bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of the screen-failure (SF) patient population in an early castrate-resistant prostate cancer vaccine clinical trial: Lessons for future trial design.
Authors: Vaena Daniel A. , Zehr Pamela , Griffith Karen , Brown Erica , Brown James A , Eastman Julie , Lubaroff David 
Published: February 2017

241 Background: AdPSA is an investigational replication-deficient adenovirus-based PSA vaccine. A prior phase I trial in patients (pts) with metastatic CRPC showed safety and ability to generate immune responses. We are conducting a phase II trial in early CRPC in our comprehensive cancer center + VA. This study contains an analysis of the SF (post-informed consent) population. Methods: Patients with CRPC defined as rising PSA despite androgen deprivation therapy are eligible for this trial. Main eligibility criteria requires a bone scan, chest X-ray and abdomen pelvis CT without evidence of metastatic disease (any PSA or PSA doubling time allowed). Pts with metastatic disease are also eligible if they have a PSA doubling time greater than 6 months and a PSA less than 10 and are asymptomatic. Prior antiandrogens or ketoconazole are allowed, provided the PSA is rising. Prior chemotherapy or sipuleucel-T is not allowed. Results: 38 pts have been consented for the clinical trial, of which 21 pts have proceeded with study therapy. 17 pts were SF for the following reasons: 13 had positive CT and/or bone scans with exclusionary PSA or PSADT values, 1 had declining PSA prior to starting therapy, and for 3 pts initiation of study therapy was contraindicated (second cancer discovered on CT, aggressive pace of progression, and unrelated patient death). Median PSA was 10.2 for SF vs 1.9 ng/mL for treated pts. 6 SF patients had PSA < 5 ng/mL. 26 pts had prior bicalutamide (12 SF, 14 treated group). Prior ketoconazole was rare in both groups. The vast majority of pts who were treated did not have metastatic disease. Conclusions: In a large academic cancer center, it is challenging but possible to find patients with early non-metastatic CRPC. Higher PSA may predict SF, but several patients with PSA < 5 ng/mL also had metastases on screen. Prior antiandrogen is not a predictor for SF. Since this abstract only relates to patients who consented for the trial, the denominator of cancer center patients with early CRPC (but not eligible) is even larger. This information will help accrual estimates in cancer centers and feasibility assessment of early CRPC studies.
Use of sector analysis of I-125 permanent prostate brachytherapy to evaluate and compare pre- and postimplant dosimetry.
Authors: Mohamed Yoosuf Ahamed Badusha , Workman Geraldine , O'Toole Monica M , Straney Margaret , Verghis Rejina , Napier Eoin , Mitchell Darren M. 
Published: February 2017

242 Background: To evaluate 12 sector analysis in the assessment and comparison of pre- and post- implant dosimetric parameters during the development of an I-125 prostate brachytherapy (PPB) service. Methods: 50 consecutive men being treated with PPB had dose volume analysis in 12 sectors of their pre implant ultrasound (PIUS) and post implant CT (PICT) data using a Variseed 8.0 treatment planning system. PIUS dosimetry was performed 2 weeks prior to implantation and PICT dosimetry 4 weeks post implant. Individual sectors were created by dividing the cranio-caudal prostate length into 3 equal lengths creating prostate base (PB), midgland (PM) and apex (PA). Each of these volumes was then divided into four axial sectors (right and left anterior, right and left posterior). The planning target volume (PTV), dose to 90% of prostate (D90), prostate volume enclosed by 100% (V100), 150% (V150) and 200% (V200) dose were recorded in each sector on PIUS and PICT. Adjacent sectors on PIUS were assessed for dose-volume homogeneity as were adjacent sectors on PICT. Differences in individual sectors on PIUS and PICT were evaluated. Results: Adjacent sector analysis demonstrated dose homogeneity in all sectors of PIUS and the majority of sectors on PICT. Statistically significant differences between PIUS and PICT were noted in target volume, particularly in PB with PICT >PIUS. When individual sectors on PIUS and PICT were compared, statistically significant differences were noted in the majority of dosimetric parameters. The anterior PB and PM were significantly lower on PICT (p value < 0.001) and significantly higher at the posterior PM and PA (p value < 0.05). These changes were consistent across all analysed parameters. In particular, significant absolute differences in D90 in equivalent sectors on PIUS and PICT were seen. Conclusions: 12 sector analysis allows rapid assessment of PIUS and PICT dose and volume homogeneity. It offers a scientific method of identifying areas of relative over and under dosing on PICT when compared with PIUS providing both clinicians and physicists with a learning tool to refine dosimetric analysis and highlight sectors where implant quality could be improved.
Variability in prostate volume as determined by MRI versus ultrasound and its impact on treatment recommendations for patients with favorable-risk prostate cancer.
Authors: Murciano-Goroff Yonina R. , Wolfsberger Luciant D. , Parekh Arti , Fennessy Fiona M. , Tuncali Kemal , Orio Peter F. , Niedermayr Thomas , Suh W. Warren , Devlin Phillip M. , Tempany Clare M. , Nguyen Paul Linh 
Published: February 2017

