bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab combined with tyrosine kinase inhibitors in the treatment of patients with advanced renal cell carcinoma: A single-center prospective exploratory study.
Authors: Xu Jing , Zhu Dongyuan 
Published: June 2023

e16522 Background: At present, both NCCN and CSCO guidelines recommend tyrosine kinase inhibitors (TKIs) or immunotherapy combined with TKIs as the first-line treatment of advanced renal cell carcinoma, but no large-scale clinical research data has been disclosed on the treatment of clear cell renal cell carcinoma with camrelizumab combined with TKIs. This study aims to explore the efficacy and safety of camrelizumab combined with TKIs in advanced renal cell carcinoma. Methods: Patients with stage Ⅳ renal cell carcinoma confirmed by histopathology, aged 18-75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, previously not received systematic treatment or only received one systematic treatment regimen were included in this study. The patients received (1) camrelizumab (200 mg/time, i.v., D1, q2w) (2) sunitinib (50mg, q.d., p.o.): 4 weeks on 2 weeks off, or pazopanib (800 mg, q.d.) or axitinib (5 mg, bid), until the disease progresses, intolerable toxicity occurs or the patient dies. The primary endpoint was the objective response rate (ORR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), and the secondary endpoint was safety, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between August 21，2021，and November 10, 2022, A total of 17 patients were enrolled in the study, with an average age of 58 years old. Of all the patients included, ten (58.8%) had not received systematic treatment, and seven (41.2%) patients had received it. Of these patients, four (23.5%) patients were treated with camrelizumab combined with sunitinib, nine (52.9%) with pazopanib, four (23.5%) with axitinib. All 17 patients received at least one imaging evaluation, 11 (64.7%) patients of which had a partial response (PR) of efficacy evaluation, with an ORR of 64.7%, including 70% for first-line patients and 57.1% for second-line patients; additionally, with 3 (17.6%) cases of stable disease (SD), DCR was 82.4%; 3 (17.6%) patients of progress disease (PD). PFS has not yet been reached, with the PFS rate of 75% in 6 months and 63% in 12 months. Only three patients died, and the median OS has not reached. The main grade 3 adverse events were alanine aminotransferase (ALT) increased, Aspartate Transaminase (AST) increased, and lymphocyte count decreased, all of which were 6 cases (35.5%). No grade 4-5 adverse events occurred. Conclusions: Camrelizumab combined with TKIs in the treatment of patients with advanced renal cell carcinoma has good efficacy and controllable safety, which needs to be further verified by large-scale clinical research. Clinical trial information: ChiCTR2300068189 .
SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis through activating Rac1-mediated lamellipodia protrusion.
Authors: Kim Jin Young , An Sunho , Lee Seungmee , Kim Byung Hoon , Shin Sojin , Choe Misun , Ha Eunyoung , Seo Ji Hae 
Published: June 2023

e16523 Background: Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. Methods: HK-2 (#22190, a normal kidney cell line), Caki-1 (#30046), Caki-2 (#30047), SN12C (#80025), and ACHN (#21611) cells were obtained from the Korean Cell Line Bank (Seoul, Korea). SN12C and ACHN cells were transfected with siRNA targeting SAMHD1. From the Broad GDAC Firehose database ( https://gdac.broadinstitute.org/ ), we downloaded RNA-sequencing (RNA-seq) and clinical data from the pankidney cohort (KIPAN), clear cell renal cell carcinoma (KIRC, ccRCC in the present study), renal papillary cell carcinoma (KIRP, PRCC in the present study), and kidney chromophobe (KICH, chRCC in the present study) datasets. We analyzed 20 pairs of human tissues (tumor and normal specimens) from Dongsan Hospital. The results are expressed as the mean ± SD or SEM. We used a two-tailed Student’s t test for single comparisons or two-way ANOVA for multiple comparisons. Results: We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. Conclusions: In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway.
