bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of metastatic spinal cord compression from prostate cancer.
Authors: Wang Jianbo 
Published: February 2020

248 Background: Spinal cord compression (SCC) is one of the most debilitating conditions in metastatic prostate cancer patients (pts). A comprehensive analysis of pts could shed lights on predisposing factors and help with devising new ways for early detection and prompt treatment. Methods: 52 pts with magnetic resonance imaging-confirmed metastatic SCC from prostate cancer were identified at MD Anderson Cancer Center. Characteristics including age, anatomical site, Gleason score, overall survival(OS), time to diagnosis of SCC, underlying gene mutations, numbers of bone metastasis, number of lines of treatment and clinical outcome were analyzed. Results: 96.15% of SCC occurred in thoracic spine in comparison to 74% as reported previously. At the time of diagnosis of SCC, median age is 70 years, median OS is 1537 days, median time to development of SCC is 1222.5 days, median lines of systemic treatment is 4, median PSA value is 66.4, 100% of pts have a Gleason score above 7, 94% of pts have >4 bone metastasis, roughly 20% of pts had visceral metastases. 55% of 9 evaluable pts harbored P53 gene mutation. About 80% of pts received radiation treatment; 17% of pts received surgery; 49% of pts had fair clinical outcome after treatment (Table). Conclusions: The observed predominance of SCC in thoracic spine (96.15%) suggests an underlying mechanism governing development of SCC in preferential sites. Further research to define this mechanism will help with prevention, detection and treatment of SCC. Additionally, characterized potential predictive factors (Gleason score≥7, >4 bone mets, presence of P53 mutation) could be used to develop an algorithm to improve the management of SCC.[Table: see text]
Artificial intelligence for streamlined immunofluorescence-based biomarker discovery in prostate cancer.
Authors: de la Calle Claire Marie , Nguyen Hao Gia , Hosseini-Asl Ehsan , So Clarence , Socher Richard , Xiong Caiming , Xue Lingru , Carroll Peter , Cooperberg Matthew R. 
Published: February 2020

279 Background: Immunofluorescence (IF) performed on tissue microarrays (TMA) is used for biomarker discovery but is limited by the arduous and subjective human visual assessment with an IF microscope. We aim to implement deep learning-based artificial intelligence (AI) models to automate and speed up the analysis of numerous biomarkers and generate prediction models of recurrence and metastasis after surgery. Methods: A TMA was constructed consisting of 648 samples (424 tumors, 224 normal tissue) generated from prostatectomy specimens. IF staining was performed on the TMA using anti Ki-67, ERG antibodies and analyzed for differential expression using “gold standard” manual microscopy and using an AI algorithm. Analysis was done blinded to any clinicopathological data. For manual microscopy, relative mean fluorescence intensity of cancerous versus normal tissue was determined. The AI algorithm was generated using a training cohort of digitized images. To do so the Otsu method thresholding algorithm combined with mean shift clustering was employed to find cell centers, followed by a level-set algorithm, to compute cell boundaries.These predictions were then combined with pixel predictions of a fully convolutional deep model to refine the regions of overlapping epithelium, stroma, and artifact. The algorithm was then validated using a separate cohort. Results from the algorithm were then compared to the data from manual microscopy. Results: Ki-67 and ERG expression levels generated by the algorithm showed only a 5% variance compared to the manually generated results. The algorithm was able to pick out which tumor were positive for ERG with 100% accuracy in spite of variance from artifacts. The algorithm also had the ability to improve its accuracy after each iteration of modifications and feedback through the training cohort. Conclusions: The AI algorithm produced similar outcomes than manual quantification with high accuracy but with more efficiency, cost effectiveness and objectivity. We are now developing more complex algorithms that will include the differential pattern of expression of PTEN, MYC and others with the objectives of streamlining biomarker discovery.
Does size matter? Lesion size as an indicator of number of cores needed to detect clinically significant prostate cancer.
Authors: Lebastchi Amir H. , O'Connor Luke P. , Wang Alex Z. , Yerram Nitin , Gurram Sandeep , Hale Graham , Bloom Jonathon B. , Gold Samuel A. , Rayn Kareem N. , Mehralivand Sherif , Wood Bradford J. , Shih Joanna H. , Turkbey Baris , Pinto Peter A. 
Published: February 2020

