bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormonal therapy for localized prostate cancer in Japan: The outcome of J-CaP database.
Authors: Hinotsu Shiro , Akaza Hideyuki , Ogawa Osamu , Oya Mototsugu , Kitamura Tadaichi , Suzuki Kazuhiro , Tsukamoto Taiji , Naito Seiji , Namiki Mikio , Nishimura Kazuo , Hirao Yoshihiko ,   J-CaP Study Group
Published: February 2017

54 Background: In Japan, the J-CaP database was established in 2001 when the Japan Study Group of Prostate Cancer (J-CaP Study Group), commenced a study to gather information about hormone therapy administered to Japanese patients and to analyze the outcomes of treatment. From the results of prostate cancer registry conducted by Japanese Urological Association revealed that 45% of localized prostate cancer patients diagnosed in the year of 2000 treated by hormonal therapy in Japan. The J-CaP database is the largest cohort of over 20,000 prostate cancer patients treated by hormonal therapy. Therefore, the objective of the current study was to estimate the outcome of hormonal therapy for the localized prostate cancer patients in the J-CaP database. Methods: The study cohort included 9,127 men with localized prostate cancer who treated by hormonal therapy. All patients were diagnosed by biopsy as having prostate cancer and began to receive hormonal therapy between January 2001 and December 2003. In this study, initial hormonal treatment contained anti-androgen monotherapy, surgical castration only, LHRH agonist monothrerapy, LHRH agonist plus short-term anti-androgen, surgical castration plus anti-androgen, and LHRH agonist plus anti-androgen. All patients evaluated risk category of D’Amico classification. The percentage of Low-risk, intermediate-risk, and high-risk was 19%, 22%, and 59% of men, respectively. Prognosis analyses were performed using Kaplan–Meier methods. Progression-free survival and overall survival were estimated for each risk classification. Results: After a median follow-up of 2.9 years (interquartile range, 1.5-5.3 years) and five year progression-free survival of low-risk, intermediate-risk and high risk were 74.5%, 68.1%, and 57.1%, respectively. The five-year overall survival of low-risk, intermediate-risk, and high risk were 90.0%, 87.2%, and 81.8%, respectively. Conclusions: Comparing the results of radical prostatectomy in US, the five-year progression free survival was 54.6% in high-risk patients. Japanese patients with localized prostate cancer who treated hormonal therapy were comparable outcome of radical treatment in US considering the patients’ risk classification.
Is histoscanning a valid tool to detect prostate cancer in repeat biopsy?
Authors: Epplen Robin , van Essen Julius , Pfister David J. K. P. , Porres Daniel , Heidenreich Axel 
Published: February 2017

57 Background: Histoscanning is a novel ultrasound-based software programme, which uses back-scattered ultrasound, to detect and visualize prostate carcinoma. It is not clear to date which additive information histoscanning will deliver terms of additive information to ultrasound guided transrectal biopsy as research is scarce.Therefore we aimed to analyze our data on repeat biopsy with histoscanning prior to intervention. Methods: From Sept. 2009 till present, 61 patients, mean age 62 yrs, that were scheduled for repeat biopsy received Histoscanning prior to intervention. Acquired data were retrospectively processed with Histoscanning software version 2.2 and prostate was divided into a 6 grid pattern. Lesions ≥0,5ml were considered positive. Biopsies were taken according to Vienna normogram and processed by an experienced uropathologist. Results: Mean number of biopsies prior to repeat was 2. Mean PSA at repeat biopsy was 7,135 ng/ml, mean prostate volume accounted for 45.5 ml. A total of 15/61 men were diagnosed with cancer (24,59%), Gleason Score (Gl.) of 6 n=10, n=2 Gl. 3+4=7, n=2 Gl. 4+4; n=2 Gl. 4+5=9 respectively. A total of 43/834=5.15% positive cores were obtained, averaging 0.7 per person. Mean Volume of Histoscanning lesions per scan: 1,48 ml; no statistical significance can be detected regarding the volume per sextant and a positive core. False positive rate was 90/366=24,6%; false negative rate was 19/366=5,2%. Overall sensitivity was 29,69%, specifity accounted for 73.3%. PPV was calculated at 8.16% and NPV at 92,88%. PSA had no influence on detection rate. Conclusions: In this highly seleted patient cohort Histoscanning had no beneficial nor additive information on detecting prostate cancer. Further research should has to be done regarding Histoscanning lesions with different histopathological features such as prostatitis and fibrosis.
Cost-effectiveness of denosumab (Dmab) versus zoledronic acid (ZA) for prevention of skeletal-related events (SREs) in patients (pts) with castrate-resistant prostate cancer (CRPC) and bone metastases (BM).
Authors: Rader Michael E. , Danese Mark , Cong Ze , Halperin Marc , Qian Yi , Goessl Carsten Dietrich , Chung Karen 
Published: February 2017

