Kidney cancer journal : official journal of the Kidney Cancer Association最新文献

{"title":"\"PROBE\"ing the Role of Cytoreductive Nephrectomy in Advanced Renal Cancer.","authors":"Hannah Bell,&nbsp;Brittney H Cotta,&nbsp;Simpa S Salami,&nbsp;Hyung Kim,&nbsp;Ulka Vaishampayan","doi":"10.3233/kca-210010","DOIUrl":"https://doi.org/10.3233/kca-210010","url":null,"abstract":"<p><p>The Southwest Oncology Group (SWOG)1931 trial, also known as PROBE (ClinicalTrials.gov Identifier: NCT04510597) is a phase III study evaluating the role of cytoreductive nephrectomy (CN) in metastatic renal cell cancer (RCC). Kidney cancer presenting with synchronous metastases has demonstrated shorter survival outcome compared to the patients relapsing with metastases after nephrectomy. Previously, CN has been associated with survival improvement when interferon-based systemic therapy was used. In the setting of antivascular therapy sunitinib, a prospective randomized clinical trial demonstrated no benefit of CN. Immune checkpoint-based combination therapy has now become the standard-of-care in the frontline setting for RCC. The role of nephrectomy or primary resection has not been evaluated in the setting of immune checkpoint-based systemic therapy. The sequence and optimal timing of nephrectomy is also not established. The PROBE study design attempts to answer the question whether CN has an impact on overall survival outcomes in RCC within the context of immune checkpoint-based combination regimens. The study requires starting with systemic therapy; any one of the FDA approved immunotherapy-based regimens at the time the study was activated are permitted. The disease status and response are evaluated at 9-12 weeks of therapy and then consented patients are randomized 1:1 to receive CN or to continue systemic therapy. The patients who have rapid disease progression are considered ineligible for randomization as they need a switch in systemic therapy. Both groups should continue systemic therapy as long as they are tolerating the treatment and continuing to derive clinical benefit. Quality-of-life, tumor genomic testing, microbiome, radiomics and circulating tumor DNA assessments as predictive biomarkers are planned as study correlatives. The study hypothesis is that CN will improved OS in synchronous metastatic RCC when surgery is performed after starting systemic immune checkpoint-based combination therapy. A potential mechanism leading to improved survival is the broader antigen spread and higher neoantigen load enabled by the primary tumor enhancing the efficacy of the immune therapy. CN after initial systemic therapy would help select the patient subset most likely to benefit and will potentially enable eradication of immune resistant clones within the primary tumor.</p>","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"6 1","pages":"3-9"},"PeriodicalIF":0.0,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929722/pdf/nihms-1771327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40309093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney Cancer Research Highlights from ASCO GU 2022 Meeting.","authors":"Yasser Ged,&nbsp;Nirmish Singla","doi":"10.52733/KCJ20n1-GU1","DOIUrl":"https://doi.org/10.52733/KCJ20n1-GU1","url":null,"abstract":"","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":" ","pages":"30-32"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272854/pdf/nihms-1793026.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40597488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Latinx Disparity in Surgery for Kidney Cancer: Data from The South Texas Region.","authors":"F. Dursun, Rahul Patel, D. Hui, Hanzhang Wang, A. Mansour, D. Pruthi, D. G. Alonso, L. Jayakumar, R. Rodriguez, R. Svatek, M. Liss, D. Kaushik","doi":"10.52733/kcj20n1-a1","DOIUrl":"https://doi.org/10.52733/kcj20n1-a1","url":null,"abstract":"The South Texas region, with a predominantly Latinx population, has a very high incidence of renal cell carcinoma (RCC), including those with tumor extending into the major blood vessels called venous tumor thrombus (VTT). There is currently no data on outcomes of Latinx patients with VTT as most published studies are from predominantly Caucasian population. Therefore, we performed this study to fill an urgent, unmet need. We reviewed patients who underwent radical nephrectomy with removal of VTT (called tumor thrombectomy) between 2015 and 2020. We collected data on demographics, clinical, pathological characteristics and outcomes of patients. Univariate and multivariate Cox regression analyses were used to evaluate the associations between ethnicity and disease progression or survival. We identified 112 patients, of which 67 (62%) were Latinx, and 41 (38%) were non-Latinx. Approximately 60% of patients had Level II-IV VTT; Latinx