bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ga-68 PSMA-11 impacting prostate cancer management in a real-world setting: A pilot experience using the total-body PET/CT scanner.
Authors: Kulkarni Harshad R , Rogers Dan , Maupin Kevin , Faasse Todd , Forsberg Jens , DeLong Matt , Mancini Brandon Robert 
Published: March 2023

62 Background: PET/CT using Ga-68 PSMA-11, which received FDA approval, can detect early biochemical recurrence of prostate cancer at greater sensitivity than conventional imaging, as well as more accurately clinical stage and impact treatment management, particularly vital for high-risk patients. We present our first experience with Ga-68 PSMA-11 PET/CT using the total-body PET/CT scanner (uExplorer). Methods: PET/CT imaging (1-bed acquisition of the entire body for 5 minutes) was performed on the uExplorer scanner 56-65 minutes after administering 150-200 MBq of Ga-68 PSMA-11 (Illucix) in 14 patients with prostate cancer at our clinic. The medical records of these patients were reviewed. Results: Of the 14 patients who underwent Ga-68 PSMA-11 total-body PET/CT, 6 had high risk, 6 had intermediate risk and 2 had low risk cancers. The scan was negative in 1 patient, whereas local recurrence and pelvic lymph nodes could be identified in the other patient with low-risk prostate cancer. The smallest size of the lymph node identified was 2 mm. All patients with intermediate and high-risk cancers had metastatic disease – 2 had metastases to the lymph nodes only. Of the 10 patients with widespread metastases to bones and lymph nodes, 4 had additional visceral metastases – in 3 patients to the lungs and in 1 to the liver. The line of management changed in 10/13 patients with a positive scan – 5 were treated with Lu-177 PSMA radioligand, 4 with chemotherapy and 1 with local irradiation. Conclusions: Our pilot experience is consistent with the clinical value of Ga-68 PSMA-11 PET/CT (Illucix) imaging to better inform patient management, in addition to demonstrating the role of rapid and high-resolution imaging with the total-body PET/CT scanner (uExplorer). With the availability of PSMA PET/CT, it should be considered the new standard of care for men who have prostate cancer for staging or localization of recurrence.
The predictive value of hematological markers in renal cell carcinoma.
Authors: Al Ta'ani Omar , Abu-Shawer Osama , Abdelhadi Saja Jamil , Alkderat Murad , Sultan Hala , Alshahwan Hebah , Safi Diya' Maher Y , Abuelbeh Ibrahim , Safi Mohannad Maher Y , Al-Hussaini Maysa 
Published: March 2023

621 Background: Renal cell carcinoma (RCC), which accounts for about 3% of adult malignancies, is regarded as a major cause of morbidity and mortality. The neutrophil-lymphocyte ratio (NLR) is a simple, reliable, and cost-effective biomarker of systemic inflammation that has been linked to oncologic outcomes in a variety of malignancies. The objective of this study is to determine whether NLR, along with other hematological parameters such as absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and the Systemic Immune-Inflammation Index (SII; defined as neutrophils counts X platelets counts divided by lymphocyte count), are related to baseline distant metastases and overall survival (OS) in RCC patients. Methods: Clinical data from 203 RCC patients treated at King Hussein Cancer Center (Amman, Jordan) were retrospectively reviewed. We examined the relationship between age, sex, ANC, AMC, ALC, AEC, NLR, MLR, PLR, and SII with baseline distant metastasis and patients’ OS. Results: Of the 203 patients, 97 patients (48.5%) were stage 4 at the time of diagnosis. Univariate analysis showed that patients with high baseline ANC (>5400), AMC (>600), AEC (>120), NLR (>4.36), MLR (>0.33), PLR (>140.44), WBC count (>8.2), SII (>757.7) and low baseline ALC (≤1900) had more baseline metastasis. (p-value: <0.001, 0.007, 0.020, <0.001, <0.001, <0.001, 0.006, <0.001, and 0.004, respectively). On multivariate analysis, patients who had elevated NLR (>4.36) were more likely to have distant metastasis at the time of diagnosis (p-value = 0.0076, odds ratio (OR): 4.45, CI: 1.49–13.33). Moreover, univariate and multivariate analysis showed that patients with elevated NLR (>4.36) were associated with poorer OS (p-value: <0.0001 and 0.0065, respectively). In addition, patients with elevated baseline ANC, AMC, MLR, PLR, SII, WBC count, and low ALC values were associated with poorer OS (p-value: <0.0001, 0.0234, <0.0001, <0.0001, <0.0001, 0.0290, and <0.0001, respectively). Conclusions: The results of this study indicate a substantial correlation between several hematological parameters, including NLR, with the presence of distant metastases at the time of diagnosis and OS. Further research is required to uncover whether these hematological markers may be used to identify patients who are more likely to develop metastases and predict treatment response.
Assessing treatment preferences among patients with advanced/metastatic renal cell carcinoma in the United States: A discrete choice experiment.
Authors: Ornstein Moshe Chaim , Rosenblatt Lisa , Ejzykowicz Flavia , Guttenplan Sarah , Del Tejo Viviana , Yin Xin , Beusterien Kathleen M. , Mackie deMauri S , Will Oliver , Skiles Grace , DeCongelio Marc , Senglaub Steven S. 
Published: March 2023

