bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of the outcomes after neoadjuvant (NC) or adjuvant chemotherapy (AC) for muscle-invasive urothelial bladder cancer (UC): A French contemporary retrospective multicenter cohort.
Authors: Pouessel Damien , Chevret Sylvie , Roubaud Guilhem , Aarab-Terrisse Safae , Chevreau Christine , Vordos Dimitri , Rolland Frederic , Boudin Laurys , Joly Florence , Joly Charlotte , Beuzeboc Philippe , Boyle Helen Jane , Farneti Delphine , Dauba Jérôme , Moriceau Guillaume , Alexandre Ingrid , Deplanque Gael , Loriot Yohann , Houede Nadine , Culine Stephane 
Published: February 2017

325 Background: Our aim was to investigate outcome of patients (pts) treated with AC or NC for organ-confined UC, or with NC for clinical lymph node involvement (cN+). Methods: We retrospectively analyzed 482 pts treated in 22 French hospitals between 2000 and 2013 in 3 settings: 226 pts with radical cystectomy (RC) and AC (AC group), 193 cN0 (NC group), and 63 cN+ (cN+ group) pts received NC before a planned RC for cT2-T4, M0 UC. The primary outcome was overall survival (OS). Cancer-related survival (CRS) was also evaluated. Multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios with 95% confidence interval. Results: Median age was 62, 61.7, and 62.1 in AC, NC, and cN+, respectively. Median time between diagnosis and first treatment (RC or NC) was 2.1, 1.4 and 1.6 months, respectively (p<0.001). In AC, stages were p≤T2 (n=46) or pT≥3 (n=180), pN0 (n=37), pN+ (n=168), or pNx (n=21). Gemcitabine-cisplatin and gemcitabine-carboplatin regimen were mainly delivered as AC in 71.2% and 21.7% of pts. In NC, all pts received methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) or dose-dense MVAC. Median number of cycles was 4 in each group. After NC, RC has been realized in 173 (90%) and 51 pts (82%) in NC and cN+, respectively. In 17 unoperated pts, concomitant chemoradiotherapy was performed. Median follow-up was 24.6 months. Respectively, 133 (59%), 61 (32%), and 22 (35%) pts have relapsed in AC, NC, and cN+; 74%, 63%, and 71% of them received chemotherapy for metastasis. Also 133 (59%), 41 (21%), and 18 (29%) pts died, mostly (90%) due to recurrence. Three-year OS and CRS rates were 54%, 68%, and 56% (p=0.02), and 37%, 53%, and 49% (p=0.038) in AC, NC, and cN+, respectively. In multivariate analysis, only AC (HR: 1.64, 95% CI 1.18-2.30, p=0.001) remained significantly associated with shortened OS. Conclusions: In this large retrospective study reporting real-life survivals, 3-year OS was longer in pts receiving NC, both in cN0 and in cN+ groups, than in pts treated with AC. Although several selection bias can be emphasized preventing us from drawing definitive conclusions, AC appeared to be associated with a poorer prognosis.
Circulating tumor cells (CTC) as potential biomarkers in neoadjuvant chemotherapy of muscle invasive bladder cancer (MIBC).
Authors: Alva Ajjai Shivaram , Daignault-Newton Stephanie , Huebner Tamara , Clark Melanie , Hussain Maha , Ionescu Cristian , Schwartz Mike 
Published: February 2017

