bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRP kinetics to predict long-term efficacy of first-line immune-checkpoint inhibition combination therapies in metastatic renal cell carcinoma: An updated multicenter real-world experience applying different CRP kinetics definitions.
Authors: Hoeh Benedikt , Cano Garcia Cristina , Banek Severine , Klümper Niklas , Cox Alexander , Ellinger Joerg , Schmucker Philipp , Hahn Oliver , Mattigk Angelika , Zengerling Friedemann , Becker Philippe , Erdmann Kati , Buerk Bjoern , Flegar Luka , Huber Johannes , Kalogirou Charis , Zeuschner Philip 
Published: January 2024

405 Background: Although biomarkers predicting therapy response in 1st line metastatic renal carcinoma (mRCC) therapy remain to be defined, C-reactive protein (CRP) kinetics have recently been associated with immunotherapy (IO) response. To assess the predictive and prognostic power of two contemporary CRP kinetics definitions in a large, real-world 1st line mRCC cohort. Methods: mRCC patients treated with IO-based 1st line therapy within 5 years were retrospectively included in this multi-center study. According to Fukuda et al., patients were defined as ‘CRP flare-responder’, ’CRP responder’ and ‘non-CRP responder’; according to Ishihara et al., as ‘normal’, ‘normalized’ and ‘non-normalized’ based on their early CRP kinetics. Patient and tumor characteristics were compared, and treatment outcome was measured by overall (OS) and progression-free survival (PFS), including multivariable Cox regression analyses. Results: Out of 316 mRCC patients, 227 (72%) were assigned to CRP groups according to Fukuda. Both CRP flare- (HR [Hazard ratio]: 0.59) and CRP responders (HR: 0.52) had a longer PFS, but not OS, than non-CRP responders. According to Ishihara, 276 (87%) patients were assigned to the respective groups, and both normal and normalized patients had a significantly longer PFS and OS, compared to non-normalized group. Conclusions: Different early CRP kinetics may predict therapy response in 1st line mRCC therapy in a large real-world cohort. However, further research regarding the optimal timing and frequency of measurement is needed.
Comparison of financial toxicity among patients with non-metastatic versus metastatic renal cell carcinoma.
Authors: Staehler Michael D. , Vaishampayan Ulka N. , Pal Sumanta Kumar , Msaouel Pavlos , Derweesh Ithaar , Battle Dena 
Published: January 2024

408 Background: Little is known about the financial impact of renal cell carcinoma (RCC). We sought to ascertain real world data on financial implications and how financial toxicity (FT) impacts quality of life in patients with localized RCC versus patients with metastatic RCC. Methods: An online survey was conducted by the Kidney Cancer Research Alliance (KCCure), a non-profit patient advocacy organization, from 7/22 to 9/22. The survey included questions about costs and financial concerns and the COST questionnaire. Pearson’s correlation (r) and Kendal’s tau test were used to analyze the COST questionnaire, financial burden and hardship. Results: Out of 1062 responders 623 had localized RCC. Out of these patients 395 did not recur and 204 were willing to answer questions related to cost and financial hardship. 289 responders had metastatic disease and were on systemic therapy and 177 pts answered the COST questionnaire. In localized disease 28% reported that their diagnosis has not reduced their income, in 26% the diagnosis had reduced their income very much.31% experienced insurance denials for imaging, 30% faced delays in care due to pre-approval requirements, 45% faced high out-of-pocket costs for medical care. 24% of patients reported taking a hardship withdrawal from a retirement account, 28% stopped funding or lowered contributions to an existing retirement account, 20% borrowed from friends or family. In metastatic patients 14% reported difficulties to pay their premiums. 28% reported that their medical situation has not reduced their income and 26% claimed that their disease reduced their income very much. 36% reported high out of pocket costs are a barrier to care. 44% have received financial support through a manufacturer or a foundation. Median COST score in non-metastatic RCC was 32 (range 19-44)) and was significantly correlated to age, NCCN distress score, risk of recurrence and supplement intake (p < 0.05). Metastatic patients had a significantly higher median COST score of 22 (range 4-36)) that was also correlated to age, NCCN distress score, time since diagnosis and supplement intake (p < 0.05). Conclusions: RCC imposes financial hardship on patients. Younger patients with a higher NCCN distress score and a shorter time since diagnosis are more likely to suffer financial hardships. Patients are willing to pay for supplements. Financial counseling should be considered in these patient subgroups regardless of stage. [Table: see text]
The feasibility of an educational and monitoring smartphone application for patients with advanced renal cell carcinoma undergoing combination immunotherapy.
