Current Treatment Options: Uterine Sarcoma.

OPINION STATEMENT: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.

Treatment of vulvar and vaginal dysplasia: plasma energy ablation versus carbon dioxide laser ablation.

OBJECTIVE: Plasma energy ablation vaporizes tissues similar to carbon dioxide laser ablation, but is not hindered by the unique hazards and regulation of laser technology. We aimed to evaluate the complication rate and effectiveness of plasma versus laser ablation in the treatment of vulvovaginal high-grade squamous intra-epithelial lesions (HSIL). METHODS: We performed a retrospective cohort study of women treated with plasma or carbon dioxide laser ablation for histologically proven HSIL of the vulva or vagina from January 2014 to October 2019 at a single institution. Demographic factors, surgical characteristics, and complications were compared by ablation type using Fisher's exact tests. Recurrence-free survival was evaluated by ablation type using Kaplan-Meier curves, weighted log-rank tests, and Cox proportional hazards ratio estimates. RESULTS: Forty-two women were included; 50% underwent plasma and 50% underwent carbon dioxide laser ablation. Demographic factors were similar between the groups. 50% (n=21) were immunosuppressed, 45.2% (n=19) had prior vulvovaginal HSIL treatment, and 35.7% (n=15) were current smokers. Most women (n=25, 59.5%) were treated for vulvar HSIL, 38.1% (n=16) for vaginal HSIL. Complication rates did not differ by treatment: 9.5% (n=2) for laser ablation versus 4.8% (n=1) for plasma ablation (p=1.0). Over a median follow-up time of 29.3 months (IQR 11.0-45.0 months), recurrence rates were similar: 28.6% in the laser ablation group versus 33.3% in the plasma ablation group (weighted log rank p=0.43; 24-month HR 0.54, 95% CI 0.15 to 2.01). CONCLUSION: Plasma energy ablation of vulvovaginal HSIL has similar complication rates and recurrence risk to carbon dioxide laser ablation. This technique could be considered as an alternative treatment modality for vulvovaginal HSIL and warrants further investigation.

Iterative approach to journal club.

To identify, evaluate and refine a journal club (JC) format that increases faculty and resident engagement. An initial needs assessment followed by a trial of three JC formats: traditional single presenter, debate style and facilitated small group discussion was piloted over 6 months. Anonymous feedback was collected. The facilitated small group format was chosen. Narrative and quantitative feedback were collected from residents and faculty at 6-month intervals for the next 24 months. Changes to the format were made using feedback. Fourteen residents (n=20, 70%) and 10 faculty (n=20, 50%) completed baseline surveys. We initially observed low resident (8/14, 57%) interest in JCs. Additionally, 9/14 (64%) of residents and 1/15 (7%) of faculty reported low confidence presenting articles publicly. After implementation of the new JC format, resident reported enjoyment, on a scale of 1-5, improved from 3.6 to 4.4 (p<0.01). We observed improvement in resident confidence in the ability to critique a paper (2.7 to 4.1, p<0.01) and in confidence speaking in front of both peers (3.8 to 4.6, p<0.01) and faculty (3.0 to 3.8, p=0.04). Faculty confidence with literature critique decreased (from 4.2 to 3.8), but enjoyment remained stable (4.3 to 4.2). A facilitated small group JC format was preferred in our programme. We observed measurable improvements in both resident interest and confidence, as well as sustained faculty interest in JCs. We fostered an environment of inquiry and identified areas of continued professional development.

Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG Oncology/GOG study.

