bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and distribution of HER2-positive gastric and gastroesophageal junction (GEJ) adenocarinomas in British Columbia (BC).
Authors: Lim H. J. , Aubin F. , Kollmannsberger C. K. , Huntsman D. , Carter B. , Zhou C. , Woods R. , Gill S. 
Published: February 2017

91 Background: HER2-positive rates have been reported as 20% of GC and 34% in GEJ adenocarcinoma in a recent global phase III trial with trastuzumab and chemotherapy. This study examines the incidence and distribution HER2-positive GC and GEJ adenocarcinomas in the province of BC. Methods: Formalin fixed embedded tissue from patients (pts) with resected gastric or GEJ adenocarcinoma from 2004-2007 were identified retrospectively through the BC Cancer Agency registry and prospectively for pts with a new diagnosis of advanced disease. Biopsies and resection samples were analyzed via previously validated methods IHC (Ventana 4B5 antibody), FISH (Eurovision probes) and SISH (Ventana probes). IHC scores of 3 were considered positive, 2 were cequivocal and 0 or 1 were negative. A 10% cut-off was used to determine positive samples. Equivocal staining was considered positive via FISH or SISH. A ratio of > 2.0 was considered amplified for FISH and SISH. P values were calculated using a logistic regression model with HER2 positive as the endpoint. Results: Of the 87 samples, 64 (74%) were gastric and 23 (26%) GEJ. Overall, HER2 was positive 20% (IHC), 18% (FISH) and 18% (SISH). 13% of cases tested IHC 3+ while 24% tested IHC 2+. In equivocal IHC 2+ cases, 7% were considered positive by FISH. Positivity rates were higher for GEJ (26%, 22% and 17%) vs. gastric (8%, 11% and 9%) via IHC (p = 0.02), but did not significantly differ by FISH (p = 0.19), or SISH (p = 0.30) respectively. The majority of positive cases were intestinal type vs. other (diffuse type or mixed) 25% vs. 0% IHC p = 0.0002, 25% vs. 3% FISH p = 0.001, 20% vs. 3% SISH p = 0.006. The positivity rates were similar with biopsy vs resection specimens (12% vs. 16% IHC p = 0.64, 12% vs. 21% FISH p = 0.30, 12% vs. 10%, SISH p = 0.88). Conclusions: The rates of HER2-positive disease in a Western population based study were similar to the ToGA study. HER 2 positivity was associated with cancers arising in the GEJ and of intestinal type. The frequency of positivity was similar for testing by biopsy versus resection specimens. This study is ongoing and updated results will be reported. No significant financial relationships to disclose.
Under- and upgrading of prostate cancer after radical prostatectomy in a screening setting.
Authors: Zhu X. , Bul M. , van Leeuwen P. J. , Roobol M. J. , Schröder F. H. 
Published: February 2017

105 Background: It has been well established that there is an upward drift in assigned Gleason score (GS) to prostate cancer (PC) biopsies. However, few studies have examined the concordance between biopsy GS and pathological GS after radical prostatectomy (RP) in a screening setting over time. We assessed the proportion of under and upgrading of PC after RP by comparing the prevalence screen with the incidence screens from the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. Methods: From 1993 to 1999, a total of 42.376 men identified from population registries in the Rotterdam region (55-74 yrs) were randomized into a screening or control arm. Men with PSA ≥3.0 ng/ml were recommended for sextant prostate biopsy, which were lateralized since 1996. The screening interval was 4 yrs. Men with screen-detected PC, who underwent RP within 1 yr, were eligible for this study. Results: In all, biopsy and pathological GS were known for 639 men who underwent RP. Of these RPs, 405 were performed between 1994 and 2000 (prevalence screen) whereas 235 cases were performed between 1998 and 2008 (incidence screens). In the prevalence screen, 49.8% of the biopsy GS matched the pathological GS ( Table ). This percentage improved to 58.3% in the incidence screens (p=0.045). The proportion of undergrading after RP was 23.0% in the prevalence screen, which declined to 16.2% in the incidence screens (p=0.049). Upgrading occurred in 27.2% of the cases in the prevalence and 25.5% in the incidence screens (p=0.71). Conclusions: We have demonstrated an improved concordance between biopsy and pathological GS over time by comparing cancers detected in the prevalence screen with those detected in the incidence screens, which is in line with the upward shift of GS classification over time. In addition, significant less undergrading occurred in the incidence screens. However, one should keep in mind that within this screening program still a quarter of the biopsy GS were upgraded after RP in the incidence screens. [Table: see text] [Table: see text]
Use of a surgically derived nomogram to predict high likelihood of Gleason score upgrading for favorable-risk prostate cancer treated with permanent seed brachytherapy.
Authors: Bowes D. , Crook J. M. , Wallace K. , Evans A. , Toi A. , Finelli A. , Jewett M. A. 
Published: February 2017

