bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of perioperative venous thromboembolism with long-term oncologic outcomes following radical cystectomy.
Authors: Zaid Harras B. , Tollefson Matthew K. , Frank Igor , Parker William P. , Thompson Robert Houston , Tarrell Robert F. , Thapa Prabin , Cheville John C. , Boorjian Stephen A. 
Published: March 2017

364 Background: Venous thromboembolism (VTE) has been reported to occur in 2-5% of patients undergoing radical cystectomy (RC). While VTE is an important cause of perioperative morbidity, the association of these events with long-term cancer prognosis has not been established. Herein, we evaluated the association of perioperative VTE with patients’ risk of subsequent disease recurrence and mortality. Methods: We reviewed 2889 patients undergoing RC between 1980−2009 at the Mayo Clinic to identify patients diagnosed with a VTE within 90 days of RC. These cases were then matched in a 1:2 fashion to control patients undergoing RC who did not develop VTE. Matching was performed on the basis of age, BMI, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were estimated utilizing the Kaplan-Meier method and compared with the log-rank test. Results: A total of 132 patients with a VTE within 90 days of RC were identified, accounting for 4.6% of all patients analyzed. These cases were matched to 257 controls per criteria noted above, and were overall well-matched. Of the 389 patients in this study, median follow-up after RC was 9.2 years, during which time 152 (39%) patients experienced recurrence and 306 (78%) died, including 157 (40%) who died of bladder cancer. We found no significant difference in 5-year RFS (59% versus 61%; p = 0.75); CSS (57% versus 64%; p = 0.13); or OS (45% versus 50%; p = 0.15) between patients with versus without perioperative VTE, respectively. Conclusions: We found that VTE within 90 days of RC did not significantly impact long-term cancer outcomes. While these events represent an important cause of perioperative morbidity, no interaction with oncologic control was noted, and patients may be counseled accordingly.
Adjuvant radiotherapy use after radical cystectomy in muscle-invasive bladder cancer: A survey of U.S. radiation oncologists.
Authors: Solanki Abhishek Ashok , Martin Brendan , Korpics Mark , Small Christina , Harkenrider Matthew M. , Mitin Timur 
Published: March 2017

369 Background: Historic trials suggested significant toxicity with adjuvant radiotherapy (ART) after radical cystectomy for muscle-invasive bladder cancer (MIBC). However, recent trials have found improved locoregional control and the 2016 NCCN guidelines recommend ART consideration for select patients at high risk of local recurrence. ART practice patterns among U.S. radiation oncologists (ROs) are unknown, and we performed a survey to explore current trends. Methods: We conducted a survey of U.S. ROs regarding the management of patients with cT2-3N0M0 transitional cell MIBC. Responses were reported using descriptive statistics. Chi-square and univariate logistic regression (UVA) of clinical and demographic covariates were conducted, followed by multivariable logistic regression analyses (MVA) to identify factors predicting for ART use. Results: 277 ROs completed our survey. Nearly half (46%) use ART for MIBC. In ART-users, indications for ART include gross residual disease (93%), positive margins (92%), pathologic nodal involvement (64%), pT3 or T4 disease (46%), lymphovascular invasion (16%), and high-grade disease (13%). On UVA, ART use was associated with the number of years in practice (p=.043), pre-cystectomy RO consultation (p=0.004), primarily treating MIBC patients fit for cystectomy (p=0.009), and intensity-modulated radiotherapy (IMRT) use (p=0.009). On MVA, routine pre-cystectomy RO consultation (odds ratio [OR] 1.91, 95% confidence interval [CI]: 1.04-3.51; p=.037) and IMRT use (OR 2.77, 95% CI: 1.48-5.22; p=.002) remained associated with ART use. Conclusions: ART use is controversial in bladder cancer, yet is unexpectedly commonly used among U.S. radiation oncologists treating patients with MIBC after radical cystectomy. NRG GU001 is a randomized trial currently accruing patients with high-risk pathologic findings for observation or ART after cystectomy, and will hopefully clarify the role of ART and help identify patients benefiting from this adjuvant therapy. Whenever possible, patients should be enrolled in this study.
Overall survival advantage with radical prostatectomy for prostate cancer.
Authors: Kosarek Christopher David , Williams Stephen Bentley , Huo Jinhai , Chamie Karim , Smaldone Marc C. , Fang Justin Edwin , Ghaffary Cameron , Kerr Preston , Ynalvez Leslie , Kim Simon P. , Giordano Sharon Hermes , Chapin Brian F. 
Published: March 2017

