bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of prostate cancer on overall cancer stage migration over time.
Authors: Ciezki Jay P. , Reddy Chandana A. , Klein Eric A. 
Published: February 2017

35 Background: To define cancer stage migration according to year of diagnosis and type of cancer diagnosis. Methods: Cancer stage, site, and year of diagnosis information were retrieved from an academic radiation oncology center's database. The Jonckheere-Terpstra test was used to assess changes over time. Results: From 2005 to 2014, 12,807 newly diagnosed patients (pts) were seen. The distribution of pts by stage was 2% stage 0, 17% stage I, 33% stage II, 16% stage III, and 32% stage IV. The pattern of stage distribution significantly changed over time as seen in the table (p = 0.0016). For 4 of the 5 most commonly seen cancers, (female breast, lung, esophagus, head and neck, and prostate (CaP)) over time fewer late stage cancers were diagnosed or had no change in stage. The only exception was CaP, the largest number of pts (26.5% of total). In 2005, 10.76% of new CaP cases presented with stage IV disease, dipped to 4.6% in 2011, and rose to 8.47% in 2014 (p < 0.0001). The changes in stage I definition accounted for the increase seen in stage I disease, but could not account for the dip and subsequent increase in stage IV disease. Conclusions: The presentation of cancer by stage has changed over time, and it was predominately driven by CaP. The changes seen in stage IV CaP incidence in which it fell and then rose over the study period suggests that global practice changes may be present. An increased preference for active surveillance, recommendations against PSA screening, and increasing insurance deductibles may have favored a delay in treating/diagnosing CaP pts in the recent past. [Table: see text]
Examination of current Algoma District cancer program practices and local referral processes for patients with prostate cancer.
Authors: Febbraro Daniella , Spadafora Silvana 
Published: February 2017

352 Background: The Algoma District Cancer Program (ADCP) is located in Sault Ste. Marie, ON, Canada and services the needs of the 125,000 individuals residing in the Algoma District, which has an area of approximately 49,000 square kilometres. Due to its geographic isolation in Northern Ontario, maintaining standards of care can be challenging to deliver. The objective of this project is to document any improvements in the referral process and treatment of patients with prostate cancer at the ADCP since the arrival of new medical oncologists in July 2013. Methods: Patients who had been seen by a medical oncologist at ADCP from July 2013 to July 2015 were included in this study. Patient charts were analyzed in order to gather information including date of diagnosis, stage at time of referral, date of consult with medical oncologist, previous treatments trialed, and dates of treatment. Patients were divided into two groups, diagnosed prior to 2014 and after 2014, to examine progress at ADCP. Results: From July 2013 to July 2015, there were 73 patients seen by a medical oncologist at ADCP with a diagnosis of prostate cancer. Of these patients, 54 were diagnosed prior to 2014 and 19 were diagnosed after 2014. For all patients diagnosed prior to 2014, the average number of years from diagnosis to a medical oncology consult was 5.24 years, with the longest being 19 years for two patients. In comparison, for all patients diagnosed after 2014, a medical oncologist saw them only 0.26 years on average after they were diagnosed. Since 2014, lines of therapy administered after referral to medical oncology have become greater than before 2014. Specifically for stage IV prostate cancer patients, the average number of lines of therapy ordered by a medical oncologist has increased for patients diagnosed after 2014. Conclusions: Since the arrival of new medical oncologists at ADCP in July 2013, the average number of years after diagnosis that a patient is referred to the clinic has decreased, while the average lines of therapies utilized after their consult with a medical oncologist has increased, showing an improvement in both referral processes and adherence to standard guidelines in the treatment of prostate cancer patients.
Quality of life outcomes after neobladder and ileal conduit following cystectomy for bladder cancer using a validated bladder-specific instrument: A prospective multi-institutional study.
Authors: Irani Jacques , Nicolas Gaunez , Huyghe Eric , Roupret Morgan , Briffaux Raphael , Larre Stephane , Pfister Christian , Mottet Nicolas , Neuzillet Yann 
Published: February 2017

