bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial.
Authors: Tannir Nizar M. , Escudier Bernard , McDermott David F. , Burotto Mauricio , Choueiri Toni K. , Hammers Hans J. , Plimack Elizabeth R. , Porta Camillo , George Saby , Powles Thomas , Donskov Frede , Atkins Michael B. , Kollmannsberger Christian K. , Grimm Marc-Oliver , Tomita Yoshihiko , Rini Brian I. , Jiang Ruiyun , Desilva Heshani , Lee Chung-Wei , Motzer Robert J. 
Published: January 2024

363 Background: First-line NIVO+IPI has provided substantial long-term survival benefits over SUN in patients (pts) with aRCC in CheckMate 214. We report survival, response per independent radiology review committee (IRRC) and safety after 6 y minimum (80 mo median) follow-up in all randomized pts, by IMDC risk and in pts with overall survival (OS) ≥ 6 y (long-term survivors; LTS). Longer follow-up data (minimum, 7.5 y) will be presented. Methods: Pts with clear cell aRCC were randomized 1:1 to NIVO 3 mg/kg + IPI 1 mg/kg Q3W×4 then NIVO 3 mg/kg Q2W vs SUN 50 mg QD for 4 wk on, 2 wk off. Endpoints: OS, progression-free survival (PFS) and objective response rate (ORR; both per IRRC using RECIST v1.1) in IMDC intermediate/poor risk (IP; primary), intent-to-treat (ITT; secondary) and favorable risk (FAV; exploratory) pts. Exploratory outcomes in LTS pts were assessed post hoc. Results: OS with NIVO+IPI vs SUN remained superior in ITT (HR 0.72) and IP (HR 0.68) pts; OS benefits were similar between arms in FAV pts (HR 0.87; Table). Median PFS was consistent with previous reports. ORR per IRRC was higher with NIVO+IPI vs SUN, with more ongoing responses in ITT (60% vs 50%) and IP (60% vs 50%) pts. In FAV pts, ORR was lower with NIVO+IPI vs SUN, yet more responses were ongoing (59% vs 52%, respectively). Median duration of response (DOR) was longer and complete response (CR) rate was higher with NIVO+IPI vs SUN regardless of IMDC risk. Incidence of any and grade 3-4 treatment-related adverse events remained largely unchanged. No new drug-related deaths occurred in either arm since the previous database lock. In the LTS subgroup (NIVO+IPI, n = 208; SUN, n = 151), ORR was higher (66% vs 53%), more pts had a CR (27% vs 9%) and fewer progressed (4% vs 11%) with NIVO+IPI vs SUN. Median DOR was longer with NIVO+IPI (n = 137) vs SUN (n = 80) among LTS with confirmed response (76 vs 40 mo). Updated survival, response and safety data with 7.5 y minimum follow-up, along with additional subgroup analyses, will be presented. Conclusions: NIVO+IPI demonstrated long-term survival and more durable response benefits vs SUN in ITT and IP pts. CR rates were higher and median DOR was longer with NIVO+IPI vs SUN regardless of IMDC risk group, and in LTS pts. No new safety signals emerged. Clinical trial information: NCT02231749 . [Table: see text]
Real-world efficacy and toxicity of ipilimumab and nivolumab as first line treatment of metastatic renal cell carcinoma (mRCC) in a subpopulation of elderly and poor performance status patients.
Authors: Beltran-Bless Ana-Alicia , Shani Shrem Noa , Ghosh Sunita , Tajzler Camilla , Wood Lori , Kollmannsberger Christian K. , Basappa Naveen S. , Graham Jeffrey , Fallah-rad Nazanin , Heng Daniel Yick Chin , Soulieres Denis , Lalani Aly-Khan A. , Breau Rodney H. , Finelli Antonio , Tanguay Simon , Bhindi Bimal , Bjarnason Georg A. , Pouliot Frederic , Canil Christina M. 