37 Background: To compare overall survival of patients who underwent radical prostatectomy or radiotherapy versus non-cancer controls in order to discern if there is a survival advantage according to prostate cancer treatment. Methods: A matched cohort study was performedusingthe Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. We identified 34,473 patients age 66 to 75 years without significant comorbidity from who were diagnosed with localized prostate cancer treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a non-cancer control cohort. We compared the rates of all-cause mortality that occurred within the study period. We used Cox Proportional Hazards Regression analysis to identify determinants associated with overall survival. Results: Of the total 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy and 12,733 (37%) received surgery. When compared to the non-cancer control, there was no significant difference between the prostate cancer cohort and the non-cancer control group with exception of race/ethnicity (p < 0.001). There was improved survival in patients treated with surgery (hazard ratio [HR], 0.35; 95% CI, 0.32-0.38) as well as with radiotherapy (HR, 0.72; 95% CI, 0.68-0.75) when compared to non-cancer controls. There was significantly improved overall survival among both treatment groups with most benefit observed among patients who underwent surgery ( log rank p < 0.001). Conclusions: Using population based data, treatment with either surgery or radiotherapy demonstrated improved overall survival when compared to a cohort of matched non-cancer controls. Treatment with surgery resulted in longer overall survival compared to those receiving radiation therapy. These results suggest inherent selection-bias due to unmeasured confounding variables when using cancer registry data.
Systemic therapy and overall survival trends in patients with non-urothelial histologic variants of muscle invasive bladder cancer undergoing radical cystectomy.
Authors: Joshi Shreyas , Handorf Elizabeth , Correa Andres , Kutikov Alexander , Ristau Benjamin T. , Haifler Miki , Viterbo Rosalia , Greenberg Richard E. , Chen David , Uzzo Robert G. , Geynisman Daniel M. , Smaldone Marc C. 
Published: March 2017

376 Background: Histological variants of urothelial carcinoma (UC) of the bladder have a poorer prognosis than histologically pure UC, and the role of neoadjuvant chemotherapy (NAC) in this group is unclear. Our objective was to evaluate NAC practice patterns and survival outcomes in patients with histologic variants undergoing radical cystectomy (RC). Methods: Patients with cT2-4N0-3M0 muscle invasive bladder cancer (MIBC) who underwent RC from 2003-2012 were selected from the National Cancer Database (NCDB). Patients were categorized by histology code as pure UC or histologic variants. Adjusting for patient and clinical characteristics, generalized estimating equations were used to test the association between histology and receipt of NAC. The association between receipt of NAC and overall survival (OS) was evaluated using Kaplan Meier curves and Cox regression models. Results: In 19,976 patients meeting inclusion criteria, receipt of NAC in histologic variants was less (11-14%) than in pure UC (22%), with the exception of micropapillary disease (23%) (Table). Median OS was lower in variant histologies than for pure UC (8.4 – 30.2 vs. 37.6 months). Receipt of NAC was associated with improved survival compared to RC or RC+adjuvant chemotherapy in patients with pure UC (HR 0.91, p=0.0016). There was no evidence of a survival benefit for NAC in the variant histologies, or that treatment effects differed by histology (P-val for interaction=0.84). Conclusions: In the NCDB, a substantial proportion of patients (13%) with histologic variants of MIBC undergoing RC receive NAC in the absence of a proven survival benefit. Clinical trials inclusive of patients with variant histologies are necessary to elucidate the role of NAC prior to RC. [Table: see text]
Clinical and translational investigation of pan-HDAC inhibition in advanced urothelial carcinoma (UC).
Authors: Gupta Sumati , Albertson Daniel Joseph , Parnell Timothy , Dalley Brian , O Shea John , Weston Alexis , Butterfield Andrew , Pappas Lisa M. , Schiffman Joshua David , Sharma Sunil , Agarwal Neeraj 
Published: March 2017

