bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world outcomes of patients with operable renal cell carcinoma from the German translational cancer research consortium (DKTK) network.
Authors: Grünwald Viktor , Thomas Christian , De Santis Maria , Gratzke Christian , Chun Felix , Mager Rene , Retz Margitta , Von Amsberg Gunhild , Ivanyi Philipp , Christian Bolenz , Kübler Hubert , Hadaschik Boris A. , Hahn Svenja , Erhard Ian , Reiter Bastian , Lablans Martin , Vehreschild Janne , Brucker Daniel , Maier Daniel 
Published: January 2024

394 Background: Nephrectomy and risk-adapted adjuvant pembrolizumab are standard treatments in localized renal cell carcinoma (RCC). Risk of recurrence from clinical trials is utilized to council patients. However, recurrence and survival in real-world practice may differ. We report real-world outcome data of patients with RCC from the German Cancer Consortium’s Clinical Communication Platform, a federated data warehouse infrastructure for oncological real-world evidence. Methods: Adult patients from routine care and nephron sparing surgery (NSS) or nephrectomy (Nx) for non-metastatic RCC between 2013-2022 at tertiary German cancer centers were retrospectively analyzed. Clear cell (cc), papillary (p) or NOS histologies were eligible. Kaplan-Meier-analyses were conducted stratified by pathological stage for DFS (Disease-Free-Survival) and OS (overall Survival). Results: 1,291 patients received NSS/Nx. 1,271 (98.5%) were R0/1. Median follow-up: 37.8 mo. (IQR 13.08; 65,74). 754 patients had ccRCC with a mean age of 63.5 y (SD: 12.1), 40% were female. 221 had pRCC, mean age was 62.1 (SD 12.6) and 36.8% were female. 165 had NOS, mean age was 63.3 (SD 12.4) and 36.8% were female. 151 patients had other histologies. Survival outcomes are reported in table 1. Conclusions: Morphologic RCC types and T-stages inform on recurrence and prognosis. Our study advises on real-world recurrence and survival rates in patients with different RCC types, which may be used to counsel patients with regards to adjuvant therapy in the clinic. A major limitation is the retrospective nature of the analysis. [Table: see text]
Pembrolizumab plus lenvatinib vs nivolumab plus cabozantinib in patients with metastatic renal cell carcinoma: A matching adjusted indirect comparison (MAIC).
Authors: Rane Pratik , Walton Laura , Schmidinger Manuela , Peer Avivit , Mt-Isa Shahrul , Burgents Joseph E. , Sundaram Murali 
Published: January 2024

399 Background: Nivolumab plus Cabozantinib (nivo/cabo) and Pembrolizumab plus Lenvatinib (pem/len) have been approved and available for patients in first-line metastatic renal cell carcinoma (RCC). There is no direct evidence of the relative efficacy between pem/len and nivo/cabo from head-to-head clinical trials. Therefore, we conducted MAIC to better inform clinical decision-making on treatment choices. Methods: Individual patient data in the intention to treat (ITT) population from KEYNOTE-581 (pem/len vs. sunitinib; 50.1 months median follow-up) were compared to published aggregated data in the same population from CheckMate-9ER (nivo/cabo vs. sunitinib; 44 months median follow-up). Efficacy outcomes compared were overall survival (OS), progression free survival (PFS), objective response rate (ORR) and complete response (CR). Effect modifiers identified included liver/bone metastasis, sarcomatoid features and IMDC risk category. Using a MAIC, KEYNOTE-581 data were reweighted to match the effect modifiers distribution of CheckMate-9ER participants. Then, matching-adjusted hazard ratios (HR) for OS and PFS, and risk difference (RD) for ORR and CR of pem/len vs. sunitinib were calculated using the reweighted KEYNOTE-581 data. Bucher method was subsequently applied to indirectly compare pem/len to nivo/cabo on these outcomes. Two-sided p-values were calculated. Results: MAIC analyses show that, while OS were comparable between treatments (HR: 1.06 [95% CI:0.77,1.48]; p=0.7072), PFS (HR: 0.75 [95% CI:0.56,0.99]; p=0.0457) and ORR (RD: 11.29 [95% CI:1.10,21.49]; p=0.030) showed a statistically significant result in favor of pem/len when compared to nivo/cabo. The CR rate among pem/len users was higher compared to nivo/cabo but was not statistically significant (RD: 5.75 [95% CI:-0.64,12.15]; p=0.078). Conclusions: In first-line metastatic RCC patients, the MAIC shows a statistically significant result in favor of Pembrolizumab plus Lenvatinib in PFS and ORR, and comparable CR and OS benefit.
Kidney cancer metastases to breast and other genitourinary (GU) organs: A pooled analysis.
Authors: Taboada Phillip , Lee Matthew , Smith Parker , Wang Jue 
Published: January 2024

