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ObjectiveTo characterize lymphatic vessel morphology in lower extremity lymphedema using MR lymphography at 3T.Study DesignForty females with lower extremity lymphedema secondary to gynecologic carcinoma treatment underwent MR lymphography (MRL) at 3T. Lymphatic vessel morphology in normal and affected limbs was compared.ResultsThe median diameter of the lymphatic vessels in swollen calf and thigh were significantly larger than that in the contralateral calf and thigh, respectively (p<0.05). The median number of lymphatic vessels visualized in normal calf was less than that in the lymphedematous calf (p<0.01), while no significant difference was found between the normal thigh and swollen thigh. Lymphatic vessel number in the affected calf was significantly greater than that in affected thigh and the mean diameter of affected calf was also significantly wider than that of affected thigh (p<0.01). Mean diameter of lymphatic vessels in the affected calf was significantly different between stage I and stage III (p<0.05), but not significantly different between stages I and II, and between stages II and III (p>0.05). The median number of lymphatic vessels for affected calf showed significant difference between stage I and stage III, and between stage II and stage III (p<0.05), but no significant difference between stage I and stage II (p>0.05). There was no significant difference in mean diameter or median number of lymphatic vessels in the affected thigh found between different stages (p>0.05).ConclusionThere are significant differences in the number or diameter of lymphatic vessels between normal and affected limbs and there are significant differences for affected calf between early and late stages of lymphedema; therefore, MR lymphography can be helpful in diagnosis or clinical staging for lower extremity with gynecologic oncology-related lymphedema.

Activating mutations of the MAPK pathway are reported in over half of myeloma tumors. Experience with MEK inhibitors in solid tumors suggest that although tumors harboring BRAF or RAS mutations are more likely to respond, response rates are low and duration of responses short. Potential explanations include the activation of alternative signaling pathways and in particular PI3K/AKT signaling. Studies of multiple myeloma (MM) tumors suggest that AKT activation is independent of oncogenic RAS and that combined inhibition of RAS and AKT enhances MM cell death. Based on these observations, we initiated a clinical trial to evaluate the activity of trametinib (TMTB) in MM patients (pts) with or without RAS/RAF mutations, as a single-agent and in combination with AKT inhibition for pts who fail to respond to TMTB alone. Methods: Pts were independently recruited into biomarker positive (K/NRAS or BRAF mutated) or biomarker negative (K/NRAS, BRAF wild type) groups. All pts received TMTB, 2 mg/day on a 28 day cycle. In pts who developed progressive disease (PD) or achieved less than a partial response (PR) after 4 cycles of TMTB monotherapy, GSK2141795 (pan-AKT inhibitor) was added. TMTB combined with GSK2141795 was dosed at 1.5 mg/50 mg taken daily. The M-protein at the time of adding GSK2141795 was considered the new baseline for response assessment to the combination. The main objectives were to evaluate overall response rates (ORR; IMWG) to TMTB in the 2 groups and determine the clinical benefit of adding GSK2141795 to TMTB. Results: At the data cutoff, 25 pts were enrolled: 12 in the mutated (MUT) and 13 in the wild type (WT) groups. Median age and prior lines of therapy were 65 years (range 42-76) and 4 (range 4-8) for the MUT group and 64 years (range 51-81) and 4 (range 2-8) for the WT group. 96%, 100%, 60% and 96% of pts had received prior proteasome inhibitor (PI), immunomodulatory drugs (IMiDs), pomalidomide or PI+IMiD therapy, respectively. The most common (>30%) adverse events (AEs) possibly related to study drugs were thrombocytopenia (40%) and diarrhea (32%) for TMTB monotherapy and nausea (72%), rash (63%), thrombocytopenia (36%) and anorexia (36%) with the addition of GSK2141795. The most frequent grade 3-4 AEs (>20%) were thrombocytopenia (24%) for TMTB monotherapy and thrombocytopenia (45%), anemia (45%), lymphopenia (36%), hyponatremia (27%), and neutropenia (27%) in combination with GSK2141795. One death occurred due to gastrointestinal bleed unrelated to study drugs. Of 24 pts assessable for response, confirmed ORR was 8% (1 PR) for the MUT group (N=12), Further, 1 pt had an unconfirmed minimal response (MR) and 4 pts had stable disease (SD). For the WT group (N=12), we observed 2 MR (1unconfirmed) and 3 SD. For clinical benefit rate (CBR) of 17% in both groups. With the addition of GSK2141795 to TMTB (N=11), the ORR was 27% (3 PR, 1 unconfirmed) and 1 pt had an MR (CBR=36%). The median PFS is estimated to be 3.2 (range 0.9-3.8) and 1.8 (range 0.9-NR) months (p=0.91), for the MUT and WT groups, respectively. Correlative studies are ongoing and are designed to identify predictors of response and resistance to TMTB. These include, assessment of pre- and post-treatment expression of phospho-ERK1/2, serial monitoring of clonal dynamics in bone marrow and cell-free DNA and pharmacogenomic studies. Analyses will be presented. Conclusions: The MEK1/2 inhibitor, TMTB demonstrates clinical activity in MM pts with RAS mutated tumors. In addition, disease control was observed for pts with WT RAS/RAF tumors. However, single agent activity in heavily pre-treated pts is modest. The addition of GSK2141795 to block the alternative signaling pathway improved the ORR to 27% supporting further exploration of this treatment strategy for MM. Disclosures Trudel: Celgene: Consultancy, Equity Ownership, Honoraria; Novartis: Consultancy, Honoraria; Glaxo Smith Kline: Honoraria, Research Funding; Oncoethix: Research Funding; BMS: Honoraria; Amgen: Honoraria. Bahlis:Amgen: Consultancy, Honoraria; BMS: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau. Venner:Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Research Funding; J+J: Research Funding; Janssen: Honoraria. Hay:Amgen: Research Funding; Novartis: Research Funding; Janssen: Research Funding; Kite Pharmaceuticals: Research Funding.