359 Background: Cystectomy followed by urinary diversion impacts significantly patients' quality of life. The aim of this study was to evaluate health-related quality of life of patients who had neobladder or ileal conduit. Methods: Eight centers participated in this prospective study that included consecutive patients. They had to complete the validated self-administered Bladder Cancer Index (BCI) and a Visual Analogic Score (VAS) preoperatively and at 6 and 12 months postoperatively. The primary outcome measure was the diversion satisfaction (VAS) at 12months. Results: Between May 2012 and November 2013 the study was proposed to 106 patients of whom 95 gave their informed consent and 71 completed their pre-operative questionnaires. No patient had neo-adjuvant chemotherapy. Patients' peri-operative characteristics by diversion procedure are reported in the table. Baseline urinary, bowel, sexual function, and body image were not different between both groups. At month 6, 58 patients completed their questionnaires (Ileal conduit 30; Neobladder 18) showing significant differences in favor of the neobladder group for body image, urinary pain (mostly because of stoma problems) and constipation, but on the other hand the ileal conduit group reported a better urinary control and less leaks (day and night). At month 12, 34 patients completed their questionnaires (Ileal conduit 19; Neobladder 15). The findings were similar to those of month 6. All patients reported a poor sexual life and the related lack of satisfaction. VAS assessing diversion overall satisfaction was not different between the groups at the 6th and the 12th month. Conclusions: Even if the results of this prospective non randomized study reflect partly the age difference between groups, they clearly show an advantage for the neobladder regarding body image and an advantage for ileal conduit regarding urinary control. In both groups, overall self-assessed satisfaction of the diversion was excellent. [Table: see text]
The risk-based STHLM3 model to improve prostate cancer testing in men 50-69 years: Further health, economic, and clinic evaluation.
Authors: Gronberg Henrik , Adolfsson Jan , Aly Markus , Nordström Tobias , Wiklund Peter , Brandberg Yvonne , Thompson James , Wiklund Fredrik , Lindberg Johan , Clements Mark , Egevad Lars , Eklund Martin 
Published: February 2017

36 Background: Prostate-specific antigen (PSA) is used to screen for prostate cancer but suffers from a high false-positive rate that translates into unnecessary prostate biopsies and over-diagnosis of low-risk prostate cancers. We aimed to develop a model for prostate cancer screening with better test characteristics than PSA. Methods: STHLM3 is a prospective, population-based, paired screen-positive diagnostic study. It investigates whether the predefined STHLM3 model, a combination of 6 plasma protein biomarkers (PSA, free-PSA, intact-PSA, HK2, MIC-1, and MSMB), genetic polymorphisms (232 SNPs), and clinical variables (age, family history, previous biopsies, DRE, and prostate volume) can substantially reduce the proportion of men biopsied while maintaining the same sensitivity to diagnose Gleason score ≥ 7 prostate cancer as PSA ≥3 ng/ml. In addition, a health economic evaluation was performed comparing the STHLM3 model with current clinical practice in Stockholm. Results: 58,818 men without prostate cancer aged 50-69, participated in the STHLM3 study, with 6,700 undergoing subsequent prostate biopsy. The STHLM3 model performed significantly better (p<0.001) than PSA for detecting GS ≥7 cancers, increasing the Area Under the Curve from 0.56 to 0.74. All variables used in the STHLM3 Model were significantly associated with Gleason score ≥7 prostate cancers (p<0.05) in a multiple logistic regression model. Using the same sensitivity as PSA ≥3 ng/ml to diagnose Gleason score ≥7 prostate cancer, the STHLM3 model reduced the number of biopsies by 32% (95% CI 24%-39%) and avoided 44% (95% CI; 35%-54%) of the negative biopsies. The number of Gleason score 6 cancers was reduced by 17% (95% CI; 7%-26%). Positive ICER for the STHLM3 model was seen in all models of the health economic analysis. Conclusions: The STHLM3 model reduces unnecessary biopsies without compromising the ability to diagnose Gleason score ≥7 prostate cancer in a cost-efficient way. This is a significant step towards personalized risk-based prostate cancer diagnostic programs. Clinical trial information: ISRCTN84445406.
Patterns of failure after radical cystectomy for pT3-4 bladder cancer: Implications for adjuvant radiation therapy.
Authors: Reddy Abhinav V. , Pariser Joseph J. , Pearce Shane M. , Weichselbaum Ralph R. , Smith Norm D. , Steinberg Gary D. , Liauw Stanley L. 
Published: February 2017

