bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testosterone kinetics after proton therapy for low- and intermediate-risk prostate cancer.
Authors: Nichols Romaine Charles , Morris Christopher G. , Hoppe Bradford S. , Henderson Randal H. , Mendenhall William M. , Li Zuofeng , Williams Christopher R , Costa Joseph A , Harris Stephanie , Mendenhall Nancy Price 
Published: February 2017

237 Background: Evaluate long term changes in serum testosterone levels in patients with low and intermediate risk prostate cancer treated with proton therapy (PT) on two prospective clinical trials. Methods: Between August, 2006 and October, 2007, 171 patients with low and intermediate risk prostate cancer were enrolled and treated on the University of Florida Proton Therapy Institute institutional review board (IRB) approved PR01 and PR02 protocols. Of the 171 patients, 20 were excluded for having received hormonal therapy prior to PT. The pretreatment serum testosterone level was available for 149 of the remaining 151 patients. These 149 patients were included in the present study. Proton doses ranged from 78 Cobalt Gray Equivalent (CGE) to 82 CGE to the prostate using passively scattered protons. No patient underwent pelvic nodal irradiation. Results: The median baseline serum testosterone level was 358ng/dL (range 112 to 791ng/dL). Immediately after completion of PT, median serum testosterone was 365ng/dL which was not significantly different from the pre-PT level (p=0.2039). Subsequent median testosterone levels with associate P-Values are shown in the Table. At no point in the 60 month follow up period was the median serum testosterone value significantly different from the baseline value. Conclusions: Conformal proton therapy to the prostate, as delivered using the University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect serum testosterone levels within 60 months after PT. [Table: see text]
Generation of virtual control groups for single-arm prostate cancer (PCa) adjuvant trials.
Authors: Jia Zhenyu , Lilly Michael B. , Koziol James A. , Ruckle Herbert , McLaren Christine E. , Ahlering Thomas , Skarecky Douglas , Mercola Dan 
Published: February 2017

239 Background: It is difficult to construct a control group for trials of adjuvant Rx of PCa after radical prostatectomy (RP) due to ethical issues, patient acceptance. We present an algorithm involving 8 regression models to generate virtual control groups based on the Kattan post-prostatectomy nomogram. Methods: The online Kattan nomogram gives the probability of being progression-free at 2, 5, or 7yr after RP without adjuvant Rx. For each subject we estimate the progression-free survival (PFS) from these data by applying 8 models that use curve fitting and estimation of time to relapse. The models estimated time to 60%, 65%, . . . 95% chance of relapse for each subject. To prepare a virtual control group for a single-arm adjuvant Rx trial, the predicted PFSs generated from the optimum model are compared with the observed PFSs by the logrank test. Results: The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx. The optimum model depended on the clinical features of the test population. Higher relapse risk required a higher stringency model. The algorithm was validated with an independent dataset of 155 post-RP patients. When analyzed by the optimum model there was high correlation between the group observed, predicted PFSs (p = 0.792 for no difference). We created a virtual control group for pts on a Ph II trial of adjuvant chemohormonal Rx post RP. The observed PFSs for these subjects were significantly longer than the PFSs predicted by the new algorithm, indicating that the adjuvant Rx is highly effective in prolonging PFS after RP in pts at high risk for PCa recurrence. This was confirmed by comparing observed PFSs with PFSs of a matched historical group. Conclusions: The algorithm can accurately generate control groups for single arm adjuvant Rx trials for PCa, facilitating development of new therapeutic strategies.
The effects of age, stage, treatment, and Charlson comorbidity index (CCI) on quality of life after prostate cancer diagnosis in a single cohort.
Authors: Cross Deanna S. , Islam Rezwan , Mullins C. Daniel , Hussain Arif , Jacobson Crystal , Foth Wendy , Ritter Mark A. 
Published: February 2017