379 Background: Pan-HDAC inhibitors were studied in two separate phase I pharmacokinetic solid tumor trials at Huntsman Cancer Institute. The objective of this study was to investigate the clinical efficacy of HDAC inhibition in those study subjects with UC and correlate response to molecular subtype of tumor with translational studies to validate clinical benefit. Methods: Patients with UC treated with a pan-HDAC inhibitor in two Phase I trials were included. RECIST 1.1 was used to categorize responses. Expression profiling and TCGA clustering were performed using archived tissue (obtainable for seven of the ten subjects). To elucidate the mechanisms of clinical benefit bladder cancer cell lines with varied mutational profiles and differential sensitivity to cisplatin were tested for sensitivity to panobinostat with characterization of phenotypic changes upon treatment. Results: Ten subjects with advanced UC received either belinostat or panobinostat. The best overall responses in the pooled data were: 1 complete response (CR), 1 partial response (PR), 6 stable disease (SD), 2 progressive disease (PD). The patient with CR had failed two prior lines of chemotherapy (including cisplatin), had a Cluster IV tumor and remains in CR for 3.5 years now. All tumors with SD belong to Cluster I. For those with SD, the progression free survival ranged from 6 to 7.5 months on treatment. One tumor with PR and one tumor with PD had characteristics partly consistent with Cluster III. Validating the broad spectrum of clinical activity of pan-HDAC inhibition, potent cytotoxicity with panobinostat was noted in bladder cancer cell lines with varied chromatin remodeling mutations. Panobinostat causes inhibition of colony formation, cell cycle arrest and proinflammatory cytokine release in these cells. Cisplatin-resistant HT1197 cells (with ARID1A mutation) are tenfold more sensitive. Conclusions: Pan-HDAC inhibition may be an effective treatment option in both luminal and basal subtypes of UC and in platinum-resistant setting. Translational studies suggest options for rational therapeutic combinations to enhance efficacy. HDAC inhibition may be particularly effective in UC with mutations affecting the SWI/SNF complex.
Intratumoral heterogeneity of ERBB2/HER2 expression in micropapillary urothelial carcinoma.
Authors: Isharwal Sumit , Huang Hongying , Nanjangud Gouri , Audenet Francois , Chen Yingbei , Gopalan Anuradha , Fine Samson , Tickoo Satish , Iyer Gopa , Rosenberg Jonathan E. , Bajorin Dean F. , Herr Harry W. , Donat S. Machele , Dalbagni Guido , Bochner Bernard H. , Solit David B. , Reuter Victor E. , Al-Ahmadie Hikmat 
Published: March 2017

383 Background: Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. Histologically, most of these tumors are associated with variable amounts of “not otherwise specified (NOS)” urothelial carcinoma. MPUC has been shown to be associated with ERBB2/HER2 amplification and protein overexpression. However, the status and distribution of these findings within the different components of tumors containing both MP and NOS urothelial carcinoma have not been addressed. Methods: We identified 44 cases of MPUC that had tissue available for FISH and IHC at our institute, of which an NOS component sufficient for both FISH and IHC was identified in 37 cases. We followed the updated ASCO/CAP Guidelines for breast cancer and as such amplification was defined by a HER2/CEP17 ratio of ≥ 2.0 or > 6 copies of the gene and HER2 overexpression was considered with IHC scores of 2+ and 3+. Results: In urothelial tumors with both MP and NOS components (n = 37), ERBB2 amplification in MP and NOS components was present in 25 and 16 cases respectively. ERBB2 amplification was significantly higher in the MP component compared to NOS component within the same tumor (67.57% vs. 43.24%, p = 0.049). HER2 overexpression in MP and NOS components was present in 25 and 13 cases respectively. HER2 overexpression was significantly higher in the MP component compared to NOS component within the same tumor (67.56% vs. 35.13%, p = 0.012). In addition, ERBB2 amplification strongly correlated with HER2 overexpression in both MP (rho = 0.65, p < 0.001) and NOS (rho = 0.74, p < 0.001) components. In this cohort (n = 44), tumor stage and lymph node status were significant predictors for overall survival (p = 0.01, < 0.001 respectively). However, ERBB2 amplification and HER2 overexpression in MP component were not associated with patients’ survival outcome (p = 1.00, 0.75 respectively). Conclusions: In MPUC, ERBB2 amplification and HER2 overexpression were preferentially but not exclusively identified in MP component compared to NOS component within the same tumor. Our findings provide evidence for intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC.
Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.
Authors: Shimizu Fumitaka , Muto Satoru , Taguri Masataka , Ieda Takeshi , Okegawa Takatsugu , Yamaguchi Raizo , Horie Shigeo 
Published: March 2017

