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Tsai YC, Li JR, Chiu KY, Su PJ, Su YL, Chung HJ, Li CC, Huang CP, Guo JC, Chen CS, Chang I, Perrot V, Chang YH. Real-world study of cabozantinib treatment of advanced renal cell carcinoma in Taiwan. J Formos Med Assoc 2025:S0929-6646(25)00117-2. [PMID: 40221295 DOI: 10.1016/j.jfma.2025.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 09/27/2024] [Accepted: 03/14/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND There is a lack of real-world evidence from Taiwan on the use of cabozantinib for advanced renal cell carcinoma (aRCC). We evaluated cabozantinib treatment for aRCC after previous antiangiogenic therapy in real-world Taiwanese clinical practice. METHODS Medical records from seven Taiwanese hospitals were retrospectively analyzed. Eligible patients were adults with aRCC who initiated cabozantinib between October 2018 and August 2021 after ≥1 antiangiogenic therapy. Patient characteristics and treatment patterns were described. Outcomes included objective response rate (ORR [complete or partial]; primary endpoint) assessed by RECIST v1.1 or local investigator assessment, progression-free survival (PFS), and tolerability. RESULTS Fifty-one patients were included: 39.2 % received cabozantinib second-line, 33.3 % third-line, and 27.5 % fourth- or later-line. Mean patient age was 61.2 years; most were male (80 %), had clear-cell (80 %), metastatic (92 %) disease, and had previous nephrectomy (78 %). Sunitinib and pazopanib were the most common previous (any line) treatments (63 % and 53 % of patients, respectively). Dose reductions occurred in 47 % of patients and were more common in patients (57 %) who initiated cabozantinib at 60 mg/day than in those (33 %) who initiated at 40 mg/day (72 % vs 12 %, respectively); discontinuation rates were similar for these groups (48 % vs 47 %, respectively). Overall, ORR was 39.2 % (95 % CI: 25.8, 53.9) and median PFS was 12.4 months (95 % CI: 8.2, 16.3). Rates of serious treatment-emergent adverse events related to cabozantinib were low (7.8 %). CONCLUSION This Taiwanese study found the real-world effectiveness and tolerability of cabozantinib after previous antiangiogenic therapy to be consistent with the results of the METEOR trial.
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Affiliation(s)
- Yu-Chieh Tsai
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jian-Ri Li
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kun-Yuan Chiu
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Po-Jung Su
- Division of Hematology-Oncology, Chang Gung Memorial Hospital Linkou, Linkou, and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Li Su
- Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Genomic & Proteomic Core Lab, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsiao-Jen Chung
- Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Urology, College of Medicine and Shu-Tien Urological Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Chia Li
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chi-Ping Huang
- Department of Urology, China Medical University and Hospital, Taichung, Taiwan
| | - Jhe-Cyuan Guo
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chuan-Shu Chen
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | | | | | - Yen-Hwa Chang
- Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
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Choueiri TK, Merchan JR, Figlin R, McDermott DF, Arrowsmith E, Michaelson MD, Tykodi SS, Heath EI, Spigel DR, D'Souza A, Kassalow L, Perini RF, Vickery D, Bauer TM. Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study. Lancet Oncol 2025; 26:64-73. [PMID: 39756444 DOI: 10.1016/s1470-2045(24)00649-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/31/2024] [Accepted: 11/04/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumour activity as monotherapy and in combination with cabozantinib in patients with previously treated advanced kidney cancer. The phase 2 LITESPARK-003 study was designed to determine the antitumour activity and safety of belzutifan in combination with cabozantinib in patients with advanced clear-cell renal cell carcinoma that was previously untreated (cohort 1) or previously treated with immunotherapy (cohort 2). Here, we report results from cohort 1 of this clinical trial. METHODS LITESPARK-003 is an open-label, single-arm, phase 2 study at ten hospitals and cancer centres in the USA. In cohort 1, eligible patients were at least 18 years of age, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had received no previous systemic therapy for locally advanced or metastatic renal cell carcinoma. Patients received belzutifan 120 mg orally once daily and cabozantinib 60 mg orally once daily until unacceptable adverse events, disease progression, or patient withdrawal. The primary endpoint was investigator-assessed confirmed objective response according to Response Evaluation Criteria in Solid Tumors version 1.1. Antitumour activity and safety were assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03634540, and is ongoing. FINDINGS Between Sept 27, 2018, and Jan 10, 2023, we screened 138 patients for eligibility, and 50 (36%) were enrolled and assigned to cohort 1. The median age was 64 years (IQR 57-72). 40 (80%) of 50 patients were male and ten (20%) were female. 48 (96%) patients were White, one (2%) patient was Black or African American, and one (2%) was of a race in the other category. As of the data cutoff (May 15, 2023), median follow-up was 24·3 months (IQR 13·9-32·0). 35 (70%, 95% CI 55-82) of 50 patients had a confirmed objective response, including four (8%) who had a complete response and 31 (62%) who had a partial response. The most frequent grade 3-4 treatment-related adverse events were hypertension (six [12%] patients), anaemia (five [10%] patients), and fatigue (four [8%] patients). Seven (14%) of 50 patients had serious treatment-related adverse events. No treatment-related deaths occurred. INTERPRETATION Belzutifan plus cabozantinib has promising antitumour activity in treatment-naive patients with advanced clear-cell renal cell carcinoma and further investigation of an HIF-2α inhibitor in combination with a multitargeted tyrosine kinase inhibitor as a treatment option in this population is warranted. FUNDING Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and the National Cancer Institute.