630 Background: The introduction of immunotherapies has changed the first-line treatment landscape for advanced/metastatic renal cell carcinoma (aRCC). This study examines patient preferences in this rapidly changing environment to better understand the tradeoffs patients with aRCC are willing to make when choosing treatment. Methods: Patients with self-reported aRCC in the United States completed an online, cross-sectional survey. A discrete choice experiment was used to assess preferences for attributes of aRCC treatments. Patients completed a series of choice tasks showing 2 treatment profiles that varied in 7 important attributes identified through literature and qualitative research: overall survival, progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), risk of adverse events, quality of life (QOL) changes, and treatment administration. Descriptive statistics were reported, and a hierarchical Bayesian logistic model was used to calculate preference weights. Relative importance estimates (mean ± standard error) were computed for each attribute; these represent the mean percentage of the variation in preferences explained by the attribute. Results: Survey results from a total of 299 patients were analyzed (male, 50%; mean age, 56 years). All 7 attributes were statistically significant for influencing the choice of treatment. Key attributes included treatment regimen convenience and QOL improvement, which ranked similarly to increasing survival time. Among the efficacy attributes, increasing survival time was most important, followed by ORR, PFS, and DOR. Reducing the risk of serious adverse events from 82% to 65% was prioritized after the efficacy parameters. Conclusions: Patients with aRCC highly value less burdensome treatment regimens and improved QoL in addition to improvement in survival. This highlights the need for a broader context beyond efficacy and safety when discussing treatment options with patients. Funding: This study was supported by Bristol Myers Squibb.
Characterization and survival benefit of drugs approved for advanced renal cell carcinoma.
Authors: Benjamin David Joseph , Rezazadeh Arash 
Published: March 2023

633 Background: The treatment landscape of advanced renal cell carcinoma (RCC) drastically changed with the approval of tyrosine kinase inhibitors (TKIs). Since then, immunotherapy (IO) and now TKI plus IO combination therapies is considered standard-of-care. Despite multiple drug approvals, it remains unclear how much improvement in survival these therapies have provided. Methods: We reviewed the US Food and Drug Administration (FDA) website to evaluate all approvals for RCC from 2005 to 2022. We collected progression-free survival (PFS) and overall survival (OS) from the approval notification or from the corresponding clinical trial cited for drug approval. Results: Between 2005 and 2022, there were 16 drug (single or combination) approvals for advanced RCC. Most therapy approvals (93.75%) were granted through accelerated approval. Eight approvals were TKIs, 6 approvals were TKI plus IO combination therapies, and 1 approval each were for immunotherapy and a VEGF inhibitor. Average PFS benefit for 1st line approvals was 5.63 months (range 1.9-14.7) and average PFS benefit for 2nd or later line approvals was 2.95 months (range 0.2-9.1). Average OS benefit in the 1st line setting was 3.6 months and average OS benefit in the 2nd or later line setting was 5.4 months. Conclusions: Despite 16 drug (single or combination) approvals for advanced RCC since 2005, the improvements in average PFS and OS were modest. As OS data matures from recent TKI plus IO combination therapies, OS benefit may improve. Nonetheless, continued drug development is urgently warranted in advanced RCC. [Table: see text]
The survival outcomes of metastatic non-clear cell renal cell carcinoma in the immunotherapy era: Princess Margaret Cancer Centre (PMCC) experience.
Authors: Al-Ezzi Esmail Mutahar , Mittal Abhenil , Veitch Zachary William Neil , Zahralliyali Amer , Diaz Mejia Nely Mercy , Abdeljalil Osama , Alqaisi Husam , Kumar Vikaash , Fallah-Rad Nazanin , Sridhar Srikala S. 
Published: March 2023