59 Background: It has become more important to understand the incremental cost/benefit of new medicines as healthcare costs rise. Subcutaneous Dmab is superior to intravenous ZA for prevention of SREs in pts with CRPC and BM (Fizazi, 2011). In addition, a lower proportion of pts receiving Dmab progressed to moderate/severe pain than those receiving ZA (Brown, 2011). Dmab can be used in pts regardless of renal status or concomitant use of nephrotoxic drugs. These analyses assess the lifetime, real world cost-effectiveness of Dmab vs ZA in pts with CRPC and BM from a US managed care perspective. Methods: A lifetime Markov model was developed to estimate SREs, quality adjusted life-years (QALYs), and costs. The relative rate reduction in SREs for Dmab vs ZA was based on a large head-to-head phase 3 trial (N=1,901). The real world SRE rate in ZA pts was derived from a large commercial claims database analysis (Hatoum, 2008). SRE QALY decrements were estimated using the time trade-off method (Matza, 2011). SRE costs were estimated from a nationally representative commercial claims database (Barlev, 2010). Wholesale acquisition drug cost (Analysource, 2011), drug administration, and renal monitoring costs (National Fee Analyzer, 2011) were included. Compliance and mortality were assumed to be the same in both groups. Costs and QALYs were discounted at 3% annually. Results: With a median pt survival of 1.7 years, Dmab reduced the number of SREs and increased pts’ QALY vs ZA. The lifetime cost/pt on Dmab was $7,430 higher than ZA. Cost/QALY gained was $65,134, commonly considered good value based on oncologists’ implied threshold in the US (Nadler, 2006). Cost/SRE avoided was $9,212. Conclusions: Dmab is cost-effective in preventing SREs in pts with CRPC and BM compared with ZA in the US. The overall value of Dmab is based on superior efficacy and more efficient administration. [Table: see text]
Comparison of acute toxicity in patients treated with a 4-field box or IMRT to deliver elective pelvic nodal irradiation for localized high-risk prostate cancer.
Authors: Jain Suneil , Cheung Patrick , Loblaw D. Andrew , Morton Gerard , Danjoux Cyril , Szumacher Ewa , Chu William , Chung Hans T. , Vesprini Danny , Sahgal Arjun , Zhang Liying , Deabreu Andrea 
Published: February 2017

