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ObjectiveTo assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS).MethodsThe National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion.ResultsThere were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040-6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of

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. 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. 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. 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. [Display omitted] • Treatment of HPV-associated VIN2/3 with self-applied topical artesunate ointment is feasible, tolerable, and safe. • The most common adverse events associated with artesunate topical ointment are vulvovaginal pain, burning and pruritus. • We observed preliminary evidence of histologic regression and HPV clearance of VIN2/3 treated with artesunate ointment. [ABSTRACT FROM AUTHOR]

To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities. Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19–0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28–0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63–1.66) or negative (HR 0.92, 95% CI 0.70–1.21) nodal pathology. For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care. • The uptake of sentinel lymph node biopsy for early-stage vulvar cancer remains low, though is increasing over time. • Patients receiving care at minority-serving or low-volume hospitals were less likely to undergo sentinel lymph node biopsy. • Escalation of sentinel lymph node biopsy use was most evident in low-volume hospitals. • Sentinel lymph node biopsy was not associated with worse overall survival compared to full groin dissection. [ABSTRACT FROM AUTHOR]

The management of vulvar cancer with clinically negative groin lymph nodes but with positive sentinel lymph node biopsy (SLNB) is controversial, with options including inguinofemoral lymphadenectomy (IFL) and/or adjuvant chemotherapy and radiotherapy. We used the National Cancer Database (NCDB) to examine trends in the management of clinically node negative, pathologically node positive (cN-/pN+) patients. The NCDB was used to identify cN-/pN+ vulvar cancer patients. Demographic and clinical data were compared with chi-squared and Wilcoxon rank-sum tests. OS was analyzed with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine factors associated with OS. A total of 885 cN-/pN+ vulvar cancer patients were identified between 2012 and 2016, during which the rate of SLNB alone increased from 3.6% to 11.7%, while the rate of IFL +/− SLNB decreased from 89.7% to 78.1% (p < 0.05). Radiation was used in 68.5% and 64.6% of the SLNB-alone and IFL +/− SLNB cohorts, respectively, with chemoradiation in 37.1% and 33.6%, respectively. OS was not different between patients who received SLNB-alone vs. IFL +/− SLNB (p = 0.644). Receipt of chemotherapy and radiation was associated with improved OS (p < 0.001). Among cN-/pN+ vulvar cancer patients in the NCDB, the practice of performing IFL decreased over time as SLNB-alone became more common and the majority received radiation +/− chemotherapy. There was no difference in OS between SLNB-alone vs. IFL +/− SLNB. Patients treated with adjuvant chemoradiation had improved survival. Whether the favorable outcomes in the SLNB-alone cohort may be attributed to radiotherapy dose escalation or use of chemotherapy warrants further study. • From 2012 to 2016 the rate of SLNB alone increased, while the rate of IFL +/− SLNB decreased. • Overall, radiation was used in two thirds of patients, with chemoradiation in approximately one third. • OS was not different between patients who received SLNB-alone vs. IFL +/− SLNB. • Receipt of chemotherapy and radiation was associated with improved OS. [ABSTRACT FROM AUTHOR]

The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV– tumors. • Local recurrence occurred significantly more often in N+ pts without adjuvant radiotherapy to the vulva (HR 1.79; p=0.019). • The effect of RT on local recurrence was independent of the resection status. • 50% disease free survival time (DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV + pts. [ABSTRACT FROM AUTHOR]

To investigate the relation of pathologic tumor-free margins and local recurrence in patients who underwent primary surgery for vulvar squamous cell carcinoma. In this retrospective analysis, patients with stage I-III vulvar squamous cell carcinoma who underwent primary surgery between 2000 and 2018 were identified from the Mayo Clinic Cancer Registry. A total of 335 patients were included and divided into three groups according to tumor-free margins: group 1 (<3 mm, n = 32); group 2 (≥3 to <8 mm, n = 151); group 3 (≥8 mm, n = 152). The median follow-up time was 73 months (range 2–240). A total of 78 (23.3%) patients developed local recurrence. With the inverse propensity score weighing method adjusting baseline characters, margins <8 mm had inferior local control (HR 1.98, 95% CI 1.13–3.41). The 5-year local disease-free survival (DFS) was 48.2%, 81.5% and 84.6% for group 1, 2 and 3 respectively (p < 0.001). There were no differences in groin lymph nodes relapse (p = 0.850), distant metastases (p = 0.253), or disease-specific survival (DSS) (p = 0.289) among the three groups. Margins <8 mm, midline involvement, multifocal disease, precancerous lesions on margins and depth of invasion >1 mm were found to be poor prognosticators for local DFS in univariate analysis. Multifocal disease was the strongest predictor for local recurrence in multivariate analysis (HR 4.32, 95% CI 2.67–6.99). Patients undergoing primary surgery for vulvar squamous cell carcinoma with tumor free-margins <8 mm have a higher local recurrence rate. • Pathologic tumor-free margins <8 mm is associated with a higher local recurrence in vulvar cancer. • 5-year local DFS is 84.6% in patients with tumor-free margins ≥8 mm. • Local recurrence is related with midline involvement, VIN3, multifocal disease and stromal invasion >1 mm. • Multifocal disease is the strongest predictor for local recurrence. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the vulva is a rare female malignancy, with an incidence increasing with age. Unfortunately, one third of the patients are diagnosed with locally advanced disease, which constitutes a clinical challenge for the clinicians who treat these patients. The main challenges are represented by: 1. The primary site of the disease, which can be proximal to anatomical structures like the anal canal posteriorly, or the urethra and the bladder anteriorly, that in some circumstances cannot be spared without a bowel and/or urinary stoma; 2. The locoregional nodes that can be involved by the tumor, and they can be bulky, fixed or ulcerated; 3. The clinical condition of the patient, who may carry several comorbidities. Treatment modalities include radiation with or without chemotherapy, and surgery. In order to preserve the bowel and the urinary function without a permanent stoma, a personalized management with a multimodality approach is warranted. In this systematic review, we first clarify the different definitions of "locally advanced vulvar carcinoma". Secondly, we evaluated the different treatment modalities described in the literature, and the impact of the different treatment strategies on prognosis and on preservation of bowel/urinary function. Finally, we offer a possible algorithm that may help the clinicians in treating patients with these uncommon and challenging situations with a multidisciplinary approach. • Advanced vulvar carcinoma is based on the primary tumor (T3-T4), or on the presence of bulky, fixed or ulcerated nodes. • Preservation of the bowel and/or urinary function without permanent stomas may require multimodality approaches. • A personalized approach with RT with/without concurrent chemo and/or surgery may be justified to avoid permanent stomas. • A multidisciplinary approach is warranted for patients with locally advanced vulvar carcinoma. [ABSTRACT FROM AUTHOR]

Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities — benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva. • The incidence of vulvar cancer is increasing, but there is no screening strategy. • Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases • Many different diseases of the vulva are noticed by the women with similar symptoms. • New classification of clinical findings of the vulva to simplify decision making [ABSTRACT FROM AUTHOR]

All cervical cancers and some vulvar, vaginal and anal cancers are caused by high-risk human papillomavirus (hrHPV). However, little is known about the association between cervical HPV infection and subsequent intraepithelial neoplasia and cancer at other anogenital sites. In this prospective cohort study, we estimated the risk of vulvar, vaginal and anal intraepithelial neoplasia grade 2/3 or cancer (VIN2+, VaIN2+, AIN2+) according to cervical hrHPV status. Liquid-based cervical cytology samples were collected from 40,399 women screened against cervical cancer in Copenhagen, Denmark, during 2002–2005. Samples were tested for hrHPV using Hybrid Capture 2 (HC2) and genotyped using INNO-LiPA. We linked the cohort with Danish nationwide registries to identify cases of VIN2+, VaIN2+ and AIN2+ during up to 15 years of follow-up. We estimated age-adjusted hazard ratios (HRs) using Cox regression and cumulative incidences using Aalen-Johansen's estimator. Women with cervical HPV16 infection had increased hazard of VIN2+ (HR = 2.6; 95% confidence interval [CI], 1.2–5.5), VaIN2+ (HR = 23.5; 95% CI, 6.8–81.6) and AIN2+ (HR = 3.7; 95% CI, 1.1–12.2) compared with HC2 negative women. Women with other hrHPV types than HPV16 also had increased hazard of VaIN2+ (HR = 7.1; 95% CI, 2.3–22.3) and a borderline statistically significantly increased risk of AIN2+ (HR = 2.2; 95% CI, 0.9–4.9) compared with HC2 negative women. The 10-year cumulative incidences of VIN2+, VaIN2+ and AIN2+ in women with cervical HPV16 were 0.3% (95% CI, 0.2%–0.7%), 0.2% (95% CI, 0.1%–0.5%) and 0.1% (95 CI, 0.0%–0.4%). Cervical HPV16 infection is associated with increased risk of VIN2+, VaIN2+ and AIN2+. • This study investigated the association between cervical HPV infection and HPV-related disease at other anogenital sites. • Cervical HPV infection was associated with an increased rate of vulvar, vaginal and anal high-grade neoplasia and cancer. • This finding was especially pronounced for cervical HPV16 infection. • These findings underscore the important interplay between HPV infection and disease at various anogenital sites. [ABSTRACT FROM AUTHOR]

To evaluate the clinicopathological characteristics, management and prognosis of patients with vulvar extramammary Paget disease of the vulva (EMPD). The U.S National Cancer Database was accessed and patients diagnosed between 2004 and 2015 with microscopically confirmed vulvar EMPD were selected. Overall survival (OS) was calculated for patients diagnosed between 2004 and 2014, who had at least one month of follow-up. Five year OS rates were calculated following generation of Kaplan-Meier curves while comparisons were made with the log-rank test. A total of 2602 patients were identified. Median age at diagnosis was 72 years (range 31–90 years) and the majority were of White race (92%), without any co-morbidities (80.9%). Personal history of another tumor was present in 36.9% of patients. In situ EMPD was diagnosed in 994 cases (38.2%) and the majority (95.1%) were managed with local excision or vulvectomy. Five-year OS was 85.8%, while presence of positive margins was not associated with worse OS (p = 0.38). Invasive EMPD was diagnosed in 1608 (61.8%) patients. Staging information was available for 1172 patients, 75.3% had early stage disease. Most patients underwent surgical treatment (91.6%); 53.6% had positive margins. Performance of lymphadenectomy was infrequent (6.8%). Moreover, immunotherapy (4.5%), chemotherapy (1.5%) and radiation therapy (2.2%) were rarely employed in the management of invasive EMPD. Patients with early stage disease (n = 766) had better OS compared to those with advanced stage (n = 278) (5-yr OS rates were 84.3% and 73.6% respectively, p = 0.015) while presence of positive margins was not associated with worse OS (p = 0.35). Extramammary Paget disease is a rare vulvar tumor. Surgical excision is the main treatment option while other modalities are rarely employed. Overall survival rates are encouraging. • Approximately 95.% of patients with invasive vulvarl EMPD had excision. • Only 6.8% had lympadenectomy • Presence of positive margins was not associated with overall survival. [ABSTRACT FROM AUTHOR]