636 Background: Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients (pts) with advanced clear cell renal cell carcinoma. The evidence to support their use in metastatic non-clear cell renal cell carcinoma (nccRCC) is based on smaller prospective trials and retrospective analyses. Here, we report the survival outcomes of pts with nccRCC treated with IO containing regimens or TT. Methods: This retrospective survival analysis was performed in metastatic nccRCC pts treated with IO and/or TT at the PMCC, Toronto between 2002 and 2021. Demographics, disease characteristics and survival outcomes were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method (log-rank). Chi-square and fisher’s exact tests were used to evaluate response rates where appropriate. Interaction between variables was estimated using Cox proportional hazards. Results: We identified 530 metastatic RCC pts, of these 69 (13%) were nccRCC treated either with an IO containing regimen or TT. Among nccRCC pts, 42 (60.9%) had papillary subtype, 10 (14.5%) chromophobe, 14 (20.3%) unclassified, and 3 (4.3%) had an XP translocation. Median age was 54 years (range: 26-75) and 48 (69.5%) were male. Overall, as per the IMDC score, 15 (21.7%), 41 (59.5%) and 13 (18.8%) pts were categorized as good, intermediate and poor risk, respectively. Median follow-up was 116 months (95%CI: 30.8-201.1 months). Pts received sunitinib (n=41), ipilimumab plus nivolumab (n=8), sorafenib (n=5), savolitinib (n=3), pembrolizumab (n=3), pazopanib (n=2), temsirolimus (n=2), pembrolizumab plus axitinib (n=1), and other TT (n=4) in the first line treatment. Everolimus (n=13), nivolumab (n=7), sunitinib (n=7), axitinib (n=2), cabozantinib (n=2), chemotherapy (n=2), pembrolizumab plus axitinib (n=1), and other TT (n=2) were given in the second line treatment. The survival outcomes and responses are shown in the table. There was no interaction between age, gender, IMDC, RCC subtypes and survival outcomes. Conclusions: While the number of pts included in our retrospective review was small, our analysis suggested that pts with metastatic nccRCC have improved survival outcomes with IO containing regimens. Validation in a prospective dataset is required before widespread clinical utilization and many trials are currently ongoing. [Table: see text]
Real-world outcomes in patients with metastatic renal cell carcinoma (mRCC) receiving dual immune checkpoint inhibitor (ICI-ICI) regimens or immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) combinations as first-line therapy: A British Columbia (BC) population-based analysis.
Authors: Morin Coulombe Antoine , Alsadoun Faisal Abdullah , Ye Xin (Cynthia) , Soleimani Maryam , Nappi Lucia , Eigl Bernhard J. , Chi Kim N. , Kollmannsberger Christian K. 
Published: March 2023

