bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Personalized Medicine for Prostate Cancer (PMPC) Study: The role of race, genomics, and patient complexity in treatment outcomes.
Authors: Greenfield Sheldon , Uchio Edward M. , Litwin Mark S. , Gin Gregory , Garraway Isla , Daskivich Timothy J. , Garland Harwood , Kaplan Sherrie H. 
Published: February 2020

302 Background: Matching of patients with optimal treatment for localized prostate cancer (PCa) requires accurate estimates of risk for progression or recurrence. Traditional risk assessment methods may underestimate risk for certain patient subgroups, (e.g. minorities). In the PMPC study, we replicated an expanded risk model, adding genomic data to improve risk prediction and optimize treatment assignment for PCa. Methods: A prospective cohort of 660 patients with early PCa was identified from 3 teaching hospitals and 2 VA Hospitals in Southern California. Risk model data were collected from electronic medical records, patient questionnaires and tissue-based genomic data provided by GenomeDx. Complexity variables included demographic characteristics, clinical markers (PSA levels, Gleason score), patient-reported health status measures (e.g. comorbidity burden, depression, stress) and Decipher score. We compared individual components of the complexity score for 425 Non-Hispanic White (NHW) and 104 African American (AA) men using t-tests. Composite complexity scores were derived from weights from general linear models. Mean complexity scores were compared using t-tests. Results: Compared with NHW men, AA men had statistically significantly more comorbidity, poorer health ratings, poorer physical functioning, more depression, less energy, more fatigue, more stress and less resilience. More AA men had Gleason scores >6 (60.0%) than NHW men (46.6%), p=.0134. Fewer AA men (41.5%) had ‘low risk’ Decipher scores compared to NHW men (53.8%). More AA men had high complexity scores compared with NHW men (63.4% vs. 45.1%, p=.008), however, there were no statistically significant differences in the proportion of NHW vs. AA men on active surveillance, 46.0% vs. 40.7%, p=.384. Using clinical variables alone there were no significant differences in low risk between NHW and AA men. Conclusions: The addition of genomic data improved the complexity model developed earlier. AA men may be at higher risk for suboptimal treatment than predicted by clinical variables alone. Data from the longitudinal cohort will test accuracy of model prediction for disease progression or recurrence. Clinical trial information: NCT03770351.
A prospective study evaluating oral-only hormonal therapy with radiation for intermediate or high-risk prostate cancer in men age ≥ 70 years or with moderate comorbidity.
Authors: Onderdonk Benjamin Ernst , Dorn Paige L. , Arif Fauzia , Golden Daniel William , Karrison Theodore , Pitroda Sean P. , Szmulewitz Russell Zelig , Liauw Stanley L. 
Published: February 2020

303 Background: Androgen deprivation therapy (ADT) improves disease control in intermediate (IR) and high risk (HR) prostate cancer (PCa) treated with radiation therapy (RT), but also causes toxicity which may be worse in men of older age or with comorbidity. We hypothesized that dual agent ADT, replacing GnRH agonist for an oral 5-alpha-reductase inhibitor (5AR), would improve hormonal health-related quality of life (HRQOL) without compromising PCa outcomes. Methods: Patients with localized IR or HR PCa, age > 70 years and/or with Charlson comorbidity index (CCI) score > 2 were treated with bicalutamide and finasteride or dutasteride (oADT). A synchronous standard of care (SOC) cohort received bicalutamide and GnRH agonist. Median RT dose was 78 Gy. Dual agent ADT was given for 4 months (mo), while 5AR or GnRH agonist continued for an additional 2 years. The primary endpoint was the Expanded Prostate Cancer Index Composite (EPIC-26) hormonal HRQOL global score at 6 mo, with success defined as < 30% decline, requiring 40 men in the oADT group. Secondary endpoints included a log-rank comparison of freedom from biochemical failure (FFBF), and overall survival (OS). Results: Between 1/2011 and 8/2018, 40 and 30 men were prospectively enrolled in the oADT and SOC cohorts, respectively, with similar CCI scores > 2 (73% vs 66%, p=0.58), and age (mean 71, p=0.99). Median follow-up was 36 mo. Global scores for hormonal HRQOL at baseline, 6 mo, and 2 yr were 89, 88, 84 for the oADT group, and 92, 81, 83 for the SOC group; the declines from baseline to 6 mo (p=0.04) and 2 yr (p=0.05) were smaller in the oADT group. Sexual HRQOL was better preserved at 6 mo (p<0.01) in the oADT group, which maintained higher testosterone at 2 years (452 vs 44, p<0.01). There were no differences in urinary or bowel HRQOL. The 3-year FFBF was 90% vs 96% (p=0.83) and OS was 83 vs 86% (p=0.77) between the oADT and SOC groups, respectively. Conclusions: oADT improves hormonal and sexual HRQOL compared to SOC ADT in men age ≥ 70 or moderate comorbidity treated with RT. These groups could be further evaluated in a randomized comparison; post-ADT RNA expression to evaluate the relative biologic effects will be performed. Clinical trial information: NCT01342367.
A prospective comparison of MRI-planned versus CT-planned radiotherapy for prostate cancer.
Authors: Schmidt Daniel R , Bhagwat Mandar , Glazer Daniel I. , Chen Ming-Hui , D'Amico Anthony Victor 
Published: February 2020