114 Background: Crook et al have reported a 7-year disease-free survival (DFS) of 95.2% in 1,111 men with prostate cancer treated with Iodine-125 permanent seed brachytherapy (BT) at Princess Margaret Hospital. Two nomograms have been developed that estimate the likelihood of Gleason score (GS) upgrading for patients with favorable risk prostate cancer undergoing radical prostatectomy (RP). The purpose of this project was to apply these nomograms to a cohort treated with BT. Methods: Records were examined for all men receiving prostate BT in 2006-7. 217 had favorable risk disease. The likelihood of GS upgrading was predicted using RP-derived nomograms created by Kulkarni et al (PMH, 2007) and Budaus et al (2010). Clinical and pathologic information were available on 208 patients to allow completion of the Kulkarni nomogram, and on 193 patients for the Budaus nomogram. Results: The median age of the BT cohort was 62 years (range 44–77), and the median PSA level 4.68 ng/ml. Clinical stage was T1 in 65%, and 47.6% had positive findings on transrectal ultrasound. Median prostate volume was 33.3 cc (15.0–72.3). Uro-pathology review was available for 93%. 84.1% had extended biopsies, with 40.9% showing prostatic intraepithelial neoplasia and 10.1% inflammation. The median % of positive cores was 25%, with a median maximum % involvement per core of 20%. Two men received androgen deprivation therapy for prostate downsizing. The median predicted likelihood of GS upgrading was 51.6% using the Kulkarni nomogram, and 43.6% using the Budaus nomogram. The median PSA after 3.2 years median follow-up is 0.18 ng/mL. Conclusions: In a population of men with favorable risk prostate cancer treated with BT, the estimated likelihood of GS upgrading using two surgical nomograms was substantial. The study cohort was taken from a larger population of patients treated over 10 years for whom 7-year DFS is 95.2%. This suggests that permanent seed brachytherapy is a highly effective treatment option for patients with favorable risk disease despite unfavorable clinical and pathologic factors. Patients should not be discouraged from brachytherapy on the basis of a high likelihood of GS upgrading. No significant financial relationships to disclose.
11c-choline-PET/CT versus transrectal ultrasound-guided prostate biopsy to diagnose locally recurrent prostate cancer following radiation therapy.
Authors: Heidenreich A. , Pfister D. A. , Epplen R. , Brehmer B. 
Published: February 2017

119 Background: Radical salvage prostatectomy (SRP) represents one local secondary treatment option with curative intent in patients failing radiation therapy (RT) for localized prostate cancer (PCA). 11C-PET/CT represents an innovative imaging study to detect systemic spread of prostate cancer. However, there is only limited experience with regard to the sensitivity of C-PET/CT to detect locally recurrent PCA following radiation therapy. The purpose of our study was to analyse the sensitivity of C-PET/CT to diagnose PCA and extra- and intraprostatic extension. Methods: 45 patients with the suspicion of locally recurrent PCA underwent 12-core transrectal ultrasound- guided biopsy of the prostate, C-PET/CT, bonne scan and radical salvage prostatectomy. Findings of the imaging studies were correlated with the pathohistological findings of the prostate biopsy and the radical prostatectomy specimen. All prostatectomy specimens were proceeded according to the Stanford protocol and the number and location of intraprostatic cancer foci > 5mm were correlated with the PE/CT findings. Results: The mean preoperative serum PSA was 7.8 (2–24) ng/ml; the mean biopsy Gleason Score was 5.6 (4–9). Prostate biopsy was positive in 37/45 (82.2%) patients whereas 8/45 (17.8%) had a negative biopsy despite positive PET/CT findings. PET/CT was positive in 45/45 patients. Radical prostatectomy specimens identified locally recurrent PCA in 44/45 (97.8%). One patient turned out to have pT0pN0 disease despite increasing PSA. PET/CT identified 1, 2, and > 2 intraprostatic cancer foci of significant volume in 23 (51.1%), 13 (28.9%) and 9 (20%) patients, respectively. Sensitivity to detect intraprostatic, histologically proven PCA foci is 95.6% which is significantly superior to the biopsy results. There was a high correlation between the PET/CT results and the final histology of the radical prostatectomy specimens. Conclusions: Choline PET/CT is an innovative imaging to identify patients with locally recurrent PCA following radiation therapy. PET/CT is superior to prostate biopsy and we recommend a PET/CT in patients who are candidates for radical salvage prostatectomy. No significant financial relationships to disclose.
Inappropriate utilization of radiographic imaging in men with newly diagnosed prostate cancer.
Authors: Prasad S. M. , Gu X. , Lipsitz S. R. , Nguyen P. L. , Hu J. C. 
Published: February 2017

