bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravesical rad-IFNα/Syn3 for patients with high-grade, bacillus Calmette-Guérin (BCG) refractory or relapsed non-muscle invasive bladder cancer: A phase II randomized study.
Authors: Boorjian Stephen A. , Shore Neal D. , Canter Daniel , Ogan Kenneth , Karsh Lawrence Ivan , Downs Tracy , Gomella Leonard G. , Kamat Ashish M. , Lotan Yair , Svatek Robert S. , Bivalacqua Trinity J. , Grubb Robert , Krupski Tracey , Lerner Seth P. , Woods Michael , Inman Brant Allen , Milowsky Matthew I. , Parker Nigel , Sawutz David , Dinney Colin P.N. 
Published: March 2017

279 Background: While bacillus Calmette-Guérin (BCG) is the most effective intravesical treatment for reducing recurrence and progression for high-risk non-muscle invasive bladder cancer (NMIBC), many patients are either refractory to treatment or relapse. We assessed the efficacy and safety of rAd-IFNα/Syn 3 (Instiladrin, FKD Finland), a replication deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG refractory or relapsed NMIBC. Methods: In this open-label, US multicenter (n=13), parallel-arm Phase II study (NCT01687244), 43 patients with HG BCG refractory or relapsed NMIBC were randomized 1:1 to receive intravesical rAd-IFNα/Syn3 at 1x1011 or 3x1011viral particles/mL. Patients responding at months 3, 6, and 9 were re-treated at months 4, 7, and 10. Most patients (n=21) had a primary tumor classification of carcinoma in situ (CIS); 9 had both CIS and Ta/T1 disease and 10 had Ta/T1 disease alone. The primary endpoint was 12-month HG recurrence-free survival (RFS). All patients receiving at least one dose were included in efficacy and safety analyses. Results: Forty patients received rAd-IFNα/Syn3 (1 x 1011 vp/mL: n=21; 3 x 1011vp/mL: n=19) between November 2012 and April 2015. Fourteen patients (35.0%; 90% CI 22.6%, 49.2%) remained free of HG tumor recurrence 12 months after initial treatment. Comparable 12 month HG RFS was noted between dosage arms, as well as between patients with refractory and relapsed NMIBC. Interestingly, the 12 month HG recurrence-free survival for patients with Ta/T1-only disease was 50% (5/10). rAd-IFNα/Syn3 was well-tolerated, with no Grade 5 adverse events (AEs), one Grade 4 AE (COPD; unrelated to treatment), and no patient discontinuing treatment due to an adverse event. The most frequently reported AEs were micturition urgency (n=16), dysuria and pollakiuria (n=13 each), fatigue (n=9), and nocturia (n=10). Conclusions: rAd-IFNα/Syn3 was well tolerated and demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who are unable or unwilling to undergo radical cystectomy. A phase III trial utilizing this novel agent is ongoing. Clinical trial information: 01687244.
Temporal trends and factors associated with overuse of neoadjuvant androgen deprivation therapy in low and very low risk prostate cancer.
Authors: Delancey John Oliver , Matulewicz Richard , Schaeffer Edward M. 
Published: March 2017

28 Background: Evidence has emerged that androgen deprivation (ADT) use prior to radical prostatectomy or radiation therapy in low risk prostate cancer patients does not provide a survival benefit and may subject patients to adverse side effects and clinical outcomes. We examined trends and factors associated with ADT use prior to definitive therapy in low and very low risk prostate cancer. Methods: We identified men diagnosed with low or very low risk prostate cancer in the National Cancer Database from 2004-2013 who elected definitive treatment with radical prostatectomy (RP), external beam radiation (EBRT) or brachytherapy (BT). Neoadjuvant ADT use was defined as receipt of ADT prior to definitive treatment. Trends in neoadjuvant ADT use were assessed and multivariable logistic regression was used to evaluate associations between treatment, age, race, insurance status and urban/rural status and receipt of neoadjuvant ADT. Results: Of 199,933 patients with low or very low risk prostate cancer, neoadjuvant ADT use decreased from 14.6% in 2004 to 2.7% in 2013 (23.0% to 8.8% for BT, 20.6% to 6.0% for EBRT and 2.3% to 0.5% for RP; each p for trend < 0.001). Controlling for covariates and year, we found increased odds [OR (95% CI)] of neoadjuvant ADT use in patients undergoing BT [12.01 (11.23-12.83)] or EBRT [8.75 (8.16-9.39)], African Americans [1.08 (1.02-1.14)] vs. whites, patients 75 or older [1.93 (1.80-2.06)] and 65-74 [1.52 (1.44-1.60)] vs. less than 65, patients in communities less than 250,000 [1.28 (1.23-1.34)] vs. metropolitan areas and patients with Medicare or Medicaid [1.22 (1.16-1.29)] vs. private insurance. Conclusions: Use of ADT prior to definitive prostate cancer treatment has declined over the past decade. However, patients receiving radiotherapy, African Americans, patients of older age, rural location, and insured by Medicare or Medicaid more frequently received neoadjuvant ADT. Since this treatment is unlikely to provide a survival benefit and may subject patients to adverse side effects or clinical outcomes, strategies to minimize overuse of ADT in low or very low risk patients prior to definitive therapy may help limit overtreatment and its associated harms.
Long-term incidence of venous thromboembolic events following cystectomy: A population-based analysis.
Authors: Wallis Christopher J.D. , Magee Diana , Satkunasivam Raj , Nam Robert 
Published: March 2017

