bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in survival among non-urothelial bladder cancers: Analyses of SEER 1988-2008.
Authors: Aragon-Ching Jeanny B. , Henson Donald 
Published: February 2018

425 Background: Non-urothelial cancers of the urinary bladder are rare, and typically < 5% incidence. They are generally considered more aggressive without clear guidelines for treatment. Methods: Incident cases of non-urothelial bladder cancers that included squamous cell carcinoma, adenocarcinoma, small cell carcinoma and sarcomas were identified in the SEER (Surveillance, Epidemiology, and End Results) Database. Demographic information, pathologic characteristics and 5-year disease-specific survival were calculated and compared using multivariate Cox regression and Kaplan-Meier curves. Results: A total of 235,537 incident cases of bladder carcinomas were identified in the years 1998 – 2008, of which 3096 cases were squamous cell carcinoma, 1175 were neuroendocrine carcinoma where small cell carcinomas made up the majority with 859 patients, 671 was comprised of adenocarcinomas, representing 0.28%, and sarcomas were 88 cases, making up 0.03% of all cases combined. The majority of patients were White (90%) although more African-Americans (15%) were seen with adenocarcinoma. The table shows the number of cases and 5-year survival according to stage. Median survival was greatest for adenocarcinoma at 179 months with a 5–year survival rate of 58%, followed by sarcomas with a median survival of 23 months, with a 5-year survival rate of 47%, followed by squamous cell carcinomas with a median survival time of 15 months and a 5-yr survival rate of 37% and the least favorable survival was for small cell carcinoma, 17 months median time, with a 5-yr survival rate of 31%. Conclusions: Non-urothelial cancers have a uniformly less favorable survival compared to urothelial cancers, highlighting the need for improved therapeutic strategies in these cohorts of patients. [Table: see text]
A genomic classifier for identifying a neuroendocrine-like bladder cancer subtype.
Authors: Wright Jonathan L. , Dall'era Marc , Bivalacqua Trinity , Seiler Roland , Liu Yang , Gibb Ewan , Wang Natalie Qiqi , Erho Nicholas , Alshalalfa Mohammed , Davicioni Elai , Efstathiou Jason A. , Douglas James G. , Boormans Joost L , Van Der Heijden Michiel Simon , Lotan Yair , Black Peter C. 
Published: February 2018

440 Background: Neuroendocrine (NE) carcinoma is a rare and aggressive variant of muscle invasive bladder cancer (MIBC). Molecular subtyping studies found 5-15% of bladder tumors had transcriptome profiles consistent with NE carcinoma but lacked NE histology (Robertson 2017, Sjödahl 2017). Identifying NE variants may have prognostic implications and modify treatment recommendations. In this study, we present a robust genomic classifier trained to identify NE carcinoma. Methods: Transcriptome-wide expression profiles were generated for 576 MIBC patients collected from seven institutions. Model training included profiles generated from TURBT and RC specimens from 320 patients prior to treatment with NAC or chemo-radiation. The validation cohort consisted of 256 RC specimens (no prior systemic treatment). Using 10 MIBC-related gene sets, a GLMNET model was built to predict patients with a NE carcinoma expression profile. Uni- and multi-variable survival analyses were used to characterize outcomes of the predicted NE tumors. Results: In the training set, hierarchical clustering using a panel of 54 genes showed a cluster of 17 patients (5.3%) with a NE carcinoma expression profile. These patients had significantly worse 1 year progression free survival (65% vs 82% for NE vs overall; p = 0.046). In the validation set, 7 tumors were classified (2.7%) as NE with 4 (57%) patients dying from the disease at 1 year after RC. Within 3 years of RC, 100% (7/7) of patients with NE tumors had died. After adjusting for various clinical and pathological factors, patients with predicted NE tumors had a 6.40 increased risk of all-cause mortality (p = 0.001). Conclusions: We have developed a gene expression signature that predicts a particularly high-risk group that may need treatment intensification, alternative chemotherapy or clinical trials. Validation will be required to assess the potential clinical utility of this NE carcinoma classifier.
Outcomes in bone predominant (BP) urothelial carcinoma (UC).
Authors: Nelson Ariel Ann , Opneja Aman , Nezami Behtash Ghazi , Fu Pingfu , Dawsey Scott , Wright Matthew David , Eitman Cheryl , Kim Simon P. , Cooney Matthew M. , Grivas Petros , MacLennan Gregory , Hoimes Christopher J. 
Published: February 2018

