Clinicopathological Prognostic Factors Influencing Survival Outcomes of Vulvar Cancer

Backgroud: Squamous cell carcinoma (SCCA) is the most common vulva cancer. This study purpose to evaluate the clinicopathological prognostic factors for survival outcomes of this disease after treated with surgery. Methods: All SCCA vulva cancer patients who underwent surgery between January 2006 and December 2017 were reviewed. The clinicopathological factors were analyzed to identify the prognostic factors for the progression-free survival (PFS) and overall survival (OS) using the Kaplan- Meier method and Cox-Proportional Hazard model.Results: One hundred twenty-five patients were recruited with a median age of 57 years. The recurrence rate was 35.2%. Patients with recurrence revealed a significant poorer five-year OS rate than those who did not recur (23.7% vs. 79.4%, P < 0.001). About 58.1% of palpable groin nodes revealed metastasis. The independent poor prognostic factors for PFS were groin node-positive and a tumor diameter more than 25 mm. whereas postmenopausal status, preoperative tumor area more than 11 cm2, and groin node enlargement were independent poor prognostic factors for OS. Conclusion: Groin node-positive and tumor diameter longer than 25 mm. were independent poor prognostic factors for PFS whereas postmenopausal status, large tumor area than 11 cm2, and enlargement of groin nodes were independent poor prognostic factors for OS. Patients with these factors should be closely followed.

18F-FDG PET/CT imaging of vulva cancer recurrence: A comparison of PET-derived metabolic parameters between women with and without HIV infection

Objective To assess the patterns of recurrence of vulva cancer on 18F-FDG PET/CT and to compare the 18F-FDG PET metabolic metrics in patients with and without Human Immunodeficiency Virus (HIV). Methods Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV and total lesion glycolysis (TLG) were obtained on Flourine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) images of women referred with suspected or confirmed vulva cancer recurrence. We compared HIV-infected and HIV-uninfected patients regarding pattern disease recurrence, age at diagnosis, and the PET-derived metabolic indices. Results We analyzed 33 patients with a mean age 50.76 ± 15.78 including 21 HIV-infected women. The majority of patients (94 %) had squamous cell carcinoma and 84.85 % were Blacks. Of the HIV-infected individuals, the median CD4 count was 526.0 cells/mm3 (IQR: 379.0–729.0). HIV infected patients were younger than the HIV uninfected at the time of diagnosis: 40.50 ± 8.87 vs 66.54 ± 9.71 respectively, p < 0.001. We found a local (vulvar) recurrence rate of 75.8 %. Nodal pelvic recurrences were higher in the HIV-infected patients than in the HIV uninfected patients (70 % vs 30 %, p = 0.027). Three patients had distant metastasis and all three were HIV-infected. There was a higher whole-body MTV and TLG among HIV-infected women compared with HIV-uninfected women, 103.39 vs 17.58 and 852.64 vs 101.79, respectively (p < 0.05 for both). Conclusion HIV-infected women are diagnosed with vulva cancer at a younger age. HIV-infected patients had a higher rate of pelvic lymph node recurrence. There is a higher tumor burden at vulva cancer recurrence among women with HIV infection.

A Phase 2 Study of Combined Chemo-Immunotherapy with Cisplatin-Pembrolizumab and Radiation for Unresectable Vulvar Squamous Cell Carcinoma

