KRAS mutations in endometrial cancers: Possible prognostic and treatment implications.

BACKGROUND/OBJECTIVES: Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options. METHODS: A molecular database of 7870 ECs was queried for presence of oncogenic mutations and immunotherapy biomarkers. Comparisons were performed using Fisher-Exact/ChiSquare (p-values) and adjusted for multiple tests by Benjamini-Hochberg (q) and pairwise nonparametric analysis using Wilcoxon Method. RESULTS: KRAS-mut is a relatively frequent genotype in EC, detected in 16% of cases. Codon 12 was most frequently mutated, with G12D (31%) and G12V (27%) the most common subtypes. Biomarkers of immunotherapy response co-occur with KRAS-mut. Microsatellite instability-high and tumor mutational burden-high status were observed in 34.1% and 36.5% in KRAS-mut compared to 19.8% and 16.9% in KRAS-WT, respectively (p < 0.05). PD-L1 >1% was detected in 8.4% vs 6.4% of KRAS-mut vs KRAS-WT (p < 0.05). BRCA1/2 mutations were detected with similar low frequency (5.9% vs 4.9%) among KRAS-mut and KRAS-WT ECs (p > 0.05). KRAS-mut was inversely associated with Her-2 overexpression (1.8% KRAS-mut vs 13% KRAS-WT. (p < 0.001). CONCLUSIONS: KRAS-mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed.

Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.

BACKGROUND: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. METHODS: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. RESULTS: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. CONCLUSIONS: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.

Standardized Titration Protocol Reduces the Incidence of Paclitaxel Infusion-Related Hypersensitivity Reactions.

PURPOSE: Infusion-related hypersensitivity reactions with paclitaxel are common despite the use of dexamethasone and diphenhydramine premedications. Paclitaxel titration protocols that may reduce reactions are empirically derived from clinical observations, and there are no phase III trials that confirm superiority of any management recommendations. The purpose of this study was to compare the frequency and severity of hypersensitivity reactions associated with a recently initiated standardized paclitaxel titration protocol verses standard-of-care (SOC) infusion protocols. MATERIALS AND METHODS: This was a retrospective review of hypersensitivity reactions in patients receiving paclitaxel infusions at five ambulatory infusion centers using a standardized titration protocol (February 2021 to April 2021) versus SOC paclitaxel (November 2018 to December 2019). Patients were age 18 years or older and presented for their first or second infusions. The primary study measure was the rate of hypersensitivity reactions. Secondary evaluations included the timing of the reaction after the start of the infusion, use of premedications, and severity of reactions. RESULTS: A total of 451 patients were included in this study. Eighty-four (18.6%) patients were identified in the titration protocol group and 367 (81.4%) patients in the SOC group. Hypersensitivity reactions occurred in 4.8% of the titration group and 18.3% of the SOC group (odds ratio [OR], 0.224; 95% CI, 0.09 to 0.74; P = .002). Grade 3 or greater infusion reactions were 0% in the titration group versus 18% in the SOC group (OR, 0.28; P < .008). Reactions occurred later with the titration protocol, compared with the SOC paclitaxel infusion. Finally, no differences were observed in the use of appropriate premedications. CONCLUSION: A standardized paclitaxel titration protocol was associated with a significant reduction in the rate of infusion-related hypersensitivity reactions in patients receiving their first and second infusions. A prospective randomized trial is needed to validate these observations.

Multidisciplinary approach to pelvic leiomyomatosis with intracaval and intracardiac extension: A case report and review of the literature.

Intravenous leiomyomatosis (IVL) is an uncommon variant of leiomyoma characterized by intravascular proliferation of a histologically benign smooth muscle tumor extending beyond the uterus into the distant great vessels. Leiomyomatosis may reach the inferior vena cava, right atrium, and pulmonary arteries. Owing to its rare occurrence, intracardiac leiomyomatosis has been reported as isolated case reports and small case series. Early diagnosis and prompt surgical intervention are vital to prevent cardiac symptoms, pulmonary embolism, and sudden death. Complete tumor resection is essential for a favorable outcome, usually assisted with multimodal surgical imaging and multidisciplinary surgical planning. Herein, we report the case of a 50-year-old female that presented with a three-month history of abdominal pain and lower extremity edema with evidence of IVL extending to the inferior vena cava and right atrium. The patient was managed with a single-stage surgery involving cardiopulmonary bypass and excision of the right atrial and inferior vena cava tumors, as well as modified radical total abdominal hysterectomy and bilateral salpingo-oophorectomy.