In vulvar cancer (VSCC), the course of disease with regard to localization of recurrence and relation of different recurrence sites is poorly described. The AGO CaRE-1 study is a retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Patients (pts) with primary VSCC, FIGO stage ≥1B treated in Germany from 1998 to 2008 were included in a centralized database (n = 1618). In the current subgroup analysis, different sites of primary recurrence and their impact on disease course and survival were analyzed using multistate and competing risks methods. 1249 pts with surgical groin staging and known lymph-node status (35.8% N+) were included in the analysis. 360 pts (28.8%) developed disease recurrence; thereof 193 (53.6%) at the vulva only, with a cumulative incidence of 12.6% after 2 years. Generally, prognosis after disease depended on recurrence site: Hazard ratios (HRs) (95% confidence interval) to die for pts with compared to without recurrence at the same time: vulvar only: 5.9 (4.3–8.2); groins only: 6.0 (3.0–10.2); vulvar and groins: 14.1 (7.6–26.4); pelvic/distant: 21.2 (15.3–29.4). Fifty-eight (30.1%) pts with local recurrence developed second recurrence. 2-year mortality after any recurrence was 56.3%. After vulvar recurrence pts had a 2-year and 5-year overall survival rate of 82.2% and 66.9%. Prognosis after recurrence is highly depending on recurrence site. Pts with isolated vulvar recurrence have an impaired prognosis as many affected pts develop second recurrences. • N+ pts have a higher risk for isolated vulvar recurrences than N-pts (2-y recurrence rate 19% vs. 13.5%, p = 0.001). • Nodal involvement and R1 resection were the most relevant prognostic factors for an increased risk of vulvar recurrence. • 58 (30.1%) of the pts with local recurrence developed second recurrence. 2-year mortality after any recurrence was 56.3%. • Pts with isolated local recurrence had a 2-and 5-year OS of 82.2% and 66.9%, respectively [ABSTRACT FROM AUTHOR]

Abstract Purpose Human papillomavirus (HPV) is implicated as a causative factor in vulvar squamous cell carcinoma (VSCC). This study evaluates if p16-positivity, a surrogate for HPV, predicts for better response rates to chemoradiation therapy and survival. Materials and methods We conducted a retrospective chart review of women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000 to 2016 for VSCC. p16 stain-positivity was defined as diffuse strong "block" immunoreactivity within invasive tumor. Results Seventy-three women with median follow-up of 13.4 months were analyzed. Thirty-three (45.2%) had p16+ tumors. Median age was 73 years (range: 37–89); with p16+ tumors, the median age was 60 years vs 73 years for women with p16− tumors (p < 0.001). The distribution of tumor size and stage by p16−status were similar. The complete clinical response (cCR) rate for p16+ tumors was 63.6% vs 35.0% for p16− tumors (p = 0.014). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 53.8% vs 31.4% for p16+ vs p16−, respectively (p = 0.067). The combined complete response (cCR orpCR [CCR]) rate was 63.6% for p16+ and 30.0% for p16− (p = 0.004). Two-year vulvar control (VC) for women with p16+ tumors was 75.5% vs. 49.5% for p16− (p = 0.008). In women with p16+ tumors who achieved CCR, 2-year VC was 92.3% vs 52.1% for CIR (p = 0.009). For p16− tumors, 2-year VC was 67.3% vs 41.1% for CCR and CIR (p = 0.072). No woman with a p16+ tumor developed distant metastases vs. 7 with p16− tumor (p = 0.013). OS was not statistically different between p16+ cohorts, but was improved for p16− patients with CR vs CIR, 72.9% vs 18.8% (p = 0.026). Conclusions p16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes. Highlights • The first study of its kind to evaluate the impact of p16 on intact vulvar cancers. • P16 expressing vulvar cancers have higher pathologic response rates. • P16 expressing vulvar cancers have improved local control. [ABSTRACT FROM AUTHOR]

Primary melanomas originating from the gynecological tract are rare and aggressive cancers. The vulva is the most frequent site (70%), followed by vagina and more rarely by cervix. The clinical outcome of patients with female genital tract melanoma is very poor, with a 5-year overall survival (OS) of 37–50% for vulvar, 13–32% for vaginal, and approximately 10% for cervical melanoma. In this systematic review, we analyzed the pathogenesis and the different factors influencing the prognosis of melanomas of the lower genital tract, with particular emphasis on biologic variables that may influence new therapeutic approaches. We evaluated the different treatment modalities described in the literature, in order to offer a possible algorithm that may help the clinicians in diagnosing and treating patients with these uncommon malignancies. [ABSTRACT FROM AUTHOR]

Objective We studied a large population of women with high-grade vulvar intraepithelial neoplasia (VIN) in order to identify patient and treatment-related risk factors for recurrence and progression to cancer. Methods For this retrospective cohort study of women with a histologic diagnosis of VIN within Southern California Permanente Medical Group between 1995 and 2007 medical records were reviewed; clinical, demographic and pathologic data were collected. Statistical analyses included Chi-squared and Student's t -tests, univariate and multivariate logistic regression, and cumulative incidence analysis. Results 914 patients with high-grade VIN were identified; 784 met inclusion criteria. We found 26.3% recurrences among treated women, with 2.2% progression to cancer (8.2% among those with recurrence). Risk factors for recurrence on multivariate analysis were: age > 50 years (OR, 1.44; 95%CI 1.01–2.07), immunosuppression (OR 2.08; 95%CI 1.42–3.06), metasynchronous VAIN or CIN (OR 1.76; 95%CI 1.08–2.88) in addition to margin status (OR 8.17; 95%CI 4.60–14.51) and adjacent LSA (OR 9.91; 95%CI 1.53–31.32) or HPV (OR 2.15; 95%CI 1.13–3.37) with excisional treatment. Recurrence rates did not differ significantly by smoking status and treatment modalities. Median time to recurrence was 16.9 months; 25% had late recurrences (44–196 months). Cumulative incidence analyses of time to recurrence shows a significantly higher risk among patients over age 50 (log-rank p = 0.0031). Conclusion We identified independent risk factors for recurrence including age > 50 years, immunosuppression, metasynchronous vaginal or intraepithelial neoplasia, positive excision margins, and adjacent lichen sclerosus or human papilloma-virus. Regardless of treatment modality, 25% of recurrences occurred late, highlighting the need for long-term surveillance in women treated for VIN. [ABSTRACT FROM AUTHOR]

