bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of trial-eligibility as factor for clinical outcome of patients with renal cell carcinoma treated with first-line pazopanib: Subgroup analysis from the prospective, non-interventional study PAZOREAL.
Authors: Schostak Martin , Boegemann Martin , Goebell Peter J. , Gruenwald Viktor , Welslau Manfred , Ehness Rainer , Degenkolbe Elisa , Witecy Stefanie , Doehn Christian 
Published: June 2022

e16511 Background: In a real-world setting, a substantial number of patients (pts) with metastatic renal cell carcinoma (mRCC) do not meet all eligibility criteria for a clinical trial. Thus, data on effectiveness and safety of 1st-line (1L) treatment with pazopanib (PAZO) as well as quality of life (QoL) is underrepresented for those pts and data on treatment sequences implementing PAZO as 1L are sparse. Methods: PAZOREAL is a prospective, multi-center, non-interventional study to evaluate effectiveness, safety and QoL in pts with mRCC treated with 1L PAZO, and nivolumab (NIVO) or everolimus in second and third line. In this subgroup analysis, the clinical outcome of trial-eligible (TE) and trial-ineligible (TIE) pts with mRCC was assessed by means of overall survival (OS), time on drug (ToD), treatment-emergent adverse events (TEAE) and QoL evaluated by EQ-5D-5L. Pts were rated TIE if they met at least one of the following three ‘TIE criteria’: (i) Karnofsky Performance Status < 70%, (ii) hemoglobin below the lower limit of normal, and (iii) non-clear cell carcinoma1. Results: Of 398 pts treated between December 2015 and February 2021, 376 pts received 1L treatment with PAZO. The median age was 69.7 years. 146 pts were categorized TE and 184 pts TIE, for 46 pts assessment was not applicable. Most of all pts were initially treated with PAZO 800 mg (TE: 71.9% vs TIE: 63.0%). Median ToD for PAZO was 7.7 months (95% CI 6.1-9.0) for TE and 6.0 months (95% CI 4.5-8.1) for TIE. A similar fraction of TE and TIE pts were treated with 2L NIVO (43.8% vs 44.0%). Median OS was 53.2 months (95% CI 38.9-NA) for TE and 26.0 months (95% CI 17.3-35.9) for TIE. The 12-month OS rate was 77.9% for TE and 67.1% for TIE. In patient reported outcome (PRO) measures, baseline QoL was estimated higher for TE than TIE, i.e., 63.2% TE vs 49.2% TIE pts had no limitations for mobility and 82.9% TE vs 61.7% TIE pts were independent in self-care. Frequency of related TEAEs grade 3/4 were comparable for TE and TIE (26.7% vs 25.0%), while TE tended to have less related serious TEAEs (13.0% vs 16.3%). Treatment was discontinued due to related TEAEs in 19.2% of TE and 13.0% of TIE pts. Conclusions: PAZOREAL provides real-world data for mRCC pts usually not represented in clinical trials during the study period. As it was to be expected, median OS and PRO were more favorable for TE than for the TIE pts, reflecting the difference in general condition between these groups. But more importantly, these data underline the tolerability of 1L PAZO treatment even for TIE pts, which is supported by comparable ToD for 1L PAZO and the comparable safety profile in both subgroups.1 Marschner, N. et al. Clin Genitourin Cancer 2017; 15(2):e209-215. doi:10.1016/j.clgc.2016.08.022.
Socioeconomic factors associated with stages of bladder cancer at diagnosis: Analysis of the National Cancer Database.