Anemia in patients aged ≥75 years with metastatic clear cell renal cell carcinoma: An important IMDC prognostic factor for systemic therapy.
Authors: Mizuno Ryuichi , Tanaka Nobuyuki , Oya Mototsugu 
Published: June 2023

e16524 Background: Due to an increase in life expectancy, the incidence of metastatic renal cell carcinoma (mRCC) in patients aged ≥75 years has been increasing. In this study we investigated the characteristics before treatment and the outcomes of systemic therapies for patients aged ≥75 years with mRCC and compared the results with those for patients aged < 75 years in order to determine whether differences in age influenced survival. Methods: A total of 206 consecutive Japanese patients with mRCC, including 47 patients aged ≥75 years, who received systemic therapy were included. Clinical data from medical records were retrieved and analyzed retrospectively. Differences of several factors between the two groups were analyzed by the Chi-squared and Wilcoxon tests. Matching and balancing of the empirical distributions were performed by logistic regression analyses. Survival analyses were determined using a Kaplan–Meier method, and analyzed with a log-rank test. P values less than 0.05 were judged as statistically significant. Results: Elderly patients categorized as favorable risk group based on the International Metastatic RCC Database Consortium (IMDC) stratification system were significantly lower (p = 0.0241). Among IMDC risk factors, the rate of anemia was significantly higher in elderly patients (p = 0.006). No statistically significant benefit in PFS for first (p = 0.2183) and second line treatment (p = 0.2219) was observed, whereas improvements in OS (p = 0.0082) as well as CSS (p = 0.0083) were seen in patients aged < 75 years. Furthermore, mRCC patients aged ≥75 years tend to receive BSC instead of second line active treatment. To determine the impact of higher rates of IMDC intermediate/poor risk group in patients aged ≥75 years, we used propensity score matching using IMDC risk stratification to minimize potential bias. After propensity score matching, the well-matched 46 patients in each group demonstrated similar OS (p = 0.203) and CSS (p = 0.172). Conclusions: For mRCC patients aged ≥75 years, a higher proportion of base line anemia, which resulted in higher rates of IMDC intermediate/poor risk, would be responsible for shorter OS/CSS. In addition, mRCC patients aged ≥75 years tend to receive BSC instead of second line active treatment. Overcoming under-treatment in elderly patients might help to prolong survival in mRCC.
Immune checkpoint inhibitor effects on male reproduction.
Authors: Leong Sally , Wang Christina , Onyshchenko Mykola , Ilangovan Preethi , Rock Adam , Shodiya Michael , Swerdloff Ronald , Yoon Steve , Gianoukakis Andrew G. 
Published: June 2023

e16528 Background: Immune checkpoint inhibitors (ICI) have been shown to improve overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) as compared to previous therapy with multi-kinase inhibitors (MKI). However, little is known about the effects of these drugs on male reproductive capacity and the current data regarding effects of MKI and ICI therapies on gonadal function and fertility are both limited and conflicting. We sought to evaluate effects of MKI and ICI on male reproductive function in patients with RCC. Methods: Male patients with RCC receiving MKI or ICI for a period of at least 3 months were identified. Inclusion criteria included age ≤ 50 years, no prior history of chemotherapy, and no prior history of medical or surgical conditions that would affect spermatogenesis such as hypogonadism, Klinefelter syndrome, or vasectomies. Patients were instructed to abstain from ejaculation 2 to 7 days prior to study collection. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), morning testosterone, and a semen analysis was obtained for each patient and analyzed. Results: Of 10 patients, 5 (50%) were on ICI and 5 (50%) were on MKI. Of the patients on ICI, 2 (40%) exhibited abnormal semen morphology, motility, and sperm concentration. Of the patients on ICI, one exhibited elevated LH and FSH levels and one exhibited elevated LH levels only. Of the patients on MKI, 2 (40%) exhibited abnormal semen morphology, motility, and sperm concentration. One patient on MKI exhibited elevated LH and FSH levels. All patients had normal testosterone levels. Conclusions: Our preliminary descriptive data analysis suggests that both ICI and MKI may affect semen morphology and motility, sperm concentration, and LH and FSH levels, but does not affect testosterone levels. Due to the currently limited sample size, abnormal semen analysis and hormone levels may be attributable to confounding factors, such as performance status, the metastatic disease itself, comorbidities, etc. Study recruitment and analysis are ongoing.
