Kidney Cancer最新文献

{"title":"Targeted Therapy and Immunotherapy: Effect of Body Mass Index on Clinical Outcomes in Patients Diagnosed with Metastatic Renal Cell Carcinoma","authors":"P. Bergerot, C. Bergerot, E. Philip, L. Meza, N. Dizman, J. Hsu, S. Pal","doi":"10.3233/KCA-180047","DOIUrl":"https://doi.org/10.3233/KCA-180047","url":null,"abstract":"Background: Previous research has identified an association between high body mass index (BMI) and better overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs). Objective: The current study sought to determine whether the effect of BMI on OS extends beyond VEGF-TKIs to mTOR inhibitors or immunotherapy (IO). Design, Setting and Participants: A retrospective study was conducted among patients diagnosed with mRCC treated at a single institution from 2009 to 2017. Demographic and clinical variables were collected. BMI was characterized as high (≥25 kg/m2) versus low (<25 kg/m2). Outcomes Measurement and Statistical Analysis: The Kaplan-Meier method was used to estimate the difference in OS, with comparisons based on BMI and by treatment type. Results and Limitations: Among 353 patients (M = 64 years old, 73% male) 66% were overweight or obese (BMI ≥ 25 kg/m2). Patients were treated with VEGF-TKI (65%), mTOR (23%), or IO (12%). Among patients treated with VEGF-TKI with low BMI, median OS was 24.0 months (95% CI, 20.7–27.2) versus 36.0 months (95% CI, 18.6–53.3) among patients with high BMI (P = 0.02). The median OS for patients with low BMI treated with mTOR was 18.0 months (95% CI, 2.8–33.1), versus 25.0 months (95% CI, 16.6–33.4) among patients with high BMI (P = 0.04). In contrast, patients with low BMI treated with IO had a median OS of 23.6 months (95% CI, 17.5–29.7) versus 19.9 months (95% CI, 10.6–29.2) among patients with high BMI (P = 0.26). The retrospective nature and the small sample size are the main limitations of this study. Conclusions: High-BMI was associated with improved OS in patients with mRCC treated with VEGF-TKI and mTOR, but the inverse trend was observed among patients receiving IO. Our data highlight the need to reassess this phenomenon in the context of IO-based regimens.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70125819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Instability in Kidney Cancer: Etiologies and Treatment Opportunities","authors":"P. Pilié","doi":"10.3233/KCA-190052","DOIUrl":"https://doi.org/10.3233/KCA-190052","url":null,"abstract":"Genomic instability is a hallmark of cancer, allowing for cancer initiation, proliferation, and progression through the accumulation of driver mutations. This instability seen in cancer arises due to a variety of factors in the cancer cell itself as well as in the cell’s environment, including endogenous and exogenous stressors leading to DNA damage in the setting of deficiency in DNA damage response (DDR). While genomic instability is beneficial to cancer cell growth and survival, it also creates targetable vulnerabilities in the cell. Kidney cancer displays low to moderate genomic instability, yet does not have frequent mutations in canonical DDR genes and is not typically responsive to DNA damaging therapies. In this review, the etiology of genomic instability in kidney cancer, with a primary focus on clear cell renal cell carcinoma (ccRCC) histology, is discussed; and, pre-clinical data supporting the use of agents targeting DDR in ccRCC is summarized with associated progress towards clinical applications.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapies Following First-Line Immune Checkpoint Inhibitor Combination in Metastatic Renal Cell Carcinoma: A Single Center Experience","authors":"N. Dizman, P. Bergerot, C. Bergerot, J. Hsu, S. Pal","doi":"10.3233/KCA-190056","DOIUrl":"https://doi.org/10.3233/KCA-190056","url":null,"abstract":"Background: Both late and early phase immune checkpoint inhibitor (CPI) combination trials indicate an impending role of combinations in the first-line treatment of metastatic renal cell carcinoma (mRCC). Sequencing the options following failure of CPI combinations is an emerging conundrum. Objective: To present our single-center clinical experience with targeted therapies (TT) following first-line CPI combinations. Methods: mRCC patients who received TT following failure of a combination regimen with CPI were identified from an institutional database. Clinical information including tumor characteristics, survival outcomes, and adverse events was retrieved