OBJECTIVES: Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy for bevacizumab. METHODS: Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The presence of ascites was determined prospectively. Chi-square and Wilcoxon-Mann-Whitney tests compared baseline variables between subgroups. Survival was estimated by Kaplan-Meier method, and Cox proportional hazard models were used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on survival. RESULTS: Treatment arms were balanced with respect to ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221 (20%) did not. Those with ascites were more likely to have: poorer performance status (p<0.001); serous histology (p=0.012); higher baseline CA125 (p<0.001); and suboptimal cytoreduction (p=0.004). In multivariate survival analysis, ascites was prognostic of poor OS (Adjusted HR 1.22, 95% CI 1.00-1.48, p=0.045), but not PFS. In predictive analysis, patients without ascites treated with bevacizumab had no significant improvement in either PFS (AHR 0.81, 95% CI 0.59-1.10, p=0.18) or OS (AHR 0.94, 95% CI 0.65-1.36, p=0.76). Patients with ascites treated with bevacizumab had significantly improved PFS (AHR 0.71, 95% CI 0.62-0.81, p<0.001) and OS (AHR 0.82, 95% CI 0.70-0.96, p=0.014). CONCLUSIONS: Ascites in women with advanced ovarian cancer is prognostic of poor overall survival. Ascites may predict the population of women more likely to derive long-term benefit from bevacizumab.

Integrating Social Needs Screening and Resource Referral Into Standard Ambulatory Oncology Care: A Quality Improvement Project.

PURPOSE: We previously implemented paper-based screening for health-related social resource needs (HRSN) in our gynecologic oncology clinic and found that 36% of patients who completed the screening reported HRSN. We identified two primary deficiencies with our process. First, only 52% of patients completed the screening. Second, 37% of patients with needs failed to indicate if they desired resource referral or not. Therefore, we conducted a quality improvement project to integrate screening and referral processes into the electronic medical record (EMR) and routine clinic workflow to achieve at least 90% screening compliance and 90% elicited referral preference. METHODS: A multidisciplinary team consisting of physicians, a health outcomes researcher, a computer programmer, project assistants, and the staff of a partner community organization designed and implemented an intervention that screened for HRSN online via the EMR patient platform or in person during visits. The primary outcome was the percentage of eligible patients who completed the HRSN screening (ie, reach). Outcomes were reviewed weekly, and feedback was provided to stakeholders monthly. Iterative changes were incorporated into five successive Plan-Do-Study-Act (PDSA) cycles completed from January 2021 to March 2023. RESULTS: Screening compliance increased from the baseline of 52% (paper-based) to 97% in PDSA 4. Completion via the online patient portal increased from 17% in prelaunch to 49% in PDSA 4. Of patients who reported needs, 100% had a documented referral preference. CONCLUSION: Compared with paper-based screening, an EMR-integrated HRSN screening and referral system significantly improved reach to patients at a gynecologic oncology clinic. Implementation efforts to expand to other ambulatory clinic settings are in process.

Incorporation of immunotherapy into the treatment of metastatic neuroendocrine carcinoma of the cervix: A case report.

•Ideal treatment for advanced neuroendocrine carcinoma of the cervix (NECC) remains unclear.•A patient with metastatic NECC experienced a durable complete response to multi-modal therapy that included atezolizumab.•Atezolizumab may improve response rates and overall survival when incorporated into therapy for NECC.

Cancer surveillance for transgender and gender diverse patients with Lynch syndrome: a practice resource of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

Transgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals. There are no clinical guidelines specific for TGD individuals with LS, highlighting a need to improve the quality of care for this population. There is an urgent need for cancer surveillance recommendations for TGD patients. This commentary provides recommendations for cancer surveillance, risk-reducing strategies, and genetic counseling considerations for TGD patients with LS.

Does significant medical comorbidity negate the benefit of up-front cytoreduction in advanced ovarian cancer?

BACKGROUND: The objective of the study was to determine if initial surgery (IS) or initial chemotherapy (IC) affects rates of optimal surgery and survival in a population with significant medical comorbidities. METHODS: Data of all patients with stage III-IV ovarian, peritoneal, and fallopian tube cancers diagnosed from 1995 to 2008 were reviewed. Clinical and pathologic data were abstracted. RESULTS: There were 551 cases for review: 255 (46.3%) received IS, and 296 (53.7%) received IC. Patients who received IC had higher stage (P < 0.001), higher-grade cancers (P < 0.001), higher mean CA-125 (P = 0.015), higher rates of diabetes (P = 0.006), hypertension (P = 0.008), and presurgical embolism (P < 0.022) and were older (P = 0.043). There was no difference with respect to body mass index, albumin, extent of surgery, or intensive care use. Rates of optimal cytoreduction were higher with IC compared with IS (72.7% vs 56.1%, P < 0.001). IS was associated with more blood loss (P = 0.005) and higher rates of postsurgical venous thrombosis (P < 0.001). Optimal cytoreduction predicted survival in both groups. Among optimal patients, IS improved median survival: progression-free survival of 14 months (IS) versus 12 months (IC), P = 0.004; overall survival of 58 months (IS) versus 34 months (IC), P = 0.002. Factors influencing this difference were receipt of IC and history of diabetes; both predictors of mortality: hazard ratios, 1.9 (95% confidence interval, 1.3-2.8; P < 0.001) and 1.8 (95% confidence interval, 1.02-3.1; P = 0.042), respectively. CONCLUSIONS: The achievement of optimal cytoreduction continues to be a significant predictor of survival, regardless of treatment approach. Patients selected for IS and in whom optimal cytoreduction was achieved had improvements in both progression-free survival and overall survival. However, the differences could not be explained by surgical effort alone as diabetes was independently associated with mortality.

