bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer: Final results.
Authors: Aragon-Ching Jeanny B. , Simmens Samuel J. , Andrawis Ramez , Hendricks Frederick , Frazier Harold , Phillips Michael , Jarrett Thomas , Patierno Steven R. , Siegel Robert S. 
Published: February 2017

179 Background: CTCs have known prognostic implications in metastatic prostate cancer. We presented initial data on the role of CTCs in BR of prostate cancer (Aragon-Ching et. al., ASCO GU 2011). The primary aim of this study was to determine whether there is a correlation between the number of CTCs with prostate specific antigen (PSA) levels and PSA doubling time (PSADT) in men with BR. Methods: BR was defined as patients who have undergone primary treatment with prostatectomy or radiation or both, with a rise to ≥ 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise for post-nadir radiotherapy. 36 patients (pts) were enrolled from May 2010 to May 2012. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: The median age for 36 pts was 69.5 (range: 51 – 91) with a median PSA of 1.65 ng/mL (range 0.2 – 65.8) and testosterone levels of 315 ng/dL (range: 31 – 727). Gleason scores ranged from 5 to 9 (median=7). Prostatectomy was the primary treatment in 25 pts, radiotherapy in 9 pts, Cyberknife in 1 pt and combined radiohormones in 1 pt. PSADT varied between 0.35 to 55 months, with a median of 7.43 mos. The incidence of positive CTCs was 8.3% (3 out of 36 pts) of whom 2 had biopsy-proven bony lesions upon presenting with equivocal scans. The 3 pts who had measurable CTCs had PSADT of 2.27, 4.99 and 3.08 months, respectively. Conclusions: Obtaining CTCs in unselected patients presenting with biochemical recurrence have low yield. However, obtaining a positive CTC raises the suspicion of presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.
15-year survival after radical prostatectomy (RP): Which prognostic factors are available for patient counseling?
Authors: Fossa Sophie D. , Waehre Haakon , Cvancarova Milada , Danielsen Haavard E 
Published: February 2017

181 Background: Studies on 15-year Post-RP survival including data on PSA relapse (PSA-Rel) are rare. We established the 15-year post-RP prostate cancer specific mortality (PCSM), to explore the time to PSA-Rel and PCSM thereafter, and to identify clinically available prognostic factors. Methods: In men prostatectomized from 1987-2004 slightly modified D`Amico risk groups were identified (T1: No palpable tumor ;”T2 unilateral”/”T2 bilateral” according to tumor palpability in one or both lobes). PSA –Rel was defined as PSA ≥4 µg/l before 2000, and thereafter as PSA >0.2 µg/l. Delay of RP was defined as RP performance 3-12 months after diagnosis. Competing risk modeling was performed with a significance level of <0.05. Results: After a median observation time of 12 years (range: 0-22), of 309 men (median age:62 years [range:40-74]) 40 have died from prostate cancer ( PCa) and 68 due to other causes (15-year PCSM: 15% [95%CI: 10-19%). No difference of PCSM was found between the low (N: 12) and the intermediate group (N: 121), the “conventional” high risk group ( N: 121) displaying a 24% PCSM rate (95% CI:16-32%) with particularly poor prognosis for men who presented with two high risk factors ( N. 32 ; PCSM: 33% [95% CI:20-46%]). The median time to PSA relapse (N: 152) was 5 years (range: 0-17), the median overall survival time after PSA- Rel being 7 years (range: 0-17). PCSM continued to increase after 10 years. Delay of RP had no impact on PCSM. Conclusions: After a median observation time of 12 years approximately 1 of 7 men with localized PCa, most of them diagnosed before the PSA- era, have died of prostate cancer. The “conventional” high-risk group is prognostically heterogeneous: Men with two high risk criteria have a particularly poor prognosis. PSA-Rel 10 years after RP is no rare event followed by survival times of >10 years. Delay of RP for up to one year had no impact on PCSM.
Evolving patterns of metastatic disease in castration-resistant prostate cancer (CRPC) reported in clinical trials from 1990 to 2011.
Authors: Oh William K. , Doctor Stephanie , Godbold James H. , Galsky Matt D. , Tsao Che-Kai 
Published: February 2017

