bluuebunny/crossref_metadata_2025_split huggingface dataset:
EAU and NCCN surveillance guidelines for bladder cancer: Do they effectively capture recurrences following cystectomy?
Authors: Stewart Suzanne B. , Boorjian Stephen A. , Psutka Sarah P. , Cheville John C. , Thapa Prabin , Tarrell Robert F. , Tollefson Matthew K. , Thompson Robert Houston , Frank Igor 
Published: February 2017

310 Background: The European Association of Urology (EAU) and the National Comprehensive Cancer Network (NCCN) provide general guidelines for bladder cancer (BC) surveillance following radical cystectomy (RC). However, it is unclear how well these guidelines capture recurrences after surgery. Herein, we assess the ability of current guidelines to effectively capture BC recurrence following RC and propose a risk stratified and recurrence site-specific surveillance strategy. Methods: We reviewed our institutional database of 1,800 patients who underwent primary RC between 1980-2007. Guideline effectiveness was assessed by calculating the percentage of recurrences detected within the prescribed follow-up periods: EAU—5yrs; NCCN—2yrs. Patients were then stratified according to stage: < = pT1Nx-0, > = pT2Nx-0, pN+, and recurrence site: urothelium, abdomen, chest, other. Recurrence free survival estimates for stage groups and recurrence site were assessed with Kaplan Meier models. Results: Of the 1,800 patients, 634 (35.2%) were classified as > pT2Nx-0 and 234 (13%) as pN+ and overall 228 (12.7%) received perioperative chemotherapy. Median postoperative follow-up was 10.6yrs (IQR 6.8-15.2), during which 716 (39.8%) patients developed recurrence. Of these recurrences, 492 (68.7%) would have been detected using the NCCN guidelines and 644 (89.8%) by EAU recommendations. However, ending oncologic surveillance at 5 years would only capture 81.7% of all recurrences for < = pT1Nx-0 patients and 83% of urothelial specific recurrences across all stage groups. Capture of 90% of recurrences, by stage group, in the urothelium, abdomen and chest would require surveillance for 8yrs, 8yrs and 4yrs, respectively in < = pT1Nx-0, 6yrs, 4yrs and 3yrs in > = pT2Nx-0 and 3yrs, 3yrs and 2yrs for pN+ patients. Conclusions: Duration of surveillance recommended for BC following RC by the EAU and NCCN do not comprehensively capture recurrences seen, specifically, in low risk patients and in cases of urothelial recurrence. Guidelines using risk stratification and site-specific recurrence patterns to assign length of surveillance may allow providers to better individualize surveillance regimens.
Multi-institutional evaluation of the prognostic significance of altered mammalian target of rapamycin (mTOR) pathway biomarkers in upper-tract urothelial carcinoma (UTUC).
Authors: Bagrodia Aditya , Krabbe Laura-Maria , Gayed Bishoy A. , Kapur Payal , Darwish Oussama M. , Bernstein Ira , Xie Xian-Jin , Wood Christopher G. , Zigeuner Richard , Weizer Alon Z. , Raman Jay D. , Remzi Mesut , Langner Cord , Roscigno Marco , Bolenz Christian , Bensalah Karim , Sagalowsky Arthur I. , Shariat Shahrokh F. , Lotan Yair , Margulis Vitaly 
Published: February 2017

