bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site of metastasis and clinical outcomes in patients with advanced renal cell carcinoma treated with TKI monotherapy or combination therapy: A real-world analysis.
Authors: Nuvola Giacomo , Navarro Victor , Mollica Veronica , Marmolejo Castañeda David Humberto , González Macarena , Morales-Barrera Rafael , Vega Sharela , Santoni Matteo , Catalan Laia , Trilla Enrique , Carles Joan , Massari Francesco , Suárez Cristina 
Published: June 2024

e16513 Background: Tyrosine kinase inhibitors (TKIs), either in monotherapy or in combination with immunotherapeutic agents (IO), have become the standard of care for the first-line treatment of advanced or metastatic renal cell carcinoma (RCC). Common sites of metastasis in RCC include the lymph nodes, lungs, liver, pancreas, bones, and brain. This study aims to analyze the clinical outcomes of patients treated with TKI monotherapy and TKI-IO combination therapy based on the site of metastasis. Methods: A retrospective analysis was conducted on the clinical characteristics and outcomes of RCC patients treated with first-line TKI and TKI-IO in Spanish and Italian institutions. The study employed a descriptive analysis, calculating the median follow-up using the reverse Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional-hazard models were utilized to determine hazard ratios (HRs) with a 95% confidence interval. Results: Out of 369 eligible patients, 285 received TKI monotherapy, and 84 were treated with TKI-IO. The median follow-up was 84.34 months (95% CI; 73.82 - 101.91) in the TKI group and 17.58 months (95% CI; 13.11 - 45.77) in the TKI-IO group. PFS was significantly longer with TKI-IO compared to TKI in patients with lung metastasis (48.79 months vs. 21.95 months) (HR 0.59 [0.39;0.91]; p=0.02). While PFS was longer in patients with bone metastasis (41.3 months vs. 19.09 months) (HR 0.56 [0.28 ; 1.13]; p=0.11), liver metastasis (41.3 months vs. 15.97 months) (HR 0.52 [0.25 ; 1.06]; p=0.07), and lymph node metastasis (32.82 months vs. 20.14 months) (HR 0.67 [0.43 ; 1.04]; p=0.08) with TKI-IO, these differences were not statistically significant. TKI monotherapy showed longer PFS in patients with pancreatic metastasis (41.64 months vs. 22.7 months) (HR 1.37 [0.5 ; 3.72]; p= 0.54). OS was numerically longer in TKI-IO-treated patients across various subgroups but did not reach statistical significance. Notably, OS was significantly higher in patients with pancreatic metastasis compared to those with other metastatic locations (139 months vs. 42.74 months) (HR 0.35[0.18;0.69]; p<0.01). Conclusions: Our study underscore the superiority of TKI-IO combination therapy over TKI monotherapy, revealing consistently favourable outcomes across various metastatic sites. Notably, an intriguing exception emerged in the context of pancreatic metastasis, where patients exhibited an extended PFS with TKI monotherapy. The implications of our data suggest a tailored approach for this specific subset, wherein frontline immunotherapy may not be the optimal choice.
Single cell RNA sequencing to reveal genetic biomarkers and immune microenvironment of patients with aggressive small renal cell carcinoma.