242 Background: Long term quality of life after diagnosis of prostate cancer (PC) is an important factor in determining treatment success and satisfaction. Here we investigate the quality of life in a rural cohort of individuals treated for PC within a single institution. Methods: The Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Short-Form 36 (SF 36) were completed by a rural population based cohort diagnosed with prostate cancer between January of 2005 and December of 2010, enrolled in a population based biorepository. Medical records were interrogated electronically for information such as age at treatment, stage, CCI, and first course of treatment. Results: Of the 173 individuals within the cohort, we received 95 completed survey instruments. No differences in age group, stage at treatment, or treatment type between individuals who completed the survey and those who did not were observed. Median summary score for the sexual domain was 10 (min -6 max 77), median summary score for urinary domain was 85 (min 36 max 100), and median summary score for the bowel domain was 95 (min 68 max 100). Median physical health score was 80 (min 20 max 100) and median general health score was 67 (min 20 max 100). Overall satisfaction score was 75 (min 25 max 100). Scores for bowel and urinary function were not significantly associated with treatment, age, CCI, or stage at diagnosis. For the sexual domain, individuals with hormonal treatment scored worse than other treatments (ttest p=0.05). Overall physical health was associated (anova, p<=0.05) with treatment, age, CCI, and stage. In a multivariate model only treatment and an interaction term with treatment and CCI were significant. Satisfaction score varied with treatment, individuals who received radiation treatment had a higher mean satisfaction score (87 vs 68 for the other groups ANOVA p=0.03). Conclusions: The treatment for prostate cancer affected an individual's quality of life in the domains of physical function, and sexual health. Treatment also affected satisfaction score regardless of age or stage at diagnosis.
Rectal dose-volume differences for scanning proton beam therapy with or without an endorectal balloon for the treatment of prostate cancer.
Authors: Desai Anand , Stoker Joshua B. , Wages Cody A. , Zhu X. Ron , Lee Andrew 
Published: February 2017

243 Background: Endorectal balloons (ERB) are routinely used in proton radiation for prostate cancer (PCa). The dosimetric implications, however, in conjunction with scanning proton beam therapy (SPT) have not been studied. We sought to describe dose-volume values with the use of an ERB vs no ERB for SPT for PCa. Methods: We analyzed 10 patients with localized PCa. Each patient underwent two CT simulations, one with a water-filled ERB (50-60 ml) and one with no ERB. For 8 patients, the prostate and proximal 1 cm of the seminal vesicles was the clinical target volume (CTV), with the prostate only as CTV for 2 patients. We defined 3 structures: rectum (R), anterior rectal wall (ARW) as a 3 mm rim of the anterior half of the rectum, and AR-CTV as the ARW only on slices with a contoured CTV. SPT plans were created in both cases for each patient, with the creation of a scanning target volume (STV), which expanded the CTV by 6 mm in all dimensions except 4 mm posteriorly and 12 mm laterally. Two opposed lateral beams were used to plan to the STV. Total dose was 78 Co-60 Gy equivalent in 39 fractions, to cover 95% of the STV. RBE was 1.1. We compared the dose-volume values for the R, ARW, and AR-CTV between the two arms. Results: The ERB significantly increased the R volume for all cases (61 ± 11 ml vs 105 ± 10 ml (p<0.01)). Rectal volumes radiated for all cases: V10, 55%; V50, 23%; and V70, 11%. The ERB significantly decreased the R volume radiated for all dose levels V5-V82 (p<0.05). The absolute difference was larger at low dose levels (8% at V10) and intermediate dose levels (5% at V50) compared to high dose levels (3% at V70). For the ARW, the ERB did not significantly change the volume radiated at any dose level. For the AR-CTV, the ERB significantly decreased the volume radiated for dose levels V20-V60 (p<0.05). Conclusions: The ERB provided a significant decrease in R volume radiated at all dose levels, and significantly decreased the AR-CTV volume, which represents a high risk volume, radiated at intermediate dose levels. Rectal doses with SPT, however, were low whether using an ERB or not. In the setting of the low rectal doses delivered, further study regarding the clinical benefit is warranted.
Evaluation of a novel irreversible pan-HER inhibitor in bladder cancer models.
Authors: Grivas Petros , Karatsinides Andreas , Day Kathleen C. , Kunju Priya , Paul Alyssa , Shakir Nazia , Keller Evan T. , Hussain Maha , Day Mark L. 
Published: February 2017

