bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between human epidermal growth factor receptor 2 (HER2) status and central nervous system (CNS) involvement in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gernone Angela , Pagliarulo Vincenzo , Silvestris Francesco , Pagliarulo Arcangelo 
Published: February 2017

210 Background: The incidence of CNS metastasesin prostate cancer is very low. Recent data suggest that HER-2/neu is involved in progression of prostate cancer. Docetaxel-based chemotherapy has provided a survival advantage for mCRPC. The purpose of this retrospective study was to evaluate the relation between HER-2 status and risk of CNS metastases in pts with mCRPC treated with docetaxel. Methods: From 2003 to 2010, 130 pts with mCRPC were treated with 3wk docetaxel 75 mg/mq. 72/130 pts were retreated with the same regimen on disease progression. 50 out of these 72 pts received second docetaxel retreatment. All pts had bone metastases. Pts underwent total body CT scan before starting docetaxel chemotherapy and every 6 months during treatment. The median age was 66 (41–88), median baseline PSA: 110 ng/ml (range 5–1100), median ECOG Performance Status: 1 (range 0–2). The data on 130 pts, who underwent diagnostic biopsy or potentially curative resection , were reviewed. Tissue blocks from primary prostate cancer tissues were obtained. Grade 3 of the HER-2 by IHC staining was defined as a positive result or gene amplification by FISH. 10 out of these 50 pts receiving second docetaxel retreatment were diagnosed with CNS metastases. Results: CNS metastases were observed in HER-2 positive pts. 6/10 pts presented parenchymal metastases: 4 pts were asymptomatic, 3 pts underwent metastasectomy and all of them received palliative whole-brain RT. 4/10 pts presented leptomeningeal metastases with neurological symptoms and 2 of them received palliative whole-brain RT. The median time from prostate cancer diagnosis to the date of diagnosis of CNS metastases was 6 years (1–8). The median time from first cycle of docetaxel to the date of diagnosis of CNS metastases was 3 years (1.5–4). Conclusions: These preliminary data demonstrated that HER-2 expression confers an increased risk of CNS metastases in mCRPC and constitutes a therapeutic challenge. The apparent increase of CNS presentation may be related to the effectiveness of systemic therapy. These informations support the further evaluation of neurological symptoms in long-term docetaxel treated pts.
Balancing efficacy with tolerability: The conversational mechanics of shared decision making in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ellis Lorie , Davidson Brad , DiChiara Matthew , Senbetta Mekre 
Published: February 2017

229 Background: Discussions of therapeutic risk or benefit have a different tone in patients facing metastatic cancer. The literature predicts misalignment on therapy selection and communication gaps between patients and physicians. Gaps in assumed reasons for therapy selection may hinder the mCRPC patient’s ability to make fully informed decisions. (Fine, E. et al; J. Palliative Med, 2010, 13(5); 595-603.) Methods: This IRB-approved, observational, linguistic study describes naturally occurring conversations between mCRPC patients (n=42; 69% African American) and their treating urologist (n=7) or oncologist (n=7) during a normal clinic visit in Summer 2011. Clinic interactions were videotaped without 3rd party observers present. Patients and physicians were interviewed again separately after the clinic visit. All conversations were transcribed and analyzed using standard techniques from anthropology and discourse analysis fields. Results: At both a lexical and goal-oriented level, several disparities were observed. When discussing treatment options and goals for mCRPC, lexically, words used by physicians differed from those used by patients. This difference was found in physicians’ use of technical language and in language describing goals and results of therapy. Of interest, physicians consistently used vague language to describe therapeutic effect (e.g. “working”), and frequently presented treatment options without presenting treatment risks (e.g. “maybe go to another treatment altogether”). Patients and physicians also differed in the way they framed goals of therapy. Conclusions: The current research highlights communication gaps between clinicians and mCRPC patients about treatment options and risks. These results suggest that patient decision making may be hindered by a lack of clear understanding of treatment choice implications and poorly defined treatment goals. Treatments with an optimum balance of efficacy and tolerability may present an opportunity to improve this dialogue.
Aggressive phenotype for prostate cancer cells that survive high-dose ionizing radiation.
Authors: Wang Tao , Carraway Robert , Briggs Joshua , Fitzgerald Thomas J 
Published: February 2017

