The most debated topic on renal cell carcinoma 9 (RCC) during the EAU 2022 in Amsterdam was 10 the 30 month follow-up update of the Keynote-564 11 trial. In this trial patients with intermediate and high 12 risk for recurrence after nephrectomy with curative 13 intent, and with no evidence of disease at the time of 14 inclusion were randomized between adjuvant treat15 ment with pembroluzimab for 1 year or placebo. 16 A small group of patients with M1 disease who 17 underwent metastasectomy were also included. In 18 the intermediate risk (pT2 with Grade 4 or sarco19 matoid differentiation, N0, M0; pT3, any grade, N0, 20 M0), the high risk (T4, any grade, N0, M0; any pT, 21 any grade, N+, M0) and M1 (no evidence of dis22 ease after surgery) groups disease-free survival was 23 better with pembrolizumab compared with placebo 24 (HR 0·63 [95% CI 0·50–0·80]). Although the median 25 disease-free survival was not reached in any of the 26 groups, the estimated number of participants alive 27 and disease free after 30 months was 75·2% (95% CI 28 70·8–79·1) in the pembrolizumab group and 65·5% 29 (60·9–69·7) in the placebo group [1]. 30 Despite these positive findings the study was much 31 debated during several highlight sessio s. The sur32 vival benefit for the intermediate risk group is less 33 compared to the high risk and M1 groups. This 34 was especially true for those patients with a moder35
在阿姆斯特丹EAU 2022期间，关于肾细胞癌(RCC)最具争议的话题是Keynote-564试验的30个月随访更新。在这项试验中，具有治疗目的的肾切除术后复发中高风险且在纳入试验时无疾病证据的患者被随机分为pembroluzimab辅助治疗1年或安慰剂组。还有一小部分M1患者接受了转移瘤切除术。18例中危患者(pT2伴4级或肉瘤样分化，N0, M0;pT3，任意分级，N0, 20m0)，高风险(T4，任意分级，N0, M0;任何pT组、任何分级组、N+组、M0组和M1组(手术后无疾病缓解的证据)，派姆单抗组的无病生存率优于安慰剂组(HR 0.63 [95% CI 0.50 - 0.80])。虽然26组中的任何一组均未达到中位无病生存期，但在30个月后，派姆单抗组的存活和无病存活的估计人数为75.2% (95% CI 2870.8 - 70.1)，安慰剂组的存活和无病存活的估计人数为65.5%(60.9 - 60.7)。尽管有这些积极的发现，但在几次重点会议上，这项研究仍存在很多争议。与高风险和M1组相比，中等风险组的生存获益更少。对于那些患有中度糖尿病的患者尤其如此
{"title":"EAU 2022 Highlights on Renal Cell Carcinoma","authors":"T. V. van Oostenbrugge, P. Mulders","doi":"10.3233/kca-220013","DOIUrl":"https://doi.org/10.3233/kca-220013","url":null,"abstract":"The most debated topic on renal cell carcinoma 9 (RCC) during the EAU 2022 in Amsterdam was 10 the 30 month follow-up update of the Keynote-564 11 trial. In this trial patients with intermediate and high 12 risk for recurrence after nephrectomy with curative 13 intent, and with no evidence of disease at the time of 14 inclusion were randomized between adjuvant treat15 ment with pembroluzimab for 1 year or placebo. 16 A small group of patients with M1 disease who 17 underwent metastasectomy were also included. In 18 the intermediate risk (pT2 with Grade 4 or sarco19 matoid differentiation, N0, M0; pT3, any grade, N0, 20 M0), the high risk (T4, any grade, N0, M0; any pT, 21 any grade, N+, M0) and M1 (no evidence of dis22 ease after surgery) groups disease-free survival was 23 better with pembrolizumab compared with placebo 24 (HR 0·63 [95% CI 0·50–0·80]). Although the median 25 disease-free survival was not reached in any of the 26 groups, the estimated number of participants alive 27 and disease free after 30 months was 75·2% (95% CI 28 70·8–79·1) in the pembrolizumab group and 65·5% 29 (60·9–69·7) in the placebo group [1]. 30 Despite these positive findings the study was much 31 debated during several highlight sessio s. The sur32 vival benefit for the intermediate risk group is less 33 compared to the high risk and M1 groups. This 34 was especially true for those patients with a moder35","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45511503","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}
Renal cell carcinoma (RCC) has long been found to be responsive to immunotherapy. While high dose interleukin-2 resulted in some durable remissions, this treatment has largely been replaced by immune checkpoint inhibitor therapy, due to the safer toxicity profile and emerging evidence for long term remissions. However, the majority of patients continue to face disease progression and death from metastatic RCC. Chimeric antigen receptor T-cells (CAR T) represent the next step in immunotherapy for this malignancy and hold promise for a higher rate of durable remissions. The realization of this therapeutic strategy for RCC will require identification of the best tumor antigen and T cell modifications and will depend on achieving remissions with an acceptable toxicity profile. This review summarizes current CAR T-cell treatment targets and clinical trials for metastatic RCC, highlighting the potential therapeutic impact as well as obstacles to successful development.