Authors: Park Jee Soo , Kim Eun Chae , Song Seol , Kim Jongchan , Jang Won Sik , Hwang Byungjin , Ham Won Sik 
Published: June 2024

e16517 Background: While active surveillance for small renal cell carcinoma (RCC) gained acceptance due to harmless behavior, controversy still continues on aggressive potential of small RCC. Despite small tumor size, there still remains a risk for distant metastasis and recurrence. The biology of small RCC, especially the risk factors for metastasis and recurrence, has not been fully elucidated. It is therefore important to evaluate the aggressive potential of small RCCs to ensure that necessary treatments are given, but also to avoid overtreatment. Therefore, we used bulk RNA sequencing and single cell RNA sequencing (scRNA-seq) to reveal genetic biomarkers and distinct immune microenvironment in aggressive small RCC patients. Methods: Five cases of T1a (≤ 4cm) clear cell RCCs (ccRCCs) that were reported to have synchronous metastasis or recurrence were identified as an aggressive group and four cases with age, sex, and tumor size-matched ccRCCs patients with no metastasis or recurrence were identified as a non-aggressive group among prospective cohort (ClinicalTrials.gov Identifier: NCT03694912) RCC database. For the control, two healthy kidney donors were enrolled. We performed scRNA-seq using the 10X Genomics platform and bulk analysis for the total eleven cases of peripheral blood mononuclear cell (PBMC) samples. We demultiplexed pooled 11 samples using Souporcell and sequencing reads were normalized and analyzed using R/Seurat package. Cellular components of each sample were determined based on known marker genes. Bulk analysis involved differential gene expression analysis and pathway enrichment analysis. Results: The mean tumor size and age was 2.6 cm and 63 years old, respectively. Among 5 aggressive ccRCC patients, two patients had synchronous lung metastasis and two patients had synchronous bone metastasis. One patient had recurrence after partial nephrectomy. We analyzed 36,303 cells and identified 31 cell subpopulations. Our single-cell analysis unveiled distinct variations in T cell and natural killer (NK) cell proportions among aggressive, non-aggressive, and normal groups, highlighting significant differences in these ratios. Additionally, a notable pattern of gene expression levels was found between non-aggressive and aggressive groups, with a substantial increase in the expression levels of GSTP, ASRG, and SNORD142 genes in aggressive group. Conclusions: As T1a ccRCCs present low but non-negligible risk of metastasis and recurrence, patients with small RCCs should be counseled on such risk when offered active surveillance. Patients with higher NK cells and lower naïve CD8+ T cell are associated with higher risk of metastasis and recurrence in T1a RCC. This study suggests a promising potential for leveraging genetic markers and immune cell dynamics in the diagnosis of aggressive ccRCC using non-invasive screening methods.
Clinical characteristics of renal cell carcinoma in the transplanted kidney in renal transplant recipients: A systematic scoping review.
Authors: Tanariyakul Manasawee , Saowapa Sakditad , Aiumtrakul Noppawit , Wittanakorn Onsinee , Wannaphut Chalothorn , Polpichai Natchaya , Yingchoncharoen Pitchaporn , Acoba Jared David 
Published: June 2024

e16518 Background: Renal transplant recipients are at a 100-fold increased risk of developing renal cell carcinoma (RCC), with a higher incidence of RCC in native kidneys than in allografts. Given that kidney transplant recipients typically possess only one functional kidney, it is critical for clinicians to heightened disease awareness. This systematic scoping review aims to provide an updated overview of the clinical characteristics, treatment, and outcomes of RCC in the allograft kidneys. Methods: We comprehensively searched the databases of MEDLINE and EMBASE until January 2024. Included studies were case reports, case series and retrospective analyses reporting RCC in the allograft kidney of renal transplant recipients. The review delineates the clinical presentation, time between kidney transplant and diagnosis, donor characteristic, mass size, histopathology and treatment outcome of RCC in the allograft kidneys. Results: Forty-two case reports and case series, along with eleven retrospective cohorts were found. 65 patients were identified in the case reports and case series, while 209 patients were reported in the retrospective study reviews. The review emphasizes that 75.4% of patients with allograft RCC were asymptomatic at the time of diagnosis, with the majority diagnosed through imaging surveillance. Symptomatic patients most commonly presented with gross or microscopic hematuria, elevated creatinine, abdominal or graft pain, respectively. 61.9% of recipients received their allograft from deceased donors, and 38.1% from living donors. The average time interval between kidney transplantation and the diagnosis of RCC spans 11.6 years, ranging from 6 months to 30 years. Papillary RCC and clear cell RCC (ccRCC) were the two most common histopathological diagnoses, with papillary RCC accounting for 53.3% and ccRCC for 34.2% of cases. A potential limitation is the inconsistent of long-term follow-up data for most of the subjects, which makes the outcome of this population uncertain. Conclusions: This systematic scoping review identified an average time interval of 11.6 years between kidney transplantation and RCC diagnosis, with a range from 6 months to 30 years. The majority of kidney transplant recipients with allograft RCC (75.4%) were asymptomatic, while the remainder presented with symptoms such as hematuria, elevated creatinine, abdominal or graft pain, weight loss, fever, malaise, or hypertension. The incidence of asymptomatic allograft RCC among kidney transplant recipients underscores the importance of vigilant post-transplant screening. Future research should investigate clinical outcomes and the cost-effectiveness of the screening practices in allograft kidney to develop preventive strategies.