441 Background: The clinical phenotype of BP UC includes those patients (pts) with at least as many or more bone lesions than non-bone lesions. UC molecular subtypes that may correlate with prognosis have been defined. Better understanding of the clinical BP phenotype, which might correspond to the p53-like molecular subtype, is needed. Methods: We searched our biorepository to identify pts with metastatic UC. Electronic records of identified pts were reviewed and those with accessible records who received treatment at our institution were selected. Demographic, pathologic, treatment, response, progression-free and overall survival (PFS, OS) data were recorded. Imaging was reviewed to identify non-bone predominant (NBP) or BP disease based on imaging criteria. Results: 23 NBP and 9 BP pts, (59% men) were identified. Of BP pts, 44% had bone metastatic disease present at diagnosis (dx) vs. none of the NBP. Only 8% of NBP pts developed bone metastases during their course. The median number of lines of therapy in the metastatic setting was 2 for each cohort. All BP pts received platinum therapy vs. 74% of NBP. 11% of BP pts were treated with checkpoint immunotherapy (CPI) vs. 34% of NBP. 70% of BP pts received palliative radiation (all to bone) vs. 4% of the NBP cohort. The median OS from date of UC dx was 27.5 months. There was a significant difference in OS between BP and NBP cohorts from UC dx date (16.9 vs. 30.6 months, p < 0.0001) as well as from muscle invasive bladder cancer (MIBC) dx date (15.2 vs. 22.8 months, p = 0.019), respectively. OS from initiation of 1st line treatment in the metastatic setting for the entire cohort was 12.5 months and was not significantly different between the cohorts (p = 0.633). PFS from dx of MIBC to date of 1st progression or death was not significant (p = 0.08) with median PFS of 8.4 vs. 13.6 months for BP vs. NBP cohorts, respectively. Conclusions: BP pts require more frequent palliative radiation and have shorter OS measured from time of dx, but not significantly different when measured from the initiation of 1st line treatment, compared to NBP pts. Further analysis with a larger cohort is ongoing for validation. Molecular analysis on pathological specimens is planned.
Genomic analysis of same-patient metachronous upper-tract and bladder urothelial carcinoma.
Authors: Petros Firas G. , Qi Yuan , Choi Woonyoung , Li Roger , Su Xiaoping , Guo Charles , Dinney Colin P.N. , McConkey David , Matin Surena F. 
Published: February 2018

449 Background: Despite similarities between upper-tract (UTUC) and bladder urothelial carcinoma (BUC), distinctive clinicopathologic and genomic differences are being described. We further investigate the genomic landscape of these two interrelated malignancies in same-patient metachronous (m) UTUC and BUC using next generation sequencing (NGS). Methods: Following institutional board approval, UTUC and BUC samples were obtained from patients via surgical resection or endoscopic biopsy. Tumors were macrodissected from unstained formalin-fixed, paraffin-embedded slides. Study inclusion was untreated patient samples of UTUC and/or BUC divided into 4 groups: 1) UTUC with mBUC, 2) BUC with mUTUC, 3) Synchronous BUC and UTUC, 4) UTUC with no bladder history. Exclusions were for inadequate clinical data or histological tumor purity < 30%. Whole transcriptome RNA sequencing was performed and analyzed using BASE47 panel (includes basal, luminal, p53-like and cell cycle genes). Results: A total of 95 (UTUC = 61, BUC = 34) samples from 40 patients were analyzed. UTUC samples were 33 primary ureter and 28 renal pelvis cancer. Median age was 72 years, 68% male, 76% Caucasian, 60% former smokers. Groups samples were: 1) UTUC (n = 19), mBUC (n = 12); 2) BUC (n = 12), mUTUC (n = 9); 3) Synchronous UTUC/BUC (n = 10); and 4) UTUC (n = 23). Unsupervised hierarchical clustering segregated tumors into basal-like and luminal subtypes, with 87.5% of metachronous tumors displaying conserved subtype membership. For the groups with UTUC and BUC, only 3/24 (12.5%) clusters (2 patients in Group 2, and 1 patient in Group 3) had unmatched basal/luminal subtypes. Conclusions: NGS analysis of same-patient metachronous UTUC and BUC shows that the majority stay within the same molecular subtype regardless of chronologic development or anatomic origin. Additional studies are necessary to explore differences that may occur within the subtypes, the role of methylation, and clinical correlates.
Low testosterone at first PSA failure and assessment of the risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.
Authors: Atkins Katelyn Mae , Chen Ming-Hui , Wu Jing , Renshaw Andrew A. , Loffredo Marian , Kantoff Philip W. , Small Eric Jay , D'Amico Anthony Victor 
Published: February 2018