312 Background: Chronic rectal toxicity significantly decreases the quality of life for men who receive radiotherapy for prostate cancer. The volume of rectum exposed to 70 Gy or more is a validated metric that predicts the risk of late rectal toxicity. We hypothesized that MRI as compared to CT-based prostate radiotherapy treatment planning can reduce the volume of rectum exceeding 70 Gy. Methods: This prospective study single arm study enrolled 15 men treated with external beam radiation therapy for localized prostate cancer. At the time of treatment planning a 3 Tesla T2-weighted magnetic resonance imaging examination of the prostate was obtained. A radiotherapy plan was designed by a medical physicist using identical constraints for both CT and MRI-based consensus volumes defined by a radiologist and radiation oncologist. The volume of rectum exposed to 70 Gy or more was calculated and compared using the paired Signed Rank Test. Results: The median age was 70 years (range 56-84), median PSA 7.3 ng/mL (range 3.2 – 22.1), and median prostate volume 40 mL (range 25 - 65) by transrectal ultrasound. Sixty percent (n=9) were intermediate risk and 40 percent (n=6) high risk by NCCN guidelines. The majority were either clinical stage T1c (n=7) or T2 (n=6). Two men had extracapsular extension (T3a). None of the participants had seminal vesicle invasion (T3b), rectal or bladder involvement (T4), or lymph node metastasis (N1). All 15 men enrolled on the study completed both a standard radiation planning CT and research MRI examination. For CT-based treatment plans the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) [IQR 7.0 to 10.2] compared with 4.9 cc [IQR 4.1 to 8.7] for MRI-based plans. This resulted in a median volume reduction of 2.1 cc [IQR 0.5 to 5.3, P < .001]. Conclusions: MRI-planned prostate radiotherapy can reduce the volume of rectum receiving radiation doses in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity. Clinical trial information: NCT02470910.
Risk of secondary sarcoma after abdominopelvic cancer treatment: Results from a contemporary cohort.
Authors: Hird Amanda Elizabeth , Matta Rano , Magee Diana E. , Kulkarni Girish S. , Kodama Ronald , Herschorn Sender , Nam Robert 
Published: February 2020

317 Background: Our objective was to explore the risk of sarcoma in a large cohort of patients with localized abdominopelvic cancer treated with radiotherapy (RT) compared to surgery. The risk of other secondary non-sarcoma solid organ tumors was also explored. Methods: This is a population-based retrospective cohort study examining the risk of sarcoma in patients with localized prostate, bladder, colorectal, cervical, uterine, and testis cancer between January 1, 2002-December 31, 2016. Multivariable Cox proportional hazard analysis was used to compare time from primary treatment (radical surgery or RT) to second cancer, adjusting for age, comorbidity, income quintile, and rurality, accounting for death as a competing risk. The standardized incidence rate (SIR) was calculated as the ratio of the observed divided by the age- and sex-stratified expected number of sarcoma cases from the Ontario population. Results: 173,580 patients were included (79,662 underwent surgery and 93,918 underwent RT). Most patients had genitourinary (51.4%) or colorectal cancer (39.9%) and 24.4% received chemotherapy. Overall, 332 sarcomas developed over a median 5.7 years (IQR: 2.2-8.9) and were more common in the RT group (239/93918 [0.3%]) compared to the surgery group (93/79662 [0.1%], p<0.001). RT exposure (unadjusted HR=2.67, 95%CI:2.10-3.40, p<0.001, adjusted HR=2.59, 95%CI:2.03-3.31, p<0.001) and perioperative chemotherapy use (HR=1.31, 95%CI:1.03-1.69, p=0.038) were associated with an increased relative rate of sarcoma. Patients who received RT had an increased risk of sarcoma compared to the general population (SIR=1.46, 95%CI:1.12-1.90, p=0.005). For our secondary outcome, patients who received RT had an increased hazard of developing a second non-sarcoma solid malignancy compared to patients who underwent surgery (HR=1.16, 95%CI:1.10-1.22, p<0.001). Conclusions: This is the largest cohort investigating sarcoma in patients with abdominopelvic cancer. Patients treated with RT have a markedly increased risk of sarcoma compared to the general population. RT was an independent risk factor for sarcoma and non-sarcoma second malignancy.
Evaluating the tolerability of a simultaneous focal boost to the gross tumor in prostate SABR: A toxicity and quality-of-life comparison of two prospective trials.
Authors: Alayed Yasir , Davidson Melanie , Chu William , Liu Stanley K. , Tseng Chia-Lin , Cheung Patrick , Vesprini Danny , Chung Hans T. , Morton Gerard , Musunuru Hima Bindu , Ravi Ananth , Korol Renee , Deabreu Andrea , Commisso Kristina , Bhounr Zeeba , D'alimonte Laura , Mittmann Nicole , Dragomir Alice , Zhang Liying , Loblaw Andrew 
Published: February 2020

