bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular determinants of prostate specific antigen (PSA) kinetics and clinical response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN.
Authors: Saad Fred , Graff Julie N , Hadaschik Boris A. , Oudard Stephane , Mainwaring Paul N. , Bhaumik Amitabha , Gormley Michael , Londhe Anil , Thomas Shibu , Lopez-Gitlitz Angela , Mundle Suneel , Davicioni Elai , Small Eric Jay , Smith Matthew Raymond , Feng Felix Y 
Published: May 2020

5521 Background: In SPARTAN, APA + androgen deprivation therapy (ADT) prolonged metastasis-free survival (MFS) and improved PSA kinetics over placebo (PBO) + ADT in high-risk nmCRPC. All molecular subtypes derived benefit in MFS from APA (Feng FY, et al. ASCO GU 2019; abstract 42). We evaluated the association of PSA decline and efficacy outcomes in SPARTAN pts with different molecular subtypes. Methods: Gene expression from archival primary tumors (biomarker population) was assessed with the DECIPHER platform (Decipher Biosciences, Inc.) and stratified into genomic classifier (GC) high- and low-to-average risk using GC score > 0.6 and ≤ 0.6, respectively, and ADT-resistant or -sensitive basal or luminal A/B (PAM50 classifier) subtypes. PSA nadir and confirmed PSA decline (Table) were assessed in APA pts overall and at 3, 6, and 12 mo. Associations between molecular subtypes and outcomes were assessed. Results: Of 233 available samples, 154 were from APA pts; 49% of APA pts had high GC score and 66% had basal subtype. PSA levels at baseline were similar across all subtypes. Regardless of GC score or basal/luminal subtype, > 50% of patients achieved ≥ 90% reduction in PSA with APA. PSA declined faster and PSA reduction was deeper at 6 mo (Table) in GC low to average vs GC high risk and luminal vs basal subtypes. Overall, only luminal vs basal subtypes had a significantly higher % of pts with ≥ 90% PSA decline (Chi square p = 0.037). In luminal pts, deeper PSA decline with APA was consistent with improved MFS vs basal pts. In GC high pts, MFS benefit with APA was similar to that in GC low to average pts despite lower PSA decline. Although GC low to average and luminal pts had more rapid and deeper PSA responses than GC high or basal pts, respectively, all pts derived MFS benefit. Association of long-term outcomes with PSA decline in these molecular subtypes will be presented. Conclusions: In SPARTAN, all molecular subtypes of pts with nmCRPC treated with APA + ADT had MFS benefit and rapid and sustained PSA decline. PSA responses were deepest and most rapid in GC low to average and luminal subtypes. Clinical trial information: NCT01946204 . [Table: see text]
Clinical analysis of the extracellular vesicle-fingerprint score blood test to refine the prediction of clinically significant prostate cancer and avoid prostate biopsy.
Authors: Fairey Adrian S. , Paproski Robert J , Pink Desmond , Sosnowski Deborah L , Vasquez Catalina , Donnelly Bryan , Hyndman M. Eric , Aprikian Armen G. , Beatty Perrin , Lewis John D 
Published: May 2020

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]
KEYNOTE-199 cohorts (C) 4 and 5: Phase II study of pembrolizumab (pembro) plus enzalutamide (enza) for enza-resistant metastatic castration-resistant prostate cancer (mCRPC).
Authors: Hoimes Christopher J. , Graff Julie N , Tagawa Scott T. , Hwang Clara , Kilari Deepak , Ten Tije A. J. , Omlin Aurelius , McDermott Raymond S. , Vaishampayan Ulka N. , Elliott Tony , Gerritsen Winald R. , Wu Haiyan , Kim Jeri , Schloss Charles , De Bono Johann S. , Antonarakis Emmanuel S. 
Published: May 2020

