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Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer.Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30mg orally daily for a 28daycycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]).Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD.Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.

Objective The objective of this study was to examine SLN evaluation alone in women with squamous cell carcinoma (SCC) of the vulva and evaluate the inguinal recurrence and complication rates. Methods An IRB approved prospective study enrolled patients with SCC of the vulva. Peritumoral injection of Tc-99 sulfur colloid and blue dye was used to identify SLNs intraoperatively. Patients with negative SLN for metastasis were followed clinically without further treatment. Patients with metastasis to a SLN underwent full groin node dissection followed by standard treatment protocols. Results A total of 73 women were enrolled onto protocol with 69 patients undergoing SLN dissection. Mean age was 66.9years (range: 29–91) with 47 stage I, 12 stage II, 9 stage III, 2 stage IV and 3 unstaged patients. SLN dissections were successful in 63 patients. Of the 111 groins evaluated with a SLN dissection 93% had a SLN identified with an average of 2 SLN per groin. There were 92 groins with negative SLN and 11 groins with positive SLN. 57 patients had negative SLN and underwent conservative management with the median follow-up of 58.3months. Three patients experienced groin recurrences (2 unilateral, 1 bilateral) for a recurrence rate of 5.2% (3/57). The complication rate for the inguinal incisions was 17.5% (1 cellulitis, 1 abscess, 2 lymphoceles, 5 lymphedema and leg pain). Conclusions Isolated SLN dissection alone has a low inguinal recurrence rate with decreased complications and should be considered as an option for women with SCC of the vulva.

To determine predictive factors for the presence of malignant transformation in ovarian endometriotic cysts.This was an IRB approved, case control study analyzing patient data from 2004 to 2013. Pathology database records were searched to identify patients with benign endometrioma and ovarian carcinoma arising in the background of endometriosis. Inclusion criteria required each patient to have a preoperative diagnosis of adnexal mass and no other findings concerning for malignancy. Patient clinical records were queried for preoperative symptoms, serum CA125 levels and radiologic findings. Pathologic data were collected including histology, tumor grade and stage.A total of 138 patients met inclusion criteria; 42 women with ovarian cancer arising in the background of endometriosis and 96 women with benign endometrioma. Women diagnosed with ovarian cancer were significantly older than women with endometriosis (53.6 vs. 39.2 years). There was no difference in presence of symptoms between the two groups. Women with malignant tumors were found to have significantly larger cysts (14 cm vs. 7.5 cm; p0.0001) that were more often multilocular (45.7% vs. 12.2%; p0.0001), and contained solid components (77.1% vs. 14.5%; p0.0001). Among patients that were observed prior to surgery there was a significant difference in the change in size of the mass over time with 4.2 cm increase for cases vs. 1.0 cm increase for controls (p=0.02). Multiple logistic regression analysis indicated that for every 5 years increase in age there was an adjusted OR of 2.17 (p=0.003). An age of 49 years or greater had an 80.6% sensitivity (95% CI: 62.5-92.5%) and an 82.9% specificity (95% CI: 67.9-92.8%) for malignancy, and solid component on imaging had an adjusted OR of 23.7 (p0.0001). Serum CA125 levels tended to be higher in patients with malignant tumors but did not reach statistical significance with a mean of 204.9 vs. 66.9 (p=0.1).Significant predictors for malignant transformation of endometriosis include cyst characteristics and age. Women above the age of 49 with multilocular cysts and solid components are at high risk for malignant transformation of endometriosis. Serum CA125 level is not a significant predictor of malignant transformation.

Objectives: PTEN mutations are frequently observed in endometrioid uterine cancer and lead to hyperactivation of the PI3K/Akt pathway. However, the role of BRCA1 and 2 mutations, leading to homologous recombination deficiency, is not known in this disease. We sought to determine the frequency and clinical significance of BRCA mutations in patients with uterine cancer and PTEN mutations. Methods:We assessed PTEN, BRCA1, and BRCA2mutation status for 248 uterine tumor samples using level 3 data fromThe Cancer GenomeAtlas (TCGA). We performed mutation analysis for PTEN, BRCA1, and BRCA2 for an additional 251 samples from TCGA using ANNOVAR. A total of 499 patientswere included in the analysis. Clinical data, including stage, tumor histology, and overall survival, were also extracted. Fisher's exact tests were used to identify the association betweenmutation status and histologic subtype. Kaplan–Meier plots were constructed to demonstrate survival differences between groups. Results: Among the samples analyzed, 335 (67%) had endometrioid histology, 76 (15%) had serous histology, 18 (44%) had mixed histology, and histology was unknown in the remainder of cases. Of the patients with endometrioid histology, 260 (78%) had a PTEN mutation, 23 (7%) had both BRCA1 and 2 mutations, 4 (1%) had mutations in BRCA1 only, and 25 (8%) hadmutations in BRCA2 only. A total of 52/335 patients (16%) had mutations in either BRCA1 or 2; 18/52 (35%) of these had stage II or above disease and the remainder had stage I disease. No survival advantage was detected in patients with BRCA1 mutations over wildtype BRCA1, independent of PTEN mutation status (P=0.16 and 0.19, respectively). Patients with both PTEN and BRCA2 mutations had improved overall survival compared to patients with wild-type PTEN and BRCA2 (P=0.03). A singlemutation in BRCA1, BRCA2, or PTEN did not confer a significant survival advantage compared towild-type (P=0.15). Conclusions: BRCA1 and 2 mutations are prevalent in patients with endometrioid uterine cancer, and PTEN/BRCA2 double mutations are associated with prolonged patient survival. These findings may have significant clinical and treatment implications.