Search

Uterine leiomyosarcoma (ULMS) is an aggressive malignancy for which hysterectomy is often the primary treatment approach. Due to the rarity of these tumors, the role of oophorectomy in the management of ULMS is not clearly established. This study aimed to describe the impact of oophorectomy and estrogen/progesterone (ER/PR) receptor status on clinical outcomes and survival.Women with ULMS treated between 1/2013 and 1/2018 were retrospectively identified. Clinical data was collected; descriptive statistics were performed and predictors of overall survival (OS) and event free survival (EFS) were analyzed using Cox regression and Kaplan-Meier methodology.189 patients were included. Median age was 53 years (20-84 years). The majority of patients had stage IB (58%) and grade 3 (94%) tumors. On pathologic analysis, ER/PR expression was positive in 41% and 33%, respectively. The majority of patients (179, 94.7%) underwent surgery as their primary treatment approach, of which 51 (28.5%) had ovarian conservation. 59.0% were treated with chemotherapy, while 9.9% received radiation therapy. 84.6% of patients experienced a recurrence, but there was no difference in EFS or OS by oophorectomy status, including among those with uterine confined disease. Additionally, ER/PR status was not independently associated with EFS/OS (p = 0.14, p = 0.07) nor did it impact survival among those with ovaries left in situ.Oophorectomy did not influence OS, even though many tumors were hormone receptor positive. ER/PR status was not independently associated with survival, including in the subset of women with uterine confined disease and those who had undergone oophorectomy.

An estimated 2-5% of endometrial cancers and 15-20% of high-grade, non-mucinous epithelial ovarian cancers have an underlying hereditary cause. Appropriate risk assessment, genetic counseling, and germline genetic testing for cancer predisposition genes in both gynecologic cancer patients and their at-risk relatives is essential for effective delivery of tailored cancer treatment and cancer prevention. However, significant disparities exist within medically underserved and minority populations in the United States regarding awareness of, access to, and use of genetic services. The objectives of this review are to summarize the literature on genetic counseling and genetic testing of gynecologic cancer patients, the cascade genetic testing of their families following the identification of a germline mutation associated with susceptibility to cancer, to highlight disparities between populations, and to present some potential remedies.

Objective To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy. Methods Women with recurrent ovarian cancer treated with an immune checkpoint inhibitor between 1/2012 and 8/2017 were included. RECIST criteria determined disease status, and immune related adverse events (irAE) were graded per trial protocols. Predictors of response, irAE, progression free survival (PFS) and overall survival (OS) were investigated. Results Forty-four women were included with a median age of 53 years, median of 4 prior lines of chemotherapy, and most commonly high grade serous pathology (59.1%). 3 patients had partial response and 3 had pseudoprogression, for a response rate of 14.2%. In subset analysis of high grade serous (HGSOC) pathology, platinum sensitivity at time of checkpoint inhibitor therapy was correlated with response (p = 0.01). There were 28 grade 3/4 irAEs in 21 patients (47.7%). Combination therapy rather than monotherapy predicted irAE (OR 5.7, CI 1.6–20.9, p = 0.02). The most common severe irAE was elevation in hepatic or pancreatic enzymes in 12 total patients (13.6% each). Interestingly, the number of genes mutated was protective from hepatic/pancreatic AE (p = 0.02). Conclusions While response rate was similar to prior literature, in patients with HGSOC platinum sensitivity at time of checkpoint inhibitor initiation was correlated to response. Grade 3/4 hepatic and pancreatic enzyme elevations were more common in ovarian cancer patients than has been previously reported in other tumor types. The number of genes mutated was inversely correlated to risk of this type of irAEs but not to total irAEs.

The success of targeted and immune therapies in other malignancies has led to an exponential increase in the number of active and pending clinical trials using these therapeutic approaches in patients with gynecologic cancers. These novel investigational agents are associated with unique and potentially life-threatening toxicities and many require special multidisciplinary logistical considerations. The objective of this review is to describe a practical approach for the safe implementation of targeted and immune therapies in academic gynecologic oncology practices based on our experience at M.D. Anderson Cancer Center.