Authors: Roman Souza Gabriel , Paravathaneni Mahati , Ionescu Filip , Gullapalli Keerthi , Raymond Sarah , Jameel Ghazal , Chadha Juskaran , Jain Rohit K. , Trujillo Gillian , Budet DeJesus Amayla M. , Manley Brandon J. , Schneider Amy , Kim Youngchul , Semaan Adele , Jim Heather S.L. , Spiess Philippe E. , Chahoud Jad 
Published: January 2024

413 Background: Renal Cell Carcinoma (RCC) is a global public health burden with over 400,000 new cases and over 175,000 deaths annually. Immune checkpoint inhibitors (ICI) in combination with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI) has become an integral part of the management of patients with advanced RCC which requires adaptation of healthcare systems to provide information and optimize the management of drug-related adverse events. This study aims to improve the education on therapy-related symptoms and the quality of life of patients with RCC treated with these drugs. Methods: We created a smartphone application (mHealth) that combines educational data, patient-reported outcomes, and peer-to-peer interactions. We aim to assess the feasibility of expansion of this pilot study. We prospectively enrolled stage IV RCC patients (n=20) undergoing treatment with combination ICI and VEGF-TKI. Therapy-related symptom education, knowledge PRO questionnaires, and peer-to-peer support were provided at baseline and at different time points throughout this study duration (Table 1). Time-course data of PROs were visualized using line plots and then compared with paired t-tests. The study's primary endpoint was to assess acceptability and feasibility of mHealth, defined as acceptable if 50% of patients offered participation agree to be enrolled and feasible if 50% of enrolled patients complete the intervention with 70% of these completing at least 50% of survey instruments. Results: Eighty percent of patients were male, 80% were white, 75% had at least some college education, 70% were married, and the mean age of the cohort was 66 years.A total of 22 patients were approached for the study with an acceptance rate of 90%. Sixty percent of patients completed every questionnaire and knowledge assessment at every timepoint of the intervention and 75% of those completed at least 50% of instruments. PROs data showed no significant difference compared to baseline in global health status, functional scales, and symptom scales across the 24 weeks. We noticed an improvement in the patients' knowledge assessment on symptom management after completion of the mHealth knowledge component. Conclusions: Our pilot study was considered acceptable and feasible, showing preliminary evidence of improvement in patient knowledge with mHealth. Our future direction will be to assess, in a larger randomized study, the efficacy of mHealth in improving the quality of life of patients with advanced RCC treated with ICI and VEGF-TKI. Clinical trial information: NCT05579847 . [Table: see text]
Association of radiographic and pathologic outcomes in patients (pts) with advanced renal cell carcinoma (RCC) with and without thrombus receiving preoperative immune checkpoint inhibitor (ICI) regimens and circulating biomarkers.