{"title":"Chimeric Antigen Receptor (CAR) T-cell Treatment in Renal Cell Carcinoma: Current clinical trials and future directions","authors":"Y. Lyou, T. Dorff","doi":"10.3233/kca-220001","DOIUrl":"https://doi.org/10.3233/kca-220001","url":null,"abstract":"Renal cell carcinoma (RCC) has long been found to be responsive to immunotherapy. While high dose interleukin-2 resulted in some durable remissions, this treatment has largely been replaced by immune checkpoint inhibitor therapy, due to the safer toxicity profile and emerging evidence for long term remissions. However, the majority of patients continue to face disease progression and death from metastatic RCC. Chimeric antigen receptor T-cells (CAR T) represent the next step in immunotherapy for this malignancy and hold promise for a higher rate of durable remissions. The realization of this therapeutic strategy for RCC will require identification of the best tumor antigen and T cell modifications and will depend on achieving remissions with an acceptable toxicity profile. This review summarizes current CAR T-cell treatment targets and clinical trials for metastatic RCC, highlighting the potential therapeutic impact as well as obstacles to successful development.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42512528","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}
J. S. Maurits, Loes F. M. van der Zanden, M. Diekstra, V. Ambert, D. Castellano, J. García-Donas, R. G. Troyas, H. Guchelaar, U. Jaehde, K. Junker, A. Martínez-Cardús, M. Radu, C. Rodríguez‐Antona, M. Roessler, A. Warren, T. Eisen, E. Oosterwijk, L. Kiemeney, S. Vermeulen
BACKGROUND: Application of the MSKCC and IMDC models is recommended for prognostication in metastatic renal cell cancer (mRCC). Patient classification in MSKCC and IMDC risk groups in real-world observational studies is often hampered by missing data on required pre-treatment characteristics. OBJECTIVE: To evaluate the effect of application of easy-to-use logical, or deductive, imputation on MSKCC and IMDC risk classification in an observational study setting. PATIENTS AND METHODS: We used data on 713 mRCC patients with first-line sunitinib treatment from our observational European multi-centre study EuroTARGET. Pre-treatment characteristics and follow-up were derived from medical files. Hospital-specific cut-off values for laboratory measurements were requested. The effect of logical imputation of missing data and consensus versus hospital-specific cut-off values on patient classification and the subsequent models’ predictive performance for progression-free and overall survival (OS) was evaluated. RESULTS: 45% of the patients had missing data for≥1 pre-treatment characteristic for either model. Still, 72% of all patients could be unambiguously classified using logical imputation. Use of consensus instead of hospital-specific cut-offs led to a shift in risk group for 12% and 7% of patients for the MSKCC and IMDC model, respectively. Using logical imputation or other cut-offs did not influence the models’ predictive performance. These were in line with previous reports (c-statistic ∼0.64 for OS) CONCLUSIONS: Logical imputation leads to a substantial increase in the proportion of patients that can be correctly classified into poor and intermediate MSKCC and IMDC risk groups in observational studies and its use in the field should be advocated.