330 Background: Biomarkers to assess early response to cisplatin based neoadjuvant chemotherapy (NAC) in MIBC is a clinical need. We hypothesized that CTC enumeration and genomic profiling using a novel microfluidic immunomagnetic assay IsoFlux (Fluxion Biosciences Inc., CA) could provide novel biomarkers in individual patients during NAC. Methods: Peripheral blood was drawn at baseline and after one cycle (3-4 weeks) of NAC in patients (pts) with locally advanced resectable bladder cancer in an IRB approved prospective study at the University of Michigan. CTCs were enumerated by the CellSearch and IsoFlux assays in parallel and by IsoFlux in duplicate samples. We correlated CTC numbers with pStage at cystectomy, a known prognostic variable for survival. We assessed gene expression by RT-PCR and gene mutational status by Ion Torrent sequencing on CTCs. Results: We analyzed 21 pts with localized muscle invasive bladder cancer (cT2-T4aNx). Mean age was 65 yrs with 84% male. Clinical stage was 71% cT2N0, 14% cT3N0, 10% cT4N0, 5% cT4aN1. NAC was GC in 9 pts and MVAC in 12 pts. The IsoFlux assay detected more CTCs per sample than CellSearch at baseline (median =10 vs. 0, n=5) and after 1 cycle (5.5 vs. 0, n=4). IsoFlux assay in parallel tubes had 80% of samples with <5 CTC difference between the pairs. Baseline CTC concordance with pStage was 75% (12/16) (concordance=either <pT1N0 with <10 CTCs or ≥ pT1N0 with ≥10 CTCs). On the other hand, concordance of cStage with pStage was only 62.5% (10/16). PDGFRA, PIK3CA and MET mutations were detected on CTCs. Interrogation of CTCs for gene expression by RT-PCR and application of next generation sequencing (NGS) to CTCs were feasible. Conclusions: IsoFlux detects more CTCs than CellSearch in patients undergoing NAC. Baseline CTC number is a potential prognostic variable superior to cStage. However, changes in CTC number before and after 1 NAC cycle do not appear to reflect benefit in individual patients. Gene expression and genomic profiling of CTCs are feasible. CTCs are potential liquid biopsies in patients undergoing NAC in bladder cancer.
Impact of first-line cisplatin versus non-cisplatin based chemotherapy on progression-free survival in patients with advanced urothelial carcinoma previously treated with perioperative cisplatin based chemotherapy.
Authors: Locke Jennifer A , Pond Gregory Russell , Sonpavde Guru , Necchi Andrea , Giannatempo Patrizia , Paluri Ravi Kumar , Niegisch Guenter , Albers Peter , Buonerba Carlo , di Lorenzo Giuseppe , Vaishampayan Ulka N. , North Scott A. , Agarwal Neeraj , Hussain Syed A. , Eigl Bernhard J. 
Published: February 2017

335 Background: Perioperative cisplatin based chemotherapy (PCBC) is a standard of care in the management of muscle invasive urothelial carcinoma (UC). Cisplatin based (C) therapy also represents the historical first line treatment of metastatic disease. There is however no data to guide the optimal choice of first line chemotherapy regimen – C re-treatment vs other second-line or non cisplatin regimens (NC) –in UC patients who relapse after receiving PCBC. This multicenter retrospective study compares C vs NC first line treatment on progression-free survival (PFS) for patients (pts) with advanced UC after PCBC and cystectomy. Methods: Data were collected for patients who received various first-line chemotherapies for advanced UC following previous PCBC therapy. Cox proportional hazards models were used to investigate the prognostic ability of type of peri-operative / first-line chemotherapy, visceral metastasis, ECOG status, time from prior chemotherapy (TFPC), anemia, leukocytosis and albumin on PFS. Results: Data were available for 145 pts from 12 centers. The mean age was 62 years, 113 (77.9%) were men and ECOG-PS was 0 or >0 in 74 (51.0%) and 61 (42.0%) patients. Ninety-one (62.8%) pts received C first line, the median number of cycles was 4 (range 1-17) and the median TFPC was 6.2 months (range 1-154). Median overall survival was 86 weeks (95% CI 70-106) and median PFS was 24 (95% CI 18-27) weeks. Time from perioperative chemotherapy (TFPC) (>52 weeks vs ≤52 weeks; HR 0.63 p=0.027) and ECOG-PS at first line (1+ vs 0; HR 1.73 p=0.010), were prognostic of PFS. No significant effect was noted for C vs NC first line (p=0.70); however, among patients with TFPC >52 weeks, patients with NC had worse PFS (median 4.6 months, 95% CI 1.8-12.2) than those who received C (median 8.1, 95% CI 3.2-16.3). Conclusions: There is no evidence to suggest overall superiority of C vs NC based first line chemotherapy or a second-line regimen in patients with advanced UC who received prior PCBC. However, those with TFPC >52 weeks should probably receive C first line chemotherapy given better PFS with C.
Platinum concentration in bladder tissue treated with neoadjuvant chemotherapy and pathologic response.
Authors: Guancial Elizabeth A. , Kilari Deepak , Messing Edward M. , Kim Eric S. 
Published: February 2017