288 Background: Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario. Methods: We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality. Results: Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Table 1). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE. Conclusions: Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE. [Table: see text]
The positive predictive value of PI-RADS 4 lesions stratified by lesion number in biopsy naïve men.
Authors: Syed Jamil , Javier-desloges Juan , Nguyen Kevin , Sheridan Alison , Levi Angelique , Weinreb Jeffrey , Sprenkle Preston 
Published: March 2017

29 Background: To assess the positive predictive value (PPV) of PI-RADS 4 lesions stratified by suspicion for tumor multi-focality. Methods: Between April 2015 and July 2016, 62 biopsy naïve men with at least one PI-RADS 4 lesion underwent mpMRI/US fusion biopsy. Patients were placed into group 1 if they had a single lesion, group 2 if they had an additional PI-RADS 3 or 2 lesion, and group 3 if they had an additional PI-RADS 4 or 5 lesion. Image interpretation was performed prospectively and assessed using PI-RADS version 2. The ANOVA and chi-square tests were used to assess differences between continuous and categorical variables, respectively. Results: Using systematic and targeted biopsy combined, the overall and GS ≥ 7 cancer detection rate for the entire cohort was 80.6% (50/62), and 53.2% (33/62), respectively. There were a total of 88 lesions with 26,14, and 48 lesions in groups 1,2, and 3, respectively. There were no significant differences in mean age, PSA density, race, or lesion location between groups; p = 0.107, p = 0.694, p = 0.511, and p = 0.558, respectively. The PPV for any prostate cancer was 65.4% (17/26), 100% (14/14), and 90% (43/48) for groups 1,2, and 3 respectively (p = 0.005). The PPV for GS ≥ 7 was 42% (11/26), 50% (7/14), and 75% (36/48) for groups 1,2, and 3, respectively (p = 0.001). Conclusions: Our data indicate that the PPV for a PI-RADS category assessment score of 4 may be influenced by tumor multi-focality on imaging. Further assessment with increased sample size will be useful to confirm our initial results.
Epidermal growth factor receptor (EGFR) targeted photoimmunotherapy (PIT) for the treatment of EGFR expressing bladder cancer.
Authors: Railkar Reema , Krane Spencer , Li Q. Quentin , Sanford Thomas , Choyke Peter L. , Kobayashi Hisataka , Agarwal Piyush K. 
Published: March 2017

291 Background: There are limited treatment options for patients with non-muscle invasive bladder cancer (NMIBC) who fail intravesical bacillus Calmette-Guerin (BCG). The use of light as a means of therapy for bladder cancer (BC) has a long history but has been hampered by a lack of tumor specificity and toxicity. Monoclonal antibody (mAb)-conjugates represent an emerging therapeutic approach for malignancies that improves upon tumor specificity. The use of a mAb-photo-absorber (PA) conjugate is a more selective method of delivering light therapy and has been termed “photoimmunotherapy” (PIT). In this report, PIT is used to target the epidermal growth factor receptor (EGFR). EGFR is a good tumor-specific target as it is enriched in the basal molecular subtype of BC. In the present study, anti-EGFR antibody panitumumab (pan) was labeled with the PA, IRDye 700Dx (IR700), to create a pan IR700 mAb-PA conjugate which is activated by near-infrared radiation (NIR). Methods: BC tissue microarray (TMA) and BC cell lines were analyzed for expression of EGFR. Mechanism of PIT induced cell death was studied using proliferation assays, transmission electron microscopy (TEM), and production of reactive oxygen species. Finally, the in vivo effect was studied in xenografts. Results: EGFR staining of TMAs showed that while most BCs have expression of EGFR to some degree, squamous cell carcinomas (SCC) have the highest expression of EGFR. Pan IR700 activated by NIR light rapidly killed UMUC-5 cells, a bladder SCC line. Pan alone, pan IR700 without NIR, or NIR alone had no effect on cells. TEM demonstrated that cell death is due to necrosis. Singlet oxygen species contributed towards cell death. NIR-PIT with pan IR700 reduced growth compared to only pan IR700 treated UMUC-5 xenograft tumors. Conclusions: PIT is a new targeted treatment for BC. Our data demonstrate that pan IR700-induced PIT selectively kills EGFR-expressing bladder cancer cells in vitro and in vivo and hence warrants further studies in orthotopic models and in patients. We suspect that EGFR-directed therapy with PIT is a viable strategy for the basal molecular subtype of BC and will be testing this hypothesis in the future.
Effectiveness of adjuvant chemotherapy after radical nephroureterectomy for locally advanced and/or positive regional lymph node upper tract urothelial carcinoma.
Authors: Krasnow Ross Erik , Seisen Thomas , Bellmunt Joaquim , Roupret Morgan , Leow Jeffrey J. , Lipsitz Stuart R. , Vetterlein Malte , Preston Mark A , Hanna Nawar , Kibel Adam S. , Sun Maxine , Choueiri Toni K. , Trinh Quoc-Dien , Chang Steven Lee 
Published: March 2017