323 Background: Alterations in the MTOR and HIF pathways may have prognostic significance in bladder carcinoma. We evaluated the predictive value of altered MTOR-pathway biomarkers in upper tract urothelial carcinoma (UTUC). Methods: Multi-institutional review of clinicopathological data on patients receiving extirpative surgery for UTUC from 1990-2008. Immunohistochemistry for phosphorylated-S6, mTOR, phosphorylated-mTOR, PI3K, p4E-BP, phosphorylated-AKT, PTEN, HIF-1a, Raptor and Cyclin D was performed on tissue microarrays from radical nephroureterectomy specimens. Predictive markers were identified by regression analyses. Significance of altered markers was assessed with Kaplan-Meier and Cox regression analysis. Results: 620 patients with a mean age of 69 years were included. 37% of patients had non-organ confined (T3/T4 and/or N+) disease. 74% of patients had high-grade disease and 22% had LVI on final pathology. Over a median follow-up of 27.3 months, 24.6% of patients recurred and 21.8% died of UTUC. On multivariable analysis, PI3K (OR 1.28, p=0.001) and Cyclin D (OR 3.45, p=0.05) were significant predictors of clinical outcomes. Cumulative marker-score was defined as low-risk (zero/one altered marker) or high-risk (Cyclin D AND PI3K altered). Patients with high-risk marker-score had a significantly higher proportion of high-grade disease (91% vs. 71%, p<0.001), non-organ confined disease (61% vs. 33%, p<0.001), LVI (35% vs. 20%, p=0.001), and lymph node metastases (22% vs. 6%, p<0.001). Kaplan-Meier analysis demonstrated a significant difference in CSM based on risk groups. On multivariable analysis for CSM incorporating non-organ confined disease, grade, LVI, tumor architecture, and marker-score, high-risk biomarker-score was an independent predictor of CSM (HR 1.5, 95%CI 1.04-2.3, p=0.03). Conclusions: Alterations in MTOR pathway correlate with established adverse pathologic features and independently predict inferior oncologic outcomes. Incorporation of MTOR-based marker profiles may allow for enhanced patient counseling, risk stratification, and individualized treatment regimens.
Clinical T1 urothelial bladder cancer: USC experience.
Authors: Alemozaffar Mehrdad , Djaladat Hooman , Cai Jie , Miranda Gus , Schuckman Anne , Daneshmand Siamak 
Published: February 2017

327 Background: Patients with clinical T1 (cT1) urothelial bladder cancer (UBC) present a dilemma regarding the decision to proceed with radical cystectomy (RC) or conservative therapy. We review outcomes of patients with cT1 UBC who underwent RC. Methods: Retrospective review of 1,964 patients undergoing RC for UBC at our institution from 1971-2008 revealed 442 patients with cT1 disease on last TURBT (excluding patients with any TURBT with >cT1 or receiving neoadjuvant therapy) of whom 97 had muscle present on last TURBT. Results: Of 442 patients with cT1 UBC, 260 (58.8%) remained <pT1, 124 (28.1%) were upstaged to >pT2, and 58 (13.1%) had positive lymph node (LN+) at RC; therefore, 182 (41.2%) had more extensive disease pathologically than clinically. LN+ patients were more likely than <pT1 or >pT2 to have LVI on TURBT (24.1% vs 11.5% vs 11.3%, p=0.029) and RC (67.2% vs 5.8% vs 36.3%, p<0.001). No clinical variables were associated with upstaging to >pT1 or LN+ disease on multivariate analysis (MVA). 5-yr recurrence-free survival (RFS) was 75.4% with MVA associating worse RFS with >pT2 (HR=1.819, p=0.02), LN+ (HR=8.202, p<0.001), pathologic LVI (HR=2.022, p=0.002), multifocal disease (HR=1.306, p<0.001), and increasing TURBTs (HR=1.306, p<0.001). 5-yr overall survival (OS) was 68.4% with MVA associating worse OS with increasing age (HR=2.234, p<0.001), >pT2 (HR=1.557, p=0.0055), LN+ (HR=4.391, p<0.001), pathologic LVI (HR=1.641, p=0.002), and increasing TURBTs (HR=1.116, p=0.005). When limited to patients with muscle present on last TURBT (N=97), following RC there were 65 (67%) remaining <pT1, 23 (23.7%) were upstaged to >pT2, and 9 (9.3%) were LN+; therefore, 31 (33%) had more extensive pathologic disease than thought clinically. Their 5-yr RFS was 81.4% with MVA associating worse RFS with LN+ (HR=9.111, p=0.007) and increasing TURBTs (HR=1.408, p=0.028). Their 5-yr OS was 73.5% with MVA associating worse OS with LN+ (HR=7.976, p=0.004). Conclusions: Patients with cT1 UBC have a significant rate of upstaging to >pT1 or LN+ disease at cystectomy, even with muscle present at last TURBT. Although LVI may be associated with more extensive disease favoring cystectomy over conservative management, there are no reliable clinical predictors to determine upstaging.
Assessment of bone metastases in patients (pts) with urothelial carcinoma using 18F-sodium fluoride PET/CT (18F-NaF) versus 18F-fluorodeoxyglucose PET/CT (18F-FDG).
Authors: Weinberg Benjamin Adam , Lindenberg Maria Liza , Kurdziel Karen A. , Steinberg Seth M. , Liewehr David J. , Khadar Kattie , McKinney Yolanda , Choyke Peter L. , Apolo Andrea Borghese 
Published: February 2017