{"title":"Logical Imputation to Optimize Prognostic Risk Classification in Metastatic Renal Cell Cancer","authors":"J. S. Maurits, Loes F. M. van der Zanden, M. Diekstra, V. Ambert, D. Castellano, J. García-Donas, R. G. Troyas, H. Guchelaar, U. Jaehde, K. Junker, A. Martínez-Cardús, M. Radu, C. Rodríguez‐Antona, M. Roessler, A. Warren, T. Eisen, E. Oosterwijk, L. Kiemeney, S. Vermeulen","doi":"10.3233/kca-220007","DOIUrl":"https://doi.org/10.3233/kca-220007","url":null,"abstract":"BACKGROUND: Application of the MSKCC and IMDC models is recommended for prognostication in metastatic renal cell cancer (mRCC). Patient classification in MSKCC and IMDC risk groups in real-world observational studies is often hampered by missing data on required pre-treatment characteristics. OBJECTIVE: To evaluate the effect of application of easy-to-use logical, or deductive, imputation on MSKCC and IMDC risk classification in an observational study setting. PATIENTS AND METHODS: We used data on 713 mRCC patients with first-line sunitinib treatment from our observational European multi-centre study EuroTARGET. Pre-treatment characteristics and follow-up were derived from medical files. Hospital-specific cut-off values for laboratory measurements were requested. The effect of logical imputation of missing data and consensus versus hospital-specific cut-off values on patient classification and the subsequent models’ predictive performance for progression-free and overall survival (OS) was evaluated. RESULTS: 45% of the patients had missing data for≥1 pre-treatment characteristic for either model. Still, 72% of all patients could be unambiguously classified using logical imputation. Use of consensus instead of hospital-specific cut-offs led to a shift in risk group for 12% and 7% of patients for the MSKCC and IMDC model, respectively. Using logical imputation or other cut-offs did not influence the models’ predictive performance. These were in line with previous reports (c-statistic ∼0.64 for OS) CONCLUSIONS: Logical imputation leads to a substantial increase in the proportion of patients that can be correctly classified into poor and intermediate MSKCC and IMDC risk groups in observational studies and its use in the field should be advocated.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49512797","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}
Disparities in cancer screening, prevention, therapy, clinical outcomes, and research are increasingly recognized and pervade all malignancies. In response, several cancer research and clinical care organizations have issued policy statements to acknowledge and address barriers to achieving health equity in cancer care. The increasingly specialized nature of oncology warrants a disease-focused appraisal of existing disparities and potential solutions. Although clear improvements in clinical outcomes have been recently observed for patients with renal cell carcinoma (RCC), these improvements have not been equally shared across diverse populations. This review describes existing RCC cancer disparities and their potential contributing factors and discusses opportunities to improve health equity in clinical research for all patients with RCC.
{"title":"Disparities in Clinical Care and Research in Renal Cell Carcinoma","authors":"Debanjan Pain, Samuel U. Takvorian, V. Narayan","doi":"10.3233/kca-220006","DOIUrl":"https://doi.org/10.3233/kca-220006","url":null,"abstract":"Disparities in cancer screening, prevention, therapy, clinical outcomes, and research are increasingly recognized and pervade all malignancies. In response, several cancer research and clinical care organizations have issued policy statements to acknowledge and address barriers to achieving health equity in cancer care. The increasingly specialized nature of oncology warrants a disease-focused appraisal of existing disparities and potential solutions. Although clear improvements in clinical outcomes have been recently observed for patients with renal cell carcinoma (RCC), these improvements have not been equally shared across diverse populations. This review describes existing RCC cancer disparities and their potential contributing factors and discusses opportunities to improve health equity in clinical research for all patients with RCC.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45523126","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}
V. Gonçalves, F. Monteiro, Antonia Angeli Gazola, Felipe Pizzolo, Júlia Elisa Hübner, R. Pellegrini, Alessandra Borba, A. Fay
BACKGROUND: Immune checkpoint inhibitors (ICI) have shown clinical benefit among patients with advanced kidney cancer. Their cost burden hardens its access, especially in low- and middle-income countries. To set solutions, the impact of geographical and socioeconomic differences in the clinical outcomes and survival of renal cell carcinoma (RCC) patients needs to be explored. OBJECTIVE: This review aimed to understand if geographical differences affected the clinical outcomes of RCC patients receiving immunotherapy. METHODS: This study reviewed 45 studies that examined the OS and PFS of RCC patients undergoing ICI (2010–2020) selected from a 3028-study database search conducted on PubMed and grey literature. The selected studies were divided into groups: Asia, multicentric studies, Europe and Anglo-America. The lethality and income of the geographical locations were measured and discussed. RESULTS: Weighted average (WAVG) of mPFS and mOS were 8,47 months, and 40,6 months in Asia. The WAVG of mOS were 12.2 months, and 20.22 months in the Anglo-American population (15 studies; 943 patients). In multicentric studies (4 studies; 1834 patients) the WAVG mPFS was 10,06. European group (13 studies; 3143 patients) had 6.1 and 20.24 months mPFS and mOS, respectively. The exploratory analysis on income and RCC lethality has shown an absolute decline of 8.7% (CI 10.1 to 7.3% - p < 0.05) in RCC lethality, when income is raised by 100% . CONCLUSION: Clinical benefit from ICI varies across the globe. A wide access to ICI, and evaluation of biological aspects of the disease will allow a better understanding of the impact of geographic regions in the clinical outcome of patients receiving ICI and the etiology of potential differences.