319 Background: Dose-escalated SABR to the whole prostate may be associated with better outcomes, but at a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on MRI. We report the toxicity and quality of life (QOL) outcomes of two phase II trials of prostate and pelvic SABR, with or without a simultaneous DIL boost. Methods: The first trial treated patients with high-risk prostate cancer (PCa) to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk PCa to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities and QOL were assessed. Results: 30 patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 GI or GU toxicity between the two trials, or cumulative worst late GI or GU toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the two trials. Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible and did not lead to a significant change in toxicity or QOL when compared to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes. Clinical trial information: NCT02911636.
Real-world analysis of prostate-specific antigen (PSA) outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide (ENZA).
Authors: Freedland Stephen J. , Schultz Neil M. , Coutinho Anna D. , Fuldeore Rupali , Hedlund Nancy , Feng Qi , Ramaswamy Krishnan , Hong Agnes 
Published: February 2020

33 Background: ENZA showed efficacy in chemotherapy-naïve men with mCRPC in a clinical trial setting (PREVAIL). We report real-world outcomes with ENZA for this population in a urology practice setting. Methods: This retrospective cohort study included men with prostate cancer newly initiating ENZA in the IntrinsiQ Specialty Solutions™ urology electronic medical records database between September 1, 2014 and February 28, 2018. Due to the approved indication in the study time frame, prescription of ENZA (first claim date = index date) was used as a proxy for mCRPC. Patients with evidence of prior chemotherapy and/or abiraterone were excluded. PSA value closest to index date (±30 days) was used as baseline. Men were followed until the earliest of: discontinuing ENZA, leaving practice, death, or study end. Best PSA response (largest decline or smallest increase in absence of decline from baseline), PSA declines of ≥50% and ≥90%, undetectable PSA, and time to PSA progression were analyzed. Results: We identified 931 eligible men. Most (>95%) were ≥60 years old; hypertension (54.6%) and diabetes (17.0%) were the most common comorbidities. Median (interquartile range [IQR]) baseline PSA was 9.0 (2, 37) ng/dL. Median (IQR) follow-up time was 12.5 (7.6, 19.4) months, during which a median (IQR) of 4 (3, 6) PSA tests were observed. Median time between two adjacent PSA tests was 2.0 months. A ≥50% and ≥90% PSA decline was observed in 55.0% and 23.8%, respectively. Best PSA response was a median (IQR) PSA decline of 58% (-89%, 1%), with 14.2% reaching an undetectable PSA value. Median time to PSA progression was 18.5 months (95% confidence interval 15.6, 23.7). Conclusions: This real-world study supports the effectiveness of ENZA in patients with mCRPC. The median PSA at treatment was much lower than PREVAIL, potentially explaining the longer time to PSA progression vs. PREVAIL. However, a lower proportion had PSA declines of ≥50% and ≥90% vs. PREVAIL, which may be attributed to more frequent PSA monitoring within a clinical trial setting and thus more opportunity to capture the true best PSA response.
The risk of death from prostate cancer in men with Gleason Score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy.
Authors: Yang David Dewei , Chen Ming-Hui , Braccioforte Michelle H. , Moran Brian Joseph , D'Amico Anthony Victor 
Published: February 2020

