bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normative data for two challenging tests of face matching under ecological conditions
Authors: Stacchi Lisa , Huguenin-Elie Eva , Caldara Roberto , Ramon Meike 
Published: February 2020

Abstract
Background
Unfamiliar face processing is an ability that varies considerably between individuals. Numerous studies have aimed to identify its underlying determinants using controlled experimental procedures. While such tests can isolate variables that influence face processing, they usually involve somewhat unrealistic situations and optimized face images as stimulus material. As a consequence, the extent to which the performance observed under laboratory settings is informative for predicting real-life proficiency remains unclear.

Results
We present normative data for two ecologically valid but underused tests of face matching: the Yearbook Test (YBT) and the Facial Identity Card Sorting Test (FICST). The YBT (n = 252) measures identity matching across substantial age-related changes in facial appearance, while the FICST (n = 218) assesses the ability to process unfamiliar facial identity despite superficial image variations. To determine the predictive value of both tests, a subsample of our cohort (n = 181) also completed a commonly used test of face recognition and two tests of face perception (the long form of the Cambridge Face Memory Test (CFMT+), the Expertise in Facial Comparison Test (EFCT) and the Person Identification Challenge Test (PICT)).

Conclusions
Focusing on the top performers identified independently per test, we made two important observations: 1) YBT and FICST performance can predict CFMT+ scores and vice versa; and 2) EFCT and PICT scores neither reliably predict superior performance in ecologically meaningful and challenging tests of face matching, nor in the most commonly used test of face recognition. These findings emphasize the necessity for using challenging and ecologically relevant, and thus highly sensitive, tasks of unfamiliar face processing to identify high-performing individuals in the normal population.
Analysis of prevalence and prognostic implications of early versus delayed PSA declines during radium-223 (Ra223) treatment among men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sidhu Amanjot , Zalewski Pawel , Kapoor Anil , Fleshner Neil , Chow Edward , Emmenegger Urban 
Published: February 2020

117 Background: Ra233 is a well-tolerated, bone-seeking alpha emitter that prolongs the survival of men with mCRPC. Since there is a lack of validated biomarkers useful for disease monitoring during Ra223 therapy, we sought to characterize prostate-specific antigen (PSA) response patterns within a retrospective cohort study of real-world Ra223 treatment in four cancer centres across Ontario. Methods: Of 198 patients (pts) overall, 64 were not included due to incomplete data. The remaining 134 pts were grouped into (i) early PSA responders with a ≥30% PSA decrease (PSA30) within 12 weeks of treatment start, (ii) pts with an initial PSA flare followed by decreasing PSA, and (iii) non-responders. We analyzed the overall survival (OS) of these three cohorts using the Kaplan-Meier method and log-rank testing. Results: PSA30 responses were rare (n = 11; 8.2%), PSA flares were seen in 20.2% of pts (n = 27), but the majority of pts did not achieve a PSA response (n = 96; 71.7%). Of the pts identified as having a PSA flare, 11/27 (40.7%) presented with a post-flare PSA decrease below baseline, whereas in 16/27 (59.3%) the PSA decreased below the flare peak but not below baseline. 5/27 (18.5%) pts with a PSA flare achieved a PSA30. The median OS was not reached, 15.8 months and 14.7 months in responders, flare pts and non-responders, respectively (p > 0.05). Similarly, one year OS was 90.9%, 67.7% and 63.9% in responders, flare pts and non-responders. Conclusions: PSA flares are seen in one fifth of men undergoing Ra223 therapy for mCRPC. Despite delayed PSA declines of varying degrees, the survival of PSA flare pts is comparable to men without any PSA decline.
TALAPRO-1: A phase II study of talazoparib (TALA) in men with DNA damage repair mutations (DDRmut) and metastatic castration-resistant prostate cancer (mCRPC)—First interim analysis (IA).
Authors: De Bono Johann S. , Mehra Niven , Higano Celestia S. , Saad Fred , Buttigliero Consuelo , Mata Marielena , Chen Hsiang-Chun , Healy Cynthia G. , Paccagnella M. Luisa , Czibere Akos , Fizazi Karim 
Published: February 2020