Objectives: Uterine leiomyosarcoma (ULMS) is a rare tumor with limited therapeutic options and no clearly established best treatment sequence strategy. The objective of this study was to evaluate treatment sequencing for ULMS following primary surgical management and determine predictors of survival. Methods: Women with a diagnosis of ULMS between 1/2013 and 1/2018 were identified. Clinical data was collected; for this analysis, only women treated with primary surgical management were included. Descriptive statistics were performed and predictors of overall survival (OS) and progression free survival (PFS) were analyzed using Cox regression and Kaplan-Meier methodology. Results: 179 patients were included. Median age was 52 years (20-78), 94% had grade 3 tumors, and over half the total population were treated with adjuvant chemotherapy (n=100, 56%). In the subset of patients with early stage disease (126), 49% were treated with surgery only while 51% received adjuvant chemotherapy. There was no difference in PFS between early stage patients who did or did not receive adjuvant chemotherapy (p=0.60). For the overall cohort, the most common adjuvant therapy regimens were gemcitabine/docetaxel (gem/doce, 40.9%) or ifosphamide/doxorubicin (ifos/doxo, 11.4%).137 patients (76.5%) experienced recurrence, progression or death during their follow up. The median PFS was 1.76 years (95% CI: 1.27- 2.08). The median survival for those treated with surgery alone was 1.79 years, for those treated with gem/doce was 1.27 years, and other chemotherapy regimen was 0.43 years. Median survival was not estimated for the ifos/doxo regimen due to small patient number. Upfront therapy regimen significantly impacted PFS (Figure 1, p=0.003), but was not significantly associated with OS (p=0.069). The one-year PFS probability was 0.58 for gem/doce (95% CI 0.45-0.68) compared with 0.80 for ifos/doxo (95% CI 0.54-0.91). Download : Download high-res image (94KB) Download : Download full-size image Conclusions: Median PFS was 1.76 years, despite many women undergoing adjuvant therapy after surgery, most commonly with either gem/doce or ifos/doxo regimens. Primary treatment with ifos/doxo was associated with higher one-year PFS. This finding warrants additional evaluation to determine the optimal adjuvant therapy for these women.

Objectives: Minority participation in clinical trials is important for expanding opportunities in access to cancer therapies and may aid in understanding racial disparities in oncology care. Prior studies have identified underrepresentation in gynecologic oncology phase I recruitment and large group trials in the United States, but minority participation specific to trials that drive current treatment recommendations remains unclear. We sought to evaluate minority participation as described in publications of curated, high quality clinical evidence for ovarian cancer therapies as identified by the National Comprehensive Cancer Network (NCCN). Methods: NCCN Clinical Practice Guidelines for Ovarian Cancer, Version 1.2020, was accessed in order to identify evidence provided for ‘preferred’ primary and recurrent systemic therapies and dosing regimens in advanced epithelial ovarian cancer using explicitly listed citations. Race and ethnicity data of trial enrollment provided in publications listed as references was manually abstracted. Results: We identified 26 prospective trials including 13,887 participants, published across 5 journals: New England Journal of Medicine, Lancet, Lancet Oncology, Gynecologic Oncology, and Journal of the National Cancer Institute. All were phase II or III trials and 96% of trials were published in or more recently than 2003. Of these trials, race or ethnicity was reported in only 9 publications (35%). Of these 9 publications, there was marked language variation between trials in reporting race and ethnicity. There were 7 trials that included a description of participants as Black or African American. Of the 4,701 women who participated in these trials, 206 were Black or African American, representing approximately 4% of trial participants. There were 4 trials that included a description of participants as Hispanic. Of the 3,436 women who participated in these trials, 152 were Hispanic, representing approximately 4% of trial participants. Conclusions: Of the clinical trial evidence for preferred systemic therapies identified in the NCCN clinical practice guidelines for advanced ovarian cancer, minority participation was reported in less than half of publications and description of race and ethnicity varied between trials. Of trials that reported minority participation, Black and hispanic women represented