370 Background: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined using follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariable analysis for association with LF and overall survival. Results: 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 and median follow up was 11 months. On univariate analysis, margin status, pT stage, pN stage, and gender were all associated with LF (p < 0.05), however, on multivariable analysis, only pT and pN stage were significantly associated with LF (p < 0.01). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external/internal iliac LNs and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.
Neoadjuvant gemcitabine and carboplatin followed by immediate radical cystectomy for muscle-invasive bladder cancer patients ineligible for cisplatin-based chemotherapy: A propensity score-matched analysis.
Authors: Koie Takuya , Ohyama Chikara , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Hashimoto Yasuhiro 
Published: February 2017

375 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin (CDDP)-based chemotherapy. We conducted a propensity score analysis to evaluate the clinical significance of neoadjuvant gemcitabine and carboplatin (GCarbo) chemotherapy for CDDP-ineligible patients with MIBC. Methods: We enrolled 381 patients with MIBC, and retrospectively compared two cohorts of CDDP-ineligible patients with MIBC. The GCarbo cohort consisted of 63 patients, who received 2 courses of GCarbo consisting of 800 mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin with an area under the curve of 4 on day 2, prior to RC. The RC alone cohort consisted of 56 patients receiving RC without neoadjuvant or adjuvant chemotherapy. The endpoints were overall (OS), cancer-specific (CSS), and disease-free survival (DFS). The oncological outcomes were analyzed using log-rank test and multivariate Cox regression model. Results: Propensity score-matched analysis indicated 56 matched pairs from both groups. The 3-year OS rates were 77.9% for the GCarbo cohort and 50.7% for the RC alone cohort (P = 0.002). The 3-year CSS rates were 92.8% for the GCarbo cohort and 52.6% for RC alone group (P < 0.001). The 3-year DFS rates were 80.6% for the GCarbo cohort and 48.1% for the RC alone cohort (P = 0.005). Multivariate analysis revealed that GCarbo was an extremely strong predictor of improved survival. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC significantly improved OS, CSS, and DFS in CDDP-ineligible MIBC patients.
Blue-light cystoscopy’s effects on management of bladder cancer when compared to traditional white-light cystoscopy.
Authors: Mount Andrew , Williams Stephen Bentley , Dinney Colin P. N. , Grossman H. Barton , Pettaway Curtis Alvin , Chapin Brian Francis , Navai Neema , Matin Surena F. , Graber William F. , Kamat Ashish M. 
Published: February 2017

378 Background: Fluorescence cystoscopy (also known as blue-light cystoscopy (BL)) is an adjunct to white light cystoscopy (WL) and aids in visualization of tumors that may be missed with WL as well as allow more complete resection of tumors. Herein we present the impact of BL on subsequent patient management in a real world setting. Methods: A total of 116 consecutive patients who underwent simultaneous BL and WL from January 2013 through December 2014 were included in the study. Pathology and operative reports were reviewed to determine the grade and stage of the tumors and whether they were viewed under BL or WL. Results: Of the 116 patients, a total of 161 biopsies and/or transurethral resected specimens were analyzed. Of these, 46 (28.6%) lesions were seen only with BL, none were seen only with white light, 109 (67.7%) were seen with both, and 7 (4.4%) were identified via random biopsies. Of the 46 lesions seen only on BL, 17 (37%) were positive for cancer, while, of the 109 lesions seen with WL and BL, 84 (77%) were positive. Of the 17 (37%) true positive tumors seen only on BL, the stage and grades were; 5 (29.4%) low-grade Ta, 2 (11.8%) high-grade Ta, 1 (5.9%) high-grade T1, and 9 (52.9%) CIS. There were no instances of a tumor being found on WL that was not also visualized with BL. In this patient cohort, the false positive rates were 23% and 63% for WL and BL, respectively. The false negative rates were 0.9% and 2.1% for WL and BL, respectively. For the 46 (28.6%) lesions that were visible by BL, WL cystoscopy was not able to visualize 10 (21.7%) tumors visualized by BL. In addition, there was one patient who had multiple lesions sent for pathology by BL and WL, and the lesions identified by BL were of higher stage than the lesions visualized by WL. Conclusions: BL identified additional tumors that would have been missed with WL. Moreover, in patients who had tumors visualized only with BL, 11 (26.8%) were high-grade, including one (2.4%) patient with T1 tumor and 8 (19.5%) with CIS. Thus, BL identified a number of high-risk tumors, which had a significant impact on the subsequent management of patients with bladder cancer.
Integrated whole exome and RNA sequencing to reveal distinct genomic and transcriptomic landscape of upper tract urothelial carcinoma.
Authors: Faltas Bishoy , Bareja Rohan , Beltran Himisha , Cyrta Joanna , Rai Manoj Ponadka , Tagawa Scott T. , Nanus David M. , Mosquera Juan Miguel , Sboner Andrea , Scherr Douglas , Elemento Olivier , Robinson Brian D. , Rubin Mark A. 
Published: February 2017