283 Background: MRI/US fusion guided prostate biopsy (FBx) has been shown to detect clinically significant prostate cancer (csCaP) at higher rates and with fewer cores than standard prostate biopsy. Size plays an important role in assigning a suspicion level (PI-RADS) to lesions identified on MRI. However, tumor characteristics may pose challenges to accurately characterizing the lesion despite the size. This study sought to determine if there are size cutoffs at which a lesion may be accurately characterized as clinically significant cancer with a single biopsy core. Methods: A retrospective analysis of a prospectively maintained database of all patients undergoing FBx at an academic referral center between May 2014 and January 2018 was conducted. At least two FBx cores were taken from each lesion identified on mpMRI. GEE-based univariate logistic regression model with exchangeable correlation was used determine if size was a significant predictor of positive and negative agreement. Predictability of size as a significant continuous predictor was quantified by AUC. Size thresholds at which multiple cores per lesion are needed to avoid missing > 2% of csCaP were calculated, allowing for a 25% discordance rate. Results: An analysis of a total of 1141 FBx of 2200 lesions was performed during the study time interval. Size was a significant predictor of both positive (OR = 2.43, 1.83-3.23, p < 0.01) and negative (OR = 0.58, 0.44-0.76, p < 0.01) agreement of csCaP. AUC% for positive and negative agreement was 65.8 and 57.6, respectively. Size thresholds of 0.65 and 1.70 cm limited CS cancers missed by skipping a second targeted biopsy core to 2% while allowing for a 25% discordance. Conclusions: These data indicate that clinically significant prostate cancer in lesions less than 0.65 cm and greater than 1.70 cm may be characterized with a single targeted biopsy core, sparing 33.5% of lesions (21% patients) a double core targeted biopsy.
Detection of clinically significant prostate cancer after negative fusion and systematic biopsy.
Authors: Twum-Ampofo Jeffrey , Ceraolo Carl , Gusev Andrew , Feldman Adam S. 
Published: February 2020

288 Background: MRI/Ultrasound fusion biopsy of the prostate has enhanced the detection of clinically significant prostate cancer (csPCa). Detection of csPCa is greatest when fusion and systematic biopsies are combined. However, the finding of a negative fusion and negative systematic biopsy in patients with suspicious lesion on imaging raises the question of either falsely positive imaging or a false negative biopsy. Methods: We retrospectively reviewed our database of patients undergoing MRI/transrectal US-guided fusion biopsy. All images were graded according to the Prostate Imaging Reporting and Data System version (PIRADS) 2.0. Patients underwent targeted biopsy followed by systematic 12-core double sextant biopsy within the same session. csPCa was defined as Grade Group (GG) ≥2 PCa. Patients with no prostate cancer (PCa) found on biopsies were followed. MRI studies with PIRADS v2 score ≤ 2 were considered to have no MRI evidence of PCa. Results: A total of 400 patients had at least one PIRADS ≥3 lesion and underwent fusion/systematic biopsy. Of these, 113 (28.3%) patients had no evidence of PCa on either fusion or systematic biopsy. Median follow-up was 32.5 months. 44 (39%) patients underwent repeat MRI and of these, 24 (54%) had no evidence of PCa on repeat MRI. PIRADS lesion disappearance was associated with lower PSA Density (PSAd) (0.12 vs 0.20; P = 0.0319) and decreased progression to repeat biopsy (8.33% vs 95%; P < 0.0001). Patients who had a repeat biopsy had a greater PSAd ( 0.21 vs 0.12; P = 0.0054). Of 113 patients with negative initial biopsy, 23 (20.4 %) underwent repeat biopsy: 16 (14.2 %) had PCa and 11 (9.7%) had csPCa. Thus, 48% of patients who underwent repeat biopsy had csPCa. Among patients with a PCa on repeat biopsy, cancer was sampled by MRI targeted cores in 80% of patients. Conclusions: Despite a negative initial fusion/systematic biopsy, at least 10% of patients were subsequently diagnosed with clinically significant PCa. The combination of elevated PSAd and the persistence of a suspicious lesion on repeat MRI appears selective for previously missed PCa. However, after negative fusion biopsy, repeat MRI yields a high rate of PIRADS lesion disappearance in patients with low PSAd.
Advancing age and the risk of adverse pathology at radical prostatectomy in men with biopsy Gleason score 6 prostate cancer.
Authors: Kim Daniel , Chen Ming-Hui , Huland Hartwig , Graefen Markus , Tilki Derya , D'Amico Anthony Victor 
Published: February 2020

