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Objective: To evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus (HPV)-associated Vulvar intraepithelial neoplasia (VIN) 2/3., Methods: Participants were enrolled on a prospective, IRB-approved, dose-escalation phase I trial testing either 1, 2 or 3 treatment cycles (5 days), every other week, as applicable. Clinical assessments were completed prior to each dose cycle and included exam and review of adverse event (AE) diary cards. HPV testing and colposcopy was completed at 15 and 28 weeks. AEs were assessed according to CTCAE 4.0 criteria. Complete responders (CR) underwent biopsy of the treated site at the 28-weeks while partial (PR) and non (NR)-responders underwent surgical resection or biopsy and ablation., Results: Fifteen patients consented to and began treatment. Per-protocol assessments were completed in 100% at 15- and 80% at 28-weeks. All patients completed prescribed cycles with no grade 3 or 4 AEs. Vulvovaginal burning/ was the most common AE occurring in 93.3%. AEs were grade 2 in 23.7% and included vulvovaginal pruritus (n = 3), swelling (n = 3) and candidiasis (n = 2). The highest ORR was in the 3-cycle group (88.9% with 55.6% CR). HPV-16 was detected either alone (46.7%) or with other subtypes (33.3%) in 80% of lesions and 5 of 8 (62.5%) with CR had complete viral clearance., Conclusions: Topical artesunate for treatment of high-grade VIN shows high tolerability, low toxicity and evidence for clinical response in this initial small series. The safety and observed responses support further study in a Phase II trial., Competing Interests: Declaration of Competing Interest MP is employed by Frantz Medical Group, JLB has advised and run investigator-initiated clinical trials for multiple biotech companies including many that are involved in HPV related science. Specifically in regards to this study Dr. Belinson serves as a medical advisor to Frantz Viral Therapeutics. Outside of the presented work, CMM has recent/ current stock options/ ownership of MedaSync. All other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs)., Methods: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded., Results: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months)., Conclusions: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup., Competing Interests: Declaration of Competing Interest The authors confirm there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate overall survival (OS) in women with advanced endometrial cancer (EC) following chemotherapy alone (CT), neoadjuvant chemotherapy and interval debulking surgery (NACT + IDS) or primary cytoreductive surgery and chemotherapy (PCS + CT)., Methods: The National Cancer Database (NCDB) was queried for patients with stage III/IV EC from 2004 to 2015. Univariable and multivariable Cox proportional hazards analyses assessed the impact of treatment modality upon OS., Results: Of 48,179 women identified, 5531 received CT (11.5%), 2614 NACT + IDS (5.4%) and 40,034 PCS + CT (83.1%). Median OS was 11.1 months for CT, 25.1 months for NACT + IDS and 60.9 months for PCS + CT (p < 0.001). On multivariate analysis, NACT + IDS (HR 0.44 (0.40, 0.49); p < 0.001) and PCS + CT (HR 0.32 (0.30, 0.35); p < 0.001) were associated with improved OS vs. CT alone. Age, African American race, income, higher Charlson comorbidity index and grade were predictors of worse OS (p < 0.001). On subgroup analysis by stage (III/IV) and histology (Type I/II), PCS + CT improved OS for all patients, compared to NACT + IDS (p < 0.001) and CT (p < 0.001). NACT + IDS was associated with improved OS vs. CT in stage III type I (HR 0.50; 95% CI 0.38, 0.67; p < 0.001), stage IV type I (HR 0.43; 95% CI 0.35, 0.52; p < 0.001), and stage IV type II EC (HR 0.43; 95% CI 0.36, 0.51; p < 0.001), but not stage III type II EC (HR 0.76; 95% CI 0.56, 1.03; p = 0.08)., Conclusions: In women with advanced EC, PCS + CT is associated with improved OS compared to NACT + IDS or CT alone, regardless of stage or histology. Additionally, NACT + IDS is associated with superior OS in stage III type I and all stage IV EC compared to CT alone. Where feasible, surgery should be incorporated into treatment planning in women with advanced EC., Competing Interests: Declaration of Competing Interest All authors have no relevant conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To develop a risk-scoring system (RSS) for the prediction of lymphatic dissemination after hysterectomy in endometrioid endometrial carcinoma (EC)., Methods: Patients who underwent surgery from 1/1/1999-12/31/2008 were evaluated. Patients with non-endometrioid histology, stage IV with macroscopic extrauterine disease, or receiving adjuvant therapy (excluding brachytherapy) without pelvic and/or paraaortic (P/PA) lymphadenectomy (LND) were excluded. Lymph node dissemination was defined as nodal metastasis when P/PA LND was performed or P/PA lymph node recurrence after negative LND or when LND was not performed. Logistic regression analysis was used to identify predictors for lymphatic dissemination and develop a RSS and nomogram. The RSS was assessed for calibration and verified for discrimination., Results: Overall, 883 patients were assessed of which 521 (59.0%) underwent P/PA LND and 57 (10.9%) had positive lymph nodes. Of patients who did not undergo P/PA LND (N=362) or had negative nodes (N=464), 10 (1.2%) patients had P/PA lymph node recurrence. Myometrial invasion, tumor diameter (TD), FIGO grade, cervical stromal invasion and lymphovascular space invasion were significant on univariable analysis. All preceding variables were included in a multivariable logistic model. A parsimonious model and an alternative full model not including TD were considered. The full model with TD (illustrated in nomogram) had the highest predictive ability (concordance index 0.88)., Conclusion: Our RSS allows accurate quantification of the probability of lymphatic dissemination and can be used as an adjunct to clinical decision-making after hysterectomy in the absence of staging. TD is an important component of the RSS and should be routinely assessed., (© 2013 Elsevier Inc. All rights reserved.)

Objective: To estimate the incidence of synchronous endometrial cancer (EC) and ovarian cancer (OC) in the female population, among all women with EC, and in women under 50 years of age with EC, and to identify factors associated with synchronous EC/OC., Methods: All cases of synchronous EC/OC and EC diagnosed in women residing in Olmsted County, Minnesota between 1/1/1945 and 12/31/2008 were identified. Incidence was estimated using the population denominator from decennial census data, corrected for hysterectomy prevalence. A case-control study using 15 identified cases (EC/OC) and 45 controls (EC alone) was performed., Results: The incidence of synchronous EC/OC and EC (age-adjusted to the 2000 US female total and corrected for hysterectomy prevalence) in 1945-2008 was 0.88 and 30.3 per 100,000 person-years, respectively. Among women under 50 years of age, the corrected incidence of EC/OC and EC was 0.51 and 5.1 per 100,000 person-years, respectively. Among all women with EC, 3.1% had a synchronous OC compared to 9.4% of women under 50 years of age with EC. Patients with synchronous EC/OC were more likely than those with EC alone to present with a pelvic mass (57.1% vs. 8.9%, p<0.001). Patients with EC alone were more likely to have used oral contraceptive pills (OCPs) than synchronous EC/OC cases (22.7% vs 0%; Odds ratio, 0.10; 95% CI, <0.01-0.87)., Conclusion: Although the incidence of synchronous EC/OC in the general population is lower than previously reported, nearly 1 in 10 women diagnosed with EC under 50 years of age will have a synchronous OC., (Copyright © 2011 Elsevier Inc. All rights reserved.)