69 Background: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. Even though studies show a clear dosimetric benefit to bowel and bladder, there is a lack of good data demonstrating decreased toxicity with the use of IMRT in this setting. Methods: From 2004-2010, 230 patients with localized high risk prostate cancer were enrolled into 3 sequential prospective phase I/II trials of delivering EPNI (45 Gy) along with a concomitant hypofractionated IMRT boost to the prostate (67.5 Gy total) in 25 fractions over 5 weeks time. All patients were to receive 3 years of adjuvant androgen deprivation. During the accrual period, the method used to deliver the EPNI portion of the treatment changed as new literature emerged about target volumes for EPNI. The 3 methods used to deliver EPNI in this large cohort were 1) 4FB, 2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al (IMRT-Shih), and 3) IMRT with nodal volumes as suggested by RTOG (IMRT-RTOG). Common Terminology Criteria for Adverse Events v3.0 was used to assess acute toxicity prospectively during treatment and then at 3 months. Results: For EPNI, 94 patients were treated with a 4FB, 53 were treated with IMRT-Shih, and 83 were treated with IMRT-RTOG. There were no acute grade 3 GI toxicities. Patients in the 4FB group had higher rates of acute grade ≥ 2 proctitis compared to the IMRT-Shih and IMRT-RTOG groups (16.0% vs 2.0% vs 2.4%, p=0.0009). The 4FB group also had higher rates of grade ≥ 2 flatulence compared to the 2 other IMRT groups (17.0% vs 7.6% vs 0%, p<0.0001). With regards to acute GU toxicities, patients in the 4FB group had higher rates of grade ≥ 3 urinary frequency compared to the 2 other IMRT groups (5.3% vs 0% vs 0%, p=0.027). Conclusions: In this non-randomized comparison, IMRT resulted in statistically significant decreases in acute proctitis, flatulence, and urinary frequency when compared to a 4FB technique to deliver EPNI in localized high risk prostate cancer. Analysis for possible confounding factors will be performed.
Comprehension and preferences for graphical representations of quality of life after prostate cancer treatment.
Authors: Gore John L. , Izard Jason , Avery Daniel I. , Shih Cheryl , Hartzler Andrea 
Published: February 2017

76 Background: Integration of quality of life (QoL) measurement into clinical prostate cancer (PCa) practice may enhance patients’ communication with clinicians, improve satisfaction with care, and affect the delivery of secondary therapies. A necessary step to achieve these benefits is illustrating QoL in ways patients can understand and use. Through a patient-partnered project, we developed graphical representations of prostate cancer QoL (dashboards) and compared patients’ comprehension and preferences among four alternative formats: table, bar chart, line graph, and pictograph. Methods: We conducted interviews with PCa patients and assessed health literacy, subjective numeracy, and graphic literacy with validated instruments (REALM, Subjective Numeracy Scale, Graphic Literacy Scale). We then presented patients the 4 candidate dashboards counterbalanced for format order, and assessed participants’ comprehension, helpfulness rating, and rank order preferences. Results: Our study included 29 PCa patients, with mean age 71 years (range 53-90). Patients were mostly white (86%) and had at least a college degree (76%). Most had localized PCa (90%) and 55% were treated within the last 5 years; 9 patients had undergone more than one type of treatment. Patients’ health literacy (mean score 6.9±0.26 out of 7), numeracy (mean score 4.3±0.94 out of 6), and graphic literacy (mean score 11.4±1.4 out of 13) was high. Comprehension did not vary by dashboard format (p=0.39), ranging from 84% correct for line graph to 91% correct for bar chart. The pictograph exhibited lower helpfulness ratings (p=0.001). Preference elicitation strongly favored the bar chart (p=0.004), ranked 1st by 52% of patients, and disfavored pictograph, ranked 4th by 69% of patients. Conclusions: Among a high literacy and numeracy sample of PCa patients, comprehension and preference ranking strongly favored bar charts for QoL dashboards. Pictographs, known to benefit low literacy patients, were not preferred despite good comprehension. Inclusion of lower literacy patients may yield different results. Future work will determine if clinical integration of QoL dashboards is associated with improved health outcomes.
Overall survival benefit and safety profile of radium-223 chloride, a first-in-class alpha-pharmaceutical: Results from a phase III randomized trial (ALSYMPCA) in patients with castration-resistant prostate cancer (CRPC) with bone metastases.
Authors: Parker Chris , Heinrich Daniel , O'Sullivan Joe M. , Fossa Sophie D. , Chodacki Ales , Demkow Tomasz , Logue John P. , Seke Mihalj , Widmark Anders , Johannessen Dag Clement , Nilsson Sten , Hoskin Peter , Solberg Arne , James Nicholas David , Syndikus Isabel , Cross Andrew , O'Bryan-Tear C. Gillies , Garcia-Vargas Jose E. , Sartor A. Oliver 
Published: February 2017