341 Background: Platinum (Pt) resistance is a major limitation in the treatment of muscle-invasive bladder cancer (MIBC), for which Pt-based chemotherapy remains the standard of care. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our previous studies in lung cancer demonstrate significant correlation between tissue Pt concentration and tumor response to neoadjuvant chemotherapy (NAC). Tissue Pt concentration was measured in bladder specimens exposed to Pt-based NAC and correlated to pathologic response. Methods: A cohort of 19 clinically annotated, archived frozen bladder specimens from MIBC patients treated with three to four cycles of Pt-based NAC was identified [pT0 (pathologic complete response, pCR), n=4; pTis or pT1 (pathologic partial response, pPR), n=6; >/= pT2 (minimal pathologic response/progression), n=9]. Two cystectomy specimens from MIBC patients treated with Pt-based adjuvant therapy were used as controls. Non-tumor bearing adjacent bladder tissue (“normal”) was identified in cystectomy specimens by a genitourinary pathologist. Total Pt concentration in normal tissue was measured by flameless atomic absorption spectrophotometry. Three group Kruskal-Wallis tests were used to compare the distributions of Pt concentrations by pathologic response (pCR, pPR, minimal response/progression). Mann-Whitney non-parametric two-sided tests were used for two group comparisons. Results: Total Pt concentration in normal adjacent bladder tissue differed by tumor pathologic response (p=0.011). Specimens with a pCR had the highest Pt concentrations compared to those with a pPR (p=0.0095) or no response/progression (p=0.0196). There was no significant difference in Pt levels between PR and no response/progression group (p=0.37). Conclusions: Our findings suggest that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Studies investigating factors that modulate intracellular Pt concentration, such as expression of influx/efflux Pt transporters, may serve as predictive biomarkers and promote increased use of Pt-based NAC.
Long-term effects of Bacilles Calmette-Guerin perfusion therapy for upper urinary tract urothelial carcinoma in situ.
Authors: Yoneyama Takahiro , Tobisawa Yuki , Yoneyama Tohru , Yamamoto Hayato , Imai Atsushi , Mori Kazuyuki , Hatakeyama Shingo , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

343 Background: Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for muscle noninvasive bladder cancer. Although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract urothelial carcinoma in situ(CIS), it is not well established yet. We conducted a retrospective study to assess the long-term effects of BCG perfusion therapy for the upper urinary tract CIS. Methods: Thirty-one subjects (24 male, 7 female) who received BCG perfusion therapy for the upper urinary tract CIS from December 1997 to December 2013 were enrolled. 11 subjects had the entire urinary tract CIS, 8 had bilateral, 12 had unilateral CIS of the urinary tract. The average period of observation was 49.9 months (ranging from 5 to 196 months), and the average subject age was 74.8 years (ranging from 56 to 90 years). We used a double-J catheter for 22 cases, a transvesical single-J catheter whose curl was positions in an upper calyx for 8 cases, and a straight ureteral catheter inserted for ureterocutaneostomy for 1 case. We used 80 mg of BCG for the first five cases, 40 mg for the late 26 cases. Urine cytology was performed to assess the treatment validity. Results: Of the 31 cases, the treatment protocol was completed in 27 cases. Urine cytology tests became negative in 25 of the 31 subjects (80.7%) who underwent upper urinary tract perfusion. Among these 22 subjects who had negative tests, 8 subjects had a recurrence in their upper urinary tracts. Side effects were observed in 28 subjects (90.3%), and the most common side effect was bladder irritation. Localized renal tuberculosis, which was successfully treated with conservative therapy, was seen in two cases. Conclusions: BCG perfusion therapy for the upper urinary tract CIS is effective. However, severe side effects are possible, and careful observation is essential while using this therapy.
Complication rates in patients with uncontrolled diabetes undergoing radical cystectomy: A population-based study.
Authors: Faiena Izak , Dombrovskiy Viktor Y. , Sultan Raymond C. , Barbalat Yanina , Salmasi Amirali H. , Singer Eric A. , Weiss Robert E. 
Published: February 2017

355 Background: Radical cystectomy is known to be associated with a relatively high incidence of postoperative morbidity and mortality. We evaluated the complication rates of a population-based cohort of patients with uncontrolled diabetes who underwent radical cystectomy. Methods: The data for this analysis was captured from the NIS (Nationwide Inpatient Sample) 2002-2009. Among patients who underwent radical cystectomy (ICD-9 diagnosis code 188.x and 57.71), we selected those with uncontrolled diabetes, which is defined by the billing physician (ICD-9 diagnosis code 250.02) and compared to patients without diabetes. We also identified postoperative complications. Patient socio-demographic characteristics, principal and secondary diagnoses, principal and secondary procedures, comorbid diseases, disposition of patient at discharge, hospital length of stay, and hospital cost for our analysis. A chi-square test was employed for categorical variables and Student’s t-test for continuous variables. A multivariable logistic regression analysis was also employed with computing OR and 95% CI. P<0.05 was considered statistically significant. Results: There were significant differences in the postoperative outcomes between groups. In the univariable analysis, patients with uncontrolled diabetes were more likely to have complications (OR=3.21; 95%CI= 2.59-4.00) including infectious complications (OR=2.46; 95%CI= 1.98-3.06) and were more likely to die during the index hospitalization (OR=3.27; 95%CI= 1.41-7.61). Hospital resource utilization was also significantly greater in patients with uncontrolled diabetes. Mean length of stay in this group was 17.3 days compared to 11.4 days in non-diabetic group (P=0.0007); total hospital cost was, respectively, $47,960 and $32,422 (P=0.0009). Conclusions: This study demonstrates a significant association between uncontrolled diabetes and in-hospital post-cystectomy complications, mortality, and hospital resource utilization. This study highlights the recognition of uncontrolled diabetes as a potential modifiable risk factor for patients undergoing cystectomy.
Impact of perioperative blood transfusion on oncologic outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.
Authors: Bagrodia Aditya , Kaffenberger Samuel D. , Vacchio Michael J , Murray Katie S , Winer Andrew G. , Cha Eugene K. , Sankin Alexander , Dalbagni Guido , Coleman Jonathan A. 
Published: February 2017