45 Background: Low testosterone at prostate cancer diagnosis has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at first PSA failure following definitive therapy and prior to the documentation of metastatic disease has not been elucidated and was studied. Methods: Between 1995 to 2001, 58 men with unfavorable-risk prostate cancer treated on clinical trials with radiation and androgen deprivation therapy (ADT) had testosterone levels at PSA failure available. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone at PSA failure was associated with the risk of prostate cancer-specific, other-cause and all-cause mortality (PCSM, OCM, ACM) adjusting for age, salvage ADT use and known prostate cancer prognostic factors. Results: After a median follow-up of 6.68 years following first PSA failure, 31 men (53.4%) died; 10 from prostate cancer (32.3%), of which 8/11 (72.7%) versus 2/47 (4.3%) occurred in men with low versus normal testosterone at PSA failure, respectively. A significant increase in the risk of ACM (adjusted hazard ratio, AHR [2.54, 95% CI 1.04-6.21]; P = 0.04) and PCSM (AHR [13.71, 95% CI 2.4-78.16]; P = 0.003), with a reciprocal trend toward decreased risk of OCM (AHR [0.18, 95% CI 0.02-1.55]; P = 0.12) was observed in men with low versus normal testosterone at first PSA failure. Conclusions: Low testosterone at first PSA failure confers a very poor prognosis. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic prostate cancer and possibly in men with localized high-risk prostate cancer provides rationale to support their use with ADT in men with low testosterone at PSA failure in the setting of a phase II trial.
Long-term results of organ preservation rate and progression risk in high-risk non-muscle-invasive bladder cancer (NMIBC) patients treated with radiofrequency-induced thermochemotherapy effect (RITE) with the Synergo system.
Authors: Kilb Jill-Isabel , Hauptmann Arne , Wagenlehner Florian , Luedecke Gerson 
Published: February 2018

456 Background: High risk NMIBC is a dangerous BC with a challenging treatment by BCG or early cystectomy to cure. The first has bad treatment tolerance and a remission of about 35%, whereas the last offer a curing perspective of 84% with extremely bad living conditions. RITE checked prospectively the therapy in respect to organ preservation, curing rate and risk of progression over 10 years in a single institution experience. Methods: All patients were EORTC high risk NMIBC. Treatment with induction phase: 8 treatments weekly with 2x40 mg Mitomycin C, 42°C intravesically induced by RITE. Followed by a re-resection of the bladder at week 11 to ensure complete remission and maintenance with treatments every 6 weeks with 2x20 mg Mitomycin C for 6 times. Cystoscopy controls were performed first 2 years every 3 month and following in 6 month until now. Study started in 2006 ongoing until today. Results: We enrolled 67 patients (4 female, 63 male), 65.7% Cis positive rate. 85% of the patients were treated alternatively to BCG with primary RITE whereas 15% were BCG failure patients treated alternatively to indicated cystectomy. Tumor persistence at week 11 after induction therapy proven by TURB was (10/67) 14.9% resulting in early cystectomy (4/10). Mean recurrence free time 3.5 years. In case of recurrence 10.4% progressed to MIBC including 6% metastatic tumors, high risk NMIBC was observed in 6% resulting in cystectomy and low risk NMIBC recurrence was 1.5% with organ preservation. BC death rate was 1 out of 67. Incomplete treatments induced by SAE of RITE was 9%. Bladder preservation rate was 80.6% with a long-lasting effectiveness ( > 5 years) of 14/26 (53.8%). Conclusions: The RITE method is in short- and long-term manner a powerful procedure to cure and maintain a recurrence free BC status in high risk NMIBC with a very low risk for cystectomy and a minimal risk for systemic progression resulting in BC death. The organ preservation rate was achieved in 80.6% lasting for up to 11 years longest. RITE is an alternative to BCG and preferable to early cystectomy in high risk NMIBC.
Association of somatic mutational burden with depression and anxiety in patients with metastatic urothelial cancer (mUC).
Authors: Bergerot Cristiane Decat , Clark Karen L. , Bergerot Paulo Gustavo , Ashing Kimlin Tan , Hahn Andrew W , Obenchain Richard , Dizman Nazli , Hsu Joann , Philip Errol James , Loscalzo Matthew J. , Pal Sumanta K. 
Published: February 2018