195 Background: Bone remains the most common site of metastasis in CRPC. With new therapies extending survival in metastatic CRPC (mCRPC), we hypothesized that the incidence of non-osseous metastases is increasing over time. In this study, we evaluated the pattern of metastatic disease in mCRPC as reported in baseline characteristics of prospective clinical trials over 2 decades. Methods: We identified all therapeutic studies in patients with mCRPC in Pubmed and ASCO abstracts from 1990-2011. Inclusion criteria included phase 2 or 3 clinical trials in mCRPC with available baseline demographic data and no exclusion of specific site of metastatic disease (except brain). ASCO abstracts were limited to presentations in which data were available online. For each study, demographic data and study-reported sites of non-osseous metastatic disease were recorded (lymph node, visceral, soft tissue, liver). For each type of metastasis, weighted least squares linear regression models were used to evaluate temporal trends. Results: We identified a total of 290 eligible studies (270 phase II and 20 phase III) involving 19,110 patients. Of these, 127 studies reported data on non-osseous metastases and prior chemotherapy. There was a significant trend over time (p=0.001) of increasing proportions of patients with non-osseous metastasis in both chemotherapy- naïve and treated groups (1.4% per year increase). Increased lymph node, visceral, and soft tissue metastases were seen over the study period. However, the proportion of patients with liver metastasis remained relatively stable. Conclusions: In this study, we noted an increasing trend of non-osseous metastatic disease in patients with mCRPC over 20 years. This included lymph node, visceral and soft tissue metastatic disease, and this trend was observed in both chemotherapy-naïve and treated patients. Longer survival and new therapies may be changing the clinical presentation of patients with mCRPC.
Evaluation of a genomic-based prognostic test for metastasis in high-risk post-prostatectomy patients: Does it impact physician decision making?
Authors: Badani Ketan K. , Thompson Darby J. S. , Mitra Anirban Pradip , Ghadessi Mercedeh , Buerki Christine , Davicioni Elai , Wood Penelope J. 
Published: February 2017

196 Background: Currently, identification of individual patients who are truly at risk of developing lethal prostate cancer after radical prostatectomy (RP) is based on clinical nomograms. A prospectively validated genomic classifier (Decipher) has been shown to more accurately predict metastatic disease post RP than established clinical predictors and can identify patients with adverse pathology who may be cured by RP alone and may therefore not require additional treatment. Methods: An IRB-approved study assessed the impact of a genomic classifier (GC) test in 240 pathologically high-risk post RP case reviews. Twenty (20) urologic oncologists from 18 institutions reviewed 12 cases presented in a randomized, de-identified fashion via a secure online platform to provide treatment recommendations pre- and post- patient GC test results. Possible recommendations included referral to radiation oncologist and/or initiation of adjuvant hormones, close observation, or other. The primary endpoint was any change in treatment recommendation after unblinding of GC test results. Confidence in treatment recommendations was assessed using a 5-point Likert scale. Results: Following unblinding of GC test results, treatment recommendations changed in 43% (95% CI: 37-49) of all cases. Specifically, among cases with a pre-GC recommendation involving treatment, 31% (95% CI: 23-41) of respondents changed their recommendation to observation post-GC.Respondents considered the GC result to have influenced their recommendation in 63% (95% CI: 56-68) of cases. The addition of information provided by the GC result increased decision making confidence in 39% (95% CI: 30-49) of cases where a change of treatment recommendation was made. Following unblinding, physicians reported that the GC result was clinically relevant in 84% (95% CI: 79-84) of cases. Conclusions: GC appears to influence treatment recommendations and decision making confidence for high-risk prostatectomy patients. This study suggests that clinical implementation of GC may potentially impact treatment recommendations.
Effect of the ERα agonist GTx-758 on bone turnover markers in men with advanced prostate cancer.
Authors: Yu Evan Y. , Keane Thomas E. , Tutrone Ronald , Belkoff Laurence , Bass Joel , Chu Franklin , Gambla Mike , Gaylis Franklin , Bailen James , Getzenberg Robert H. , Coss Christopher , Hancock Michael L. , Dalton James T. , Steiner Mitchell S. 
Published: February 2017

