bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Gleason 9-10 prostate cancer with worse outcomes compared to Gleason 8 disease.
Authors: Tsao Che-Kai , Gray Kathryn P. , Nakabayashi Mari , Evan Caroline , Galsky Matt D. , Kantoff Philip W. , Oh William K. , Pomerantz Mark 
Published: March 2020

e16032 Background: Use of pathological Gleason score for risk stratification of localized prostate cancer is widely accepted. However, data are lacking regarding differences in presentation and outcome among those with Gleason 8-10 disease. Methods: Using the Dana-Farber Cancer Institute Prostate Clinical Research Information Systems database, we identified a cohort of patients with biopsy Gleason 8-10 disease who received definitive radical prostatectomy (RP) or radiation therapy (RT) (external beam or brachytherapy) for curative intent. The study endpoints, time to biochemical recurrence (BCR), time to metastatic disease (MD), and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to investigate the association of the study endpoints and Gleason score groups (8 vs. 9 and 10) adjusted for clinical and pathological factors including age, PSA at diagnosis, type of local therapy, and tumor stage. Results: We identified 848 patients who received either local definitive RT (n=411) or RP (n=437). Median follow-up from diagnosis was 5.3 years. Patient characteristics at diagnosis (race, age, and clinical stage) were similar between the two groups (Gleason 8 vs. Gleason 9-10). Patients with Gleason 9-10 disease were more likely to receive radiotherapy as primary local therapy (58% vs. 46%, p=0.001), and to receive hormonal therapy as a part of their definitive treatment course (64% vs. 48%, p<0.001). Patients with Gleason 9-10 disease had shorter time to BCR, time to MD, and a trend towards worse OS using multivariate analysis adjusted for significant clinical and pathological factors (detailed in the Table below). Conclusions: In our study, we found that patients with localized Gleason 9-10 disease who were treated with definitive therapy with curative intent had worse outcomes compared to patients with Gleason 8 disease. More aggressive, multimodality treatments may be indicated for men diagnosed with the highest Gleason grades. [Table: see text]
Incidence of skeletal-related events (SREs) among prostate cancer patients.
Authors: Ulcickas Yood Marianne , Zyczynski Teresa Maria , Wells Karen , Casso Deborah , Gutierrez Benjamin , Woodcroft Kimberley J. , Cheng Shinta 
Published: March 2020

e16035 Background: Skeletal related events (SREs) occur in men with prostate cancer and may result from both bone metastases and exposure to androgen deprivation therapy (ADT). The objective of this study was to quantify the incidence of SREs in patients with prostate cancer treated with ADT or orchiectomy in clinical practice. Methods: Prostate cancer patients served by Henry Ford Health System (HFHS) were identified via the HFHS tumor registry. Eligible patients were newly diagnosed with prostate cancer between 2004 and 2010 and treated with ADT or orchiectomy. Comprehensive population-based data were compiled using tumor registry with linkages to pharmacy, laboratory results, and healthcare encounter databases. SREs included spinal cord compression, surgery to bone, pathologic fracture and radiation to bone. Disease progression and metastases were identified by medical record review. Results: We identified 702 patients with prostate cancer and receipt of ADT or orchiectomy; 57.6% were >70 years of age and 43.7% were African American. 56.3% of patients were initially diagnosed at AJCC stage II, 9.8% at stage III, 22.1% at stage IV, and 11.8% had missing or unknown stage. A total of 93 patients (13.2%) had one or more SREs: radiation to bone (8.5%) and spinal cord compression (3.1%) were the most common SREs. We then limited the cohort to patients initially diagnosed with or progressing to AJCC stage IV prostate cancer (N=207). Among this group, 47.8% were >70 years of age. The mean time from stage IV diagnosis to end of follow-up was 35.6 months. In this subgroup, 16.4% of patients were initially diagnosed at AJCC stage II, 8.2% at stage III, 69.6% at stage IV, and 5.8% had missing or unknown stage. 57 patients (27.5%) had one or more SREs. Conclusions: Some clinical trials have found 36-41% of high-risk metastatic prostate cancer patients developed SREs during 3 years of follow-up. In this population-based cohort of patients with prostate cancer receiving ADT or orchiectomy and treated in real-world clinical practice, we found the incidence of SREs to be lower than what has been reported in clinical trials. Additional analyses exploring the incidence of SREs in patients diagnosed with metastatic castrate resistant prostate cancer will be presented.
Safety profile of recombinant poxviral TRICOM vaccines.
Authors: Kim Joseph W. , Marte Jennifer L. , Singh Nishith K. , Heery Christopher Ryan , Madan Ravi Amrit , Pazdur Mary , McMahon Sheri , Rauckhorst Myrna , Schlom Jeffrey , Kantoff Philip W. , Gulley James L. 
Published: March 2020

