ovarian Cancer) and analyzed., Results: Fifty-five (38.2%) patients were affected by dysgerminomas, 49 (34%) by immature teratomas, 26 (18.1%) by yolk sac tumors and 14 (9.7%) by mixed tumors. Seventy-three (50.7%) patients receive surgery plus chemotherapy, while 71 (49.3%) patients underwent surgery alone. The latter group included 32 dysgerminomas (14 IA-13 Ix, 3 IB, and 2 IC), 34 immature teratomas (20 1A-13 IA grade 1, 6 Ix, 1 IB, and 7 IC), 4 mixed tumors and 1 yolk sac tumor. Forty-four patients did not received chemotherapy, even if it would have been indicated by recommended approach. 94 (65.3%) patients received peritoneal surgical staging. Twenty-three (15.9%) developed a recurrence. Incomplete surgical staging was associated with recurrence (P < 0.05; OR 2.37) at Cox regression analysis. Seven patients died. Four patients were affected by yolk sac tumors, two by mixed tumors and one by immature teratoma. Five patients died for disease, one for acute leukemia and one for suicide. Prognostic parameter analyses showed that yolk sac component is a predictor for survival (P < 0.05). Five-years OS rates were 96.8% and 88.7% in the surgically staged and the incomplete staged group, respectively, while 93.8% and 94.1% in the standard treatment and in the surveillance group, respectively., Conclusions: This study shows that surveillance seems not to affect survival; chemotherapy should be reserved for relapse resulting in high cure rate. Incomplete peritoneal surgical staging is associated with recurrence. Yolk sac histology worsens the prognosis., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy., Methods: A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples., Results: Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%)., Conclusions: Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The prognosis of patients affected by ovarian cancer has not substantially changed in the last decades and improving survival still remains a challenge. In the promising era of 'personalized therapy' several new biologic therapies are currently being investigated: in this setting, targeting the folate receptor (FR) has been considered a new potential strategy for biologic therapy. Areas covered: The aim of the current review is to summarize, giving a critical overview,promising folate receptor alpha antagonists under preclinical or early clinical development for ovarian cancer. Expert opinion: Two categories of therapeutics are included in this class: FRα targeted mAbs and FRα-binding-ADC (Antibody drug conjugates); both share the interesting possibility of selecting patients via a biomarker which is already available. In the first class, farletuzumab has reached the most advanced stage in clinical evaluation and results of a Phase II randomized trial are awaited to assess its efficacy in a specific patients' setting. MOv18 IgE represents a novel strategy to target FRα expressing cells, which has shown encouraging results in preclinical studies: further evaluation is needed in the clinical setting. IMGN 853 is an innovative FRα-binding ADC under development, with only preliminary results of a Phase I trial available.

Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Therefore, there is the obligation to put emphasis on fertility preservation in affected women. On the other hand, it has also been underlined that the disease should be managed with caution because these tumours can relapse and, albeit rare, malignant transformation can also occur. Unfortunately, evidence on fertility preservation in women with BOT is scanty. In this opinion paper, we tried to draw some clinical indications based on the few available studies on the clinical management of BOT and their possible relation with controlled ovarian hyper-stimulation (COH). We ultimately came to the following conclusions: (1) Fertility counselling should become an integral part of the clinical management of women with BOT. Conservative management without pre-surgical counselling may expose women without reasonable chances of future conceptions to undue risks. (2) Despite some epidemiological concerns on the possible relation between COH and BOT, the conservative surgical treatment should be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. (3) Letrozole during COH should be considered to temper the theoretical risk of increased recurrences. (4) Pregnancy should not be delayed in women at low-moderate risk of recurrences. Fertility preservation may be avoided in these women provided that they start active pregnancy seeking early. (5) Albeit experimental, oocytes retrieval from affected ovaries removed at the time of surgery can be considered. Conversely, ovarian cortex cryopreservation is not justified given the possible risks of malignant reseeding., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype., Patients and Methods: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (≥2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed., Results: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported., Conclusions: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum., Eudract Number: 2011-001298-17., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Two types of epithelial ovarian carcinoma (EOC) have been recently distinguished. Type I comprises low-grade serous, endometrioid and clear-cell tumors. High-grade endometrioid and serous tumors belong to type II. The aim of this study was to compare patterns of disease spread in advanced-stage type I and II EOCs at primary surgery., Methods: Surgical and pathological data of 233 patients with advanced-stage EOCs were collected, 42 with type I and 191 with type II. The two groups were compared for tumor localization at primary surgery. Intraoperative mapping of ovarian cancer (IMO) was used to assess tumor dissemination., Results: Tumor involvement was significantly higher in the type II group for the following: peritoneum (68.1 vs. 40.5%, p < 0.001), pouch of Douglas (60.2 vs. 40.5%, p = 0.06), vesicouterine ligament (40.8 vs. 19%, p = 0.027), diaphragm (45.0 vs. 11.9%, p < 0.001), serosa of liver (17.2 vs. 4.8%, p = 0.05), omentum (81.1 vs. 59.5%, p = 0.007), mesentery (42.9 vs. 16.7%, p = 0.005), pleural effusions (19.4 vs. 4.6%, p = 0.01) and ascites (60.7 vs. 21.4%, p < 0.001). IMO levels were different between the two groups (p = 0.001)., Conclusions: This study provides clinical evidence in favor of the dualistic model of carcinogenesis, since types I and II are characterized by different findings at primary surgery., (© 2015 S. Karger AG, Basel.)

Purpose: To compare the oncological and reproductive outcomes of patients with apparent early stage pure ovarian immature teratomas (IMTs) treated with unilateral salpingo-oophorectomy (USO) or cystectomy., Patients and Methods: We retrospectively reviewed the medical records of patients with apparent early stage pure ovarian IMTs who received fertility-sparing surgery (FSS) between 1984 and 2019. FSS was defined as preservation of the uterus and at least one adnexa. Recurrence rates were compared between patients receiving USO and cystectomy. Reproductive outcomes and menstrual histories were assessed by telephone interview., Results: A total of 124 patients were included, of whom 83 underwent USO and 41 underwent cystectomy. After a median follow-up of 70.6 months (range: 6.2-410.6 months), eight patients suffered recurrences (5 in the USO group and 3 in the cystectomy group). The median times to recurrence were 5.0 and 5.1 months in the USO and cystectomy groups, respectively (P = 0.764). All patients with recurrence were successfully salvaged by surgery, except for one death. Univariate analysis showed no difference in disease-free survival and overall survival between the groups (P = 0.781, 0.155). Of the 111 patients contacted by telephone, 97 resumed menstruation following the surgery. Of the 31 patients desiring pregnancy, 26 achieved 28 pregnancies. USO (83.3%), like cystectomy (85.7%), resulted in excellent pregnancy rates., Conclusions: A USO is the standard treatment for women with early stage pure IMTs who want to preserve fertility. However, a cystectomy with adjuvant chemotherapy may be a suitable fertility-sparing therapy when a cystectomy is the only surgical option., (© 2021. Society of Surgical Oncology.)