401 Background: As the number of kidney cancer survivors increases, the appearance of second malignancies and unusual metastatic patterns is increasing. We performed a pooled analysis to assess the clinicopathologic findings, treatment, and outcomes of cases involving breast and GU organs. Methods: Pooled analysis of published case reports and case series of renal cell carcinoma (RCC) metastasis to breast and genitourinary (GU) organs, including four cases from our institution. Parameters were compared between GU organ cohorts using a one-way ANOVA test and subgroup analysis. Results: 127 patients with GU metastasis of RCC were analyzed. The overall mean age was 61.2 years (Range: 14-92). GU organs with reported metastasis included 24 to testis (18.9%), 18 to penis (14.2%), 18 to breast (14.2%), 17 to vagina (13.4%), 17 to bladder (13.4%), 14 to ovary (11%), 7 to prostate (5.5%), and 6 to urethra (4.7%). Median Fuhrman grade was 2.5 overall, with penis metastases (n=4) having a median grade of 4. 95 of 111 (86%) cases reported patients with GU metastasis that had a prior nephrectomy for RCC. Patients with breast metastasis (n=16) had a significantly longer time between nephrectomy and metastatic diagnosis (90.1±63.1 months) than penile (12.7±16.1 months, n=6, p<0.01), bladder (28.7±26.6 months, n=15, p<0.01), or vaginal cohorts (6.7±5.2 months, n=3, p<0.05). Co-metastasis to extra-GU sites were most prevalent in penile metastasis (47.4%, n=9). The primary treatments for metastases were excisional surgery (79%), immunotherapy (18%), radiotherapy (14%), and tyrosine kinase inhibitors (13%). The breast cohort (n=10) reported a 90% survival rate at final follow-up, while the vaginal (n=8) and penile (n=12) cohorts reported survival rates of 50%. The urethra cohort (n=2) had a median survival time of 53 months, while the breast cohort (n=10) had a median survival time of 6 months. Conclusions: While kidney cancer's metastasis to other GU organs is relatively uncommon, it presents unique diagnostic and therapeutic challenges. Recognizing these patterns and understanding the biology behind such spread can offer insights into RCC's behavior and drive more effective treatments. [Table: see text]
Real world data on treatment of chromophobe renal cell carcinoma.
Authors: Battle Dena , Griffith Meghan , Msaouel Pavlos , Voss Martin H , Staehler Michael D. 
Published: January 2024

409 Background: Chromophobe renal cell carcinoma (ChRCC) is the third most common subtype of renal cell carcinoma (RCC), accounting for 5%–7% of all RCCs. ChRCCs are generally viewed to have a favorable clinical outcome compared to clear cell RCC, yet up to 10% of patients with ChRCC will develop metastases. To date, there are no genomic biomarkers that predict post-surgical metastatic recurrence, and no standard of care exists for treating metastatic chRCC. We sought to better understand real world patient experiences in this underrepresented and understudied patient population. Methods: The survey was developed by the Kidney Cancer Research Alliance (KCCure) and was broadcast between 07/2022 and 09/2022 to patients via website, mailing lists and social media platforms. Those who agreed to participate were surveyed for demographics (age, gender, race, income, country) and clinical characteristics (date of the diagnosis, disease stage, treatment history). Out of 1,062 participants 121 patients self-identified with chRCC, 34 patients had metastatic disease, and 23 patients had received systemic therapy. Results: The majority of patients were from the United States (75%), median age was 49.7 years (range 19-74), 70 percent of patients identified as female, and 30 percent of patients identified as male. Stage distribution at initial diagnosis was stage 1 in 37.3%, 27.3% were stage 2 and stage 3 respectively, 8.3% were metastatic at diagnosis. 14% of patients reported having sarcomatoid dedifferentiation. 20 percent of patients (24) experienced recurrent metastatic disease after a median duration of 3.3 years (range 1-6). Of the 23 patients who received treatment, first line therapy consisted of TKI monotherapy (9), combination IO and TKI (7), combination IO/IO (4), mTOR mono-therapy (1), other therapies (2). Second and later line therapies were combination IO/IO (3), IO and TKI (9), Lenvatinib and everolimus (7), TKI monotherapy (5), mTOR monotherapy (5) and other therapies (5). Median duration of therapy was 43 months (range 2-196). The most used TKIs were cabozantinib and lenvatinib. In the metastatic setting, 4 patients reported being treated as part of a clinical trial, 9 patients reported that no one had ever talked to them about participating in a clinical trial. 6 patients said that no trials were being held at their treating center. Conclusions: Patients reported higher rates of recurrence than what is usually reported in ChRCC, however this could reflect sample bias as patients with more aggressive disease may be more likely to engage with patient communities. No standardized treatment for metastatic disease could be identified. Overall treatment duration was comparable to clear cell carcinoma. Very few patients had access to clinical trials. ChRCC-specific clinical trials and tailored treatment regimens are urgently needed.
Final results of a phase I trial of HERV-E TCR transduced T cells for the treatment of HLA-A*11 patients with metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Nadal Rosa , Barisic Stefan , Scurti Gina M. , Cherkasova Elena , Chen Long , Wood Kristen , Highfill Steven L. , Wells Brian , Aue Georg , Shalabi Reem , Hughes Thomas E. , Tian Xin , Xu Yifei , Malayeri Ashkan A. , Reger Robert N. , Nishimura Michael I. , Childs Richard W. 
Published: January 2024