236 Background: Radiation therapy (RT) is an important primary treatment for localized prostate cancer (PCa). However, certain patients can relapse and become resistant to RT. To identify the molecular mechanisms underlying RT resistance, we studied human PCa cells that survive fractionated high dose IR in vitro. Methods: DU145 (DU), a human cell line from PCa metastasized to brain, was exposed to fractionated ionizing radiation (IR) up to 40 Gy. The cancer biology of the surviving cells (DUIR) after 4 month in culture was studied. Cell growth and survival were assessed using cell counting, SRB and clonogenic assay. Invasiveness was measured using Boyden chambers. Caspase activity was determined for apoptosis. Activation of signaling molecules and expression of biomarkers was assessed using Immunoblot. Hormone binding to receptors was assayed using iodinated ligands. Results: Whereas DU was squamous in shape, DUIR displayed fibroblast-like morphology with long protrusions resembling cells undergoing epithelial-mesenchymal transition (EMT) confirmed by reduced E-cadherin and enhanced vimentin expression. DUIR cells showed higher level of neurotensin receptor 1 (NTR1) and chromogranin B resembling a neuroendocrine (NE) phenotype. DUIR has significantly higher survival than DU when exposed to IR (6–10 Gy) or zinc-directed toxins and grows significantly faster in response to serum or NT at a dose dependent manner. Addition of NTR1 antagonist SR486923 abolished the NT enhanced cell growth. DUIR had increased invasiveness through the matrigel-coated membrane. ERK and PKC, but not AKT, were constitutively active in DUIR. BCL2 level was upregulated in DUIR. NT stimulation reduced apoptosis while SR486923 enhanced apoptosis in DUIR cells upon IR. Conclusions: PCa cells that survive high dose IR display an aggressive phenotype characterized by NE and EMT features including invasion and resistance to IR/drug induced cell death. These changes could be due to constitutive activation of growth signaling pathways and upregulation of anti-apoptosis/necrosis molecules. Further study may provide insight into the mechanism of cellular resistance to therapy and establish strategies for novel therapeutic applications.
Comparison of second-line treatments in patients with castration-resistant prostate cancer with PSA relapse after or during docetaxel chemotherapy.
Authors: Pfister David J. K. P. , Porres Daniel , Piper Charlotte , Merseburger Axel S. , Klotz Theodor , Heidenreich Axel 
Published: February 2017

243 Background: Docetaxel was the first agent with a proven survival benefit and improved quality of life in patients with castration resistant prostate cancer. Recently there are two new agents, Cabazitaxel (Caba) and Abiraterone Acetate (AA) approved for the second-line treatment in case of progressive disease after Docetaxel. We compared the PSA response and complication rate of these three different second-line treatment options: Caba, AA and Docetaxel Re-Challenge (R-Doc). Methods: The data of 71 patients with progressive disease after/during Docetaxel chemotherapy were analyzed retrospectively. 25 patients with R-Doc, 27 patients with AA and 19 patients with Caba. All patients except two had a PSA-Response or stable disease to primary docetaxel chemotherapy. Mean patient age was 74 years for R-Doc, 71 for AA and 69 for Caba with a mean PSA before initiating treatment of 45 ng/ml, 162ng/ml and 563ng/ml. Results: PSA response rates (>50% regression) were seen in 14 (56%), 8 (38%) and 6 (32%) patients respectively. PSA stabilization was seen in 7 (28%), 2 (9,5%) and 7 (36,8%) patients. Haematologic complications grade >=3 were seen more frequently in R-Doce (32%) and Caba (42%) compared to AA (4%). Cardiovascular complications >= grade 3 were seen in 30% of the patients with AA whereas none of the patients with R-Doc or Caba had cardiovascular grade 3 or 4 side effects. Conclusions: With AA, Caba and the possibility of R-Doc there are compareable treatment options with regard to PSA response rates, even if a stable disease can be seen more frequently in Caba and R-Doc. As the drugs have different side effects the first second line treatment should be considered to the patient’s characteristics and comorbidity in the palliative setting. PSA progression free survival and overall survival data are awaited.
A phase II trial of chemotherapy plus hormone therapy as initial treatment of unresectable/metastatic adenocarcinoma of the prostate.
Authors: Amato Robert J. , Jac Jaroslaw , Stepankiw Mika , Ramirez Perla 
Published: February 2017