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Affiliation(s)
- Toni K Choueiri
- Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
| | | | | | | | | | | | - Scott S Tykodi
- University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA
| | | | | | - Anishka D'Souza
- Genitourinary Medical Oncology, University of Southern California, Los Angeles, CA, USA
| | | | | | | | - Todd M Bauer
- Tennessee Oncology/Greco-Hainsworth Centers for Research, Nashville, TN, USA
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Su CH, Chen CY, Liu CT, Yang YH, Wu PC. Hepatitis and Hepatitis B Virus Reactivation in Everolimus-Treated Solid Tumor Patients: A Focus on HBV-Endemic Areas. Cancers (Basel) 2024; 16:3997. [PMID: 39682184 DOI: 10.3390/cancers16233997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/06/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Everolimus is approved for treating breast, renal, and pancreatic neuroendocrine cancers but carries the risk of hepatitis B virus (HBV) reactivation (HBVr) and hepatitis. However, data on HBVr in everolimus-treated patients are limited. This study evaluates the risk of hepatitis and HBVr in cancer patients with current or past HBV infection. METHODS This retrospective study analyzed patients prescribed everolimus between 1 January 2011 and 31 May 2022, using a private healthcare system database in Taiwan. Patients with HBsAg positivity or HBsAg negativity and anti-HBs or anti-HBc results were included. The cumulative incidence function and risk of hepatitis from a competing risk model, which estimates Fine-Gray subdistribution hazard (SDH), were analyzed across different HBV serological subgroups. The risk of hepatitis B reactivation was also calculated. RESULTS Of 377 patients, 45% (36/80) of HBsAg-positive and 0.67% (2/297) of HBsAg-negative patients received nucleos(t)ide analogues (NUCs) prophylaxis. Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients. Baseline HBsAg positivity and exemestane use increased hepatitis risk. HBVr occurred in 11.36% (5/44) of HBsAg-positive patients without NUCs and 5.56% (2/36) with prophylaxis. Two HBsAg-negative, anti-HBc-positive patients developed severe HBVr-related hepatitis. CONCLUSION Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients on everolimus. HBVr was common in HBsAg-positive patients but rare in HBsAg-negative individuals. HBV screening and liver function monitoring are critical for patients with past or current HBV infection receiving everolimus, especially in endemic areas.
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Affiliation(s)
- Chien-Hao Su
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Pharmacy, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Chung-Yu Chen
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chien-Ting Liu
- Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yi-Hsin Yang
- National Institute of Cancer Research, National Health Research Institutes, No. 367, Sheng-Li Rd., North District, Tainan 704, Taiwan
| | - Pao-Chu Wu
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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Chaoul N, Lauricella E, Giglio A, D'Angelo G, Ganini C, Cives M, Porta C. The future of cellular therapy for the treatment of renal cell carcinoma. Expert Opin Biol Ther 2024; 24:1245-1259. [PMID: 39485013 DOI: 10.1080/14712598.2024.2418321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/26/2024] [Accepted: 10/15/2024] [Indexed: 11/03/2024]
Abstract
INTRODUCTION Systemic treatment options for renal cell carcinoma (RCC) have expanded considerably in recent years, and both tyrosine kinase inhibitors and immune checkpoint inhibitors, alone or in combination, have entered the clinical arena. Adoptive cell immunotherapies have recently revolutionized the treatment of cancer and hold the promise to further advance the treatment of RCC. AREAS COVERED In this review, we summarize the latest preclinical and clinical development in the field of adoptive cell immunotherapy for the treatment of RCC, focusing on lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, tumor-infiltrating T cells (TILs), TCR-engineered T cells, chimeric antigen receptor (CAR) T cells, and dendritic cell vaccination strategies. Perspectives on emerging cellular products including CAR NK cells, CAR macrophages, as well as γδ T cells are also included. EXPERT OPINION So far, areas of greater therapeutic success of adoptive cell therapies include the adjuvant administration of CIK cells and the transfer of anti-CD70 CAR T cells in patients with metastatic RCC. Bench to bedside and back research will be needed to overcome current limitations of adoptive cell therapies in RCC, primarily aiming at improving the safety of immune cell products, optimizing their antitumor activity and generating off-the-shelf products ready for clinical use.
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Affiliation(s)
- Nada Chaoul
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Eleonora Lauricella
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Andrea Giglio
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Gabriella D'Angelo
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Carlo Ganini
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Mauro Cives
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Camillo Porta
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
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Jakobsson M, Nilsson F, Strambi A, Arpegård J, Dalén J. First-line sunitinib treatment modification in patients with mRCC: nationwide analysis of the Swedish population. Future Oncol 2024; 20:3087-3097. [PMID: 39466150 DOI: 10.1080/14796694.2024.2401309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 09/03/2024] [Indexed: 10/29/2024] Open
Abstract
Aim: Assess first-line sunitinib dosing for treatment of metastatic renal cell carcinoma in Swedish clinical practice (2006-2019).Materials & methods: Retrospective analysis of three sunitinib dosing regimens: 2-weeks on, 1-week off (2:1 Start); standard 4-weeks on, 2-weeks off (4:2) and 4:2 start with switch to 2:1 (2:1 Switch).Results: Time-to-treatment discontinuation (95% CI) differed significantly (p < 0.001): 6.2 (5.6-7.2), 13.9 (8.1-20.6) and 4.6 (4.3-5.6) months for 2:1 Start (n = 320), 2:1 Switch (n = 71) and 4:2 (n = 704), respectively. Overall survival (95% CI) differed significantly (p < 0.001): 21.8 (18.1-26.1), 32.2 (25.1-48.3) and 13.5 (12.3-15.8) months for 2:1 Start (n = 320), 2:1 Switch (n = 71) and 4:2 (n = 704), respectively.Conclusion: Alternative dosing does not compromise clinical efficacy and may provide advantages in terms of improved treatment outcomes. However, due to the changing treatment patterns during this long-term study, and the absence of patient risk category data, caution is required when interpreting the main outcomes.