Purpose: Unresectable or metastatic vulva cancer has relatively poor outcomes despite chemotherapy-sensitized radiation therapy and combination cytotoxic therapy. Despite the virus-associated and immunogenic nature of this disease, novel immunotherapy options that exploit this advantage are currently lacking. Platinum agents such as cisplatin have been shown to prime dendritic cells for T-cell costimulation, promote downregulation of inhibitory checkpoint molecules, and sensitize tumor cells to cytotoxic T-cell killing. Radiation therapy has also been shown to promote immunogenetic cell death as monotherapy and in combination with cisplatin. In combination with pembrolizumab, cisplatin-sensitized radiation is hypothesized to increase overall response rates and recurrence-free survival in patients with vulva cancer, via induction of an anti-tumor inflammatory response.Methods: We propose a single-arm phase II clinical trial of pembrolizumab combined with cisplatin-sensitized radiation therapy for women with unresectable, locally advanced, or metastatic vulva cancer. The first three patients with locally advanced or unresectable disease will receive cycle 1 of pembrolizumab followed by a break and resumption of pembrolizumab at cycle 4 and as part of a safety cohort. All other patients, including the fourth patient with locally advanced/unresectable disease, will receive weekly cisplatin and pembrolizumab every 3 weeks, concurrently with daily radiation therapy. Following the completion of Cis-RT, patients will continue pembrolizumab maintenance for a total of 12 cycles. Archived tissue will be used for HPV status, MSI status, PD-L1, and TIL stratification post-hoc. Imaging will be performed at baseline and every 3 cycles (21-day cycles) as per standard-of-care. Laboratory analysis will occur on the first day of each cycle. Discussion: The combination of cisplatin-sensitized radiation and immune checkpoint blockade has not been evaluated in the upfront setting for vulvar cancer. In this rare malignancy, there are limited interventional clinical trials. This trial is designed to be as accessible as possible by allowing patients to receive cisplatin and radiation locally according to accepted standard-of-care while receiving pembrolizumab and adverse event monitoring at a centralized site. A robust suite of translational correlative studies has also been built into the trial to evaluate tumor-directed immune activation. Trial registration: NCT04430699

SQUAMOUS CELL PRECANCEROUS LESIONS OF THE VULVA: CURRENT PROBLEMS OF CLASSIFICATION AND DIAGNOSIS

This article systematizes and analyzes objective difficulties in the diagnosis of precancerous and primary vulva cancer, such as: constant changes in classification and long-term coordination, long-term systematization of clinical manifestations. It also reflects the current data and achievements of virology and molecular biology, which again led to a change in the classification and approaches to the diagnosis and management tactics of patients with squamous cell lesions of the vulva. New predictor markers, currently available for use in conventional routine morphological practice, gave new data on the development of pre-tumor and tumor process of the external genitals. Also in this article, the new clinical classification of vulva diseases is analyzed in detail, a comparison of standard and new diagnostic methods is carried out, which in clinical practice helps to correctly diagnose, determine the extent of the lesion and, depending on the molecular factors of the prognosis, choose an individual modern treatment tactics.

Search of Ways to Improve the Efficiency of the Diagnostic Results and the Quality of Treatment of Dystrophy and Vulva Cancer

With vulvar dysplasia, sclerotic deprive and suspected cancer under our observation there were respectively 115 and 97 patients. The effectiveness of treatment of vulva dystrophy (VIN II-III degree) by the method of photodynamic therapy (PDT) 45.8=4.7%. However, dysplasia II - III degree, sclerotic changes with the formation of pronounced horn scales prevents the full PDF and recurrence of the disease. Therefore, the treatment of choice is surgical treatment with a reconstructive plastic. In order to reduce bleeding and antiblastic we used krioapplikatsiya, apparate "Harmonics", and the decay of tumor angiographic chemoembolization before surgery. The use of new reconstructive plastic surgery, including with the use of abdominal skin and fascial flap combined with vascularized lower segments of the rectus muscles (patent for invention No 2580665 from 11.11.14), have helped to reduce complications, improve cosmetic effect and reduce the duration of lymphorrhea in 2-3 days.

Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics

A pumpless, reconfigurable, multi-organ–on–a–chip system containing recirculating serum-free medium can be used to predict preclinical on-target efficacy, metabolic conversion, and measurement of off-target toxicity of drugs using functional biological microelectromechanical systems. In the first configuration of the system, primary human hepatocytes were cultured with two cancer-derived human bone marrow cell lines for antileukemia drug analysis in which diclofenac and imatinib demonstrated a cytostatic effect on bone marrow cancer proliferation. Liver viability was not affected by imatinib; however, diclofenac reduced liver viability by 30%. The second configuration housed a multidrug-resistant vulva cancer line, a non–multidrug-resistant breast cancer line, primary hepatocytes, and induced pluripotent stem cell–derived cardiomyocytes. Tamoxifen reduced viability of the breast cancer cells only after metabolite generation but did not affect the vulva cancer cells except when coadministered with verapamil, a permeability glycoprotein inhibitor. Both tamoxifen alone and coadministration with verapamil produced off-target cardiac effects as indicated by a reduction of contractile force, beat frequency, and conduction velocity but did not affect viability. These systems demonstrate the utility of a human cell–based in vitro culture system to evaluate both on-target efficacy and off-target toxicity for parent drugs and their metabolites; these systems can augment and reduce the use of animals and increase the efficiency of drug evaluations in preclinical studies.