253 Background: Human epidermal receptors (HER) are overexpressed and HER signaling is biologically relevant in bladder cancer and may mediate chemotherapy resistance. Dacomitinib is a novel, potent, irreversible pan-HER inhibitor with activity against several solid tumors, currently in a phase III clinical trial in NSCLC. We hypothesized that dacomitinib has antitumor activity in bladder cancer models. Methods: Expression level of EGFR and HER2 protein was measured semi-quantitatively in 8 bladder cancer cell lines. We treated UM-UC-3, UM-UC-6, UM-UC-9 cell lines with dacomitinib (1nM-10uM) for 24-72 hours, and measured cell viability, proliferation, apoptosis, and cell cycle effects. Correlations between dose and cell viability were measured by two-way ANOVA (GraphPad Prism 5.0). We injected age-matched male NOD/SCID mice SC with 1x106 UM-UC-6 and UM-UC-9 cells, respectively, generating xenografts. Mice were randomized and treated with dacomitinib, 6mg/kg p.o. daily, starting 1 day or 1 week after cell injection; controls were treated with vehicle. Mice were monitored daily, weighed weekly, sacrificed at 4 weeks and tumors weighed. Results: In vitro, significant cytostatic effect was noted with as low as 50nM in UM-UC6 cells and 100nM in UM-UC9 cells. UM-UC3 cells did not exhibit cytostatic effect even with 1000nM, corresponding to differential target protein (HER) expression. Dacomitinib (2uM) induced apoptosis (UM-UC-6), and G1 cell cycle arrest in both cell lines. These effects corresponded to dacomitinib-mediated inhibition of EGFR, ERK, AKT phosphorylation. In vivo, xenograft weights in both cell lines were significantly lower in dacomitinib-treated mice vs control (p<0.001), corresponding to pharmacodynamic effects (decreased E-cadherin, p-EGFR, p-ERK, mitotic count). Dacomitinib 6mg/kg p.o. daily resulted in significantly lower tumor weights vs lapatinib 50 mg/kg p.o. daily in UM-UC-9 xenograft model (p=0.0052). Conclusions: Dacomitinib demonstrated single-agent activity in bladder cancer cell lines and xenografts. Induction of apoptosis and G1 phase arrest are the suggested mechanisms for anti-tumor activity. Further investigation of this inhibitor in bladder cancer models is being pursued.
Cost-effectiveness analysis of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.
Authors: Stevenson Scott M. , Deibert Chris M. , McKiernan James M. 
Published: February 2017

258 Background: Neoadjuvant chemotherapy (NAC) is an option for treating muscle invasive bladder cancer (MIBC), and is reported to increase survival for patients who obtain a complete response with no residual disease at the time of radical cystectomy (RC). However, NAC has additional costs and side effects. We seek to compare the effectiveness of NAC and RC for MIBC and to report the increase in cost and change in quality adjusted life years (QALYs) for patients who receive NAC. Methods: Patients were retrospectively reviewed from 2004 to 2011 to identify those with MIBC (stage T2 to T4a) who were treated with either RC alone or NAC. Costs for hospital admissions and surgical procedures were estimated from the Healthcare Cost and Utilization Project (HCUP) using specific Diagnosis Related Groups (DRG) or ICD-9-CM identifiers. Costs for outpatient procedures and urology visits were obtained from internal billing departments, and costs for chemotherapy were estimated based on published literature. QALYs were calculated based on clinical events and standard utility weights obtained from the medical literature. Results: 186 patients were identified, of which 64% received RC alone and 36% received NAC. Overall median survival for the RC group and the NAC group was 26.6 months and 38.3 months, respectively (p=0.056). Overall median survival in QALYs for the RC group and NAC group was 21.9 months and 32.9 months, respectively (p=0.057). 5-year overall survival in QALYs was 21.8% for the RC group and 39.8% for the NAC group (p=0.039). The mean total cost of treatment during follow-up for the RC and NAC groups was $42,890 and $52,336, respectively. The absolute increase in cost of therapy for patients receiving NAC compared to RC alone was $9,712. The increased cost per additional QALY gained for patients receiving NAC was $10,317. Conclusions: Neoadjuvant chemotherapy results in an increased overall survival for patients with muscle invasive bladder cancer. This treatment is associated with an increased cost of approximately $10,000/QALY gained. This cost effectiveness compares favorably with other cancer therapies.
Relationship of ERCC1 genotype variant with mRNA expression and ERCC1 protein levels in advanced urothelial carcinoma (UC).
Authors: Guancial Elizabeth A. , Werner Lillian , Bellmunt Joaquim , Nikitas Nikitas , Stack Edward C. , Lis Rosina , Signoretti Sabina , Loda Massimo , Regan Meredith M. , Park Rachel S. , O'Brien Robert , Berman David M. , Bamias Aristotelis , Rosenberg Jonathan E. 
Published: February 2017