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Chen R, Su Q, Li Y, Shen P, Zhang J, Tan Y. Multi-sequence MRI-based radiomics model to preoperatively predict the WHO/ISUP grade of clear Cell Renal Cell Carcinoma: a two-center study. BMC Cancer 2024; 24:1176. [PMID: 39333970 PMCID: PMC11438199 DOI: 10.1186/s12885-024-12930-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
OBJECTIVES To develop radiomics models based on multi-sequence MRI from two centers for the preoperative prediction of the WHO/ISUP grade of Clear Cell Renal Cell Carcinoma (ccRCC). METHODS This retrospective study included 334 ccRCC patients from two centers. Significant clinical factors were identified through univariate and multivariate analyses. MRI sequences included Dynamic contrast-enhanced MRI, axial fat-suppressed T2-weighted imaging, diffusion-weighted imaging, and in-phase/out-of-phase images. Feature selection methods and logistic regression (LR) were used to construct clinical and radiomics models, and a combined model was developed using the Rad-score and significant clinical factors. Additionally, seven classifiers were used to construct the combined model and different folds LR was used to construct the combined model to evaluate its performance. Models were evaluated using receiver operating characteristic (ROC) curves, area under the curve (AUC), and decision curve analysis (DCA). The Delong test compared ROC performance, with p < 0.050 considered significant. RESULTS Multivariate analysis identified intra-tumoral vessels as an independent predictor of high-grade ccRCC. In the external validation set, the radiomics model (AUC = 0.834) outperformed the clinical model (AUC = 0.762), with the combined model achieving the highest AUC (0.855) and significantly outperforming the clinical model (p = 0.003). DCA showed that the combined model had a higher net benefit within the 0.04-0.54 risk threshold range than clinical model. Additionally, the combined model constructed using logistic regression has a higher priority compared to other classifiers. Additionally, 10-fold cross-validation with LR for the combined model showed consistent AUC values (0.849-0.856) across different folds. CONCLUSION The radiomics models based on multi-sequence MRI might be a noninvasive and effective tool, demonstrating good efficacy in preoperatively predicting the WHO/ISUP grade of ccRCC.
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Affiliation(s)
- Ruihong Chen
- Department of Radiology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, Shanxi Province, 030001, P.R. China
- Department of College of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi Province, 030001, P.R. China
| | - Qiaona Su
- Department of Radiology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/ Cancer Hospital Affiliated to Shanxi Medical University, No. 3 Workers' New Street, Taiyuan, Shanxi Province, 030013, P.R. China
- Department of College of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi Province, 030001, P.R. China
| | - Yangyang Li
- Department of Radiology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, Shanxi Province, 030001, P.R. China
- Department of College of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi Province, 030001, P.R. China
| | - Pengxin Shen
- Department of Radiology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, Shanxi Province, 030001, P.R. China
- Department of College of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi Province, 030001, P.R. China
| | - Jianxin Zhang
- Department of Radiology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/ Cancer Hospital Affiliated to Shanxi Medical University, No. 3 Workers' New Street, Taiyuan, Shanxi Province, 030013, P.R. China.
| | - Yan Tan
- Department of Radiology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, Shanxi Province, 030001, P.R. China.
- Department of Shanxi Key Laboratory of Intelligent Imaging and Nanomedicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, P.R. China.
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Anderson AC, Ho J, Hall ET, Hannan R, Liao JJ, Louie AV, Ma TM, Psutka SP, Rengan R, Siva S, Swaminath A, Tachiki L, Tang C, Teh BS, Tsai J, Tykodi SS, Weg E, Zaorsky NG, Lo SS. Focal therapy for oligometastatic and oligoprogressive renal cell carcinoma: a narrative review. Future Oncol 2024; 20:2573-2588. [PMID: 39258792 PMCID: PMC11534104 DOI: 10.1080/14796694.2024.2389769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/05/2024] [Indexed: 09/12/2024] Open
Abstract
Metastatic renal cell carcinoma (RCC) can present with oligometastatic disease and/or develop oligoprogression following systemic therapy. Cytoreductive and focal metastasis-directed therapy options include resection, stereotactic ablative radiation and thermal ablation. Aggressive focal therapy may allow delay in initiation of or modification to systemic therapy and improve clinical outcomes. In this narrative review we synthesize current practice guidelines and prospective data on focal therapy management options and highlight future research. Patient selection and the choice of focal treatment techniques are controversial due to limited and heterogeneous data and patients may benefit from multidisciplinary evaluation. Prospective comparative trials with clearly defined inclusion criteria and relevant end points are needed to clarify the risks and benefits of different approaches.