119 Background: Phase 2 and 3 studies with poly(ADP-ribose) polymerase inhibitors (PARPi) have demonstrated antitumor activity in patients (pts) with mCRPC with DDRmut who were previously treated with novel hormonal therapy (NHT). We report the first IA of a Phase 2 study of TALA, a potent inhibitor and trapper of PARP. Methods: TALAPRO-1 (NCT03148795) is enrolling pts (N ≈ 100) with measurable soft tissue disease, progressive mCRPC, and DDRmut likely to sensitize to PARPi (including ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), who received 1–2 chemotherapy regimens (≥1 taxane-based) and progressed on ≥1 NHT (enzalutamide/abiraterone acetate). Pts receive oral TALA 1 mg/d (moderate renal impairment, 0.75 mg/d) until radiographic progression, unacceptable toxicity, or consent withdrawal. Primary endpoint is objective response rate (ORR; blinded independent review). Secondary endpoints are time to OR, duration of response, prostate-specific antigen (PSA) decrease ≥50%, circulating tumor cell (CTC) count conversion (to CTC = 0 and <5 per 7.5 mL of blood), time to PSA progression, radiographic progression-free survival (rPFS), overall survival, safety, pt-reported outcomes, and pharmacokinetics. A planned IA of safety and efficacy was performed after 20 pts with BRCA1/2 mutations were on treatment for ≥8 wks. Results: 81 pts received TALA as of June 5, 2019; 43 pts enrolled by Feb 12, 2019 were evaluable for the primary endpoint (20 BRCA1/2, 2 PALB2, 14 ATM, 7 other). All had received docetaxel and 49% prior cabazitaxel. Overall ORR (95% CI) was 25.6% (13.5–41.2), ORRBRCA1/2 50.0% (27.2–72.8), ORRATM 7.1% (0.2–33.9). Overall median (95% CI) rPFS was 5.6 months (mo) (3.5–8.2), rPFSBRCA1/2 8.2 mo (5.6–NE), rPFSATM 3.5 mo (1.7–8.1). Most common treatment-emergent adverse events (≥20%) were anemia, nausea, asthenia, decreased appetite, constipation, and platelet count decreased. Conclusions: TALA monotherapy demonstrates encouraging antitumor activity in docetaxel-pretreated mCRPC pts, especially those with BRCA1/2mut, and was generally well tolerated. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03148795.
Safety of BXCL701, a small molecule inhibitor of dipeptidyl peptidases (DPP), with pembrolizumab, (pembro, anti-PD-1) monoclonal antibody, in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Aggarwal Rahul Raj , Costin Dan , O'Neill Vincent J. , Burg Cedric R , Healey Diane I. , De Bono Johann S. , Zhang Jingsong , Small Eric Jay 
Published: February 2020