222 Background: Men with advanced prostate cancer are being treated with androgen deprivation therapy (ADT) for longer periods of time. The use of ADT can be limited by estrogen deficiency side effects, including a loss of bone and a higher incidence of fractures. GTx-758 is an ERα agonist that lowers serum free testosterone greater than an LHRH agonist. Herein we compare the effects of GTx-758 and leuprolide on markers of bone turnover, C-terminal telopeptides and bone specific alkaline phosphatase, in men with advanced prostate cancer treated with ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Serum samples were collected and analyzed by a reference laboratory. C-terminal telopeptides (pg/ml) and bone specific alkaline phosphatase (U/L) were measured as indicators of bone turnover. All p values describe the comparison of the GTx-758 treatment groups to the leuprolide treated men at day 120. Results: Men receiving the 1000 mg and 2000 mg doses of GTx-758 had lower C-terminal telopeptide levels with a mean percentage change of -56.9 ± 12.5 and -54.8 ± 23.1, respectively, as compared with an increase of 46.0 ± 48.9 percentage in the men receiving the leuprolide (p<0.001). Similarly, bone specific alkaline phosphatase levels were lower in men treated with GTx-758, with mean percentage changes of-28.5 ± 11.7 and -19.8 ± 14.7, respectively, compared with an increase of 8.1 ± 24.3 percent in the leuprolide treated group (p<0.001). As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion and not all of the men on the study reached the 120 day treatment dates (71 evaluable). Conclusions: Patients receiving GTx-758 experienced a significant decrease in markers of bone turnover indicating potential improvement and not a loss of bone on ADT. Since changes in bone mineral density are a major side effect that can negatively affect the quality of life in men on ADT, the improvements in bone turnover observed in men treated with GTx-758 could be significant. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed. Clinical trial information: NCT01326312.
A novel method for decreasing rectal toxicity during prostate radiotherapy by prostate-rectum separation: An evaluation of irradiation dose parameters and acute side effects.
Authors: Mathers Michael J. , Klotz Theodor , Lazar Yvonne , Eckl Thomas , Hermani Horst , Gagel Bernd 
Published: February 2017

227 Background: Prostate cancers (PCA) frequently arise in the peripheral posterior zone of the gland and therefore adjacent to the rectum. Treatment can include brachytherapy and/or radiotherapy (RT); however, rectal toxicity can complicate therapy. A dilemma therefore arises in the balance between radiation dose and rectal adverse effects. Methods: Starting February 2012, until now 37 patients were included in this investigation. Under ultrasound guidance, a synthetic hydrogel (SpaceOAR) was injected between the prostate and the rectum, thus moving the rectum away from the high radiation dose volume, allowing dose escalation. The procedure was carried out in general anaesthesia and required approx. 10 min. The prescribed dose for the prostate was 80.0 Gy in 40 fractions. In 20 patients also the pelvic lymph nodes were irradiated with 50.4 Gy. IMRT planning was realized with and without hydrogel. During the treatment and 3 months after treatment acute toxicity was documented by the use of common toxicity criteria version 3.0. Results: So far median follow up time post hydrogel injection for all patients is 6 months. No acute toxicity for the hydrogel-application was observed. In the middle plane of the gland, the space between rectal wall and prostate could be increased by an average of 1.34cm. The mean V70 with hydrogel was 1.6% (range 0-8%) and without hydrogel 17.3% (range 8- 42%) resulting in a mean reduction of V70 of 90,9%. Until now 24 patients finished RT. 14 of these patients showed gastrointestinal toxicity (GIT) grade 1. No grade 2. GIT was observed. 13 patients reached the first follow up 3 months after RT. Only 2 of these patients showed GIT grade 1. No GIT grade 2 was described. Conclusions: Injected liquid to solid inert substance for prostate-rectum separation appears to be safe. Reducing rectal irradiation doses has the potential to lower rates of rectal toxicity and therefore improving QOL in men receiving RT for prostate cancer. More research is needed before conclusions can be reached as to the technology’s potential place in therapy.
Potential cost-effectiveness of a diagnostic that identifies localized versus metastatic prostate cancer in men with biochemical recurrence after radical prostatectomy.
Authors: Bensink Mark Eliot , Berry Kristin , Musa Zahra , Bodnar Carolyn , Barocas Daniel Ari , Lin Daniel W. , Ramsey Scott David 
Published: February 2017