646 Background: Currently available first-line treatment regimens for mRCC include pembrolizumab-axitinib (ICI-TKI) and ipilimumab-nivolumab (ICI-ICI). Although both regimens are superior to sunitinib, direct comparisons between ICI-ICI and ICI-TKI are lacking and real-world data are sparse. Methods: Through BC Cancer pharmacy data and patient access programs queries, we identified 319 mRCC patients who were treated with first line ICI-TKI or ICI-ICI between May 2019 and March 2022. Patients’ charts were reviewed for baseline characteristics, including International mRCC Database Consortium (IMDC) risk criteria, pharmacy data, pathology and radiology reports, treatment toxicity, rationale for treatment choice when available, progression and survival outcomes. Treatment groups were compared using standard descriptive statistics; survival outcomes were compared using Kaplan Meier and Cox Regression analyses. Results: Among the first 214 patients, 64.9% and 35.1% received first line ICI-ICI and ICI-TKI, respectively. The most commonly cited reason for choosing ICI-ICI was unavailability of a publicly funded alternative at the time of prescription. IMDC risk group distribution was markedly different between regimens; in ICI-TKI patients, favorable, intermediate and poor-risk patients respectively represented 60.3%, 28.8% and 10.9%, versus 10.2%, 56.9% and 32.9% in ICI-ICI patients (p<0.001). Response rates in ICI-TKI compared favorably to ICI-ICI in the overall population with objective response rates (ORR) of 69% vs 50.4% (p=0.012) and primary progression rates of 12.7% vs 33.1% (p=0.001). However, in the intermediate-poor risk patients, survival outcomes were similar between ICI-TKI and ICI-ICI, with median progression-free survival (mPFS) of 7.5 versus 4.5 months respectively (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.41 to 1.09, p=0.107) and median overall survival (mOS) of not reached (NR) vs 22.6 months (HR 0.86, 95% CI 0.44 to 1.69, p=0.665). Of interest, in patients treated with ICI-ICI, more ipilimumab infusions in the induction phase was associated with improved mOS, rising from 3.9 to 13.6, 21.8 and 37.5 months for 1, 2, 3 or 4 infusions respectively (statistically significant by Log Rank [Mantel-Cox], p<0.001). Conclusions: In the real-world mRCC experience from BC, Canada, ICI-TKI was associated with statistically significantly improved ORR over ICI-ICI although the treated population was comparatively enriched for favorable risk patients by IMDC. PFS and OS did not differ between the two regimens in the intermediate-poor risk population. Updated results on all 319 patients will be presented.
Drug-drug interactions (DDIs) in elderly patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib within the multicenter prospective trial ZEBRA/Meet-URO 9.
Authors: Mattana Alvise , Del Re Marzia , Bimbatti Davide , Buti Sebastiano , Claps Melanie , Di Napoli Marilena , Fratino Lucia , Santini Daniele , Sorarù Mariella , Grillone Francesco , Mazzaschi Giulia , Maruzzo Marco , Pierantoni Francesco , Ballestrin Melissa , De Toni Chiara , Lai Eleonora , Dionese Michele , Zagonel Vittorina , Basso Umberto 
Published: March 2023

648 Background: The oral tyrosine kinase inhibitor Cabozantinib (CABO) is frequently used to treat patients with metastatic RCC. Polypharmacy is common in elderly pts, thus several drug-drug interactions (DDIs) with cabozantinib may ensue. Methods: ZEBRA /MEET-URO 9 was a prospective, real world trial enrolling pts ≥ 70 years with mRRC treated with CABO at 13 Italian Oncology Centers. All concomitants drugs administered to pts were collected and categorized according to active principles and indication. DDIs were identified through a dedicated software (Lexicomp), scientific databases (Sider4.1) and published articles. Results: we enrolled 104 pts, median age 75.8 years (range 70.2-87.4 yrs). Overall, 91.4% of the cohort was treated at a reduced dose either upfront or due to side effects. Pts took a median of 6 concomitant drugs (IQR: 4-9), for a total of 131 active principles. Software analysis identified 4 DDIs (warfarin, apixaban, diltiazem and furosemide); whereas scientific reports allowed us to identify 15 additional DDIs involving metoprolol, nebivolol, olmesartan, amiloride, simvastatin, rosuvastatin, polyenoic omega-3 fatty acids, loperamide, metoclopramide, metformin, dutasteride, dexamethasone, prednisone, cetirizine and doxazosin. Seventy pts with potential DDIs experienced a trend for higher rate of grade 3-4 adverse events compared to other pts, although difference was not statistically significant (48.7% v 23.5 %, p=0.485). The table summarizes the main DDIs and suggestions to avoid or mitigate their effects Conclusions: the risk of DDIs was not negligible in our cohort of elderly mRCC pts treated with CABO, although the frequent dose reductions of CABO probably confounded their impact on toxicities. Unremitting attention to concomitant medications in the elderly is thus warranted. [Table: see text]
Real-world time-to-castration resistance (CR) among patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) initiating apalutamide (APA), enzalutamide (ENZ), or abiraterone acetate (ABI) from an oncology database.
Authors: Lowentritt Benjamin H , Rossi Carmine , Du Shawn , Muser Erik , Kinkead Frederic , Waters Dexter , Lefebvre Patrick , Pilon Dominic , Agarwal Neeraj 
Published: March 2023

