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Objectives: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST)., Methods: This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522., Results: At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%)., Conclusions: The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST., Competing Interests: Declaration of competing interest Dr. Brown has participated in the Speakers' Bureau for Clovis and for Eisai and has received funding for this. Dr. Brown has participated in Advisory Boards or as a consultant with AstraZeneca, Caris, Biodesix, Janssen, Tempus, Olympus, Clovis, Invitae, Verastem, and GSK/Tesaro. Dr. Brown has participated in research with GSK/Tesaro and Genentech. Dr. Austin Miller reports that his institution received payments for serving on a Data Safety Monitoring Board or Advisory Board for Agenus, AstraZeneca, VBL Therapeutics. Dr. Floor Backes reports research grants to Institution from Merck, Eisai, ImmunoGen, Clovis, Beigene, Natera, Tempus, AstraZeneca. Dr. Backes reports receiving personal fees from UptoDate. Dr. Backes reports receiving personal fees for serving on Advisory boards for Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, Myriad, BioNTech and Daiichi Sankyo. Dr. Backes received honoraria for CME lectures from Clinical Educational Concepts, Clinical Care Options, Medscape/WebMD, Med Learning 13Health, CMR Institute, Global Learning Initiative/Prova, OncLive, Targeted Oncology and Research to Practice. GlaxoSmithKline provided Dr. Backes with support for travel. Dr. Backes served as a Board member for the Society of Gynecology Oncology (unpaid), Dr. Backes served as Co-Chair for NRG Oncology Developmental Therapeutics Committee as well as Co-Chair for IGCS Education 360. Dr. David Bender reports receiving grant support from Merck, Sharp & Dohme Company, Clovis Oncology, Inc. and Genentech. Dr. David Miller reports Grants to Institution from Advenchen, Forty Seven, Merck, Syros, US BIOTEST and Regeneron. He also reports receiving royalties from Karyopharm. Dr. Miller received consulting fees from Karyopharm, Incyte, Eisai, Merck, GlaxoSmithKline and Immunogen. Dr. Matthew Powell reports personally receiving consulting fees from GSK, Merck, Eisai, Seagen, Jazz, Clovis Oncology, AstraZeneca, Asdi Bioscience and AbbVie. He also reports participating on an Advisory Board for GSK and receiving compensation for the same. Additionally, Dr. Powell served in Leadership roles for SGO, NRG and GCSC and receiving compensation for the same. Dr. Westin has received research support to institution from AstraZeneca, Avenge Bio, Inc., Bayer, Bio-Path, Clovis Oncology, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, Roche/Genentech, Zentalis. Dr. Westin has received consulting fees from AstraZeneca, Caris, Clovis Oncology, Eisai, EQRX, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mereo, Mersana, NGM Bio, Nuvectis, Roche/Genentech, SeaGen, Verastem, Vincerx, Zentalis and ZielBio. Dr. Bonebrake reports providing patients with diagnosis of stromal ovarian tumors. Additionally, Dr. Bonebrake reports participating on Advisory Board for Blueprint Medicine (no consulting fee received), Merck – Global Cervical and Ovarian Cancer Virtual Advisory Board (no consulting fee) and AstraZeneca – AZ eVOLVE DMC (ongoing). Dr. Bonebrake served on the Board of Directors for the GOG Foundation (unpaid) and reports receiving occasional travel reimbursement to attend meetings and NRG Oncology Board of Directors (unpaid). Dr. Muller reports grants to her Institution, New Mexico Minority Underserved NCORP) to support enrollment to all NCI NCTN trials. Dr. Muller also reports contracts to institution to enroll to GOG Partner trials from GOG Partners Foundation (Seagen, GSK, Mersana, Alkermes Inc., Merck, Verastem, Immunogen, etc.) as well as contracts to her Institution for enrollment to specific clinical trials, Linnaeus Therapeutics. Dr. Muller also reports serving as advisory on disparity advisory councils for GSK and Seagen to advise on ways to increase minority enrollment to clinical trials. Dr. Secord reports grants received to Institution from AbbVie, Aravive Inc., AstraZeneca, Clovis, Eisai, Ellipses, I-MAB Biopharma, GSK, Immunogen, Merck, Mersana OncoQuest/CanariaBio, Roche/Genentech, Seagen Inc., TapImmune, Tesaro/GSK, VBL Therapeutics. Dr. Secord reports personally receiving honoraria from @Point of Care, Clinical Care Options, Curio Science, PeerView, Bio ASCENT, RTP, GOG Foundation (Highlight reel) and GOG Foundation Symposium. Also, patents planned, issued or pending on “Blood based biomarkers in ovarian cancer” without compensation, She reports serving on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova and OncoQuest/Canariabio without compensation. Dr. Secord reports serving in leadership role for SGO (uncompensated), GOG (personal fee received), AAOGF (uncompensated) and NRG who provided grant to her institution. Finally, Dr. Secord receiving medical writing from AstraZeneca. Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio), all without compensation. Dr. Crane reports serving on the Speakers Bureau for Merck and GlaxoSmithKline but the relationship for each of these has been terminated. Dr. Crane served on the Advisor Board for both AstraZeneca and GlaxoSmithKline. Dr. Schorge reports receiving Williams Gynecology royalties from McGraw-Hill and royalties for 2 articles from UpToDate. Dr. Schorge also reports receiving Consulting fees from Best Doctors. Dr. Tew reports receiving consulting fees from UpToDate and honoraria for the Chemotherapy Foundation Symposium 2022. Dr. Sood reports NCI grant received relative to this study as well as receiving the American Cancer Society Research Professor Award. Dr. Sood reports consulting fees received from KIYATEC, ImmunoGen, Merck & Co, Lyon, GSK, AstraZeneca and Onxeo. He also reports patents planned issued or pending for the EGFL6 antibody. Dr. Sood participated on an Advisory Board for Advenchen and has stock in Bio-Path Holdings. Dr. Bookman reports serving on a DMC for Immunogen as well as an Advisory Board for Clovis, and his institution received payment for both. Dr. Aghajanian reports Clinical trial funding to Institution (MSK) from AbbVie – MSK PI, GOG3005; AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator & MSK PI, D081RC00001; ENGOT-ov6; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, Ariel 2 & 3 and Genentech/Roche-MSK PI, GOG3015 (1Magyn050). Dr. Gershenson reports grants received from Novartis to his Institution. He also reports royalties personally received from Elsevier and UpToDate. Dr. Gershenson also received consulting fees from Verastem and Genentech. Dr. Gershenson also reports personal fees received for serving on the Advisory Boards for Aadi, Verastem and Beigene/Springworks. He received no compensation for serving as Chair, International Consortium for Low-Grade Serous Ovarian Cancer and reports stock ownership for Bristol Myers Squib, Johnson & Johnson and Procter and Gamble. The following Coauthors have no conflicts of Interest to disclose: Dr. Holman and Dr. Nagel., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate fulvestrant efficacy in women with estrogen receptor-positive low-grade gynecological cancers. The primary objective was to determine the response rate. Secondary objectives were progression-free survival, clinical benefit, duration of response, safety, tolerability, and quality of life., Methods: FUCHSia is an open-label, single-arm, prospective, multi-center phase II study. The study population included patients with recurrent/metastatic low-grade gynecological malignancies with estrogen receptor positivity who received a maximum of two lines of previous hormonal therapy. Patients received fulvestrant (FASLODEX, AstraZeneca) via two intramuscular injections (250 mg/5 mL each) in the gluteal muscle on day 1, day 15, day 29, and then every 28 days thereafter until disease progression, withdrawal from the trial due to any unacceptable adverse event, or withdrawal of patient consent., Results: A total of 15 patients (uterine sarcoma n=4; sex cord-stromal ovarian tumors n=3; endometrial carcinoma n=4; serous ovarian cancer n=4) were enrolled. Median follow-up was 48 weeks (interquartile range (IQR) 26-122) in the uterine sarcoma cohort, 63 weeks (IQR 28-77) for sex cord-stromal tumors, 19 weeks (IQR 17-21) for endometrial carcinoma, and 60 weeks (IQR 40-119) for serous ovarian cancer. One partial response according to Response Evaluation Criteria in Solid Tumors v1.1 was observed in one uterine sarcoma patient. No responses were observed in the other cohorts. However, stable disease was observed in three uterine sarcomas (median duration 12 weeks), three sex cord-stromal tumors (median duration 32 weeks), and four low-grade serous ovarian cancer patients (median duration 20 weeks), leading to a disease control rate of 100% for these tumor types. All patients with endometrial carcinoma showed progressive disease., Conclusion: Fulvestrant may control tumor growth in recurrent/metastatic estrogen receptor-positive low-grade gynecological malignancies of specific histology. Further studies are needed to confirm these results., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges., Methods: We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015., Results: 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS., Conclusion: Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Most testicular tumors are germ cell tumors; sex cord stromal tumors are infrequent, accounting for only 3-5% of testicular tumors. Unclassified sex cord stromal tumors are extremely rare. Generally, 10% of sex cord stromal tumors are malignant. We report a case of malignant unclassified sex cord stromal tumor with retroperitoneal lymph node metastasis at first visit and a corresponding literature review., Case Presentation: A 72-year-old Japanese man visited our department primarily for indolent right scrotum enlargement in September 2020. Blood biochemistry examination, urinalysis, and tumor markers (alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) showed no abnormal findings. Contrast-enhanced computed tomography showed enlarged para-aortic lymph node (18 × 16 and 10 × 10 2  mm); a 50 × 45 2  mm mass with uneven contents was found in the right testicle. The patient underwent inguinal orchiectomy in September 2020. As per immunohistochemistry, the tumor cells were diffusely positive for SF-1 and Ki-67, partially positive for inhibin, and negative for CAM5.2, CK7, CK20, C-KIT, CD30, LCA, GATA-3, TTF-1, and PAX8. Calretinin was expressed in approximately 5% of tumor cells; thus, sex cord/gonadal stroma components were considered to be involved. The final pathological diagnosis was unclassified malignant sex cord stromal tumor. The patient was diagnosed with pT1, N1, M0, S0, and tumor-node-metastasis stage IIA disease. The patient received postoperative chemotherapy with four courses of etoposide and cisplatin therapy from November 2020. Post-chemotherapeutic computed tomography showed new metastatic lesions including lung, liver, pancreas, and para-aortic lymphadenopathy, which increased in size. Disease progression was observed. Cancer genome research was performed using the OncoGuide National Cancer Center oncopanel system; however, no gene mutation for which the drug could be expected to be effective was found. The patient opted for best supportive care at a nearby hospital and died from cancer progression in January 2022., Conclusion: We encountered a case of malignant testicular unclassified sex cord stromal tumor pathologically diagnosed as testicular tumor with retroperitoneal lymph node metastasis in a patient who underwent inguinal orchiectomy. Future data collection is necessary to establish multimodality therapy for malignant testicular unclassified sex cord stromal tumor., (© 2022. The Author(s).)

