tbuckley/cabot-search huggingface dataset:
Phase II clinical study of the safety and efficacy of sintilimab in combination with axitinib and stereotactic radiotherapy in the treatment of local-regional recurrent renal cell cancer.
Authors: Ruiqi Liu, Yang Liu, Zhiling Zhang, Jianming Gao, Xinyue Zhang, Qiwen Pan, Yilin Li, Lingling Cai, Shengjie Guo, Hui Han, Fangjian Zhou, Pei Dong, Liru He
Journal: Journal of Clinical Oncology (2024)

e16511 Background: Currently, targeted agents and immunotherapy are applied to local-regional recurrent renal cell carcinoma (LRRCC). The combination with systemic therapy and stereotactic radiotherapy (SBRT) is worth exploring. In the present study, we aimed to investigate the efficacy and safety profile of sintilimab plus axitinib combined with SBRT in the treatment for LRRCC. Methods: This was a single-arm, phase II study enrolled LRRCC patients (pts), for whom the SBRT can be safety applied for all the recurrent lesions visible on imaging. Eligible pts received sintilimab (200mg, day 1) and axitinib (5mg, bid, day 1-21) in a 21d cycle. SBRT (35-45Gy/5 fractions) was performed before the third administration of sintilimab. The primary endpoint was progression-free survival (PFS). Results: From Oct 2021 to Jan 2024, 19 pts with a median age of 58 (range: 33-74) were enrolled. Among them, 9 (47.37%) pts had clear cell carcinoma. Nine (47.37%) pts were IMDC intermediate (7 pts) or high risk, and 8 (42.11%) pts recurred in less than 1 year after surgery. Seven(36.84%) pts received at least one prior systemic therapy. Four (21.05%) pts had recurrence in the renal fossa, while 3(15.79%) pts in retroperitoneal lymph node, 2(10.53%) pts in retroperitoneal lymph node with renal fossa and 10(52.63%) pts in intra-abdominal soft tissue. With a median follow-up of 9.5 months (range: 3.0-27.1m), 18 pts were evaluable for response. The median tumor volume was 37.47cc (range: 2.44-493.19cc). The overall response rate was 55.56% with 4 complete responses and 6 partial responses per RECIST v1.1. The median time-to-response was 5 months. The local control rate and the disease control rate were 100% and 94.44%, respectively. The median PFS was not reached, and the 9-month PFS rate was 94.44%. All 19 pts were evaluable for toxicity. Any-grade treatment-related adverse events (TRAEs) occurred in 16(84.21%) pts. The most common TRAEs were albuminuria (8/19; 42.11%), nausea (8/19; 42.11%), hypertension (7/19; 36.84%), and diarrhea (7/19; 36.84%). Grade 3 or higher TRAEs occurred in 6/19(31.58%). Conclusions: Sintilimab plus axitinib combined with SBRT showed promising antitumor activity and manageable toxicity in pts with LRRCC. Clinical trial information: ChiCTR2100049523 .
Exploring genetic ancestry and tumor mutation profiles in renal clear cell carcinoma: A comprehensive analysis using The Cancer Genetic Ancestry Atlas.