OBJECTIVE: Early-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity. METHODS: From 2010–2013, patients were randomized (1:1) to receive OPT-821±vaccine-KLH conjugate subcutaneously at weeks 1, 2, 3, 7, 11, and then every 12 weeks (total 11). Dose delay or reduction was not permitted. Patients were removed for pre-defined dose-limiting toxicity. RESULTS: Of 171 patients randomized, 170 were treated. Most had disease of serous histology (85%), stage 3 disease at diagnosis (77%), and had received 2 prior regimens (68%). 32% received >6 treatment cycles [median 6, each arm (p=0.33)]. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Maximum toxicity was grade 4 MDS and depression/personality change (1 each, unlikely related) and others including grade 3 gastrointestinal disorders (n=21, 4 related). Lesser adverse events were injection site reactions (82%) and fever (11%). Estimated HR for progression-free survival (PFS) of the vaccine+OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71–1.36). At a median follow-up of 60 months, median OS was 47 and 46 months, respectively. CONCLUSIONS: Vaccine+OPT-821 compared to OPT-821 alone was modestly immunogenic and did not prolong PFS or OS. Multi-remission patients are a viable, well-defined population for exploring innovative consolidation and maintenance approaches.

To identify clinical and non-clinical factors associated with utilization of primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) in women with advanced stage epithelial ovarian cancer (EOC).Using the National Cancer Database, we identified women with stage IIIC and IV EOC diagnosed from 2012 to 2014. The primary outcome was receipt of NACT, defined in the primary analysis as utilization of chemotherapy as the first cancer-directed therapy, irrespective of whether interval surgery was performed. Univariable and multivariable associations between clinical and non-clinical factors and receipt of NACT were investigated using mixed-effect logistic regression models. A secondary analysis excluded women who received primary chemotherapy but did not receive interval cytoreductive surgery.Among 17,302 eligible women, 10,948 (63.3%) underwent PCS and 6354 (36.7%) received NACT. Older age, stage IV disease, high-grade, and serous histology were associated with receipt of NACT in univariate (p0.001) and multivariable analyses (p0.001). Analysis of non-clinical factors revealed that residency in the Northeast region and receipt of treatment closer to home were associated with NACT in univariate (p0.05) but not multivariable analysis (p0.05). In multivariable analysis, African-American race/ethnicity (p=0.04), low-income level (p=0.02), treatment in high-volume centers (p0.01), and insurance by Medicare or other government insurance (p0.001) were associated with receipt of NACT. When women who received no surgery were excluded, all factors that were independent predictors of NACT in the main analysis remained significant, except for race/ethnicity.Non-clinical factors were associated with the use of NACT at a magnitude similar to that of clinically relevant factors.

Objective Admissions to intensive care units (ICU) are costly, but are necessary for some patients undergoing radical cancer surgery. When compared to primary debulking surgery (PDS), neoadjuvant chemotherapy (NACT) with interval debulking surgery, is associated with less peri-operative morbidity. In this study, we compare rates, indications and lengths of ICU stays among ovarian cancer patients admitted to the ICU within 30days of cytoreduction, either primary or interval. Methods A retrospective chart review was performed of patients with stage III-IV ovarian cancer who underwent surgical cytoreduction at two large academic medical centers between 2010 and 2014. Chi square tests, Student t -tests, and Mann- U Whitney tests were used. Results A total of 635 patients were included in the study. There were 43 ICU admissions, 7% of patients. Compared to NACT, a higher percentage of PDS patients required ICU admission, 9.4% vs 3.9% of patients (P=0.004). ICU admission indications did not vary between PDS and NACT patients. NACT patients admitted to the ICU had comparable mean surgical complexity scores to those PDS patients admitted to the ICU, 6.2 (95%CI 5.3–7.1) vs 4.5 (95%CI 3.1–6.0) (P=0.006). Length of ICU admission did not vary between groups, PDS 2.7days (95%CI 2.3–3.2) vs 3.5days (95%CI 1.5–5.6) for NACT (P=0.936). Conclusions The rate of ICU admissions among patients undergoing PDS is higher than for NACT. Among patients admitted to the ICU, indications for admission, length of stay and surgical complexity were similar between patients treated with NACT and PDS.