249 Background: Prostate volume affects whether patients qualify for brachytherapy (desired size ≥20mL and ≤60mL) or active surveillance (desired PSA density ≤0.15). This study examines variability in prostate volume as determined by contoured axial ultrasound slices, ultrasound ellipsoid (HxWxL) calculation, and endorectal coil MRI (erMRI) ellipsoid calculation, and quantifies the impact of this variability on treatment recommendations for men with favorable-risk prostate cancer. Methods: The study examined 72 patients who presented consecutively for consideration of brachytherapy for favorable-risk prostate cancer who had 3 volume estimates from direct contouring on ultrasound axial slices (2.5mm thickness), the ultrasound ellipsoid method, and the erMRI ellipsoid method. Results: Average gland size by the contoured ultrasound, ellipsoid ultrasound, and eMRI methods were 34.22, 37.15, and 39.58 mLs, respectively. All pairwise comparisons between methods were significant (all p<0.02). Of the 68 patients who anatomically qualified for brachytherapy on ellipsoid ultrasound measures (size ≥20mL and ≤60mL), 22 (32.35%) did not qualify on eMRI (5 patients <20 mL, 11 patients >60 mL) or contoured ultrasound measures (7 patients <20 mL, 3 patients >60 mL). 40 patients (55.56%) were very low risk (PSA density ≤0.15 ng/dl) as calculated using ellipsoid ultrasound volumes, while 35 (48.61%) and 39 patients (54.17%) were very low risk using contoured ultrasound and eMRI volumes, respectively. Conclusions: The ultrasound ellipsoid and erMRI ellipsoid methods appeared to overestimate ultrasound contoured volume by an average of 8.56% and 15.65% respectively. 32.35% of those who qualified for brachytherapy based on ellipsoid ultrasound volume would be disqualified based on ultrasound contoured and/or erMRI volume. As treatment recommendations increasingly rely on estimates of prostate size, clinicians must consider method of volume estimation.
Long-term outcomes in patients with muscle-invasive bladder cancer after bladder-preserving combined-modality therapy: A pooled analysis of RTOG 8802, 8903, 9506, 9706, 9906, and 0233.
Authors: Mak Raymond H. , Hunt Daniel , Shipley William U. , Efstathiou Jason Alexander , Tester William J. , Hagan Michael P. , Kaufman Donald S. , Heney Niall M. , Zietman Anthony L. 
Published: February 2017