Efficacy and safety of first-line TKI plus ICI therapy in metastatic non-clear cell renal cell carcinoma: A real-world multiple-centre study.
Authors: Zhong Xi , Huang Tingxuan , Peng Yulu , NG Cheoklong , Liu Xuhao , Jing Taile , Wei Wensu , Zhang Zhiling , Han Hui , Chen Minfeng , He Liru , Huang Jiwei , Dong Pei 
Published: June 2024

e16519 Background: The combination of immune checkpoint inhibitor (ICI) and tyrosine kinase inhibitor (TKI) has emerged as the standard first-line therapy for metastatic renal cell carcinoma (mRCC), however, limited clinical trials have investigated the role of ICI plus TKI in the treatment of metastatic non-clear cell renal carcinoma (mnccRCC) for its heterogeneity and low incidence. Our study presents multiple center real-world data with the optimal sample size so far to assess the efficacy and safety profile of ICI plus TKI in patients with mnccRCC. Methods: We performed a retrospective analysis including patients previously untreated with mnccRCC receiving TKI plus ICI or TKI in four institutions participated in this study. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors version 1.1, others including overall survival (OS), the objective response rate (ORR) and treatment related adverse events (AEs). Results: A total of 214 patients were included for this study with 122 patients receiving TKI monotherapy and 92 patients receiving TKI plus ICI. Median follow-up time was 29.4 months (IQ1-IQ3, 15.7-48.5). The median age of patients was 49 years, with the majority being male (70.6%) and intermediate/poor risk. The most prevalent pathological subtype of nccRCC was papillary RCC (44.4%), followed by MIT family translocated RCC (16.4%), fumarate hydratase RCC (10.3%), chromophobe RCC (9.3%), other nccRCC (6.5%), and unclassified RCC (13.1%). The median PFS of the TKI monotherapy group and the TKI plus ICI combination group were 5.9 months (95%[CI], 4.3-7.5) versus 15.2 months (95%CI, 6.6-23.7), while mOS was 38.5 months (IQ1-IQ3=17.1-70.0) for TKI cohort and unreached (IQ1-IQ3=23.4-N) in TKI plus ICI cohort. The ORR and disease control rate (DCR) was 16.4% versus 29.4% and 48.4% versus 78.3% in the two cohorts. Any grade of AEs was 93.44% and 96.74% occurred in the monotherapy group and combination therapy group, while the incidence of grade ≥3 AEs was 23.77% and 35.87%, respectively. Conclusions: The findings from our retrospective real-world cohort of mnccRCC patients demonstrate that the combination of ICI plus TKI could significantly enhance PFS, ORR and OS compared to TKI monotherapy and no new safety signals were found. [Table: see text]
Cabozantinib (CABO) after prior immune checkpoint inhibitor (ICI) and tyrosine-kinase inhibitors (TKI) therapy in metastatic renal cell carcinoma (mRCC): Real-world evidence (RWE) from a Moscow observational program.
