Kidney Cancer最新文献

{"title":"First-Line Immune-Oncology Combinations for Metastatic Clear Cell Renal Cell Carcinoma (mRCC): A Systematic Review of Phase III Clinical Trials","authors":"A. Hahn, A. Shah, M. Campbell","doi":"10.3233/kca-210123","DOIUrl":"https://doi.org/10.3233/kca-210123","url":null,"abstract":"BACKGROUND: The introduction of immune checkpoint inhibitors rapidly changed treatment for patients with metastatic clear cell renal cell carcinoma (mRCC). First-line treatment now includes multiple immuno-oncology (IO) combinations that were approved over a short time period and were not directly compared in randomized clinical trials. Thus, clinicians face a challenge in individualizing first-line treatment to optimize clinical outcomes. OBJECTIVE: We sought to systematically review clinical outcomes for first-line IO combinations for patients with mRCC. METHODS: Literature reporting outcomes from phase III clinical trials that evaluated first-line IO combination therapies was identified through a search of the PubMed electronic database following PRISMA guidelines. Abstracts were screened to identify manuscripts that fit the search criteria, and then, a descriptive review was performed. RESULTS: Our literature search identified 2,229 abstracts that met the initial search criteria, and then, it was narrowed to 431 abstracts using filters for “clinical trial” and a “ten year” time window. After review of the abstracts, six manuscripts were selected for data extraction and subsequent review. CONCLUSION: When compared to sunitinib, four IO combinations improved overall survival as first-line treatment, and five improved progression free survival for patients with mRCC. These IO combination therapies have unique characteristics, so clinicians should take into account patient and cancer factors to individualize treatment recommendations.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47640585","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":"Bim Expression in Peritumoral Lymphocytes is Associated with Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma","authors":"B. Bhindi, E. Bearrick, J. Cheville, C. Lohse, R. Mason, Paras H Shah, S. Harrington, Henan Zhang, Haidong Dong, S. Boorjian, R. Thompson, B. Leibovich","doi":"10.3233/kca-210116","DOIUrl":"https://doi.org/10.3233/kca-210116","url":null,"abstract":"BACKGROUND: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. OBJECTIVE: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS: Immunohistochemistry staining for Bim was performed on paraffin-embedded tumor tissue blocks from patients with metastatic ccRCC who underwent nephrectomy between 1990-2004. Associations of Bim expression with cancer-specific survival (CSS) and overall survival (OS) from date of metastasis were evaluated using multivariable Cox regression models, adjusting for age, sex, and metastases-score. RESULTS: 525 patients with metastatic ccRCC, of whom 169 (32%) had metastases at time of nephrectomy were studied. After multivariable adjustment, high Bim expression remained associated with worse CSS (HR = 1.31; 95% CI 1.07–1.59; p = 0.008) and OS (HR = 1.28; 95% CI 1.06–1.55; p = 0.01). The interaction between Bim and PD-L1 was not statistically significant for CSS (p = 0.68) or OS (p = 0.57), suggesting that the associations between Bim and survival outcomes were not significantly different based on tumor PD-L1 expression. CONCLUSION: High Bim expression in PTLs at nephrectomy is prognostic of worse CSS and OS in patients with metastatic ccRCC, irrespective of tumor PD-L1 expression. The role of earlier PD-1/PD-L1-directed therapy warrants evaluation in these patients.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-210116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48049220","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":"Renal Cancer Without Primary Cancer in the Kidney: Extra-Renal TFE3 Translocation Associated Renal Cell Carcinoma","authors":"Benjamin Petrinec, B. Vargas, Lara R. Harik, V. Master","doi":"10.3233/KCA-200102","DOIUrl":"https://doi.org/10.3233/KCA-200102","url":null,"abstract":"We report a case of an isolated para-aortic retroperitoneal renal cell carcinoma (RCC) in the absence of a primary cancer in the kidney. Single case reports in the literature have described extra-renal RCC in different locations with no evidence of primary renal tumor. We present the initial presentation, diagnostic imaging, surgical treatment, and pathologic evaluation. Immunohistochemistry demonstrated positivity for TFE3 and TFEB, both of which are Microphthalmia associated transcription factors (MiT) associated with translocation RCCs. We hypothesize these few cases of extra-renal RCC represent rare forms of translocation RCC.