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Affiliation(s)
- August C Anderson
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
| | - Joel Ho
- Pfizer Inc., Bothell, WA 98011, USA
| | - Evan T Hall
- University of Washington, Division of Hematology & Oncology, Seattle, WA 98195,USA
- Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA 98195, USA
| | - Raquibul Hannan
- The University of Texas Southwestern Medical Center, Radiation Oncology, Dallas, TX 75235, USA
- Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Kidney Cancer Program, Dallas, TX75235, USA
| | - Jay J Liao
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
| | - Alexander V Louie
- Sunnybrook Health Sciences Centre, Department of Radiation Oncology, Toronto, ON, M4N 3M5, Canada
| | - Ting Martin Ma
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
| | - Sarah P Psutka
- Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA 98195, USA
- University of Washington, Department of Urology, Seattle, WA 98195, USA
| | - Ramesh Rengan
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
| | - Shankar Siva
- Peter MacCallum Cancer Centre, Division of Radiation Oncology & Cancer Imaging, Melbourne, VIC, 3052, Australia
- The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC, 3052, Australia
| | - Anand Swaminath
- Juravinski Cancer Centre, Radiation Therapy, Hamilton, ON, L8V 5C2, Canada
- McMaster University, Division of Radiation Oncology, Hamilton, ON,L8S 4L8,Canada
| | - Lisa Tachiki
- University of Washington, Division of Hematology & Oncology, Seattle, WA 98195,USA
- Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA 98195, USA
| | - Chad Tang
- The University of Texas MD Anderson Cancer Center, Genitourinary Radiation Oncology, Houston, TX 77030, USA
- The University of Texas MD Anderson Cancer Center, Investigational Cancer Therapeutics, Houston, TX 77030, USA
- The University of Texas MD Anderson Cancer Center, Translational Molecular Pathology, Houston, TX 77030, USA
| | - Bin Sing Teh
- Houston Methodist Hospital, Radiation Oncology, Houston, TX 77030, USA
| | - Joseph Tsai
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
| | - Scott S Tykodi
- University of Washington, Division of Hematology & Oncology, Seattle, WA 98195,USA
- Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA 98195, USA
| | - Emily Weg
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
| | - Nicholas G Zaorsky
- University Hospitals Seidman Cancer Center, Case Western Reserve University, Department of Radiation Oncology, Cleveland, OH 44106, USA
| | - Simon S Lo
- University of Washington, Department of Radiation Oncology, Seattle, WA 98195, USA
- Fred Hutchinson Cancer Center, Radiation Oncology Division, Seattle, WA 98195, USA
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Xu Z, Wu Y, Chen X, Jin B. Identification of tumor-antigen signatures and immune subtypes for messenger RNA vaccine selection in advanced clear cell renal cell carcinoma. Surgery 2024; 176:785-797. [PMID: 38851900 DOI: 10.1016/j.surg.2024.04.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 04/08/2024] [Accepted: 04/19/2024] [Indexed: 06/10/2024]
Abstract
BACKGROUND Advanced clear cell renal cell carcinoma still lacks reliable diagnostic and prognostic biomarkers. Recently, tumor vaccines targeting specific molecules have been proposed as a promising treatment in mitigating tumor progression, which was rekindled under the background of the COVID-19 pandemic. However, the application of messenger RNA vaccine against advanced clear cell renal cell carcinoma antigens remains stagnant, and no subgroup of patients deemed suitable for vaccination has been extensively studied or validated. Our study aims to explore novel advanced clear cell renal cell carcinoma antigen signatures to select suitable patients for vaccination. METHODS Gene expression profiles of advanced clear cell renal cell carcinoma samples and their corresponding clinical data were retrieved from The Cancer Genome Atlas. The least absolute shrinkage and selection operator model was applied to develop signatures to stratify patients with advanced clear cell renal cell carcinoma. Receiver operating characteristic analysis was used to compare the prognostic accuracy of each factor. Tumor Immune Estimation Resource was used to visualize the relationship between the proportion of antigen-presenting cells and the expression of filtered genes. The "CIBERSORT" and "WGCNA" R Packages were employed to ascertain disparities in immune infiltration levels between advanced clear cell renal cell carcinoma subgroups. The Search Tools for the Retrieval of Interacting Genes database and Cytoscape were used to construct the protein-protein interaction network. CCK-8 and colony formation assays were included in the invitro experiment. RESULTS In total, 244 potential tumor antigens were identified. Using the least absolute shrinkage and selection operator Cox regression, 21 tumor antigens were selected for developing a risk evaluation signature. The risk score signature can be a useful tool to predict the outcome of advanced clear cell renal cell carcinoma patients. According to the differential clinical, molecular, and immune-related genes, we divided advanced clear cell renal cell carcinoma patients into the immune "cold" subtype and immune "hot" subtype. By developing a logistic score, the immune subtype signature can better distinguish a patient more likely to be immune "cold" subtype or immune "hot" subtype. Interestingly, patients with high risk scores had a higher proportion of immune "hot" subtype than those with a low risk score. Furthermore, the prognostic value was significantly improved when combining risk score and immune subtype. Distinct immune landscapes and signal pathways were observed between different tumor subtypes. Finally, novel tumor antigens related to oxidative stress were identified. CONCLUSION The tumor-antigens-based risk score and immune subtype signatures identified potentially effective neo-antigens for advanced clear cell renal cell carcinoma messenger RNA vaccine development, and patients with low risk scores and immune "cold" subtype tumors are more prone to benefit from messenger RNA vaccination. Furthermore, our study highlights the significant role of oxidative stress in determining the efficacy of the messenger RNA vaccine.
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Affiliation(s)
- Zhijie Xu
- Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Engineering Research Center for Bladder Tumor Innovation Diagnosis and Treatment, Hangzhou, China.
| | - Yunfei Wu
- Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Engineering Research Center for Bladder Tumor Innovation Diagnosis and Treatment, Hangzhou, China
| | - Xiaoyi Chen
- Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Engineering Research Center for Bladder Tumor Innovation Diagnosis and Treatment, Hangzhou, China
| | - Baiye Jin
- Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Engineering Research Center for Bladder Tumor Innovation Diagnosis and Treatment, Hangzhou, China
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Bentahila R, Bensalah K, Benziane-Ouaritini N, Barthelemy P, Rioux-Leclerc N, Correas JM, Belhomme S, Bigot P, Sargos P. Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU. THE FRENCH JOURNAL OF UROLOGY 2024; 34:102660. [PMID: 38823486 DOI: 10.1016/j.fjurol.2024.102660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 05/08/2024] [Accepted: 05/26/2024] [Indexed: 06/03/2024]
Abstract
INTRODUCTION The incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. MATERIAL AND METHODS We conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. RESULTS Studies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately -5 to -17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. CONCLUSION Stereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. LEVEL OF EVIDENCE: 5
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Affiliation(s)
- Rita Bentahila
- Department of radiotherapy, Bergonié Institute, Bordeaux, France
| | - Karim Bensalah
- Urology Department, Rennes University Hospital, Rennes, France
| | | | - Philippe Barthelemy
- Medical Oncology Department, Institut de Cancérologie Strasbourg Europe, Strasbourg, France
| | | | | | - Sarah Belhomme
- Department of Medical Physic, Bergonié Institute, Bordeaux, France
| | - Pierre Bigot
- Urology Department, Angers University Hospital, Angers, France
| | - Paul Sargos
- Department of radiotherapy, Bergonié Institute, Bordeaux, France; Amethyst Radiotherapy Group, Paris, France.