Authors: Michelle J Lee, Shalini Vemuru, Christopher H Rhee, Marcus Moses, Deven Patel, Bassel Nazha, Mehmet Asim Bilen, Jacqueline T Brown
Journal: Journal of Clinical Oncology (2024)

e16512 Background: Addressing health disparities in renal cell carcinoma (RCC) has been an enduring challenge globally, with notable variations in incidence and outcomes among different racial groups. Genomic ancestry serves as a valuable tool in capturing biological variations among diverse populations and offers insights into clinical, histopathological, and molecular distinctions. We utilized The Cancer Genetic Ancestry Atlas (TCGAA) to investigate tumor mutation profiles of RCC with focus on the influence of genetic ancestry on the intricate genomic landscape of this malignancy. Methods: Genomic and clinical data of TCGA PanCancer Atlas KIRC were downloaded through the GDC Data Portal. We utilized The Cancer Genome Ancestry Atlas (TCGAA) and the STRUCTURE algorithm for estimation of genetic ancestry. Primary ancestry was specified as comprising greater than or equal to 50% of genetic ancestry from a single reference population. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods. Results: 64.5% were male and 41% were locally advanced or metastatic (stage III-IV). Genomic analysis revealed 438 individuals with European ancestry (mean European ancestry of 95.78%), 50 patients with African ancestry (mean African ancestry of 77.7%), and 8 patients with Asian ancestry (mean Asian ancestry of 92.5%). The mean age of patients was 61.0, 58.5, and 49.5 for the European, African, and Asian ancestry groups, respectively. African ancestry correlated with a trend towards reduced overall survival (OS) compared to European ancestry (median OS 62.89 vs 90.48 months). African ancestry patients harbored lower frequency of VHL and PBRM1 alterations, but with significant enrichment in MTOR, FREM2, UNC80, LRP2 alterations compared with European ancestry group. Conclusions: This study reveals genetic heterogeneity in RCC across diverse ancestry groups, indicating presence of distinct oncogenic genes and pathways in African American populations.These findings suggest potential contributions to racial disparities in clinical presentation, outcomes, and treatment responses. Future research should include exploring the role of genetic ancestry in tumorigenesis and disease progression, alongside developing targeted therapies to mitigate health inequities and enhance outcomes for all populations. [Table: see text]
Incidence and outcomes of thromboembolic events in renal cancer related hospitalization in the United States: A propensity matched national study.
Authors: Muhammad Sultan, Manoj Kumar, Faryal Farooq, Muhammad Sohaib Afzal, Bilal Nasir, Laxman Yashwant Byreddi, Sundeep Atluri, Vishal Devarkonda, Shafaqat Ali
Journal: Journal of Clinical Oncology (2024)

e16544 Background: Venous thromboembolic events (VTE) are a significant cause of morbidity and mortality in cancer patients. We aim to investigate the incidence and outcomes of acute DVT and PE in renal cancer compared to all other malignancies. Methods: The National Readmission Database (2016-2020) was queried to identify all-cause admissions for patients with any active malignancy. Cohorts were divided into renal cancer vs other cancers. A Propensity Score Matching (PSM) model matched both cohorts. Multivariate regression &amp; Mahalanobis distance propensity matching were used to compare incidence rates and outcomes. Results: Among 1.2 million all-cause hospitalizations of patients with renal cancers, about 3.8% suffered an acute VTE. The majority had DVT (1.8%), followed by PE (1.4%) &amp; DVT with PE (0.6%). On a propensity-matched &amp; multivariate analysis, patients with renal cancers have a lower incidence of DVT (2.1% vs 2.8%, aOR: 0.76) &amp; DVT with PE (0.7% vs 1%, aOR: 0.73) [p &lt;0.001] as compared to other malignancies. Interestingly, rates of acute PE are similar to other malignancies (p&gt;0.05). Among VTEs, acute PE was associated with the highest mortality (aOR: 3.17), followed by DVT with PE (aOR: 2.52) &amp; DVT (aOR: 2.15) [p &lt;0.001]. Resource utilization is also higher in renal cancers complicated by VTE, with patients suffering a DVT having the highest LOS (8 vs 3 days) &amp; total cost of hospitalization ($24,403 vs $16,628) [p&lt;0.001] followed by DVT with PE and only PE [p&lt;0.05]. Interestingly, readmission rates are similar in patients with different VTEs (DVT, PE, or DVT with PE, p &gt;0.05). Conclusions: Hospitalizations in renal cancers were less frequently complicated by venous thromboembolism as compared to other malignancies. Mortality was highest for PE while resource utilization was highest for the DVT group.
Racial and gender disparities in the incidence of bladder cancer: A nationwide analysis.
