•HPV vaccination is not consistently offered (31.3%) to patients being treated for high-grade cervical or vulvar dysplasia.•Patients undergoing surgery for HPV-related dysplasia are likely to accept ...HPV vaccination (65.6%).•The rate at which adjuvant HPV vaccination is offered may improve over time.
Eligibility for the human papillomavirus (HPV) vaccine now includes adults 27 through 45 years. It has not been reported how providers are addressing HPV vaccination in patients with existing preinvasive disease. Our objectives were to determine the rates at which vaccination is offered to and received by patients undergoing surgery for high-grade cervical or vulvar dysplasia.
This was a single-institution retrospective cohort study including patients ages 18 through 45 years undergoing surgery for high-grade cervical or vulvar dysplasia from 10/2018 to 2/2020. Our primary outcome was the rate at which HPV vaccination was discussed at the pre- and/or post-operative visits. The secondary outcome was the rate of vaccine uptake in these individuals. Characteristics of those offered HPV vaccination were compared to those not offered vaccination.
Of the 115 patients included, 36 (31.3%) had HPV vaccination addressed in the perioperative setting. Thirty-two of these patients had never been vaccinated, and 21 of these (65.6%) went on to receive partial or complete HPV vaccination. Those in whom HPV vaccination was addressed were more likely to be under 27 years (RR 3.2; 95% CI 2.1–4.8) and less likely to be smokers (RR 0.5; 95% CI 0.2–0.9) or have prior excisional procedures (RR 0.3; 95% CI 0.1–0.9). The absolute rate of discussing HPV vaccination with patients improved from 26.0% within six months of vaccine age eligibility expansion, to 35.4% after six months (P = 0.32).
Providers did not consistently address HPV vaccination among patients being treated for high-grade cervical or vulvar dysplasia despite the potential benefits. However, a high proportion of these patients are amenable to vaccination. Quality improvement initiatives are warranted to increase the rate of HPV vaccine counseling in this context.
Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).
Black and White patients diagnosed with EEC who underwent ...hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.
Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87–2.23) for CRD and 1.22 (1.09–1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46–1.58) dropping to 1.29 (1.23–1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77–2.71) persisting to 1.32 (1.09–1.61) after matching for grade, stage, and treatment arm while balancing age and performance status.
Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.
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•Risk of cancer-related and non-cancer-related death was 200% and 22% higher in Black vs. White patients with EEC in SEER.•Risk of all-cause death was 1.52 (1.46–1.58) dropping to 1.29 (1.23–1.36) in matched NCDB Black vs. White patients.•Black vs. White patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR and CCND1 mutations and similar TMB-high status.•Advanced/recurrent disease, grade 3, and worse performance status were more common in Black vs. White EEC patients in RCTs.•Risk of death in Black vs. White patients in RCTs was 2.19 (1.77–2.71), persisting in matched analysis 1.32 (1.09–1.61).
•The Khorana score VTE risk assessment model has not been validated in patients with uterine cancer.•Patients with uterine cancer undergoing chemotherapy had a VTE rate of 6.5%.•Uterine cancer ...patients that had a VTE during treatment had a non-statistically significant higher average Khorana score.•A high Khorana score is a poor predictor of VTE in patients with uterine cancer undergoing chemotherapy.
Gynecologic cancers are associated with a high risk of venous thromboembolism (VTE). The Khorana score is a validated tool to assess risk of VTE in cancer patients. The purpose of this study is to determine if the Khorana score can be used as a risk stratification tool for VTE in patients with uterine cancer undergoing chemotherapy.
A retrospective cohort study of patients with newly diagnosed uterine cancer receiving chemotherapy over a 4-year period was conducted. The patients were stratified based on their Khorana score as well as their chemotherapy sequence, neoadjuvant or definitive versus adjuvant.