435 Background: Human endogenous retrovirus type E (HERV-E) is specifically expressed in ccRCC providing a safe target for T cell-based therapies. We investigated T cells transduced with a TCR targeting HERV-E (HERV-E T cells) for the treatment of mccRCC. Methods: This first-in-human study assessed the safety & efficacy of escalating doses of HERV-E T cells and manufacturing/clinical endpoints correlative analysis. HLA-A*11+ mccRCC patients (pts) were treated with a conditioning regimen, infusion of HERV-E T cells & IL-2. (NCT03354390). Results: Nineteen of185 pts tested were found to express HLA-A*11. 17 HLA-A*11 + pts enrolled on the study: 3 pts on each DL1-3 & 6 pts on DL4. 2 pts did not receive HERV-E T cells given disease progression during manufacturing period. Median age was 57 years. 86% received ≥ 3 prior systemic treatment (range 1-8). The manufacturing failure rate after first apheresis was 12% (n=2); both met target dose after second apheresis and repeat in vitro expansion. All HERV-E T cell products met release criteria for infusion including INF-γ production in response to HERV-E/HLA-A11-expressing tumor cells. Median HERV-E vector copy number (VCN) was 1.9. No dose-limiting toxicities (DLT), off-target toxicities or treatment-related deaths occurred. Pt#17 is on DLT monitoring period. 7 pts completed the planned 14 doses of IL-2 and all received at least 8 doses. Reasons for IL-2 discontinuation: hemodynamic (57%), cardiovascular (28%), pulmonary (28%), renal (14%) criteria & pts decision (14%). The best response was partial response in 7% & stable disease at least 8 weeks in 29% pts. HERV-E mRNA expression was detected in 5 primary & 9 metastatic specimens. HERV-E T cells were measurable in circulation post-dosing, with peak concentrations in the peripheral blood mononuclear compartment on day(D)+7. [DL1: 0.3 %, DL2: 1.2%, DL3: 0.5%, DL4: 12.3%]. Median HERV-E T cell VCN showed no correlation with HERV-E T cells peak concentration on D+4 & D+7. Conclusions: Proof of concept that HERV-T cells can induce tumor regression without evidence of causing off-target toxicities has been established by this trial. Infused HERV-E T cells were detectable transiently in vivo and induce effector cytokine production. Our initial results support the further development of HERV-E-directed therapies that focus on methods to improve in vivo persistence of TCR engineered T-cells and to target HERV-E antigens expressed on more commonly expressed HLA alleles.[Table: see text]
Breaking boundaries: Exploring extended pembrolizumab in first-line treatment of renal cell carcinoma with axitinib-pembrolizumab combination.
Authors: Aydogdu Can , Paffenholz Pia , Stelmach Ramona , Schlack Katrin , Roghmann Florian , Handke Analena , Mandal Subhajit , Schnabel Marco , Merseburger Axel , Ivanyi Philipp , Zschaebitz Stefanie , Darr Christopher , Grünwald Viktor , Stief Christian G. , Casuscelli Jozefina 
Published: January 2024