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10
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Ushijima Y, Okamoto D, Fujita N, Ishimatsu K, Wada N, Takao S, Murayama R, Itoyama M, Ishigami K. Effect of lipiodol marking before CT-guided cryoablation on the outcome of sporadic renal cell carcinoma. Diagn Interv Radiol 2024; 30:117-123. [PMID: 38164892 PMCID: PMC10916531 DOI: 10.4274/dir.2023.232381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 12/08/2023] [Indexed: 01/03/2024]
Abstract
PURPOSE This retrospective study evaluates the impact of preoperative lipiodol marking on the outcomes of computed tomography (CT)-guided cryoablation for histologically diagnosed sporadic renal cell carcinoma (RCC). METHODS This study analyzed the data of 173 patients who underwent CT-guided cryoablation for histologically proven sporadic RCC at a single institution between April 2014 and December 2020. The local control rate (LCR), recurrence-free survival rate (RFSR), overall survival rate (OSR), changes in renal function, and complications in patients with (n = 85) and without (n = 88) preoperative lipiodol marking were compared. RESULTS The 5-year LCR and 5-year RFSR were significantly higher in patients with lipiodol marking (97.51% and 93.84%, respectively) than in those without (72.38% and 68.10%, respectively) (P value <0.01, log-rank test). There were no significant differences between the two groups regarding the 5-year OSR (97.50% vs. 86.82%) or the deterioration in chronic kidney disease stage (12.70% vs. 16.43%). Grade ≥3 complications occurred in patients with lipiodol marking (n = 2, retroperitoneal hematoma and cerebral infarction in 1 patient each) and without (n = 5; urinary fistula in 2, colonic perforation in 2, urinary infection in 1). CONCLUSION Lipiodol marking before CT-guided cryoablation for sporadic RCC is a feasible approach to improving local control and RFS while mitigating the decline in renal function. Additionally, it may help reduce complications.
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Affiliation(s)
- Yasuhiro Ushijima
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Daisuke Okamoto
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Nobuhiro Fujita
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Keisuke Ishimatsu
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Noriaki Wada
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Seiichiro Takao
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Ryo Murayama
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Masahiro Itoyama
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
| | - Kousei Ishigami
- Kyushu University, Graduate School of Medical Sciences, Department of Clinical Radiology, Fukuoka, Japan
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11
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Tsukamoto S, Aiba H, Zuccheri F, Mavrogenis AF, Kido A, Honoki K, Tanaka Y, Donati DM, Errani C. Reoperation after surgery for bone metastasis of renal cell carcinoma. J Surg Oncol 2024; 129:629-640. [PMID: 37929793 DOI: 10.1002/jso.27501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/29/2023] [Accepted: 10/20/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND AND OBJECTIVE The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC. METHODS We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions. RESULTS Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival. CONCLUSION The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method.
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Affiliation(s)
- Shinji Tsukamoto
- Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
| | - Hisaki Aiba
- Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
- Department of Orthopedic Surgery, Nagoya City University, Nagoya, Japan
| | - Federica Zuccheri
- Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Andreas F Mavrogenis
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Akira Kido
- Department of Rehabilitation Medicine, Nara Medical University, Nara, Japan
| | - Kanya Honoki
- Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
| | - Yasuhito Tanaka
- Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
| | - Davide Maria Donati
- Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Costantino Errani
- Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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12
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Sahoo TP, Desai C, Agarwal S, Rauthan A, Dhabhar B, Biswas G, Batra S, Saha R, Philip A, Agarwal V, Dattatreya PS, Mohapatra PN, Deshmukh C, Bhagat S, Patil S, Barkate H. ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA). BMC Cancer 2023; 23:737. [PMID: 37558975 PMCID: PMC10413514 DOI: 10.1186/s12885-023-11237-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 07/29/2023] [Indexed: 08/11/2023] Open
Abstract
In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.
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Affiliation(s)
| | - Chirag Desai
- Medical Oncology & Director Hemato-Oncology Clinic Vedanta, Ahmedabad, Ahmedabad, India
| | - Shyam Agarwal
- Medical Oncology, Sir Gangaram Hospital, Delhi, India
| | - Amit Rauthan
- Medical Oncology, Manipal Hospital, Bangalore, India
| | - Boman Dhabhar
- Medical & Hemat-Oncology, BND Onco Center, Mumbai, India
| | | | - Sandeep Batra
- Medical Oncology, Max Superspeciality Hospital, Saket, New Delhi, India
| | - Rajat Saha
- Medical Oncology, Max Superspeciality Hospital, Saket, New Delhi, India
| | - Arun Philip
- Medical Oncology Amrita Institute of Medical Sciences, Cochin, India
| | - Vijay Agarwal
- Medical Oncology Aster, CMI Hospital, Bangalore, India
| | | | | | - Chetan Deshmukh
- Medical Oncology, Deenanath Mangeshkar Hospital, Pune, India
| | - Sagar Bhagat
- DGM, Global Medical Affairs, Glenmark Pharmaceutical Limited, B D Sawant Marg, Chakala, Andheri East, Maharashtra, 400099, Mumbai, India.
| | - Saiprasad Patil
- GM, Global Medical Affairs, Glenmark Pharmaceutical Limited, Mumbai, India
| | - Hanmant Barkate
- Medical Affairs, Glenmark Pharmaceutical Limited, Mumbai, India
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13
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Barbour AB, Kirste S, Grosu AL, Siva S, Louie AV, Onishi H, Swaminath A, Teh BS, Psutka SP, Weg ES, Chen JJ, Zeng J, Gore JL, Hall E, Liao JJ, Correa RJM, Lo SS. The Judicious Use of Stereotactic Ablative Radiotherapy in the Primary Management of Localized Renal Cell Carcinoma. Cancers (Basel) 2023; 15:3672. [PMID: 37509333 PMCID: PMC10377531 DOI: 10.3390/cancers15143672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/11/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment.