329 Background: 18F-NaF has shown improved sensitivity for bone imaging when compared to conventional planar imaging or SPECT/CT using 99mTc-MDP. We compared the number of bone lesions detected on 18F-NaF versus 18F-FDG in urothelial cancer pts with known bone metastases undergoing treatment. Methods: Pts enrolled in a prospective single-arm phase II study of cabozantinib underwent 18F-NaF and 18F-FDG scans at baseline and at 8 weeks of therapy. In a lesion-based analysis independently confirmed by a nuclear medicine physician, abnormal foci of radiotracer uptake were categorized by location (skull, spine, pelvis, thorax, or long bones) and by disease state (benign, malignant, or indeterminate). A patient-based analysis was performed to determine if findings indicated disease progression, stable disease, or improvement of disease, based on the number of lesions and standardized uptake values (SUVs). Results: 294 total bone lesions were identified at baseline in 10 pts (8 male and 2 female, ages 44-73). 18F-NaF identified more lesions than 18F-FDG at baseline, 294 vs. 119. In a paired analysis, the median difference was 11.5 more lesions detected per patient on 18F-NaF vs. 18F-FDG (by Wilcoxon signed-rank test, p = 0.023). More total thoracic bone lesions at baseline, 100 vs. 23, were also detected on 18F-NaF vs. 18F-FDG, median 6.5 vs. 1.0 with a median difference of 6 more lesions per patient on 18F-NaF (p = 0.016). 18F-NaF also detected more skull lesions at baseline, 19 vs. 1, which was clinically but not statistically significant (p = 0.250). There was general concordance in the patient-based analysis; only 1 18F-NaF scan demonstrated progressive disease while its corresponding 18F-FDG scan showed stable disease. Conclusions:18F-NaF identified more lesions than 18F-FDG at baseline, making it a good staging exam. However, there was agreement between 18F-NaF and 18F-FDG in terms of tumor response in almost all the follow-up scans. Therefore, although a greater number of bone lesions are seen in 18F-NaF compared with 18F-FDG, the clinical significance in assessing treatment response remains to be determined. Clinical trial information: NCT01688999.
Venothromboembolism and radical cystectomy: Prevalence of risk factors and comparison of anticoagulation use.
Authors: Sun Andrew , Djaladat Hooman , Schuckman Anne , Miranda Gus , Daneshmand Siamak 
Published: February 2017

339 Background: Radical cystectomy is a major pelvic surgery associated with relatively high rates of venothromboembolism (VTE). This study focuses on prevalence of known risk factors in patients undergoing radical cystectomy who suffered a symptomatic VTE and compared use of warfarin and heparin in prophylaxis. Methods: We conducted a retrospective review of 2,730 patients who underwent open cystectomy at USC between 1971-2012 using the IRB approved bladder cancer database. Patients who suffered VTE during the peri-operative period were identified. Preoperative, operative, and postoperative risk factors for VTE were analyzed. Data on use of anticoagulation was obtained and used to compare a historical cohort of warfarin use as prophylaxis (1971-2007) to the modern cohort of subcutaneous heparin use (2009-2012). A Chi-squared test was used to determine significance of any differences in prophylaxis use. Results: A total of 129 patients (4.7%) with symptomatic VTE were identified. 112/129 (86.8%) fit intent to cure inclusion criteria and were further evaluated for demographic information (85% male, median age 69.9, median BMI 27.9, and smoking history in 61.6%) and risk factors. Of pre-operative VTE risk factors, previous chemotherapy (9.8%) and other active medical illness (17.4%, e.g. atrial fibrillation, hypothyroidism, congestive heart failure) were most common. Median operative time was 363 minutes; median EBL was 800 ml with median transfusion of 2.0 units of PRBCs. The median day of first ambulation was POD 3, median LOS was 11 days, and a median interval between surgery and VTE diagnosis was 20.5 days. 15.1% of VTE patients also had a post-op infection. Of the 129 VTE cases, the overall rate from 1971-2007 (treated with warfarin) was 4.1%, while the rate from 2009-2012 (treated with heparin) was 6.3% (p=0.054). Percent of patients with a VTE occurring after discharge from 1971-2007 and 2009-2012 were 2.3% and 4.1%, respectively (p=0.052). Conclusions: Most VTEs occur after discharge, indicating a possible need for VTE prophylaxis beyond the immediate post-op period. There was a trend toward reduced risk of VTE with post-operative use of warfarin compared to heparin.
Assessment of bowel disorders following radial cystectomy and urinary diversion for muscle-invasive transitional cell carcinoma of the bladder.
Authors: Kramer Mario W. , Kabbani Mohammad , Kabbani Abdul-Rahman , von Klot Christoph A. J. , Tezval Hossein , Peters Inga , Herrmann Thomas R. W. , Kuczyk Markus A. , Merseburger Axel S. 
Published: February 2017