e16036 Background: Recombinant (rec) poxviruses have been developed as therapeutic cancer vaccines. A multi-institutional, randomized phase II trial of poxviral vaccine, PROSTVAC-V/F, suggested an improvement in median overall survival in men with metastatic castration resistant prostate cancer. A phase III trial in this same population is accruing. Accumulating data suggest a favorable safety profile of the poxviral vaccines (vacs). Methods: We reviewed all vaccine injections (inj) from 297 patients (pts) in 9 clinical trials involving poxviral vaccines. Vacs consisted of rec vaccinia and rec fowlpox encoded with 3 human costimulatory molecules (TRICOM), and a) prostate specific antigen, or b) carcinoembryonic antigen +/-mucin-1. Vacs were administered at doses between 1.2x108 to 2x109 pfu, subcutaneously, in all pts. 21 pts were also vaccinated intra-tumorally. 84 pts received concurrent treatments, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide in 4 of these trials. All 9 trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF), or rec fowlpox encoding GM-CSF as an immune adjuvant. We report the grade >=2 adverse events (AEs) at least possibly attributed to vaccine. Results: A total of 1,793 poxviral inj were given. 33% (593) of all inj were associated with grade >=2 vaccination emergent AEs. Of those, 25.3 % (454) were local inj site reactions; none serious. There was no contact transmission or inadvertent inoculation. One patient experienced grade 4 myocardial infarction and thrombotic thrombocytopenic purpura (TTP) reported as possibly related to vaccine. Below is the summary of AEs. Conclusions: Recombinant poxviral TRICOM vaccines appear safe and well tolerated at a broad range of doses, routes of administration and in combination with other treatments. Clinical trial information: NCT00081848, NCT00088413, NCT00060528, NCT00060528, NCT00078585, NCT00096551, NCT00113984. [Table: see text]
Determinants of the combined use of external beam radiation therapy and brachytherapy for low-risk localized prostate cancer.
Authors: Quek Ruben G. W. , Master Viraj A. , Ward Kevin C. , Lin Chun Chieh , Virgo Katherine S. , Portier Kenneth M. , Lipscomb Joseph 
Published: March 2020

e16039 Background: Prostate cancer treatment patterns have been shown to vary by physician and patient characteristics. For low-risk localized prostate cancer patients, we examined the association between their region of residence and their radiation oncologists’ practice affiliations with medical schools on the likelihood they would receive both external beam radiation therapy (EBRT) and brachytherapy (BT) – a treatment regimen that is at variance with clinical guidelines and has not been shown to improve survival or other patient centered outcomes. Methods: Using the Surveillance, Epidemiology and End Results – Medicare linked database and the American Medical Association Physician Masterfile, we conducted a retrospective cohort study of 4,479 patients aged 66 years or older who were diagnosed between 2004-2007 with low-risk localized prostate cancer, and the 401 radiation oncologists who saw them. Multilevel regression analyses were used to evaluate the influence of patients’ region of residence and radiation oncologists’ practice affiliations with medical schools on the combined use of EBRT and BT on patients within 6 months of diagnosis. Results: Overall, 231 (5.2%) patients received combined EBRT and BT. After adjusting for patient, tumor and radiation oncologist characteristics, patients who saw radiation oncologists with no practice affiliation with medical schools were significantly more likely to receive combined EBRT and BT (odds ratio [OR], 3.14; 95% confidence interval [95% CI], 1.50-6.59, p = 0.003). Regional variations were also observed; the odds of receiving combined therapy for patients residing in California (OR, 0.1; 95% CI, 0.03-0.33, p<0.0001) were significantly less than those in Georgia (OR, 1.0; referent). Conclusions: Low-risk localized prostate cancer patients residing in Georgia were significantly more likely to receive combined EBRT and BT when compared to those in other SEER Regions. Radiation oncologists without practice affiliations with medical schools were significantly more likely to treat patients with combined therapy; such treatment patterns are not consistent with clinical guidelines and unlikely to have significant survival benefit.
Impact of a genomic classifier of metastatic risk on treatment recommendations post-radical prostatectomy: Report from the DECIDE study group.
Authors: Badani Ketan K. , Thompson Darby J. S. , Buerki Christine , Davicioni Elai , Garrison Jill , Ghadessi Mercedeh , Mitra Anirban Pradip , Wood Penelope J. , Hornberger John C. 
Published: March 2020