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-200102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41995107","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":"Active Surveillance of Small Renal Masses: A Systematic Review","authors":"Elizabeth E. Ellis, E. Messing","doi":"10.3233/kca-210114","DOIUrl":"https://doi.org/10.3233/kca-210114","url":null,"abstract":"BACKGROUND: Our goal is to review current literature regarding active surveillance (AS) of small renal masses (SRMs) and identify trends in survival outcomes, factors that predict the need for further intervention, and quality of life (QOL). METHODS: We performed a comprehensive literature search in PubMed and EMBASE and identified 194 articles. A narrative summary was performed in lieu of a meta-analysis due to the heterogeneity of selected studies. RESULTS: Seventeen articles were chosen to be featured in this review. Growth rate (GR) was not an accurate predictor of malignancy, although it was the characteristic most commonly used to trigger delayed intervention (DI). The mean 5-year overall survival (OS) of all studies was 73.6% ±1.7% for AS groups. The combined cancer specific survival (CSS) for AS is 97.1% ±0.6%, compared to 98.6% ±0.4% for the primary intervention (PI) groups, (p = 0.038). CONCLUSIONS: Short and intermediate-term data demonstrate that AS with the option for DI is a management approach whose efficacy (in terms of CSS) approaches that of PI at 5 years, is cost effective, and prevents overtreatment, especially in patients with significant comorbidities.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-210114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126642","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":"First-Line Immunotherapy Combinations in Advanced Renal Cell Carcinoma: A Rapid Review and Meta-Analysis","authors":"Jason Shpilsky, P. Catalano, D. McDermott","doi":"10.3233/kca-210120","DOIUrl":"https://doi.org/10.3233/kca-210120","url":null,"abstract":"BACKGROUND: Combination or multi-agent therapy including immune checkpoint inhibitors has shifted the landscape of the treatment of advanced/metastatic renal cell carcinoma. There are several approved immune checkpoint inhibitor (ICI) combinations featuring antibodies against programmed cell death protein 1 (PD-1) receptor or its ligand 1 (PD-L1) combined with other immune checkpoint inhibitors, multi-targeted tyrosine kinase inhibitors (TKIs), or other agents active in renal cell carcinoma. OBJECTIVE: This study aims to compile the evidence of available first-line combination therapies compared to sunitinib monotherapy in advanced renal cell carcinoma. METHODS: A systematic literature search was conducted according to the PRISMA statement to identify all randomized Phase III clinical trial data in previously untreated metastatic renal cell carcinoma featuring an immune checkpoint inhibitor combination compared against sunitinib. A two-stage selection process was utilized to determine eligible studies. Of a total of 124 studies and 94 additional abstracts, 6 studies were considered for final analysis. These studies were evaluated for progression free survival (PFS), overall survival (OS), Grade III or higher adverse events (AEs), objective response rate (ORR), and complete response rate (CRR). RESULTS: 6 studies with 5,121 patients met our search criteria. For OS, ICI combination therapy was favored over sunitinib with an estimated combined hazard ratio of 0.74 (0.67–0.81 95% CI). For PFS, ICI combination therapy was favored over sunitinib with an estimated combined hazard ratio of 0.65 (0.52–0.82, 95% CI). The combination of nivolumab and ipilimumab had the longest duration of response and less incidence of grade III or higher adverse events compared to the combination of anti-PD-1/PD-L1 with TKI. The combination of anti-PD-1/PD-L1 with TKI had higher rates of overall response and longer PFS than the combination of nivolumab/ipilimumab. CONCLUSIONS: This meta-analysis supports the recommendation of immune checkpoint inhibitor combination therapy over sunitinib monotherapy for previously untreated advanced renal cell carcinoma by virtue of improved PFS and OS. The choice of which ICI combination therapy to use may be guided by patient-specific characteristics including IMDC risk status, adverse effect profile, and need for early response.