289 Background: We evaluated the impact of age > 65 years versus younger on the odds of finding adverse pathologic features (pT3/T4 and/or R1 and/or Gleason score 8, 9, 10) at radical prostatectomy (RP) among men with biopsy Gleason score 6 prostate cancer (PC). Methods: The study cohort comprised 3191 men with biopsy Gleason score 6 PC treated with a RP between February 28, 1992 and February 15, 2016 at the Martini-Klinik Prostate Cancer Center. Multivariable logistic regression was used to evaluate the impact of age > 65 years versus younger on the adjusted odds ratio (AOR) of finding adverse pathology at RP adjusting for pre-RP prostate specific antigen (PSA), clinical tumor category, year of diagnosis, percent positive biopsies (PPB), and PSA density (PSAd). Results: Men age > 65 years as compared to younger had significantly lower median PPB (16.67% vs 20.0%; p = 0.01) and PSAd (0.13 ng/mL vs 0.15 ng/mL; p < 0.0001). Yet, while both increasing PPB (AOR 1.018, 95% CI 1.013, 1.023; p- < 0.0001) and PSAd (AOR 4.28, 95% CI 1.66, 11.01; p = 0.003) were significantly associated with an increased odds of finding adverse pathology at RP, men age > 65 years versus younger had a higher odds of adverse pathology at RP (AOR 1.28, 95% CI 1.002, 1.62; p = 0.048). Conclusions: Despite a more favorable median PPB and PSAd, men with biopsy Gleason score 6 PC and who are age > 65 years compared to younger men are at higher risk for having adverse pathology at RP and may benefit from a multiparametric MRI and targeted biopsy before proceeding with active surveillance. If higher grade/stage disease is discovered and treatment indicated then this information could guide both the use and duration of supplemental androgen deprivation therapy in men considering radiation therapy.
Comparison of micro-ultrasound and multiparametric MRI imaging for prostate cancer: A multicenter prospective analysis.
Authors: Klotz Laurence , Lughezzani Giovanni , Sanchez Andrrea , Staerman Frederic , Cash Hannes , Gaston Richard , Sanchez-Salas Rafael , Klein Eric A. , Eure Gregg 
Published: February 2020

296 Background: This study aims to compare the sensitivity, specificity, NPV and PPV of mpMRI with the novel high-resolution micro-ultrasound imaging modality. This approach offers the benefits of simplicity, a single intervention for imaging and biopsy, leveraging the low cost of ultrasound. Micro-ultrasound may be used to image suspicious lesions and target biopsies in real-time with or without additional MRI-based targets. Methods: Data from 9 sites was aggregated, totaling 866 subjects presenting for ExactVu micro-ultrasound guided biopsy with available mpMRI studies. Samples in all subjects were taken from mpMRI targets and micro-ultrasound targets, with up to 12 systematic samples filled in. Various strategies were used for mpMRI target sampling including cognitive fusion with micro-ultrasound, separate software-fusion systems, and software-fusion using the micro-ultrasound FusionVu system. Clinically significant cancer was considered any Gleason Sum > 6 and targeted samples were taken for PI-RADS > 2 or PRI-MUS1 > 2 lesions. Results: Overall, 39% of all biopsy cases were positive for clinically significant PCa. mpMRI demonstrated 89% sensitivity and NPV of 77%. Compared to mpMRI, micro-ultrasound sensitivity (95%) and NPV (87%) were higher. Micro-ultrasound was less specific (21% vs 23% for mpMRI) with similar PPV (44% vs 43%). The aggregate effect demonstrates higher sensitivity for csPCa with micro-ultrasound compared to mpMRI (p<0.01). Conclusions: Micro-ultrasound is an attractive option for screening and targeted biopsy. Sensitivity and NPV appear superior to MRI, but specificity is mildly reduced. Further larger-scale studies are required for validation of these findings. References: Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, 2016 Aug;196(2):562-9. Clinical trial information: NCT03938376.
The deleterious association between proton pump inhibitors and prostate cancer specific death.
Authors: Goldberg Hanan , Moshin Faizan , Saskin Refik , Kulkarni Girish S. , Berlin Alejandro , Kenk Miran , Wallis Christopher J.D. , Chandrasekar Thenappan , Klaassen Zachary William Abraham , Saarela Olli , Penn Linda , Alibhai Shabbir M.H. , Fleshner Neil Eric 
Published: February 2020