e16044 Background: Only a minority of prostate cancer patients with adverse pathology and biochemical recurrence (BCR) post radical prostatectomy (RP) experience metastasis and die from prostate cancer. Improved risk prediction models using genomic information may enable clinicians to better weigh the risk of metastasis and the morbidity and costs of treatment in a clinically heterogeneous population. We present a clinical utility study that evaluates the influence on urologist treatment recommendations for patients at risk of metastasis using a genomic-based prediction model (Decipher). Methods: A prospective, pre-post design was used to assess urologist treatment recommendations following RP in both the adjuvant (without any evidence of PSA rise) and salvage (BCR) settings. Urologists were presented de-identified pathology reports and genomic classifier (GC) test results for 24 patients from a previously conducted GC validation study in high-risk post RP men. Participants were fellowship trained, high-volume urologic oncologists (n=21) from 18 US institutions. Treatment recommendations for secondary therapy were made based solely on clinical information (pre-GC) and then with genomic biomarker information (post-GC). This study was approved by an independent IRB. Results: Treatment recommendations changed from pre-GC to post- GC in 43% of adjuvant, and in 53% of salvage setting case evaluations. In the adjuvant setting, urologists changed their treatment recommendations from treatment (i.e. radiation and/or hormones) to close observation post-GC in 27% of cases. However, for cases with low GC risk (<3% risk of metastasis), 79% of these men were recommended for observation post-GC. Consistent trends were observed in the salvage setting including 24% patients with low GC risk recommended for observation even after BCR. Conclusions: These results indicate that urologists across a range of practice settings are likely to change many treatment decisions when presented with genomic biomarker information following RP. Implementation of the GC test into routine clinical practice may better direct treatment decision-making post-RP.
Correlation of PSMA ADC exposure with reduction in tumor growth rate determined using serial PSA measurements from a phase I clinical trial.
Authors: Rotshteyn Yakov , Mercier Francois , Bruno Rene , Stambler Nancy , Israel Robert Joseph , Wong Vivien 
Published: March 2020

e16047 Background: PSMA ADC is a fully humanized antibody to PSMA conjugated to the potent microtubule disrupting agent monomethyl auristatin E (MMAE). The safety and PK of PSMA ADC as well as changes in PSA levels were evaluated in a phase I dose escalation study in patients with taxane-refractory metastatic castration-resistant prostate cancer (mCRPC) (PSMA ADC 1301). Stein et al. (2010) has previously demonstrated correlation between growth rate derived from serial PSA measurements with survival in patients with mCRPC and suggested that growth rate could serve as a novel endpoint indicative of response to therapy and overall survival. Methods: The PK parameters for PSMA ADC, Total antibody (Ab) and free MMAE obtained from PSMA ADC Study 1301 (N=52) were calculated using non-compartmental analysis. The final data set contains 253 longitudinal PSA observations from 52 subjects dosed with 0.4-2.8 mg/kg PSMA ADC. The Stein model was re-expressed as a 7-parameter population model to describe the longitudinal PSA data which includes: Baseline PSA level (Y0), PSA decrease rate (D), PSA increase rate (G), inter-patient variability for Y0, G and D respectively, and residual variance. Model parameters were estimated using Phoenix/NLME. Exposure-efficacy relationships and correlation between G and covariates were determined. Results: PSMA ADC, Total Ab, and MMAE exposure increased linearly with increasing PSMA ADC dose. Longitudinal PSA data were correctly fitted to the re-expressed Stein model. G continuously decreased with increasing PSMA ADC exposure, suggesting an exposure dependent drug effect. There was no apparent saturation of this effect at the maximum observed exposure, and no influence of age, baseline albumin and ALT/AST levels on G was evident. Conclusions: In a phase I study where PSMA ADC (0.4-2.8 mg/kg) was administered to patients with mCRPC, we observed a correlation of PSMA ADC exposure with the reduction of G, suggesting that PSMA ADC may provide dose-dependent therapeutic benefit to subjects with mCRPC.
A new parameter of bone scintigraphy: Relation between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases.
Authors: Wakabayashi Hiroshi , Nakajima Kenichi , Mizokami Atsushi , Namiki Mikio , Inaki Anri , Taki Junichi , Kinuya Seigo 
Published: March 2020