A total of 276 patients were included: 40 received neoadjuvant or definitive, 236 adjuvant chemotherapy. Most patients had advanced stage disease (64.5%). 18 (6.5%) patients developed VTE within 180 days of initiating chemotherapy. High Khorana score was associated with a non-significant increase in VTE (K ≥ 2 OR 1.17, CI 0.40–3.39, K ≥ 3 OR 1.69, CI 0.61–4.69) but had poor predictive accuracy based on area under the curve (K ≥ 2 0.51, K ≥ 3 0.55). The VTE rate was higher in the neoadjuvant/definitive chemotherapy group to adjuvant (12.5% vs 5.5%, p = 0.11). While the former group had a higher average Khorana score (2.35 vs 1.93, p = 0.0048), this was not predictive of VTE.
While validated in other cancer types, the Khorana score was found to be a poor predictor of VTE in patients with uterine cancer. The use of the Khorana score to guide routine thromboprophylaxis in these patients should be used with caution and further investigation is warranted.
•Despite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, the risk of recurrence was 37%.•Recurrence rate was higher for homologous recombination deficiency (HRD, ...70%) cases compared to proficient/unknown cases.•Shorter recurrence-free survival was seen among HRD cases compared to proficient/unknown cases.•Only 25% of HRD cases were due to germline BRCA mutations, with the remaining 75% identified as HRD by somatic testing.•Studying the role of PARP inhibitors in patients with early stage HRD ovarian cancer to improve outcomes is warranted.
To determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status.
Single institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed.
89 stage I/II cases were included. 4/89 (4.5%) had a germline BRCA1/2mutation, 8 (9%) were germline negative but had a somatic BRCA mutation, and 8 (9%) were BRCA wild-type but had evidence of LOH/GIS on somatic testing; these 20/89 (22%) cases comprised the HRD group. The remaining tumors were confirmed homologous recombination proficient (HRP, 35/89, 39%) or homologous recombination unknown (HRU, 34/89, 38%). The overall recurrence rate was 33/89 (37%). There were more recurrences among HRD cases (14/20, 70%) compared to HRP/HRU cases (19/69, 27.5%, p = 0.0012). Median Recurrence-Free Survival (RFS) was 35 months for HRD cases and 225 months for HRP/HRU cases (p = 0.001). At 2 years, there were 60% HRD cases and 88% HRP/HRU cases recurrence-free. At 5 years there were 29% HRD and 69% HRP/HRU cases recurrence-free (p = 0.001).
Despite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, recurrence rate was high in this early-stage cohort. Higher recurrence rates were seen in the HRD group, however these data are likely biased by the clinical practice of tumor testing primarily at the time of recurrence rather than the upfront setting. RFS was significantly lower for HRD cases.
We examined associations between patient and treatment characteristics with longitudinally collected patient-reported outcome (PRO) measures to provide a data-informed description of the experiences ...of women undergoing treatment for endometrial cancer.
We administered National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires at the preoperative visit and at 6 and 12 months after surgery. Anxiety, depression, fatigue, sleep disturbance, pain, physical function, and ability to participate in social roles were assessed. Analysis of variance (ANOVA) and linear mixed models were used to examine associations between patient characteristics and PRO measures at baseline and through time.
Of 187 women enrolled, 174 (93%) and 103 (69%) completed the 6- and 12-month questionnaires, respectively. Anxiety was substantially elevated at baseline (half of one population-level standard deviation) and returned to general population mean levels at 6 and 12 months. Younger age, Medicaid/None/Self-pay insurance, prevalent diabetes, and current smoking were associated with higher symptom burden on multiple PRO measures across the three time points. Women with aggressive histology, higher disease stage, or those with adjuvant treatment had worse fatigue at 6 months, which normalized by 12 months.
We observed a high symptom burden at endometrial cancer diagnosis, with most PRO measures returning to general population means by 1 year. Information on risk factor-PRO associations can be used during the clinical visit to inform supportive service referral.
These findings can inform clinicians' discussions with endometrial cancer survivors regarding expected symptom trajectory following diagnosis and treatment.
•Advanced age alone should not serve as contraindication to same-day discharge following minimally invasive hysterectomy.•Elderly patients who undergo same-day discharge are not at increased risk of ...30-day hospital readmission.•Elderly, frail patients encompass a higher-risk group where prehab and heightened peri-operative monitoring are warranted.