Gynecologic oncology HPV vaccination practice patterns: Investigating practice barriers, knowledge gaps and opportunities for maximizing cervical cancer prevention.

Objective: HPV vaccination is an important form of cancer prevention. Gynecologic oncologists have an opportunity to improve adult vaccination rates. We aimed to describe current HPV vaccination practices and barriers to vaccination reported by gynecologic oncologists. Methods: An online survey was developed, pilot tested and sent to U.S. members of the Society of Gynecologic Oncology. Results: Of the 226 respondents, most were female (73%), < 45 years old (64%) and practiced in urban (60%) and academic settings (69%). Ninety percent had recommended the HPV vaccine in the past year. Nearly half (47%) had facilitated vaccination by: administering the HPV vaccine in clinic (40%), stocking the vaccine (35%), or prescribing the vaccine (30%). Recommending the vaccine was associated with higher outpatient volume, practicing in the South vs. Northeast, and having higher levels of vaccine knowledge.Of the 90% who recommended the vaccine, 60% did not prescribe or know if they could prescribe the vaccine in their state. Prioritization of cancer treatment was the most commonly reported barrier to HPV vaccination (88%). Approximately half of providers reported other systems-level hinderances such as high cost of stocking the vaccine, clinic flow disruption, or uncertainty surrounding insurance coverage. Almost all recommenders offered the vaccine at HPV-related dysplasia (92%) or cancer (80%) visits, while only 24-50% offered it at non-HPV-related visits. Conclusions: These survey results identify patient, provider, and systems-level barriers that could be targeted to help increase adult HPV vaccination in gynecologic oncology clinics.

Creating Breast and Gynecologic Cancer Guidelines for Transgender Patients With BRCA Mutations.

More than 1.5 million individuals in the United States identify as transgender. Transgender individuals have lower rates of health care utilization and higher rates of health care discrimination than cisgender patients. With a growing interest in providing comprehensive and compassionate care to the transgender community, there has been a concurrent increase in research on transgender health. However, lack of long-term data limits understanding the effects of hormone therapy on cancer risk factors in this population. This is particularly relevant for patients with hormonally mediated cancers and those at elevated risk from hereditary breast and ovarian cancer syndromes. Few cancer-screening and management guidelines currently exist for this population. Specific practices guided by the nuances of gender identity and gender-affirming care are essential to improve clinical management and to avoid further alienating a population that is already marginalized from the health care system. This commentary summarizes screening, management, and surveillance strategies devised for cisgender patients to offer corresponding recommendations tailored for transgender BRCA mutation carriers. In doing so, it highlights critical unanswered questions pertaining to the care of these patients. To address these questions, we must prioritize this population and adopt more inclusive frameworks in medicine and research.

Diffuse large B cell lymphoma of the cervix with rectal involvement.

•Diffuse large B cell lymphoma of the cervix is a very rare gynecologic malignancy and difficult to diagnose.•This case is the youngest reported occurrence of cervical DLBCL with interesting considerations of GI involvement and fertility.

Use of image-guided stereotactic body radiation therapy in lieu of intracavitary brachytherapy for the treatment of inoperable endometrial neoplasia.