305 Background: There is limited evidence supporting the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with an overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Methods: Within the National Cancer Data Base (2004-2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients in the two treatment groups. Additionally, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathological stage (pT3/T4N0, pT3/T4Nx and pTanyN+) and surgical margin status. Results: Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation after RNU, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC vs. observation (47.41 [IQR, 19.88-112.39] vs. 35.78 [IQR, 14.09-99.22] months; P< 0.001). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 43.90% vs. 35.85%, respectively. In IPTW-adjusted Cox regression analysis, AC was associated with a significant OS benefit (HR = 0.77; 95% CI = [0.68-0.88]; P< 0.001). This benefit was consistent across all subgroups examined (all P< 0.05) and no significant heterogeneity of treatment effect was observed (all Pinteraction> 0.05). The 3-month conditional landmark IPTW-adjusted analysis demonstrated little impact of immortal time bias (HR = 0.79; 95% CI = [0.70-0.91]; P = 0.001). Conclusions: We report an OS benefit in patients who received AC vs. observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.
Results of the GETUG-AFU 19 trial: A randomized phase II study of dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with or without anti-epidermal growth factor receptor (EGF-R) monoclonal antibody panitumumab (PANI) in advanced transitional cell carcinoma (ATCC).
Authors: Culine Stephane , Flechon Aude , Gravis Gwenaelle , Roubaud Guilhem , Loriot Yohann , Joly Florence , Barthelemy Philippe , Assaf Elias , Mahammedi Hakim , Beuzeboc Philippe , Van Hulst Sylvie , Rolland Frederic , Guillot Aline , Gross-Goupil Marine , Kayat David , Tartas Sophie , Deblock Mathilde , Habibian Muriel , Thezenas Simon , Allory Yves 
Published: March 2017

307 Background: Frequent overexpression and correlation with stage and survival has been reported with the EGF-R pathway in ATCC. Methods: 93 patients (pts) with locally advanced or metastatic bladder or upper urinary tract (UUT) transitional cell carcinoma were planned with a 1:2 randomisation ratio. Patients with K-Ras or H-Ras mutations were excluded. dd-MVAC included M 30 mg/m2d1, V 3 mg/m2d2, D 30 mg/m2d2 and cisplatin 70 mg/m2d2 (d1 = d14) with G-CSF support. PANI 6 mg/kg was given on d2. The number of pts was determined from the 9-month median progression-free survival (PFS) rate reported with dd-MVAC. Using a one stage Fleming design, the dd-MVAC+PANI combination will be considered to be active if at least 37 patients among 70 do not show tumor progression at 9 months (p0 = 0.50, p1 = 0.70, alpha = 0.08 and beta = 0.03). As basal-like subtype might be related to Anti-EGFR treatment response, the phenotype was determined using a Keratin 5/6 and GATA3 double immunostaining (8 basal like among 58 cases tested). Results: From September 2010 to November 2015, 96 patients (bladder 68, UUT 21, both 8) received dd-MVAC (33) or dd-MVAC+PANI (63). No significant difference was observed among baseline characteristics and prognostic factors. The median number of cycles was 6 (1-6) in both arms. At least one grade > 2 toxicity was observed in 79% and 76% of patients in the dd-MVAC and PANI arms, respectively. More dermatological adverse events were observed in the PANI arm. Objective responses were reported in 23 (70%) pts in the dd-MVAC arm and 30 pts (48%) in the PANI arm. With a median follow-up of 27 months, PFS was 6.8 months and 5.7 months in the dd-MVAC and PANI arms respectively; OS was 20.2 months and 12.5 months in the dd-MVAC and PANI arms, respectively. No association was observed between PFS and basal-like feature for patients treated by MVAC+PANI. Molecular subtyping is in progress to confirm this observation at mRNA level. Conclusions: When combined with dd-MVAC, PANI does not seem to improve efficacy in pts with ATCC. Clinical trial information: NCT02818725.
A model for predicting focal ablation candidates in patients with prostate cancer based on MRI and biopsy criteria.
Authors: Calio Brian P. , Sidana Abhinav , Sugano Dordaneh , Gaur Sonia , Jain Amit L , Maruf Mahir , Valera Vladimir , Merino Maria J , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Pinto Peter A. 
Published: March 2017