247 Background: Chemotherapy for hormone-refractory prostate cancer reduces PSA levels and enhances overall survival (OS), suggesting that administration in earlier disease stages may be beneficial. If expansion of an androgen-independent clone is present during androgen deprivation mediates the transformation from an androgen-dependent to an androgen-independent phenotype, combination chemohormonal therapy could be effective initial treatment for locally advanced or metastatic prostate cancer. This study examined the efficacy and safety of chemohormal therapy approach. Methods: Patients received medical castration plus an anti-androgen and chemotherapy (nab-paclitaxel, leuprolide, bicalutamide). Patients were followed with PSA levels and radiographic assessments. Results: Forty-six men (median age) 64.7 years were treated. Fifty-eight percent underwent prior local therapy including prostatectomy (30%), prior radiation (15%), or both (13%). Median baseline PSA was 8.9 ng/ml, and 96% of patients had a Gleason score of ≥7%. At 2 years, 78% of patients experienced tumor regression with a median reduction in PSA level of >90%. Median time to progression was 28.43 months measured by PSA and 34.52 months measured radiographically. Median OS was 62.4 months. The most frequent significant adverse events included grade 3 hypokalemia (17%) and lymphopenia (59%). Conclusions: Combination chemohormonal therapy for locally advanced and metastatic prostate cancer delayed disease progression and enhanced OS. Information presented will include curves and correlation detailing efficacy and adverse events of various sub-populations.
Impact of race on prostate cancer selection and cause-specific mortality: A SEER database analysis.
Authors: Duarte Catherine , Sarkisian Natasha , Nguyen Paul Linh , Garroutte Eva , Hurwitz Mark D 
Published: February 2017

248 Background: The objective of this study was to assess relationships between race, treatment, and cause-specific mortality for prostate cancer. Methods: The Surveillance, Epidemiology and End Results (SEER) database yielded 328,151 prostate cancer patients diagnosed between 1990–2007 including 5,129 Japanese-American, 50,717 Black-American, and 282,305 White-American men. Japanese-American men were selected as they have the lowest incidence of prostate cancer and best treatment outcomes. Cox proportional-hazards regression analysis was used to assess association of race with prostate-cancer specific mortality before and after adjusting for age, health, and treatment. To assess impact of race on treatment selection, we compared mean incidence of treatment type [external beam radiation therapy (EBRT), brachytherapy, and surgery] by race using one-way ANOVA and post-testing with Bonferroni correction. Results: Race significantly impacted survival after prostate cancer treatment. Blacks had the highest (HR= 1.198; 95% CI: 1.159 to 1.239, p< .001) and Japanese the lowest (HR= .618; 95% CI: .560 to .682, p< .001) mortality hazard compared to Whites. Tumor grade was the strongest predictor of survival (p< .001). Treatment was also significant: Brachytherapy had the lowest mortality hazard for radiation treatments and surgery was associated with lower mortality hazard compared to no surgery. 37.8%, 44.1%, and 29.1% of Blacks, Whites, and Japanese-Americans underwent surgery (p< .05), 27.3%, 23.8%, and 38.2% of Blacks, Whites, and Japanese-Americans underwent EBRT, (p< .05), and 4.9%, 6.7%, and 4.7% of Blacks, Whites, and Japanese-Americans underwent brachytherapy, with Whites significantly different from the other groups( p<.05). Conclusions: SEER database analysis revealed race impacts prostate cancer survival. Treatment selection for prostate cancer differs among racial groups and race is associated with differential treatment outcomes. Comparisons between treatments must be viewed with caution as confounding variables likely exist not accounted for in the SEER database. Future research on race, treatment, and socioeconomic impact on cancer-specific mortality is warranted.
Dosimetric comparison of targeted high-dose-rate brachytherapy versus whole gland treatment.
Authors: Chung Melody P , Kayode Oluwatosin , Wang Jason , Park Sang-June , Marks Leonard S. , Demanes D. Jeffrey , Kamrava Mitchell 
Published: February 2017