436 Background: The standard first-line treatment for metastatic renal cancer (mRCC) combines immune checkpoint- (ICI) and tyrosine kinase inhibitors (TKI). While TKI therapy continues until disease progression, ICI treatment is typically stopped after 24 months or 35 cycles, aligning with approval study criteria. However, in real-world practice, the decision to discontinue ICI therapy upon achieving a positive response can be distressing for both patients and healthcare providers; thus ICIs are not stopped. We conducted an initial analysis of prolonged pembrolizumab (Pem) use in axitinib-pembrolizumab (Axi-Pem) combination therapy to evaluate its effects and toxicity. Methods: We retrospectively analyzed data from mRCC patients treated with first-line Axi-Pem in 10 German tertiary care centers between 2019 and 2023. After completing 35 cycles or 24 months of Pem, patients were offered continued ICI therapy if positive response was assessed. We calculated objective response rate (ORR) and progression-free survival (PFS) from the treatment start to achievement of 36 therapy months. Adverse events (irAEs) were reported following CTCAE 5.0 criteria. Results: Out of 72 patients, 27 met strict eligibility criteria from the Keynote-426 study (NCT02853331), with a response at 24 months and continuous Pem therapy. Patients had a median age of 65.7 years (range: 34-84), and IMDC risk was favorable/intermediate/poor in 22.2%/55.5%/18.5%. Median follow-up was 33.2 months (range: 25.3-48.4). At the 36-mos landmark, median PFS was not reached (PFS 64.7%), ORR was 63.6%, with complete response, partial response, and stable disease observed in 9.1%(1)/54.5%(6)/9.1%(1) of cases, respectively. Permanent Pem discontinuation occurred due to progressive disease in two cases and complete response in one case. Another case led to Pem discontinuation due to immune-related toxicity. Conclusions: In our selected real-world patient cohort seeking prolonged ICI therapy, responders who received continuous Pem beyond 24 months achieve sustained efficacy in first-line treatment. Furthermore, the incidence of irAEs does not increase with prolonged exposure to ICI therapy. Additional results beyond the 36-month landmark are urgently needed to further support the clinical necessity and feasibility of ongoing ICI treatment in light of its impact on the overall financial burden of cancer care.
Lenvatinib plus everolimus (LenEve) in patients with pre-treated advanced renal cell carcinoma (mRCC): Real world evidence (Relevance).
Authors: Ivanyi Philipp , Eggers Hendik , Stelmach Ramona , Boegemann Martin , Strauß Arne , Thomas Christian , Landmesser Johannes , Kramer Mario W , Zschaebitz Stefanie 
Published: January 2024

437 Background: The therapeutic armamentarium in mRCC underwent a rapid change during the recent past. LenEve, proved to be effective as subsequent treatment in mRCC in clinical trials.Here, we evaluate efficacy and safety in mRCC patients in a real-world setting. Methods: mRCC patients who started LenEve treatment between 08/2016 and 12/2021 at 6 tertiary German centers were retrospectively analyzed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), were evaluated per local investigator. Subgroup analyses by risk scores, previous therapies and initial dosing were performed. Results: Eighty-one patients were assessed: Median age was 61 years (range 42-80), 81.5% were males, ECOG score was 0 to 1 in 80.2%. Synchronous metastases were found in 39.5% of patients. The median number of treatment lines prior to LenEve was 3. Median treatment duration with LenEve was 6.1 months (range 0.2-29.2). The ORR, DCR, median OS and PFS was 28.4%, 61.7%, 11.3 months (95% CI 8.7-13.9) and 6.5 months (95% CI 5.4-7.6), respectively. Across patients with 0-2 compared to ≥3 previous therapeutic lines median PFS, OS and ORR were similar, as well as for patients with or without previous immunotherapy. Safety was manageable, with 6.2% of patients discontinuing treatment due to treatment related adverse events. Conclusions: High efficacy in second- and later-line in a heavily pre-treated real-world cohort of mRCC patients was demonstrated by LenEve, regardless of treatment line, IMDC risk group, initial dosing or previous treatment with immunotherapy.
Upfront (uCN) vs. deferred (dCN) cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC): A systematic review and individual patient data (IPD) meta-analysis of 3323 patients.
Authors: Esagian Stepan M. , Karam Jose A. , Msaouel Pavlos , Makrakis Dimitrios 
Published: January 2024