Published: January 2024

367 Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) and response rates compared to sunitinib in the pivotal Checkmate 214 trial of intermediate/poor risk mRCC. A subgroup analysis showed no significant difference in OS for ipi/nivo in pts 65 to 75 years old (yo), as well as pts >75 yo. In another subgroup analysis, Karnofsky performance status (KPS) <70 was associated with worse median OS compared with pts with KPS ≥ 70. We evaluated efficacy and toxicity of ipi/nivo in an older and frailer population in a real-world cohort. Methods: Analysis was conducted on a real-world cohort with mRCC (N=378) treated with ipi/nivo as first line treatment from the Canadian Kidney Cancer Information System (CKCis) database from January 2011 to March 2022. Median follow-up was 14.3 m (range 0 to 87.6). A comparison was made between outcomes and toxicity in pts ≥ versus (vs) <70 yo, ≥ vs <75 yo, KPS < vs ≥70, and ≥70 yo with KPS <70 vs <70 yo with KPS >70. Toxicity was graded as per CTCAE v4.03 or any toxicity that resulted in a dose/schedule change. OS, progression free survival (PFS) and time to treatment failure (TTF) were calculated by Kaplan-Meier analysis. Log rank tests were used for comparison between groups. Multivariate analysis was done including IMDC for all outcomes. Results: Median OS was worse in older patients at 30.0 m in pts ≥ 70 yo vs 45.4 m in pts < 70 yo (p=0.060), and 19.0 m in the pts ≥ 75 yo vs 45.5 m in pts < 75 yo (p=0.003) despite similar disease control rates and toxicity. Median PFS was similar in younger and older pts: < vs ≥ 70 yo (p=0.560) and < vs ≥ 75 yo (p=0.296). Median TTF was comparable in < 70 yo and ≥ 70 yo (p=0.106) and < 75 and ≥ 75 yo groups (p-value=0.733). Median OS, PFS and TTF were comparable in pts KPS < 70 vs pts KPS ≥ 70 and in pts ≥70 yo with KPS < 70 vs pts < 70 yo with KPS >70. Adjusted and unadjusted analysis showed no difference in OS and PFS between groups. Conclusions: Use of ipi/nivo in mRCC in older patients was associated with inferior OS, while decreased performance status had equivalent OS. Both groups had equivalent TTF and PD without higher toxicity. We believe that ipi/nivo is a reasonable treatment option for older and low performance status patients. [Table: see text]
Impact of 18F-flotufolastat PET on management of patients with recurrent prostate cancer: Data from the SPOTLIGHT study.
Authors: Twardowski Przemyslaw ,   SPOTLIGHT Study Group
Published: January 2024

38 Background: 18F-Flotufolastat (18F-rhPSMA-7.3) is a newly approved high affinity PSMA-targeting PET radiopharmaceutical for diagnostic imaging in patients with prostate cancer (PCa). SPOTLIGHT (NCT04186845) evaluated 18F-flotufolastat in patients with recurrent PCa. Here, we report available SPOTLIGHT data to assess the impact of 18F-flotufolastat on planned treatment after curative-intent primary therapy. Methods: Patients underwent PET 50–70 min after IV administration of 296 MBq 18F-flotufolastat. The protocol instructed onsite investigators to record patients’ management plans (MP) before and after 18F-flotufolastat PET. These MP were compared and categorized as: ‘no change’, ‘major change’, ‘other change’, ‘additional information required’ or ‘intended plan not valid’. A ‘major change’ was defined as a change to treatment modality (e.g., salvage radiation therapy [RT] to systemic therapy), while ‘other change’ represented a change within a modality (e.g., modified RT field). Plans categorized as ‘no change’, ‘major change’ or ‘other change’ were considered evaluable. All imaging data were subsequently submitted for blinded image evaluation (BIE) by 3 central readers. Results: Of 389 patients who had 18F-flotufolastat PET, 97 had sufficient MP data for evaluation. These 97 patients were comparable to the overall population in terms of prior treatment (84% vs 79%, respectively, were post-prostatectomy), Gleason Score (63% vs 60% had Score 7), and median baseline PSA (0.8 vs 1.1 ng/mL). Moreover, BIE data show the detection rate in this subgroup (81/97; 84%) to be equivalent to that in the overall population (322/389; 83%). Most patients, 86/97 (89%) had a change to their MP post-scan. A ‘major change’ was noted for 78 (80%) patients, while 8 (8.2%) had an ‘other change’ (Table). Onsite imaging reads show that both positive and negative 18F-flotufolastat scans influenced MP. While 88% of revisions occurred after a positive scan, 75% of those whose MP were revised to watchful waiting (WW) had negative scans. All patients with MP revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic 18F-flotufolastat-avid lesions. Conclusions: 18F-Flotufolastat located recurrence sites in the majority of patients with recurrent PCa, frequently resulting in major changes to MP. Treatment based on visualization of 18F-flotufolastat-avid lesions may facilitate optimal targeting of recurrence sites and avoid futile salvage therapy. Future studies of the outcome of such MP changes are warranted. Clinical trial information: NCT04186845 . [Table: see text]
Treatment options and outcome of patients with metastatic renal cell carcinoma with brain or bone metastases: Real world evidence from a German retrospective multi-center analysis.