347 Background: Articles reporting and specifying bowel disorders after radical cystectomy as long-term complications are sparse. However, numerous patients report on bowel function alteration and/or defecation disorders or even stool incontinence. For better qualification and quantification we present our data of a large cohort of patients evaluated with a newly developed questionnaire. Methods: For this purpose a novel non validated questionnaire was developed. The questionnaire was sent to 253 patients who had been treated with radical cystectomy between 2006 and 2012 to assess possible changes in bowel function and its impact on health related quality of life. Of those, 89 patients reported on their current status. Questions were related to their overall satisfaction as well as to their quality and severity of bowel disorders following pelvic surgery for bladder cancer. Results: In total 40 (44.9%) patients reported of a persistent change in bowel function after surgery. Most frequent were constipation (28.9%), diarrhea (18.4%) or both (21.1%) followed by flatulence (31.6%). Patients who experienced bowel function alteration but who are still satisfied reported predominantly of constipation (35.3%) and flatulence (41.2%) but not diarrhea. Twenty-three (25.8%) patients are currently not satisfied with their bowel function. Of those, 82.6% complaint about frequent flatulence, 75% report on softer stools, 65.2% have irritable bowel symptoms, 26.1% experience faecal incontinence and 73.9% are affected by serious life restrictions due to bowel disorder. Defecation frequency increased significantly (p<0.001). There is a significant reduction in life quality (p=0.004), medical condition (p=0.008) and energy level (p=0.035). A significant correlation could be found for higher T-stage (p<0.05) and positive lymph nodes (p<0.03). No differences could be observed between patients who received ileal-conduit vs. orthotopic neobladder or MAINZ I pouch urinary diversion. Conclusions: Long-term bowel disorders after cystectomy are an underestimated issue. A better understanding might lead to modifications of surgical procedures.
Validation of a whole-blood RNA prognostic signature in metastatic castration-resistant prostate cancer (mCRPC) patients.
Authors: Oh William K. , Chippada Venkata Uma , Wang Li , Reese Emma , Yee Tiffany , Kochukoshy Teena , Tsao Che-Kai , Galsky Matt D. , Zhu Jun , Gong Yixuan 
Published: February 2017

36 Background: We developed a whole-blood RNA transcript-based six gene signature (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, CDKN1A), which separates patients with metastatic castration-resistant prostate cancer (mCRPC) into high- and low-risk survival groups (Ross et al. Lancet Oncology, 2012). In this study, the prognostic utility of the signature is validated on two independent platforms: an updated qPCR platform and an RNA-sequence platform in a new cohort of patients. The dynamic changes in the gene expression are examined during disease progression in serial samples from individual patients. Methods: Whole blood RNA was extracted from PAXgene tubes drawn from 63 patients with prostate cancer representing a range of clinical disease states. Serial samples were collected from a subset of patients (n=34). Survival prediction scores were derived independently based on the RNA-transcript levels of the six genes as quantified by a new ViiA 7 qPCR platform and by Illumina RNA-sequence. Results: The six gene signature scores generated on both qPCR and RNA-sequence platforms remain highly prognostic, separating mCRPC patients into high- and low-risk survival groups (logrank test; p-value for qPCR <0.001; p-value for RNA-seq <0.001). In contrast, prostate-specific antigen (PSA) fails to predict survival in the same cohort. There is a weak correlation between PSA and the six gene score (p-value of spearman correlation=0.14), indicating that the six gene score provides unique information regarding disease status. Patients with serial blood draws demonstrated no relationship with PSA changes. Patients with localized and hormone sensitive prostate cancer had significantly lower six gene scores (p-value=0.036). Individual gene analysis revealed that two genes, ABL2 and ITGAL, as the major contributors to the prognostic score. Conclusions: Our results further validate the prognostic significance of a six gene whole blood RNA signature, using an independent cohort and independent platforms.
United States trends in patterns of care in clinical stage I testicular cancer: Results from the National Cancer Database (1998-2011).
Authors: Jeldres Claudio , Nichols Craig R. , Pham Khanh , Daneshmand Siamak , Kollmannsberger Christian K. , Hayes-Lattin Brandon M. , Wolff Erika , Odem-Davis Katherine , Porter Christopher R. 
Published: February 2017