Background: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs., Methods: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity., Results: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade., Conclusions: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs., Competing Interests: Declaration of Competing Interest SB: Institutional grants from Astrazeneca, Tesaro, GSK. Personal fees for advisory boards/lectures: Amgen, Astrazeneca, Clovis, Genmab, GSK, Immunogen, Mersana, MSD, Merck Sereno, Mersana, Oncxerna, Pfizer, Roche, Takeda, Tesaro, outside the submitted work. KS: Research funding to institution, Bayer and Amgen. Personal fees from Merck, Amgen, Servier, BMS, IPSEN, Competitive Drug Development, outside the submitted work. AC: Grants from Cancer Research UK and Astrazeneca, personal fees from AstraZeneca, GSK, Tesaro, Clovis Oncology, Eisai, outside the submitted work. RL: Personal fees from Tesaro and Roche outside the submitted work. MH: Research funding to institution Merck, BMS, Clovis Oncology. Honoraria for Advisory Boards/ Lectures: Amgen, AZ, Clovis Oncology, GSK, MSD, Roche outside the submitted work. CG: Research funding to institution: AstraZeneca, Novartis, Aprea, Nucana, Tesaro, BerGen Bio. Honorary for advisory boards/lectures: Roche, AstraZeneca, MSD, GSK, Tesaro, Nucana, Clovis, Foundation One, Sierra Oncology, Cor2Ed, Takeda. PS: Grant from University of Sydney. RE: Personal fees from Arquer Diagnostics, GSK, Clovis oncology outside submitted work. MF: personal fees from Astra Zeneca, MSD, GSK, Tesaro, Lilly, Takeda and Novartis; institutional grants from Astra Zeneca, Novartis and Beigene, other from Abbvie and ACT Genomics outside the submitted work. All other authors (MT, ROC, DM, SN, VMM, TB, JCG, PTG, OM, LA, CK, KC, LD, NB) report no disclosures of interest., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Pediatric sex cord stromal tumors (SCSTs) are extremely rare and there are no reported data from Africa. The authors evaluated the outcomes of children and adolescents with biopsy-proven SCSTs in preparation for the introduction of a national protocol., Materials and Methods: Retrospective data were collated from 9 South African pediatric oncology units from January 1990 to December 2015. Kaplan-Meier analysis was performed to estimate overall survival (OS) and event-free survival., Results: Twenty-three patients were diagnosed with SCSTs, 3 male and 20 female individuals, during the study period. Histologies included 1 thecoma, 9 Sertoli-Leydig cell tumors, and 13 juvenile granulosa cell tumors. Stage I tumors predominated (n=14; 60.9%), with 2 stage II (8.7%), 5 stage III (21.7%), and 2 stage IV tumors (8.7%). The upfront resection rate was 91.3% with no reported surgical morbidity or mortality and an OS of 82.1%. Chemotherapy approaches were not standardized. Most children (81.8%), except 2, had recognized platinum-based regimens. Chemotherapy-related toxicity was minimal and acceptable. Assessment of glomerular filtration rate and audiology assessments were infrequent and not standardized. Three patients were lost to follow-up., Conclusions: Although the numbers in this cohort are small, this study represents the first national cohort in Africa. The 5-year OS of 82.1% was encouraging. Standardized management of rare tumors like SCSTs is critical to improve ensure OS and address potential long-term sequelae., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ovarian steroid-cell tumors (SCTs) are a rare subgroup of sex-cord tumors of the ovary, accounting for less than 0.1% of all ovarian tumors. Not otherwise specified (NOS) tumors are the most common subtype. More than half of patients with SCTs-NOS show hyperandrogenic symptoms. The primary treatment for SCTs is surgery, as most cases are early-staged and benign. Because of the low incidence of metastatic disease, there is insufficient reliable information on the role of adjuvant therapy and the most effective treatment regimen. In this report, a rare case of a recurrent SCT-NOS in a 36-year-old female patient without endocrine symptoms is presented, highlighting the significance of appropriate pathological evaluation and immunohistochemical testing for the accurate diagnosis of this malignancy, particularly in the case of hormonally "silent" tumors. The metastatic tumor described here showed no response to four courses of adjuvant chemotherapy after several debulking surgeries. Based on the clinical findings, the neoplastic etiology should always be considered during the resection of ovarian tumors to prevent possible disease dissemination due to inappropriate surgical techniques.