{"title":"Geographical Differences in Kidney Cancer Outcomes of Patients Treated with Immunotherapy: A Systematic Review","authors":"V. Gonçalves, F. Monteiro, Antonia Angeli Gazola, Felipe Pizzolo, Júlia Elisa Hübner, R. Pellegrini, Alessandra Borba, A. Fay","doi":"10.3233/kca-210124","DOIUrl":"https://doi.org/10.3233/kca-210124","url":null,"abstract":"BACKGROUND: Immune checkpoint inhibitors (ICI) have shown clinical benefit among patients with advanced kidney cancer. Their cost burden hardens its access, especially in low- and middle-income countries. To set solutions, the impact of geographical and socioeconomic differences in the clinical outcomes and survival of renal cell carcinoma (RCC) patients needs to be explored. OBJECTIVE: This review aimed to understand if geographical differences affected the clinical outcomes of RCC patients receiving immunotherapy. METHODS: This study reviewed 45 studies that examined the OS and PFS of RCC patients undergoing ICI (2010–2020) selected from a 3028-study database search conducted on PubMed and grey literature. The selected studies were divided into groups: Asia, multicentric studies, Europe and Anglo-America. The lethality and income of the geographical locations were measured and discussed. RESULTS: Weighted average (WAVG) of mPFS and mOS were 8,47 months, and 40,6 months in Asia. The WAVG of mOS were 12.2 months, and 20.22 months in the Anglo-American population (15 studies; 943 patients). In multicentric studies (4 studies; 1834 patients) the WAVG mPFS was 10,06. European group (13 studies; 3143 patients) had 6.1 and 20.24 months mPFS and mOS, respectively. The exploratory analysis on income and RCC lethality has shown an absolute decline of 8.7% (CI 10.1 to 7.3% - p < 0.05) in RCC lethality, when income is raised by 100% . CONCLUSION: Clinical benefit from ICI varies across the globe. A wide access to ICI, and evaluation of biological aspects of the disease will allow a better understanding of the impact of geographic regions in the clinical outcome of patients receiving ICI and the etiology of potential differences.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47879169","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}
Upfront cytoreductive nephrectomy (CN) was the standard treatment for selected patients with metastatic Renal Cell Carcinoma (RCC) in the cytokine era for many years. In the recent ‘targeted therapy era’ it has been re-challenged by both the CARMENA and SURTIME trials. As first-line therapy for treatment-naive metastatic clear-cell RCC has now changed to immune checkpoint inhibitor combination therapy (ICI), and previous studies concerning CN were built in the targeted therapy era, the role and sequence of CN needs to be revisited. Here we address what we learned from both trials and how future trials should be designed to investigate CN.