Authors: Polshina Natalya , Filonenko Daria , Karulina Sofia , Zhukova Lyudmila 
Published: June 2024

e16526 Background: Cabozantinib is approved for metastatic renal cell carcinoma (mRCC). Data of CABO efficacy after prior ICI/ICI-TKI therapy are limited by several RWE trials. Here we report real-world evidence of CABO in Russian patients from a Moscow observational program. Methods: Patients (pts) with mRCC treated with CABO monotherapy through the Moscow observational prospective program between Feb’2022 and Jan’2024 were identified. All pts received 1-3 prior lines of therapy, all received prior ICI and TKI, either in combination or consequently. Pts with active CNS metastases were excluded from the program. Baseline clinical and treatment characteristics were collected. Rates of partial response (PR), stable disease (SD), progressive disease (PD), and disease control rate (DCR, PR+SD) were analyzed, and survival outcomes (overall survival (OS) and progression-free survival (PFS)) were calculated. Results: A total 59 patients (pts) treated with CABO were included in our analysis. Median age was 59 years (range 40-78), 46 (78%) pts were male, 54 (91,5%) pts had clear-cell histology. At time of CABO start 5 pts (8,5%) had the ECOG PS 0, 37 pts (62,7%) had ECOG PS 1, 17 pts (28,8%) had ECOG PS 2. 40 pts (67,8%) had intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, 19 pts (32,2%) had poor IMDC risk. 45 (76,3%) pts had prior nephrectomy. 15 pts (25,4%), 27 pts (45,8%), 17 pts (28,8%) had 1, 2 and ≥3 previous treatment lines respectively; 22 pts (37%) received prior treatment with combination of ICI and TKI. 4 pts (7%), 26 pts (44%), 29 pts (49%) had 1, 2-3 and > 3 sites of metastases respectively. 31 pts (53%) had bone metastases. Median (min-max) follow-up was 14 (1-22) months (mo). Rates of best response were: PR - 20%, SD - 56%, PD - 19%. Overall DCR was 76%. Median PFS was 14 mo (12,3-15,7) with 12-mo PFS 59%. Median OS was not reached, and the 12-mo OS rate was 76%. 41% of patients had a dose reduction, 32% needed treatment interruption and 19% of pts discontinued treatment due to toxicity. Conclusions: The effectiveness of CABO observed in this real-world observational program was consistent with results from clinical trials: DCR – 76%, median PFS – 14 mo with 12-mo PFS 59% and 12-mo OS 76%. Dose modifications may be required to optimize CABO use in routine clinical practice.
Efficacy and safety of axitinib in combination with sintilimab as neoadjuvant therapy for patients with locally advanced renal cell carcinoma: A phase II clinical study.
Authors: Huang Yixin , Zhang Zhiling , Zou Xiangpeng ,   Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Published: June 2024

e16534 Background: NCCN, EAU and CUA guidelines recommend radical nephrectomy (RN) for patients with locally advanced renal cell carcinoma (RCC). However, some patients experience complex local invasion, resulting in the difficulty of operation and the high rate of postoperative recurrence. Preoperative neoadjuvant therapy has been shown to reduce tumor volume effectively, consequently increasing the success rate of RN. The objective of this study is to evaluate the effectiveness and safety of combining neoadjuvant Axitinib with sintilimab in these patients. Methods: This is a phase II study to assess the efficacy and safety of neoadjuvant Axitinib combined with sintilimab in RCC patients. Patients diagnosed with locally advanced RCC enrolled in this study received Axitinib (5 mg bid) plus sintilimab (200mg Q3W) until progressive disease or unacceptable toxicity, and then patients will withdraw from the study and explore the option of surgical resection or alternative targeted/immunotherapy. Surgical intervention will be conducted after patients complete four cycles of PD-1 therapy. Results: A total of 12 patients were enrolled in the study. All patients had computerized tomography at screening and after treatment. The median reduction rate of primary tumor volume and active volume in that study were 26.4% and 58.6%, respectively. Stable disease was observed in 10 patients, and partial response was observed in 2 patients and progressive disease was observed in 1 patient. All patients (100.0%) enrolled in the study experienced a treatment-related adverse event (TRAE) of any grade. TRAEs of any grade leading to discontinuation occurred in 2 patients. Only one patient experienced a Grade 3 TRAEs, manifested as increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Only one patient did not undergo RN due to cardiovascular disease. Conclusions: Most of the patients showed a certain degree of tolerance to the medication and underwent RN successfully. But, only a minority of patients can benefit from Axitinib in Combination with Sintilimab in neoadjuvant therapy for locally advanced RCC. The combination of AKI and PD-1 is still a potential choice for preoperative tumor reduction in locally advanced RCC. There is an urgent need to explore a more effective and safe neoadjuvant therapy for these patients.
Cabozantinib tolerability in metastatic renal cell carcinoma: A meta-analysis.