Importance: To our knowledge, this is the first randomized trial in sex cord-stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting., Objective: To determine the efficacy of weekly paclitaxel with or without bevacizumab as treatment for relapsed sex cord-stromal tumors and evaluate whether the addition of bevacizumab to weekly paclitaxel improves 6-month progression-free rate., Design, Setting, and Participants: This open-label, academic, international, randomized phase 2 trial (ALIENOR) was conducted at 28 referral centers in France, Germany, Italy, Japan, and Belgium in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup and used an adaptive bayesian design. It included 60 women with sex cord-stromal tumors that had relapsed after at least 1 platinum-based chemotherapy. Enrollment occurred from 2013 to 2016, and the final analysis database lock was on March 27, 2020 (median follow-up, 38.9 months)., Interventions: Participants were randomized to receive either paclitaxel (80 mg/m2, days 1, 8, and 15 every 4 weeks) alone or paclitaxel with bevacizumab (10 mg/kg, every 2 weeks) for 6 cycles followed by maintenance bevacizumab (15 mg/kg, every 3 weeks) for up to 1 year or until progression or unacceptable toxicity. Crossover to bevacizumab was permitted after progression during or following paclitaxel alone., Main Outcomes and Measures: Six-month progression-free rate., Results: Sixty patients (predominantly with granulosa cell tumors) were randomized, 32 to receive single-agent paclitaxel (median [interquartile range] age at inclusion, 60 [53-64] years) and 28 to receive paclitaxel-bevacizumab (median [interquartile range] age at inclusion, 55 [47-61] years; 1 did not receive treatment). The estimated 6-month progression-free rate was 71% (95% credible interval, 55%-84%) with paclitaxel alone and 72% (95% credible interval, 55%-87%) with paclitaxel-bevacizumab. The bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination than with paclitaxel alone was 57%, less than the predefined superiority threshold. The objective response rate increased from 25% (95% CI, 12%-43%) to 44% (95% CI, 26%-65%) with the addition of bevacizumab. One patient discontinued combination therapy within 6 months because of toxicity., Conclusions and Relevance: Weekly paclitaxel is a new option for relapsed sex cord-stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord-stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit., Trial Registration: ClinicalTrials.gov Identifier: NCT01770301.

Rare sex cord-stromal tumors of the ovary cannot be further subclassified and are therefore designated "sex cord-stromal tumor-not otherwise specified." These tumors have highly varied morphology, and the literature describing them is limited. Herein, we report the pathology and clinical course of a 46-yr-old woman diagnosed with sex cord-stromal tumor-not otherwise specified. The tumor was composed predominantly of juvenile granulosa cell tumor histology, with elements of thecoma, adult granulosa, Sertoli, as well as poorly differentiated epithelioid and sarcomatoid components. Next-generation sequencing revealed a FOXL2 C134W mutation, seen most commonly in adult granulosa cell tumors, as well as mutations in TP53 (V172F) and TERT promoter (-124C>T). The patient exhibited an aggressive clinical course involving rapid recurrence with distant metastases that responded to 4 cycles of cisplatin, bleomycin, and etoposide.

We present a case of unclassified sex cord-stromal testicular tumor with lung metastasis. A 48-year-old man consulted our hospital for left testicular enlargement that began 3 years ago. Computed tomography revealed a heterogeneously enhanced left testicular tumor 11 cm in diameter and a 5 mm metastatic lung tumor. The human chorionic gonadotropin (hCG) level was elevated (141.6 mU/ml), whereas the levels of α-fetoprotein (AFP) and LDH were normal. The external genitalia were normal and gynecomastia was not observed. Left high orchiectomy followed by 3 cycles of BEP chemotherapy (bleomycin, etoposide, and cisplatin) every 4 weeks was performed. The pathology of the excised specimen was unclassified sex cordstromal testicular tumor containing hCG-positive cells. On immunohistochemistry, the tumor cells were partly positive for AE1/AE3, hCG, and calretinin. Vimentin was diffusely positive, but OCT3/4, SALL4, GATA3, and CK7 were negative. After BEP treatment, the metastatic lung lesion disappeared. Unclassified sex cord-stromal testicular tumor is a rare disease and its treatment has not been established. Thus, further accumulation of cases is needed.

