In this study, we highlighted some variants among many, modulating negatively the promoter activity of BRCA1 or 2 and thus having a potential impact on the risk of developing cancer. This selection makes it possible to conduct future validation studies on a limited number of variants.
466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.
Background: Combined hepatocellular carcinoma and mass-forming cholangiocarcinoma (cHCC-MFCCC) is a rare tumor. The aim of this study was the survival analysis comparing such tumor with classic hepatocellular carcinoma (HCC) and mass-forming cholangiocarcinoma (MFCCC). Methods: Our prospectively maintained database was queried, and 20 patients with cHCC-MFCCC were identified. A 2:1 match was performed with 40 patients operated in the same period for HCC, and with 40 operated for MFCCC. Only T1 or T2 patients N0 M0 were considered. Primary endpoint was the overall survival (OS) and disease-free survival (DFS). Results: Median tumor diameter of cHCC-MFCCC group was 3.8 cm (range 1.3-5), and single tumor was detected in 13. After a median follow-up of 26 months (range 6-77), the 1-, 3-, and 5-year OS rates were 95%, 71%, and 71% respectively. The 1-, 3-, and 5-year DFS rates were 70%, 46%, and 35% respectively. Both OS and DFS did not differ significantly among the three histotypes. Conclusion:Patients with cHCC-MFCCC showed similar rates of OS and DFS to those patients with classic HCC and MFCCC. Further evaluations of differences in tumor features and biology are necessary to better characterize the prognosis of patients with cHCC-MFCCC.
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