Objectives: Vulvar cancer is a rare gynecologic malignancy. The majority of patients present with early-stage disease and undergo standard surgical treatment, which includes either a simple or radical vulvectomy. The main goal of surgical treatment was to obtain clear margins. This study aimed to investigate pathologic prognostic factors associated with overall survival among patients with stage IB squamous cell carcinoma (SCC) of the vulva. Methods: The National Cancer Database was accessed to identify patients diagnosed with stage IB squamous cell carcinoma of the vulva between 2010-2015. Patients who underwent surgical excision and lymphadenectomy and had at least one month of follow-up were included. Those with complete pathological data (tumor grade, tumor size, presence of lymph-vascular invasion [LVSI], and surgical margin status) were selected for further analysis. Overall survival was evaluated with Kaplan-Meier curves, and univariate analysis was performed with the log-rank test. A Cox model was constructed to control for a priori selected confounders. Results: A total of 2,656 patients with a median age of 63 years were identified. Most patients had tumors < 2 cm (n =1168, 44%), while 35% (n =930) and 21% (n =558) had tumors 2-3.9 cm and ≥4 cm, respectively. Rate of positive margins and LVSI were 7.7% (n =204) and 8.9% (n =237). Almost half of all patients (52%, n =1383) had grade 2 tumors, while 34.7% (n =921) and 13.3% (n =352) had grade 1 and grade 3 tumors, respectively. The 4-year OS rate of the present cohort was 80.9% with a median OS of 93.24 months. By univariate analysis, tumor size (p<0.001; 4-yr OS rates: 87.2% for <2 cm, 78% for 2-3.9 cm, and 72.9% for >4 cm), grade (p=0.006; 4-yr OS rates: 83.3% for grade 1, 80.3% for grade 2 and 77.1% for grade 3) and presence of LVSI (p<0.001; 4-year OS rate: 69.2% vs 82%) were associated with OS. After controlling for patient age, race, insurance status and presence of comorbid conditions, LVSI (HR: 1.61, 95% CI: 1.22-2.12), grade 3 (HR: 1.45, 95% CI: 1.09-1.94), and size >4 cm (HR: 1.91, 95% CI: 1.49-2.45) or 2-4 cm (HR: 1.64, 95% CI: 1.31-2.06) but not positive margins (HR: 1.20, 95% CI: 0.87-1.67) were associated with worse overall survival. In the present cohort, radiation therapy was rarely administered (7.8%, n =207). In a group of patients who had at least one risk factor (grade 3, LVSI or size >4 cm), those who received radiation therapy (n =123) did not have better survival compared to those who did not (n =848, p=0.21); 4-year OS rates were 74.1% and 75.1%, respectively. Conclusions: In a large cohort of patients with stage IB SCC of the vulva, surgical margins status was not associated with overall survival. However, large tumor size, presence of LVSI, and grade 3 tumors were identified as independent negative prognostic factors. Further research is greatly warranted to identify patients who may benefit from adjuvant treatment. [ABSTRACT FROM AUTHOR]

Objectives: Examine patterns of adjuvant radiation therapy delivery to patients with lymph node-positive vulvar squamous cell carcinoma and its impact on overall survival. Methods: Patients diagnosed between 2004 and 2015 with T1/M0 squamous cell carcinoma (SCC) of the vulva, who had no history of another tumor, underwent surgical resection and lymphadenectomy (LND), had positive lymph nodes (LNs) per pathology report, received adjuvant external beam radiation therapy of at least 45 Gy within six months from surgery and had at least one month of follow-up were identified. We examined three quality metrics as previously described in the literature: utilization of radio-sensitizing chemotherapy, receipt of adjuvant radiation therapy within eight weeks from surgery, and completion of treatment within eight weeks from radiotherapy initiation. Clinical-pathologic characteristics were compared with the Chi-square test. Overall survival was evaluated following the generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders. Results: A total of 1181 patients were identified. The median number of resected LNs was 10 (range: 1-51), while the median number of positive lymph nodes was 2 (range: 1-29). For 984 patients (83.3%), the total duration of adjuvant radiotherapy treatment was < 8 weeks, while 569 (48.2%) patients-initiated adjuvant radiotherapy within eight weeks from surgery and 537 (45.5%) received chemotherapy. All three-quality metrics were met for 238 patients (20.2%). These patients were younger (median age: 59 vs 67 years, p<0.001), more likely to have private insurance (52.1% vs 33.4%, p<0.001), be managed in academic facilities (45.7% vs 38.6%, p=0.053) and less likely to have comorbid conditions (22.7% vs 30.5%, p=0.017). There were no differences between the two groups in terms of patient race, margin status, income, tumor size, and performance of comprehensive LND (defined as at least ten lymph nodes removed). The Median follow-up of the present cohort was 64.2 months. Patients who met all three-quality metrics had better OS compared to those who did not (p<0.001); 5-year OS rates were 62.6% and 42.8%, respectively. Following stratification by the number of positive LNs, a survival benefit was observed for patients who met all three-quality metrics and had one positive LN (p<0.001; 5-year OS rates: 76.2% vs 53.5%), 2-3 positive LNs (p<0.001; 5-year OS rates 56.2% vs 38.3%) or ≥4 positive LNs (p<0.001; 5-year OS rates: 51.4% vs 21.6%). After controlling for patient age, race, insurance status, presence of comorbid conditions, tumor size, the performance of comprehensive LND, and the number of positive LNs meeting all three-quality metrics of adjuvant radiation therapy was associated with better OS (HR: 0.56, 95% CI: 0.44-0.72). Conclusions: Approximately one in five patients with lymph nodepositive SCC of the vulva met all quality metrics of adjuvant radiation therapy. These patients had superior outcomes regardless of lymph node disease burden. [ABSTRACT FROM AUTHOR]