Neoadjuvant chemotherapy and interval debulking surgery for the treatment of advanced ovarian cancer has remained controversial, despite the publication of two randomized trials comparing this modality with primary cytoreductive surgery. This study describes temporal trends in the utilization of neoadjuvant chemotherapy and interval debulking surgery in clinical practice in the United States.We completed a time trend analysis of the National Cancer Data Base. We identified women with stage IIIC and IV epithelial ovarian cancer diagnosed between 2004 and 2013. We categorized subjects as having undergone one of four treatment modalities: primary cytoreductive surgery followed by adjuvant chemotherapy, neoadjuvant chemotherapy followed by interval debulking surgery, surgery only, and chemotherapy only. Temporal trends in the frequency of treatment modalities were evaluated using Joinpoint regression, and χWe identified 40,694 women meeting inclusion criteria, of whom 27,032 (66.4%) underwent primary cytoreductive surgery and adjuvant chemotherapy, 5429 (13.3%) received neoadjuvant chemotherapy and interval surgery, 5844 (15.4%) had surgery only, and 2389 (5.9%) received chemotherapy only. The proportion of women receiving neoadjuvant chemotherapy and surgery increased from 8.6% to 22.6% between 2004 and 2013 (p0.001), and adoption of this treatment modality occurred primarily after 2007 (95%CI 2006-2009; p=0.001). During this period, the proportion of women who received primary cytoreductive surgery and chemotherapy declined from 68.1% to 60.8% (p0.001), and the proportion who underwent surgery only declined from 17.8% to 9.9% (p0.001).Between 2004 and 2013 the frequency of neoadjuvant chemotherapy and interval surgery increased significantly in the United States.

To investigate racial disparities with respect to adjuvant treatment and survival in patients presenting with malignant ovarian germ cell tumors (OGCT).The National Cancer Database (NCDB) was used to identify women diagnosed with OGCT. Demographic data were abstracted, including stratification by race and histology. Standard univariate and multivariate analyses using logistic regression were performed to describe predictors of adjuvant treatment. Kaplan-Meier and Cox proportional hazards survival methods were used to evaluate racial differences in survival between African American (AA) and white (W) women.The study population included 2196 patients, with 1654 (75.3%) W and 328 (14.9%) AA women. Histologic distribution varied significantly by race (p0.0001), but neither age nor stage at presentation showed racial differences (p=0.086 and p=0.209, respectively). AA received more chemotherapy than W (W: 54.6%, AA: 65.5%, p=0.008), but in multivariate analysis there was no statistically significant difference in any adjuvant treatment modality. Despite similar treatment, and independent of histology, survival varied significantly by race with 91% (CI 0.89-0.93) five year survival in W patients compared to 84% five year survival in AA (CI 0.8-0.89) (p=0.02). These disparities were most pronounced in advanced stage disease, with 5 year survival of 84% (CI 0.79-0.89) in W compared to 61% (CI 0.48-0.78) for AA in stage III (p=0.0002), and 54% (CI 0.42-0.68) compared to 14% (CI 0.03-0.71) for stage IV (p=0.05).AA with OGCT have significantly worse 5 year survival when compared to W patients despite similar rates and modalities of adjuvant treatment.

Objective To describe the role of immediate re-exploration in patients with inadvertently morcellated uterine leiomyosarcoma (ULMS) and smooth muscle tumors of uncertain malignant potential (STUMP). Methods All patients with ULMS/STUMP who were managed or referred to the participating institutions from January 2005 to January 2012 following minimally invasive gynecology surgery with morcellation were detected through the pathology database. The diagnosis was confirmed by gynecologic-pathologists following post-surgery pathology review. Results Twenty-one patients with the diagnosis of ULMS (N=15) and STUMP (N=6) after morcellation were identified. The median age of occurrence was 46years (range, 25–58years). Median follow-up duration was 27months (range, 1.8–93.1months). None of the 21 patients had documented evidence of extra-uterine disease at the time of original surgery. Ultimately 12 patients were immediately re-explored to complete staging. The median time to the staging surgery was 33days (range 15–118days). Two (28.5%) out of seven patients with presumed stage I ULMS and one (25%) out of four patients with presumed stage I STUMP had significant findings of disseminated intraperitoneal disease detected at immediate surgical re-exploration. One of the 8 patients with confined early ULMS and STUMP at the second surgery had intraperitoneal recurrence, while the remaining 7 patients have had no recurrence and remain disease free. Conclusion Surgical re-exploration is likely to show findings of disseminated peritoneal sarcomatosis in a significant number of patients diagnosed with ULMS after a morcellation procedure. Findings from re-exploration can contribute to the knowledge of natural history of morcellated ULMS/STUMP and allow for accurate prognostication.