140 Background: BXCL701 (talabostat previously PT100) is an oral small molecule inhibitor of dipeptidyl peptidases (DPP) specifically DPP4, DPP8 and DPP9, which trigger macrophage cell death via pyroptosis resulting in proinflammatory stimulation of the innate immunity pathway. BXCL701 also inhibits fibroblast activation protein (FAP) releasing the FAP-mediated block of T-cell migration into the tumor. Expression of PD-L1 correlates with amplification of DPP8 and DPP9. In syngeneic animal models, significant tumor responses were observed when BXCL701 was used with checkpoint inhibition. Methods: A phase 1b, multicenter study was undertaken. Eligible patients (pts) had progressing mCRPC (PCWG3), at least 1 line of systemic therapy and ≤ 2 lines of cytotoxic chemotherapy for mCRPC, no prior anti-PD-1/PD-L1 or other T-cell directed anti-cancer therapy, and an ECOG PS of ≤ 2. Pts received fixed dose pembro (200mg IV q21 days) with escalating doses of BXCL701 (0.4mg and 0.6mg PO QD days 1-14 of 21-day cycles) using a 3 X 3 design. The key endpoints were safety and identification of the recommended phase 2 dose (RP2D) for the combination. Composite response (RECIST, PSA, CTC) was also assessed. Results: 3 pts were treated at the initial dose level for at least 4 cycles. All pts remain on treatment. No DLT or SAEs were reported. Grade 3 treatment related adverse events (TRAE) were limited to thrombocytopenia with transfusion in 1 pt. The only TRAE reported in more than one pt was hypocalcemia (2 pts). Safety assessment of BXCL701+pembro is ongoing at the final dose escalation cohort. As DPP9 is amplified in approximately 17% of treatment associated small cell/neuroendocrine prostate cancer (tSCNC) compared to 5% or less in the broader prostate cancer population, the Phase 2 portion of this study will be limited to patients with evidence of t-SCNC or de novo SCNC, an aggressive phenotype with poor outcomes. Conclusions: BXCL701 0.4mg QD on days 1 to 14 of 21-day cycle plus pembrolizumab 200 mg IV on day 1 every 21 days is safe in pts with mCRPC. The final dose escalation supporting RP2D will be presented. Clinical trial information: NCT03910660.
Factors associated with positive germline testing results in men with prostate cancer following NCCN guideline expansion.
Authors: Hunt Trevor Charles , Greenberg Samantha , Ambrose Jacob P. , O'Neil Brock B. , Tward Jonathan David 
Published: February 2020

230 Background: Pathogenic variants (PV) in genes associated with hereditary cancer risk account for over 10% of cases in men with metastatic prostate cancer (PCa). NCCN guidelines encouraging germline testing (GT) in metastatic PCa were recently expanded to include all men with high risk, very high risk, or regional PCa. Previously, we showed that the rate of PV findings did not significantly decrease after expansion of these criteria. In this study, we sought to identify factors associated with a PV finding. Methods: Men with PCa underwent multi-gene GT for PVs from April 2016 – December 2018 according to NCCN guidelines pre- (2016-17) and post-expansion (2018). The association of patient-level factors of interest with a positive GT result, where at least one PV was identified, was modeled with univariate logistic regression while overall model significance was validated with ANOVA. Results: Of 410 men undergoing GT, 44 (10.7%) positive and 366 (89.3%) negative tests resulted. Mean age at diagnosis was 62.2 years. Positive testing remained stable from 9.4% to 11.2% following guideline expansion (p=0.62). None of the patient-level factors of interest were significantly associated with increased odds of a positive GT result in any model generated. These factors included age at diagnosis, race, pretreatment PSA, Gleason grade group, NCCN risk group, and family history of cancer (breast and ovarian, prostate, any cancer). Model p-values ranged from 0.84 for Gleason grade group to 0.12 for family history of any cancer. Conclusions: Future work will need to further elucidate the role of patient-level factors in identifying men with PCa at increased risk for harboring a germline PV. Nonetheless, the lack of identification of other factors associated with positive GT results and a stable PV detection rate of roughly 10% support the recent expansion of NCCN testing guidelines. Given these findings, consideration of even broader NCCN criteria for GT may be justified.
Evaluation of Proclarix, a prostate cancer risk score, used together with magnetic resonance imaging for the diagnosis of clinically significant prostate cancer.
Authors: Pye Hayley , Ahmed Hashim , Heavey Susan , Stopka-Farooqui Urszula , Johnston Edward , Schiess Ralph , Gillessen Silke , Punwani Shonit , Emberton Mark , Whitaker Hayley 
Published: February 2020

