Background: This study investigated the efficacy and toxicity of sorafenib and sunitinib as primary treatment for patients with metastatic renal cell carcinoma (mRCC). Methods: We identified 49 and 220 patients treated with sorafenib and sunitinib, respectively, as first-line therapy in the Asan Medical Centre from April 2005 to March 2011. Results: Disease control rates of 71 and 74% were achieved with sorafenib and sunitinib, respectively (p = 0.687). After a median follow-up of 27.6 months, progression-free survival (PFS) and overall survival (OS) were not significantly different between the sorafenib and the sunitinib group (PFS 8.6 vs. 9.9 months, respectively, p = 0.948, and OS 25.7 vs. 22.6 months, p = 0.774). Patients treated with sorafenib required dose reduction due to toxicities less frequently than those treated with sunitinib (37 vs. 54%, p = 0.034). Haematological toxicity of grade 3 or 4 was more common in the sunitinib group than in the sorafenib group (45 vs. 4%, p < 0.001). Multivariate analysis showed old age, Heng's risk group, and bone and liver metastases, but not the type of vascular endothelial growth factor tyrosine kinase inhibitor, were independent prognostic factors affecting OS. Conclusion: The results of this study indicate that sorafenib has comparable efficacy to sunitinib in the treatment of mRCC patients and fewer and less severe toxicities, but the number of patients included in the study was small.
Sequential therapy is a standard strategy used to overcome the limitations of targeted agents in metastatic renal cell carcinoma. It remains unclear whether a mammalian target of rapamycin (mTOR) inhibitor is a more effective second-line therapy after first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) has failed than the alternative, VEGF TKI. A clinical database was used to identify all patients with renal cell carcinoma who failed at first-line VEGF TKI and then treated with second-line VEGF TKI or mTOR inhibitors in the Asan Medical Center. Patient medical characteristics, radiological response and survival status were assessed. Of the 83 patients who met the inclusion criteria, 41 received second-line VEGF TKI [sunitinib (n = 16) and sorafenib (n = 25)] and 42 were treated with mTOR inhibitors [temsirolimus (n = 11) and everolimus (n = 31)]. After a median follow-up duration of 23.9 months (95 % CI, 17.8-30.0), progression-free survival was 3.0 months for both groups [hazard ratio (HR, VEGF TKI vs. mTOR inhibitor) = 0.97, 95 % CI 0.59-1.62, P = 0.92]. Overall survival was 10.6 months for the VEGF TKI group and 8.2 months for the mTOR inhibitor group (HR = 0.98, 95 % CI 0.57-1.68, P = 0.94). The two groups did not differ significantly in terms of disease control rate (51 % for VEGF TKI and 59 % for mTOR inhibitor, P = 0.75). Second-line VEGF TKI seems to be as effective as mTOR inhibitors and may be a viable option as a second-line agent after first-line anti-VEGF agents have failed.
PurposeIn about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival.MethodsBetween January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients.ResultsThe iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22).ConclusionPrior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.
BackgroundAge and performance status are important prognostic factors in primary central nervous system (CNS) lymphoma. Although several prognostic models have been proposed, there is no consensus on the optimal model for patients with diffuse large B-cell histology.MethodsSeventy-seven patients with primary CNS diffuse large B-cell lymphoma were retrospectively analyzed to determine factors affecting survival. Three Western models were applied to our eligible patients; we devised a novel model based on our findings.ResultsThe median patient age was 59 years (range, 29–77); the median event-free and overall survival (OS) durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and Memorial Sloan Kettering Cancer Center models were applicable to our cohorts. Multivariate analysis showed that advanced age, multifocal lesions, and high cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A novel model for predicting prognosis was then developed based on these variables. Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3 were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very high-risk groups (N=4), respectively. Sixty-one patients were eligible considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the low-, moderate-, high-, and very high-risk groups, respectively (P<0.01).ConclusionAdvanced age, multifocal lesions, and high CSF protein concentration were adversely related with prognosis. Our model can be helpful in pre-treatment risk stratification for patients with primary CNS lymphoma with diffuse large B-cell histology.
This study provides an analysis of the applications of optimization routines for designing fluid mounts. After summarizing the concept of fluid mounts and their dynamic characteristics, we review the importance of the notch and resonance peak that occur in dynamic stiffness of fluid mounts. Fluid mounts are tuned for specific application so that their notch frequency coincides with the disturbance frequency, by selecting the proper parameters for the mount. Additionally, the mount parameters are selected such that the notch remains as deep (close to zero) as possible and the resonance peak is kept as short as possible. The notch depth and resonance peak present opposing requirements for the selection of mount parameters in the sense that lowering one will result in increasing the other. Using a bond graph model, this study will evaluate the effect of various parameters on the mount notch depth and resonance peak height characteristics. The results show that different parameters can have a varying effect on the notch frequency and depth, as well as the resonance frequency and peak height. The results of the study are extended by examining the effectiveness of two different optimization methods-namely, the Enhanced Genetic Algorithm (EGA) and Sequential Quadratic Programming (SQP)-for selecting the combination of parameters that can yield the deepest notch and shortest resonance peak. Using two different design cases, the study shows that SQP exhibits much more sensitivity to the initial conditions that are selected for the mount parameters than EGA. Both methods, however, are able to converge to an optimal solution within the constraints that are selected for the parameters. For both cases, EGA is able to converge to the set of parameters that provide a deep notch and a short resonance peak.
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