Authors: Taylor Alexandra , Gallegos Jillian Marie , Verplancke Kiana , McMahon Kevin , Silberstein Peter T. , Dahl Mary Elizabeth 
Published: June 2022

e16531 Background: The average 5-year survival rate of Bladder Cancer (BC) in the US is 77%, yet the 5-year survival for BC with metastatic disease is 5%. The extreme differences in survival rate based on stage and metastasis highlight the importance of determining the social factors at the time of diagnosis. The objective of this study is to identify the socioeconomic and demographic factors associated with receiving a delayed bladder cancer diagnosis (stage IV) vs an early (stage 0-I) diagnosis. Methods: Using the National Cancer Database, this study analyzed 511,177 patients diagnosed with stage 0-I and stage IV BC between 2004 and 2018. Patients were analyzed based on race, sex, insurance type, Charlson-Deyo comorbidity score, level of education, income, geographic location, and education. Socioeconomic factors of patients were analyzed using multivariate analysis, chi square analysis, and one-way ANOVA. Results: Significant (P < 0.05) associations were identified between certain socioeconomic factors and presentation of bladder cancer at an advanced stage (stage IV). African Americans were 66% more likely to be diagnosed with stage IV diagnosis compared to Caucasians (p < .001 and 95% CI = 1.598-1.724). Hispanics were 22% more likely than non-Hispanics to present with a stage IV diagnosis (p < .001 and 95% CI = 1.114-1.327). Females were 34% more likely than men to present with stage IV diagnosis (p < .001 and 95% CI = 1.307-1.367). Patients with private insurance were 53% less likely to be diagnosed with a stage IV diagnosis than those who were uninsured (p < .001 and 95% CI = 0.448-0.509). Patients with one or more co-morbidities (Charleson-Deyo score ≥1) were more likely to present with a stage IV diagnosis than those with no co-morbidities (p < .001). Patients whose median household income was ≥ $63,000 were 33% less likely to present with a stage IV diagnosis than those whose median household income was < $63,000 (p < .031). Conclusions: Factors associated with increased likelihood of bladder cancer presentation at advanced stage compared to early stage include race, ethnicity, sex, insurance status, one or more co-morbidities, and a median household income under $63,000.
Real-world, population-based study of treatments, survival and healthcare use in advanced urothelial carcinoma of the bladder.
Authors: Cheung Winson Y. , Batra Atul , Syed Iqra A. , Moldaver Daniel , Clouthier Derek L. 
Published: June 2022

e16538 Background: Prior single institutional studies and case series suggest that management of urothelial carcinoma of the bladder (UCB) can be highly variable across different centers. To better contextualize emerging therapies and their place in management, we aimed to characterize current population-based treatment patterns, outcomes, and healthcare resource utilization. Methods: Using real-world registries and administrative data, we analyzed a contemporary cohort of patients diagnosed with advanced UCB from 2010 to 2017 in the large province of Alberta, Canada. The study time period was selected to allow for adequate follow-up. The Kaplan-Meier method was used to plot estimates of overall survival (OS) and Cox proportional hazards model was constructed to determine the associations of clinical characteristics with outcomes. Summary statistics were used to describe healthcare resource use. Results: We included 1,146 advanced UCB patients. Median age was 73 (IQR 65-81) years, majority (78%) were men, and most (69%) had a Charlson comorbidity index of 0 to 1. Only 363 (32%) were referred, consulted with oncologists, and received palliative systemic therapy. Common regimens consisted of platinum-based doublet in the first-line (1L) setting and single-agent chemotherapy or immunotherapy in the second-line (2L) setting. Only 116 (32%) of the 1L treated patients proceeded to 2L. Median OS was 9.8 months (10.2 and 5.3 months in treated and untreated patients, respectively). After adjusting for confounders, receipt of at least one line of systemic therapy was associated with improved OS (HR 0.79, 95% CI 0.65-0.95, P = 0.011) as was urban residence with more access to oncology care (HR 0.82, 95% CI 0.73-0.92, P = 0.001). Median number of emergency department visits was 4 (IQR 2-7) per patient. Median number of hospitalizations and duration of admissions were 3 (IQR 2-5) per patient and 10 (IQR 6-16) days, respectively. Conclusions: In our population-based sample, the poor prognosis of UCB may be largely attributed to the low receipt of systemic therapy rather than the burden of comorbidities or acute care encounters. Since treatment attrition is significant, efforts to streamline referral to and consultation with oncologists at the time of metastatic diagnosis may optimize the use of appropriate systemic therapies and improve survival. This is increasingly important as novel, more effective therapies for advanced UCB are introduced into the treatment armamentarium.
Activated protein kinase C-alpha as a simple test for urothelial cancer screening.