264 Background: Multiple prospective RTOG studies have evaluated bladder preserving combined-modality therapy (CMT) including local resection with chemo-radiation for the treatment of muscle invasive bladder cancer (MIBC) reserving cystectomy for salvage. Here we report a pooled analysis of long-term outcomes. Methods: We performed a pooled analysis of 468 patients (pts) with MIBC enrolled on six RTOG bladder preservation studies, including five Phase II studies: RTOG 8802, 9506, 9706, 9906, and 0233, and one phase III study: 8903. Overall survival (OS) was estimated with the Kaplan-Meier method, and disease specific survival (DSS), local failure (LF) and distant metastasis (DM) were estimated by the cumulative incidence method. Results: The median age of the pts was 66 (range, 34-93), and the majority had a Zubrod performance status (PS) of 0 (89.1%). The most common tumor histology was transitional cell carcinoma (94.2%). Clinical tumor stage distribution included 60.6% T2, 29.1% T3a, 6.2% T3b, and 3.9% T4a. A complete response to CMT was observed in 72.0% of pts. With a median follow-up of 4.29 years among all pts, and 7.80 years among survivors (n=205), the 5-year and 10-year results were as follows (Table). Examining outcomes by subgroups, higher clinical T-stage (T2 vs. T3/T4) was associated with decreased DSS (5-year DSS: 74% vs. 66%; 10-year DSS: 69% vs. 60%; p=0.05), and OS (5-year OS: 62% vs. 49%; 10-year OS: 41% vs. 30%; p=0.002). On multivariate analysis, after adjusting for age and PS, higher T-stage was associated with decreased DSS (Hazard ratio: 1.65; 95% confidence interval: 1.19-2.27; p=0.002). Among pts with non-transitional cell carcinoma histology (n=29), the 5-year and 10-year DSS was 66% and 60%, respectively, and 5-year and 10-year OS was 41% and 21%. Conclusions: This pooled analysis of RTOG trials of bladder preserving CMT for MIBC demonstrates long-term OS and DSS comparable to modern immediate cystectomy-based strategies with and without neoadjuvant chemotherapy. CMT can be considered as an alternative to radical cystectomy in selected pts. [Table: see text]
Prognostic value of SPINK1 expression in bladder cancer after radical cystectomy.
Authors: Rink Michael , Shariat Shahrokh F. , Park Kyung , Volkmer Bjoern , Cha Eugene K. , Robinson Brian D. , Hautmann Richard , Scherr Douglas , Fisch Margit , Rubin Mark A. , Chun Felix K. , Kuefer Rainer , Mosquera Juan Miguel 
Published: February 2017

274 Background: Serine peptidase inhibitor Kazal type 1 (SPINK1) overexpression has been associated with poor outcomes. In one small study, loss of SPINK1 expression in urothelial carcinoma of the bladder (UCB) was associated with advanced tumor stage. We assessed the expression of SPINK1 in normal urothelium and UCB and analysed the association of SPINK1 with pathological features and clinical outcomes of patients treated with radical cystectomy (RC). Methods: The study used TMAs containing samples from 438 consecutive UCB patients treated with RC. 62 cases of normal urothelium were included as controls. A monoclonal antibody was used for immunohistochemical SPINK1 staining. SPINK1 expression of UCB was evaluated by two pathologists, blind to clinical outcome. Samples demonstrating less than 50% staining extent and 0 to 1 intensity (scale 0 to 3), were considered to have loss of expression. Results: SPINK1 expression was noted in umbrella cells of normal urothelium in 32/62 controls (52%). UCB of 254 patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with advanced pathological stage (p=0.002) and presence of lymph node (LN) metastasis (p=0.04). Within a median follow-up of 130 month (IQR 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (5-year RFS: 52±3 vs. 61±4 months; p=0.02) and cancer-specific mortality (5-year CSS: 59±3 vs. 68±3 months; p=0.03). In multivariable Cox regression analyses that adjusted for the effects of age, gender, tumor stage and grade, concomitant CIS, LN status and adjuvant chemotherapy, SPINK1 was not associated with disease recurrence (p=0.09) or cancer-specific death (p=0.12). Conclusions: While umbrella cells in normal urothelium commonly expresses SPINK1, more than half of UCB specimen exhibit loss of SPINK1 expression. Loss of SPINK1 expression is strongly correlated with local disease stage and LN metastasis. SPINK1 revealed no independent prognostic value for outcome prognostication, but it is a very promising marker for tumor staging which could be used for tailored follow-up protocols and possibly as a target for therapy as it has similarities with epidermal growth factor.
Contribution of C-reactive protein to predicting overall survival in patients with advanced urothelial carcinoma: Development of a nomogram and evaluation by decision curve analysis.
Authors: Ishioka Junichiro , Saito Kazutaka , Sakura Mizuaki , Yokoyama Minato , Matsuoka Yoh , Numao Noboru , Koga Fumitaka , Masuda Hitoshi , Kihara Kazunori 
Published: February 2017