Authors: Paffenholz Pia , Ivanyi Philipp , Casuscelli Jozefina , Stelmach Ramona , Guer Melis , Schlack Katrin , Darr Christopher , Rinderknecht Emily , Hilser Thomas , Flegar Luka , Klee Melanie , Seidl Daniel , Handke Analena , Nestler Tim , Mattigk Angelika , Augustin Marinela , Hijazi Sameh , Rehlinghaus Marc , Heidenreich Axel , Gruenwald Viktor ,   GUARDIAN
Published: January 2024

387 Background: Brain (BM) and bone metastases (BOM) in renal cell carcinoma (RCC) are associated with poor outcome. We evaluated real-world treatment paradigms of RCC patients with BM and BOM. Methods: We retrospectively analyzed RCC patients with BM and/or BOM treated at 18 German tertiary cancer centres from 2003 to 2023. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to local standard. Overall survival (OS) was calculated from start of treatment to progression or death, respectively and determined by KM plots. Results: We included 453 patients with a median age of 64 years (IQR 56-71). 93% of all patients had BOM, 15% BM and 8% both. Most patients (79%) had clear cell RCC, 7% of all patients had sarcomatoid differentiation. 82% of patients had an ECOG PS of 0/1. IMDC risk was favorable/intermediate/poor in 20/56/24%. 64% received prior nephrectomy. Patients with BOM received first-line IO-combinations in 61% (IO-IO: 38%, TKI-IO: 62%), TKI-monotherapy in 39%, while patients with BM received IO-combinations in 68% (IO-IO: 37%, TKI-IO: 63%) and TKI in 32%. IO-based first-line therapy increased from 2003 to 2023. AE of all grades occurred in 87% and 69% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥ 3 in 42% or 25%. Best ORR and survival outcomes with median follow-up of 23 months (IQR 9-42) are described in table 1. 56% and 58% of all patients with BOM and BM received second-line treatment, with Cabozantinib (34%; 34%) and Nivolumab (17%, 23%) being the most common treatment options. In the subgroup of RCC with sarcomatoid features (n=36), 34 patients had BOM and 7 had BM, of which were treated with IO-combinations in 88% (BOM; IO-IO: 41%, TKI-IO: 59%) or 66% (BM; IO-IO: 50%, TKI-IO: 50%) and TKI-monotherapy in 12% (BOM) or 34% (BM) of all patients. Response rates (ORR/SD/PD) were 48%/28%/24% for IO-based therapy and 0%/50%/50% for TKI-monotherapy in RCC with sarcomatoid features, mOS was 41 months (95% CI 16.7-65.3). Conclusions: RCC patients with BOM and BM are increasingly treated with IO-combinations but lead to higher rates of AE grade ≥ 3. In patients with BOM, IO-TKI revealed higher ORR compared to IO-IO combination, but not in patients with BM. However, the small sample size and retrospective design are major limitations of our analysis. Prospective studies evaluating treatment options for BOM and BM in patients with RCC is critical. [Table: see text]
The role of cytoreductive nephrectomy (CN) in the immune checkpoint inhibitor (ICI) era of metastatic renal cell carcinoma (mRCC): A systematic review and individual patient data (IPD) meta-analysis of 2319 patients.
Authors: Makrakis Dimitrios , Msaouel Pavlos , Karam Jose A. , Esagian Stepan M. 