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Affiliation(s)
- Andrew B Barbour
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) Partner Site Freiburg, 79085 Freiburg, Germany
| | - Anca-Liga Grosu
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) Partner Site Freiburg, 79085 Freiburg, Germany
| | - Shankar Siva
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Center, University of Melbourne, Parkville, VIC 3052, Australia
| | - Alexander V Louie
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Hiroshi Onishi
- Department of Radiology, School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Anand Swaminath
- Division of Radiation Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, Canada
| | - Bin S Teh
- Department of Radiation Oncology, Cancer Center and Research Institute, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sarah P Psutka
- Department of Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Emily S Weg
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Jonathan J Chen
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Jing Zeng
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - John L Gore
- Department of Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Evan Hall
- Department of Medical Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Jay J Liao
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Rohann J M Correa
- Department of Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Simon S Lo
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
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14
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Liang W, Pan Y, Liu A, He Y, Zhu Y. Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis. Front Oncol 2023; 13:1132177. [PMID: 37519780 PMCID: PMC10372419 DOI: 10.3389/fonc.2023.1132177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 03/14/2023] [Indexed: 08/01/2023] Open
Abstract
Background Statin may confer anticancer efficacy, while the studies evaluating the influence of statin on survival of patients with renal cell cancer (RCC) yielded inconsistent results. A systematic review and meta-analysis was performed to investigate the association between statin use and survival of patients with RCC. Materials and Methods Cohort studies were identified by search of PubMed, Embase, and Web of Science databases according to the objective of the meta-analysis. A random-effect model incorporating the possible between-study heterogeneity was used for meta-analysis. Subgroup analyses according to study characteristics were also performed. Results Seventeen cohort studies involving 42528 patients with RCC were available for the meta-analysis. Results showed that statin use was associated with a better overall survival (OS, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.65 to 0.84, p < 0.001; I2 = 40%), progression progression-free survival (PFS, HR: 0.82, 95% CI: 0.68 to 0.98, p = 0.03; I2 = 52%), and cancer-specific survival (CSS, HR: 0.76, 95% CI: 0.59 to 0.99, p = 0.04; I2 = 38%). Besides, for the outcome of OS and PFS, subgroup analyses showed similar results in patients with surgical and non-surgical anticancer treatments, and in patients with stage I-III and stage IV RCC (p values for subgroup difference all > 0.05). Conclusions Statin use may be associated with improved survival outcomes in patients with RCC. Although prospective clinical studies should be considered to validate these results, these findings suggest that statins may be potential adjuvant therapy for patients with RCC.
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Affiliation(s)
- Wenli Liang
- Oncology Department, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Yongmei Pan
- Department of Medical Imaging, the First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, China
| | - Aixue Liu
- Oncology Department, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Yan He
- Oncology Department, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Yan Zhu
- Oncology Department, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China
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15
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Kang DH, Lee JY, Lee Y, Ha US. Optimal sequencing of the first- and second-line target therapies in metastatic renal cell carcinoma: based on nationally representative data analysis from the Korean National Health Insurance System. BMC Cancer 2023; 23:483. [PMID: 37254112 DOI: 10.1186/s12885-023-10991-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 05/22/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND The authors intend to compare the effects of each targeted therapy (TT) in the treatment of patients with metastatic renal cell carcinoma (mRCC) using big data based on the Korean National Health Insurance System (NHIS) and determine the optimal treatment sequence. METHODS Data on the medical use of patients with kidney cancer were obtained from the NHIS database from January 1, 2002, to December 31, 2020. Patient variables included age, sex, income level, place of residence, prescribing department, and duration from diagnosis to the prescription date. The primary outcome was overall survival (OS) for each drug and sequencing. We performed propensity score matching (PSM) according to age, sex, and Charlson Comorbidity Index based on the primary TTs. RESULTS After 1:1 PSM, the sunitinib (SUN) (n = 1,214) and pazopanib (PAZ) (n = 1,214) groups showed a well-matched distribution across the entire cohort. In the primary treatment group, PAZ had lower OS than SUN (HR, 1.167; p = 0.0015). In the secondary treatment group, axitinib (AXI) had more favorable OS than cabozantinib (CAB) (HR, 0.735; p = 0.0118), and everolimus had more adverse outcomes than CAB (HR, 1.544; p < 0.0001). In the first to second TT sequencing, SUN-AXI had the highest OS; however, there was no statistically significant difference when compared with PAZ-AXI, which was the second highest (HR, 0.876; p = 0.3312). The 5-year survival rate was calculated in the following order: SUN-AXI (51.44%), PAZ-AXI (47.12%), SUN-CAB (43.59%), and PAZ-CAB (34.28%). When the four sequencing methods were compared, only SUN-AXI versus PAZ-CAB (p = 0.003) and PAZ-AXI versus PAZ-CAB (p = 0.017) were statistically significant. CONCLUSIONS In a population-based RWD analysis of Korean patients with mRCC, SUN-AXI sequencing was shown to be the most effective among the first to second TT sequencing methods in treatment, with a relative survival advantage over other sequencing combinations. To further support the results of this study, risk-stratified analysis is needed.
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Affiliation(s)
- Dong Hyuk Kang
- Department of Urology, Inha University College of Medicine, Incheon, Korea
| | - Joo Yong Lee
- Department of Urology, Severance Hospital, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
- Center of Evidence Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea
| | - Yunhee Lee
- Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Korea
| | - U-Syn Ha
- Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Korea.