Authors: Inokuchi Junichi , Murata Masaharu , Kawano Takahito , Kang Jeong-Hun , Kinoshita Fumio , Matsumoto Takashi , Monji Keisuke , Kashiwagi Eiji , Takeuchi Ario , Shiota Masaki , Eto Masatoshi 
Published: June 2022

e16552 Background: The development of a non-invasive, highly predictive diagnostic test for urothelial cancer (UC) would greatly benefit patients. Although numerous urine-based tests have been developed, it is not widely used, except for urine cytology, due to insufficient sensitivity, negative predictive value and high cost. Previously we reported that protein kinase C-alpha (PKCα) is overexpressed or activated in several cancer tissues but not in normal tissue, and we developed an activated PKCα-specific peptide substrate (FKKQGSFAKKK; Patent No. 5476559). The purpose of this study was to investigate the potential for UC screening of simple test detecting activated PKCα. Methods: This institutional review board-approved prospective study included patients with bladder cancer or upper urinary tract UC who underwent surgery at Kyushu University Hospital between September 2018 and December 2020. Patients with benign urologic disorders or healthy volunteers were included as a control group. Patients with prostate cancer (PC) or renal cell carcinoma (RCC) who underwent curative surgery were included as other genitourinary (GU) cancer group. Patients with other coexisting malignant tumors were excluded. Urine samples were collected prior to surgery, 20 mL of urine was centrifuged, and the pellet was lysed for analysis. We evaluated the phosphorylation status of the activated PKCα-specific peptide substrate by MALDI-TOF mass spectrometry. The utility of activated PKCα as a urinary biomarker was evaluated by its sensitivity and negative predictive value when compared to control group or other GU cancers group. Results: Urine samples were obtained from 226 individuals, which included 98 patients with UC, 51 with other GU caners, and 77 with control group. Of the 98 patients with UC, activated PKCα was detected in 75 patients, with sensitivity of 76.5%. The sensitivity in patients with high-grade and low-grade UC were 84% and 62%, respectively. The sensitivity in those with high-grade UC increased to 93% when combined with urine cytology. On the other hand, activated PKCα were rarely detected in non-UC patients which includes other GU cancers group and control group. The specificity among the non-UC patients was 74.2%. In the comparison between patients with UC and non-UC, the negative predictive value of activated PKCα was 80.5%. The area under the receiver operating characteristic curve (AUC) for detecting UC of activated PKCα was 0.80. Conclusions: This study demonstrates the utility of activated PKCα as a novel urine screening test for UC. (Patent Application No. PCT/JP2020/045257) Since this test is based on a single target, inexpensive detection devices can be developed.
Clinical and epidemiological features of penile squamous cell carcinoma according to pathological nodal stage in a Brazilian cancer reference hospital.
Authors: Preto Daniel D Almeida , Lordelo Bruno , Tavares Rosielly Melo , Gimenes Afonso Nathália , Araujo Hadson Silva , Neif Joao , Zucca Luis Eduardo Rosa , Carcano Flavio Mavignier 
Published: June 2022

e17017 Background: Penile cancer is a rare disease worldwide, but in the developing countries represent 2% of male cancers, and sociocultural issues are closely related to risk. Lymph node status is a key prognostic factor, and almost 60% of patients has lymph node disease at diagnosis. Perioperative treatment for patients with regional lymph node disease is essential for a better outcome. Methods: We retrospectively reviewed all penile cancer patients, with histological confirmation, between 2009 and 2019 at Barretos Cancer Hospital (Brazil). Only squamous cell carcinoma that performed lymphadenectomy were included. Univariable analysis were performed to explore association between clinical and pathological features. Cumulative survival probabilities were calculated using the Kaplan-Meier method and differences between survivals were tested using the log-rank test. Results: One hundred and thirteen patients were eligible for analyses. The mean age was 55.7 year. Most of the patients were declared white, in a stable relationship and had a lower education level, with more than 70% of patients attending only elementary school. Clinical-pathological staging concordance was 43%. Overall survival was related to pathologic lymph node staging (pN), ranging from 111 months for pN0 individuals to 46.9 months for pN3 (p < .001). Considering only pN2-3 stages, only 54% of patients were submitted to adjuvant treatment and those had significantly improved 5 years cumulative survival, almost 50% versus 20% (p = .027). Only one patient was submitted to neoadjuvant therapy. Conclusions: The epidemiological profile matches with the current literature, reaffirming this public health issue in low-income countries. Accurated lymph node staging is essential to define the prognosis and an agressive multi-modality approach could improve results in the perioperative nodal metastatatic setting. Further prospective controlled studies should be stimulated in this context.