Background: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies. Enrolled patients included seven patients with relapsed or refractory germ cell tumors or metastatic sex cord stromal tumors described in this case series., Materials and Methods: Forty patients with relapsed or refractory germ cell tumors, metastatic sex cord stromal tumors, or testicular tumors were screened for CD30 expression; 14 patients had tumors that expressed CD30. Seven patients with CD30-expressing testicular cancer were enrolled in the treatment study: five patients with germ cell tumors, one patient with a Leydig cell tumor, and one patient with a Sertoli cell tumor. Patients were treated with brentuximab vedotin at initial doses of 1.8 or 2.4 mg/kg every 3 weeks. Response assessments were performed at cycles 2 and 4 and every 4 cycles thereafter while the patient was receiving treatment., Results: Two of seven patients achieved an objective response, including one durable complete response and one partial response at a single time point. Both responding patients had germ cell tumors. Treatment with brentuximab vedotin was generally well tolerated., Conclusion: Treatment of relapsed or refractory germ cell tumors with brentuximab vedotin can induce durable responses with a manageable toxicity profile., Implications for Practice: This case series of seven patients with relapsed or refractory CD30-expressing germ cell tumors (GCTs) or sex cord stromal tumors demonstrates that brentuximab vedotin has activity against GCTs and is well tolerated in heavily pretreated patients with these aggressive tumor types. One patient achieved a complete response that has been durable for almost 4 years since the discontinuation of treatment with brentuximab vedotin. Therefore, brentuximab vedotin may be a valuable option for physicians who care for this difficult-to-treat patient population., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Background: To retrospectively investigate reproductive outcomes after fertility-sparing surgery and postoperative adjuvant chemotherapy in malignant ovarian germ cell tumors (MOGCT) and sex cord-stromal tumors (SCST)., Methods: Data from 32 MOGCT (6 dysgerminomas, 6 yolk sac tumors, 17 immature teratomas, and 3 mixed germ cell tumors) and 9 SCST (4 granulosa cell tumors and 5 sertoli-leydig cell tumors) aged from 18 to 35, treated in the Obstetrics and Gynecology Hospital of Fudan University from October 2003 to October 2013 were collected and analyzed., Results: Average follow up was (86.3 ± 34.4) months. Average diagnosed age was (25.3 ± 3.5) years. Average chemotherapy course was (4.4 ± 1.3) times. Patients are all living. Thirty one patients (75.6%) reported normal menstrual cycles. Twelve patients (29.3%) wished to conceive, 10 (83.3%) naturally conceived and 8 (66.7%) had lived birth., Conclusions: Reproductive outcomes after fertility-sparing surgery and postoperative adjuvant chemotherapy in MOGCT and SCST are favorable, meanwhile education and consultation is needed.

Background: Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency., Case Presentation: A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol. Her rapidly progressive Cushing's syndrome ultimately led to her death, despite aggressive medical management with spironolactone, ketoconazole, mitotane, and mifepristone., Conclusions: We report an unusual and rare case of Cushing's syndrome secondary to a malignant steroid cell tumor of the ovary. The case is highlighted to discuss the complications of rapidly progressive Cushing's syndrome, an underreported and often unrecognized endocrine emergency, and the best available evidence for treatment.

Objective: To investigate the clinicopathological features of testicular malignant Leydig cell tumor (TMLCT) and improve the non-invasive diagnosis of the disease., Methods: We retrospectively analyzed the clinicopathological data on a case of TMLCT, detected the circulating tumor cells (CTC) in the peripheral venous blood, and reviewed the related literature., Results: The patient, a 47-year-old male, underwent radical orchidoepididymectomy under general anesthesia. Postoperative pathology confirmed the lesion to be TMLCT, which was mainly composed of Leydig cells and suspected with vessel carcinoma embolus. Immunohistochemistry showed the tumor cells to be positive for α-inhibin, Ki67, CD30, vimentin, EMA, and PLAP, but negative for CK, CK7, S100, CD10, SMA, Des, AFP, hCG, CEA, CK19, CD117, Oct-4, LCA, CD20, Pax-5, CD3, and CD43. Two CTCs were detected in the peripheral venous blood. The patient received 3 courses of chemotherapy for retroperitoneal multiple lymph nodes metastasis post-operatively. Subsequent CT imaging manifested no obvious reduction of the retroperitoneal lymph nodes and consequently the patient again underwent retroperitoneal lymphadenectomy and cryoablation. At 8 months after treatment, CT examination revealed notably enlarged retroperitoneal lymph nodes with the right adrenal gland evidently invaded., Conclusion: TMLCT is an extremely rare sex-gonad stromal tumor with high malignancy and poor prognosis, and CTCs may be used for its early diagnosis and prognostic prediction.