278 Background: The use of multi-parametric magnetic resonance imaging (mpMRI) has been a significant advance in the diagnosis of prostate cancer (PCa) recommended in a number of guidelines. There are considerable resource implications in scanning all men at risk of PCa. Furthermore, a significant number of mpMRIs are reported as indeterminate, leading to unnecessary biopsies. Proclarix is a CE-marked test based on two novel biomarkers, thrombospondin 1 (THBS1) and cathepsin D (CTSD), combined with PSA and age. A software algorithm returns a risk score that can be used as an aid in the identification of clinically significant PCa (any Grade Group 2 or greater). We aimed to assess the potential of Proclarix to identify those men who could safely avoid an upfront mpMRI or those men who could avoid biopsy when the mpMRI was indeterminate. Methods: Proclarix was correlated retrospectively with diagnostic data from 282 men recruited in the INNOVATE study (NCT02689271). INNOVATE involved men undergoing mpMRI followed by targeted and systematic biopsies in those with a suspicious mpMRI. Results: Median age and PSA were 66 (IQR 59-70) and 5.4 (3.8-7.8) ng/mL. 182 (65%) men underwent biopsy and 78 (43%) had GG≥2 PCa. Application of Proclarix in all 282 men undergoing mpMRI resulted in a sensitivity for clinically significant PCa (GG≥2) of 91%, a negative predictive value (NPV) of 92% and 38% specificity. When normalized to the same sensitivity of 91%, %fPSA resulted in both lower NPV (89%) and specificity (28%) when compared to Proclarix. 144 (51%) men had an indeterminate mpMRI of whom 84 (58%) had a biopsy and 13 (15%) had GG≥2 PCa. In these men, Proclarix had an NPV of 100%, at 100% sensitivity and a specificity of 34%. When results were compared using equal sensitivity, PSA density (cut-off 0.05 ng/mL), which is frequently used to inform the need for biopsy, had 10% specificity. Conclusions: The use of Proclarix could potentially allow 38% of men to avoid undergoing an mpMRI. In men with an indeterminate mpMRI, Proclarix could allow one-third to safely avoid biopsies without missing any clinically significant cancer.
Urine exosome gene expression assay net benefit analysis in a large pooled cohort.
Authors: McKiernan James M. , Tutrone Ronald F. , Donovan Michael Joseph , Torkler Phillipp , Noerholm Mikkel , Alter Jason , Skog Johan 
Published: February 2020

287 Background: Over-diagnosis of indolent prostate cancer (PCa), supports the need for non-invasive tools that can differentiate low-grade (≤ Gleason score 6, GS 6) from high-grade (≥ GS 7). We examined the clinical benefit of ExoDx™ Prostate (IntelliScore) (EPI) results in a pooled cohort over a range of probabilities using net benefit analysis. Methods: A pooled dataset of two prior validation cohorts and additional cases from a large group practice provided a large data set (N=1,212) for net benefit analysis. The pooled population consisted of men > 50 years, scheduled for initial biopsy and with a PSA measurement. Urine specimens were collected at enrollment using a provided urine collection device and the EPI tests were run at a CLIA-certified central laboratory at Exosome Diagnostics, Waltham, MA. The clinical decision value of the urine exosome gene expression assay (EPI) was assessed using net benefit analysis and compared EPI results with standard of care information across a range of probabilities for which a patient might decide on a prostate biopsy. The net benefit is determined by adding the true positive results and subtracting the false negatives across different biopsy probability thresholds. Results: The ExoDx IntelliScore or EPI assay (green) demonstrated superior clinical benefit when compared to the Prostate Cancer Prevention Trial (PCPT) prostate cancer risk calculator or PSA. Conclusions: In this new analysis of a large pooled cohort, the EPI exosome gene expression assay had the highest clinical net benefit across the 10% - 50% decision threshold compared to decision support methods currently used in the clinic.
Clinical utility of biomarkers 4K score, SelectMDx and ExoDx with MRI for the detection of high-grade prostate cancer.
Authors: Fasulo Vittorio , de la Calle Claire Marie , Cowan Janet E. , Herlemann Annika , Chu Carissa , Gadzinski Adam John , Au Yeung Reuben , Saita Alberto , Cooperberg Matthew R. , Shinohara Katsuto , Carroll Peter , Nguyen Hao Gia 
Published: February 2020