309 Background: Proton pump inhibitors (PPIs) are a commonly prescribed class of medications. Although in-vitro and in-vivo data have shown PPIs to have anti-tumor effects, more recent studies suggest an increased cancer risk in several solid organs. Pantoprazole, a commonly prescribed PPI, has been shown to harbor a protective effect in human prostate cancer (PCa) cells. We aimed to investigate the effect of pantoprazole and other PPIs on PCa-specific death and additional PCa outcomes. Methods: In this retrospective, population-based cohort study, data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all men aged 66 and above with a history of a single negative prostate biopsy between 1994 and 2016. We used multivariable Cox regression models with time-dependent covariates, to assess the effect of PPIs on PCa diagnosis, androgen deprivation therapy (ADT) use, and PCa-specific death. All models included other medications with a putative effect on PCa. All models were adjusted for age, rurality, comorbidity, and year of patient study inclusion. Results: Overall, 21,512 men were included, with a mean follow-up time of 8.06 years (SD 5.44 years). A total of 10,999 patients (51.1%) used a PPI. A total of 5,187 patients (24.1%) were diagnosed with PCa, 2,043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. Pantoprazole was associated with a 3.0% (95% CI 0.3%-6,0%) increased rate of being treated with ADT for every six months of cumulative use, while any use of all other PPIs was associated with a 39.0% (95% CI 18.0%-64.0%) increased PCa-specific mortality. No significant association was found with PCa diagnosis. Conclusions: Upon validation of the potentially negative association of PPIs with PCa outcomes, the expansive use of PPIs may need to be reassessed, especially in PCa patients.
A randomized phase III trial between adjuvant docetaxel and surveillance after radical radiotherapy (RT) for intermediate and high-risk prostate cancer (PC): Quality-of-life results (QoL) in SPCG-13 trial.
Authors: Kellokumpu-Lehtinen Pirkko-Liisa , Hjälm-Eriksson Marie , Thellenberg-Karlsson Camilla , Astrom Lennart , Franzen Lars , Fransson Ann-Sofie , Leskinen Markku J. , Huttunen Teppo , Ginman Claes 
Published: February 2020

313 Background: Six docetaxel cycles did not improve PSA relapse free survival as an adjuvant treatment after radical RT (Kellokumpu-Lehtinen EURURO-8532). Here we report SPCG-13 trials QoL results. Methods: A total of 376 PC patients (T2 with Gleason score (GS) 4+3, PSA>10; T2, GS 8-10 any PSA; or any T3) were randomised to receive either 6 cycles of docetaxel 75mg/m2 every 3 weeks (Arm A, n=188) or surveillance (Arm B, n=188) after radical RT NTC006653848. Neoadjuvant/adjuvant ADT was mandatory. Primary end-point was a rising PSA > 2 ng/ml above the nadir. Patients were followed for 5 years with PSA every 3 months for two years and thereafter every 6 month. FACT-P QoL questionnaires were used at baseline, during and after docetaxel treatment and in the follow-ups (at 1 year, 2 years and 4 years after treatment) in both groups, and analysed using analysis of variance (ANOVA) models. Results: Median follow-up was 59.4 months (range 1 to 111 months). 147 (78.2%) patients completed all six cycles in arm A. Mean age was 66.2 years in Arm A and 66.4 years in Arm B. The total QoL scores at baseline did not differ between the Arms (mean 119.0, SD±18.9, n=177 vs 118.2, SD±18.1, n=180). In Arm A the total score declined to 116.3 (SD+15.2), at 24 weeks and was 118.5 (SD±21.3) after chemotherapy. In Arm B at 24 weeks the QoL score had increased to 123.3 (SD±19.2) and was significantly higher than in Arm A (estimated difference of 8.2 with p<0.0001, ANOVA model adjusted for baseline). However, in the first follow-up (1 year) the QoL score was same in both Arms (123.7 vs 123.6, respectively, p=0.344, ANOVA model adjusted for baseline) and remained at the same level during further follow-ups. The decline in QoL scores during the docetaxel treatment were seen only in two sub-scores; functional and physical. Conclusions: Adjuvant docetaxel did decrease the QoL of patients during the treatment. However, in the later follow-ups it increased to the same level as those patients without docetaxel treatment. These results further support our conclusions of showing no benefit from docetaxel as adjuvant treatment in this patient group after radical curative treatment. Clinical trial information: RT NTC006653848.
Quality of life outcomes from a phase III trial exploring optimal sequencing of androgen deprivation therapy with external beam radiotherapy in localized prostate cancer.
Authors: Roy Soumyajit , Grimes Scott , Eapen Libni , E Choan , Malone Kyle , Craig Julia , Morgan Scott Carlyle , Malone Shawn 
Published: February 2020