Authors: Farooq Hafsa , Andrzejczyk Anna , Farooq Amna , Wu Shenhong 
Published: June 2024

e16546 Background: Cabozantinib, an oral multiple receptor-tyrosine kinase inhibitor, has been used as a single agent or in combination with immunotherapy in the treatment of metastatic renal cell carcinoma, and is associated with discontinuation due to adverse events. We conducted a meta-analysis of clinical trials to evaluate the tolerability of cabozantinib in this setting. Methods: A systematic literature search (from January 2014 to January 2024) was conducted to identify clinical trials of cabozantinib in metastatic renal cell carcinoma. Eligible studies included clinical trials with single‐agent cabozantinib or in combination with chemotherapy/immunotherapy in metastatic renal cell carcinoma reporting treatment discontinuation due to adverse events. Incidence, relative risk and 95% confidence intervals (CI) were calculated by a fixed or random effects model. Results: A total of 2,993 patients from 14 studies were included in the meta‐analysis (cabozantinib group n = 1532, control n = 1404). The summary discontinuation rate for cabozantinib due to adverse events was 13.3% (95% CI: 9.6-18.3%). There was no significant difference between cabozantinib as a single agent and in combination with other agents (P=0.52). No significant difference was identified between clear cell and non-clear cell RCC (P=0.25). When compared with controls, cabozantinib overall has similar discontinuation rate due to adverse events (RR: 0.79, 95% CI: 0.43-1.44, P=0.44). However, cabozantinib has significantly lower discontinuation rate as compared to sunitinib (OR: 0.57, 95% CI: 0.39-0.84, P=0.004). Conclusions: The tolerability of cabozantinib is comparable to other therapies overall, and it may be better tolerated than sunitinib in the treatment of advanced renal cell carcinoma.
Systematic literature review and network meta-analysis of first-line therapies for locally advanced/metastatic urothelial carcinoma.
Authors: Bloudek Lisa , Huang Shirley , Wright Phoebe , Shih Vanessa , Dillon Ryan , Martirosyan Anna , Pandey Rajshree , Williams Troy , Chang Nancy N. 
Published: June 2024

e16547 Background: Platinum-based chemotherapy (PBC) has been the standard of care for first-line (1L) locally advanced/metastatic urothelial carcinoma (la/mUC). This systematic literature review (SLR) and network meta-analysis (NMA) analyzed the latest 1L clinical trial data to assess the comparative efficacy of the novel regimen enfortumab vedotin in combination with pembrolizumab (EV+P) against PBC and other approved and investigational 1L regimens for patients with la/mUC. Methods: English language publications (1/2000-10/2023) and congress presentations (1/2015-10/2023) of Phase 2 and 3 clinical trials assessing efficacy and safety of 1L therapies in la/mUC were identified in the SLR. Studies were categorized as: mixed eligibility (cisplatin [cis]-eligible and -ineligible), cis-eligible, and cis-ineligible. An NMA assessed comparative efficacy of EV+P to guideline-recommended therapies and emerging therapies with demonstrated survival benefit. 1L switch maintenance therapies were not included due to differences in study design. Comparative efficacy for overall survival (OS) was assessed under a Bayesian framework assuming constant hazard ratio (HR). Results: The SLR identified 69 unique studies, 2 of which demonstrated survival benefit over PBC (EV-302 and CheckMate-901 substudy). Across all mixed eligibility studies, median OS for PBC ranged from 12.1-16.1 months. Five studies were included in the NMA (3 mixed eligibility, 4 cis-eligible, 3 cis-ineligible). NMA results for the mixed eligibility network showed that EV+P improved OS over all comparator regimens (HR 0.47-0.51; Table). In the cis-eligible network, EV+P subgroup analysis showed improved OS over nivolumab+PBC (HR 0.68 [95% CI 0.47, 0.98]) and PBC (HR 0.53 [95% CI 0.39, 0.72]) and numerically improved OS over ddMVAC (HR 0.76 [95% CI 0.48, 1.20]). In the cis-ineligible network, EV+P subgroup analysis showed improved OS over all comparator regimens (HR range 0.43-0.52). Limitations include few studies contributing to the networks and heterogeneity in patient populations. Conclusions: EV+P is the only regimen shown to improve survival compared with PBC regardless of cisplatin eligibility. This indirect comparison suggests that EV+P has a favorable survival benefit compared with other approved and investigational 1L regimens in patients with previously untreated la/mUC. [Table: see text]