5543 Background: Initial evidence suggests activity of pembro + enza in patients (pts) resistant to enza. We present results from the multicohort phase II study KEYNOTE-199 (NCT02787005) in chemotherapy-naive pts with mCRPC treated with pembro + enza after progression with enza and who had RECIST-measurable (C4) or bone-predominant (C5) disease. Methods: Pts who did or did previously receive abiraterone and for whom enza treatment failed after clinically meaningful response received pembro 200 mg Q3W, with continuation of enza for up to 2 y or until progression, toxicity, or withdrawal. End point was ORR per RECIST v1.1 (C4) by blinded independent central review (primary); DOR (C4), time to PSA progression, rPFS, OS, and safety. Results: A total of126 pts (C4, 81; C5, 45) were treated. Median (range) PSA was 31 ng/mL (0.4-1667) in C4 and 19 ng/mL (1-1750) in C5.Median (range) time from enrollment to data cut off was 15 mo (7-21) in C4 and 19 mo (7-21) in C5. In C4, ORR (95% CI) was 12% (6-22; 2 CRs, 8 PRs) and median (range) DOR was 6 mo (3+ to 13); 60% of pts had DOR ≥6 mo. DCR (CR + PR + SD) was 51% in C4 and C5. Median (95% CI) time to PSA progression was 4 mo (4-4) in C4 and 4 mo (4-4) in C5. Median (95% CI) rPFS was 4 mo (3-6) for C4 and 4 mo (3-6) for C5; 12-mo rPFS rate was 17% in C4 and 23% in C5. Median (95% CI) OS was NR (16-NR) in C4 and 19 (14-NR) mo in C5; 12-mo OS rate was 70% in C4 and 75% in C5. Shorter median OS was more associated with prior enza treatment <6 mo than with prior enza treatment ≥6 mo. Liver metastasis was associated with shorter median OS however, median OS in visceral disease subgroups appeared longer than expected. Any-grade/grade ≥3 treatment-related AEs occurred in 75%/26% of pts in C4 and 69%/24% in C5. Two pts in C5 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Any-grade/grade 3/4 rash (regardless of relatedness) was higher than that in prior reports for individual agents (33%/6%). Conclusions: Pembro + enza after enza resistance had manageable safety and showed antitumor activity for RECIST-measurable and bone-predominant mCRPC. This combination is being evaluated in an ongoing phase III combination trial. Clinical trial information: NCT02787005 . [Table: see text]
Detection of prostate cancer and determination of its significance using explainable artificial intelligence.
Authors: Eminaga Okyaz , Loening Andreas , Lu Andrew , Brooks James D , Rubin Daniel 
Published: May 2020

5555 Background: The variation of the human perception has limited the potential of multi-parametric magnetic resonance imaging (mpMRI) of the prostate in determining prostate cancer and identifying significant prostate cancer. The current study aims to overcome this limitation and utilizes an explainable artificial intelligence to leverage the diagnostic potential of mpMRI in detecting prostate cancer (PCa) and determining its significance. Methods: A total of 6,020 MR images from 1,498 cases were considered (1,785 T2 images, 2,719 DWI images, and 1,516 ADC maps). The treatment determined the significance of PCa. Cases who received radical prostatectomy were considered significant, whereas cases with active surveillance and followed for at least two years were considered insignificant. The negative biopsy cases have either a single biopsy setting or multiple biopsy settings with the PCa exclusion. The images were randomly divided into development (80%) and test sets (20%) after stratifying according to the case in each image type. The development set was then divided into a training set (90%) and a validation set (10%). We developed deep learning models for PCa detection and the determination of significant PCa based on the PlexusNet architecture that supports explainable deep learning and volumetric input data. The input data for PCa detection was T2-weighted images, whereas the input data for determining significant PCa include all images types. The performance of PCa detection and determination of significant PCa was measured using the area under receiving characteristic operating curve (AUROC) and compared to the maximum PiRAD score (version 2) at the case level. The 10,000 times bootstrapping resampling was applied to measure the 95% confidence interval (CI) of AUROC. Results: The AUROC for the PCa detection was 0.833 (95% CI: 0.788-0.879) compared to the PiRAD score with 0.75 (0.718-0.764). The DL models to detect significant PCa using the ADC map or DWI images achieved the highest AUROC [ADC: 0.945 (95% CI: 0.913-0.982; DWI: 0.912 (95% CI: 0.871-0.954)] compared to a DL model using T2 weighted (0.850; 95% CI: 0.791-0.908) or PiRAD scores (0.604; 95% CI: 0.544-0.663). Finally, the attention map of PlexusNet from mpMRI with PCa correctly showed areas that contain PCa after matching with corresponding prostatectomy slice. Conclusions: We found that explainable deep learning is feasible on mpMRI and achieves high accuracy in determining cases with PCa and identifying cases with significant PCa.
Safety outcomes of darolutamide versus apalutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC): Matching-adjusted indirect comparisons.
Authors: Jiang Shan , Terasawa Emi , Horton Viviana Garcia , Ayyagari Rajeev , Waldeck A. Reginald , Halabi Susan , Shore Neal D. 
Published: May 2020