To determine the safety and feasibility of same-day discharge (SDD) following minimally invasive hysterectomy (MIH) for elderly patients and to evaluate associations between age, frailty, and postoperative outcomes.
Retrospective review was conducted of patients aged ≥ 70 who underwent MIH within a single gynecologic oncology institution from 2018 to 2020. Demographics, peri-operative factors, postoperative complications, and 30-day readmission rates were collected. Frailty was determined by an 11-point modified frailty index ≥ 2. Outcomes were compared between SDD and observation groups using Fisher’s exact and Wilcoxon rank-sum tests.
Of 169 patients included in the analysis, 8.9% (n = 15) underwent SDD, and 91.1% (n = 154) were admitted for OBS following MIH. Demographics, peri-operative factors, and frailty rates (33% SDD vs 43.5% observation; p = 0.59) were similar between groups. 86.7% (n = 13) of SDD cases were completed before 12PM, and none were completed after 6PM. No SDD patients had early post-operative complications or hospital readmissions. Early postoperative complications were diagnosed in 9 (5.8%) patients admitted for OBS, and the 30-day hospital readmission rate for patients who underwent OBS was 8.4% (n = 13). While elderly patients who met objective frailty criteria (n = 72) did not have a higher likelihood of early post-operative complications (44.4% vs 55.6%; p = 0.909), they did have a higher likelihood of ED visit within 30 days of discharge (15.3 vs 3.1%; p = 0.009), and a trend was noted toward a higher rate of 30-day hospital readmission (12.5% vs 4.1%; p = 0.080).
Elderly patients undergoing SDD following MIH did not have increased morbidity or mortality. Elderly patients who meet objective criteria for frailty, however, represent a more vulnerable population.
Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific ...recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes.
MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed. EC cell lines stably expressing MAXH28R were established and used for functional experiments. DNA binding was examined using electrophoretic mobility shift assays and chromatin immunoprecipitation. Transcriptional profiling was performed with microarrays. Murine flank (six to 11 mice per group) and intraperitoneal tumor models were used for in vivo studies. Vascularity of xenografts was assessed by MECA-32 immunohistochemistry. The paracrine pro-angiogenic nature of MAXH28R-expressing EC cells was tested using microfluidic HUVEC sprouting assays and VEGFA enzyme-linked immunosorbent assays. All statistical tests were two-sided.
Twenty-two of 509 tumors harbored mutations in MAX, including 12 tumors with the p.His28Arg mutation. Patients with a MAX mutation had statistically significantly reduced recurrence-free survival (hazard ratio = 4.00, 95% confidence interval = 1.15 to 13.91, P = .03). MAXH28R increased affinity for canonical E-box sequences, and MAXH28R-expressing EC cells dramatically altered transcriptional profiles. MAXH28R-derived xenografts statistically significantly increased vascular area compared with MAXWT and empty vector tumors (P = .003 and P = .008, respectively). MAXH28R-expressing EC cells secreted nearly double the levels of VEGFA compared with MAXWT cells (P = .03, .005, and .005 at 24, 48, and 72 hours, respectively), and conditioned media from MAXH28R cells increased sprouting when applied to HUVECs.
These data highlight the importance of MAX mutations in EC and point to increased vascularity as one mechanism contributing to clinical aggressiveness of EC.
There is a paucity of literature regarding the outcomes following vulvar excision for nonmalignant lesions. This is a common procedure among gynecologists and gynecologic oncologists, and a body of ...evidence is warranted to guide clinical care and future research.
This study aimed to estimate the rate of wound complications following simple vulvar excision and to identify the risk factors for these outcomes. Our secondary objectives were to determine the rates of (1) positive margins and (2) occult carcinoma in the cases of vulvar dysplasia.