330 Background: We evaluated whether the intermediate-risk factors of percentage of positive biopsies (PPB), clinical tumor category, and prostate-specific antigen (PSA) level, in addition to age, were associated with the risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer treated with brachytherapy (BT) alone or BT and a short course of androgen deprivation therapy (ADT). Methods: We conducted a prospective cohort study of 1920 consecutively treated men with Gleason 3+4 adenocarcinoma of the prostate who received BT or BT and a median of 4 months of ADT between 10/14/1997 and 5/28/2013. Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether PPB, cT2b-T2c, and PSA of 10.1-20.0 ng/ml, in addition to age greater than the median of 70 years, were associated with the risk of PCSM after adjustment for comorbidity. Results: After a median follow-up of 7.8 years (interquartile range 5.2-10.4 years), 284 men (14.8%) had died, including 31 (10.9% of deaths) from PC of which 18 (58.1%) and 13 (41.9%) occurred in men treated with BT or BT and ADT, respectively. For men treated with BT alone, increasing PPB, PSA of 10.1-20.0 vs 4.0-10.0 ng/mL, and age >70 vs ≤70 years were significantly associated with an increased risk of PCSM (adjusted hazard ratio [AHR] 1.015 95% confidence interval [CI] 1.000-1.031, P=0.048; AHR 5.55, 95% CI 2.01-15.29, P<0.001; and AHR 3.66, 95% CI 1.16-11.56, P=0.03, respectively). The respective results for men treated with BT and ADT were AHR 1.009, 95% CI 0.987-1.031, P=0.44; AHR 4.17, 95% CI 1.29-13.50, P=0.02; and AHR 3.74, 95% CI 0.87-16.05, P=0.08. The clinical tumor category was not significantly associated with the risk of PCSM. Conclusions: Among men with biopsy Gleason score 3+4 PC, both age >70 years and PSA of 10.1-20.0 ng/ml were significantly associated with an increased risk of PCSM following BT, and adding 4 months of ADT may not be sufficient to mitigate this risk. Advanced imaging and targeted biopsy of suspicious areas should be considered to personalize treatment in order to minimize the risk of PCSM in these men.
Clinical-genomic sub-classification of high-risk prostate cancer: Implications for tailoring therapy and clinical trial design.
Authors: Muralidhar Vinayak , Alshalalfa Mohammed , Spratt Daniel Eidelberg , Liu Yang , Karnes R. Jeffrey , Schaeffer Edward M. , Davicioni Elai , Feng Felix Y , Klein Eric A. , Tosoian Jeffrey J. , Berlin Alejandro , Den Robert Benjamin , Nguyen Paul L. 
Published: February 2020

337 Background: Current risk stratification schema have limited prognostic performance in predicting outcome within National Comprehensive Cancer Network (NCCN) high-risk to very high-risk prostate cancer. Methods: Two multicenter high-risk cohorts were used for training (n = 214) and validation (n = 151) of a novel RNA microarray-based integrated clinical-genomic Classifier Optimized for Outcome in High-risk Prostate cancer (COOHP) to classify patients as COOHP favorable high-risk, standard high-risk, or very high-risk. Cox analysis was used to model metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Model performance was compared to prior sub-classification systems using time-dependent c-indices. Results: Among NCCN high/very high-risk patients in the training cohort, 11% were classified as COOHP favorable high-risk, 70% as COOHP standard high-risk, and 18% as COOHP very high-risk. Patients with COOHP favorable high-risk disease had better rates of 5-year MFS compared to those with COOHP standard high-risk disease (94% vs 76%, hazard ratio [HR] 0.10, p = 0.02), and patients with COOHP very high-risk disease had worse 5-year MFS compared to those with COOHP standard high-risk disease (34% vs 76%, HR 3.5, p < 0.0001). Similarly, patients with COOHP very high-risk disease had worse 10-year PCSS compared to those with COOHP standard high-risk disease (36% vs 82%, HR 4.4, p < 0.0001). The c-indices for 5-year MFS and 10-year PCSS in the training cohort were 0.80 and 0.74, significantly improved compared to prior clinical and clinical-genomic risk stratification systems (0.62-0.69 for 5-year MFS and 0.56-0.63 for 10-year PCSS). These results were consistent in the validation cohort, where 5-year MFS significantly varied among the three COOHP subgroups (100% vs 89% vs 79%, p = 0.020), as did 10-year OS (100% vs 71% vs 53%, p = .040). Conclusions: A clinical-genomic risk stratification system specifically designed to discriminate prognosis in high-risk prostate cancer better identified favorable high-risk and very high-risk subsets of disease compared to prior clinical and clinical-genomic stratification systems.
Overall survival of black and white men with metastatic castrate-resistant prostate cancer: A retrospective analysis across 20 years in the largest healthcare trust in the United Kingdom.
Authors: Ng Kenrick , Wilson Peter , Mutsvangwa Katherine , Shamash Jonathan 
Published: February 2020