5561 Background: Randomized nmCRPC trials comparing darolutamide (D), apalutamide (A) and enzalutamide (E) have not been reported. Safety of these therapeutics has important implications in assessing patient risk-benefit concerns. Matching-adjusted indirect comparison (MAIC) is a method to perform indirect treatment comparisons adjusting for cross-trial heterogeneity. Objective: To compare the safety outcomes of D vs. A or E using MAIC. Methods: Data from the ARAMIS (D vs. placebo [PBO]), SPARTAN (A vs. PBO) and PROSPER (E vs. PBO) trials were used. Key safety outcomes including adverse events (AEs) that have central nervous system relevance were compared using anchored MAIC. Individual patient level data (IPD) from ARAMIS were selected and re-weighted to match the inclusion criteria and baseline characteristics published in SPARTAN and PROSPER (no access to their IPD). The Benjamini-Hochberg approach was applied to adjust for multiplicity. The D vs A MAIC matched on 7 covariates: age, prostate-specific antigen (PSA) level and doubling time, Eastern Cooperative Oncology Group (ECOG), Gleason score, bone-sparing agent use and prior surgery. Sensitivity analyses were conducted matching on different sets of covariates. D vs. E were matched on age, region, PSA level and doubling time, ECOG, Gleason score and bone-sparing agent use. Risk difference (RD) ([DARO – PBOARAMIS] – [ENZA – PBOPROSPER]) and odds ratio (OR) (ORARAMIS/ORPROSPER) were calculated. RD<0 or OR<1 indicate lower AE risk for D. Results: For D vs. A, the effective sample sizes (ESS) of D and its placebo (PBO) arm were 604 and 391 after matching. Fall, fracture, and rash were statistically significantly lower for D vs. A (Table). For D vs. E, the ESS of D and PBO arm were 580 and 395, respectively. Fall, dizziness, mental impairment, hypertension, fatigue and severe fatigue were statistically significantly lower for D vs. E. Conclusions: After adjusting for trial differences, D showed favorable safety profile in fall, dizziness, mental-impairment, hypertension, rash, fatigue, and fracture. [Table: see text]
The quantitation of thioredoxin 1 from serum as a novel means to detect breast cancer (BC).
Authors: Suh Kyoung Hoon 
Published: May 2020

