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      Efficacy and safety of perioperative appliance of sunitinib in patients with metastatic or advanced renal cell carcinoma : A systematic review and meta-analysis

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          Abstract

          Background:

          The aim of this systematic review and meta-analysis is to comprehensively evaluate the efficacy and safety of the perioperative use of sunitinib in patients with metastatic and advanced renal cell carcinoma (RCC).

          Materials and methods:

          We searched authenticated databases for related clinical studies. The baseline characteristics, parameters concerning the efficacy and safety of the perioperative use of sunitinib were extracted for subsequent comprehensive analysis. The parameters which reflected the efficacy and safety as overall survival (OS), progression-free survival (PFS), occurrence rate of all-grade and grade ≥3 adverse effects (AEs) were carefully pooled using comprehensive meta-analysis.

          Results:

          We finally recruited 411 patients from 14 eligible studies. We found proteinuria (75.0%, 95% CI 62.1%–84.6%), anemia (71.6%, 95% CI 60.9%–80.3%), athesia (60.0%, 95% CI 40.3%–77.0%), pause symptoms (59.2%, 95% CI 49.2%–68.4%), arterial hypertension (53.1%, 95% CI 43.2%–62.7%), and thrombocytopenia (52.5%, 95% CI 44.8%–60.0%) to be the most common all-grade AEs. And arterial hypertension, athesia, cutaneous toxicity, hypophosphatemia, leukopenia, pain, pause syndrome, renal dysfunction, and thrombocytopenia were the most common types of grade ≥3 AEs. In addition, objective response rate (ORR) of sunitinib to both the original and metastatic tumor sites increased with the use of sunitinib, so did the OS and PFS.

          Conclusion:

          Common all-grade and grade ≥3 AEs were carefully monitored. The perioperative use of sunitinib showed superior ORR, OS, and PFS rates. Nevertheless, more studies are required to further verify these findings.

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          Most cited references30

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          Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.

          There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
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            Nomograms for predicting long-term overall survival and disease-specific survival of patients with clear cell renal cell carcinoma

            Objectives The aim of this study was to establish comprehensive and practical nomograms, based on significant clinicopathological parameters, for predicting the overall survival (OS) and the disease-specific survival (DSS) of patients with clear cell renal cell carcinoma (ccRCC). Patients and methods The data of 35,151 ccRCC patients, diagnosed between 2004 and 2014, were obtained from the database of the Surveillance, Epidemiology, and End Results (SEER) program. The Kaplan–Meier method and Cox proportional hazards regression model were used to evaluate the prognostic effects of multiple clinicopathological variables on survival. Based on Cox models, a nomogram was constructed to predict the probabilities of OS and DSS for an individual patient. The predictive performance of nomograms was evaluated using the concordance index (C-index) and calibration curves. Results According to univariate and multivariate analyses, age at diagnosis, sex, race, marital status, surgical approach, tumor node metastasis (TNM) stage, and Fuhrman grade significantly correlated with the survival outcomes. These characteristics were used to establish nomograms. The nomograms showed good accuracy in predicting 3-, 5-, and 10-year OS and DSS, with a C-index of 0.79 (95% CI, 0.79–0.80) for OS and 0.87 (95% CI, 0.86–0.88) for DSS. All calibration curves revealed excellent consistency between predicted and actual survival. Conclusion Nomograms were developed to predict death from ccRCC treated with nephrectomy. These new prognostic tools could aid in improving the predictive accuracy of survival outcomes, thus leading to reasonable individualized treatment.
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              Renal cell carcinoma with tumor thrombus extension into the vena cava: prospective long-term followup.

              We prospectively evaluated long-term survival in patients with renal cell carcinoma extending to the inferior vena cava. From 1993 and thereafter we followed 86 men and 48 women with a median age of 64 years (range 28 to 86) with renal cell carcinoma and tumor thrombus involvement of the inferior vena cava. Cancer specific survival was analyzed based on clinical therapy, tumor extent, thrombus level and grading. Median followup was 16.4 months (range 0 to 178.9). At the time of this report 97 cancer specific deaths had occurred. Of the 134 patients 111 underwent radical nephrectomy, cavotomy and thrombus extraction, of whom 30 had distant metastases at surgery, and 23 were treated with embolization and immunotherapy. These nonsurgical patients who refused surgery had a high tumor load or a low Karnofsky performance status that may have affected survival. They died at a median of 6.9 months (range 0.1 to 23.6). Patients treated surgically, including those with metastases, had a significantly higher median survival of 19.8 months (range 0 to 178.9). Surgical patients with localized tumor (N0M0) had significantly higher median survival than those with metastatic (NxM1) disease (51.7 months, range 0 to 178.9 vs 6.9, range 0.6 to 149.7). Surgical patients with metastatic disease who underwent interferon and interleukin based immunotherapy had significantly higher median survival than those who did not (13.5 months, range 2.5 to 149.7 vs 5.1, range 0.6 to 24.0). On multivariate analysis localized tumor stage (N0M0) vs advanced tumor stage (N+M0 and NxM1), Fuhrman grade groups 1 and 2 vs 3 and 4, and tumor thrombus levels I and II vs III and IV were independent prognostic factors. Currently radical surgery represents the only chance of long-term survival for patients with renal cell carcinoma and tumor thrombus extension in the inferior vena cava. Median cancer specific survival is significantly higher with localized tumor. However, even with metastatic disease radical surgery can prolong survival, especially when immunotherapy is added. Fuhrman grade and tumor thrombus level are also prognostic factors.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                May 2019
                17 May 2019
                : 98
                : 20
                : e15424
                Affiliations
                [a ]Department of Biotherapy and Cancer Center, State Key Laboratory of Biotherapy, West China Hospital
                [b ]West China School of Medicine
                [c ]Department of Liver Surgery, Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China.
                Author notes
                []Correspondence: Xuelei Ma, West China Hospital, No.37, Guoxue Alley, Chengdu 610041, China (e-mail: drmaxuelei@ 123456gmail.com ).
                Article
                MD-D-18-09282 15424
                10.1097/MD.0000000000015424
                6531174
                31096438
                8dd169ad-edf4-498a-924e-be0bb3c8551c
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 15 December 2018
                : 11 March 2019
                : 28 March 2019
                Categories
                4200
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                adverse effects,efficacy,perioperative use of sunitinib,safety

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