Objectives: With the results of the recent GROINSS-V II study, completion of inguinal femoral lymphadenectomy (IFLND) prior to radiation (RT) is recommended for women with macro-metastatic involvement of inguinal lymph nodes (IFLN) due to increased groin failures with RT alone. However, it is unknown if the increased failure rate could be overcome with the use of radiosensitizing chemotherapy (Chemo/RT). Therefore, the primary objective of this study was to evaluate the effect of selective, complete, or sentinel lymphadenec- tomy alone on overall survival among women with macro-metastatic (>2 mm) squamous cell carcinoma (SCC) of the vulva that underwent treatment with primary surgery and Chemo/RT. Secondary objectives included evaluating the effect of the surgical approach on 30-day readmission rates. Methods: Women with FIGO Stage III, macro-metastatic (>2mm), SCC of the vulva treated with surgery followed by Chemo/RT were identified in the National Cancer Database from 2012-2017. Patients were categorized into one of three cohorts based on surgical exposure: ') Sentinel lymphadenectomy (SLND) only, 2) complete IFLND +/- SLND, or 3) selective lymph node debulking. Women who did not have lymph node assessment during the initial surgery, had >90 days between surgery and start of Chemo/RT or had neoadjuvant Chemo/ RT were excluded from the analysis. Overall survival was examined using Kaplan-Meier curves, log-rank tests, and adjusted Cox proportional hazard models. Demographic variables and re-admission rates were evaluated using Chi-square and Fisher's exact tests. Results: A total of 994 individuals were identified; 847 (85%) had a complete IFLND +/- SLND, 80 (8%) had SLND only, and 67 (7%) had selective lymph node debulking. The cohorts did not differ in age, race, ethnicity, insurance status, or Charleson-Deyo comorbidity score (all p>0.05). Overall survival did not differ among the three cohorts (Figure 1). At five years, 50% of the complete IFLND +/- SLND cohort, 58% of the SLND only cohort, and 58% of the selective lymph node debulking cohort were alive (p=0.22). After adjusting for demographic and tumor factors, including age, race, ethnicity, insurance, Charleson-Deyo comorbidity score, tumor grade, and lymphovascular space invasion [ELB1], there was no difference in the risk of death when comparing SLND only (aHR: 0.72; 95% CI: 0.46-1.13) or selective lymph node debulking (aHR: 0.98; 95% CI: 0.61-1.58) to complete IFLND +/- SLND. However, complete IFLND +/- SLND was associated with a non-significant, higher rate of 30-day readmissions with 3.7% compared to 2.5% and 1.5% for SLND only and selective lymph node debulking, respectively (p=0.70). [Display omitted] Conclusions: For women with macro-metastatic SCC of the vulva, there was no difference in overall survival for selective, complete, or sentinel lymphadenectomy when patients were treated with adjuvant Chemo/RT. However, there was a non-significant trend of higher 30-day re-admission rates for patients undergoing complete IFLND +/- SLND. Further randomized trials are needed to validate the safety of forgoing complete IFLND in patients with macro-metastatic SCC of the vulva, who undergo either SLND or selective IFLND debulking followed by adjuvant Chemo/RT. [ABSTRACT FROM AUTHOR]

Objectives: There are limited data to guide the counseling and management of patients with stage IVB vulvar squamous cell carcinoma (SCC). We aimed to examine patterns of care and survival outcomes using a large hospital-based database. Methods: The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with a pathologically confirmed stage IVB squamous cell carcinoma of the vulva who had at least one month of follow-up and no history of another tumor were identified. Median overall survival (OS) was evaluated with Kaplan-Meier curves, and univariate analysis was performed with the log-rank test. Results: A total of 710 patients with a median age of 65 years were identified. Of them, 338 (47.6%) had metastases to distant lymph nodes only (IVB-LN), while 310 (43.7%) had metastases to other distant sites (IVB-other), and 62 had stage IVB not specified. The majority received radiation therapy (70.1%), chemotherapy (60.6%), and did not undergo surgical excision at the primary site (70.1%). In the present cohort, immunotherapy was rarely administered (n <10, 1%). Patients with IVB-LN had a better prognosis compared to patients with IVB-other (median OS: 13.4 vs 6.01 months, respectively, p<0.001). For patients with IVB-LN, the longest survival was observed for those who had chemoradiation (n =213, median OS: 17.84 months) or chemotherapy alone (n =25, median OS: 19.84 months) compared to those who had radiation therapy alone (n =56, median OS: 7.39 months) or supportive care (n =44, median OS: 7.79 months) (p<0.001). Similarly, for patients with IVB-other, the longest survival was observed for those who had chemoradiation (n =126, median OS: 8.6 months) or chemotherapy alone (n =32, median OS: 7.43 months) compared to radiation therapy alone (n =65, median OS: 5.49 months) or supportive care (n =87, median OS: 3.19 months, p<0.001). For patients who received chemotherapy alone, there was no difference in OS between single agent (n =12) and multi-agent regimen (n =47) (median OS: 7.98 vs 10.94 months, p=0.73). Similarly, for patients who received chemoradiation, there was no difference in OS between single agent (n =218) and multi-agent (n =122) chemotherapy (median OS: 13.4 vs 16.2 months, p=0.30). Conclusions: Stage IVB vulvar carcinoma has a dismal prognosis. Patients with distant LN involvement alone have a better prognosis compared to those with metastases to other distant sites, especially when multi-modal treatment is employed. Immunotherapy was rarely utilized during the study time frame. The efficacy of multiagent chemotherapy, even when combined with radiation therapy, is limited, and novel treatment options are urgently needed. [ABSTRACT FROM AUTHOR]