280 Background: To accurately estimate the individual survival of patients with advanced urothelial carcinoma (UC), the application of prediction models such as nomograms has been warranted in clinical use. We therefore constructed a nomogram which included C-reactive protein (CRP) as a novel biomarker in order to increase its predictive accuracy. Furthermore, the clinical usefulness of this nomogram was evaluated by decision curve analysis which incorporated the negative consequences of each decision to generate a net benefit (Vickers et al, BMC Med Inform Decis Mak, 2008). Methods: A total of 232 consecutive patients with locally advanced or metastatic urothelial carcinoma (UC) were treated at our institute. Among them, 9 patients with missing data were excluded. The current study cohort was comprised of the remaining 223 patients. A nomogram predicting 6- and 12-month survival probability was developed based on the results of the final multivariate analytic model. To evaluate the efficacy of this nomogram, a quantified concordance-index (c-index) was computed and a decision curve analysis was performed. Results: Overall, 184 patients died of the primary disease and the remaining 39 were censored. The median follow-up period and length of overall survival were 5 and 6 months, respectively. The 6- and 12-month survival rates were 48% and 30% respectively. A nomogram was developed which included the parameters of age, PS, visceral metastasis, hemoglobin and CRP. The c-index of this prediction model was 0.79 compared with 0.75 for that of a model without CRP. The decision curve analysis revealed that a novel nomogram which incorporated CRP had a superior net benefit to that without CRP for most of the examined threshold probabilities. Conclusions: Incorporation of CRP increased the predictive accuracy of a prognostic nomogram for advanced UC. In clinical practice, this nomogram would contribute to the decision making process in the treatment of patients suffering from this form of carcinoma.
Frequency of cisplatin administration in patients presenting with advanced urothelial carcinoma in the community.
Authors: Sonpavde Guru , Watson Deidre , Tourtellott Marcia , Higgins Erica , Cowey Charles Lance , Hellerstedt Beth A. , Hutson Thomas E. , Zhan Feng , Vogelzang Nicholas J. 
Published: February 2017

285 Background: Renal dysfunction, poor performance status, advanced age, and comorbidities may preclude standard frontline cisplatin-based chemotherapy in patients with advanced urothelial carcinoma (UC). We hypothesized that cisplatin-based regimens are not administered to the majority of patients in the community. A study was conducted to identify chemotherapy regimens administered by medical oncologists in community-based cancer centers. Methods: A retrospective study was conducted on patients with AJCC stage 4 UC presenting from 2001 to 2010 to Texas Oncology Cancer Centers. The frontline chemotherapy regimen was classified as cisplatin-based, carboplatin-based, non-platinum based and no chemotherapy administered. The association of age with administration of cisplatin was studied. Results: A total of 298 patients with stage 4 disease were eligible for this analysis out of 3574 patients with UC in this database. Of the 298 patients, 197 (66.1%) were male, the median age was 70 years (range 28-97), and the primary sites of disease were bladder (243, 81.5%), renal pelvis (41, 13.8%) and ureter (14, 4.7%). The regimens administered were cisplatin-based in 107 patients (35.9%), carboplatin-based in 81 (27.2%), non-platinum in 25 (8.4%), no chemotherapy was administered in 71 (23.8%) and data were not available in 14 patients (4.7%). Cisplatin administration appeared more common in patients aged ≤70 years (62 of 150, 41.3%) as opposed to >70 years (45 of 148, 30.4%), p=0.05. Non-cisplatin regimens or no chemotherapy were trending to be more commonly administered to patients >70 years (64.2 vs. 54.7%, p=0.10). Limitations of a retrospective database study apply and the reasons for not administering cisplatin are unclear. Conclusions: Cisplatin-based chemotherapy was administered to 35.9% of patients presenting with AJCC stage 4 UC to community cancer centers. Given that the majority of patients may not be cisplatin-eligible or candidates for chemotherapy, this population has a significant unmet need. Drug development focused on single agent therapy with tolerable, convenient and efficacious agents or combination regimens without a cisplatin backbone should be a priority.
External beam radiotherapy for small cell carcinoma of the urinary bladder: The Memorial Sloan-Kettering experience.
Authors: Kollmeier Marisa , Kan Chu-Cheng , Bochner Bernard , Dalbagni Guido , Bajorin Dean F. , Zelefsky Michael J. 
Published: February 2017