Authors: Vivian Li, Saad Javaid, Kelly Frasier, Julia Vinagolu-Baur, Nataly Ortega Yaguachi, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

e16623 Background: Several studies have been conducted to examine racial and gender disparities in various common malignancies. However, there remains a notable lack of comprehensive data addressing ethnic and gender disparities, specifically in relation to patients with Bladder cancer. This study sought to evaluate these disparities and their potential impact on the risk of developing bladder cancer. Methods: Using the National Inpatient Sample 2020, we identified patients diagnosed with Bladder cancer as their primary condition (local/regional and advanced metastatic).We analyzed disparities in the baseline characteristics, including age, gender, insurance status, income, comorbidities, and the risk associated with Bladder cancer. We utilized a log Binomial regression model to determine the risk ratios after adjusting for any confounding variables. Results: A total of 6,471,165 patients were analyzed, and it was found that 24,400 of them (0.4%) had bladder cancer. Among these patients, 76% were male, and 23% were female, p&lt;0.001.The mean age of patients with and without Bladder cancer was 72(SD +/- 11.39) vs. 49(SD+/- 27.18) years, respectively, p&lt;0.001. Female patients demonstrated a lower risk of developing bladder cancer than males (RR=0.31(0.24-0.27); p&lt;0.001). Compared to white females, white and black males exhibited an increased risk of bladder cancer (RR=3.45(3.20-3.73); p&lt;0.001 and RR=1.71(1.48-1.98); p&lt;0.001, respectively). Hispanic males also showed an increased risk (RR=2.20(1.88-2.58); p&lt;0.001), while Hispanic females demonstrated a decreased risk (RR=0.72(0.56-0.94); p=0.016). Males of other races had a higher risk of bladder cancer (RR=2.95(2.36-3.70); p&lt;0.001), and no significant difference was observed in the risk of bladder cancer in Asian males and females (RR=1.39(0.66-2.92); p=0.384 and RR=0.83(0.34-2.01); p=0.694, respectively). The risk of bladder cancer increased with age (36-45: RR=4.45(2.21-8.96),p&lt;0.001,46-64: RR=10.94(5.67-21.12),p&lt;0.001, &gt;65: RR =21.02(10.87-40.63), p&lt;0.001). Conclusions: Disparities in healthcare access and understanding of specific challenges faced by high-risk groups deeply impact patients with bladder cancer. Gaining a deeper knowledge of these disparities can better support this vulnerable patient population and illuminate effective preventive measures for reducing the incidence of bladder cancer among high-risk demographic segments.
Dietary interventions selectively target dysregulated metabolism and reveal metabolic vulnerabilities in preclinical models of advanced renal cell carcinoma.
Authors: Sabrina Orsi, Musea Chang, Ilaria Delle Fontane, Abbas Jawadwala, Sean Colligan, Filomena De Nigris, Roberto Pili
Journal: Journal of Clinical Oncology (2024)

e16545 Background: Long-term toxicities and acquired resistance to targeted therapies represent a critical clinical challenge for the treatment of advanced clear cell and non-clear cell renal cell carcinoma (RCC), thus highlighting the need for novel therapeutic strategies. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of RCC. As diet has been reported to alter the availability of circulating metabolites available to tumors, dietary interventions represent an innovative strategy to selectively target metabolically dysregulated tumors. Unfortunately, tumor cell plasticity, intratumor heterogeneity, and a lack of understanding regarding metabolic vulnerabilities in tumors are a critical roadblock in the use of dietary restrictions in patients. Therefore, the overall goals of the present study were to better understand nutrient utilization and metabolic dysfunction in RCC to provide biologic rationale for incorporating dietary interventions with standard cancer care. Methods: Using Seahorse, immunohistochemistry, immunofluorescence, metabolomics, and transcriptomics in patient-derived cell lines and murine xenograft models, we investigated the impact protein restriction and alternate day fasting have on energy dynamics in preclinical models of clear cell and translocation RCC. Results: Interestingly, regardless of inherent metabolic phenotype, alternate day fasting was more effective than protein restriction at reducing tumor growth in vivo. Integrated multi-omics analyses of these tumors revealed increased bile acid metabolism with alternate day fasting, indicating a potential tumor suppressive role for these metabolites. Surprisingly, alternate day fasting induced a strong reduction of circulating amino acids that was not observed with protein restriction. Similarly, protein restriction significantly reduced serum triglyceride levels which were not observed in the alternate day fasting group to the same extent. Furthermore, analysis of non-tumor bearing animals revealed distinct metabolite signatures for each dietary restriction that can be easily detected in the blood as a marker of the metabolic state of the host during treatment. Ongoing combination studies with either protein or calorie restriction and targeted therapies, such as standard of care receptor tyrosine-kinase inhibitors, suggest the benefit of using dietary interventions as an adjunct therapy in RCC. Conclusions: Overall, these studies reveal that selective dietary interventions alter the metabolic landscape of RCC and expose vulnerabilities that can be exploited further with targeted therapy.
Practice patterns of high-risk non-muscle invasive bladder cancer (HR-NMIBC) in real-world Canadian practice.