Objective Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. Methods A large retrospective cohort of patients with MOGS ( n = 59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF , KIT , NRAS , and CTNNB1 . Results Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. Conclusions Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS. [ABSTRACT FROM AUTHOR]

Aim There is limited knowledge in the field of glandular vulvar malignancies. The aim of this study is to describe the incidence and survival of women with glandular vulvar malignancies. Methods We searched PALGA, a nation-wide database registering all histo- and cytopathology in the Netherlands, for all cases of glandular vulvar malignancies between 2000 and 2015. Additional data were retrieved via the Netherlands Cancer Registry. Incidence rates were calculated per 1,000,000 women per year. Five-year net survival rates were calculated. Results We identified 197 patients with a glandular vulvar malignancy. Of these patients 55% had a primary malignancy while 45% had secondary malignancies: expansion of another tumour in 17% and metastases or recurrences of another malignancy in 28%. There is a great variety of different diagnoses of primary vulvar malignancies: 11 different types were identified. We found an overall incidence rate of glandular vulvar malignancies of 0.9–2.5 per 1,000,000 women per year. Five-year net survival for patients with a primary malignancy was 68.5%. Most of the secondary vulvar malignancies originated from (ano-)rectal malignancies. Conclusion Glandular vulvar malignancies are extremely rare and primary tumours are slightly more common. Overall survival of patients with primary glandular vulvar malignancies is comparable to patients with a vulvar squamous cell carcinoma, with five-year survival around 70%. The great variety in diagnoses combined with the low incidence should lead to routine pathologic revision and treatment in specialised gynaecologic oncology centres. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to evaluate the efficacy of fat grafting in the treatment of severe vulvar lichen sclerosus (LS). Our primary outcome was to assess the improvement of mucocutaneous trophism, the resolution/reduction of symptoms, and the histological features of the vulvar skin after treatment. The secondary outcome was to evaluate the improvement in life quality, and in resumption and quality of sexual life. Methods Between 2011 and 2014, 36 patients were offered fat grafting to treat LS. Inclusion criteria were age between 25 and 80 years, histopathologic diagnosis of LS, good health, failure of previous first line treatments. Results 34 out of 36 patients (94%) showed a better vulvar trophism of the skin and mucosae; 27 (75%) had an improvement in caliber and elasticity of the vaginal introitus; clitoris burying degree was reduced in 18 patients (50%), 30 (83%) reported an increased volume of labia majora and minora, 34 (94%) had a complete disappearance of scratching lesions, and 28 (78%) showed a remission of white lesions. Eventually 34 patients (95%) stopped using topical corticosteroids routinely. The improvement in life quality was significant for both DLQI (p < 0001) and FSFI (p < 0001). Conclusions Fat grafting may have a role as a support and completion treatment in selected cases of women with vulvar LS who do not respond to first line therapy or in severe cases where the anatomical impairment does not allow a regular sexual function and a good quality of life. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2–3 and VAIN 1–3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients. [ABSTRACT FROM AUTHOR]

Objective Vulvar and vaginal reconstruction can be challenging for the reconstructive surgeon. The reconstructive goal is to provide wound healing, adequate function, and acceptable appearance. In the present study, we introduce a new design called the "angel wing" flap, which is a modification of a transposition flap and is based on the perforator concept for vulvar and vaginal reconstruction. Methods From January 2002 to December 2013, 23 women underwent reconstruction of vulvar and vaginal defects. Causative factors were vulvar cancer in 14 patients, extramammary Paget's disease in 2, vulvar dysplasia in 5, and combined vulvar and vaginal cancer in 2 patients. Results A total of 41 flaps were applied. All patients underwent surgical reconstruction in a single step using the "angel wing" flap. Flap size ranged from 4 x 7 to 13 x 6 cm² and the operative duration for reconstructive surgery ranged from 30 to 100 min. All the flaps survived with good coverage of the defect. Mean follow-up time after the procedure was 16.1 months (range, 6-30 months). Conclusion In this article, we introduce a simple and easy reconstructive procedure of the "angel wing" flap. For restoring function, as well as for esthetic purposes, the flap was designed in accordance with the defect since the natural contour of the vulva and vagina is three-dimensional. [ABSTRACT FROM AUTHOR]