Objective: To estimate the probability of complete clinical response and toxicity of paclitaxel as second-line chemotherapy in measurable disease patients with malignant tumors of the ovarian stroma, and to evaluate the value of inhibin for predicting response., Methods: Thirty-one patients with histologically confirmed ovarian stromal tumor were enrolled from 2000 to 2013. Patients were required to have measurable recurrent disease, and to have received only one prior chemotherapy regimen. Paclitaxel 175 mg/m2 was administered over a 3 hour infusion, cycling every 21 days. Inhibin levels were drawn within two weeks of initiation of treatment., Results: Of 31 women enrolled, there was only one complete response (3.2%), and partial response in eight of 31 cases (25.8%). The pretreatment inhibin level for the single patient who had complete response was 88 pg/mL. Median progression-free survival was 10.0 months and overall survival was 73.6 months. Myelosuppression was common with 12 of 31 patients (38.7%) suffering grade 3 or 4 neutropenia, leukopenia, or anemia., Conclusion: There were too few complete responses to warrant continued evaluation of paclitaxel as a single agent treatment for women with recurrent malignant ovarian stromal tumors with measurable disease according to the primary objective of the study. Toxicity of the regimen was acceptable. Pretreatment inhibin is not a reliable tumor marker as it was not elevated in the majority of patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment., Methods: We performed a systematic literature review of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and published from 1986 to 2014., Results: Eight studies totaling 221 patients were included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2-11.2) and mortality (1.8%; 95% confidence interval, 0.1-3.6) related to bleomycin were significant. However, these results were very similar to those reported for men who were treated with bleomycin for a male germ cell tumor, suggesting that women with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity. The main risk factors of bleomycin-induced pneumonitis are high cumulative bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal function. Whether granulocyte colony-stimulating factor is a risk factor remains controversial., Conclusions: Bleomycin-induced pneumonitis frequently occurs in patients with SCSTs and lacks effective treatment. Prevention lies in limiting cumulative bleomycin dose, monitoring pulmonary function during treatment, discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary function is impaired, and avoiding bleomycin in older patients.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) cause difficulties, both with respect to diagnosis as well as to the nomenclature. They belong to the group of low-grade malignant neoplasms, and their clinical course likely depends on the percentage of the sex cord-like component. Morphologically, they can be divided into type I and type II with less or more than 50% of sex cord-like areas, respectively. Six patients with an age range of 24 to 63 years underwent the treatment for primary UTROSCT at the Cancer Center and Institute of Oncology in Warsaw, Poland, between 2000 and 2011. In addition to the surgery, 4 patients were treated with gestagens. Biopsies or excisions from the tumors were examined microscopically and immunohistochemically. Two cases were classified as type I, and 4 cases, as type II tumors. The tumor size ranged from 3 to 24 cm. The sex cord component varied from 25% to 70%. By immunohistochemical examination, the sex cord-like component was calretinin positive, whereas the stromal component was positive for CD10 and negative for h-caldesmon in all the cases studied. In addition, progesterone receptor positivity was found in all the cases, and 4 tumors were positive for smooth muscle actin, cytokeratin AE1/3, and inhibin. No recurrences were noted in any of the 6 patients over 3 to 14.5 years of follow-up period. A correct subclassification of sarcomas of UTROSCT type is of crucial importance because most patients with this rare neoplasm respond well to gestagen therapy and have a good prognosis, compared with other uterine stromal sarcomas., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Sex-cord stromal tumors (SCSTs) with annular tubules (SCTATs) are a small class of ovarian lesions that possess histologic features of both Sertoli and granulosa cells. Approximately one-third of patients with SCTAT also have Peutz-Jaghers syndreome, which makes these cases especially rare. Patients with non-PJS-associated SCTAT make up the remaining two-thirds; 20% of these cases have a metastatic presentation. Metastasis of these tumors to the head and neck region has only been reported in a few instances. In this article we report a case of a 25-year-old woman who presented with "a lump in her throat" and was ultimately diagnosed with SCTAT. We also discuss the current protocols in the diagnosis and treatment of this entity.

Background: The Gynecologic Oncology Group conducted this phase 2 trial to estimate the antitumor activity of bevacizumab and to determine the nature and degree of toxicity in patients with recurrent sex cord-stromal tumors of the ovary., Methods: A prospective, multi-institutional cooperative group trial was performed in women with recurrent, measurable ovarian stromal tumors. Patients were allowed to have unlimited prior therapy, excluding bevacizumab. Bevacizumab 15 mg/kg was administered intravenously on day 1 of every 21-day cycle until patients developed disease progression or adverse effects that prohibited further treatment. The primary endpoint was the response rate (RR). Inhibin A and B levels were measured before each cycle, and the values were examined in relation to response and progression., Results: Thirty-six patients were enrolled, and all were eligible and evaluable. Patients received a median of 9 cycles of treatment (range, 2-37 cycles). Six patients (16.7%) had partial responses (90% confidence interval, 7.5%-30.3%), 28 patients (77.8%) had stable disease, and 2 patients (5.6%) had progressive disease. This met the criterion for declaring the regimen active. The median progression-free survival was 9.3 months, and the median overall survival was not reached in during reporting period. Two grade 4 toxicities occurred, including hypertension and proteinuria; and the most common grade 3 toxicities were hypertension (n = 5) and pain (n = 5). Inhibin A and B values were lower in patients who responded to treatment., Conclusions: Bevacizumab has activity in the treatment of recurrent sex cord-stromal tumors of the ovary, and its toxicity is acceptable. Further investigation is warranted., (© 2013 American Cancer Society.)

Context: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established., Objective: This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer., Evidence Acquisition: Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned., Results: There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended., Conclusions: These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account., Take Home Message: Although testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment., (Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.)

Background: Ovarian sex-cord stromal tumors (SCST) are rare in childhood and include a variety of neoplasms with different clinical features and biologic behavior. Aim of the analysis was to report the clinical findings and treatment results of a series of patients with SCST of the ovary, registered in a multi-institutional Italian network on rare tumors in children and adolescent between 2000 and 2009., Methods: Data on 23 patients, 5-176 months old, from 13 Centers were reviewed. All patients were grouped on the basis of the results of the first surgical approach, according to the Children Oncology Group staging system. A cisplatin based chemotherapy was recommended in patients with a localized disease, who had undergone an incomplete excision/initial biopsy, and in case of metastatic spread., Results: A frequent symptom was abdominal pain; 9/23 cases had signs of hormonal secretion and two patients were hospitalized for acute pain following ovarian torsion. Twelve patients had a Juvenile-Granulosa Cell tumor, six a Sertoli-Leydig Cell tumor, three a Fibrothecoma, and two a Sclerosing-Stromal tumor. Twenty-one patients maintained the complete remission (follow-up: 9-91 months), 2 with a ST II Sertoli-Leydig Cell tumor relapsed and one of them died. Immonohistochemical studies could be done in 10 cases., Conclusions: Completeness of resection and histology were important prognostic factors; in our series the Sertoli-Leydig Cell tumor was the most aggressive variety. Hormonal signs (precocious puberty, telarca, menarche) were common in younger patients and led to an early diagnosis. Cisplatin based chemotherapy seemed to be effective for locally advanced tumors., (Copyright © 2010 Wiley-Liss, Inc.)