471 Background: Depression and anxiety are highly prevalent in patients (pts) with genitourinary tumors, including UC (Yang et al PLoS ONE 2016). Given that mUC has a high rate of somatic genomic alterations (GAs), we sought to determine if tumor mutational burden (TMB) or specific alterations were related to the incidence of these psychiatric disorders. Methods: From a single institution, we identified consecutive pts with mUC who had comprehensive genomic profiling done in the course of routine clinical care. In a CLIA-certified laboratory, DNA was extracted from 40 microns of FFPE sections. Hybridization-captured, adaptor ligation based libraries were used to a mean coverage depth of 718X for up to 315 cancer-related genes plus introns from up to 28 genes frequently rearranged in cancer. TMB was estimated based on the cumulative number of GAs. ICD-9 diagnoses corresponding to adjustment disorder (309.28), anxiety (300) and depression (311) were derived from detailed chart review, including review of established diagnoses and medication history. Results: A total of 43 pts (74.4% M / 25.6% F) were assessed with a median age of 65.5 (range, 49-81). Formal diagnoses of adjustment disorder, anxiety and depression were noted in 16.3%, 9.3% and 7.0% pts, respectively. An average of 6.3 GAs/pt (range, 0-14) were observed over the entire cohort. The rate of GA was higher in pts with anxiety vs adjustment disorder or depression (8.5 vs 6.8 or 4.0, P=0.01). No significant difference was observed in adjustment disorder or depression based on the frequency of GAs. GAs in BAP1, PIK3CB, NOTCH1, ALK, CDH1 and FANCC were noted to be associated with higher rates of anxiety (P=0.02). Similarly, GAs in FGFR1 was noted to be associated with higher rates of depression (P=0.002) and in CHEK2 in depression and adjustment disorder (P=0.03). Conclusions: Our study represents the first pyschogenomic analysis of pts with mUC. While higher TMB has been associated with favorable prognosis (Isharwal et al EU Focus 2017), we paradoxically found this to be related to higher rates of anxiety. Our findings suggest that genomically selected subsets of patients may be prime candidates for early psychosocial screening and intervention.
Size-focality-invasion in upper tract urothelial carcinoma (SFI-UTUC): A novel imaging-based score to predict survival outcomes.
Authors: Hamilton Zachary , Haifler Miki , Krabbe Laura-Maria , Ryan Stephen , Reddy Madhumitha , Berquist Sean , Clinton Timothy N , Bloch Aaron , Field Charles , Patel Sunil , Cotta Brittney , Margulis Vitaly , Uzzo Robert , Derweesh Ithaar 
Published: February 2018

475 Background: Upper tract urothelial cell carcinoma (UTUC) is an uncommon malignancy with disparate outcomes. We developed a novel morphometric scoring system for prediction of oncologic and survival outcomes before nephroureterectomy (NU). Methods: Retrospective, multicenter analysis of UTUC patients who underwent NU after negative metastatic workup. Preoperative CT-urography was used to evaluate scores, based on 3 factors (Tumor Size, Focality, Invasion of architecture) with a score of 1-3 based on degree of each factor (total score 3-9). Primary outcome was overall survival (OS). Secondary outcomes were recurrence and recurrence free survival (RFS). Multivariable (MVA) and Kaplan-Meier (KMA) analyses were utilized. Results: We analyzed 244 patients (mean age 70.9, mean follow up 29.5 months). 61% with SFI-UTUC score 3-6 and 39% were score 7-9. No difference in age, gender, comorbid conditions, surgical approach, or complications between groups. Score 7-9 had a higher rate of pN+ disease (24.2% vs. 8.1%, p=0.002) but similar nuclear grade. All-cause mortality was higher for score 7-9 (47.4% vs. 28.9%, p=0.004). On MVA for all-cause mortality, age (OR 1.1), recurrence (OR 4.4) and score 7-9 (OR 2.0) were significant (p<0.05). KMA for OS demonstrated 5 year OS of 57.0% for score 3-6 and 34.1% for score 7-9 (p<0.01). KMA for RFS was significant for renal UTUC location with 5 year RFS of 72.3% for score 3-6 and 54.2% for score 7-9, (p<0.01). Conclusions: A novel scoring system for UTUC preoperative imaging may predict OS for tumors in renal and ureteral locations, as well as RFS for renal locations. Renal location. [Table: see text]
Transcriptome-wide analysis of alternative splicing events in bladder cancer: Novel biomarkers discovery for early diagnosis.
Authors: Jeldres Claudio , Bouchard Sabrina , Carmel Michel , Richard Patrick O , Sabbagh Robert , Bisaillon Martin 
Published: February 2018