307 Background: Although adoption of new biomarkers and MRI has become widespread, their utility when deciding to biopsy is unclear. We aim to evaluate and compare 4K, SelectMDx, ExoDx and their added value when combined with prostate MRI in the detection of high-grade prostate cancer (HG PC) and avoidance of unnecessary biopsies. Methods: Patients referred for consideration of prostate biopsy at UCSF between 2016-2019 were enrolled and had either 4K, SelectMDx or ExoDx testing with/without MRI. Logistic regression and AUC were used to determine the performance of each biomarker in detecting HG PC (≥Gleason grade (GG) 3+4). In the subgroup of patients that underwent biopsy, with PSA 2.5-10 and negative DRE, we determined the number of avoided unnecessary biopsies (with GG 3+3 cancer or no cancer) and missed HG PC for each biomarker with/without MRI. Results: A total of 896 patients were enrolled, 457 were biopsied. Mean age was 65.5 years, median PSA was 6.32. Logistic regression showed that having an abnormal biomarker score or PI-RADS 4/5 on MRI (P4/5) was strongly associated with finding HG PC: 4K OR 12.9 (CI 4.58-36.1), ExoDx OR 14.7 (CI 3.31-65.3), SelectMDx OR 3.62 (CI 1.44-9.11), P4/5 OR 6.20 (CI 3.93-9.79), TRUS ≥T2a OR 4.33 (CI 2.78-6.75), PSAD >0.15 OR 4.01 (CI 2.59-6.20), p<0.01). Combining biomarker and P4/5 lesion on MRI increased AUC for detecting HG PC. In the biopsy subgroup, a normal 4K or ExoDx test missed only 4-5% HG PC, while an abnormal test resulted in avoiding 14-20% unnecessary biopsies. Combining MRI with ExoDx or 4K missed 0-1.43% HG PC but avoided only 7-9% unnecessary biopsies (Table). Conclusions: 4K and ExoDx outperformed MRI and SelectMDx but combining the biomarkers with MRI resulted in the best predictive ability for detecting HG PC. Negative MRI avoided more biopsies than a normal 4K or ExoDxbut missed more aggressive cancers. Our data suggest that MRI alone is not sensitive enough to detect all HG PC and that 4K or ExoDx testing alone could be sufficient when deciding to proceed with biopsy.[Table: see text]
Results from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in muscle invasive bladder cancer (MIBC) undergoing cystectomy.
Authors: Gupta Shilpa , Sonpavde Guru , Weight Christopher J. , McGregor Bradley Alexander , Gupta Sumati , Maughan Benjamin Louis , Wei Xiao X. , Gibb Ewan , Thyagarajan Bharat , Einstein David Johnson , Dechet Christopher B. , Lowrance William Thomas , Murugan Paari J , Kilbridge Kerry L. , Agarwal Neeraj , Davicioni Elai , Eckstein Markus , Mossanen Matthew , Preston Mark A. , Konety Badrinath R. 
Published: February 2020