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-210120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126799","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 for Metastatic Clear Cell Renal Carcinoma: A Systematic Review","authors":"A. Schmidt, P. Bain, B. McGregor","doi":"10.3233/kca-200103","DOIUrl":"https://doi.org/10.3233/kca-200103","url":null,"abstract":"Background: Treatments for metastatic clear cell renal carcinoma (mccRCC) are evolving with multiple targeted and immune therapy drugs currently approved by regulatory agencies as single agents or in combination. Developing predictive biomarkers to determine which patients derive a differential benefit from a particular treatment is an area of ongoing clinical research. Objective: We sought to systematically evaluate the role of tumour tissue-based biomarkers that assist in selection of therapy for mccRCC. Methods: Literature addressing the role of biomarkers in mccRCC was identified through a search of the electronic databases MEDLINE, Embase, and the Web of Science and a hand search of major conference abstracts (from Jan 2010 –Sep 2020). Abstracts were screened to identify papers meriting full-text review. Studies with a comparison arm were included to assess biomarker relevance. A narrative review of studies was performed. Results: The literature search yielded 6784 potentially relevant articles. 133 articles met criteria for full text review, and 10 articles were identified by scanning bibliographies of relevant studies. A total of 33 articles (involving 13 studies) were selected for data extraction and subsequent review. Conclusions: Predictive biomarkers for immediate use in the clinic are lacking, and embedding their evaluation and validation in future clinical trials is needed to refine practice and patient selection.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-200103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41749177","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":"A Shared Decision-Making Model for Management of Small Renal Masses: Optimizing the Patient Experience","authors":"A. Caruso, K. M. Ardisson, Roshan Ravishankar, S. Malkowicz","doi":"10.3233/KCA-200091","DOIUrl":"https://doi.org/10.3233/KCA-200091","url":null,"abstract":"Background: The finding of a small renal mass (SRM) on radiological imaging and the potential of a cancer diagnosis is anxiety provoking in most patients. The decision-making process often occurs in the absence of any framework regarding the nature and treatment outcomes. This project aimed to educate patients newly diagnosed with a SRM, implement a shared decision-making (SDM) model, and assess the educational attainment and effect on a SDM intervention. Methods: This project assessed the educational attainment and its effect on a SDM intervention using a pre-and post- intervention survey, an educational video [Urology Care Foundation, “What is a renal mass?], and a structured provider discussion. The survey incorporated eight knowledge questions and two questions which addressed anxiety related to diagnosis and confidence in decision-making. Results: Fifty surveys were completed. The post intervention score showed a significant increase in patient knowledge. Wilcoxon signed rank test (P = <0.001; 2.0; CI 95% (1.54–2.46)). Thirty-nine demonstrated improvement in knowledge with a mean of 2.0, 9 were unchanged and 2 decreased. Approximately 42% of patients reported a decrease in anxiety rating by a mean of 40%. When confidence in decision-making improved, it improved by a mean of 45%. Conclusions: A significant improvement in understanding of SRMs was demonstrated. This model showed improved knowledge, alleviation of anxiety and improved confidence and denotes the feasibility of implementing a SDM model in newly diagnosed patients. Results should encourage providers who aspire to incorporate a SDM as a Best Practice.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-200091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48025362","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":"Individualised Predictions of the Survival Benefit Due to Adjuvant Therapy in a Randomised Trial of Sorafenib after Nephrectomy for Localised Renal Cell Carcinoma","authors":"N. Lawrence, A. Martin, I. Davis, S. Troon, S. Sengupta, E. Hovey, X. Coskinas, R. Kaplan, Benjamin Smith, A. Ritchie, A. Meade, J. Goh, H. Gurney, M. Harrison, K. Fife, T. Eisen, P. Blinman, M. Stockler","doi":"10.3233/kca-200104","DOIUrl":"https://doi.org/10.3233/kca-200104","url":null,"abstract":"BACKGROUND: Little has been published regarding how doctors think and talk about prognosis and the potential benefits of adjuvant therapy. OBJECTIVE: We sought predictions of survival rates and survival times, for patients with and without adjuvant therapy, from the clinicians of patients participating in a randomised trial of adjuvant sorafenib after nephrectomy for renal cell carcinoma. METHODS: A subset of medical oncologists and urologists in the SORCE trial completed questionnaires eliciting their predictions of survival rates and