Published: January 2024

425 Background: The combination of CN and systemic therapy has been established as one of the mainstay treatments for mRCC during the targeted therapy era. However, the role of CN in the ICI era remains unclear. Methods: We performed a systematic search of the MEDLINE, EMBASE, and Web of Science databases until August 26th, 2023, for studies comparing the combination of CN + ICI vs. ICI alone in mRCC. Using published Kaplan-Meier overall survival (OS) curves, we reconstructed IPD and then performed one-stage and two-stage meta-analyses with both parametric and non-parametric effect estimates. To account for immortal time bias, we performed 6-month and 12-month landmark analyses. We also performed a subgroup analysis according to ICI line of treatment. The risk of bias was assessed using the ROBINS-I tool. Results: We identified eight retrospective cohort studies fulfilling our inclusion criteria. Only two out of eight studies adjusted for immortal time bias and none of them adequately adjusted for all predetermined confounding factors. A total of 2319 (1264 CN + ICI and 1055 ICI only) patients were included in our analysis. Patients in CN + ICI group were younger (median age 58.2 vs. 62.8), had lower proportions of non-clear cell histology (8.8% vs. 15.2%), ≥2 metastatic sites (60.0% vs. 68.5%), liver metastases (9.0% vs. 21.9%), and poor IMDC risk score (21.7% vs. 43.9%), but had higher proportions of sarcomatoid histology (15.6% vs. 10.6%) and ≥2nd line treatment (38.1% vs. 17.1%). The combination of CN + ICI was associated with superior OS in the one stage (HR: 0.45, 95% CI 0.38–0.52), 6-month landmark (HR: 0.45, 95% CI 0.37–0.54), 12-month landmark (HR: 0.50, 95% CI 0.31–0.50) and two-stage (HR: 0.38, 95% CI 0.29–0.49) meta-analyses. Similarly, the combination of CN + ICI was associated with superior OS in the subgroup of patients receiving first-line ICI (HR 0.39, 95% CI: 0.30–0.48). Conclusions: The combination of CN + ICI for mRCC may be associated with superior OS compared to ICI alone, but currently available data are subject to selection bias. More studies, including well-designed randomized controlled trials, are needed to determine the role of CN in the ICI era. [Table: see text]
Effect of dipeptidyl protease 4 (DPP4) inhibitors on progression-free survival in patients with metastatic renal cell carcinoma: A single-center retrospective analysis.
Authors: Ali Soham , Fortune Kathryn , Masur Jack , Viscuse Paul Vincent , Devitt Michael Edward , Dreicer Robert , Skelton William Paul 
Published: January 2024

426 Background: Dipeptidyl peptidase IV (DPP4) is a cell surface receptor with exopeptidase activity that is expressed on most cell types, and possesses numerous substrates including growth factors, chemokines, and vasoactive peptides. These effects have implicated DPP4 in tumor growth and metastasis. Prior SEER-Medicare and retrospective studies have suggested an association between DPP4 inhibition and increases in both progression-free survival (PFS) and overall survival (OS) in patients with colorectal and lung cancers. Similar studies have shown no associated OS benefit from DPP4 inhibition in breast or pancreatic cancers, and increased OS but not PFS in prostate cancer. However, no studies to date have explored the impact of DPP4 inhibitors (DPP4i) in renal cell carcinoma (RCC). Thus, in this study we present a first-time analysis examining the impact of DPP4i use on PFS in patients with metastatic RCC and type 2 diabetes mellitus. Methods: We performed a single-center retrospective analysis of patients with diabetes and metastatic RCC at University of Virginia. The control group included patients who were on metformin, a sulfonylurea or SGLT2 inhibitor during treatment for metastatic RCC, while the study group included those who were taking a DPP4i with or without metformin and other diabetes medications during treatment. The primary and secondary endpoints of this study were PFS and OS, respectively. Results: Fifty-nine patients were eligible for the study, 11 of whom were taking a DPP4i with or without other diabetic medications during RCC treatment, while 48 were taking metformin with or without other non-DPP4i medications. Cancer progression occurred in 81.8% of patients in the DPP4i group compared to 66.7% of patients in the control group with an odds ratio of 1.58 (95% CI: 0.672-3.71), p = 0.57. No statistically significant difference on PFS (HR: 1.60; 95% CI: 0.75-3.43; p = 0.24) or OS (HR of death: 0.73; 95% CI: 0.27-1.97; p = 0.52) was found in this study. Conclusions: This retrospective study explored the effect of DPP4i on outcomes in patients with metastatic RCC and diabetes. While DPP4i have been shown in previous SEER-Medicare and retrospective studies to have favorable effects on PFS and OS in certain cancers such as colorectal and lung, the results of this study suggest that DPP4i do not confer clinical benefit in patients with RCC, similar to pancreatic and breast cancers. Given the small sample size in this study, larger studies are warranted to better elucidate the effect of DPP4i in metastatic RCC as well as the mechanisms underlying differential tumor response to these agents.
Utility of PSMA PET/CT for imaging ductal carcinoma of the prostate.