Steroidogenic acute regulatory (StAR) protein is a rate-limiting protein, which is essential for transporting cholesterol into the mitochondria for steroidogenesis. StAR protein could be a marker for steroidogenic tissues. In this study, we investigated StAR protein levels in sex-cord stromal tumors (SCSTs) including 31 adult granulosa cell tumors, 3 juvenile granulosa cell tumors, 10 fibrothecomas, 2 luteinized thecomas, 4 Sertoli-Leydig cell tumors (SLCTs), 4 sclerosing stromal tumor and 3 Leydig cell tumors (LCTs), and 219 non-SCSTs. SCSTs were used for immunohistochemical staining of StAR protein, α-inhibin, calretinin, and CD99. All the 3 LCTs (100%) strongly stained for StAR protein; 30 of the 31 adult granulosa cell tumors (96%) showed focal staining of StAR protein; all the 10 fibrothecomas and 4 sclerosing stromal tumors (100%) were negative for StAR protein staining; StAR protein stained in Leydig cells but not in Sertoli cells in the 4 SLCTs. All the non-SCSTs were negative for StAR protein except for tumor cells in 4 adrenocortical adenomas and 2 adrenocortical carcinomas. Results of the study indicate that StAR protein is a useful marker for differential diagnosis of SCSTs. It is sensitive and specific for Leydig cells in tumors containing this component (LCT, SLCT), and can express focally in granulosa cell tumors. It is negative for Sertoli cells and nonluteinized theca cells.

Some gynaecological cancers are uncommon, such as sex cord-stromal tumours, malignant germ-cell tumours, vulvar carcinoma, melanoma of the female genital tract, clear-cell carcinoma of the ovary and endometrium, neuroendocrine tumours of the cervix, and gestational trophoblastic neoplasia. All these cancers have different clinicopathological characteristics, suggesting different molecular biological pathogeneses. Despite aggressive treatment, some cancers recur or respond poorly to therapy. Comprehensive knowledge of the molecular biology of each cancer might help with development of novel treatments that maximise efficacy and minimise toxic effects. Targeted therapy is a new treatment strategy that has been investigated in various tumours in clinical and laboratory settings. Since these cancers are rare and large clinical trials are difficult to do, molecular biological techniques might allow rapid proof-of-principle experiments in few patients. Novel targeted agents either alone or in combination with other treatments offer promising therapeutic options., (2010 Elsevier Ltd. All rights reserved.)

Malignant nonepithelial ovarian tumours represent less than 20% of ovarian cancers in adults. Apart from haematological tumours, there are mainly germ cell tumours and sex cordstromal ovarian tumours. These tumours affect young women and are diagnosed in early stages associated with a good prognosis. The management of malignant nonepithelial ovarian tumours is difficult because they are rare and because we have to propose an appropriate oncological treatment, preserving fertility for these women of child-bearing age. We propose an update on recent data in the literature, focusing on management.

Objective: Given the paucity of data regarding the patterns of metastasis from ovarian sex cord-stromal tumors (SCSTs), we sought to determine the risk of lymph node metastasis in patients with SCSTs., Methods: A retrospective chart review was performed after clinical and pathology databases were queried for ovarian SCST patients who were treated at our institution between 1985 and 2005., Results: We identified 262 patients with pathology-confirmed ovarian SCSTs; 5 had additional non-stromal histology and were excluded, leaving 257 evaluable patients. Of these patients, 178 had adult granulosa cell tumors, 27 had juvenile granulosa cell tumors, 31 had Sertoli-Leydig cell tumors, 6 had sex cord tumors with annular tubules, 13 had mixed SCSTs, and 2 had SCSTs not otherwise specified. Our evaluation showed that 111 patients underwent a complete or partial staging procedure; 75 had stage I disease, 11 had stage II disease, and 25 had stage III disease. Fifty-eight of these 111 patients (52%) had lymph nodes removed as part of the staging procedure. Of the 58 patients who had lymph nodes sampled during the primary surgery, none had positive nodes. Of 117 patients whose disease eventually recurred, 6 patients (5.1%) had nodal metastases at the time of recurrence. Three of these patients had negative lymph nodes at initial staging., Conclusions: Lymph node metastasis in ovarian SCSTs is rare. These findings suggest that lymphadenectomy may be omitted when staging patients with ovarian SCSTs.

Objective: To highlight aspects of malignant ovarian sex cord stromal tumors, effects of treatment, and developments over the past 28 years., Design: Population-based cohort study., Setting: Gynecological departments within the catchment-area of the Munich Cancer Registry and associated with the project group 'Malignant Ovarian Tumors' of the Munich Cancer Center., Sample: One hundred and forty-five women with an invasive single sex cord stromal tumor diagnosed between 1978 and 2005., Methods: Overall survival was estimated with the Kaplan-Meier method, relative survival was computed by the ratio of observed to expected survival rate. The impact of age, International Federation of Gynecology and Obstetrics (FIGO)-stage, residual tumor, and chemotherapy was examined by multivariate analysis (Cox regression model)., Main Outcome Measures: Overall and relative survival and multivariate adjusted overall survival., Results: Survival data showed a five-/10-year overall survival of 55.8%/42.8% (relative survival 58.6%/49.2%) for women diagnosed before 1988 and 89.1%/78.3% (relative survival 92.7%/85.2%) for women diagnosed after 1988. After adjustment for age and FIGO-stage, the following hazard ratios and 95% confidence intervals (95% CI) for treatment methods resulted: 3.3 (95% CI 1.5-7.0) for women with compared to women without residual tumor and 2.2 (95% CI 1.2-4.2) for women with chemotherapy compared to women where no chemotherapy was given., Conclusions: Improvements in survival may be attributed to a stage-shift toward more favorable stages at diagnosis and to advances in treatment such as improved surgery without residual tumor. There is no evidence for any benefit of adjuvant chemotherapy. Surgery remains the cornerstone of treatment, yet the benefit of postoperative therapy is still under debate.

Unlabelled: Approximately 2% of of all malignant tumours in boys are localised in the testis. Among them 80% are germ cell tumours with the malignant elements of yolk sac tumour. AIM of the study was evaluation of the efficacy of malignant testicular tumour treatment programme in children., Material and Methods: Since 1998 31 boys aged 1 month to 18 years (median 14 years) with malignant testicular tumours were enrolled in the multicentre trial. Patomorphologically clear yolk sac tumour (33%) and mixed germ cell tumour (42%) with the majority of yolk sac tumour component or carcinoma embryonale, occurred most often. Alfa-feto-protein was increased in 63% and choriogonadotropin in 26 patients. 61% patients had local clinical stage and the tumour was localized in the testis. In 39% patients tumour exceeded the testis margin. 4 patients were excluded from analysis as 3 are actually treated and 1 died on the second day of admittance to hospital. All patients received TGM 95 regimen (Tumeurs Germinales Malignes). Surgery (orchidectomy) was applied in 27 boys, 26 were primary (81% complete), 3 secondary (100% complete). 33% received no chemotherapy after surgery, in 41% VBP protocol (vinblastine, bleomycin, cisplatin) was given and in 26%o VIP protocol (ethoposide, ifosphamide, cisplatin). Two patients received also ABK (adriamycine, bleomycin, carboplatin)., Results: Among 26 children with germ cell tumours, 25 (96%) are alive, 23 (88%) are in first remission after completion of treatment. One child died due to central nervous system metastases. 2 children had local recurrence treated with chemotherapy or surgery with good result. Median follow-up is 45 months., Conclusions: TGM regimen is highly efficient in the treatment of malignant testicular tumours. Problems occur in cases of disseminated disease.