229 Background: Asymptomatic men with low but detectable PSA elevation following radical prostatectomy, often receive costly, burdensome, and potentially damaging salvage radiation therapy with uncertain benefit. A new prostate cancer specific functional imaging technology capable of identifying residual localized disease vs. small volume metastatic disease, to more accurately guide therapy decisions, could be of benefit. As a guide to diagnostic development efforts, the objective of this study was to assess the potential cost-effectiveness of using a novel diagnostic in this way. Methods: A Markov model was built to reflect the life-time natural history of prostate cancer recurrence. The model was used to estimate the incremental impact on costs (US healthcare system perspective) and quality adjusted life years (QALYs) of two alternative strategies: 1) using the new diagnostic to guide therapy vs. 2) usual care - using a combination of CT, MRI and bone scan to guide therapy. Costs were based on estimates from the literature, Medicare reimbursement and expert opinion. Prostate cancer progression, survival, and utilities plus the background risk of all-cause mortality, were obtained from the literature. Base-case diagnostic sensitivity, specificity, and cost were 75%, 90%, and $2,500. Results: The new diagnostic strategy provided an average per patient gain of 1.83 (95% UI: 1.41 - 2.5) QALYs and added cost of $15,600 (95% UI: -$7,000 - 48,800) with an incremental cost-effectiveness ratio of $8,500/QALY (95% UI: -$4,100 - 22,900). Results were most influenced by utility parameters and test performance characteristics however; the new diagnostic provided clinical benefits over a wide range of specificity and sensitivity. Conclusions: This analysis suggests that a diagnostic technology capable of identifying whether men with biochemical recurrence after radical prostatectomy have localized vs. metastatic disease would be cost-effective by reducing the costs and quality-of-life burden associated with non-beneficial radiation therapy. These results support additional investment in the development and validation of such a diagnostic.
The use of electromagnetic transponder beacons to reduce planning target volume (PTV) margins in post-prostatectomy patients undergoing adjuvant or salvage radiation therapy.
Authors: Kathpal Madeera , Ninneman Stephanie , Huang Raywin Rufus , Wendt Stacie , Malmer Cynthia , Brand Timothy , Halligan John B. , Brooks Joseph P. , Brown Michael , Tinnel Brent , Macdonald Dusten 
Published: February 2017

233 Background: We determined necessary PTV margins when beacons are used to localize the prostatic fossa in post-prostatectomy patients. We hypothesized beacon localization would allow for decreased PTV margins and increased normal tissue sparing. Methods: 10 patients requiring post-prostatectomy radiation were treated on this IRB-approved prospective study. Each patient had 3 beacons placed in the prostatic fossa. Daily radiation was localized by beacons and a cone-beam CT (CBCT) taken for analysis. By measuring differences between the treated clinical target volume (CTV) and relevant anatomy on 5 equally-spaced axial CT slices we calculated necessary PTV margins for each fraction. We then auto-fused each CBCT scan with the treatment planning scan, recorded the shifts incurred, and repeated our measurements, representing a hypothetical CBCT - localized treatment. We report a PTV margin for each technique that would cover the CTV during 90% of all 304 fractions analyzed. We also used intra-fraction motion data to produce a worst-case estimate of required PTV bladder margins. Results: The average shifts from the beacon to CBCT- localized isocenter were 2.9, 3.2, 1.0 mm and 0.58 degrees in the vertical, longitudinal, lateral, and rotational planes, respectively. Necessary PTV margins for beacon and CBCT localization are listed in the Table. Conclusions: Beacon localization “attaches” the CTV to the bladder, allowing a decrease in PTV margin or the amount of posterior bladder included in the CTV. This could lead to decreased rates of bladder toxicity. Clinical trial information: NCT01624623. [Table: see text]
Metabolite assay and histology on exactly the same tissue.
Authors: Troyer Dean A. , Shuster Jeffrey R. , Baxter Sarah , Su Mingming , Lance Ray 
Published: February 2017