255 Background: To determine potential benefits of focal brachytherapy, we investigated target coverage and magnitude of decreased dose to organs at risk (OARs) with hemigland (HG) compared to whole gland (WG) high dose rate brachytherapy. Methods: 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans using Inverse Planning Simulation Annealing in Oncentra Masterplan (Nucletron). The same distribution of 17-18 catheters was used for WG and HG plans. The same dose constraints were used for all plans (D90 100-115%, V100 97-100%, V150<35%, Rectum D0.1cc <85%, Bladder D0.1cc < 95%, and Urethra D0.1cc <110%). The HG contour was a modification of the WG contour whereby the urethra divided the prostate into hemiglands. Contours for OARs were identical. HG plans were not actually delivered. The prescription dose was 7.25 Gy x 6. A D90, V100, and V150 were calculated for HG and WG, along with D0.1cc, D1cc, D2cc, and Davg to OARs. We estimated mean difference and 95% confidence intervals for outcome measures. Bonferroni correction was used to adjust for bias due to multiple comparisons. Statistical analyses were conducted using SAS 9.2 (SAS Institute, Cary, NC), with a significance level set at p=0.003. Results: Compared to WG, HG was associated with a higher D90 (108 vs 112%, p < 0.0001), lower V100 (98.8 vs 97.6%, p = 0.0001), and higher V150 (26.5 vs 33.8%, p = 0.0001). WG therapy resulted in higher tissue doses to OARs. Mean values for the rectum were D0.1cc (76.0 vs 71.2%, p=.0027), D1cc (68.4 vs 59.0%, p<0.0001), D2cc (64.1 vs 53.1%, p<0.0001) and Davg (27.5 vs 20.5%, p<0.0001). Mean values for the bladder were D0.1cc (83.8 vs 82.2%, p=0.0925), D1cc (73.4 vs 64.0%, p<0.0001), D2cc (67.5 vs 55.9%, p<0.0001) and Davg (22.1 vs 16.2%, p<0.0001). Mean values for the urethra were D0.1cc (106.5 vs 97.7, p<0.0001), D1cc (103.1 vs 82.9%, p<0.0001), D2cc (95.2 vs 69.3%, p<0.0001) and Davg (73.5 vs 57.2%, p<0.0001). Conclusions: The catheter distribution used for WG may not be ideal for HG as a higher D90 and V150 was noted. HG plans decreased Davg to the rectum, bladder, and urethra by a difference of 7.0, 5.9, and 16.3%. Further research is warranted to determine whether further dose reductions can be achieved and are clinically meaningful.
Sociodemographic and clinical characteristics among men with metastatic prostate cancer: An aged-stratified analysis.
Authors: Forlenza Jamie , Senbetta Mekre , Smalarz Amy , Riggs Kimberly 
Published: February 2017

256 Background: Data on age-specific comparisons in metastatic prostate cancer (MPC) is limited. This analysis evaluated socio-demographic and clinical characteristics among men with MPC aged <65 years versus ≥65 years. Methods: Eighty-four US men aged ≥18 years with self-reported MPC completed a cross-sectional survey in January-February 2011 which collected data on socio-demographic and clinical characteristics including treatment history and source of care. Results: Forty-nine men were aged <65 years; 35 men were ≥65 years. There were no differences (all P>0.05) between groups for marital status (80% of those <65 years and 83% of those ≥65 years were married), race/ethnicity (94% of both groups were white), education (88% of those <65 years and 77% of those ≥65 years had attended college), and annual household income (29% of those <65 years and 31% of those ≥65 years had incomes of $35,000-$54,999). Time since diagnosis differed between groups with 12%, 84%, and 4% of those aged <65 years and 3%, 69%, and 29% of those aged ≥65 years having been diagnosed <1, 1-9, and ≥10 year(s) ago, respectively (P<0.001). Respondents aged <65 years and ≥65 years reported similar experience with chemotherapy (37% in both groups had received chemotherapy), no anemia in last 4 weeks (80% and 83%, respectively), no bone fractures or spinal cord compression in last 4 weeks (90% and 94%, respectively), receiving previous radiation therapy (69% and 66%, respectively), receiving previous surgery (63% and 66%, respectively), and utilizing hormonal treatments previously or currently (86% and 90%, respectively) (all P>0.05). In addition, those <65 years versus ≥65 years did not differ regarding their self-reported source of primary care for prostate cancer (51% and 54% reported receiving their care from oncologists, respectively; 47% and 43% from urologists; 2% and 3% from family physicians/internists). Conclusions: In this study of men with MPC, those aged <65 years and those ≥65 years reported similar prostate cancer treatment utilization as well as socio-demographic and clinical characteristics with the exception of a difference in time since diagnosis. Further research in larger populations is warranted.
Trends in the adoption of robotic technology in the surgical management of prostate cancer: A population-based analysis.
Authors: Chang Steven Lee , Jiang Wei , Chung Benjamin I. 
Published: February 2017