Vulvar cancer is a relatively rare gynecologic malignancy with an annual incidence in developed countries of approximately 2 per 100,000 women. Vulvar squamous cell carcinoma (VSCC) has two etiological pathways: a high risk human papillomavirus (HPV)-dependent route, which has usual vulvar intraepithelial neoplasia (uVIN) as a precursor lesion, and an HPV-independent route, which is associated with differentiated VIN (dVIN), lichen sclerosus, and genetic alterations, such as TP53 mutations. Research on the molecular etiology of vulvar cancer has increased in the past years, not only regarding genetic alterations, but also epigenetic changes. In genetic alterations, a mutation irreversibly changes the nucleotide sequence of the DNA, or the number of copies of chromosomes per cell is altered. In epigenetics, the nucleotide sequence remains the same but genes can be 'switched' on or off by, for example, DNA methylation or histone modification. We searched the current literature on genetic and epigenetic alterations in VSCC and its precursor lesions. Many studies have reported a higher incidence of somatic mutations in HPV-negative tumors compared to HPV-positive tumors, with TP53 mutations being the most frequent. Allelic imbalances or loss of heterozygosity are more frequently found in higher stages of dysplasia and in invasive carcinomas, but it is not exclusive to HPV-negative tumors. A limited number of studies are available on epigenetic changes in vulvar lesions, with hypermethylation of CDKN2A being the most frequently investigated change. For most genes, hypermethylation occurs more frequently in vulvar squamous cell carcinomas than in precursor lesions. As most studies have focused on HPV infection and TP53 mutations, we suggest that more research should be performed using whole genome or next generation sequencing to determine the true landscape of genetic and epigenetic alterations in vulvar squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

To describe outcomes following wide local excision (WLE) of the vulva for suspected premalignant or benign disease at a tertiary care center over the years 2016 to 2020. To determine differences in the rates of wound complications and positive margins between patients treated by gynecologic oncologists (GO) and those treated by general gynecologic (GYN) surgeons. Consecutive patients were identified who underwent wide local excision of the vulva for suspected premalignant or benign lesions between June 1, 2016 and February 28, 2020. Institutional Review Board (IRB) approval was obtained and surgical records were reviewed; patients undergoing "wide local excision, vulva," "simple partial vulvectomy," or "destruction of vulvar lesion with excision" were considered for inclusion. Demographic, peri- and postoperative, and pathologic data were collected, and patients were separated by surgeon division (GO or GYN). Patients had follow up documented at least through the postoperative appointment. Surface areas of elliptical specimen were calculated using '0.25 x length x width x pi.' Wound complications and other variables were compared between these groups. All eligible patients were included in the analysis of wound complications. Only patients with pathologic diagnoses of vulvar dysplasia were included in the analysis of margin positivity. Fisher's exact tests and Chi squared tests were used to compare categorical variables and logistic regression models were used for continuous variables. P-values <0.05 were considered statistically significant. JMP 15.2.0 software was used to perform statistical analysis. Three-hundred thirty-five patients met inclusion criteria over the study period (GO, n=223; GYN, n=112). Patients in the GO group were older (median age 56y versus 40.5y, P<0.01) and more likely to be White (93% versus 75%, P<0.01). Patients in the GO group were more likely to have cardiovascular disease (RR 1.33, 95% CI 1.14-1.55), ASA class 3 or 4 (RR 1.80, 95% CI 1.34-2.43), and have history of malignancy (RR 1.33, 95% CI 1.14-1.54). The distributions of specimen length, surface area, and number of excisions per surgery were not significantly different between the groups. Wound complication occurred in 101/223 (45%) GO patients compared to 40/112 (36%) GYN patients (P=0.11). There were no significant differences specific to wound separation (43% vs 34%, P=0.12), infection (7% vs 5%, P>0.5), or hematoma (1% vs 2%, P>0.5). More patients in the GO group had pathology of high-grade vulvar dysplasia (HSIL) with or without occult carcinoma at the time of WLE (77% vs 40%, P<0.01). Of patients with HSIL, 65/171 (38%) in the GO group had dysplasia present at the margins compared to 23/45 (51%) in the GYN group (RR 0.74, 95% CI 0.53-1.05). There is renewed interest in optimal management of vulvar surgery.[1] WLE is a common procedure done by GO and GYN surgeons. In our study there was a high overall rate (42%) of postoperative wound complication; however, there were no significant differences in complication rates between GO and GYN surgeons. The rate of positive margins following WLE for vulvar dysplasia was also similar between these groups. The trend towards more frequent complications among GO patients may be explained by a population with older age and more comorbidities. It is appropriate for GO or GYN surgeons to perform WLE of the vulva for HSIL, provided the necessary expertise, comfort, and low concern for invasive disease requiring radical excision or lymph node dissection. [ABSTRACT FROM AUTHOR]