35 Background: Prostate cancer in Black (B) men has been associated with poorer outcomes than their White (W) counterparts. However, this perception has been derived from studies conducted predominantly in the localized prostate cancer setting, were based on data derived from clinical trials and usually conducted solely within the United States. Methods: We reviewed the outcomes of cases with metastatic castration resistant prostate cancer (mCRPC) treated at St Bartholomew’s Hospital – the UK's largest Healthcare Trust - between 1997-2016. Statistical analyses were conducted using Intercooled Stata 8.2 (State College, TX, USA). Results: We identified 425 cases of mCRPC in the 20 year period. A substantial minority of our patients, 103 (24%) were Black (B), and the remainder White (W). Characteristics were matched in age (73 years in both groups), proportion enrolled in clinical trials (33% in both groups) and median PSA (65.6,B vs 78,W, p=0.86), with a larger proportion of Black patients with a ECOG Performance Status ≥ 2 (19%,B vs 9%,W). In the total cohort analysis, the median Overall Survival (OS) was 25.5 months (B) vs 21.8 months (W), (Hazard Ratio, HR=0.81,p=0.08). For the subpopulation who received chemotherapy at some point of their treatment (n=306), survival was comparable in both groups (median OS 23.8 months, B vs 22.8 months, W, HR=0.97,p=0.82). Interestingly, there was a trend to prolonged survival in the Black population in those who only received hormone therapy (n=106) throughout their treatment course; 39.7 months (B) vs 17.1 months (W), HR=0.54, p=0.019. In a multivariate analysis for prognostic factors for survival from mCRPC therapy considering ethnicity (HR 0.81 p=0.08), time from diagnosis to castrate resistance (HR 1.02, p=0.136), presence of bone metastases at CRPC diagnosis (HR 1.89,p=0.001) – only bone metastases were significant. Conclusions: In the first set of real-world data in a study conducted outside the US, we demonstrate that Black patients do not do worse than White patients with mCRPC. The study suggests that there is a greater margin of benefit of hormone-based therapy in the Black subpopulation.
Early diagnosis of prostate cancer, AABH (Aspartyl Asparaginyl β-hydroxylase), a predictive biomarker: A serum immunoassay and personalized medicine.
Authors: Moshiri Kiarash 
Published: February 2020

353 Background: Prostate Cancer (PC) is the most common form of cancer in men in the United States. In their lifetime, approximately 1 out of every 6 American men will develop PC. The chances of developing PC increase dramatically after age 50 with more than 70% of cases occurring in individuals over 65 years of age. Methods: We have investigated the use of aspartyl (asparaginyl) β-hydroxylase (AABH) as a cancer biomarker. We have developed a sandwich ELISA for its detection. Here this assay was utilized to screen sera from patients with prostate cancer and PSA values in various ranges. Results: AABH levels were assessed in sera from 263 individuals with PC and 73 men over 50 years of age not known to have cancer. The levels of AABH in the two groups were >3.00 ng/ml and <3.00 ng/ml, respectively. The overall sensitivity and specificity of the test were 97.5% and 96%. AABH and PSA levels were also compared. The AABH values and sensitivities in individuals with PC and PSA values in the ranges <2 ng/ml, 2-4 ng/ml and >4 ng/ml were >3.00 ng/ml, 99% (n=115); > 3.00 ng/ml, 98% (n=64) and >3.00 ng/ml, 95% (n=114). Conclusions: The present study of AABH indicates that cancer group can be clearly distinguished from normal healthy controls. Moreover, the study indicates that AABH might be used to identify disease in individuals with questionable PSA values. These results support to the establishment of routine screening of serum AABH as a means to detect those who need referral for prostate biopsy. The use of AABH testing may enhance current prostate cancer screening practices by both identifying individuals with low but suspicious PSA values who should be recommended for biopsy and reducing the number of false positive biopsies indicated by positive PSA tests. Serum AABH levels are significantly elevated in individuals with prostate cancer. Using a cutoff value of 3ng/ml, overall sensitivity of the assay for prostate cancer is 97%. The test has a specificity of 96% in healthy men over 50 years of age. AABH is elevated in prostate cancer tissue but NOT in normal prostate or in Benign Prostatic Hyperplasia (BPH). Serum AABH levels are NOT correlate with PSA levels.