PURPOSE: Retrospective analysis of patients with invasive endometrial neoplasia who were treated with external beam radiation therapy followed by stereotactic body radiation therapy (SBRT) boost because of the inability to undergo surgery or brachytherapy. METHODS AND MATERIALS: We identified 11 women with stage I-III endometrial cancer with a median age of 78 years that were not candidates for hysterectomy or intracavitary brachytherapy secondary to comorbidities (91%) or refusal (9%). Eight patients were American Joint Committee on Cancer (AJCC) stage I (3 stage IA, 5 stage IB), and 3 patients were AJCC stage III. Patients were treated to a median of 4500 cGy at 180 cGy per fraction followed by SBRT boost (600 cGy per fraction×5). RESULTS: The most common side effect was acute grade 1 gastrointestinal toxicity in 73% of patients, with no late toxicities observed. With a median follow-up of 10 months since SBRT, 5 patients (45%) experienced locoregional disease progression, with 3 patients (27%) succumbing to their malignancy. At 12 and 18 months from SBRT, the overall freedom from progression was 68% and 41%, respectively. Overall freedom from progression (FFP) was 100% for all patients with AJCC stage IA endometrial carcinoma, whereas it was 33% for stage IB at 18 months. The overall FFP was 100% for International Federation of Obstetrics and Gynecology grade 1 disease. The estimated overall survival was 57% at 18 months from diagnosis. CONCLUSION: In this study, SBRT boost to the intact uterus was feasible, with encouragingly low rates of acute and late toxicity, and favorable disease control in patients with early-stage disease. Additional studies are needed to provide better insight into the best management of these clinically challenging cases.

Molecular requirements for transformation of fallopian tube epithelial cells into serous carcinoma.

Although controversial, recent studies suggest that serous ovarian carcinomas may arise from fallopian tube fimbria rather than ovarian surface epithelium. We developed an in vitro model for serous carcinogenesis in which primary human fallopian tube epithelial cells (FTECs) were exposed to potentially oncogenic molecular alterations delivered by retroviral vectors. To more closely mirror in vivo conditions, transformation of FTECs was driven by the positive selection of growth-promoting alterations rather antibiotic selection. Injection of the transformed FTEC lines in SCID mice resulted in xenografts with histologic and immunohistochemical features indistinguishable from poorly differentiated serous carcinomas. Transcriptional profiling revealed high similarity among the transformed and control FTEC lines and patient-derived serous ovarian carcinoma cells and was used to define a malignancy-related transcriptional signature. Oncogene-treated FTEC lines were serially analyzed using quantitative reverse transcription-polymerase chain reaction and immunoblot analysis to identify oncogenes whose expression was subject to positive selection. The combination of p53 and Rb inactivation (mediated by SV40 T antigen), hTERT expression, and oncogenic C-MYC and HRAS accumulation showed positive selection during transformation. Knockdown of each of these selected components resulted in significant growth inhibition of the transformed cell lines that correlated with p27 accumulation. The combination of SV40 T antigen and hTERT expression resulted in immortalized cells that were nontumorigenic in mice, whereas forced expression of a dominant-negative p53 isoform (p53DD) and hTERT resulted in senescence. Thus, our investigation supports the tubal origin of serous carcinoma and provides a dynamic model for studying early molecular alterations in serous carcinogenesis.

Cisplatin administration following carboplatin desensitization failure in primary peritoneal cancer: a brief report.

PURPOSE: Platinum-based therapy is the cornerstone of ovarian cancer treatment. Development of platinum hypersensitivity can limit therapeutic options. In this brief report, we present case of successful cisplatin administration following two unsuccessful carboplatin desensitization attempts, and without the need for pre-treatment steroids. METHODS: Retrospective chart review was performed. RESULTS: One case of recurrent primary peritoneal carcinoma previously treated with a carboplatin-based regimen, developed a platinum hypersensitivity. Two attempts at carboplatin desensitization were unsuccessful. Cisplatin was substituted and the patient achieved a complete response to therapy without further hypersensitivity. CONCLUSIONS: Platinum-based therapies are vital to the treatment of primary peritoneal and ovarian carcinoma. Protocols that successfully incorporate platinum agents, despite a platinum hypersensitivity, are clinically relevant.