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.

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.

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.

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.

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.