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16
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Shou Y, Yue C, Wang Q, Liu J, Xu J, Miao Q, Liu D, Yang H, Liu Y, Zhang X. circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway. Cell Death Dis 2023; 14:232. [PMID: 37002206 PMCID: PMC10066201 DOI: 10.1038/s41419-023-05717-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 02/28/2023] [Accepted: 02/28/2023] [Indexed: 04/03/2023]
Abstract
Renal cell carcinoma (RCC) is characterized by the difficulties in early diagnosis and the propensity to metastases. For advanced RCC, sunitinib targeted therapy is the clinically recommended first-line drug and the major challenge of sunitinib treatment is adaptive resistance. Therefore, it is imperative to research the mechanisms underlying sunitinib resistance. In this study, we discovered that circPTPN12 was highly expressed in RCC tissues and was associated with poorer clinical outcomes. circPTPN12 could promote the proliferation, migration, invasion, and sunitinib resistance of RCC cells. Mechanistically, circPTPN12 was found to form a complex with hnRNPM, which was involved in the regulation of mRNA processing. The combination with circPTPN12 enhanced the ability of hnRNPM to maintain the stability of IL-6 mRNA and further activated the STAT3 signaling pathway. The study revealed that circPTPN12/hnRNPM/IL-6/STAT3 axis promoted RCC progression and sunitinib resistance, which might be a promising therapeutic target for relieving sunitinib resistance in RCC.
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Affiliation(s)
- Yi Shou
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China
| | - Changjie Yue
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qi Wang
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jingchong Liu
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jiaju Xu
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qi Miao
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Di Liu
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hongmei Yang
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuenan Liu
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Xiaoping Zhang
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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17
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Eto M, Takagi T, Kimura G, Fukasawa S, Tamada S, Miura Y, Oya M, Sassa N, Anai S, Nozawa M, Sakai H, Perini R, Yusa W, Ikezawa H, Narita T, Tomita Y. Lenvatinib plus pembrolizumab versus sunitinib for advanced renal cell carcinoma: Japanese patients from the
CLEAR
study. Cancer Med 2022; 12:6902-6912. [PMID: 36457273 PMCID: PMC10067092 DOI: 10.1002/cam4.5483] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 11/08/2022] [Accepted: 11/16/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND The phase 3 CLEAR study demonstrated statistically significantly improved efficacy with lenvatinib plus pembrolizumab versus sunitinib, including progression-free survival and overall survival, in patients with previously untreated advanced renal cell carcinoma. This subset analysis investigated efficacy and safety in Japanese patients randomized to lenvatinib plus pembrolizumab or sunitinib in the CLEAR study. METHODS Progression-free survival, overall survival, tumor response, and safety were assessed in Japanese patients with previously untreated advanced renal cell carcinoma randomized to receive lenvatinib plus pembrolizumab (n = 42) or sunitinib (n = 31). Efficacy outcomes were analyzed by independent imaging review per Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 22.1 vs. 10.9 months; hazard ratio, 0.39; 95% CI, 0.20-0.74). Median overall survival was not estimable in the lenvatinib plus pembrolizumab arm and 30.6 months in the sunitinib arm (HR, 1.20; 95% CI, 0.39-3.66). Overall survival adjusted for the imbalance of Memorial Sloan-Kettering Cancer Center prognostic risk group favored lenvatinib plus pembrolizumab (hazard ratio, 0.67; 95% CI, 0.18-2.39). Objective response rate (69.0% vs. 45.2%; odds ratio, 2.71; 95% CI, 1.03-7.10) was higher and median duration of response (20.3 vs. 9.1 months) was longer with lenvatinib plus pembrolizumab versus sunitinib. Grade ≥ 3 treatment-emergent adverse events occurred in 95.2% versus 87.1% of patients in the lenvatinib plus pembrolizumab versus sunitinib arms. CONCLUSIONS These findings support lenvatinib plus pembrolizumab as a potential first-line treatment for Japanese patients with advanced renal cell carcinoma.
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Affiliation(s)
- Masatoshi Eto
- Department of Urology Kyushu University Hospital Fukuoka Japan
| | - Toshio Takagi
- Department of Urology Tokyo Women's Medical University Hospital Tokyo Japan
| | - Go Kimura
- Department of Urology Nippon Medical School Hospital Tokyo Japan
| | - Satoshi Fukasawa
- Prostate Center and Division of Urology Chiba Cancer Center Chiba Japan
| | - Satoshi Tamada
- Department of Urology Bell‐land General Hospital Osaka Japan
| | - Yuji Miura
- Department of Medical Oncology Toranomon Hospital Tokyo Japan
| | - Mototsugu Oya
- Department of Urology Keio University Hospital Tokyo Japan
| | - Naoto Sassa
- Department of Urology Aichi Medical University Aichi Japan
| | - Satoshi Anai
- Department of Urology Nara Medical University Nara Japan
| | - Masahiro Nozawa
- Department of Urology Kindai University Hospital Osaka Japan
| | - Hideki Sakai
- Department of Urology Nagasaki University Hospital Nagasaki Japan
| | | | - Wataru Yusa
- Japan and Asia Clinical Development Department Oncology Business Group, Eisai Co., Ltd. Tokyo Japan
| | - Hiroki Ikezawa
- Clinical Data Science Department, Medicine Development Center Eisai Co., Ltd. Tokyo Japan
| | | | - Yoshihiko Tomita
- Department of Urology, Department of Molecular Oncology Niigata University Graduate School of Medicine Niigata Japan
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Yu D, Zhang X, Gao L, Qian S, Tang H, Shao N. Development and validation of a novel immunotype for prediction of overall survival in patients with clear cell renal cell carcinoma. Front Oncol 2022; 12:924072. [PMID: 36237315 PMCID: PMC9552763 DOI: 10.3389/fonc.2022.924072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 09/06/2022] [Indexed: 11/14/2022] Open
Abstract
Background Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor. The purpose of the present study was to establish a novel immunotype for different immune infiltration and overall survival (OS) of patients with ccRCC. Methods Based on the Cancer Genome Atlas Project (TCGA) database (discovery set), a novel immunotype was established using ssGSEA methods. The databases of Fudan University Shanghai Cancer Center (FUSCC) and Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHH) served as an external validation set. GSEA was carried out to identify the immunotype associated signal transduction pathways. Results A total of 652 ccRCC patients were included in our study. We constructed a novel immunotype of ccRCC to classify patients into three groups: high-immunity, moderate-immunity, and low-immunity. The high-immunity and moderate-immunity groups had higher ImmuneScores, ESTIMATEScores, StromalScores, and lower tumor purity than that of the low-immunity group in both sets. Additionally, the patients from the high-immunity and moderate-immunity groups had longer survival than patients from low-immunity group in both discovery set and validation set (HR = 2.54, 95% CI: 1.56–4.13, p < 0.01; HR = 2.75, 95% CI: 1.24–6.11, p = 0.01). Conclusion In summary, we defined a novel immunotype of ccRCC. The immune types could be used as a clinical predictive tool to identify ccRCC patients with different survival. In addition, the immune-related biological signaling pathway also brought new insights on the mechanism of ccRCC.