369 Background: There has been significant evolution in worldwide guidelines for management of clinical stage I (CS1) testicular cancer where active surveillance (AS) strategies are now considered a first choice, especially for patients with lower recurrence risk after orchiectomy. Conversely, local therapies for CS1 such as primary retroperitoneal lymphadenectomy (RPLND) in non-seminoma and regional radiation in seminoma are phasing out of recommendations. In the US, there have been no comprehensive efforts to measure uptake of guideline recommendations and modern patterns of care for early-stage testicular cancer. Methods: Access to the testicular cancer data set within the National Cancer Data Base (NCDB) was granted to Virginia Mason Medical Center (A SWOG affiliated cancer research program) for this retrospective cohort study. We identified all patients with CS1 testicular cancer between 1998 and 2011. Management options after orchiectomy such as adjuvant radiotherapy, adjuvant chemotherapy, RPLND, or AS were analyzed using cross tabulation and trend analysis. Results: Within the NCDB, of 75,902 patients with testicular cancer, 31,208 and 13,301 were diagnosed with CS1 seminoma and non-seminoma, respectively. For CS1 seminoma, AS use increased from 25.2% in 1998 to 55.8% in 2011. Similarly adjuvant chemotherapy use also increased (1.9 % to 16.7%). Conversely, use of adjuvant radiation decreased from 72.9% to 27.5%. For CS1 non-seminoma, AS remained the main treatment modality ranging between 58.8% and 66.2%. The use of adjuvant chemotherapy increased (28.3% in 2011) and the rate of primary RPLND constantly decreased down to 12.9% that same year. Interestingly, 50.3% of patients with CS1 non-seminoma and negative lympho-vascular invasion status had chemotherapy rather than AS. Trends analyses were statistically significant for all treatment modalities (p<0.05). Conclusions: Active surveillance as a management strategy has increased and is currently the most common treatment modality used for both CS1 seminoma and non-seminoma in the US. Regional therapies in CSI seminoma and non-seminoma are decreasing but persist even in patients with a low risk of recurrence.
Dose calculation and tolerability of adjuvant AUC 7 carboplatin in 100 patients with stage I seminoma.
Authors: Basso Umberto , Diminutto Alberto , Morelli Franco , De Giorgi Ugo , Perin Alessandra , Fraccon Anna Paola , Lo Re Giovanni , Rizzi Anna , Sava Teodoro , Valcamonico Francesca , Zustovich Fable , Massari Francesco , Maruzzo Marco , Zanardi Elisa , Zattoni Filiberto , Zagonel Vittorina 
Published: February 2017

374 Background: Administration of carboplatin AUC 7 has become a standard adjuvant option to be discussed with pts following orchiectomy for stage I seminoma, as alternative to radiotherapy on retroperitoneal lymphnodes or observation. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial by Oliver et al. (Lancet, 2005), but dose ranges were not reported. Oncologists use different methods to estimate GFR and to calculate this unusually high dosage of carboplatin, and fear of toxicity may induce arbitrary dose reductions and potentially compromise the outcome. Methods: In 9 Italian centers we conducted a retrospective review focusing on adjuvant carboplatin administration to stage I seminoma pts. Modality of dose calculation, dose reductions and toxicities were recorded. Results: Since August 2006, 100 pts have been treated, median age 35 years (range 26 to 58). Adverse prognostic factors were either T >4 cm (14% of pts) or rete testis invasion (32), both (36), none or unspecified (18). Glomerular Filtration Rated was estimated mainly by Cockroft-Gault formula (55% of pts), Jeliffe formula (27%), 24-hour urine collection (17%), MDRM (1%): median value was 106 ml/min (range 75 to 209). All Oncologists declared to use Calvert formula to calculate AUC 7 dose, and administered a median of 900 mg of carboplatin (range 690 to 1535). A dose reduction > 10% was prudentially applied to 15% of pts; a second cycle was delivered in 8 pts. Acute toxicities are outlined in table 1. After a median follow-up of 20 months, 6% of patients have relapsed (all in the retroperitoneum), none of whom had been treated with reduced dose. Conclusions: AUC 7 carboplatin dosage peaked 1,535 mg in our cohort of stage I seminoma patients with no infections and nephrotoxicity, moderate nausea-vomiting, but 5% of grade 3-4 thrombocytopenia. Prudential dose reductions appeared unfrequent and should be proscribed. [Table: see text]