{"title":"What we have learnt from CARMENA and SURTIME and what should be done differently in future trials on cytoreductive nephrectomy","authors":"P. Zondervan, A. Bex","doi":"10.3233/kca-220004","DOIUrl":"https://doi.org/10.3233/kca-220004","url":null,"abstract":"Upfront cytoreductive nephrectomy (CN) was the standard treatment for selected patients with metastatic Renal Cell Carcinoma (RCC) in the cytokine era for many years. In the recent ‘targeted therapy era’ it has been re-challenged by both the CARMENA and SURTIME trials. As first-line therapy for treatment-naive metastatic clear-cell RCC has now changed to immune checkpoint inhibitor combination therapy (ICI), and previous studies concerning CN were built in the targeted therapy era, the role and sequence of CN needs to be revisited. Here we address what we learned from both trials and how future trials should be designed to investigate CN.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43612034","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: Predictive immune signatures such as the T-effector, the 26-gene “Renal 101 Immuno signature” and the 18-gene T-cell inflamed gene expression profile were developed in clinical trials enrolling predominantly Caucasians and there is a dearth of literature comparing tumor biology between African American (AA) and Caucasian patients. OBJECTIVE: To compare the immune gene signature expression in AA (n = 55) and Caucasian (n = 457) patients. METHODS: Raw gene expression count data were downloaded from the TCGA KIRC dataset and tumor samples from “white” and “black or AA” patients were selected. The gene expression values of the immune signatures were VST-transformed normalized counts and compared between the groups. RESULTS: There were 457 Caucasian and 55 AA patients in the TCGA. The immune gene expression in all three signatures was significantly lower in AA patients compared to Caucasians (p < 0.05). We validated our findings in an independent dataset using Nanostring Immune Profile Panel. Since the majority of AA tumors in TCGA were stage I (71%), we compared gene expression between stage I AA tumors (n = 39) with stage I Caucasian tumors (n = 220). Once again, the immune gene expression was significantly lower in AA patients compared to Caucasians (p < 0.05), indicating differences in tumor biology between the races. CONCLUSIONS: Low expression of predictive immune gene signatures in AA compared to Caucasian patients indicates a possible difference in the biology of their tumors. Future studies are needed to validate our findings in other datasets and to study the predictive role of these signatures in AA patients.
{"title":"Immune Gene Signature Expression Differs between African American and Caucasian Patients with Renal Cell Carcinoma","authors":"P. Ghatalia, Aangi J Shah, M. Slifker","doi":"10.3233/kca-220003","DOIUrl":"https://doi.org/10.3233/kca-220003","url":null,"abstract":"BACKGROUND: Predictive immune signatures such as the T-effector, the 26-gene “Renal 101 Immuno signature” and the 18-gene T-cell inflamed gene expression profile were developed in clinical trials enrolling predominantly Caucasians and there is a dearth of literature comparing tumor biology between African American (AA) and Caucasian patients. OBJECTIVE: To compare the immune gene signature expression in AA (n = 55) and Caucasian (n = 457) patients. METHODS: Raw gene expression count data were downloaded from the TCGA KIRC dataset and tumor samples from “white” and “black or AA” patients were selected. The gene expression values of the immune signatures were VST-transformed normalized counts and compared between the groups. RESULTS: There were 457 Caucasian and 55 AA patients in the TCGA. The immune gene expression in all three signatures was significantly lower in AA patients compared to Caucasians (p < 0.05). We validated our findings in an independent dataset using Nanostring Immune Profile Panel. Since the majority of AA tumors in TCGA were stage I (71%), we compared gene expression between stage I AA tumors (n = 39) with stage I Caucasian tumors (n = 220). Once again, the immune gene expression was significantly lower in AA patients compared to Caucasians (p < 0.05), indicating differences in tumor biology between the races. CONCLUSIONS: Low expression of predictive immune gene signatures in AA compared to Caucasian patients indicates a possible difference in the biology of their tumors. Future studies are needed to validate our findings in other datasets and to study the predictive role of these signatures in AA patients.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43950704","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. Beserra, Ethiene C. Estevan, S. Bezerra, G. Torrezan, A. Ikegami, H. Dellê, I. Cunha, Isabella T. Meira, D. Carraro, P. Lara, S. Zequi, V. Martins, T. G. Santos
BACKGROUND: Patient-derived xenografts (PDX) have emerged as one of the most promising model systems to study cancer biology and to develop new antineoplastic drugs. Renal cell carcinoma (RCC) represents up to 90% of all kidney tumors, exhibits aggressive behavior, and has a propensity for metastasis. At diagnosis, 30% of patients with RCC have metastases, while up to 50% of those with localized disease treated with curative protocols experience recurrence. OBJECTIVE: This study aimed to establish an RCC PDX platform to identify novel clinical and molecular biomarkers of recurrence risk in order to facilitate precision medicine. METHODS: Tumor samples were obtained from surgical specimens of 87 RCC patients; fragments were implanted in immunodeficient NOD/SCID/gamma (NSG) mice. Seventeen fragments were implanted subcutaneously in an initial group while a second group of 70 samples were implanted orthotopically in the subcapsular space. RESULTS: A total of 19 PDX developed only after orthotopic implantation, and included 15 cases of clear cell RCC subtype, 3 cases of papillary subtype, and one unclassifiable tumor. One PDX of clear cell RCC recapitulated the phenotype of vena caval tumor thrombus extension that had been diagnosed in the source patient. PDX characterization by immunohistochemistry and targeted sequencing indicated that all PDXs preserved RCC identity and major molecular alterations. Moreover, the capacity of tumor engraftment was a strong prognostic indicator for patients with locally advanced disease. CONCLUSION: Taken together, these results suggest that the orthotopic xenograft model of RCC represents a suitable tool to study RCC biology, identify biomarkers, and to test therapeutic candidates.