Authors: Issa Wadih , Gunenc Damla , Zhang Song , Zhou Qinhan , Gerald Thomas , Tachibana Isamu , Bhanvadia Raj Ramnik , Kapur Payal , Woldu Solomon L. , Lotan Yair , Cadeddu Jeffrey A. , Gaston Kris , Qin Qian , Brugarolas James , Hammers Hans J. , Wang Andrew Zhuang , Margulis Vitaly , Zhang Tian 
Published: January 2024

415 Background: Primary RCC tumors and associated IVC thrombus have similar histology, however response to ICI is not always concordant. RCC with IVC thrombus is often difficult to manage, and perioperative ICI treatment responses remain largely unstudied. Methods: We conducted a retrospective analysis of pts with advanced RCC receiving preoperative ICI-based regimens at UTSW stratified by the presence of tumor thrombus. The primary objectives were pathologic change in both groups and radiographical response by RECIST 1.1 criteria for tumor and thrombus level change. The secondary objective was to evaluate biomarkers associated with thrombus. Comparisons were performed using a two-sample t-test or aChi-square test. Results: 65 pts were included (median age 64 years), 31 (48%) with baseline thrombus (9 (29%) renal vein thrombus; 6 (19%) level 1 IVC thrombus; 10 (32%) level 2; 2 (7%) level 3; and 4 (13%) level 4). 28 pts (43%) received ICI+ICI, while 20 pts (31%) received ICI+TKI and the rest received ICI monotherapy. 18/31 pts (58%) with thrombus and 20/34 without thrombus (59%) had metastasis at baseline. Pathological Tumor (pT) downstaging occurred in 13 pts with and 11 pts without thrombus; of these, 12 pts had received ICI+TKI and 12 pts ICI+ICI. Radiographic tumor (cT) downstaging occurred in 8/31 pts with thrombus and 7/34 pts without. 12/31 pts experienced thrombus downstaging. 5 pts with thrombus vs 2 pts without had complete tumor necrosis/pCR in the primary and radiographic PR, of whom 4/7 received ICI+TKI. In pts with IVC thrombus, preoperative ICI based regimens reduced median tumor size from 9.1 to 7.7 cm. Among responders in pts with IVC thrombus, ICI+TKI had a trend toward higher tumor shrinkage median (-3.3 vs -1.9 cm, p=0.3) and thrombus downstaging median ( -2 vs -1 levels , p=0.27) than ICI+ICI. Baseline anemia (Hemoglobin (Hgb), 11.1 vs 13.1 g/dL, p=0.002), lower Absolute Lymphocyte Count (ALC) (1.35x10^3 vs 1.55 x10^3 cells/uL, p=0.03), and higher Neutrophil-to-Lymphocyte ratio (NLR) (3.6 vs 3.2, p=0.03) were observed in pts with IVC thrombus. Conclusions: ICI+TKI regimens tend to have tumor downstaging, complete tumor necrosis/pCR in primary tumors, and some IVC thrombus control compared to ICI+ICI regimens. IVC thrombus is associated with lower Hgb and ALC and higher NLR levels. Prospective trials are ongoing to investigate perioperative treatment in pts with IVC thrombus. [Table: see text]
Systemic and surgical treatment in renal cell carcinoma: Does timing matter?
Authors: Seitzer Konstantin Egon , Darr Christopher , Hilser Thomas , Schrader Andres Jan , Huberth Linda , Mausbach Anne , Janssen Martin , Krabbe Laura-Maria , Heitplatz Barbara , Hadaschik Boris A. , Boegemann Martin , Schlack Katrin , Grünwald Viktor 
Published: January 2024

417 Background: Today, targeted systemic therapy is standard 1st line treatment of advanced/metastatic renal cell carcinoma (aRCC). Upfront cytoreductive nephrectomy (CN) has been an important treatment option. Recently its role is under debate, especially in combination with the new 1st line treatments. Our study evaluated the current relevance of initial surgical intervention and the role of inductive systemic therapy in aRCC. Methods: We included 33 patients with aRCC from the University Hospitals in Essen and Münster initiating 1st line treatment from 03/18 to 01/23 pre or post surgery. We retrospectively formed two cohorts, either CN followed by systemic therapy (cohort 1; 13 patients) or vice versa (cohort 2; 20 patients). Patients received either Ipilimumab/Nivolumab (Ipi/Nivo) (42.4%) or a checkpoint inhibitor and tyrosine kinase inhibitor (CPI/TKI) combination (57.6%). Progression-free survival (PFS) was estimated with Kaplan-Meier-method from initiation of systemic therapy or CN to progression or death. In Cohort 2, we additionally analyzed the radiologic response of the primary measured by change of the longest diameter. The radiographic response was analysed according to RECIST1.1. Results: Patients’ age ranged from 44 to 80 years with a median of 63 years. Intermediate and poor prognosis occurred in 61.3% and 38.7% of cases. The two cohorts did not differ significantly regarding baseline characteristics. Median PFS was 8 vs. 23 months (p=0.03) in cohort 1 (95% CI 0.9-15.1) compared to cohort 2 (95% CI 18.8-27.2). In cohort 2 the time between start of systemic therapy and surgery was in median 8.5 months (95% CI 3.3-21.1), the primary had a median diameter of 10.7 cm (95% CI 4.5-13.3). Median reduction of the primary was in total 32.2%, 28.9% in the Ipi/Nivo and 34.7% in the CPI/TKI group (p=0.74). In seven patients (35%) response led to modification of the surgical approach, enabling partial instead of radical nephrectomy. Conclusions: The sequence of systemic therapy followed by surgery was associated with a significant PFS benefit. In addition, prior systemic therapy led to a primary reduction and better operability, in some cases even to kidney sparing surgery. Major limitation is the retrospective nature of our analysis and a potential selection bias. However, the sequence of prior systemic therapy followed by surgery in aRCC was associated with notably better outcomes.