Financial impact of generic therapeutic interchange of abiraterone in the oncology care model for the U.S. Oncology Network.
Authors: Indurlal Puneeth , Ives Hope , Garey Jody S. , McGuinness Margaret , Pacheco Alonso Victor , Wilfong Lalan S. 
Published: June 2022

e17019 Background: Therapeutic interchange (TIC) to lower-cost generic products offers significant cost savings to payers and patients while maintaining equivalent quality of care. The Oncology Care Model (OCM) is a value-based care program from Medicare that rewards practices for decreasing the total cost of care (TCOC) compared to historical baseline prices that are adjusted by a trend factor to account for rising cost trends in oncology. One strategy for bending the cost curve is to utilize lower cost medications. A generic version of abiraterone acetate (FDA approved for treatment of Prostate Cancer) was first introduced into the market in late 2018. This led to a concerted approach to interchange the brand product with the generic equivalent in The US Oncology Network (The Network) as an opportunity to reduce TCOC. Here we describe utilization and the financial impact of abiraterone TIC in The Network during OCM performance period 8 (PP8) which enrolled patients from 1/2/2020 to 7/1/2020. Methods: Prescription drugs dispense data for the 14 US Oncology Network practices participating in the OCM were used to determine brand and generic abiraterone utilization. The impact of TIC on TCOC was measured by comparing the cost of the generic product vs. the estimated cost of the brand agents. Results: TIC resulted in an increase in generic abiraterone use from prior performance periods. Generic abiraterone increased from 0% in PP4 to 24% in PP5, 55% in PP6, 67% in PP7 and 80% in PP8 within the Network. We compared the actual cost of all abiraterone dispenses in PP8 vs. the calculated cost (based on Average Wholesale Price less 17.5%) of the brand product if the more expensive brand drugs were used instead. The difference in the actual cost vs estimated cost led to a savings of $4.37 million in PP6, $6.34 million in PP7 and $9.37 million in PP8 (about 1% of TCOC) by using generic versus brand abiraterone alone. Conclusions: TIC from brand to generic abiraterone in The Network generated significant savings for OCM. Continued shift towards lower cost generics will increase savings to CMS in the Oncology Care Model. We estimate that 100% Network adoption of the generic abiraterone could save nearly 1.25% of the TCOC compared to continued use of brand product.
Augmented alpha-beta PSMA radioligand therapy in metastatic prostate cancer: Analysis of prognostic factors for survival.
Authors: Kulkarni Harshad , Khushalani Jaya , Mancini Brandon Robert , Maupin Kevin , Robiller Franz Christoph , Baum Richard , Almaguel Frankis 
Published: June 2022

e17025 Background: PSMA-targeted radioligand therapy (PRLT) using the alpha-emitter Ac-225 PSMA-617 is effective in metastatic prostate cancer progressing after beta-emitter-based PRLT using Lu-177 PSMA-617, and in the presence of diffuse bone marrow metastases. Xerostomia is a dose-limiting factor in PRLT using Ac-225. Augmented Alpha-Beta PRLT is a concept of concomitantly administering Lu-177 and Ac-225 PSMA in lower activities, as a trade-off between efficacy and the dose-limiting toxicity, i.e., xerostomia. The objective of this study was to compare overall survival (OS), progression-free survival (PFS), and incidence of xerostomia among metastatic prostate cancer patients who received Ac-225 PSMA-617 augmentation in the initial phase of Lu-177 PSMA-617 RLT compared to those who received it in the late phase. Initial phase is defined as first two cycles of PSMA radioligand therapy (PRLT) vs late phase as after two cycles. We also examined prognostic factors associated with OS and PFS. Methods: Kaplan Meier method was used to examine survival curves and log-rank tests were conducted to examine differences in survival by groups. Cox Proportional Hazard (CPH) model was used to examine the impact of bone marrow and visceral metastasis and age on OS and PFS. Progression was defined