65 Background: CR is an important clinical indicator of disease progression and worsening overall survival among pts with mCSPC. This study describes real-world time-to-CR progression in an oncology setting among pts with mCSPC who initiated APA, ENZ, or ABI in the United States. Methods: Clinical data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry Electronic DataMart (1/1/2013 – 07/31/2022) were evaluated. Metastatic pts without evidence of CR before initiating a next-generation androgen inhibitor (AAI) were classified into exclusive treatment cohorts based on the start date (index date) for APA, ENZ, or ABI. CR was identified by a Flatiron algorithm searching for: 1) mention of CR in patient charts, 2) rising prostate-specific antigen (PSA) levels documented from laboratory testing, or 3) mention of rising PSA while on hormonal therapy from unstructured data sources. Pts had ≥12 months (mo) of clinical data pre-index date and were followed from the index date until the end of clinical activity (including death) or data availability. The proportion of pts developing CR was described separately for each cohort using Kaplan-Meier analysis up to 24 mo post-index, with no adjustment for baseline confounders. CR progression rates in the current analysis were descriptively compared to those observed in Phase 3 trials where available. Results: A total of 155 APA, 385 ENZ and 711 ABI pts were evaluated. Mean age at index was ~73 years in each group. Mean follow-up was 12.8 mo (APA), 13.4 mo (ENZ) and 20.6 mo (ABI). Use of androgen deprivation therapy prior to initiation of AAI was observed in ~85% of pts. The median time between documented metastasis and the index date was 2.3 mo (APA), 2.8 mo (ENZ), and 2.3 mo (ABI). Progression rates to CR are shown. By 24 mo, the median time-to-CR was not reached with any treatment studied. By 24 mo, progression to CR was observed in 26% of APA pts in this analysis (32% in TITAN); 36% of ENZ pts in this analysis (25% in ARCHES); and 33% of ABI pts in this analysis (progression to CR not reported in LATITUDE). Conclusions: In this real-world database, the observed proportions of pts progressing to CRPC for the APA and ENZ cohorts were generally consistent with results of Phase 3 trials and include a small proportion of pts with early progression to CRPC. Increased physician awareness of the benefits of early initiation of an AAI along with identification of baseline biomarkers associated with early progression to CRPC may improve clinical outcomes. [Table: see text]
Heterogeneity in physician and patient preferences for the treatment of renal cell carcinoma: Evidence from latent class analysis.
Authors: Vass Caroline , Pinto Cathy Anne , Myers Kelley , Imai Kentaro , Bussberg Cooper , Bhattacharya Rituparna , Calhoun Shawna R , Poulos Christine 
Published: March 2023

661 Background: To inform shared decision-making, it is important to learn how patients or physicians trade off the features of adjuvant treatments and whether there is heterogeneity within preferences. Methods: An online discrete-choice experiment survey was administered to patients with physician-confirmed renal cell carcinoma (RCC) and physician-defined intermediate high/high risk of recurrence and physicians who treat such patients. Hypothetical treatment choices were defined by median disease-free survival (DFS); 5-year overall survival (OS) rate; mode and frequency of administration; need for concomitant daily pill; treatment duration; and the risks of severe diarrhea, fatigue, and dizziness. After making an adjuvant treatment choice, respondents were presented with the opportunity to opt out of treatment. Patient and physician choice data were analyzed separately using latent class (LC) models, which identify clusters within patients and physicians making similar choices. Each class’ preference weights were used to calculate the conditional relative attribute importance. Results: LC analysis identified three classes among the 250 patients (% respondents) that placed greater relative importance on: 1) 5-year OS and opting into treatment (37.5%), 2) median DFS and opting into treatment (26.9%), and 3) treatment duration and opting out of treatment (35.5%) (Table). Among the 250 physicians, the LC analysis identified three classes that placed greater relative importance on: 1) 5-year OS and recommending treatment (37.5%), 2) median DFS and recommending treatment (37.8%), and 3) not recommending treatment (24.7%). Additionally, each LC analysis showed that the other treatment attributes evaluated were less important, but the importance varied by LC (Table). Conclusions: Heterogeneity in physician and patient preferences for RCC adjuvant therapy was found, highlighting a need for shared decision-making. Discordance within patients and physicians in the propensity to opt out of adjuvant treatment suggests patient-physician dialogue is important. [Table: see text]