e16072 Background: A computer-aided diagnosis system for bone scan with semiquantitative index of Bone Scan Index (BSI) may be used to quantify the spread of bone metastases. This retrospective study aimed to examine associations between BSI, bone metabolic markers, and prostate specific antigen (PSA) in prostate cancer patients with bone metastases. Methods: A total of 158 scintigraphy of 52 patients (mean examinations/person 3, range 1-8; mean age 71 years, range 46 to 86) were studied. The intervals between bone scan and blood examinations were 0 to 16 days (median 0 day). Subjects were divided into 4 groups according to BSI; Group A: 0 - <2, Group B: 2 - <4, Group C: 4 - <8, and Group D: 8<. The markers of PSA, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1-CTP), bone alkaline phosphatase (BAP), and tartate resistant acid phosphatase-5b (TRAP-5b) were examined. As the values of PSA, BAP, and TRAP-5b covered a large range of scales, we also used the logarithms of the variables. BSI, which corresponded amount of metastatic lesions, was automatically calculated by BONENAVI software (FUJIFILM RIPharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden). Results: All scans showed increased uptake at bone metastases. BSI correlated significantly with 1-CTP, BAP, logBAP, TRAP-5b, logTRAP-5b, and logPSA (r=0.39, 0.66, 0.71, 0.69, 0.61 and 0.41, respectively). Statistical F value was 11 in 1-CTP, 31 in BAP, 29 in logBAP, 19 in TRAP-5b, 14 in logTRAP-5b, 3 in PSA, and 9 in logPSA by ANOVA, respectively. Comparison by Dunnett’s test showed significantly higher values in Group D for all bone metabolic markers and logPSA, Group C for BAP, logBAP, TRAP-5b, and logTRAP-5b, and Group B for logTRAP-5b compared with Group A, respectively. However, PSA did not correlate significantly with extent of bone metastases as assessed by BSI. Conclusions: The changes in BSI showed close relationship with all bone metabolic markers but not with PSA. The BSI reflected the activity and extent of bone metastases, and might be used as an imaging biomarker.
Treatment timing of life-extending therapies and adherence of corticosteroids among metastatic castration-resistant prostate cancer patients with conditions sensitive to corticosteroid use.
Authors: Bui Cat N , Spalding James , Wang Li , Baser Onur 
Published: March 2020

e16080 Background: Corticosteroids (CS) have been integral in metastatic castration-resistant prostate cancer (mCRPC) treatment and can be used alongside life-extending therapies (LETs), despite potential toxicity effects. LET and CS timing and adherence were examined in CRPC patients in the Veterans Health Administration (VHA) dataset with conditions sensitive to CS use. Methods: Diagnosed prostate cancer patients with evidence of medical/surgical castration, at least two following prostate-specific antigen (PSA) increases (third PSA value date was the index), and ≥1 claim for cabazitaxel, docetaxel, or abiraterone acetate 06/2007-05/2012 were examined. Adherence was the total overlapping days of CS and LET prescriptions divided by total LET prescription days (≥0.8). Comorbid conditions were measured for 6 months pre-index date. Descriptive analysis, Cox proportional hazards, and logistic regression models summarized therapeutic/clinical features of CRPC or the CS-adherent patient subset. Results: Common CS-sensitive conditions among 15,585 mCRPC patients included hypertension (58.94%) and hyperlipidemia (42.56%). Fewer glaucoma (hazard ratio [HR]: 0.67), ischemic heart disease (HR: 0.78), and peripheral vascular disease (HR: 0.78) patients were prescribed LETs (all p<0.01). mCRPC treated patients with comorbidities (N=858) were significantly older (71.27 vs. 68.94 years, p<0.01) and more often exhibited bone metastases than those without (42.42% vs. 29.73%, p<0.01). After treatment initiation, mCRPC patients with comorbidities had a shorter LET duration (125.02 vs. 133.08 days, p=0.04) within the 6-month follow-up period. Factors associated with reduced CS adherence (≥0.8) included cerebrovascular disease (odds ratio=0.0107, 95% CI: 0.012-0.966) and peripheral vascular disease (odds ratio=0.523, 95% CI: 0.276-0.991). Conclusions: Conditions sensitive to CS influence the LET receipt and duration and are associated with lower adherence when compared to non-CS-sensitive conditions. Attention should be focused on treatments using alternatives to CS for sensitive mCRPC patients.
Japanese nationwide multi-institutional cohort study of prostate cancer brachytherapy with permanent seed implantation.
Authors: Saito Shiro , Ito Kazuto , Yorozu Atsunori , Aoki Manabu , Koga Hirofumi , Satoh Takefumi , Ohashi Toshio , Shigematsu Naoyuki , Daimon Takashi , Kojima Shinsuke , Dokiya Takushi , Fukushima Masanori , Yamanaka Hidetoshi 
Published: March 2020