Authors: Geoffrey T. Gotto, Nimira S. Alimohamed, Girish S. Kulkarni, Peter C. Black, Wassim Kassouf, Srikala S. Sridhar, Andrea Kokorovic, Bernhard J. Eigl, Normand Blais, Aly-Khan A. Lalani, Brendan J.W. Osborne, Christopher J.D. Wallis
Journal: Journal of Clinical Oncology (2024)

e16594 Background: There is a paucity of evidence pertaining to real-world treatment of localized bladder cancer, particularly in Canada. We sought to investigate real-world treatment patterns in HR-NMIBC patients, treated in Alberta to understand current treatment practices, predictors of BCG utilization and real-world survival outcomes. Methods: We conducted a retrospective, observational cohort study of de novo HR-NMIBC patients diagnosed between 2010-2022 using population-level administrative databases in Alberta. Data sources included Alberta Cancer Registry (ACR), Vital Statistics, Pharmaceutical Information Network (PIN), Health Practitioner Claims, Discharge Abstract Database (DAD) and National Ambulatory Care Report System (NACRS) databases. HR-NMIBC was defined as AJCC stage N0 and M0 with either Tis, T1, or high-grade Ta (HG-Ta). Patients were followed from diagnosis to last known contact with healthcare system, end of 2021, or death. Multivariable logistic regression analysis was used to identify features associated with receipt of BCG. Results: In this cohort, 3874 HR-NMIBC patients were identified: 82% were male and mean age was 71 years. Tumor stage was T1 in 50%, HG-Ta in 33% and Tis in 17%. Following TURBT, 60.8% of the cohort received no intravesical therapy while 35.6% received BCG treatment, 2.9% intravesical gemcitabine, and 0.6% mitomycin C. Patients who received BCG were predominantly male (83.9%), had T1 tumors (52%) and had a CCI of 0-1 (83.5%). Few (&lt;10%) patients underwent cystectomy. In patients who received BCG, 28.3% completed only one dose 56.9% completed five induction doses, and 32% received “adequate” dosing (≥5 induction doses + ≥2 maintenance doses). In multivariable regression analysis, the strongest predictor of receipt of BCG was high-grade disease (OR 1.62; 95% CI: 1.25-2.10; p &lt; 0.001). Other features associated with higher BCG utilization were younger age, fewer comorbidities, and rural residence and being diagnosed closer to 2010. Overall survival was 10.3 years (95% CI: 116-131 years). Conclusions: In this large, population-based retrospective study, we identify relatively poor utilization of BCG among patients with HR-NMIBC with 32% of patients receiving adequate BCG therapy, per FDA definitions. These data, while concordant with other jurisdictions, do not address underlying causes which may relate to BCG supply issues, patient preference, or fitness to receive therapy, or physician beliefs regarding treatment efficacy. Additional research is needed to identify strategies to improve utilization of guideline recommended therapy among HR-NMIBC patients in real-world settings.
Impact of cytoreductive nephrectomy (CN) and treatment (trt) sequence on overall survival (OS) in metastatic non-clear cell renal cell cancer (nccRCC).