120 Background: The use of radiographic imaging (bone scan, computerized tomography and magnetic resonance imaging) following diagnosis of prostate cancer is recommended only in the setting of high-risk pathologic features. This study sought to characterize utilization patterns of imaging in men with newly diagnosed prostate cancer. Methods: We identified 30,183 men diagnosed with prostate cancer from 2004-2005 using Surveillance, Epidemiology and End Results-Medicare linked data to characterize the determinants of radiographic staging following prostate cancer diagnosis. Results: 36% of men with low risk and 49% of those with intermediate risk prostate cancer underwent unnecessary imaging for staging, while only 61% of men at high risk received any imaging test prior to treatment. Use of imaging was more common in men who were older than 75 (OR 1.25, CI 1.17–1.33) black (OR 1.11, CI 1.01–1.21), wealthier (OR 1.19, CI 1.08–1.32 for median income >$60,000 vs <$35,000), living in rural regions (OR 1.22, CI 1.11–1.34) and who underwent radiation therapies ( Table ). It was less common in men who were educated (OR 0.84, CI 0.76–0.92 between highest and lowest education levels) and chose active surveillance. There was no association between use of imaging and either marital status or Charlson score. Conclusions: There is widespread overutilization of staging in low and intermediate risk patients, while a worrisome number of men at high risk undergo treatment without appropriate diagnostic imaging. Physicians may be prescribing costly and unnecessary tests with associated harmful radiation in over a third of patients while forgoing the recommended metastatic workup in almost 40% of high-risk patients prior to treatment. [Table: see text] No significant financial relationships to disclose.
Preclinical evaluation of 99mtechnetium-HYNIC(tricine/TPPTS)-aca-bombesin(7–14) as a targeted imaging agent in prostate cancer.
Authors: Ananias H. J. , Yu Z. , Elsinga P. H. , de Jong I. J. 
Published: February 2017

122 Background: The peptide bombesin (BN) and derivates thereof show high binding affinity for the gastrin-releasing peptide receptor (GRPR), which is highly expressed in primary and metastasized prostate cancer. We have synthesized a new BN-based radiopharmaceutical 99mTechnetium-HYNIC(tricine/TPPTS)-Aca-BN(7–14) (99mTc-HABN) and evaluated its GRPR targeting properties in vitro and in a xenograft tumor model for human prostate cancer in athymic mice. Methods: 99mTc- HABN was synthesized and its lipophilicity and stability were investigated. The IC50, internalization and efflux properties were determined in vitro using the GRPR expressing human prostate cancer cell line PC-3. 99mTc-HABN biodistribution and microSPECT imaging were performed in PC-3 tumor-bearing athymic mice. Results: 99mTc-HABN was prepared with high labeling yield (>90%), high radiochemical purity (>95%) and a specific activity of ∼19.8 MBq/nmol. The partition coefficient log P value was −1.60±0.06. 99mTc-HABN proved to be stable in human serum for 6 hours. The IC50 of HABN was 12.81±0.14 nM. Incubation of PC-3 cells with 99mTc-HABN demonstrated rapid cellular internalization and a long intracellular retention time. When mice were injected with 99mTc-HABN the activity was predominantly cleared via the kidneys. Uptake in the tumor was 2.24±0.64 %ID/g after 30 minutes, with a steady decrease during the 4 hours study period. In vivo experiments with a blocking agent showed GRPR mediated uptake. 99mTc-HABN microSPECT imaging resulted in clear delineation of the tumor. Conclusions: 99mTc-HABN is a novel BN-based radiopharmaceutical that appears to be suitable for targeted imaging of prostate cancer. No significant financial relationships to disclose.
A randomized, double-blind phase II trial of docetaxel plus prednisone (DP) combined with either AT101 or placebo for the first-line therapy of metastatic castration-resistant prostate cancer (CRPC).
Authors: Sonpavde G. , Matveev V. B. , Burke J. M. , Caton J. R. , Fleming M. T. , Karlov P. A. , Holmlund J. , Wood B. A. , Brookes M. , Leopold L. H. 
Published: February 2017