557 Background: Breast cancer (BC) is the most common cancer and the second leading cause of cancer death in women. Enormous effort has been conducted without success to develop a means to detect BC using the blood. We have reported that the level of thioredoxin 1 (Trx1) in serum could be a novel standard to evaluate the risk of BC. Therefore, we have investigated the clinical utility of Trx1 as a biomarker to detect BC by testing sera from normal women, women with BC, women with five other types of cancer. Methods: We have developed an ELISA kit that quantitates Trx1 in sera. The level of Trx1 was determined in each serum from normal healthy women (n = 114), as well as patients with BC (n = 106), cervical cancer (n = 17), lung cancer (n = 14), stomach cancer (n = 9), and thyroid cancer (n = 4). BC patients were recruited according to their age and cancer stage. Each test was duplicated more than three times, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests. Results: The mean value of Trx1 from normal women was 5.60±4.39(±SD) and that from BC was 22.25±7.07. The Trx1 level was effective to distinguish BC serum from healthy serum with a sensitivity of 94.3% and specificity of 93.9% (AUC 0.985, p< 0.001). The levels of Trx1 from BC patients were higher than the cut-off value of 14.13 U/ml regardless of age, stage, histological grade, type, ER/PR/HER2 expression profile, and proliferation activity of BC cells. The levels of Trx1 from the other five types of cancers (2.34±1.82 - 3.64±2.99) were low enough to be distinguishable from BC. Especially, Trx1 levels could rescue patients whose mammography resulted in a false judgement. Conclusions: These results indicated that the blood level of Trx1 is an effective and accurate method to detect breast cancer, and particularly as a complement to mammography.
Incidence of PI3K pathway alteration and response to neoadjuvant therapy (NAT) in triple negative breast cancer (TNBC) subtypes.
Authors: Basho Reva K , Yam Clinton , White Jason B , Zhao Li , Huo Lei , Mittendorf Elizabeth A. , Thompson Alastair Mark , Litton Jennifer Keating , Arun Banu , Lim Bora , Valero Vicente , Tripathy Debu , Zhang Jianhua , Adrada Beatriz E , Santiago Lumarie , Ravenberg Elizabeth , Moulder Stacy L. , Damodaran Senthil 
Published: May 2020

561 Background: Limited cell line and human data suggest that TNBCs characterized as mesenchymal and luminal androgen receptor (LAR) commonly have alterations in the PI3K pathway. More data is needed to better characterize the role of the PI3K pathway across TNBC subtypes. Methods: Pre-treatment tumor biopsies were collected from operable TNBC patients (pts) enrolled on a clinical trial of genomically tailored NAT (ARTEMIS; NCT02276443). Tumors were categorized into 5 groups using the Pietenpol criteria: basal-like (BL) comprised of BL-1 and BL-2, mesenchymal and mesenchymal stem-like (M), immunomodulatory (IM), LAR, or unspecified (UNS). Using whole exome sequencing data, variants (single nucleotide polymorphisms and insertions/deletions) and copy number variations (CNVs) were identified in 32 genes known to activate the PI3K pathway. Results: Tumor subtyping and pathologic response to NAT was available in 127 pts (clinical stage I: 9; II: 84; III: 34). PI3K pathway alteration defined as a variant in one of the evaluated genes and/or deletion of PTEN was seen in 76 (60%) tumors. The most frequent alterations were: PTEN deletion (21%), PIK3CA variant (11%), and PIK3R1 variant (8%). PI3K alteration and residual cancer burden (RCB) rates across TNBC subtypes are shown in the table. There was a significant difference in pathologic complete response (pCR)/RCB 0 rate after NAT across TNBC subtypes (chi2 test; P = 0.02). There was a significant difference in the incidence of PI3K pathway alteration across TNBC subtypes (chi2 test; P < 0.01). Overall, the presence of PI3K alteration was not associated with pCR (Fisher exact test; P = 0.85). Pts with M tumors had a higher rate of substantial residual disease (RCB II-III) after NAT. Presence of PI3K pathway alteration was common in the M subtype and associated with RCB II-III (82% in PI3K-altered vs 33% in wild-type tumors; Fisher exact test; P = 0.02). Presence of PI3K pathway alteration was common but not associated with response in the LAR subtype. Conclusions: The incidence of PI3K pathway alteration varied by TNBC subtype but was not associated with pathologic response to NAT with the exception of increased substantial residual disease (RCB II-III) in the M subtype. [Table: see text]
Validation of nomograms to predict non-sentinel lymph node metastasis after positive sentinel lymph node in breast cancer: Indian cohort background.
Authors: Reddy Asha , Nair Nita S. , Mokal Smruti , Shet Tanuja , Parmar Vani , Joshi Shalaka P , Chitkara Garvit , Thakkar Purvi , Badwe Rajendra 
Published: May 2020