440 Background: Despite the well-established role of CN in the management of mRCC, the optimal timing of CN in regard to systemic therapy remains unclear. Methods: We systematically searched the MEDLINE, EMBASE, and Web of Science databases until August 26th, 2023, for studies comparing uCN and dCN and reconstructed overall survival (OS) IPD from their published Kaplan-Meier survival curves. We then performed one-stage and two-stage meta-analyses of OS, using parametric and non-parametric effect estimates. Landmark analyses using 6-month and 12-month cutoffs were used to account for immortal time bias. We also performed subgroup analyses according to MSKCC/IMDC risk and systemic therapy type. The risk of bias was assessed using the ROBINS-I and RoB2 tools. Results: We identified twelve studies (ten retrospective cohort and two randomized controlled trials) eligible for inclusion. Only two out of ten retrospective studies adjusted for immortal time bias and none of them appropriately adjusted for all predetermined confounding factors. A total of 3323 (2610 uCN and 713 dCN) patients were included in our analysis. Baseline characteristics, including age, gender, histology, IMDC/MSKCC risk score, and location of metastases were comparable between the two groups; the dCN group had more patients with ≥2 metastases (65.4% vs. 47.6%). Deferred CN was associated with superior OS in the one stage (HR: 0.75, 95% CI 0.67–0.84), 6-month landmark (HR: 0.74, 95% CI 0.65–0.84), 12-month landmark (HR: 0.78, 95% CI 0.68–0.91) and two-stage (HR: 0.69, 95% CI 0.58–0.84) meta-analyses. Similarly, dCN was associated with superior OS in the TKI-treated (HR: 0.61, 95% CI 0.51–0.74), ICI-treated (HR: 0.67, 95% CI 0.46–0.97), and intermediate IMDC/MSKCC risk (HR: 0.73, 95% CI: 0.55–0.97) subgroups. Conclusions: Deferred CN for the treatment of mRCC is associated with superior overall survival compared to uCN. Randomized studies are warranted to validate or refute these findings. Further studies to establish predictive models are needed to optimize selection of mRCC patients most likely to benefit from dCN. [Table: see text]
Response evaluation criteria in PSMA PET/CT (RECIP 1.0) in metastatic castration-resistant prostate cancer.
Authors: Gafita Andrei , Djaileb Loic , Rauscher Isabel , Fendler Wolfgang P. , Hadaschik Boris A. , Rowe Steven P. , Herrmann Ken , Calais Jeremie , Rettig Matthew , Eiber Matthias , Weber Manuel , Benz Matthias R. , Farolfi Andrea 
Published: January 2024

45 Background: Response Evaluation Criteria in Prostate-Specific Membrane Antigen (PSMA) PET/CT (RECIP 1.0) initially integrated software-based quantitative assessment of PSMA-positive total tumor volume (PSMA-VOL). Clinical implementation of such software is not expected soon, limiting the use of RECIP in practice. This study aimed to assess the agreement of RECIP determined using tumor segmentation software (quantitative RECIP) with RECIP determined by qualitative reads by nuclear medicine physicians (visual RECIP) for response evaluation in metastatic castration-resistant prostate cancer. Methods: This multicenter retrospective study at three academic centers included patients who received lutetium-177 (177Lu) PSMA treatment between December 2014 and July 2019. PSMA PET/CT images at baseline and 12 weeks were assessed qualitatively by five nuclear medicine physicians for changes in PSMA-VOL and for new lesions. Quantitative changes in PSMA-VOL were also measured using tumor segmentation software. The status of new lesions was combined with qualitative changes in PSMA-VOL to determine visual RECIP and with quantitative changes in PSMA-VOL to determine quantitative RECIP. The primary outcomes were the agreement between visual and quantitative RECIP and the interreader reliability of visual RECIP according to the Fleiss κ. The secondary outcome was the association of visual RECIP with overall survival according to Cox regression. Results: A total of 124 patients (median age, 73 years [IQR, 67–76 years]) were included. Forty (32%) and 84 (68%) patients had quantitative RECIP progressive disease (PD) and non-PD, respectively. Agreement between visual versus quantitative RECIP was excellent (κ=0.89; 118 of 124 patients [95%]). Agreement among readers in classifying visual RECIP PD versus non-PD was excellent (κ=0.81; 103 of 124 patients [83%]). RECIP-PD was associated with significantly shorter overall survival compared with RECIP-nonPD (hazard ratio, 2.6 [95%CI: 1.7, 3.8]; P <.001). Conclusions: Qualitatively assessed RECIP demonstrated excellent agreement with quantitative RECIP and excellent interreader reliability, and can be readily implemented in clinical practice for response evaluation in patients with metastatic castration-resistant prostate cancer undergoing 177Lu-PSMA therapy and possible other systemic therapies.