Authors: Ariel Ann Nelson, Aniko Szabo, Deepak Kilari
Journal: Journal of Clinical Oncology (2024)

e16543 Background: nccRCC accounts for 25% of kidney cancer diagnoses and encompasses a diverse group of kidney tumors with distinct biology for which trt in the metastatic setting is evolving. The role of CN for nccRCC population in the current trt landscape remains unclear. Methods: We retrospectively identified patients (pts) with nccRCC from The National Cancer Database (NCDB) participant user file (PUF) for Kidney and Renal Pelvis Tumors. Pts with de novo metastatic disease diagnosed between 2015 and 2020, received systemic trt with immunotherapy (IO) or non-immunotherapy (NIO) and underwent or could have undergone a CN were selected. Pts classified as having sarcomatoid histology were excluded. Demographic and disease characteristics were summarized using descriptive statistics. The cumulative incidence of CN was estimated using the Nelson-Aalen estimator. The association of demographic and disease characteristics on the cumulative incidence of CN was evaluated using univariate Fine-Gray regression. The effect of CN on survival was visualized via Simon-Makuch plot. P values were based on Mantel-Byar test. Cox regression with a time-dependent predictor was used to estimate the change in the hazard of death after CN. Results: We identified 982 pts, median age 60 (18 – 90) years, 61% male, 69% Caucasian and 28% African American. nccRCC histology included 66.5% papillary (n=653), 10.4% chromophobe (n=102), 9.9% medullary (n=97), 8.8% collecting duct (n=86), 4.4% unclassified (n= 43). 69% of pts received NIO (n= 676), 14% received IO + NIO (n= 134), 18% received IO only (n= 172). 40% had CN (n=390), the majority of CN (86%) occurred within 3 months of diagnosis. 89% had CN followed by systemic trt (n=348), 4.3% underwent initial systemic trt followed by CN (n=42). Median OS was 11 months for the entire group. For those who had CN, mOS was 13.9 vs 10 months for no CN (p=0.002). CN was associated with improved survival; HR 0.79 (95% CI 0.68,0.92; p=0.002). Median OS for pts who received systemic trt followed by CN was 32.6 vs 12.8 months for those who had CN followed by systemic trt vs 10 months for those who had no CN, (p=0.001). Upfront systemic trt followed by CN and CN followed by systemic trt were both associated with improved survival, HR 0.56 (95% CI 0.36, 0.87; p=0.009) and HR 0.83 (95% CI 0.69,0.99; p= 0.034) respectively. Choice of systemic trt was not associated with improved OS (p = 0.139). Unclassified and medullary histology were associated with worse OS, HR 1.60 (95% CI 1.09, 2.34; p=0.015) and HR 2.04 (95% CI 1.46,2.84; p=0.002) respectively. Conclusions: CN is associated with improved outcomes for pts with de novo metastatic nccRCC. Sequencing upfront systemic trt followed by CN may improve survival. Prospective randomized trials in the modern trt era are needed and ongoing (Ie. PROBE trial NCT04510597) to further assess the timing and sequencing of CN in pts with nccRCC.
Clinical features, genomic alterations, and survival outcomes for variant histology urothelial carcinoma.
Authors: Mert Sevgi, Rebecca Hassoun, Sandra K. Althouse, Mya Tran, Christopher A. Fausel, Bryan P. Schneider, Tareq Salous, Nabil Adra, Jennifer King
Journal: Journal of Clinical Oncology (2024)

e16549 Background: Twenty-five percent of urothelial tumors exhibit variant histology. Each variant exhibits unique genomic composition and has a distinct clinical course. While there is emerging work describing the clinical and genomic features of variant histology, the integration of both with their impact on clinical outcomes remains less studied. Here, we describe the clinical features, genomic alterations, and outcomes of a real-world cohort of variant urothelial histology. Methods: This was a retrospective review of patients with variant histology urothelial carcinoma who underwent genomic sequencing and were treated at our institution between 2016-2023. Genomic data was derived from standard of care CLIA-next generation sequencing. Demographics and outcomes were derived from chart review. Kaplan-Meier method was used for progression free survival (PFS) and overall survival (OS). Results: 78 patients (pts) were included. Median age was 68.6 (33.7-90.7). 69.2% were male. Variant histology included 15 pts with squamous cell component, 14 pts with plasmacytoid component, 13 pts with micropapillary component, 8 pts with adenocarcinoma. The remaining variant histologies are listed in table 1. 10 pts (12.8%) had more than one variant histology present. 60 pts (76.9%) had metastatic disease; 24 (40%) of them with de novo metastatic disease. Metastatic sites were distant lymph nodes (LN) in 37 pts, lung in 25 pts, bone in 22 pts, and liver in 14 pts. The table lists genomic findings by variant histology. Overall, 2-yr PFS was 29% and 2-yr OS was 69.4%. Median PFS was 0.3 yrs for plasmacytoid vs. 0.4 for adenocarcinoma vs. 0.7 for micropapillary vs. 0.8 for squamous. Median OS was 1.5 yrs for plasmacytoid vs. 2.9 for adenocarcinoma vs. 3 for micropapillary vs. not evaluable for squamous. Conclusions: In this cohort of patients with variant urothelial histology, the most common genomic alterations were TERT and TP53 mutations. Several targetable alterations including KRAS, PIK3CA, and TSC1 were detected across various histology subtypes and suggest a potential avenue for further therapeutic research. Though not statistically significant, PFS and OS were shorter for patients with plasmacytoid and adenocarcinoma variants. [Table: see text]