Background-Identification of preoperative factors predictive of non-home discharge after surgery for epithelial ovarian cancer (EOC) may aid counseling and optimize discharge planning. We aimed to determine the association between preoperative risk factors and non-home discharge.

Background To identify patients at risk for postoperative morbidities, we evaluated indications and factors associated with 30-day readmission after epithelial ovarian cancer surgery. Methods Patients undergoing primary surgery for epithelial ovarian cancer between January 2, 2003, and December 29, 2008, were evaluated. Univariable and multivariable logistic regression models were fit to identify factors associated with 30-day readmission. A parsimonious multivariable model was identified using backward and stepwise variable selection. Results In total, 324 (60.2%) patients were stage III and 91 (16.9%) were stage IV. Of all 538 eligible patients, 104 (19.3%) were readmitted within 30 days. Cytoreduction to no residual disease was achieved in 300 (55.8%) patients, and 167 (31.0%) had measurable disease (≤1 cm residual disease). The most common indications for readmission were surgical site infection (SSI; 21.2%), pleural effusion/ascites management (14.4%), and thromboembolic events (12.5%). Multivariate analysis identified American Society of Anesthesiologists score of 3 or higher (odds ratio, 1.85; 95% confidence interval, 1.18–2.89; P = 0.007), ascites [1.76 (1.11–2.81); P = 0.02], and postoperative complications during initial admission [grade 3–5 vs none, 2.47 (1.19–5.16); grade 1 vs none, 2.19 (0.98–4.85); grade 2 vs none, 1.28 (0.74–2.21); P = 0.048] to be independently associated with 30-day readmission (c-index = 0.625). Chronic obstructive pulmonary disease was the sole predictor of readmission for SSI (odds ratio, 3.92; 95% confidence interval, 1.07–4.33; P = 0.04). Conclusions Clinically significant risk factors for 30-day readmission include American Society of Anesthesiologists score of 3 or higher, ascites and postoperative complications at initial admission. The SSI and pleural effusions/ascites are common indications for readmission. Systems can be developed to predict patients needing outpatient management, improve care, and reduce costs.

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