Smaldone, Marc C.

560 Background: Level I evidence exists demonstrating the efficacy of the mTOR inhibitor everolimus (EVE) in decreasing tumor volume of syndromic angiomyolipomas (AMLs) among patients with Tuberous Sclerosis. No prospective data are available regarding the effect of mTOR inhibition on growth kinetics in patients with sporadic AMLs. Methods: We conducted a multi-institutional, prospective, phase 2 trial with an optimal two-stage Simon design in patients presenting with > 3cm sporadic AMLs who were candidates for surgical or percutaneous intervention. Response was defined as ≥25% volumetric reduction of the AML. Planned enrollment was 43 patients to test the null hypothesis at a 5% level of significance with 80% power. Baseline, 4- and 6-month volumetric analysis was performed by dynamic contrast-enhanced MRI (DCE-MRI). Patients received EVE 10mg for four 28-day cycles, at which point EVE was discontinued in those with < 25% volumetric reduction. Those with ≥ 25% volumetric reduction received two additional cycles of EVE. Dose reductions and interruptions were allowed to 5 mg QOD. Conservative stopping rules were established for toxicity, given the benign nature of AMLs. Results: The early stopping rules for both efficacy and toxicity were invoked. We enrolled 20 patients (median age = 68) from 5 centers with 21 sporadic AMLs. 11/20 (55%) patients completed 4 cycles of EVE, while 7/20 (35%) completed 6 cycles. Median days on treatment was 88 (2 cycles). 4/20 (20%) patients were withdrawn due to toxicity, while 8/20 (40%) withdrew due to personal preference. Dose reductions were required in 6/20 (30%) patients, and 5/20 (25%) patients had grade 3 toxicities which resolved upon discontinuation or dose reduction of EVE. At 4-month MRI, 10/16 (62.5%) patients had a ≥25% reduction in volume (mean = 54.1% decrease). At 6-month MRI, 8/12 (66.6%) patients had a ≥25% reduction in volume (mean = 51.5% decrease). Conclusions: EVE was effective in reducing tumor volume in patients with sporadic AMLs but was associated with a high rate of treatment termination due to patient preference or prespecified AEs. Neoadjuvant EVE may be useful in potentiating surgical resection of large or anatomically complex AMLs. Clinical trial information: NCT02539459.

Objective To test the association between hospital type and performance of candidate quality measures for treatment of muscle‐invasive bladder cancer ( MIBC ) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion. Patients and Methods Using the N ational C ancer D atabase, patients with stage ≥ II urothelial carcinoma treated with radical cystectomy ( RC ) from 2003 to 2010 were identified. Hospitals were grouped by type and annual RC volume: community, comprehensive low volume ( CLV ), comprehensive high volume ( CHV ), academic low volume ( ALV ), and academic high volume ( AHV ) groups. Logistic regression models were used to test the association between hospital group and performance of quality measures, adjusting for year, demographic, and clinical/pathological characteristics; generalised estimating equations were fitted to the models to adjust for clustering at the hospital level. Results In all, 23 279 patients underwent RC at community (12.4%), comprehensive ( CLV 38%, CHV 5%), and academic ( ALV 17%, AHV 28%) hospitals. While only 0.8% (175) of patients met all four quality criteria, 61% of patients treated at AHV hospitals met two or more quality metric indicators compared with ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals ( P < 0.001). After adjustment, patients were more likely to receive two or more quality measures when treated at AHV (odds ratio [ OR ] 2.4, confidence interval [ CI ] 2.0–2.9), ALV ( OR 1.3, CI 1.1–1.6), and CHV ( OR 1.3, CI 1.03–1.7) hospitals compared with community hospitals. Conclusions Patients undergoing RC at AHV hospitals were more likely to meet quality criteria. However, performance remains low across hospital types, highlighting the opportunity to improve quality of care for MIBC .