presented with a higher level of tumor thrombus (p=0.046). Latinx patients had a higher rate of no insurance (11% vs. 27%, p=0.04) and were more likely to lost to follow-up after surgery (22.4% vs. 13.3%, p=0.23) compared to non-Latinx. Fewer Latinx received systemic therapy (28% vs. 42%; p=0.13). Ninety-day mortality for the entire cohort was 3.8%. The Latinx population in the South Texas region present late, with advanced thrombus level, and do not have access to systemic therapy. Given symptomatic disease, surgical treatment, if feasible, is their only option. Our results highlight disparate treatment patterns which require further investigation and health-care policy changes.","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"20 1 1","pages":"6-13"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47282998","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":"SETD2 regulates the methylation of translation elongation factor eEF1A1 in clear cell renal cell carcinoma.","authors":"Robert Hapke,&nbsp;Lindsay Venton,&nbsp;Kristie Lindsay Rose,&nbsp;Quanhu Sheng,&nbsp;Anupama Reddy,&nbsp;Rebecca Prather,&nbsp;Angela Jones,&nbsp;W Kimryn Rathmell,&nbsp;Scott M Haake","doi":"10.3233/kca-220009","DOIUrl":"https://doi.org/10.3233/kca-220009","url":null,"abstract":"<p><strong>Background: </strong>SET domain-containing protein 2 (<i>SETD2</i>) is commonly mutated in renal cell carcinoma. SETD2 methylates histone H3 as well as a growing list of non-histone proteins.</p><p><strong>Objective: </strong>Initially, we sought to explore SETD2-dependent changes in lysine methylation of proteins in proximal renal tubule cells. Subsequently, we focused on changes in lysine methylation of the translation elongation factor eEF1A1.</p><p><strong>Methods: </strong>To accomplish these objectives, we initially performed a systems-wide analysis of protein lysine-methylation and expression in wild type (WT) and <i>SETD2</i>-knock out (KO) kidney cells and later focused our studies on eEF1A1 as well as the expression of lysine methyltransferases that regulate its lysine methylation.</p><p><strong>Results: </strong>We observed decreased lysine methylation of the translation elongation factor eEF1A1. <i>EEF1AKMT2</i> and <i>EEF1AKMT3</i> are known to methylate eEF1A1, and we show here that their expression is dependent on SET-domain function of <i>SETD2.</i> Globally, we observe differential expression of hundreds of proteins in WT versus <i>SETD2</i>-KO cells, including increased expression of many involved in protein translation. Finally, we observe decreased progression free survival and loss of EEF1AKMT2 gene expression in <i>SETD2</i>-mutated tumors predicted to have loss of function of the SET domain.</p><p><strong>Conclusion: </strong>Overall, these data suggest that <i>SETD2</i>-mutated ccRCC, via loss of enzymatic function of the SET domain, displays dysregulation of protein translation as a potentially important component of the transformed phenotype.</p>","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"6 3","pages":"179-193"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851421/pdf/nihms-1854947.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tribute to Dr. Christopher G. Wood, MD","authors":"Nizar Tannir","doi":"10.52733/kcj19n4-t","DOIUrl":"https://doi.org/10.52733/kcj19n4-t","url":null,"abstract":"Tributes to individuals who have passed away share one common purpose: to help us heal. We find comfort by sharing the legacies of the loved ones we’ve lost. Today we pay tribute to Dr. Christopher G. Wood, Professor of Urology.","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73385651","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":"IKCS2021 Top Abstracts","authors":"Robert Figlin","doi":"10.52733/kcj19n4-abs","DOIUrl":"https://doi.org/10.52733/kcj19n4-abs","url":null,"abstract":"","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81625440","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":"Radiological Correlates of pT3a Kidney Cancer: Importance of Irregular Tumor Sinus Border","authors":"Y. Ye, D. Palacios, R. Campbell, Alain Rizk, Hajime Tanaka, Carlos Munoz-Lopez, Emily Abramczyk, G. Roversi, Jianbo Li, C. Weight, R. Abouassaly, E. Remer, S. Campbell","doi":"10.52733/kcj19n4-a1","DOIUrl":"https://doi.org/10.52733/kcj19n4-a1","url":null,"abstract":"Purpose: Preoperative assessment of T3a renal-cell-carcinoma (RCC) in absence of main renal vein involvement or lymph node enlargement is challenging but has potential implications for counseling and prognosis. Materials and Methods: A retrospective review of 1129 cT1-T3aN0M0 RCC patients managed with partial/radical nephrectomy (PN/RN) in our institution (2012-2014) was performed. Exclusion criteria included radiological evidence of main renal vein involvement or