Publications by authors named "Gershenson D"
Adult type ovarian granulosa cell tumors (AGCTs) are rare malignancies with the near universal c.C402G (p.Cys134Trp) somatic mutation in FOXL2, a Forkhead box-family transcription factor important for ovarian function.
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- - The NCCN Guidelines outline a comprehensive approach to diagnosing, staging, and treating ovarian, fallopian tube, and primary peritoneal cancers.
- - Recent developments in the use of PARP inhibitors, both as maintenance therapy and standalone treatments, have significantly influenced the recommendations in these guidelines.
- - These insights highlight the collaborative effort among experts to continuously update treatment protocols based on the latest research in ovarian cancer therapies.
Objectives: To evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase () promoter mutations.
Methods: This is a retrospective cohort study using the MD Anderson Rare Gynecologic Malignancy Registry. Patients with adult granulosa cell tumors who underwent molecular testing for promoter and c.
Article Synopsis
- There are no special treatments approved for low grade serous ovarian cancer, and the usual treatments don't always work well.
- A new combination of two medicines called avutometinib and defactinib might work better and is safer than regular treatments.
- The study wants to see if using this new combo helps patients live longer without their cancer getting worse compared to other treatments doctors might choose.
Objective: Targeted therapy in folate receptor alpha (FOLR1)-positive high grade serous ovarian carcinoma (HGSOC) is now a mainstay for platinum-resistant disease. However, the rate of FOLR1-positivity in low grade serous ovarian carcinoma (LGSOC) is not well documented. Less common than HGSOC, LGSOC tends to respond poorly to traditional platinum-based chemotherapeutic regimens, particularly in recurrence.
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- The study aimed to compare the effectiveness and side effects of two chemotherapy regimens, paclitaxel and carboplatin (PC), against bleomycin, etoposide, and cisplatin (BEP) in treating newly diagnosed or recurrent ovarian sex cord-stromal tumors (SCST).
- In a phase II trial involving 63 patients, the analysis showed that PC did not meet the criteria for being as effective as BEP, with a median progression-free survival of 27.7 months for PC compared to 19.7 months for BEP.
- Although PC had fewer serious adverse events (77% vs. 90%), the study concluded that it failed to demonstrate non-inferiority to BE
Purpose: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.
Experimental Design: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model.
Introduction: Early reports of PD-1 inhibition in ovarian clear cell carcinomas (OCCC) demonstrate promising response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent OCCC.
Methods: This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens.
Background: Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness.
View Article and Find Full Text PDFBackground: Low grade serous ovarian carcinoma (LGSOC) is a distinct histotype of ovarian cancer characterised high levels of intrinsic chemoresistance, highlighting the urgent need for new treatments. High throughput screening in clinically-informative cell-based models represents an attractive strategy for identifying candidate treatment options for prioritisation in clinical studies.
Methods: We performed a high throughput drug screen of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) to identify novel candidate therapeutic approaches.
Background: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis.
View Article and Find Full Text PDFBackground: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).
Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm.
Article Synopsis
- * Out of 618 patients identified, 81.1% received adjuvant chemotherapy, but there was no significant difference in overall survival between those who had chemotherapy and those who didn't.
- * The findings suggest that adjuvant chemotherapy may not improve overall survival rates for this patient group, challenging its routine use after surgery.
Low-grade serous ovarian cancer: expert consensus report on the state of the science.
Int J Gynecol Cancer
September 2023
Article Synopsis
- * Recent advances in molecular research and targeted therapies show promise for better outcomes in low-grade serous carcinoma patients, although specifics on its pathogenesis and optimal management are still being explored.
- * An expert panel met in October 2022 to create a consensus document focused on improving diagnosis, treatment, and ongoing research for low-grade serous carcinoma, integrating scientific advancements with patient perspectives to enhance clinical management.
Article Synopsis
- A study was conducted to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) in less common types of epithelial ovarian cancer, as previous trials primarily focused on high-grade serous carcinomas.
- The research involved a retrospective analysis using data from the National Cancer Database, reviewing cases from 2006 to 2017, and included patients with advanced stages of clear cell, mucinous, and low-grade serous ovarian cancers.
- Findings showed that the use of NACT increased significantly among patients with clear cell and low-grade serous carcinomas, indicating a positive trend in treatment uptake, but overall survival comparisons were also needed for a better understanding of outcomes.
Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).
Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula.
Objective: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction.
Methods: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included.
Unlabelled: Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors.
View Article and Find Full Text PDFBackground: The optimal treatment of recurrent ovarian granulosa cell tumors is not known. Preclinical studies and small case series have suggested direct antitumor activity of gonadotropin-releasing hormone agonists in the treatment of this disease, but little is known about the efficacy and safety of this approach.
Objective: This study aimed to describe patterns of use and clinical outcomes of leuprolide acetate in a cohort of patients with recurrent granulosa cell tumors.
Low-grade serous ovarian cancer is a rare subtype of epithelial ovarian cancer clinically characterized by younger age at diagnosis, relative chemoresistance, and prolonged survival compared with its high-grade serous counterpart. It is molecularly characterized by estrogen and progesterone receptor positivity, aberrations in the MAPK (mitogen-activated protein kinase) pathway, and wild-type expression pattern. As research into low-grade serous ovarian cancer as a distinct entity has been able to accelerate independently, we have learned more about its unique pathogenesis, oncogenic drivers, and opportunities for novel therapeutics.
View Article and Find Full Text PDFBackground: Low-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women than those with high-grade disease. The current treatment is suboptimal and a better understanding of the molecular pathogenesis of this disease is required. In this study, we compared the proteogenomic analyses of LGSOCs from short- and long-term survivors (defined as < 40 and > 60 months, respectively).
View Article and Find Full Text PDFObjective: Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.
Methods: This was an open label, single-center, multi-arm phase 1b study utilizing a "3 + 3" design and a "basket-type" expansion in recurrent solid tumors.
Objective: The primary objective of the study was to estimate the 12-month progression-free survival (PFS) for carboplatin/paclitaxel + temsirolimus in women with newly diagnosed clear cell ovarian cancer (CCOC), compared to historical controls in this patient population.
Methods: Patients with Stage III or IV CCOC were treated with Paclitaxel 175 mg/m2 on Day 1, Carboplatin AUC 6 Day 1, and temsirolimus (CCI-779) 25 mg IV Days 1 and 8 every 3 weeks for Cycles 1-6 or disease progression, followed by consolidation therapy with temsirolimus 25 mg Days 1, 8, and 15 every 3 weeks cycles 7-17 or until disease progression.
Results: Ninety patients were accrued to the study: 45 in the US and Korea (US/Korea) and 45 in Japan.
Objective: The purpose of the present study is to describe a cohort who received contemporary primary treatment for stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC), including patient characteristics and determinants of relapse and disease-free survival.
Methods: The study included 99 patients: 1) with pathologically confirmed stage II-IV LGSOC of the ovary or peritoneum, 2) who underwent primary treatment consisting of cytoreductive surgery and either a) platinum/taxane chemotherapy followed by aromatase inhibitor maintenance therapy or b) aromatase inhibitor monotherapy, and 3) for whom there was availability of clinical data. Descriptive statistics were used to characterize clinicodemographic features.