125 Background: AT-101 (A), a small molecule oral inhibitor of the Bcl-2 protein family has broad preclinical activity including synergy with docetaxel (D). AT-101 has demonstrated activity alone and in combination with D in D-refractory patients with metastatic CRPC. Methods: A randomized, double-blind, placebo-controlled phase II trial was conducted to compare the combination of DP with either A or placebo in chemo-naive men with progressive metastatic CRPC. A key requirement was progression (bone scan, RECIST or rising PSA ≥ 2 ng/mL) despite androgen deprivation. Stratification factors were pain and performance status. Patients received DP (75mg/m2 day 1; 5mg PO b.i.d.) Q 21 days (1 cycle) with either A (40 mg b.i.d.) or placebo PO on days 1–3. Radiological assessments were performed every 3 cycles. Primary endpoint was overall survival (OS) and 221 patients were planned for 110 events (80% power, HR 0.67, 1-sided alpha 0.1). Results: 221 patients were randomized to ADP or placebo-DP and baseline factors were balanced. Efficacy outcomes (OS, PFS, PSA declines, disease control) were not significantly different ( Table ). In a subgroup of patients with poor-risk CRPC (n=34), efficacy endpoints appeared to favor ADP with a median OS of 19 months vs.14 months for placebo-DP. Grade 3/4 AEs that occurred with higher incidence in the ADP arm compared to placebo-DP included cardiac AEs (5% vs. 2%), lymphopenia (23% vs. 16%), neutropenia (47% vs. 40%), ileus (2% vs. 0%) and pulmonary embolism (6% vs. 2%). Conclusions: The combination of AT-101 with DP in men with chemonaive metastatic CRPC was well tolerated but did not extend OS compared to placebo-DP. There was a potential benefit in a subset of high-risk patients. [Table: see text] [Table: see text]
Intermittent androgen-deprivation therapy in the management of castrate-resistant prostate cancer (CRPCa): Results of a multi-institutional randomized prospective clinical trial.
Authors: Organ M. , Wood L. , Wilke D. , Skedgel C. , Thompson K. , North S. , Cheng T. , Winch S. , Rendon R. 
Published: February 2017

131 Background: Patients who develop CRPCa typically continue on androgen deprivation therapy (ADT). Whether these patients need to remain on ADT has not been well studied. We conducted a multicenter randomized trial to compare intermittent versus continuous approach to ADT in CRPCa patients. Overall survival, health related quality of life (QOL) and cost were the main endpoints. We hypothesized that the intermittent approach would be cost-saving while maintaining similar oncologic and QOL outcomes. Methods: CRPCa patients were randomized 1:2 to continuous or intermittent luteinizing hormone releasing hormone agonists (LHRHa). Patients were followed with clinical assessments, laboratory investigations, and QOL questionnaires (EORTC QLQ-C30 or PROSQOLI) every 2 months. If the serum testosterone rose above castrate levels (1.75nmol/L), LHRHa were re-initiated. The study was designed to close if >50% of patients needed to restart ADT in the intermittent arm. Results: 31 patients were followed with a median follow-up of 26.8 months; 18 in the intermittent arm and 13 in the continuous. 12/18 patients on the intermittent arm were re-initiated on LHRHa at a median time of 17.9 months. There was no difference in overall or cancer-specific survival between the two arms. There was no statistically significant difference in QOL between the two arms at 0 and 12 months. The total mean costs at 24 months were significantly lower in the intermittent arm (3135 $CAD vs 8253 $CAD, p=0.0167) compared to the continuous arm largely due to the reduced costs of the LHRHa. Conclusions: We have observed that intermittent ADT in patients with CRPCa, using a testosterone of >1.75 ngmol/L as a trigger to re-initiate LHRHa, results in a substantial cost savings with no negative impact on oncologic and QOL outcomes. These findings need to be corroborated in a study with a larger sample size. [Table: see text]
A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in patients (pts) with castration-resistant prostate cancer (CRPC): Preliminary results.
Authors: Slovin S. F. , Kargman M. , Durso R. , Curley T. , Israel R. J. , Olson W. C. , Morris S. , Murphy D. , Scher H. I. 
Published: February 2017