235 Background: Metabolites are emerging biomarkers of cancer described as a link between genotype and phenotype. In previous studies we used molecular preservation by extraction and fixation (mPREF) on a metabolomics platform to screen for candidate metabolites using 18 gauge core needle biopsies of prostate tissues obtained ex vivo. Methods: Single core needle biopsies are immediately placed in 80% aqueous alcohol and transferred to formalin after 12-24 hours. The alcohol is retained, dried down and the residue reconstituted with 95 µL of acetonitrile plus 95 µL of water. Histology is performed on exactly the same tissue. Results: Using metabolomics, 83 metabolites showed differences between cancer containing vs. non-cancer containing biopsies. For nine of these differential metabolites, quantitative LC-MS assays have been developed using the same 18 gauge needle biopsy protocol. Thirty mPREF samples including tumor/non-tumor were analyzed using the developed method and the concentration ranges obtained. These analytes were selected in part because they could all be assayed on a single LC/MS run. Results comparing no tumor/tumor normalized to surface area of the biopsy core were as follows (see Table). Histology and immunohistochemistry (IHC) were satisfactory, and as the biopsy cores were moved to formalin, the work flow fits well with existing histopathology processing and microtomy methods. Conclusions: Our results confirm the original discovery trends and indicate that metabolites can be quantitated in single core biopsies fixed in aqueous methanol. From our experience and the literature, the performance of DNA/RNA extraction methods, in-situ hybridization, and proteomic analysis should differ very little from the use of formalin as primary fixative. The ability to quantitate any constituent of intact tissue is significant since most available methods such as IHC are subject to many variables and are difficult to quantitate. [Table: see text]
The risk of debilitating falls in Manitobans living with prostate cancer (pc).
Authors: Gingerich Joel Roger , Lambert Pascal , Doupe Malcolm , Daeninck Paul Joseph , Pitz Marshall W. , Czaykowski Piotr , Bertram-Farough Alison 
Published: February 2017

244 Background: Falls and fall-related injuries are important patient safety problems. Some studies suggest that pc patients have higher fall rates, however the severity of these falls is unknown. We sought to measure if pc patients are at increased risk of a debilitating fall requiring hospitalization. Methods: This is a retrospective population-based study utilizing the Manitoba Cancer Registry and Manitoba Health administrative databases. Our cohort consists of all community-dwelling patients living in Manitoba Canada who were diagnosed with pc between 2004 and 2008. These individuals were matched by age, sex, and time of diagnosis with up to three cancer-free controls. Debilitating falls were defined as falls/fractures requiring hospitalization and were identified using ICD-9 and -10 billing codes. A competing risk model was used to compare debilitating falls between the pc and cancer-free cohorts and expressed as sub-hazard ratios. Follow-up ended December 31, 2009. Results: 2,903 pc patients were identified along with 8,686 matched controls. The mean age was 69.3 and 68.8 respectively. The median follow-up was 3.05 years. Debilitating falls were identified in 109 patients (3.8%) with pc and 345 (4%) matched controls. The cumulative incidence of debilitating falls for those with pc vs cancer-free controls were: 1.08% vs. 1.13% at 1-year and 5.25% vs. 5.96% at five years of follow-up (SHR = 0.95, 95% CI = 0.77 – 1.18, p = 0.65). On univariate analysis, patients with stage IV pc were at higher risk of falls compared to matched controls. This difference was not significant on multivariate analysis though (SHR = 1.19, 95% CI = 0.74 – 1.89, p = 0.48). On multivariate analysis, patients with a Gleason score of ≤6 experienced a reduced risk of debilitating falls compared to matched controls (SHR = 0.44, 95% CI = 0.27 – 0.72, p = 0.001), whereas patients with other Gleason scores did not. The analysis was similar when patients with fractures were excluded. Conclusions: In this large population-based study, the 1- and 5-year cumulative incidence of debilitating falls did not differ significantly for patients with vs without pc. In fact, compared to matched controls, low grade pc patients were less likely to experience a debilitating fall.