290 Background: To report our experience using definitive external beam radiotherapy for small cell carcinoma of the urinary bladder. Methods: We reviewed records of 17 patients (14 male, 3 female) with small cell carcinoma of the urinary bladder treated at our institution with external beam radiation therapy (median dose 64.8Gy) for small cell carcinoma of the bladder between January 1994 and June 2011. Median age was 69 years. Sixteen (94.1%) patients received neoadjuvant and/or concurrent platinum-based chemotherapy. All patients underwent pretreatment maximal transurethral resection (visibly complete (n=7); incomplete (n=10). Seven patients had radiographic or pathologic evidence of nodal spread. Patients were followed with cystoscopy and radiographic imaging post-RT. Median followup was 7 months (range, 2-161 mos). Acute (<90days) and late (≥90days) toxicity was recorded using CTCAE v 3.0. Kaplan Meier method was used for survival analysis. Results: The 2-year overall survival was 62%. Of 17 patients, 3 patients developed local recurrence (LR) with a median time to local recurrence of 19 months. Two of three patients had noninvasive LR managed with transurethral resection and had no evidence of disease at last followup. One patient with invasive LR had both LR and distant metastasis identified <3 months after RT. Four patients developed distant metastases at a median time to progression of 2.5mos in bone (n=2), lung (n=1), and retroperitoneal lymph nodes (n=1). All but one patient with distant metastases had node-positive disease at diagnosis. The 2y distant metastasis-free survival for node (-) and node (+)patients was 90% and 30% (p=0.03). Of 12 patients currently without evidence of disease, 5 have followup ≥30mos. The incidence of grade ≥2 acute and late GU/GI toxicity was 53% and 6% respectively. Conclusions: Bladder preservation therapy for small cell carcinoma is feasible with encouraging early results. Nodal disease portends a poor prognosis. Brain metastases are uncommon suggesting a limited role for prophylactic cranial irradiation. Radiation therapy with concurrent platinum-based chemotherapy was associated with a low risk of late GU/GI toxicity in our cohort.
Molecular characterization of temsirolimus-induced response in human renal and bladder cancer cell lines.
Authors: Merseburger Axel S. , Kramer Mario W. , Tezval Hossein , Kuczyk Markus , Serth Juergen 
Published: February 2017

295 Background: Targeted therapies like mTOR inhibition is a clinically esthablished treatment modality for advanced renal cell cancer (RCC). We hypothesize that common elements of molecular signalling exists in RCC and transitional cell carcinoma of the bladder (TCC) that could provide a rational of the usage of this novel compound in human TCC. Therefore the goal of this investigation was to measure the in vivo and in vitro effect of temsirolimus/CCI-779 on human RCC and TCC cell lines on the molecular level. Methods: For in vivo experiments 3 RCC (786-O, A498, ACHN) cell lines and 7 TCC (T24, 5637, RT112, EJ-28, CLS-439, HB-CLS-1, HB-CLS-2) cell lines were compared. Effect of temsirolimus/CCI-779 was measured by real time impedance analysis (XCelligence, Roche). Following mRNA isolation microarray based mRNA expression analysis with 45.015 oligoprobes (G4112F, Agilent Technologies) was performed for molecular comparison of RCC and TCC cell lines. Expression patterns of 15 pathways were analyzed using the statistical software R (2.12.0) and the LIMMA package. Results: RCC and TCC cell lines demonstrated dose dependent inhibition of cellular growth with IC50 values of 10-20nM of temsirolimus/CCI-779 as measured by quantitative real time impedance analysis. Furthermore six out of 15 pathways including the mTOR and VEGF signalling were found with similar expression patterns following treatment with CCI-779 in both tumor entities. Conclusions: In vivo and in vitro analysis of temsirolimus mTOR inhitibtion on human bladder cancer cell lines support the hypothesis that a common molecular architectur exists in both tumor entities suggesting inhibition of mTOR in TCC as a possible target for further experimental therapeutic studies.
Outcomes of radical cystectomy for micropapillary urothelial carcinoma at the University of Southern California.
Authors: Fairey Adrian Stuart , Daneshmand Siamak , Schuckman Anne , Leiskovsky Gary , Djaladat Hooman , Cai Jie , Miranda Gus , Skinner Eila C. 
Published: February 2017

300 Background: The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival. Methods: A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1681 patients underwent radical cystectomy and extended pelvic lymph node dissection for primary bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized according to the WHO/ISUP 1998 classification as urothelial carcinoma (UC; n=1648) or MUC (n=33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. Results: The median follow-up duration was 10 years (range, 0 to 25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1-3: 2% versus 9%, p=0.03) and pathologic (pTanyN1-3: 23% versus 46%, p=0.01) TNM stage, multifocality (37% versus 58%, p=0.02), and high nuclear grade (84% versus 97%, p=0.04). The predicted 5-year OS (59% and 67%, Log rank p=0.79) and RFS (67% and 58%, Log rank p=0.50) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.92, 95% CI 0.56 to 1.50, p=0.73) or RFS (HR 0.92, 95% CI 0.52 to 1.63, p=0.77). Conclusions: Outcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.