483 Background: Cystoscopy, an invasive, painful and expensive method, is currently the main clinical tool for new diagnosis and disease recurrence detection of bladder cancer (BCa). The need for new biomarkers discovery that is costless, sensitive and specific is urgent. This project aims to study and compare alternative splicing events (ASE) in BCa tissues and normal bladder tissues and ultimately, identify specific spliced events coding for proteins detectable in urine by liquid chromatography–mass spectrometry. Methods: In this study, alterations to the global RNA splicing landscape of cellular genes were investigated in a large-scale screen from 408 BCa tissues and 19 normal tissues provided by The Cancer Genome Atlas (TCGA). Three statistical thresholds were used to determine substantial modifications. All events showing a p-value<0.05 and a level of expression ≥ 50 transcripts per million; -10 ≥ Δ percent splice index ≤10; and a q-value<0.05 were conserved. Next, mRNA expression levels between cancer and normal tissues were compared for all splicing factors and the spliceosome to determine the impact of gene dysregulation on alternative splicing events. Using multiple bioinformatic platforms such as EASANA, MultAlin, ExPasy, NLS Mapper and Pfam, splicing events responsible for significant protein structural changes between cancer and healthy tissue were selected. From this sample chosen, ASEs coding for proteins that could be detected in urine were conserved. Results: Our study identifies modifications in the alternative splicing patterns of 107 transcripts encoded by 97 genes. STRING analysis revealed that many of the gene products interact either directly or indirectly with each other (enrichment p-value = 1x10-10). 61 ASEs are causing important protein changes from which 27 can be detected in urine. Finally, 16 ASEs coding for easily recognizable peptide sequences in urine represented significant targets for potential BCa biomarkers. Conclusions: The TCGA data show the relevance to investigate alternative splicing events in bladder cancer. 16 significant events were detectable in urine and may potentially discriminate between presence or absence of bladder cancer.
Effectiveness of adjuvant radiotherapy after radical cystectomy for locally advanced bladder cancer.
Authors: Fischer-Valuck Benjamin Walker , Michalski Jeff M. , Christodouleas John Paul , Kim Eric , DeWees Todd A. , Andriole Gerald L. , Arora Vivek , Carmona Ruben , Figenshau Robert S. , Grubb Robert L. , Guzzo Thomas J. , Knoche Eric Marshall , Malkowicz S. Bruce , Mamtani Ronac , Pachynski Russell Kent , Picus Joel , Venigalla Sriram , Roth Bruce J. , Gay Hiram Alberto , Baumann Brian Christopher 
Published: February 2018

484 Background: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemo and is associated with high morbidity/mortality. Adjuvant radiotherapy (adjRT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of adjRT would improve OS in LABC in a large multi-institutional cohort. Methods: We identified ≥pT3 pN0-3, M0 LABC pts in the NCDB diagnosed in 2004 – 2013 who underwent RC +/- adjRT. AdjRT cohort included pts treated to ≥40Gy to the pelvis within 1 yr of diagnosis. Propensity matching was performed to match RC pts who received adjRT vs. those who did not. OS was calculated using Kaplan-Meier. Factors significant on univariate analysis were entered into Cox proportional hazards regression model to identify predictors of OS. Results: 15,246 RC pts were identified, with 450 (3.0%) receiving adjRT. Median OS was 23.0 mo (95% CI, 22.4-23.6) for RC vs. 19.7 mo (95% CI, 17.7-21.7) for adjRT [Log-rank P = 0.002; Wilcoxon P = 0.862]. Propensity score matching on demographic, clinical, & treatment variables yielded 742 pts (371 in each group). In the matched cohort, OS was 17.1 mo [95%CI, 14.5 - 19.6] for RC vs. 20.1 mo [95% CI, 17.8– 22.5] for adjRT [Log-rank P = 0.044]. On MVA in the matched cohort, factors predictive of OS were sex, pT stage, pN+ status, surgical margin status, number of nodes removed, adjRT, & chemo (p < 0.01 for all). On MVA of subgroups, adjRT was associated with significantly improved OS in pts with positive margins [HR 0.55 (95% CI, 0.43 – 0.71), P < 0.001], pN+ disease [HR 0.62 (95% CI, 0.49 – 0.79), P < 0.001], & pT4 disease [HR 0.68 (95% CI, 0.55 – 0.85), P = 0.001]. In MVA of pts with urothelial carcinoma (N = 578), adjRT remained associated with improved OS in pts with positive margins [HR 0.57 (95% CI, 0.43 – 0.76), P < 0.001], pN+ disease [HR 0.65 (95% CI, 0.50 – 0.86), P = 0.002], & pT4 disease [HR 0.68 (95% CI, 0.54 – 0.85), P = 0.001]. Conclusions: In this observational study, adjRT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of adjRT in selected pts with LABC, regardless of histology. Prospective trials of adjRT are warranted.