as an increase of ≥ 25% in prostate-specific antigen (PSA) levels. Results: 68 patients who received Ac-225 PSMA-617 by itself, or Ac-225 PSMA-617 augmentation to Lu-PSMA-617 were included in the analysis. Out of these, 15 received early augmentation, 50 received late augmentation, and 3 received Ac-225 PSMA-617 alone. Of these, 48 experienced cancer progression and 21 died due to cancer progression. Median OS was 47 months and PFS was 11 months. Those who received early augmentation had significantly better PFS (median PFS not reached during study period) compared to those who received late augmentation (median PFS: 9 months) (p = 0.02). Early augmentation was associated with lower likelihood of xerostomia (p = 0.09). CPH model suggested that visceral or bone marrow metastasis were associated with significantly worse prognosis for PFS (p = 0.04). Conclusions: In patients progressing after Lu-177 PSMA radioligand therapy and those with diffuse bone-marrow metastases, an earlier augmentation with Ac-225 PSMA-617 is associated with better PFS and lower side effects such as xerostomia. Having visceral or bone marrow metastasis is a poor prognostic indicator for PFS in augmented alpha-beta PSMA radioligand therapy.
PTCH1 and AXIN2 modulation of AR copy number effects on AR gene overexpression in metastatic castration resistant prostate cancer (mCRPC).
Authors: Yan Raymond T. , Latourelle Jeanne , Khalid Omar , Parikh Ravi Bharat , Church Bruce W. 
Published: June 2022

e17026 Background: Androgen receptor (AR) signaling is a critical pathway in prostate cancer progression. Reactivation of the AR pathway is a key driver in mCRPC. Patients with mCRPC often develop resistance to novel AR signaling inhibitors (ARSIs) such as enzalutamide. AR inhibitor resistance leads to shorter overall and progression-free survival and can be attributed to AR gene amplification with subsequent AR overexpression and androgen-sensitization in prostate tumors. Identifying novel modulators of AR amplification in patients progressing on ARSIs may lead towards potential targets in drug discovery. Methods: In this cross-sectional study, an in silico patient model was developed on prescribed drug therapies and failed therapies patient information, PSA measures, ̃100 mutation variables including somatic, germline, and gain/loss mutations, and ̃1K gene expressions data from 275 mCRPC patients obtained from the Tempus database using GNS Healthcare’s Causal artificial intelligence technology, REFS. A causal network model was reconstructed based on patient data with inferred effect estimates. The network model was topologically surveyed for biological interactions. Results: Causal analysis of this model uncovered two germline mutations, located in PTCH1 and AXIN2, which modify the effect of AR copy number gain ( ARgain+ : copy number 6, ARgain- : copy number < 6) on AR gene expression. For PTCH1-mutant group, there was a 2-fold increase in AR gene expression in ARgain+ patients compared to ARgain- patients (p = 2.1e-12), while only 1.4 fold increase in AR gene expression from the PTCH1 non-mutant group (p = 6.3e-08). Similarly, there was a 2-fold increase in AR gene expression in ARgain+ patients compared to ARgain- patients (p = 7.2e-16) for the AXIN2-mutant group, while only one-fold increase in AR gene expression with the AXIN2 non-mutant group (p = 0.001). The C to T missense mutation in codon 3746 in PTCH1 and codon 148 in AXIN2 have higher prevalences, 55% and 72%, respectively in this mCRPC cohort compared to their population allele frequencies, 38% and 47%, respectively. Conclusions: PTCH1 and AXIN2 mutations from our analyses is consistent with a literature reported role for Hedgehog signaling and Wnt/-catenin signaling pathways, respectively, influencing the disease progression in castration-resistant prostate cancer. Our findings suggest that the missense germline mutations in PTCH1 and AXIN2 predicts response to enzalutamide and other ARSIs in CRPC setting, and propose potential targets for combination therapy to overcome ARSI drug resistance in hormone-refractory prostate cancer. [Table: see text]