Long-term liver and renal dysfunction in patients with metastatic renal cell carcinoma treated with TKI monotherapy: COMPARZ study post-hoc analysis.
Authors: Anwaier Aihetaimujiang , Zhang Hailiang , Yu Jiacui , Wan Hualin , Ong Su Miin , Tay Hao Zhe , Ye Ding-Wei 
Published: June 2023

e16536 Background: Tyrosine kinase inhibitors (TKI) are currently the recommended treatment option for advanced renal cell carcinoma (aRCC) patient. Previous studies have shown some hepatorenal toxicity of TKI regimens, but differences in toxicity and long-term toxicity of TKIs have rarely been reported. This study aims to compare short- and long-term hepatorenal toxicity differences between pazopanib and sunitinib, and to explore the factors predisposing to hepatorenal toxicity. Methods: COMPARZ study was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in aRCC patients. Patients without liver metastasis and with available alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin results were enrolled to evaluate the effect of TKI on liver function. Patients with available serum creatinine (Cr), blood urea nitrogen (BUN), urine protein/creatinine ratio (UPC), and creatinine clearance (CrCl) were enrolled to evaluate factors associated with abnormal renal function. Lab indicators were compared between baseline and at months 12, 24, and 36 by paired t-test respectively. Linear mixed models were used to compare the difference in changes between treatment arms. Multivariate logistic regression was performed to examine the factors associated with recorded adverse events of hepatorenal toxicities. Results: Patients with abnormal liver function tests at baseline had higher elevated ALT, AST and total bilirubin levels at 12 months after TKIs treatment compared with patients who had normal baseline results. ALT levels were not significantly different between pazopanib arm and sunitinib arm at 12, 24 and 36 months. However, patients in the sunitinib arm had significantly higher AST levels than the pazopanib arm at 12 months (p = 0.049). There was no significant difference in total bilirubin level between pazopanib and sunitinib arm. Asian race and pazopanib were two factors that was significantly associated with increased risk of developing abnormal liver function. At 12 months, Cr levels were higher in the sunitinib arm compared with the pazopanib arm . BUN levels were lower in the pazopanib arm at 12 months but conversely was higher in the sunitinib arm at 24 months. UPC levels were significantly elevated in both treatment arms at 12 months (p < 0.001) and 24 months (p = 0.008). CrCl levels decreased in both treatment arms, and was more obvious in the sunitinib group at 12 months and 24 months. Notably, male patients, Asian race, high BMI, and sunitinib were risk factors that were significantly associated with abnormal renal function. Conclusions: Compared with sunitinib, pazopanib was associated with a higher risk of hepatoxicity but lower risk of nephrotoxicity. Overall, Asian patients have a higher risk of developing abnormal liver and renal functions after TKI treatment.
Association of tumor homologous recombination deficiency (HRD) score with immune checkpoint inhibitor benefit in metastatic clear cell renal cell carcinoma.