survival times, with and without adjuvant sorafenib, for each of their participating patients. To compare predictions elicited as survival times versus survival rates, we transformed survival times to survival rates. To compare predicted benefits elicited as absolute improvements in rates and times, we transformed them into hazard ratios (HR), a measure of relative benefit.We postulated that a plausible benefit in overall survival (OS) should be smaller than that hypothesized for disease–free survival (DFS) in the trials original sample size justification (i.e. HR for OS should be ≥ 0.75). RESULTS: Sixty–one medical oncologists and 17 urologists completed questionnaires on 216 patients between 2007 and 2013. Predictions of survival without adjuvant sorafenib were similar whether elicited as survival rates or survival times (median 5–year survival rate of 61% vs 60%, p = 0.6). Predicted benefits of sorafenib were larger when elicited as improvements in survival rates than survival times (median HR 0.76 vs 0.83, p < 0.0001). The proportion of HR for predicted OS with sorafenib that reflected a plausible benefit (smaller effect of sorafenib on OS than hypothesized on DFS, i.e. HR ≥ 0.75) was 51% for survival rates, and 65% for survival times. CONCLUSIONS: The predicted benefits of adjuvant sorafenib were larger when elicited as improvements in survival rates than as survival times, and were often larger than the sample size justification for the trial. These potential biases should be considered when thinking and talking about individual patients in clinical practice, and when designing clinical trials.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-200104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49149755","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":"Comparing the Responses of Osseous Versus Soft-Tissue Metastases of Renal Cell Carcinoma to Receptor Tyrosine Kinase Inhibitors and Immunotherapy","authors":"K. Tai, J. M. Abiad, C. Morris, M. Markowski, A. Levin","doi":"10.3233/kca-200094","DOIUrl":"https://doi.org/10.3233/kca-200094","url":null,"abstract":"BACKGROUND: Checkpoint inhibitors and receptor tyrosine kinase inhibitors (RTKIs) have changed the standard of care for metastatic renal cell carcinoma (mRCC). Anecdotal evidence suggests these therapies may be less effective for treating bone than soft-tissue metastases. PURPOSE: We performed a retrospective review evaluating the relative clinical responses in soft-tissue and bone metastases in patients undergoing therapy using RTKIs and anti-programmed death-1 (PD-1) agents for mRCC. METHODS: Of the 2,212 patients in our institutional cancer registry with renal cell carcinoma (1997–2017), 68 (82 disease courses) were identified with measurable bone and soft-tissue metastases treated with RTKIs and/or PD-1s. Extent of metastasis was quantified at the time of therapy initiation (baseline) and at 3 months, 6 months, and 1 year. Changes in disease status were categorized as complete response, partial response, stable, mixed, or progression of disease according to RECIST v1.1 and MD Anderson criteria. These categories were further organized into “response to treatment” or “evidence of progression” to generate a generalized linear effects model with soft-tissue response as the independent variable and bone response as the dependent variable. Alpha = 0.05. RESULTS: Soft-tissue response correlated with bone response at 3 months (76 disease courses, p = 0.005) and 6 months (48 disease courses, p = 0.017). Of the patients with controlled soft-tissue disease, only 14 (19%) and 15 (32%) had progression in bone at 3 and 6 months, respectively. CONCLUSION: Contrary to anecdotal reports, osseous metastases do not appear to respond worse than soft-tissue metastases to treatment with these agents.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2020-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44266266","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":"Clinical Trials Corner: Translating Benefit to the Bone","authors":"M. Parikh","doi":"10.3233/kca-200004","DOIUrl":"https://doi.org/10.3233/kca-200004","url":null,"abstract":"The Clinical Trials Corner of Kidney Cancer highlights planned or ongoing high-impact studies in renal cell carcinoma (RCC). In this issue, we highlight a study focused on RCC patients with osseous metastases to determine if better outcomes in morbidity can be achieved with a novel combined modality approach. Phase trial of combined metastasis","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2020-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-200004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45221947","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}