140 Background: Prostate-specific membrane antigen (PSMA), a type II transmembrane protein overexpressed in prostate cells as they emerge into the androgen-independent state, remains a target to which vaccines with novel adjuvants or naked DNA has been directed. The PSMA-Viral Replicon Package (VRP) is a propagation-defective vector system from an attentuated strain of an alpha virus (VEE) encoding PSMA for use as a vaccine in prostate cancer. The PSMA gene is encoded by a subgenomic messenger RNA (mRNA), leading to high level expression of PSMA protein and presentation to the immune system.. We report preliminary results of a first in human trial using PSMA VRP to elicit immune responses targeting PSMA. Methods: Up to 18 pts with chemotherapy naïve CRPC metastatic to bone or soft tissue were permitted with 12 pts enrolled with ECOG status of 0 or 1. PSMA VRP was administered SC doses of either 0.9×107 IU or 0.36×108 IU for a total of 5 doses given on weeks 1, 4, 7, 10 and 18. Adverse events, PSA, circulating tumor cells, and clinical disease progression were assessed. Immune assessment was performed on patients' sera by ELISA and flow cytometry of serum binding to PSMA expressing tumor cells (3T3) and cellular (IFN-g EliSpot) components. Patients underwent imaging with bone and CAT scans every 3 months. Results: Three pts received 0.9×107 IU and 9 received 0.36×108 IU. Of these, 8 pts received all 5 vaccines. Four pts were taken off study for disease progression. One pt at the 0.36×108 continues on study and will be receiving his seventh vaccine. The demographic featuresof the 12 subjects enrolled were similar (mean age 69±11 yrs). No significant adverse events were noted; no aberrant laboratory abnormalities were associated with treatment. Weak humoral responses were observed in 1 patient in the 0.9×107 IU group and in 3 treated at 0.36×108. Conclusions: In this first-in-man evaluation, vaccination with PSMA VRP appeared to be well-tolerated but does not appear to show impact on disease progression. Further studies are ongoing to assess immune responses and identify potential pathways for enhancement of the PSMA VRP approach. [Table: see text]
The efficacy and safety of degarelix, a GnRH receptor antagonist: A multicenter, randomized, maintenance dose-finding phase II study with Japanese prostate cancer patients.
Authors: Ozono S. , Ueda T. , Hoshi S. , Yamaguchi A. , Maeda H. , Fukuyama Y. , Ohashi Y. , Tsukamoto T. , Naito S. , Akaza H. ,   Degarelix Japan Study Group
Published: February 2017

154 Background: Degarelix, a GnRH receptor antagonist inducing rapid, profound and sustained suppression of serum testosterone levels, without testosterone surge, was evaluated in a phase II dose finding study in Japan. Methods: A total of 278 patients with adenocarcinoma of the prostate were randomized and 273 patients (any stage; median age, approx. 76 years; median testosterone, 4.46 ng/mL; median prostate-specific antigen (PSA) level, 22.8 ng/mL) received study treatment. Degarelix was administered subcutaneously at an initial dose of 240 mg followed by monthly maintenance doses of either 80 mg or 160 mg. The treatment continued for 12 months in the study. Results: The primary endpoint was the proportion of patients with testosterone suppression to castrate level of ≤0.5 ng/mL during 12 months treatment. Both dose regimens of 80 mg and 160 mg kept 94.5% and 95.2% of patients on castrate level respectively throughout the treatment period. At 3 days of treatment, approximately 99% of the patients reached the castrate level without testosterone surge. The percentage change in serum PSA reduction exceeded 76% at 4 weeks. The overall tumor response rates (proportion of patients with complete and partial responses) were from 77.4% to 90.8% across the groups. Eighteen patients (6.6%) withdrew from the study due to adverse events. The most common adverse events were injection site reactions; other adverse events included pyrexia, weight increased, hypertension and hot flush. Degarelix appeared well tolerated. Conclusions: With an initial dose of 240 mg followed by monthly maintenance doses of 80 mg or 160 mg, Degarelix resulted in a rapid profound and sustained testosterone suppression to castrate level and PSA reduction without testosterone surge for 12 months. Degarelix was well tolerated. The maintenance doses of 80 mg and 160 mg had similar efficacy and safety profiles. The study shows results similar to those from the degarelix pivotal phase III study (CS21). Assessment of risk-benefit would support the recommendation of the maintenance dose of 80 mg as a safe and effective monthly dose for the treatment of prostate cancer. [Table: see text]