392 Background: The clinical evidence of adjuvant chemotherapy (AC ) is less robust than neoadjuvant chemotherapy (NAC). However, several surveys suggest that urologists prefer to use AC more frequently than NAC. We evaluate the clinical benefit of adjuvant platinum based chemotherapy following radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) in routine clinical practice. Methods: This observational study was conducted to compare the effectiveness of AC versus observation postcystectomy in patients with clinicallymuscle-invasive BCa. Cancer-specific survival (CSS) and overall survival (OS) between the AC group and RC alone group were compared using Kaplan-Meiyer method and log-rank test. After adjusting for background factors using propensity score weighting, differences in CSS and OS between these two groups were compared. Subgroup analyses by the pathological characteristics were performed. Results: In total, 322 patients were included in this study. Of these, 23% received AC postcystectomy. Clinicopathological characteristics showed that patients in the AC group were pathologically more advanced and were at higher risk than the RC alone group. In the unadjusted population, although it is not significantly, the AC group had lower overall survival (3-years OS; 61.5% vs 73.6%, HR 1.44, p = 0.243, log-rank test, AC vs RC alone). In the weighted propensity score analysis, although it is not significantly, AC group were superior than RC alone groups (OS: HR 0.65, 95%CI 0.39-1.09, p = 0.099, log-rank test, AC vs RC alone). Subgroup analyses showed that AC significantly reduced the hazard ratio of OS and CSS in ≥ pT3, pN+, ly+, and v+ subgroups. Conclusions: The weighted propensity score analyses showed that platinum-based AC might be associated with increased CSS and OS in patients with high-risk invasive BCa.
ATM/RB1 mutations to predict shorter overall survival (OS) in bladder cancer.
Authors: Yin Ming , Grivas Petros , Ali Siraj Mahamed , Hsu Joann , Vasekar Monali K. , Emamekhoo Hamid , Pal Sumanta K. , Li Sierra Min , Drabick Joseph J. , Joshi Monika 
Published: March 2017

393 Background: DNA repair defect plays an important role in tumorigenesis, progression and treatment outcomes of urothelial cancer. Somatic mutations of ATM/RB1 genes are frequently found in urothelial cancer and have been associated with a better response to cisplatin-based neoadjuvant chemotherapy. However, their prognostic value overall in urothelial cancer have not been determined. Methods: Exome sequencing data of 130 urothelial bladder cancer patients (pts) from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM and RB1 mutations. Results from discovery dataset were further validated by an independent cohort of 79 advanced urothelial cancer pts who received comprehensive genomic sequencing for urothelial cancer with FoundationOne. OS was measured from time of initial diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: In the discovery dataset, somatic mutations of ATM/RB1 genes were present in 24% of pts and were associated with significantly shorter OS [all stages: adjusted HR = 2.67, 95% CI, 1.45–4.92, P = 0.002; stage II-III only: adjHR = 2.76, 95% CI, 1.23–6.20, P = 0.014]. There was high mutation load in pts carrying ATM/RB1 mutations (median mutation count: 196 versus 160, P = 0.09). In the validation (stage IV) dataset, ATM/RB1 mutations were present in 31.7% of pts and tended to associate with shorter OS (adjHR = 1.97, 95% CI, 0.89–4.40, P = 0.094) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, P = 0.136), although statistical significance was not reached. Conclusions: These results suggest that ATM/RB1 mutations may be considered as a poor prognostic biomarker in unselected urothelial cancer pts and may correlate with higher mutational load. Further studies are required to determine patient characteristics that can further stratify prognosis based on ATM/RB1 mutation status, and evaluate the potential predictive role of ATM/RB1 mutation status in response to immunotherapy.
Treatment patterns and outcomes in metastatic bladder cancer in community oncology settings.
Authors: Fisher Maxine , Shenolikar Rahul , Miller Paul J. E. , Walker Mark Stephen , Fenton Moon Jung ,   Authors
Published: March 2017