379 Background: Upper tract urothelial carcinoma (UTUC) represents up to 10% of all urothelial carcinoma (UC). UTUC is a lethal malignancy, with nearly one half the patients dying within 5 years. Our objective was to understand the biological differences between UTUC and bladder UC.Methods: Fresh frozen chemotherapy-naïve primary tumors from nephroureterectomy cases and corresponding germline samples underwent whole exome sequencing (WES) and RNA sequencing (RNAseq). The Cancer Genome Atlas (TCGA) WES and RNAseq raw data was reanalyzed through our in-house bioinformatic pipeline to compare the mutational and transcriptomic landscape of UTUC to bladder UC. We evaluated the expression values for a set of 40 housekeeping genes between the two different datasets to exclude batch effects. We used gene set Enrichment Analysis (GSEA) to identify differentially enriched pathways in UTUC.Results: 17 tumors underwent WES, 20 RNAseq, with 11 analyzed for both WES and RNAseq. UTUC samples harbored several recurrent mutations including PIK3CA (4/17), FGFR3 (2/17), MLL2 (4/17), MLL3 (2/17), ATM 2/17). Three KRAS mutations were discovered in two patients (G12D, G12V and Q61H), which were confirmed by targeted sequencing. Frequent copy number alterations included CDKN2A/B deletions (3/17), BG4ALT3, SEMG1 and USP6 amplifications (2/17 each). GSEA analysis revealed significant enrichment of the KRAS signaling in UTUC whereas bladder UC showed an enrichment of genes involved in mTOR and E2F signaling. There were significant differences in the expression of several key DNA damage repair (DDR) pathway genes between the two entities including TP53, RAD51 and ERCC4 despite infrequent or absent mutations in these genes (q value 0.03 for DDR gene set). MSH5, a gene associated with cisplatin-resistance was the most highly ranked DDR overexpressed gene in UTUC compared to bladder UC (enrichment score = 0.8).Conclusions: This study generates a detailed genomic and transcriptomic profile of UTUC. RNAseq demonstrated a distinct pattern of DDR pathway expression in UTUC independent of genomic alterations; these findings may have important implications for platinum-based chemotherapy.
Baseline GFR and cisplatin-induced renal toxicity in urothelial cancer patients.
Authors: Tran Adrienne , Loh Janice , Ji Lingyun , Daneshmand Siamak , Schuckman Anne K. , Groshen Susan G. , Quinn David I. , Dorff Tanya B. 
Published: February 2017