We conducted a single-institution, retrospective cohort study of the patients who underwent simple vulvar excision procedures for suspected premalignant or benign lesions between June 2016 and February 2020. Our primary outcome was the rate of composite wound complications, including wound separation or breakdown, infection, or hematoma. Our secondary outcomes were the incidence of (1) margins positive for residual dysplasia and (2) occult minimally invasive carcinoma. The Fisher exact tests and chi-squared tests were used to compare the categorical variables and logistic regression models and independent student t tests were used for continuous variables, as appropriate. Multivariate stepwise selection and multiple logistic regression was performed to evaluate the risk factors for complications and generate the odds ratios.
Of the 338 patients included in the study, 143 (42.3%) experienced wound complication. Most of these complications were wound separation or breakdown (n=134, 39.6%), followed by infection (n=22, 6.5%), and hematoma (n=4, 1.2%). On multivariate analysis, the presence of high-grade vulvar dysplasia (adjusted odds ratio, 1.83; 95% confidence interval, 1.06–3.15), longer specimen diameter (adjusted odds ratio, 1.03; 95% confidence interval, 1.01–1.05), and lesion location on the perineum (adjusted odds ratio, 2.25; 95% confidence interval, 1.38–3.66) were independent risk factors. With high-grade vulvar dysplasia, the rate of positive margins was 50.2% (114/227) and that of occult microinvasive carcinoma was 17.2% (39/227). Notably, the primary and secondary outcomes were similar among gynecologic oncologists and gynecologists.
Wound complications following vulvar excision for nonmalignant lesions are common. Select groups may benefit from anticipatory counseling and future interventional studies to prevent complication. The incidence of positive surgical margins and occult minimally invasive carcinoma is also high, reflecting the challenging nature of treating vulvar disease.
BACKGROUND: There is a paucity of literature regarding the outcomes following vulvar excision for nonmalignant lesions. This is a common procedure among gynecologists and gynecologic oncologists, and ...a body of evidence is warranted to guide clinical care and future research. OBJECTIVE: This study aimed to estimate the rate of wound complications following simple vulvar excision and to identify the risk factors for these outcomes. Our secondary objectives were to determine the rates of (1) positive margins and (2) occult carcinoma in the cases of vulvar dysplasia. STUDY DESIGN: We conducted a single-institution, retrospective cohort study of the patients who underwent simple vulvar excision procedures for suspected premalignant or benign lesions between June 2016 and February 2020. Our primary outcome was the rate of composite wound complications, including wound separation or breakdown, infection, or hematoma. Our secondary outcomes were the incidence of (1) margins positive for residual dysplasia and (2) occult minimally invasive carcinoma. The Fisher exact tests and chi-squared tests were used to compare the categorical variables and logistic regression models and independent student t tests were used for continuous variables, as appropriate. Multivariate stepwise selection and multiple logistic regression was performed to evaluate the risk factors for complications and generate the odds ratios. RESULTS: Of the 338 patients included in the study, 143 (42.3%) experienced wound complication. Most of these complications were wound separation or breakdown (n=134, 39.6%), followed by infection (n=22, 6.5%), and hematoma (n=4, 1.2%). On multivariate analysis, the presence of high-grade vulvar dysplasia (adjusted odds ratio, 1.83; 95% confidence interval, 1.06–3.15), longer specimen diameter (adjusted odds ratio, 1.03; 95% confidence interval, 1.01–1.05), and lesion location on the perineum (adjusted odds ratio, 2.25; 95% confidence interval, 1.38–3.66) were independent risk factors. With high-grade vulvar dysplasia, the rate of positive margins was 50.2% (114/227) and that of occult microinvasive carcinoma was 17.2% (39/227). Notably, the primary and secondary outcomes were similar among gynecologic oncologists and gynecologists. CONCLUSION: Wound complications following vulvar excision for nonmalignant lesions are common. Select groups may benefit from anticipatory counseling and future interventional studies to prevent complication. The incidence of positive surgical margins and occult minimally invasive carcinoma is also high, reflecting the challenging nature of treating vulvar disease.
Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.
We enrolled patients ...with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort).
Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval CI, 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively.
MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).
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