{"title":"Patient-Derived Renal Cell Carcinoma Xenografts Capture Tumor Genetic Profiles and Aggressive Behaviors","authors":"A. Beserra, Ethiene C. Estevan, S. Bezerra, G. Torrezan, A. Ikegami, H. Dellê, I. Cunha, Isabella T. Meira, D. Carraro, P. Lara, S. Zequi, V. Martins, T. G. Santos","doi":"10.3233/kca-210011","DOIUrl":"https://doi.org/10.3233/kca-210011","url":null,"abstract":"BACKGROUND: Patient-derived xenografts (PDX) have emerged as one of the most promising model systems to study cancer biology and to develop new antineoplastic drugs. Renal cell carcinoma (RCC) represents up to 90% of all kidney tumors, exhibits aggressive behavior, and has a propensity for metastasis. At diagnosis, 30% of patients with RCC have metastases, while up to 50% of those with localized disease treated with curative protocols experience recurrence. OBJECTIVE: This study aimed to establish an RCC PDX platform to identify novel clinical and molecular biomarkers of recurrence risk in order to facilitate precision medicine. METHODS: Tumor samples were obtained from surgical specimens of 87 RCC patients; fragments were implanted in immunodeficient NOD/SCID/gamma (NSG) mice. Seventeen fragments were implanted subcutaneously in an initial group while a second group of 70 samples were implanted orthotopically in the subcapsular space. RESULTS: A total of 19 PDX developed only after orthotopic implantation, and included 15 cases of clear cell RCC subtype, 3 cases of papillary subtype, and one unclassifiable tumor. One PDX of clear cell RCC recapitulated the phenotype of vena caval tumor thrombus extension that had been diagnosed in the source patient. PDX characterization by immunohistochemistry and targeted sequencing indicated that all PDXs preserved RCC identity and major molecular alterations. Moreover, the capacity of tumor engraftment was a strong prognostic indicator for patients with locally advanced disease. CONCLUSION: Taken together, these results suggest that the orthotopic xenograft model of RCC represents a suitable tool to study RCC biology, identify biomarkers, and to test therapeutic candidates.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42014202","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}
The Clinical Trials Corner of Kidney Cancer highlights planned or ongoing high-impact studies in renal cell carcinoma (RCC). In this issue, we highlight the NORDIC-SUN trial evaluating the role of deferring cytoreductive nephrectomy and will contrast this trial to a previously mentioned SWOG PROBE trial. In the future, if you feel that you would like to draw attention to a specifi c trial, please feel free to email us Evaluating the Impact of Surgery or No Surgery. NORDIC-SUN-Trial.
{"title":"Clinical Trials Corner: Nephrectomy in the New Year","authors":"M. Parikh","doi":"10.3233/kca-229001","DOIUrl":"https://doi.org/10.3233/kca-229001","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 the NORDIC-SUN trial evaluating the role of deferring cytoreductive nephrectomy and will contrast this trial to a previously mentioned SWOG PROBE trial. In the future, if you feel that you would like to draw attention to a specifi c trial, please feel free to email us Evaluating the Impact of Surgery or No Surgery. NORDIC-SUN-Trial.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42532951","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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