380 Background: Cisplatin eligibility for clinical trials has been defined as calculated GFR > 60 mL/min due to risk of nephrotoxicity in patients (pts) with renal impairment. For urothelial cancer (UCa), substitution of cisplatin compromises outcomes. We evaluated change in GFR in pts treated with cisplatin despite baseline GFR < 60 to determine risk of nephrotoxicity. Methods: 150 USC pts were identified who received systemic therapy for UCa from 2009 to 2014. Creatinine and weight values closest to treatment start and finish were used for calculation of GFR using the Cockcroft-Gault formula. Wilcoxon rank-sum tests and analyses of variance (ANOVA) were used to compare GFR percent change by age ( < 75 vs > 75 years), pre-treatment GFR ( < 60 vs > 60), therapy setting (neoadjuvant, adjuvant, or metastatic), primary disease site, and comorbidities (diabetes, hypertension, hyperlipidemia). Log-rank tests and Cox regression models were used to examine the association between overall survival (OS) and age or GFR. Results: 114 received cisplatin-based therapy at least once; 26 in the neo-adjuvant setting, 27 adjuvant, and 61 for metastatic disease. GFR could be calculated pre- and post-treatment for 81 pts; lowest GFR in pt receiving cisplatin was 25.5 mL/min. Median GFR change was -1.6% (range: -50% ~ 49%) for pts with pre-treatment GFR < 60 compared to -10.9% (range -72%, 135%) for pts with pre-treatment GFR > 60 (p = 0.17). Treatment setting (neo-adjuvant, adjuvant, or metastatic) had significant association with GFR change (p = 0.027). Median (range) of GFR change for the neo-adjuvant setting, adjuvant setting and metastatic setting was 4.6% (95% CI -32%, 90%), -5.8% (95% CI-39%, 20%), -11.9% (95% CI -72%, 135%), respectively. Age, primary disease site, diabetes, hypertension and hyperlipidemia were not associated with GFR change. Univariate analysis showed an association between GFR > 60 at stop of treatment with worse OS (p = 0.087) in metastatic pts. Conclusions: Our data support the hypothesis that UCa pts with GFR < 60 do not experience a greater decline in renal function after cisplatin treatment compared to patients with GFR > 60. If validated, this may extend the option of cisplatin-based therapy to previously ineligible pts.
A phase 2 study of the Aurora A kinase (AAK) tyrosine kinase inhibitor (TKI) alisertib (MLN8237) in patients (pts) with pretreated urothelial cancer (UC).
Authors: Necchi Andrea , Raggi Daniele , Lo Vullo Salvatore , Mariani Luigi , Giannatempo Patrizia , Calareso Giuseppina , Togliardi Elena , Nicolai Nicola , Perrone Federica , Pelosi Giuseppe , Salvioni Roberto , De Braud Filippo G. 
Published: February 2017

382 Background: Progress in developing effective salvage therapies for UC is warranted. AAK overexpression has been described in UC and spindle checkpoint (SC) dysregulation is a common feature. Alisertib is an orally available, selective TKI of AAK. Methods: A single-group, Ph2 trial was conducted with Alisertib 50 mg orally BID for 7 days, with 14d rest until disease progression (PD) (NCT01653028). The primary endpoint was RECIST 1.1 objective response-rate (ORR), and ≥ 3/20 responses were required (H0 ≤ 5%, H1 ≥ 20%, α = 5%/β = 20%) to move to a randomized trial of paclitaxel plus either Alisertib or placebo. Eligibility included failure of ≤ 2 platinum-based regimens. Cox regression analyses were done. Targeted sequencing of pts is being performed through the Ion AmpliSeq Comprehensive Cancer Panel (Life Technologies). Results: From 10/2014 to 04/2015, 22 pts were enrolled (20 evaluable for response), 8 (36.4%) in 2nd line and 14 (63.6%) > 2ndline. 8 (36.4%) had an ECOG-PS 1-2, 3 (13.6%) had Hb < 10mg/dl, 9 (40.9%) had liver metastases. 2 PR (ORR: 10%), 7 stable disease (SD) and 11 PD were recorded. Median FUP was 6.3 mos (IQR: 4.5-8.0). 6m-PFS was 18.2% (95%CI: 7.5-44.1), including 2 pts with 9.7 and 9.5 mos FUP (still ongoing, both > 2nd line). Median PFS was 1.8 mos (IQR: 1.3-3.4), but median OS was not reached (6m-OS: 63.6%, 95%CI: 46.4-87.3). Hb < 10gr/dl was significantly associated with shorter PFS and OS multivariably (p = 0.031 and p = 0.033). AAK-IHC expression did not correlate with outcome. Tissue of pt with 9.7 month SD harbored a missense mutation of mTOR (E1813D*) and the nonsense mutation Q527STOP* of TSC1, together with HER3 and TAF1Lmissense mutations. Grade 3-4 adverse events (AE) were: 54.5% alopecia, 41% mucositis, 36.4% fatigue, 18% neutropenia (14% febrile neutropenia). There were 2 treatment-related deaths (septic shock). Conclusions: Preliminary data suggest the possibility for sustained disease control in about 20% of pts, including very long term PR/SD. Hb ≥ 10 and mutations of TSC1/mTOR (TAF1L?) might be the clinical and biological markers for patient enrichment design with SC inhibitors like Alisertib, although the incidence of AE is a major concern. Clinical trial information: NCT01653028.