substantial lymphadenopathy. Eleven radiological findings suggestive of aggressive tumor biology or invasive phenotype based on prior literature were assessed for correlation with pT3a status. These included perinephric-findings (stranding, enhancing-nodule, collateral-vessels, or irregular-perinephric-tumor-contour), findings within the sinus (stranding, collecting-system invasion, branch-vein enlargement, or irregular-tumor-sinus-border [ITSB]), and tumor-necrosis, infiltrative-features, and tumor-size. Radiological assessment was blinded to final pathology. Sensitivity/specificity and logistic-regression analyses assessed the performance of each imaging-finding for detecting pT3a tumors. Results: Median tumor-size was 4.0cm and R.E.N.A.L. was 8. Median follow-up was 53 months (IQR:28-64). pT3a tumors were found in 281 patients (25%) and strongly correlated with local and systemic recurrence (p<0.02). ITSB was found in 350 patients (31%) and was the strongest predictor of pT3a status. Sensitivity/specificity/PPV/NPV/OR/C-Index for ITSB were 75%/84%/61%/91%/15.8(11.4-21.9)/0.80, for correlation with pT3a, respectively. The best predictive model included ITSB(yes/no) and tumor-size as a continuous variable (C-index=0.84). Addition of other imaging-findings did not improve the model (C-index=0.84). ITSB was the strongest contributor in all multivariable-models and also strongly correlated with recurrence-free-survival. Inter/intra-observer correlations for assessment of ITSB were 0.89/0.98, respectively. Conclusions: Our data suggest that ITSB and tumor-size associate with pT3a RCC, which could impact patient counseling.","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"187 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81089662","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":"How Can We Predict pT3a Kidney Cancer and What Does It Mean?: Commentary for the article \"Radiological Correlates of pT3a Kidney Cancer: Importance of Irregular Tumor Sinus Border\".","authors":"N. Singla","doi":"10.52733/kcj19n4-c","DOIUrl":"https://doi.org/10.52733/kcj19n4-c","url":null,"abstract":"The ability to predict pathologically advanced renal cell carcinoma (RCC) within the primary tumor upfront can be helpful to guide prognostic counseling and hold implications for both surgical approach and multimodal therapeutic strategies. Herein, the investigators undertook a comprehensive assessment of radiographic features predictive of pT3a stage by querying 11 radiological findings across a robust retrospective cohort of patients with RCC. They found that an irregular tumor-sinus border (ITSB) correlated most strongly with pT3a stage and recurrence-free survival (RFS).","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"19 4 1","pages":"103"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42572032","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":"Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial.","authors":"Susan Halabi, Qian Yang, Andrea Carmack, Shiqi Zhang, Wen-Chi Foo, Tim Eisen, Walter M Stadler, Robert J Jones, Jorge A Garcia, Ulka N Vaishampayan, Joel Picus, Robert E Hawkins, John D Hainsworth, Christian K Kollmannsberger, Theodore F Logan, Igor Puzanov, Lisa M Pickering, Christopher W Ryan, Andrew Protheroe, Daniel J George, Andrew J Armstrong","doi":"10.52733/kcj19n3-a1","DOIUrl":"10.52733/kcj19n3-a1","url":null,"abstract":"<p><p>Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.</p>","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"19 3","pages":"64-72"},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580377/pdf/nihms-1748706.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39720785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Cell Carcinoma Associated with Germline Mutations in the Krebs Cycle","authors":"Eric Lu, B. Shuch, A. Drakaki","doi":"10.52733/kcj19n2-a2","DOIUrl":"https://doi.org/10.52733/kcj19n2-a2","url":null,"abstract":"Germline mutations in the fumarate hydratase (FH) and succinate dehydrogenase (SDH) genes lead to hereditary leiomyomatosis and RCC (HLRCC) and hereditary paraganglioma and pheochromocytoma, respectively. The renal cell carcinomas that arise in these conditions are characterized by dysregulated Krebs cycles, accumulation of oncometabolites, downstream changes in gene expression, and epigenetic modifications that carry unique therapeutic implications. In this review, we evaluate the current literature on these tumors, including the epidemiology, clinical course, screening guidelines, and management of localized and metastatic disease.","PeriodicalId":74040,"journal":{"name":"Kidney cancer journal : official journal of the Kidney Cancer Association","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84200613","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}