Authors: Grigg Claud , Sha Wei , Bose Rupali , Neelands Brittany , Brown Landon Carter , Matulay Justin T. , Clark Peter E. , Burgess Earle F 
Published: June 2023

e16538 Background: Genomic aberrations resulting in homologous recombination repair deficiency (HRD) can be successfully targeted with poly (ADP-ribose) polymerase (PARP) inhibitors. Tumors with HRD also have a higher tumor mutation burden (TMB) and immunogenic phenotypes, prompting PARP inhibitor + immune checkpoint inhibitor (ICI) trials across cancer types. Clear cell renal cell carcinoma (ccRCC) rarely harbors canonical genomic aberrations associated with HRD. However, a “BRCA-like” HRD phenotype can be detected from next-gen DNA- or RNA-sequencing using models trained on tumors with BRCA1/2 bi-allelic loss. We hypothesized that this novel HRD phenotype is associated with ICI benefit in metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy and were treated with anti-PD-1/L1 ICI monotherapy +/- ipilimumab were identified in an institutional database (N = 52), and outcomes were determined by chart review. Progression free survival (PFS) and overall survival (OS) were calculated from the start date of ICI treatment. Targeted next generation DNA and whole transcriptome sequencing were performed from archived nephrectomy specimens using the Tempus xT platform. HRD scores were calculated using DNA (HRD-DNA) and RNA (HRD-RNA) based methods as previously described (Liebowitz BD et al. BMC Cancer 2022). HRD status was analyzed as a continuous rather than binary variable, as biologically relevant cutoff thresholds have not been established for ccRCC. Multivariable Cox regression models were used to evaluate the association between HRD scores and PFS or OS when demographic/pathologic covariates were adjusted. Results: The cohort was predominantly white (n = 48; 92%) and male (n = 37; 71%) with good performance status (ECOG 0-1: n = 47; 90%). Half (n = 26) were current/former smokers; median age 67 years and BMI 28. Twenty-four (46%) nephrectomies were cytoreductive. Most tumors were staged pT3/4 (85%) and grade 3/4 (90%) including 18 (35%) with sarcomatoid histology. ICI monotherapy or ICI + ipilimumab were received by 32 (62%) and 20 (38%) patients, respectively, in the 1st (40%), 2nd (40%), 3rd (17%), or 4th (2%) line. Median PFS and OS for the cohort were 6.4 months (95% CI 4.4-11.1) and 62.7 months (95% CI 32.8-not applicable). HRD-DNA and HRD-RNA could be calculated for 47 and 46 subjects, respectively. HRD-DNA was not found to be associated with PFS nor OS. High HRD-RNA score was associated with improved PFS (HR 0.92 per unit increase; 95% CI 0.85-1.00, p = 0.052) in the multivariable model, but not OS. Conclusions: High HRD-RNA was associated with longer PFS for metastatic ccRCC patients undergoing ICI-treatment. A “BRCA-like” transcriptomic signature may be predictive of ICI benefit in ccRCC.
Genome sequencing-based prognosis, mutational analysis, and survival rate of clear cell renal cell carcinoma.
Authors: Centeno Lisa Joy , Pan Hai , Malik Preeti , Hashim Tehmina , Poursina Olia , Velez Diaz Lorena Antonella , Varma Samyukta , Bapat Prachi , Chowdhary Arsh , Alkhatib Lean , Patel Urvish , Palabindela Prasannalaxmi , Kalra Kartik , Patil Ashish , Kukreja Geetika 
Published: June 2023

e16543 Background: The clear cell renal cell carcinoma (ccRCC) is the most prevalent genitourinary cancer, and carries a poor prognosis. Information regarding whole genome sequencing, a prognostic prediction system, and overall survival in ccRCC is limited. While loss of VHL is commonly implicated in ccRCC, two genes indicated in other cancers, SDHD and ARID1A, have limited literature on their correlation to ccRCC. Hence, we aimed to analyze the genomic profile, epidemiological characteristics and overall survival of ccRCC. Methods: We utilized cBioPortal cancer genomics [The Cancer Genome Atlas (TCGA) PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2013] to study the genetic mutations associated with ccRCC. Epidemiological characteristics and genetic profiles were evaluated, and a query was generated to calculate 5 year and 10 year survival rate with the most common mutations. Log-rank test and Kaplan–Meier estimator were used in analyzing the survival function. Patients with two or more overlapping mutations (72) were excluded. Results: We identified 761 patients with ccRCC, out of which 442 had primary ccRCC with all demographic details available. 65.8% were males, 58.1% were Caucasian, and 7.2% were African American. Majority of patients (199) were between the ages of 50-65 years. 286 (64.7%) were alive and 156 (35.3%) were deceased. The common mutations associated with reduced survival were VHL, BAP1, SDHA, SDHD, and ARID1A. Median survival of patients with VHL, BAP1, SDHA, SDHD, ARID1A mutations was 118.85, 93.04, 40.70, 2.04, and 6.02 months respectively in comparison with unaltered mutation group (78.44 months) (p < 0.0001). (Table 1) Survival was lowest amongst SDHD [2.04 months] and ARID1A [6.02 months]. (p = 3.26e-10). In survival analysis, SDHD and ARID1A were associated with lowest survival after initial diagnosis at 60 months (Figure 1) and 120 months (Figure 2). (p = 2.592e-3). Conclusions: Our study found that SDHD, ARID1A, and SDHA genes were associated with the worst prognosis in ccRCC with median survival of 2.04, 6.02, and 40.70 months. This study may provide insight for targeted therapies for ccRCC and improve the prognosis of these patients. [Table: see text]
Evaluation of a novel Re-VASC score to differentiate malignant and benign T1a renal masses.