from medical records. Descriptive statistics and Kaplan-Meier survival functions were performed. Results: Of 11 patients identified, median age was 63 (31–79) and 8 (73%) patients were male. First-line treatment was a CPI and TT combination in 7 (64%) patients while the rest received combination of two CPIs. The majority of patients (82%) were intermediate risk category at the initiation of targeted therapies. TTs utilized included cabozantinib (46%), lenvatinib and everolimus (27%), sunitinib (18%), and temsirolimus (9%). Best response was stable disease for 10 (91%) and partial response for 1 (9%) patient. In a median follow up of 9.1 months (range, 4.9–34.1), median progression free survival was 7.7 (95% CI 4.6–10.8) months. Progression has occurred in 7 patients, and 3 patients remain on treatment. One patient discontinued treatment due to toxicity. Conclusions: In our report, TTs demonstrate effective disease control and safety. Further exploration in prospective setting","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Comes After Immuno-Oncology Therapy for Kidney Cancer?","authors":"H. Zahoor, V. Duddalwar, A. D'souza, A. Merseburger, D. Quinn","doi":"10.3233/KCA-190053","DOIUrl":"https://doi.org/10.3233/KCA-190053","url":null,"abstract":"The treatment landscape of advanced renal cell carcinoma (RCC) is rapidly evolving. Immune checkpoint inhibitors (ICI) have now become the preferred first line treatment with the approval of nivolumab and ipilimumab combination in intermediate to poor risk patients. Combination/s of ICI with vascular endothelial growth factor (VEGF) inhibitors will also be approved in future. The optimal treatment of patients who progress on ICI-based therapies is not well defined as of yet. In this review, we discuss the data regarding various treatment options available in this space, their limitations, and also provide our opinion regarding treatment selection.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic Body Radiation Therapy for Renal Cell Carcinoma with Inferior Vena Cava Thrombus – Initial Experience Report and Literature Review","authors":"Y. Freifeld, V. Margulis, S. Woldu, R. Timmerman, J. Brugarolas, R. Hannan","doi":"10.3233/KCA-180044","DOIUrl":"https://doi.org/10.3233/KCA-180044","url":null,"abstract":"Background: Renal cell carcinoma (RCC) with inferior vena cava thrombus (IVC-TT) represents a relatively infrequent presentation. Curative treatment includes extirpative surgery; however, this is associated with high rates of recurrence and complications. Stereotactic body radiation therapy (SBRT) has been used to treat metastatic RCC with good results. SBRT may be used as part of multimodal therapy to provide local control of IVC-TT. Objective: We report our initial experience with SBRT to IVC-TT, including extended follow-up, and review the literature. Results: We report on two patients with level IV IVC-TT. Both had progressive disease while receiving systemic therapy and were eventually treated with SBRT to the IVC-TT, which showed good local control. Overall survival from the time of SBRT was 18 and 34 months, with no additional systemic therapy; one patient underwent additional SBRT and resection of","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70125602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Data from a Metastatic Renal Cell Carcinoma Community-Academic Registry: Comparative Outcomes of Progression Free Survival and Overall Survival","authors":"S. Ramalingam, M. Walker, D. George, M. Harrison","doi":"10.3233/KCA-190059","DOIUrl":"https://doi.org/10.3233/KCA-190059","url":null,"abstract":"Background: No studies have looked at comparative outcomes in the treatment of metastatic renal cell carcinoma (mRCC) between academic and community practice settings. Methods: We created a joint academic (ACAD) and community (COMM) retrospective registry of patients treated for mRCC. This registry represents a collaboration of an academic research network (Duke Oncology Network; Durham, NC) and a community-based oncology network (ACORN Research; Memphis, TN) of multiple member practices. We compared progression free survival and overall survival between these centers. We included patients diagnosed with mRCC after January 1, 2007 and before February 7, 2011. Results: Four hundred and fifty-five patients were captured in the registry including N = 255 COMM patients and N = 200 ACAD patients. Initial analysis of COMM patients showed a median PFS of 6.24 months [95% CI, 5.4, 