e16090 Background: Brachytherapy with permanent iodine-125 seed implantation (PI) has been approved in 2003 in Japan. Multi-institutional cohort study (Japanese Prostate Cancer Outcome Study of Permanent Seed Implantation; J-POPS, NCT00534196) assessing the treatment feature, efficacy, safety and health-related quality of life (QOL) has started in July 2005. Six thousand nine hundred and twenty-seven cases were enrolled to this study until December 2010 from 68 institutes around the country, which is approximately 40% of all the cases treated in Japan at that time. Methods: Patient’s background, cancer character, treatment feature such as combined therapy of external beam or hormone, post PI dosimetric information, treatment efficacy with PSA level, voiding symptoms with IPSS and treatment related adverse events according to NCI-CTCAE are investigated. PSA was measured every 3 months and symptoms accompanied to the treatment were assessed 3 to 6 months after the treatment. Backgrounds and treatment assessments of 2,341 patients enrolled in J-POPS during the initial 2 years are evaluated. Results: Patients’ age ranged from 45 to 89 (median 69) year-old and 99.0% of the cases were performance status 0 (ECOG criteria). Family history of prostate cancer was seen in 6.2%. PSA levels on cancer diagnosis were 1.60 to 42.0 (mean 6.80) ng/ml, clinical stage T2a or less was 89.9%, T2b was 5.2%, T2c was 2.9% and T3a-T3b was 0.8%. Gleason score (GS) less than 7 was 56.6%, GS 7 was 39.7%, and GS above 7 was 3.6%. According to NCCN risk classification, 44.2% was classified as low risk, 48.3% as intermediate risk and 5.7% as high risk. Androgen deprivation therapy (ADT) was performed in 48.5% of the patients and 23.4% was combined with external beam radiation therapy (EBRT). CT scan based first post therapeutic month dosimetry revealed that prostatic mean V100 and D90 for the cases treated with seed alone were 94.8% and 160.7 Gy, respectively. As for adequate control of radiation dose at rectum (mean R100 = 0.3 cc) and urethra (mean D5 = 223.4 Gy), high grade toxicities appeared very seldom. Conclusions: Outcomes of J-POPS will produce clinical evidence of PI that can be internationally accepted.
Efficacy and safety of docetaxel-based chemotherapy in Japanese men over 80 years old with castration-resistant prostate cancer.
Authors: Kosaka Takeo , Yasumizu Yota , Mizuno Ryuichi , Miyajima Akira , Kikuchi Eiji , Shinya Morita , Kono Hidaka , Nakagawa Ken , Oya Mototsugu 
Published: March 2020

e16094 Background: Docetaxel-based chemotherapy is widely used to treat castration-resistant prostate cancer (CRPC). However, its efficacy in elderly males has not yet been fully elucidated. In Japan, the number of elderly CRPC patients continues to increase. Therefore, it is urgently necessary to evaluate the effect of docetaxel-based chemotherapy in elderly Japanese men with CRPC. Methods: Sixty-eight male patients with CRPC who were treated with first-line docetaxel-based chemotherapy in a single institution from 2006 to 2011 were evaluated retrospectively. Results: The median age was 72.4 ± 6.5 years. Ten patients (14.7 %) were ≥ 80 years old (older group), and 58 (85.3 %) were < 80 years old (younger group). All patients received docetaxel at a dose of 75 mg/m2 once every 3 weeks, and prednisolone 10 mg was given every day orally. The prostate-specific antigen (PSA) levels of the older and younger groups before docetaxel-based chemotherapy were 41.2 ± 37.4 ng/ml and 106.5 ± 184.7 ng/ml, respectively (P = 0.273). The PSA doubling times before docetaxel-based chemotherapy were 91.6 ± 92.6 days and 92.5 ± 91.9 days, respectively (P = 0.977). The performance status of the older group was 0 or 1. In the same group, 7 patients (70.0%) achieved a PSA decline of ≥ 30% and 4 patients (40.0%) achieved a PSA decline of ≥ 50%. In the younger group, the PSA decline was ≥ 30% in 37 patients (63.8%) and ≥ 50% in 26 patients (44.8%). The PSA decline rates of ≥ 30% and ≥ 50% were not significantly different between the two groups (p = 0.68 and p = 0.75, respectively). Progression-free survival (PFS) was also not significantly different between the two groups (PFS 5.3 vs. 7.3 months, p = 0.39). The major grade 3–4 toxicities were myelosuppression. Grade 3/4 neutropenia occurred in 80.0% of the older group and 78.0% of the younger group, and Grade 4 neutropenia occurred in 20.0% of the older group and 24.2% of the younger group. There were no significant differences between the two groups (Grade 3/4; p = 0.89, Grade 4; p = 0.79). Conclusions: Docetaxel-based chemotherapy showed a significant effect with a tolerable adverse event rate in elderly Japanese males over 80 years old with castration-resistant prostate cancer.