358 Background: Patients treated for urothelial carcinoma of the urinary bladder treated with radical cystectomy and pelvic lymph node dissection have worse clinical outcomes if they receive perioperative blood transfusion. We evaluated the impact of perioperative blood transfusion on oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: We conducted a single-center, retrospective review of 405 patients treated with RNU for UTUC. Clinicopathologic characteristics were recorded. Hospital charts were reviewed to determine if patients received perioperative blood transfusion. Characteristics were compared between groups based on transfusion status using Chi-square analyses. Survival was assessed using the Kaplan-Meier method. Cox regression analysis addressed cancer-specific mortality (CSM). Results: Median age was 71.4 years (IQR 63.7-76.5) and the majority of patients were male (64%). Median follow up was 43.4 months (IQR 16.7-86.6). CSM occurred in 26.2% of patients. Perioperative transfusion was associated with higher rates of invasive T stage (>/=T2), (62% vs. 47%, p=0.019) and lymph node positive disease (23% vs. 10.3%, p=0.029). Three year disease-specific survival (DSS) was 80% for the entire cohort. DSS was significantly shorter (p=0.003) for patients receiving transfusion (66.3%, 95% CI 53.7%-76.3%) than those who did not (83.3%, 95% CI 78.3%-87.3%). Transfusion was an independent predictor of CSM on multivariable analysis including gender, grade, invasive T stage, nodal status, and transfusion (Table 1). Conclusions: Perioperative blood transfusion may be associated with adverse pathologic and oncologic outcomes in patients undergoing RNU for UTUC. [Table: see text]
Postchemotherapy consolidative surgery for metastatic urothelial carcinoma.
Authors: Ercole Cesar Emilio , Campbell Steven C. , Dreicer Robert , Garcia Jorge A. , Gong Michael C. , Krishnamurthi Venkatesh , Stephenson Andrew J. 
Published: February 2017

362 Background: The role of post-chemotherapy consolidative surgery for metastatic urothelial carcinoma (UC) is controversial and supported by small, single-center series in select patients. We sought to assess our experience with post-chemo retroperitoneal lymph node (RPLN) dissection for primary metastatic or relapsed UC to the retroperitoneum (with or without concomitant cystectomy and/or nephroureterectomy). Methods: Since 2008, 15 patients with metastatic or relapsed UC of the bladder or upper tracts (UT) and associated RPLN metastases were considered for post-chemo consolidative surgery. Records were reviewed for response to therapy, final pathology, and impact of surgery on overall survival (OS). Chemo agents used were provider dependent with 9 patients treated with gemcitabine/cisplatin, 3 with gem/carboplatin, and 2 with methotrexate, vinblastine, doxorubicin, cisplatin (1 received a combination due to intolerance). A median of 3.5 cycles were given in the adjuvant (n=5) and induction (n=10) setting. Seven patients presented with UT disease, of those 3 with relapse; median follow-up was 31.6 months (mos, IQR 14, 72), with 1 patient deceased. Nine patients had a bladder primary, 5 had induction chemo (median follow-up: 22 mos, IQR 16, 40), with 1 alive, 4 dead of disease, and 2 of other causes. To date, 13 patients have undergone surgery. Overall median follow-up is 23 mos. Results: Five patients (3 bladder, 2 UT) were noted to have radiographic complete response (CR) with induction and a median survival of 21.5 mos, with one patient alive at 7 years. All but one patient in the UT group are alive. Two patients had pathological CR, both were in the bladder cohort and died at 8 and 23 mos post-op. For all other patients, final pathology noted a median of 2 LN positive for malignancy (average 3.6). Neither chemo nor timing of administration showed a difference in OS. Conclusions: There is a role for post-chemo consolidative surgery in selected patients with metastatic UC. Compared to patients with the primary tumor in the UT, those with a primary bladder tumor and RPLN fared worse with a shorter overall survival time. More studies are necessary to better define the role of surgery in this setting.
Prevalence of atypical urine cytology in patients treated with gemcitabine-cisplatin (GC) for urothelial carcinoma (UC).
Authors: Kruczek Kimberly R. , Wang Lu , Barkan Guliz , Henry Elizabeth 
Published: February 2017