Authors: Mahmoud Ahmed M. , Navin Patrick , Muniz Miguel , Quevedo Fernando , Orme Jacob , Andrews Jack R. , Kase Adam McLain , Mosalem Osama M , Bryce Alan Haruo , Riaz Irbaz Bin , Burkett Brian J. , Kendi Ayse T. , Johnson Geoffrey , Ravi Praful , Kwon Eugene D. , Sartor Oliver , Childs Daniel S 
Published: January 2024

49 Background: Ductal carcinoma (DC) is the second most commonly encountered histologic variant of prostate cancer. Previous studies have described its molecular features and aggressive behavior, but few have explored the performance of PSMA PET/CT in the initial staging and follow-up of DC. Methods: To address this gap, we performed a single-institution retrospective analysis using the Mayo Clinic PSMA PET database. All patients receiving a PSMA PET/CT scan in the interval of January 1, 2021, to December 31, 2022, were eligible for inclusion. Cases were filtered and categorized by histology at the time of diagnosis to select for pure DAC and mixed ductal variants. Trained research personnel annotated disease- and treatment-related variables. A board-certified radiologist performed tumor burden segmentation with calculations of SUV max, total lesion SUV mean and volume, and total lesion uptake, and ascribed a miPSMA expression score. Results: We queried 1792 patients from our PSMA PET/CT registry and identified 32 (1.8%) patients with a pathologically confirmed DC, including 8 (25%) patients with pure ductal and 25 (75%) patients with mixed histology. The indication for PSMA PET/CT was biochemical progression or restaging for 29 (91%) patients and initial staging for 3 (9%) patients. The median (IQR) time from prostate cancer diagnosis to PSMA PET scan was 41.6 (11.5-64.7) months, during this time 50% (n= 16) of patients developed CRPC. At the time of the PSMA PET/CT scan, the median age was 70 years, the median (IQR) PSA was 0.5 ng/mL (0.2-2.6). The distribution of metastatic spread and quantitative imaging parameters from PSMA PET are shown in the Table. Conclusions: Despite low PSA at the time of imaging, PSMA PET/CT frequently detected high volume osseous and/or visceral metastases in patients with DC. However, it is noteworthy that more than 50% of patients with DC had a low miPSMA score (0-1). Additional studies are needed to better understand the performance of novel imaging modalities when evaluating variant prostate cancers. [Table: see text]
Identification of a panel of microRNA biomarkers for the management of patients with refractory germ cell tumor of the testis.
Authors: Chen Jim Zhongning , Aydin Ahmet , Gokden Neriman , Langford Timothy , Tu Shi-Ming 
Published: January 2024

521 Background: In 1946, nearly 90% of patients diagnosed with metastatic Testicular Germ Cell Tumor (TGCT) succumbed to the disease within a year. In the present day, over 90% of such patients are successfully cured. However, there is a remaining 10% of patients have tumors that consist of chemotherapy-resistant forms of TGCT, such as yolk sac tumors and teratomas. This underlines the need for developing biomarkers that can guide the choice between additional chemotherapy and surgical intervention. MicroRNAs (miRNAs), non-coding RNA molecules that control post-transcriptional modifications, have shown promise in identifying TGCTs. Research has particularly highlighted the overexpression of miR-371a-3p and miR-375-3p in TGCTs. Nevertheless, these miRNAs are not effective in distinguishing between teratomas and other TGCT types. The Cancer Genome Atlas (TCGA), a publicly accessible database, offers clinical and miRNA data on various tumors, including TGCTs. Our objective is to leverage TCGA to identify miRNAs that can be used to classify TGCTs containing teratomas from those that do not. Methods: Between 2001 and 2013, TCGA gathered a total of 135 primary TGCT samples. We group these tumors into those without teratomas and those with any teratomatous components. We used EdgeR, a Bioconductor package designed for differential expression analysis of RNA that accounts for both biological and technical variation. A false discovery rate of less than 1e-8 was applied. A heatmap was generated to display the hierarchical clustering of differentially expressed miRNAs. Results: Based on the above cut-off, a panel of 50 miRNAs of differentially expressed miRNA were used to generate a hierarchical clustering that showed clear clustering between the two groups. Notably, tumor suppressor miRNAs such as hsa-mir-203a, hsa-mir-199, and hsa-mir-152, which are usually downregulated in non-teratoma TCGT, are overexpressed in teratomas. Other miRNA including hsa-mir-146a and hsa-mir-3607, which are downregulated tumor suppressors for non-TCGT are also downregulated in teratomas but not in teratoma-free TGCT. Conclusions: Despite the high cure rate for TGCTs, tumors containing chemotherapy-resistant teratomas still contribute to elevated mortality rates. Utilizing TCGA data, we identified a set of miRNAs that are effective in distinguishing between teratoma-containing and teratoma-free TGCTs. This miRNA panel has the potential to inform decisions related to surgical treatment plans and provide further insight into the biology of the disease.