315 Background: Dose-escalated prostate radiotherapy (PRT) with androgen deprivation therapy (ADT) is a standard curative treatment for localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. We report the patient-reported health related quality of life (HR-QoL) outcomes from a phase III study exploring optimal sequencing of PRT with ADT in LPCa. Methods: Newly diagnosed LPCa patients with Gleason score ≤7, clinical stage T1b-T3a, and PSA < 30 ng/mL were randomized to receive PRT (76 Gy/38 fractions) with 6 months (mos) of ADT starting 4 mos prior to RT (NAHT arm) or concurrently with RT (CAHT arm). HR-QoL was assessed using EORTC QLQ-C30 and PR25 at baseline, q2 mos while on ADT, q4 mos for year 1 and 2 after ADT, q6 mos from year 3 to 5 and annually thereafter. Linear mixed modelling was applied to compare change in score (relative to baseline) over time. Wilcoxon rank-sum test was used to identify between-group difference in absolute scores, at 18, 36 and 60 mos. The statistical and clinical significance was set at p≤0.01 and 10-point threshold, respectively. Results: Overall 432 men were enrolled in the study and 393 (194 in NAHT and 199 in CAHT arm) were eligible for HR-QoL evaluation. There was a significant difference in the change in score of sleep disturbance due to urinary bother (least-squared mean: 3.9 vs. 7.6, P = 0.001) between the two arms. Although there were statistically significant differences in absolute scores of global QoL (18, 60 mos), cognitive (18, 60 mos), social and emotional functions (60 mo), sexual intimacy (18 mo) and fatigue (60 mo) favoring NAHT, the only clinically meaningful difference was noted in ejaculatory dysfunction at 18 (mean: 52.5 vs. 64.6), 36 (60.2 vs. 49.2) & 60 mos (61.4 vs. 50.9), respectively. Conclusions: We did not find any notable difference between the two arms with respect to score change over time in any of the HR-QoL metrics except sleep disturbance due to urinary bother. Clinically meaningful difference was noted only in the late absolute ejaculatory dysfunction score which favored the NAHT arm. Based on these findings, both NAHT and CAHT with PRT are reasonable standards of care for LPCa. Clinical trial information: DC-990-0082.
Stereotactic body radiation therapy with androgen deprivation therapy for unfavorable-risk prostate cancer.
Authors: Patel Sagar Anil , Switchenko Jeffrey M. , Zhang Chao , Rose Brent Shane , Fischer-Valuck Benjamin Walker , Jani Ashesh B. , Chen Ronald C. , Royce Trevor Joseph 
Published: February 2020

332 Background: Current ASTRO consensus guidelines do not support routine use of SBRT in higher risk PC. However, the NCCN permits selective use of SBRT with ADT for unfavorable intermediate (UIR) and high (HiR) risk PC in cases where conventional/moderately fractionated radiation therapy (EBRT) present medical or social hardship. How SBRT+ADT compares to EBRT+ADT in UIR and HiR men is unknown. Methods: Men >40 years old with localized PC treated with RT and concomitant ADT for curative intent between 2004-2015 were analyzed from the National Cancer Database. Patients treated with brachytherapy or who lacked ADT or risk stratification data were excluded. A total of 558 men treated with SBRT (5 fractions, ≥7 Gy/fraction) versus 40,797 men treated with moderate or conventional EBRT (dose ≥60 Gy with ≤3 Gy/fraction) were included. Patients were stratified by UIR and HiR using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index. Results: With a median follow up of 62 months, there was no difference in 5-year OS between men treated with SBRT versus EBRT regardless of risk group (UIR: 87.2% SBRT versus 87.0% EBRT, p=.40; HiR: 80.4% SBRT versus 80.8% EBRT, p=.21). On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68-1.74, p=.72; HiR: adjusted HR 0.93, 95% CI 0.76-1.14, p=.51). Conclusions: We found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HiR PC. Randomized trials of SBRT versus EBRT, with standard concomitant ADT, in these risks groups are needed. If prospectively validated, more widespread use of SBRT for higher risk PC may be warranted, especially in an era of cost-effective care.