7.5], 3.88 months [95% CI, 3.0, 4.8], and 3.35 months [95% CI 2.9, 4.4] with first, second, and third line systemic therapy. ACAD patients had longer median PFS estimates of 11.3 months [95% CI, 7.5, 13.6], 4.4 months [95% CI, 2.7, 8.9], and 5.22 months [95% CI, 2.7, 6.3] respectively. Median OS was 12.06 months [95 % CI 8.7, 15.4] among COMM patients and 36.73 months [95% CI, 26.2, 42.2) among ACAD patients. Differences persisted with inclusion of well-established prognostic models and predictive factors such as treatment exposures. Conclusions: There may be differences between outcomes for mRCC patients in community versus academic settings; however, selection most likely plays a role and we need further studies to determine reasons for these potential disparities. A prospective metastatic renal cell carcinoma (MaRCC) registry has been accrued encompassing sixty academic and community treatment sites across the United States, with the goal of examining real-world treatment patterns and outcomes; MaRCC may shed further light on any potential outcomes differences.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"4 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcome of 173 Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC) Cases: The Experience of the Center Group for Genitourinary Tumors","authors":"A. Martín, J. Puente, Á. Pinto, P. Gajate, T. A. Gordoa, E. Grande, A. Herrero, C. Maximiano, M. Garrido, I. Gallegos, Maria L. Villalobos, J. García-Donas, E. Caviedes, I. García, J. Espinosa, C. Aguado, J. Arranz, L. García, J. F. Rodriguez, J. Casinello, L. Rodríguez","doi":"10.3233/KCA-180045","DOIUrl":"https://doi.org/10.3233/KCA-180045","url":null,"abstract":"Non-clear cell renal cell carcinoma (nccRCC) represents a group of multiple histologic subtypes, with different clinical outcomes and an uncertain optimal treatment. Data collected in clear cell tumors are routinely extrapolated to nccRCC, despite a different underlying biology. The Center Group for Genitourinary tumors is a network of medical oncologists from hospitals in Madrid and surrounding provinces that are focused on genitourinary tumors. A retrospective, multicenter study of the outcome of patients with nccRCC diagnosed and treated at the Center Group hospitals between 1995 and 2015 was performed. Baseline clinical features, histologic subtypes, therapeutic management and survival status were analyzed. Data was collected from 173 patients, with a median age at diagnosis of 65 years [24–90], 67.1% were male. Histologic subtypes comprised 55.5% papillary carcinoma, 23.1% sarcomatoid, 13.9% chromophobe, 6.9% unclassified tumors and 0.6% oncocytoma. 159 patients received first line therapy including tyrosine kinase inhibitors (67.9%) and mammalian target of rapamycin inhibitors (11.9%). The response rates (RR) in evaluable patients (142) were: complete response 5.6%, partial response 17.6%, stable disease 40.8% and progression in 35.9% of cases. 90 patients (52.0%) received second line treatment. At the time of the data cut-off point (April 1, 2016), 126 patients had died, with a median overall survival (OS) of 17.9 months [95% CI 15.0–20.9]. The clinical outcome reported in this study has a similar OS to other published studies. Nevertheless, there are substantial differences among the distinct subtypes. Overall, prognosis in nccRCC remains poor. No significant differences were observed in the activity of systemic agents, used as either first or second line therapy.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70125663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving Epidemiologic Trends of Renal Cell Cancer by Histologic Subtype: An Updated Analysis of the California Cancer Registry","authors":"M. Parikh, Jasmine C Huynh, A. Brunson, T. Keegan, P. Lara","doi":"10.3233/kca-190063","DOIUrl":"https://doi.org/10.3233/kca-190063","url":null,"abstract":"Background: While most renal cell carcinomas (RCC) are of the clear cell subtype, other histologic subtypes are well described and have distinct clinical behavior. This study seeks to evaluate survival of clear and non-clear cell RCC retrospectively from a large, population-based cancer registry. Objectives: The key objectives of this study were to determine cancer-specific survival (CSS) and overall survival (OS) of RCC by histologic subtype and to examine survival by histologic subtype since the advent of anti-angiogenesis therapy in","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-190063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive Surgical Margins After Partial Nephrectomy: A Systematic Review and Meta-Analysis of Comparative Studies","authors":"V. Ficarra, A. Crestani, A. Inferrera, G. Novara, M. Rossanese, E. Subba, G. Giannarini","doi":"10.3233/KCA-180037","DOIUrl":"https://doi.org/10.3233/KCA-180037","url":null,"abstract":"Objective: We performed an update of previous reviews of the literature to provide an overview on incidence, predictive factors, management and prognosis of positive surgical margins (PSMs) after partial nephrectomy (PN) including recent surgical series and studies comparing different approaches and techniques. Material and methods: A literature search was performed from January 2013 to January 2018 using the Medline database. The search strategy included a free-text protocol using the term “nephron-sparing surgery” OR “partial nephrectomy” AND “positive surgical margins” across the title and abstract fields of the records. From each selected study, we extracted the following data: number of analyzed patients, study design, approach and surgical technique used, PSMs rate, pathological features, type of PSMs treatment, mean (median) follow-up duration and final patient status. Meta-analysis was conducted using Review Manager software v. 5.2 (Cochrane Collaboration, Oxford, UK). Results: We selected a total of 36 (48%) studies. All studies were retrospective and the best statistical method used for comparison was the matched-pair analysis (level 4). Overall, 45,786 patients treated with PN were included in the selected studies. PSMs were reported in a total of 3,093 (6.7%) patients. The mean estimated PSMs rate was 7%, 5% and 4.3% in patients who underwent robot-assisted PN (RAPN), laparoscopic PN (LPN) and open PN (OPN), respectively. Comparative studies showed a significant advantage in favor of OPN compared with minimally invasive approach, while RAPN showed more favourable PSMs risk compared with LPN (odds ratio 3.02, 95% confidence intervals 2.05–4.45). No differences were detected stratifying data according to other surgical or tumor-related factors. Tumor size, nuclear grading and pT3a stage represent the most important predictors of PSMs. In 6,809 patients, follow-up data were available. Only 101 (1.4%) local recurrences and 88 (1.3%) distant recurrences were observed both in PSMs and negative surgical margins subgroups. PSMs were associated with a significant increased risk of local recurrence with a significant impact on local recurrence-free survival and metastasis-free survival. However, a significant impact on cancer-specific and overall survival could not be demonstrated. ∗Correspondence to: Vincenzo Ficarra, MD, FEBU, Department of Human and Paediatric Pathology “Gaetano Barresi”, Urologic section, University of Messina, via Consolare Valeria 1, 98124 Messina, Italy. E-mail: vficarra@unime.it. ISSN 2468-4562/18/$35.00 © 2018 – IOS Press and the authors. All rights reserved This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). 134 V. Ficarra et al. / Positive Surgical Margins After Partial Nephrectomy Conclusions: Studies published in the last 5 years confirmed that PSMs after PN are a rare condition. Although PSMs increase the risk ","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45147456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconciling the Role of Vascular Endothelial Growth Factor-Targeted Therapies in Adjuvant Renal Cell Carcinoma Treatment","authors":"W. Kim, M. Parikh, C. Ryan, P. Lara","doi":"10.3233/KCA-180034","DOIUrl":"https://doi.org/10.3233/KCA-180034","url":null,"abstract":"Up to 40% of patients with high risk, localized RCC will relapse after nephrectomy and are at risk of eventually succumbing to the disease. Historically, phase 3 clinical trials failed to demonstrate meaningful benefit of adjuvant therapy in RCC, likely because these early trials used treatments that did not demonstrate meaningful clinical efficacy in mRCC. However, the clear clinical activity demonstrated by VEGF-TKIs in mRCC patients renewed the promise of adjuvant therapy. ASSURE, S-TRAC, and PROTECT are the first three trials to examine the clinical efficacy of 1 year of adjuvant VEGF-TKI therapy in patients with high-risk RCC following nephrectomy. In this review we reconcile the results of these studies and explore the future of adjuvant RCC therapy.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41831726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}