Unlabelled: Approximately 1% of all malignant tumours among children are localized in the ovary. The majority belongs to germ cell tumours and occurs in the peripubertal period. AIM of the study was the evaluation of the efficacy of malignant ovarian germ cell tumour treatment programme in children., Material and Methods: Since 1998, 40 girls with malignant ovarian tumours were enrolled in the multicentre trial. Mixed germ cell tumours with yolk sac elements and dysgerminoma occurred the most often. Alfa-fetoprotein (AFP) was increased in almost one half of patients. Tumour exceeded the ovary margin in more than half the patients and 25% were qualified as high risk group. 38 children completed the treatment. All but one patient with neuroblastoma received TGM protocol (Tumeurs Germinates Malignes). A VBP regimen (vinblastine, bleomycin, cisplatin) was applied in 19 girls, VIP regimen (etoposide, ifosfamide, cisplatin) in 16, two received no chemotherapy. Due to delayed remission after first-line chemotherapy it was prolonged with ABK (adriamycine, bleomycine, carboplatin) in 3 patients, 1 megachemotherapy regimen with autologous bone marrow transplantation was realized, one patient received a 1.5 year long oral chemotherapy. All the children underwent surgery, 34 primary (56% complete), 12 secondary (75% complete). 8 children were operated twice., Results: Among 34 children with germ cell tumours and 3 with sex cord tumours who completed the treatment all are alive in the first remission. 1 child with neuroblastoma localised in the ovary died due to recurrence. A median follow-up period was 42 months., Conclusions: The TGM protocol appears to be highly efficient in treatment of germ cell tumours even in advanced stages.

Objective: We compared the efficacy and side effects of taxanes, with or without platinum, to bleomycin, etoposide, and cisplatin (BEP) in treating sex cord-stromal ovarian tumors., Methods: We conducted a retrospective review of all patients with sex cord-stromal ovarian tumors seen at our institution from 1985 to 2002. Eligible patients were those who underwent pathologic confirmation, clinical evaluation, and treatment with a taxane or BEP for initial or recurrent disease., Results: Of 222 patients identified, 21 received BEP for new (n = 11) or recurrent disease (n = 10); 44 received a taxane during 48 treatment episodes (four patients on two occasions each) for new (n = 11) or recurrent disease (n = 37). Newly diagnosed patients treated with BEP vs. taxanes had no significant difference in response rate (Fisher's exact test, P = 1), progression-free survival (PFS) (log-rank test, P = 0.213), or overall survival (log-rank test, P = 0.994). Among patients treated for recurrent measurable disease, the response rate was higher for BEP-treated (71%) than for taxane-treated patients (37%), but this was not statistically significant. In all patients treated for recurrent disease, there was no significant difference in failure to progress at chemotherapy completion between BEP- (70%) and taxane-treated patients (62%) or in median PFS (11.2 vs. 7.2 months). The presence of platinum in taxane-containing regimens correlated with response. Taxane-related side effects included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). BEP-related side effects included pulmonary fibrosis (n = 3) and neutropenia (n = 2)., Conclusions: Taxanes demonstrated activity against sex cord-stromal tumors of the ovary and may be less toxic than BEP. Taxane and platinum combination chemotherapy warrants further investigation in this disease.

Purpose: To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary., Patients and Methods: We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease., Results: Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane +/- platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1)., Conclusion: Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.

Purpose: To develop diagnostic standards and a risk-adapted therapeutic strategy for ovarian sex cord-stromal tumors (OSCST)., Patients and Methods: Fifty-four patients were prospectively enrolled as follow-up patients onto the German Maligne Keimzelltumoren protocols. Surgical protocols and histopathology were reviewed centrally (53 patients with complete data). Surgery included ovariectomy in 18 patients, salpingo-ovariectomy in 34 patients, and hysterectomy in one patient. Patients with stage IA tumors were followed-up at regular intervals, whereas nine patients with stage IC and six patients with stage II to III tumors were treated with cisplatin-based chemotherapy., Results: International Federation of Gynecology and Obstetrics stage was IA in 27 patients, IC in 21 patients, II in three patients, and III in three patients. After a median follow-up of 59 months (range, 6 to 193 months), event-free survival +/- SD was 0.86 +/- 0.05 (47 of 54 patients) and overall survival was 0.89 +/- 0.05 (49 of 54 patients). Prognosis correlated with stage (event-free survival +/- SD: IA, 1.0 [27 of 27 patients]; IC, 0.76 +/- 0.09 [16 of 21 patients]; and II/III, 0.67 +/- 0.19 [four of six patients]; P =.02). Ten of 15 patients treated with chemotherapy, including four of six stage II to III patients, are alive after a median follow-up of 33 months., Conclusion: On the basis of a standardized clinical and histopathologic assessment, risk-adapted therapeutic strategies for OSCST can be evaluated. Considering our experience, we would recommend that stage IA tumors be followed up at regular intervals, whereas we would recommend cisplatin-based chemotherapy in stage IC tumors with preoperative rupture or malignant ascites, especially those with high mitotic activity. Finally, cisplatin-based chemotherapy also seems to be effective in advanced-stage tumors.

We outline chemotherapy mainly for malignant ovarian germ cell and sex-cord tumors, based on studies in the literature and our own clinical experiences. With both tumors, PEB treatment is standard adjuvant chemotherapy. With regard to the number of dosage courses, 4 courses are regarded as tolerable after incomplete reduction, and 3 courses as adjuvant treatment after complete extraction. This chemotherapy is effective for preservation of fertility in young patients with malignant ovarian germ cell tumor. In both tumors, some cases show chemotherapy resistance. An effective second-line treatment strategy using a new anticancer agent needs to be established for such cases in the future.

