P. Bergerot, C. Bergerot, E. Philip, L. Meza, N. Dizman, J. Hsu, S. Pal
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.
{"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}
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.
{"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}
N. Dizman, P. Bergerot, C. Bergerot, J. Hsu, S. Pal
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
背景:晚期和早期免疫检查点抑制剂(CPI)联合试验表明，联合治疗在转移性肾细胞癌(mRCC)的一线治疗中即将发挥作用。CPI组合失败后的选择排序是一个新出现的难题。目的:介绍一线CPI联合用药后靶向治疗(TT)的单中心临床经验。方法:从机构数据库中确定在联合方案与CPI失败后接受TT治疗的mRCC患者。临床信息包括肿瘤特征、生存结果和不良事件从医疗记录中检索。进行描述性统计和Kaplan-Meier生存函数分析。结果:11例患者中位年龄为63岁(31-79岁)，男性8例(73%)。7例(64%)患者采用CPI和TT联合一线治疗，其余患者采用两种CPI联合治疗。大多数患者(82%)在开始靶向治疗时属于中等风险类别。使用的替代药物包括卡博赞替尼(46%)、lenvatinib和依维莫司(27%)、舒尼替尼(18%)和替西莫司(9%)。最佳反应是10例(91%)患者病情稳定，1例(9%)患者部分缓解。中位随访时间为9.1个月(范围4.9-34.1)，中位无进展生存期为7.7个月(95% CI 4.6-10.8)。7例患者出现进展，3例患者仍在接受治疗。一名患者因中毒而停止治疗。结论:在我们的报告中，TTs显示出有效的疾病控制和安全性。远景环境下的进一步探索
{"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}
H. Zahoor, V. Duddalwar, A. D'souza, A. Merseburger, D. Quinn
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.
{"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}
Y. Freifeld, V. Margulis, S. Woldu, R. Timmerman, J. Brugarolas, R. Hannan
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
{"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}
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.
{"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}
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
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.
非透明细胞肾细胞癌(nccRCC)代表了一组多种组织学亚型，具有不同的临床结果和不确定的最佳治疗方法。在透明细胞肿瘤中收集的数据通常被推断为nccRCC，尽管其潜在的生物学特性不同。泌尿生殖系统肿瘤中心小组是一个由马德里和周边省份医院的医学肿瘤学家组成的网络，他们专注于泌尿生殖系统肿瘤。对1995年至2015年间在中心集团医院诊断和治疗的nccRCC患者的预后进行了一项回顾性、多中心研究。分析患者的基线临床特征、组织学亚型、治疗管理和生存状况。数据来自173例患者，诊断时中位年龄65岁[24-90]，67.1%为男性。组织学亚型包括55.5%乳头状癌、23.1%肉瘤样癌、13.9%憎色瘤、6.9%未分类肿瘤和0.6%嗜瘤细胞瘤。159例患者接受一线治疗，包括酪氨酸激酶抑制剂(67.9%)和哺乳动物雷帕霉素靶点抑制剂(11.9%)。142例可评估患者的缓解率(RR)为:完全缓解5.6%，部分缓解17.6%，病情稳定40.8%，病情进展35.9%。90例(52.0%)患者接受了二线治疗。截至数据截止点(2016年4月1日)，126例患者死亡，中位总生存期(OS)为17.9个月[95% CI 15.0-20.9]。本研究报告的临床结果与其他已发表的研究具有相似的OS。然而，在不同的亚型之间存在着实质性的差异。总体而言，nccRCC的预后仍然很差。在作为一线或二线治疗的全身药物的活性方面没有观察到显著差异。
{"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}
M. Parikh, Jasmine C Huynh, A. Brunson, T. Keegan, P. Lara
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
{"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}
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.
{"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}
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