568 Background: Axillary lymph node metastasis is still the important prognostic factor in the management of breast cancer (BC). Where we have moved towards axillary conservation in clinically node negative (cN0), the debate on what after 1-2 sentinel lymph nodes positive (SLN+ve) still continues. The ideal situation would be wherein we can accurately predict which patient has a risk of additional non SLN+ve. Several nomograms have been developed to predict the risk of NonSLN+ve. But in view of the differences in tumor size and nodal burden between our patients and the western data, we conducted a study to validate some of these nomograms in our cohort of early BC with positive LN on Low axillary sampling (LAS). Methods: Clinico-pathological data was collected for operable BC (OBC) with cN0 who underwent upfront SLNB or AS. This was entered into the various nomograms and the probability of the Non SLN+ve was calculated. Nomograms with AUC of greater than 0.7 were pre-defined as considerable discrimination. Results: From 2013 to 2018, 2350 women with cN0 OBC underwent LAS. Of which, 670 (28.5%) had a positive node on LAS. Median pT size was 3 cm with 327 (48%), LVI +ve 152 (77%) ENI +ve, 525 (78.4%) Hormone receptor +ve and 485 (72.4%) grade 3 tumors. Of 670, 239 (35.7%) had a NonSLN+ve on completion axillary dissection. The AUC values for nomograms included,ie. MSKCC, MDAnderson, Tenon, Cambridge, Shanghai, Mayo clinic and Turkish were 0.769, 0.77, 0.55, 0.74, 0.65, 0.529, 0.563 respectively. Only three nomograms, MDA, MSKCC and Cambridge had an AUC of more than 0.7. However, they were associated with poor sensitivity and specificity and high FNR (Table) making them clinically unreliable for this cohort. Conclusions: All 7 nomograms were not validated in our study. The larger T size and higher nodal burden of our cohort may be responsible for the same. We thus need to develop an Indian nomogram to predict the risk of non SLN+ve for our patients. [Table: see text]
Psychosocial outcomes following surgery in women with unilateral, nonhereditary breast cancer.
Authors: Lim David Wai , Retrouvey Helene , Kerrebijn Isabel , Butler Kate , O'Neill Anne C , Cil Tulin , Zhong Toni , Hofer Stefan , McCready David R. , Metcalfe Kelly A. 
Published: May 2020

570 Background: Rates of bilateral mastectomy continue to rise in average-risk women with unilateral breast cancer. We aim to characterize psychosocial predictors of surgical procedure and how psychosocial outcomes change over time after surgery for breast cancer. Methods: A prospective cohort of women with unilateral, nonhereditary breast cancer were recruited at University Health Network in Toronto, Canada between 2014-2017. Women completed validated psychosocial questionnaires (BREAST-Q) pre-operatively, and 6 and 12 months after surgery. Outcomes were assessed between three surgical groups (unilateral lumpectomy, unilateral mastectomy, bilateral mastectomy). Predictors of surgical procedure were identified using a multinomial logistic regression model. Change in psychosocial scores over time according to procedure was assessed using linear mixed models. All models control for age, stage, reconstruction and treatment. P values < .05 were considered statistically significant. Results: 506 women underwent surgery as follows: 216 unilateral lumpectomy (43%), 181 unilateral mastectomy (36%) and 109 bilateral mastectomy (22%). In the multinomial regression model, younger age (p < .01), and lower chest physical (p = .03) and sexual well-being (p = .02) predicted having bilateral mastectomy over unilateral lumpectomy while younger age (p < .01) and lower disease stage (p = .02) predicted bilateral mastectomy over unilateral mastectomy. The mixed model demonstrates that breast satisfaction follows a non-linear pattern of change over time, with 6- but not 12-month scores being significantly different from baseline (p = .015). Procedure predicts baseline satisfaction (p = .016), with bilateral mastectomy having worse satisfaction than unilateral lumpectomy. Procedure also predicts change in satisfaction, with unilateral and bilateral mastectomy having lower scores across time than lumpectomy. While a significant improvement in psychological well-being is detected by 12 months (p = .02), those with unilateral and bilateral mastectomy have worse psychological well-being over time compared to lumpectomy. Women having mastectomy start with worse physical well-being than those in the lumpectomy group, but their physical well-being does not decline as much as the lumpectomy group over time (p < .01). Conclusions: Definitive surgical procedure affects the trajectory of psychosocial functioning over time. This emerging data may be used to further facilitate surgical decision-making in women considering contralateral prophylactic mastectomy.