Objectives: The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies., Methods: Patients with incompletely resected Stages II-IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2 x 9 weeks for a maximum dose of

A 63-year-old man underwent inguinal orchiectomy for painless enlargement of the left testis. The diagnosis of malignant gonadal stromal tumor was made on the basis of morphology and immunohistochemical studies. At computed tomography there was bulky retroperitoneal metastasis. The patient then underwent retroperitoneal lymphadenectomy and received 6 courses of platinum-based chemotherapy at the end of which complete response was documented. However, at 18 months' follow-up, computed tomography revealed recurrent retroperitoneal metastasis. The patient was put on chemotherapy regimen again. But he developed pulmonary metastasis and died 28 months after the initial diagnosis. The clinical course of this patient suggests that malignant gonadal stromal tumor, if metastatic at diagnosis, may have a poor prognosis against most aggressive treatment approaches.

Objective: To investigate the clinical activity of the combination of bleomycin, etoposide, and cisplatin for metastatic ovarian sex cord-stromal tumors of all types and poorly differentiated Sertoli-Leydig cell tumors confined to the ovary., Methods: The regimen was administered as follows: bleomycin 10-15 mg/day by continuous intravenous (IV) infusion on days 1-3; etoposide 100 mg/m2 IV per day on days 1-3; cisplatin 100 mg/m2 IV on day 1. End points for analysis included response, progression-free survival, and survival., Results: Nine patients were entered in this trial. The median age was 37 years (range 12-69). Histologic types included adult granulosa cell tumor in five patients, juvenile granulosa cell tumor in one, poorly differentiated Sertoli-Leydig cell tumor in two, and mixed tumor in one. Stage distribution was as follows: stage Ia, two; stage IIc, one; stage IIIc, one; recurrent, five. Of the six patients with measurable disease, two (33%) had a complete response (one surgical and one clinical), and three (50%) had a partial response, for an overall response rate of 83%; one patient had no response. Toxicity was acceptable; two patients had mild bleomycin pulmonary toxicity. Of the three patients with nonmeasurable disease, one relapsed, one developed progressive disease, and one remains in remission. Of the seven patients with metastatic disease, only one (14%) had a durable remission. Median progression-free survival was 14 months. Median survival time was 28 months. At the time of analysis, two patients were alive disease-free, three were alive with disease, and four were dead of disease., Conclusion: Although the overall response rate to the combination of bleomycin, etoposide, and cisplatin was high, the regimen apparently lacks durable activity in this group of tumors. More active drugs and modalities should continue to be investigated.

Recurrent sex cord tumor with annular tubules is an unusual ovarian cancer. The authors report a patient with recurrent disease that was ultimately followed with multiple tumor markers. During this period the patient was treated only with chemotherapy. Her regimen consisted of a combination of etoposide, bleomycin, and cisplatin. The tumor markers that were followed were CA-125, CEA, inhibin, and Müllerian-inhibiting substance (MIS). There was no elevation of the CA-125 or CEA, but inhibin and MIS proved to be effective markers. Serum inhibin and MIS correlated perfectly with her documented disease status and was brought into the normal range when the patient was disease-free. This disease-free status was proven by surgical reexploration. This report is the first documented complete response in this rare malignancy treated by chemotherapy alone with distant metastatic spread. It also gives strong linkage of inhibin and MIS as good markers in this particularly rare malignancy.

Malignant ovarian germ cell tumors (OGCT) and sex cord stromal tumors (SCST) are much less common than epithelial ovarian cancer, each accounting for less than 5% of all ovarian malignancies. The combination of vincristine, dactinomycin, and cyclophosphamide (VAC) became the standard chemotherapy for patients with OGCT in the 1970s; it produced excellent sustained remission rates in patients with stage I disease but less than 50% sustained remission rates in those with metastatic tumor. With the introduction of cisplatin for the treatment of testicular cancer in the late 1970s, platinum-based regimens replaced the VAC regimen by the mid-1980s. Currently, the most popular regimen for all patients with OGCT is the combination of bleomycin, etoposide, and cisplatin (BEP). The BEP regimen appears to be superior to VAC, with sustained remission rates of more than 75% in patients with metastatic tumor. For patients with metastatic pure dysgerminoma, chemotherapy appears to have supplanted radiotherapy as standard treatment with the advantage of preserving fertility in most patients. For patients with SCST, no standard therapy exists. Surgery alone is currently acceptable treatment for all patients with SCST except those with metastatic disease, sarcomas, or Sertoli-Leydig cell tumors with poor differentiation or heterologous elements. Currently, platinum-based combination chemotherapy is favored for these latter patients but activity with such regimens is only modest.

A 34-year-old man underwent left hemicastration for malignant unclassified sex cord gonadal stromal tumor. At 6 months pulmonary metastases developed and the patient received 3 courses of chemotherapy consisting of cisplatin, bleomycin and etoposide. A residual focus in the right lung was excised and proved to be viable tumor. He then received 2 adjuvant courses of cisplatin, etoposide and ifosfamide. Six months later he was without evidence of disease. A review of the literature revealed 21 previous cases of malignant unclassified sex cord gonadal stromal tumor. Although chemotherapy usually fails in treating Leydig cell tumors our case corroborates 6 previous reports of favorable response to cisplatin-based chemotherapy. This finding suggests that different subtypes of sex cord gonadal stromal tumor respond differently to chemotherapy.

A 66-year-old woman was diagnosed as having myoma of the uterus and total hysterectomy with bilateral salpingo-oophorectomy was performed. The histopathological findings were puzzling, and the case was finally diagnosed as intramural uterine stromal tumor with epithelial differentiation. Three years after the operation, a firm tumor developed in the pelvic cavity. Laparotomy failed to remove the tumor and neither CAP (cyclophosphamide 500 mg, adriamycin 50 mg, CDDP 70 mg) therapy nor radiation therapy was effective. Oral administration of etoposide (25 mg/day), however, showed PR (50% decrease) as determined by CT scanning, and ultrasonography, and no metastatic lesions were found. This tumor was coincident with the endometrial stromal tumor with epithelial elements classified by Clement and Scully. The histological feature of the tumors and the efficacy of oral etoposide therapy are discussed in this study.

Metastatic stromal cell tumors of the testis are largely refractory to chemotherapy. We report a case of a young man with widely metastatic testicular stromal cell tumor who achieved complete clinical remission following chemotherapy with etoposide, ifosfamide, cisplatin, and bleomycin.