258 Background: The adoption of the da Vinci Surgical System (Intuitive Surgical, Inc) for robotic surgery requires a substantial financial investment by hospitals, acquisition of new surgical skills by surgeons, and demand from patients. Although the benefits of this technology have been previously described, the prevalence and adoption rate for the treatment of prostate cancer is not currently known. We performed a population-based analysis to determine how the introduction of robotic technology has altered the surgical management of prostate cancer. Methods: We analyzed patient-level data from the Prospective Rx Comparative Database (Premier, Inc., Charlotte, NC), which collects data from over 600 non-federal hospitals throughout the United States. We captured all men who underwent a radical prostatectomy between January 1, 2003, and December 31, 2010, based on the International Classification of Disease, 9th edition. Radical prostatectomies utilizing the da Vinci Surgical System were identified by a detailed review of the hospital charge data. Descriptive analysis with univariate and multivariate statistical analyses were performed. Results: Prior to 2006, <10% of radical prostatectomies were performed with robotic surgery. Beginning in 2006 there was a rapid rise in adoption reaching 56% utilization in 2009 and leveling off in 2010 to 54%. Adjusted analysis demonstrated that the odds of adopting robotic surgery were higher in teaching hospital (odds ratio [OR] 1.45, p<0.001) and hospitals in the Northeast (vs Midwest [OR 2.99, p<0.001]). Smaller hospitals (<200 beds) had a lower likelihood of adopting robotic surgery (OR 0.4, p<0.001). Patient age had no impact on the odds of undergoing robotic radical prostatectomy. Conclusions: Over past 5 years, there has been widespread adoption of robotic surgery in the management of prostate cancer now with just over half of procedures performed with the da Vinci Surgical System. Our analysis suggests that the adoption of robotic surgery has been determined primarily by the acquisition of this technology by hospitals, which was more common in teaching institutions, larger hospitals, and hospitals in the Northeast.
Randomized phase II trial of maintenance sunitinib versus placebo following response to chemotherapy (CT) for patients (pts) with advanced urothelial carcinoma (UC).
Authors: Grivas Petros , Nanus David M. , Stadler Walter Michael , Daignault Stephanie , Dreicer Robert , Kohli Manish , Petrylak Daniel Peter , Vaughn David J. , Bylow Kathryn A. , Belldegrun Arie S. , Sottnik Joseph L. , Keller Evan T. , Smith David C. , Hussain Maha 
Published: February 2017

265 Background: UC response to CT is not durable. Angiogenesis may play a role in the progression of UC. We evaluated whether maintenance sunitinib delays progression after response to CT. Methods: Pts with ECOG PS 0-2, adequate organ function, stable disease, partial or complete response (SD, PR, CR) after 4-6 cycles of CT for advanced UC were randomized to oral sunitinib 50 mg/day, 28 days on, 14 days off (6-week cycle) or placebo. Disease was assessed every 12 wks. At progression, placebo pts were offered open label sunitinib. Primary endpoint: progression rate at 6 months (ms); secondary endpoints: safety, objective response rate, survival, VEGF/sVEGFR2 serum level changes. Using a randomized selection design 42 pts/arm has 90% probability of selecting sunitinib if true reduction in 6-ms progression rate is 15% (from 50% to 35%). Results: Study was closed early due to slow accrual. 54 pts with median age 69 years, median ECOG PS 1, 70% with bladder primary, 26 with SD, 23 with PR, 5 with CR to CT were randomized to sunitinib (26) or placebo (28). The median number of cycles was 2/arm (sunitinib 0-15, placebo 0-13). The 6-ms progression rate was 81% (95%CI 61-93%), median time-to-progression (TTP) 5 ms (0.3-22.2, 95%CI 2.4-6.3) for sunitinib and 75% (95%CI 55-89%), 2.7 ms (0.8-19.6, 95%CI 2.5-7.4) for placebo. Response rate in pts with SD at enrollment was 9% for sunitinib and 7% for placebo. Most common G3/4 AEs on sunitinib were diarrhea (15.4%/0%), fatigue (15.4%/3.8%), thrombocytopenia (15.4%/7.7%), hypertension (11.5%/0%). 16 placebo pts received sunitinib with best response 1 PR (6.25%), 6 SD (37.5%), 5 PD (31.25%); 4 not response evaluable. Median TTP was 3.4 ms (0.1-22, 95%CI 1.6-5.5). 11 pts had G3/4 AEs, 5 pts discontinued sunitinib due to AEs (4 related, 1 unrelated). Placebo pts had no change in VEGF/sVEGFR2 over time. Sunitinib pts had no change in VEGF but sVEGFR2 significantly decreased after 1 cycle (p<0.0001) and at progression (p=0.0002). VEGF/sVEGFR2 did not correlate with TTP. Conclusions: Maintenance sunitinib was feasible but did not improve 6-ms progression rate; open label sunitinib had limited activity. sVEGFR-2 decreased on sunitinib.