260 Background: DNA repair factors may be predictive for response to chemotherapies that produce DNA damage. While low ERCC1 protein and mRNA levels have been reported as associated with improved outcomes in metastatic UC patients treated with platinum-based chemotherapy, the relationship between genotype, mRNA expression, and protein level is unknown. The ERCC1 germline 19007C>T single-nucleotide polymorphism (SNP) is functionally associated with reduced translation of ERCC1 mRNA. We investigated the relationship between ERCC1 germline SNP, ERCC1 tumor mRNA and protein expression, in a cohort of patients with advanced UC who received first-line, platinum-based chemotherapy. Methods: A cohort of clinically annotated, uniformly-treated advanced UC patients with FFPE primary tumor tissue available was identified through the Hellenic cooperative Oncology Group (HECOG) (N=93). Genomic DNA extraction, nested PCR, and restriction fragment length polymorphism techniques for the 19007C>T SNP were performed to identify C/C, C/T and T/T genotypes. ERCC1 mRNA expression was interrogated using Nanostring nCounter profiling. IHC analysis was performed on tissue arrays using an ERCC1 antibody. Percent of positive nuclear staining was categorized as quartiles using previously identified cut-points. Results: ERCC1 C/T genotype was identified in 30/61 samples (49%) and T/T in 14/61 samples (23%). In 54 patients with both SNP and mRNA data available, T/T genotype was associated with the highest level of mRNA expression, followed by the C/T genotype (p=0.04). Neither ERCC1 genotype (N=44) nor ERCC1 mRNA expression (N=54) was associated with ERCC1 protein expression as measured by IHC (p=0.52 and p=0.13, respectively). Conclusions: ERCC1 19007C>T is associated with increased ERCC1 mRNA expression. However, neither genotype nor mRNA are surrogates for ERCC1 protein detected by IHC in advanced UC tumors. This suggests that while genotype influences mRNA expression of ERCC1, the use of the nucleotide excision repair pathway as a predictive biomarker of platinum-sensitivity may be more complex than previously appreciated and require the integrative use of proteomics, genomics and epigenomics.
Pathologic response rates between gemcitabine-cisplatin (GC) and methotrexate, vinblastine, doxorubicin hydrochloride, and cisplatin (MVAC) neoadjuvant chemotherapy in muscle-invasive urothelial cell carcinoma of the bladder.
Authors: Wright Jonathan Lawrence , Lee Franklin , Harris William Proctor , Cheng Heather H. , Zhao Song , Champion Thomas , Gore John L. , Dean James , Porter Michael P , Yu Evan Y. 
Published: February 2017

267 Background: Neoadjuvant chemotherapy for muscle invasive urothelial carcinoma (UC) of the bladder is associated with higher rates of pathologic complete response (CR) and improved disease-specific survival compared to those treated with radical cystectomy (RC) alone. Two standard regimens used are (1) gemcitabine and cisplatin (GC); and (2) methotrexate, vinblastine, adriamycin, and cisplatin (MVAC), with debate on whether there is a difference in clinical efficacy. In this analysis, we compare the pathologic outcomes at cystectomy between neoadjuvant GC and MVAC treatment. Methods: Data was retrospectively collected on patients with T2-T4 UC of the bladder who underwent RC between Sept 2003 and December 2011 at the University of Washington. Clinical and pathologic factors were recorded along with neoadjuvant chemotherapy and comorbidities. Pathologic outcomes included those with CR (pT0) and near CR (nCR = pT0/Ta/Tis). Odds ratio (OR) for CR and nCR were calculated using multivariate logistic regression adjusting for demographic (age, gender, race), medical (creatinine, diabetes mellitus, cardiac disease) and clinical factors (clinical T stage, prior BCG therapy, complete tumor debulking prior to chemotherapy). Results: A total of 78 patients received GC or MVAC neoadjuvant chemotherapy followed by RC, including 46 who received GC and 32 who received MVAC. There was no difference in gender, renal function, cardiac disease or clinical stage between the two groups. Patients over 70 years of age primarily received GC (17/18). CR was achieved in 30% and 25% (p = 0.15) of GC and MVAC patients, respectively (multivariate OR 0.42, 95% CI 0.11-1.63). nCR was more common in those receiving GC (50% vs. 38%, p = 0.04) although non-significant in the multivariate model (OR 0.30, 95% CI 0.07-1.16). Conclusions: We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of bladder cancer patients. These observations support the use of GC as an alternative regimen in the neoadjuvant setting.
Muscle invasive bladder cancer in the elderly: Treatment and prognosis in a prospective cohort study.
Authors: Slater Stephanie , Wright Thomas , Devall Adam , Pirrie Sarah , Billingham Lucinda , Cheng K K , Zeegers Maurice , Bryan Richard , James Nicholas David 
Published: February 2017