439 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) in MIBC improves survival which correlates with pathologic response (PaR) at radical cystectomy (RC). The combination of immunotherapy and NAC may improve PaR and outcomes in MIBC. We tested the efficacy and safety of nivolumab (N) with gemcitabine-cisplatin (GC) as neoadjuvant therapy for MIBC in our phase II trial (NCT03294304). Methods: Eligible pts with MIBC (cT2-T4a, N≤1, M0) who were candidates for RC were enrolled. Pts received C (70mg/m2) IV on D1, G (1000mg/m2) on D1,D8 and N (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 weeks. The primary endpoint was PaR (≤pT1,N0). Secondary objectives were safety of GC+N and PFS at 2 years. The correlative objectives based on pre-treatment biopsies were correlation of PaR with 1) WGS 2) molecular subtypes of BC; 3) PD-L1 expression; 4) baseline TILs, CD3, CD8 and CD56.. Evaluable pts. should have received at least 1 dose of N. PaR will be summarized by the PaR rate as estimated by the sample proportion with exact 95% confidence intervals. We specified a null PaR of 0.35 and an alternative hypothesis of 0.55; we will reject the null hypothesis if at least 20 of 41 pts. have a PaR. Results: Between Feb 2018 and June 2019, 41 pts. were enrolled (cT2N0 90%, cT3N0 7%, cT4N1 3%); 2 patients refused surgery but were included in ITT population. PaR was observed in 27/41 pts. (65.8%), including pts with N1 disease. The combination was safe with manageable toxicities and no deaths from treatment. Majority of AEs were from GC; the overall rates of grade 3-4 AEs was 20%, majority being neutropenia, thrombocytopenia and renal insufficiency. Immune related AEs were seen in 3 patients, 2 had "adenitis" which wasymptomatic,1 pt developed Guillian Barre Syndrome after surgery, which resolved with IVIG; and none of them required steroids. There was no delay in time to RC and no unexpected surgical complications from treatment. Patients are being followed for progression and survival. Correlative work is ongoing. Conclusions: Neoadjuvant N+GC is safe and effective in MIBC with significant pathologic downstaging rates and no added toxicities or delay to surgery. Clinical trial information: NCT03294304.
Medical oncologists’ first-line treatment preferences in metastatic urothelial carcinoma.
Authors: Apolo Andrea B. , Cambron-Mellott M. Janelle , Beusterien Kathleen , Seal Brian S. , Maculaitis Martine C. , Bernstein Andrew , Epperson Megan , Jeffress Mara Lisa , Doleh Yunes 
Published: February 2020

449 Background: Immunotherapy and combination platinum chemotherapy are effective treatment options with different adverse events (AEs) for patients (pts) with metastatic urothelial carcinoma (mUC). This study quantified treatment preferences based on perceived benefit-risk trade-offs associated with first-line (1L) therapy among medical oncologists (MOs). Methods: MOs completed a cross-sectional online survey assessing treatment preferences for 3 pt groups: cisplatin (cis)-eligible (elig) PD-L1 high, cis-ineligible (inelig) PD-L1 high, and cis-inelig PD-L1 low. Three discrete choice experiments (DCEs) showed a series of tasks where MOs chose between 2 alternative treatment profiles varying on 7 attributes identified as important in qualitative research: overall survival (OS), overall response rate (ORR), all grades (G) neuropathy, G3/4 nausea/vomiting, colitis, pneumonitis, and neutropenia. Hierarchical Bayes models were used to estimate preference weights for each attribute. Results: A total of 210 MOs, averaging 16 years in practice (65% community [C], 35% academic [A]), participated. PD-L1 testing was available to most MOs, 87.5% (C) and 74.3% (A). In cis-elig PD-L1 high and cis-inelig -PD-L1 low pts, the order of relative importance was: OS, ORR, G3/4 nausea/vomiting, G3/4 neutropenia, G3/4 pneumonitis, all G neuropathy, and G3/4 colitis. In cis-inelig PD-L1 high pts, improved OS was most important but decreasing G3/4 nausea/vomiting was more important than improving ORR. In cis-elig PD-L1 high, cis-inelig PD-L1 high, and cis-inelig PD-L1 low pts, to accept increases in AEs, MOs require OS increases of 2.0, 3.0, and 2.5 months (G3/4 nausea/vomiting by 21%); 1.6, 1.8, and 2.0 months (G3/4 neutropenia by 23%); 0.9, 0.4, and 1.1 (G3/4 pneumonitis by 3%); and 0.9, 0.6, and 0.7 months (all G neuropathy by 5%), respectively. Conclusions: OS and ORR are key drivers for MOs in the choice of 1L therapy for pts with mUC. MO selection of therapy is governed by platinum eligibility, PD-L1 status, and a desire to limit AEs. Future 1L treatments for mUC pts need to provide a substantial OS benefit in exchange for a higher risk of AEs, especially in cis-inelig PD-L1 low pts, whom are perceived as having poor outcomes.