8 Background: Radium-223 chloride (Ra-223) is a first-in-class alpha-pharmaceutical targeting bone metastases (mets) with high-energy alpha-particles of extremely short range (<100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared efficacy, in terms of overall survival (OS), and safety of Ra-223 plus best standard of care (BSC) vs placebo plus BSC in patients (pts) with bone mets in CRPC. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra‐223 (50 kBq/kg IV) q4 wks or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. A planned interim analysis (IA) was conducted to assess the effect of Ra-223 on the primary endpoint (OS) using a predefined threshold. Survival data were compared using a stratified log-rank test. Results: 922 pts (Ra-223, n = 615; placebo, n = 307) were randomized from 6/2008-2/2011. 445 (58%) of 809 pts in the IA data set received prior treatment with docetaxel. Ra-223 significantly improved OS in pts with CRPC with bone mets vs placebo (two-sided P = 0.00185; HR = 0.695; 95% CI, 0.552-0.875; median OS 14.0 mo vs 11.2 mo, respectively). Safety and tolerability of Ra-223 were highly favorable and showed low incidence of myelosuppression (eg, grades 3/4 neutropenia in 1.8% and 0.8% and thrombocytopenia in 4% and 2% of the Ra-223 and placebo groups, respectively). Conclusions: Ra-223 is an effective therapy that improved OS with a highly favorable safety profile, and may provide a new standard of care for the treatment of CRPC pts with bone mets. [Table: see text]
Biologic activity of LSD1 inhibition by novel tranylcypromine structural analogues in prostate cancer cells.
Authors: Crabb Simon J. , Hayden Annette L , Strivens Rosemary A , Benelkebir Hanae , Ganesan A , Packham Graham 
Published: February 2017

82 Background: Hormonal strategies to inhibit androgen receptor (AR) signalling remain inadequate and so novel approaches are urgently required. Lysine (K)-specific demethylase 1A (LSD1), is an epigenetic AR co-activator which modifies chromatin structure through de-methylation of histone H3 lysine 9 at androgen response elements to activate transcriptional expression of AR target genes. LSD1 is over-expressed and a poor prognostic factor in prostate cancer. We have synthesised novel analogues of the monoamine oxidase (MAO) inhibitor tranylcypromine as LSD1 inhibitors to exploit MAO and LSD1 sequence homology. Methods: We utilised prostate cancer cell line models to investigate the biological effect of LSD1 inhibition using tranylcypromine analogues. Results: Chemical inhibition of LSD1 was effective in inhibiting cell proliferation in prostate cancer models with around 1000 fold greater potency for synthesised analogues over tranylcypromine in LNCaP prostate cancer cells. Chemical inhibition of LSD1 induced the predicted histone methylation changes consequent on LSD1 inhibition of mono- and di-methylation of histone H3 lysine 9. In addition LSD1 depletion, AR depletion and reduced expression of the AR target gene prostate-specific antigen was demonstrated. Fractional effect assays demonstrated synergistic interactions in cell proliferation assays for tranylcypromine analogues with the androgen receptor antagonists bicalutamide and MDV3100. Conclusions: Our data demonstrate biological activity of LSD1 inhibition in prostate cancer cells with depletion of AR signalling using optimised structural analogues of established drugs for non-cancer indications. Therapeutic targeting of LSD1 for prostate cancer would represent a novel therapeutic paradigm for this disease.
Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy
Authors: Shlomai Gadi , Neel Brian , LeRoith Derek , Gallagher Emily Jane 
Published: February 2017

Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis. Results T2DM is associated with an increased risk and greater mortality from many cancer types. Metformin use has been associated with a decrease in cancer incidence and mortality, and there are many ongoing randomized trials investigating the effects of metformin on cancer-related outcomes. However, data regarding the association of other antidiabetes medications with cancer incidence and mortality are conflicting. Glucocorticoids, hormone-based therapies, inhibitors that target the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway, and insulin-like growth factor 1 receptor–targeted therapy have been associated with high rates of hyperglycemia. These agents mediate their deleterious metabolic effects by reducing insulin secretion and increasing insulin resistance in peripheral tissues. Conclusion Studies must be performed to optimize cancer screening strategies in individuals with T2DM. A greater understanding of the mechanisms that link diabetes and cancer are needed to identify targets for therapy in individuals with diabetes who develop cancer. Data from clinical studies are needed to further elucidate the effects of antidiabetic medications on cancer incidence and progression. As several anticancer therapies alter glucose homeostasis, physicians need to be aware of these potential effects. Careful patient screening and monitoring during treatment with these agents is necessary.
Evaluation of a Web-Based Cognitive Rehabilitation Program in Cancer Survivors Reporting Cognitive Symptoms After Chemotherapy
Authors: Bray Victoria J. , Dhillon Haryana M. , Bell Melanie L. , Kabourakis Michael , Fiero Mallorie H. , Yip Desmond , Boyle Frances , Price Melanie A. , Vardy Janette L. 
Published: February 2017

Purpose Cognitive impairment is reported frequently by cancer survivors. There are no proven treatments. We evaluated a cognitive rehabilitation program (Insight) and compared it with standard care in cancer survivors self-reporting cognitive symptoms. Patients and Methods We recruited adult cancer survivors with a primary malignancy (excluding central nervous system malignancies) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms. All participants received a 30-minute telephone consultation and were then randomly assigned to the 15-week, home-based intervention or to standard care. Primary outcome was self-reported cognitive function (Functional Assessment of Cancer Therapy Cognitive Function [FACT-COG] perceived cognitive impairment [PCI] subscale): difference between groups after intervention (T2) and 6 months later (T3). Results A total of 242 participants were randomly assigned: median age, 53 years; 95% female. The primary outcome of difference in FACT-COG PCI was significant, with less PCI in the intervention group at T2 ( P < .001). This difference was sustained at T3 ( P < .001). At T2, there was a significant difference in all FACT-COG subscales, favoring the intervention. Neuropsychological results were not significantly different between the groups at T2 or T3. There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2. There were significant improvements in stress in the intervention group at both time points. There was no significant difference in quality of life between the groups at T2, but the intervention group had better quality of life at T3. Conclusion The intervention, Insight, led to improvements in cognitive symptoms compared with standard care. To our knowledge, this is the first large randomized controlled trial showing an improvement in self-reported cognitive function in cancer survivors, indicating that this intervention is a feasible treatment.
Outcome of Men With Relapse After Adjuvant Carboplatin for Clinical Stage I Seminoma
Authors: Fischer Stefanie , Tandstad Torgrim , Wheater Matthew , Porfiri Emilio , Fléchon Aude , Aparicio Jorge , Klingbiel Dirk , Skrbinc Breda , Basso Umberto , Shamash Jonathan , Lorch Anja , Dieckmann Klaus-Peter , Cohn-Cedermark Gabriella , Ståhl Olof , Chau Caroline , Arriola Edurne , Marti Kalena , Hutton Paul , Laguerre Brigitte , Maroto Pablo , Beyer Jörg , Gillessen Silke 
Published: February 2017

Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of relapses occurred > 3 years after treatment. The majority of relapses were detected by computed tomography scan during routine follow-up, 98% in the International Germ Cell Cancer Collaborative Group good prognosis group. Chemotherapy was administered to 92% of patients, mostly as standard first-line treatment corresponding to stage; 8% of patients had additional local treatments. Only 28 patients experienced a second relapse. At last follow-up, 174 (94%) of 185 patients were alive without disease, and four patients with disease. Seven patients died, three of whom due to progressive disease. Conclusion Within the limitations of a retrospective analysis, the results suggest that the majority of patients who experience a relapse after adjuvant carboplatin for clinical stage I seminoma can be successfully treated with a cisplatin-based chemotherapy regimen adequate for stage. Because 15% of the relapses occurred > 3 years after adjuvant treatment, a minimum of 5 years follow-up is recommended.