275 Background: As the prevalence of bladder cancer increases amongst the elderly, nearly 1 in 3 muscle invasive bladder cancer (MIBC) cases are in patients aged >80 years (Taylor JA, III, Kuchel GA. Nat Clin Pract Urol 2009; 6(3):135-1440). However, radical cystectomy remains as the gold standard treatment for MIBC (Yafi FA, Kassouf W. Can Urol Assoc J 2009; 3(5):409-412). In this study we examined treatment patterns and outcomes patients aged >80 years from a prospective study of bladder cancer. Methods: The Bladder Cancer Prognosis Programme (BCPP) is a 5 year prospective cohort study (2006-2011) with 1191 patients confirmed as having newly-diagnosed bladder cancer. Recruitment took place at 9 urological centres within the West Midlands region, UK. From this cohort we identified 67 patients aged >/=80 years with newly diagnosed MIBC. Study records include overall and disease specific survival, time to disease recurrence and radiotherapy (RT) treatment. Simple descriptive statistics were used to describe the outcomes. Results: This cohort consisted of 46 male and 21 female patients with a median age of 83 (IQR=81, 87; range=80, 94). Only 4 (6%) patients underwent cystectomy and 36 (53%) underwent RT. Median survival data is summarised in the table below. Conclusions: Despite guidelines, practising urologists in the West Midlands region do not offer cystectomy to the vast majority of MIBC patients aged >80 years. Furthermore, in this patient cohort, OS was shorter than BCSS by 10 months, suggesting that quality of life after diagnosis will be far more important than cure rates due to deaths from other causes. Of particular note is that the group receiving RT had longer OS and BCSS than the rest of the cohort. This indicates that RT could be a far more appropriate standard of care in the elderly than surgery, which is clearly of limited applicability in this growing demographic. Clinical trial information: 06/MRE04/65. [Table: see text]
Thromboembolic events with cisplatin-based neoadjuvant chemotherapy for transitional cell carcinoma of urinary bladder.
Authors: Botten Joanne , Sephton Matt , Tillett Tania , Masson Susan , Thanvi Narottam , Herbert Christopher , Hilman Serena , Rowe Edward , Gillatt David , Persad Raj , Whittlestone Tim , Bahl Amit 
Published: February 2017

277 Background: Cancer is associated with an increased risk of venous and arterial thrombo-embolic events (TEEs), including deep vein thrombosis, pulmonary embolism, cerebrovascular accident and unstable angina/myocardial infarction. Several factors are known to influence the incidence of TEEs including chemotherapy agents, particularly cisplatin. Czaykowski et al reported 12.9% of patients receiving multiagent cisplatin based chemotherapy for transitional cell carcinoma between 1986 and 1996 developed TEE. Moore et al found that the rate of TEE in a similar cohort of patients receiving the same treatment to be 18.2% (6/33 patients). Methods: Retrospective case note review from an electronic database of patients allocated a cisplatin based neo-adjuvant chemotherapy regimen for transitional cell carcinoma of the bladder between April 2009 and April 2012. TEE was recorded as a chemotherapy related event if it occurred between the first dose of cisplatin and 4 weeks after the last administered dose. Results: 44 received treatment in the neoadjuvant setting. 11 out of 44 patients (25%) receiving neo-adjuvant chemotherapy developed TEE. 7 out of these 11 patients were male, 4 were female. 9 of the 11 TEEs (82%) in the neoadjuvant setting were arterial or peripheral arterial thrombi, including pulmonary emboli and thrombi within the aorta, left ventricle and iliac arteries. 5 of these thrombi were asymptomatic and only discovered on routine scanning. 2 out of the 11 TEEs were leg deep vein thromboses – both of which were symptomatic. 64% of TEEs occurred after the second cycle of cisplatin, the remainder after the third cycle. Conclusions: Neo-adjuvant chemotherapy is being adopted as the standard of care for patients with muscle-invasive TCC of bladder. The higher rate of TEE in our series compared to previous publications probably reflects the asymptomatic TEE being diagnosed on scans done for assessing response to chemotherapy. The significant rates of TEEs in this setting highlights the need to consider this complication as it may have a bearing on outcome from treatment, in particular delay in radical cystectomy.