Objectives: Sentinel lymph node (SLN) mapping is feasible for squamous cell carcinoma (SCC) of the vulva, but there is little data on the uptake and survival outcomes for these patients. We aimed to examine the trends in use and survival outcomes of SLN mapping compared to lymph node dissection (LND) for SCC of the vulva. Methods: Patients with SCC of the vulva who underwent surgical resection from 2004 to 2018 in the Surveillance, Epidemiology and End Results Program (SEER) database were included. Patients with metastatic disease or a history of neoadjuvant radiation were excluded from the cohort. Performance of lymph node evaluation was classified as SLN mapping, LND, or no nodal evaluation. The overall cohort was stratified based on TIA (tumor size < 2 cm) and TIB (tumor size > 2 cm) tumors. Kaplan-Meier curves for overall survival as well as multinominal logistic regression models for predictors of type of lymph node evaluation were created. Inverse probability treatment weighting (IPTW) was used to compare overall survival between the groups. Results: Among 6,798 patients, SLN mapping was performed in 736 (10.8%), LND in 3,541 (52.1%) and no lymphatic dissection in 2,521 (37.1%). SLN mapping increased from 7.7% in 2003 to 21.1% in 2018 (a 2.7-fold increase), while the rate of LND decreased from 58.2% in 2003 to 43.1% in 2018 (a 1.26-fold decrease). No nodal dissection remained steady at 34.1% in 2003 and 35.8% in 2018 (p<0.001). In a multinomial logistic regression model, Black race, lower T stage, and chemotherapy were associated with SLN mapping (p<0.05 for all). For patients who were TIA, there was no association between type of nodal evaluation and survival (p=0.97). However, in those who were TIB, there was improved overall survival in the SLN mapping as compared to LND (HR: 0.66, 95% CI: 0.54-0.80) (p=0.002) (Figure 1). Conclusions: The performance of SLN mapping is increasing rapidly for women with vulvar SCC. While our data suggest there may be an overall survival advantage of SLN mapping in our overall cohort and TIB patients, further studies are needed to verify this outcome and clarify which patients would benefit most from SLN mapping. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utilization and outcomes of adjuvant radiation therapy for early-stage squamous cell carcinoma of the vulva with single inguinal lymph node metastasis following comprehensive inguinal lymphadenectomy. Methods: The National Cancer Database and patients without a history of another tumor, diagnosed between 2004 and 2015 with T1b squamous cell carcinoma of the vulva who underwent surgical excision and inguinal lymphadenectomy with at least ten lymph nodes removed and had only one positive lymph node per pathology report were identified. Clinical-pathologic and demographic characteristics were compared based on the receipt of adjuvant radiotherapy (defined as receipt of external beam radiation at a dose of at least 50 Gy within six months from surgery). Overall survival (OS) was calculated and compared with the log-rank test following the generation of Kaplan-Meier curves. A Cox model was constructed to control for a priori selected confounders. Results: A total of 250 patients who met the inclusion criteria were identified; 77 (30.8%) received adjuvant radiation therapy at a median of 57 days from surgery (IQR: 22) with a median dose of 50.4 Gy and a median treatment duration of 44 days (IQR: 12), while 32 (41.6%) of them received radio-sensitizing chemotherapy. Patients who received adjuvant radiation were more likely to have tumors ≥4 cm (46.8% vs 29.5%, p=0.046). Patient age, race, insurance status, presence of comorbid conditions, type of treatment facility, tumor grade, and surgical margin status were comparable between the two groups. By univariate analysis, patients who received adjuvant chemoradiation or radiation therapy alone did not have better OS compared to patients who did not receive any treatment (p=0.45); 5-year OS rates were 61.1% compared to 53.4% and 56.5%, respectively. After controlling for patient age, presence of comorbid conditions, insurance status, and tumor size, administration of adjuvant chemoradiation (HR: 0.74, 95% CI: 0.45-1.23) or radiation therapy alone (HR: 0.87, 95% CI: 0.43-1.76) were not associated with a survival benefit. Conclusions: Administration of adjuvant radiation therapy following comprehensive inguinal lymphadenectomy may not be associated with a survival benefit for patients with early-stage SCC of the vulva and single lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background Two etiologic pathways of vulvar cancer are known, a human papillomavirus (HPV)- and a TP53-associated route, respectively, but other genetic changes may also play a role. Studies on somatic mutations in vulvar cancer other than TP53 are limited in number and size. In this study, we investigated the prevalence of genetic mutations in 107 vulvar squamous cell carcinomas (VSCCs). Methods A total of 107 paraffin-embedded tissue samples of primarily surgically treated VSCCs were tested for HPV infection and screened for mutations in 14 genes (BRAF, CDKN2A(p16), CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53) using Sanger sequencing and mass spectrometry. Results Mutations were detected in 7 genes. Of 107 VSCCs, 66 tumors (62%) contained at least one mutation (TP53 = 58, CDKN2A(p16) = 14, HRAS = 10, PIK3CA = 7, PPP2R1A = 3, KRAS = 1, PTEN = 1). Mutations occurred most frequently in HPV-negative samples. Five-year survival was significantly worse for patients with a mutation (47% vs 59%, P = .035), with a large effect from patients carrying HRAS-mutations. Conclusion Somatic mutations were detected in 62% of VSCCs. As expected, HPV infection and TP53-mutations play a key role in the development of VSCC, but CDKN2A(p16), HRAS, and PIK3CA-mutations were also frequently seen in HPV-negative patients. Patients with somatic mutations, especially HRAS-mutations, have a significantly worse prognosis than patients lacking these changes, which could be of importance for the development of targeted therapy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Vulvar reconstruction using the “lotus petal” fascio-cutaneous flap offers a relatively novel means to restore symmetry and functionality after extirpative gynecologic or oncologic procedures. We sought to assess the success rates and morbidity in a large series of consecutively treated patients. Methods: We performed a retrospective review of 59 consecutive cases of lotus petal flaps performed at a single institution to more accurately assess success and complication rates. Results: We identified 80 flaps performed among the 59 patients between September 1, 2008 and March 30, 2013. The median (range) age was 59years (24–89) and the median (range) BMI was 27kg/m2 (19–34). The indications for vulvar/perineal excision were as follows: 39 (66.1%) vulvar carcinoma or melanoma, 12 (20.3%) vulvar dysplasia, 5 (8.5%) colorectal disease and 3 (5.1%) cases of hidradenitis suppurativa. The mean defect area, determined by post-fixation pathology specimen was 29cm2. Medical or surgical complications occurred in 36% of patients of which superficial wound separation was the most common (15%). There were no cases of complete flap loss, but partial loss occurred in 7 (8.8%) cases. 3 (5.1%) patients required re-operation prior to discharge with one case requiring skin grafting. Delayed surgical revision was required in 4 patients for partial flap loss (2) or stricture/stenosis (2). Conclusion: The lotus petal flap is safe for use in gynecologic reconstruction, with acceptable short- and long-term complication rates. Previous reports of smaller series likely underestimate the risk of complications through case selection. [Copyright &y& Elsevier]