Authors: Fateri Cameron , Roth Bradley , Rao Sriram , Peta Akhil , Danza Clifford , Wignarajah Sailesh , Park Sung-Mee , Kar Nina , Houshyar Roozbeh , Landman Jaime 
Published: June 2023

e16548 Background: Early characterization of renal cell carcinoma (RCC) is pertinent for cancer prognosis and patient treatment. However, characterization of renal masses as benign or malignant on computed tomography (CT) remains a difficult clinical challenge. Angiogenesis plays a major role in RCC progression and assessing neovascularity in tumor-burdened kidneys with Re-VASC scoring has been shown to aptly predict tumor pathology and staging. In the current study, we evaluated if Re-VASC can reliably differentiate between malignant T1a ( < 4cm) RCC and benign T1a renal masses. Methods: All eligible patients had a diagnosis of T1a from pathologic or clinical evaluation. The inclusion criteria for malignant masses included a diagnosis of RCC by pathology after partial or radical nephrectomy. Our T1a benign group was comprised of patients with a diagnosis of a non-malignant renal mass (angiomyolipoma or oncocytoma) established via histopathology or CT imaging (fat containing lesions). Re-VASC score was calculated on axial preoperative contrast enhanced CT utilizing the system described below: 0 = No visible neovascularization 1 = visualized single new vessel < 3mm in diameter 2 = visualized single new vessel ≥3mm in diameter 3 = visualized multiple new vessels < 3mm in diameter 4 = visualized multiple new vessels and at least one vessel ≥3mm in diameter. Results: A total of 64 benign and 69 malignant T1a tumors were included. Comparison of the two groups demonstrated no significant differences with regards to age, sex, ASA, and BMI. The average Re- VASC scores was 0.159 and 0.753 for benign and malignant masses respectively (p < 0.001). Additionally, the tumor size for benign masses was 2.373 and for malignant masses was 2.546 (p = 0.210). There was no significant difference in Re-VASC score between the contralateral kidneys of malignant and benign kidney masses (p < 0.508). Additionally, the sensitivity, specificity and positive predictive values were 26%, 86% and 74% respectively, when utilizing a Re-VASC score of 1 as a cutoff for malignancy. Conclusions: Our results show a significantly higher Re-VASC score in T1a malignant tumors and T1a benign tumors. While biopsy remains the gold standard for confirmation of malignant tumors such as RCC, radiological evaluation with tumor scoring systems like Re-VASC may offer a useful clinical decision-making tool in a less-invasive manner. Because renal biopsy carries non-negligible risk of complications, reducing volume of biopsies among low-risk patients may lead to better overall care. The Re-VASC score shows potential as a confirmatory test with a specificity of 86%. We would like to apply the Re-VASC score to an expanded multi-center trial, in order to assess its translatability to the general population.