396 Background: Current real-world data on treatment patterns in metastatic bladder cancer in the community setting are limited. This study describes patient characteristics, treatment patterns, and efficacy outcomes for these patients in the community setting. Methods: Medical records data from adults diagnosed with stage IV or metastatic bladder cancer between 1/1/2008 and 6/1/2015 were retrospectively collected from a network of 10 US community oncology practices. Patient characteristics, treatment patterns, and efficacy outcomes were assessed. Comparisons across groups were conducted using standard analyses. Progression-free survival and overall survival (OS) were assessed using Kaplan-Meier analysis. Results: Of 508 patients, 75% were male, 79% white, 15% African American, and 71.5% were age ≥65 years (median age, 71 years; range 35-92 years). Overall, 76.4% were current or past tobacco users. The most prevalent comorbidities were diabetes (23.4%), renal disease (16.5%), and chronic obstructive pulmonary disease (COPD; 12.4%). Patients age ≥65 years vs <65 years had higher rates of renal disease (19.6% vs 9.0%; P=0.004), COPD (14.6% vs 6.9%; P=0.017) and congestive heart failure (CHF; 6.3% vs 2.1%; P=0.049), respectively. First-line platinum-based therapy was given to 56.3% of the patients, with the most common regimen being gem + carbo (23.6%) followed by gem + cis (17.0%). Overall, median OS was 9.4 months from diagnosis, 11.0 months from start of line-1, and 5.3 months from start of line-2. Cox regression analysis of OS from diagnosis showed that males (hazard ratio [HR]=1.26; P=0.046) and patients with impaired performance (HR=2.137; P<0.001) were at greater risk of death. Conclusions: Although platinum-based chemotherapy is currently the preferred treatment for metastatic bladder cancer in the community setting, there is a large unmet need in this population, particularly among the elderly. Gender and performance status were associated with efficacy outcomes.
Outcomes and predictors of survival in testicular sarcomas.
Authors: Alsidawi Samer , Westin Gustavo Figueiredo Marcondes , Okuno Scott H. 
Published: March 2017

404 Background: Testicular sarcomas represent less than 1% of all testicular tumors in adults. Because of their rarity, little is known about the features and outcomes of these tumors. We present an analysis of the prognosis and survival predictors in patients with testicular sarcomas from the Surveillance, Epidemiology, and End Results Program (SEER). Methods: Using the SEER registry, we identified adults with testicular sarcomas between 1980 and 2013. Cases were identified using a combination of ICD-O-3 site and histology codes. The JMP and SEER*STAT 8.3.2 were used for statistical analysis. Overall survival (OS) was analyzed using the Kaplan-Meier method. The prognostic effect of variables was studied using Cox proportional hazards models. Results: We identified 264 patients with testicular sarcomas with a median follow-up time of 9.2 years. The median age at diagnosis was 55 years (range 15-94) and the median tumor size was 6.6 cm (range 0.7-45). 20% of patients with documented staging presented with de novo metastatic disease. Rhabdomyosarcomas were the most common histology (37%). The median OS was 129 months (95%; CI 85-180). OS rates at 1 year and 5 years were 85% and 62% respectively. 53% of deaths were related to cancer. 1-year OS rates for localized, locally advanced and metastatic disease were 91%, 93% and 53% (P<0.0001). Variables that were significant for survival in univariate analysis included age, histology, stage, and surgical resection. Factors that negatively affected survival in multivariate analysis were age >55 years (HR 2; 95% CI, 1.1-3.7), advanced stage (HR 4.8; 95% CI, 2.7-8.4) and surgical unresectability (HR 3.7; 95% CI, 1.1-9.3). Patients with rhabdomyosarcoma had favorable outcomes compared to other histologies (59% vs 17% alive at 10 years, P=0.01). Conclusions: Testicular sarcomas are rare entities with overall good prognosis after surgical resection. Patients presenting with distant metastases, however, have worse outcomes with only about 50% of the patients alive at 1 year. Rhabdomyosarcomas are the most common histology encountered and have relatively better survival. Younger age, earlier stage and surgical resection are factors associated with significantly better outcomes.