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Affiliation(s)
- Deshui Yu
- Department of Urology, Second People’s Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, China
| | - Xuanzhi Zhang
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Lixia Gao
- Department of Operation Room, Second People’s Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, China
| | - Subo Qian
- Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hong Tang
- Department of Pathology, The Affiliated WuXi No.2 People’s Hospital of Nanjing Medical University, Wuxi, China
- *Correspondence: Ning Shao, ; Hong Tang,
| | - Ning Shao
- Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Ning Shao, ; Hong Tang,
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Du W, Guo K, Jin H, Sun L, Ruan S, Song Q. Association Between Metabolic Syndrome and Risk of Renal Cell Cancer: A Meta-Analysis. Front Oncol 2022; 12:928619. [PMID: 35832547 PMCID: PMC9271793 DOI: 10.3389/fonc.2022.928619] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 05/30/2022] [Indexed: 12/24/2022] Open
Abstract
Background Metabolic syndrome (MetS) has been related to increased risks of a variety of cancers. However, the association between MetS and the risk of renal cell cancer (RCC) remains not fully determined. This meta-analysis was conducted to investigate whether MetS is independently associated with the risk of RCC in adults. Methods Relevant observational studies were obtained by searching PubMed, Embase, Cochrane's Library, and Web of Science databases. Study characteristics and outcome data were extracted independently by two authors. The random-effect model was used for meta-analysis considering the possible influence of between-study heterogeneity. Predefined subgroup analyses were used to evaluate the possible influences of study characteristics on the outcome. Results Eight studies involving 10,601,006 participants contributed to the meta-analysis. Results showed that MetS was independently associated with a higher risk of RCC in adult population (risk ratio [RR]: 1.62, 95% confidence interval [CI]: 1.41 to 1.87, p<0.001; I2 = 85%). Subgroup analyses showed consistent association in men (RR: 1.52, 95% CI: 1.23 to 1.89, p<0.001) and in women (RR: 1.71, 95% CI: 1.28 to 2.27, p<0.001), in Asians (RR: 1.51, 95% CI: 1.25 to 1.83, p<0.001) and in Caucasians (RR: 1.76, 95% CI: 1.46 to 2.12, p<0.001), and in community derived (RR: 1.56, 95% CI: 1.34 to 1.82, p<0.001) and non-community derived population (RR: 1.87, 95% CI: 1.71 to 2.04, p<0.001). Differences in study design or quality score also did not significantly affect the association (p for subgroup difference both >0.05). Conclusions MetS may be independently associated with RCC in adult population.
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Affiliation(s)
- Wurong Du
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kaibo Guo
- Department of Oncology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Oncology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Huimin Jin
- Oncology Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University (Xinhua Hospital of Zhejiang Province), Hangzhou, China
| | - Leitao Sun
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Shanming Ruan
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Qiaoling Song
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Education Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
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Li R, Chen W, Lu C, Li X, Chen X, Huang G, Wen Z, Li H, Tao L, Hu Y, Zhao Z, Chen Z, Ni L, Lai Y. A four-microRNA panel in serum may serve as potential biomarker for renal cell carcinoma diagnosis. Front Oncol 2022; 12:1076303. [PMID: 36727070 PMCID: PMC9885090 DOI: 10.3389/fonc.2022.1076303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 12/22/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Renal cell carcinoma (RCC) is one out of the most universal malignant tumors globally, and its incidence is increasing annually. MicroRNA (miRNA) in serum could be considered as a non-invasive detecting biomarker for RCC diagnosis. METHOD A total of 224 participants (112 RCC patients (RCCs) and 112 normal controls (NCs)) were enrolled in the three-phrase study. Reverse transcription quantitative PCR (RT-qPCR) was applied to reveal the miRNA expression levels in RCCs and NCs. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to predict the diagnostic ability of serum miRNAs for RCC. Bioinformatic analysis and survival analysis were also included in our study. RESULTS Compared to NCs, the expression degree of miR-155-5p, miR-224-5p in serum was significantly upregulated in RCC patients, and miR-1-3p, miR-124-3p, miR-129-5p, and miR-200b-3p were downregulated. A four-miRNA panel was construed, and the AUC of the panel was 0.903 (95% CI: 0.847-0.944; p < 0.001; sensitivity = 75.61%, specificity = 93.67%). Results from GEPIA database indicated that CHL1, MPP5, and SORT1 could be seen as promising target genes of the four-miRNA panel. Survival analysis of candidate miRNAs manifested that miR-155-5p was associated with the survival rate of RCC significantly. CONCLUSIONS The four-miRNA panel in serum has a great potential to be non-invasive biomarkers for RCC sift to check.
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Affiliation(s)
- Rongkang Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, Anhui, China
| | - Wenkang Chen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Chong Lu
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, Anhui, China
| | - Xinji Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Xuan Chen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Guocheng Huang
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Zhenyu Wen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Hang Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
| | - Lingzhi Tao
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
| | - Yimin Hu
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
| | - Zhengping Zhao
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
| | - Zebo Chen
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
| | - Liangchao Ni
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
- *Correspondence: Yongqing Lai, ; Liangchao Ni,
| | - Yongqing Lai
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, Anhui, China
- *Correspondence: Yongqing Lai, ; Liangchao Ni,
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