Pembrolizumab plus lenvatinib (P+L) versus alternate therapies in first-line (1L) for advanced renal cell carcinoma (aRCC): A network meta-analysis (NMA).
Authors: Yan Kevin , Rane Pratik , Schmidinger Manuela , Peer Avivit , Druyts Eric , Burgents Joseph E. , Sundaram Murali 
Published: January 2024

422 Background: Patients with advanced renal cell carcinoma (aRCC) have poor prognosis resulting in significant burden. In the KEYNOTE-581/CLEAR trial, pembrolizumab plus lenvatinib (P+L) as 1L therapy showed statistically significant and clinically meaningful improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) versus sunitinib in patients with aRCC. This NMA synthesized evidence from randomized clinical trials (RCTs) to indirectly compare the relative treatment effects of P+L vs alternate therapies in treatment-naïve aRCC. Methods: A systematic literature review was conducted to identify systemic therapies in 1L aRCC. A Bayesian NMA with fixed-effect models was performed to indirectly compare P+L to alternate therapies using sunitinib as the common comparator in 1L aRCC. Hazard ratios (HRs) for OS and PFS were calculated with 95% credible intervals (CrIs). NMAs assuming constant hazard ratios (HRs) and time-varying HRs were performed for OS and PFS. For the proportion of patients experiencing response, a binomial likelihood and logit link were used, and relative effects were expressed as odds ratios (OR). Results: A total of 33 unique RCTs met the inclusion criteria and were included in the analyses. The constant HR analysis resulted in no significant differences in OS between P+L and alternatives in network. Results showed statistically significant higher ORR for P+L compared to nivolumab + ipilimumab (N+I) (OR=3.19; 95% CrI: 2.14, 4.82) and pembrolizumab + axitinib (P+A) (OR=1.84; 95% CrI: 1.21, 2.80). The analysis also favored P+L over nivolumab + cabozantinib (N+C) (OR=1.35; 95% Crl: 0.86, 2.12) and avelumab + axitinib (A+A) (OR=1.46; 95% Crl: 0.96, 2.23), but was not statistically significant. The constant HR analysis showed that P+L resulted in a statistically significant improvement in PFS compared to N+I (HR=0.55; 95% CrI: 0.40, 0.75), A+A (HR=0.68; 95% Crl: 0.49, 0.96) and P+A (HR=0.69; 95% CrI: 0.51, 0.94). The analysis also favored P+L over N+C (HR=0.81; 95% Crl: 0.58, 1.14), but was not statistically significant. Conclusions: NMA indicates P+L has higher ORR and improved PFS compared to other regimens in 1L aRCC. No significant differences in OS were observed between P+L and competing interventions.
Impact of renin-angiotensin system inhibitors on response to PD1/L1 inhibitors in patients with metastatic renal cell carcinoma (mRCC).