363 Background: The prevalence of atypical urothelial cells (AUC) in the general population is estimated to range between 2-23% with known variability between individual pathologists’ use of this diagnosis. At our institution, the AUC rate for all urinary tract cytology (UTC) is 6.1%. Increased rates of urothelial atypia have been described in pts receiving certain systemic and intravesical therapies for UC. This may confound the use of UTC for post-therapy surveillance. Our objective is to describe the prevalence of urothelial atypia in pts treated with GC, as it is currently unknown. Methods: Patients who received at least one cycle of GC for UC at a single institution from 1/1/2007-9/30/2014 were identified. Demographics, clinical characteristics, treatment setting, number of cycles, and specimen type were recorded. Urine cytology reports were reviewed and tabulated. Results: Seventy-four pts treated with GC were identified. Median age at treatment was 65 (range 42-80); 58 (78%) were male. Median number of cycles was 4 (range 1-9). Treatment settings were: 15 (20%) neoadjuvant, 38 (51%) adjuvant, and 21 (28%) metastatic. Ten (14%) pts were previously treated with intravesical therapy (9 BCG, 1 mitomycin). Thirty-six (49%) pts had urine cytology available. Twenty-seven (75%) pts had at least 1 urine cytology within 12 months post-chemotherapy, with 44 total specimens. Nine (25%) pts had cytology performed >1-year post treatment. Cytology specimens within 12 months post-chemotherapy were reviewed. Two out of 44 specimens had AUC (5%), with all other cases negative. The pts with AUC were male, received adjuvant therapy, had prior radical cystectomy with orthotopic neobladder reconstruction, and had no intravesical therapy. Conclusions: The prevalence of AUC in pts treated with GC was similar to the general population. Chemotherapy with GC does not appear to morphologically affect urothelial cells. If atypical UTC is seen in this population, the cause should be investigated, as GC does not appear to influence urothelial changes. Additional study is needed to characterize the impact of systemic therapy on urothelial atypia and to guide the use of urine cytology for post-therapy surveillance.
A single-arm, multicenter, open-label phase II trial of cabazitaxel as second-line treatment for patients with locally advanced or metastatic transitional cell carcinoma (TCC).
Authors: Peer Avivit , Neumann Avivit , Keizman Daniel , Frank Stephen Jay , Berger Raanan , Leitzin Larisa , Pinto Ester , Neiman Victoria , Rosenbaum Eli 
Published: February 2017

372 Background: For patients with advanced TCC who have progressed on a platinum-based regimen, no widely accepted standard second line therapy currently exists. A 2-stage phase II study was conducted to assess the activity and toxicity profile of the microtubule inhibitor cabazitaxel (Jevtana; FDA-approved in hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen) in patients with metastatic TCC after failure of prior platinum-based chemotherapy. ClinicalTrials.gov NCT01600339. Methods: Patients with one prior platinum based systemic therapy for metastatic TCC received cabazitaxel at a dose of 25 mg\m2every 21 days with prophylactic GCSF support, until disease progression or unacceptable toxicity. The primary endpoint was objective tumor response rate (ORR). Secondary endpoints included safety, time to progression (TTP), and overall survival (OS). Results: Twenty-three patients were enrolled to the study, 19 of whom received treatment. Male\female ratio was 15\4 and the median age was 67 (range, 56-81) years. Partial response (PR) was observed in 1 patient (5.3%), 10 patients (52.6%) achieved stable disease (SD), including 8 (42.1%) that had prolonged SD (≥16 weeks).Furthermore, the disease control rate (PR or prolonged SD) was 47.4%. The median TTP and OS were 4.2 (95% CI, 2.0-6.0) months and 9.9 (95% CI 5.6-13.2) months, respectively. The median number of treatment cycles was 5 (range 1-10). One patient experienced Grade 5 toxicity. Neutropenic fever occurred in 10.6% of patients. Most common toxicities were anemia and diarrhea. Conclusions: Cabazitaxel had modest efficacy in the treatment of advanced TCC, and there was no evidence of a significant response. Toxicity profile was considerable. The role of Cabazitaxel in urothelial carcinoma may need further evaluation in rational combination strategies, but not as a single agent. Clinical trial information: NCT01600339.