Authors: Fortune Kathryn , Ali Soham , Masur Jack , Viscuse Paul Vincent , Devitt Michael Edward , Dreicer Robert , Skelton William Paul 
Published: January 2024

424 Background: The renin-angiotensin system (RAS), traditionally associated with blood pressure regulation and fluid balance, also plays a role in tumor development and growth among several cancer types. Renin-angiotensin system inhibitors (RASI), such as angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs), have been shown in studies of various malignant neoplasms to be associated with improved outcomes. In metastatic urothelial cancer, the use of ACEI and ARBs has been associated with higher rates of tumor regression among patients (pts) receiving immunotherapy (IO) with PD1/L1 inhibitors. One potential mechanistic explanation is RASI-induced downregulation of TGF-beta, for which high expression is a known mechanism of PD1/L1 inhibitor resistance. While the development of novel IO therapies has changed the treatment landscape for mRCC, only one study to date has examined the impact of RAS inhibition in pts with mRCC receiving IO. We hypothesized that concurrent RASI in pts with mRCC receiving IO is associated with increased tumor regression. Methods: We conducted a retrospective analysis of pts with mRCC receiving immunotherapy as a first or second line of treatment from 2016-2023 at the University of Virginia. A logistic regression model was used to evaluate the impact of concurrent RASI on tumor regression. The primary endpoint in this study was any regression of tumor on imaging. Results: Data were available for 147 pts with mRCC who received IO as a first- (n=104, 70.7%) or second- (n=43, 29.3%) line treatment. 52 pts (35.4%) received ACEI/ARBs during IO; 42 pts (40.4%) who received IO as first-line treatment were on ACEI/ARBs and 10 patients (23.2%) who received IO as a second-line treatment were on ACEI/ARBs. Analysis showed that pts who received ACEI or ARBs during IO were more likely to have tumor regression compared to pts who were not on concurrent RASI (OR 7.43 [95% CI 2.70-23.53], p=0.0002). This held true regardless if pts received IO as a first-line (OR 6.02 [95% CI 1.84-23.38], p=0.005) or second-line (OR 9.71 [95% CI 1.51-122], p=0.032) treatment. Conclusions: Our hypothesis generating study suggests that in our RCC population the concurrent use of RASI in pts with mRCC receiving IO was associated with a significantly increased likelihood of tumor regression. These findings highlight the potential therapeutic advantage of RASI in combination with IO for mRCC pts. Further exploration of this association is warranted in prospective studies to improve treatment outcomes for this patient population.[Table: see text]
Immune-related adverse events (irAEs) and the association with clinical outcomes in advanced genitourinary cancers treated with immunotherapy: A systematic review and meta-analysis.
Authors: Zhang Yaowen , Chen Junru , Sun Guangxi , Zhang Xingming , Zeng Hao 
Published: January 2024

431 Background: The approval of several immune checkpoint inhibitors (ICIs) for the treatment of advanced genitourinary cancers has resulted in a significant revolution in the management of urological tumors. This study investigated the profile of the irAEs and evaluated the association between irAEs and clinical outcomes in the patients with advanced genitourinary cancers treated with ICIs. Methods: We conducted a comprehensive search of online databases up to April 2023 to identify eligible studies. We extracted the type, grade, and frequency of irAEs, the hazard ratios(HRs) and corresponding 95% confidence intervals (95%CIs) for overall survival (OS) and progression-free survival (PFS), raw data or the odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) for objective response rate (ORR) and disease control rate (DCR). RevMan5.3 software was used to calculate pooled results. Results: A total of 21 studies with 4779 patients were included. Of those, 13 studies investigated renal cell carcinoma (RCC), 6 studies investigated urothelial carcinoma (UC), and 2 investigated mixed population with RCC or UC. The pooled overall incidence was 29.0% (95%CI: 28.0%-30.0%) for any-grade irAEs in RCC and UC and 13.0% (95%CI: 11.0%-14.0%) for grade ≥3 irAEs. Furthermore, the HRs for OS and PFS in advanced genitourinary cancer patients with versus without irAEs were 0.45 (95%CI: 0.40-0.51, p < 0.001) and 0.41 (95%CI: 0.31-0.55, p < 0.001), respectively. The ORs for overall ORR and DCR in advanced genitourinary cancer patients with irAEs versus without irAEs were 3.65 (95%CI: 3.03-4.39, p < 0.001) and 4.19 (95%CI: 2.94-5.97, p < 0.001), respectively. In the subgroup analysis, we also observed a positive association between the occurrence of irAEs and improved treatment outcomes in UC and RCC, respectively. Specifically, patients with skin irAEs showed a better OS, patients with skin irAEs and thyroid disfunction were associated with better PFS. Conclusions: Our study provides a comprehensive overview of irAEs in advanced genitourinary cancers treated with immunotherapy. Our findings suggest that the occurrence of irAEs could be a favorable prognostic factor for advanced genitourinary cancer patients treated with ICIs.