31 Background: To determine the accuracy of multiparametric MRI (mpMRI) and fusion biopsy in predicting focal therapy candidates by correlating agreement between patients’ pre-prostatectomy MRI and biopsy findings with whole mount pathology. Methods: Patients who underwent mpMRI and biopsy followed by prostatectomy between 2010-2015 were included in the study. Patients were considered good candidates for focal therapy if they had intermediate risk cancer (max Gleason 3+4 or 4+3 on biopsy) in only one hemisphere of the prostate, and if they had an mpMRI visible lesion(s) on one hemisphere that did not cross midline. Patients were considered poor candidates for focal therapy if they had either low risk cancer (Gleason 6), high risk cancer (Gleason 8, 9 and 10), intermediate risk cancer bilaterally, MRI visible lesions that cross the midline, or contained extracapsular extension or seminal vesicle invasion. Whole mounts of patients considered good candidates were then examined histologically for maximum tumor involvement. Results: 501 patients who underwent prostatectomy between 2010 and 2015 were included in the study, with mean age 60.0 (±10.0) and PSA 6.21 (±6.0). 395 patients were considered poor focal candidates, and 106 were considered good focal candidates. Of these 106, 66 patients had whole mounts available for analysis (14 random biopsy, 52 fusion biopsy). 42/66 (63.6%) patients were confirmed as candidates (6/14 (42.9%) who had random biopsy and 36/52 (68.0%) who had fusion). Candidates failed prediction due to Gleason upgrade in final histopathology in 20/24 (83.3%), and for significant Gleason detection bilaterally in 4/24 (16.7%). Conclusions: Our results suggest that application of mpMRI and biopsy criteria to predict focal therapy candidates may result in undertreatment of a large portion of patients with significant cancer. Results from mpMRI guided targeted biopsy were shown to be a more accurate tool for predicting candidates for focal therapy than results from random biopsy alone. More accurate predictive capability is needed before focal therapy can be widely accepted.
Association of age with utilization of radical cystectomy for high-grade nonmuscle invasive bladder cancer: Results from the National Cancer Database.
Authors: Parker William P. , Zaid Harras B. , Habermann Elizabeth B. , Frank Igor , Thompson Robert Houston , Tollefson Matthew K. , Karnes Jeffrey , Boorjian Stephen A. 
Published: March 2017

312 Background: Radical cystectomy (RC) is a preferred option for high−grade non−muscle invasive bladder cancer (HG NMIBC), particularly after failure of intravesical therapy. However, clinicians may be reluctant to offer surgery to older patients with NMIBC given concerns regarding morbidity. We therefore sought to evaluate the association of age with use of RC and clinicopathologic outcomes after RC for HG NMIBC. Methods: The National Cancer Data Base was queried to identify patients diagnosed with HG NMIBC between 2004−2013. Patients were stratified according to age at diagnosis: <60, 61−70, 71−80, >80 years. Multivariable logistic regression was performed to assess the associations of age group with utilization of RC and with pathologic upstaging (pT2−4 or pN+). Overall survival (OS) was evaluated using unadjusted and inverse propensity score weighted (IPTW) Kaplan−Meier methods and compared with the log-rank test. Results: RC was performed in 3,641 (5.7%) of 63,402 patients with HG NMIBC. Utilization of RC remained relatively constant over the study period (4.3%−6.8%; p=0.44). On multivariable analysis, increasing age was inversely associated with RC utilization, with the lowest utilization in those >80 (2.1% rate; OR 0.24; p<0.01). Similar associations of age with RC were observed at high volume centers (> 15 cases/year), academic centers, and for patients with cT1 disease. Among patients who underwent RC, pathologic upstaging was identified in 1,445 (43.6%), and no significant association was noted with age. NMIBC pathologic tumor stage was associated with improved OS compared to progression to pT2−4 or N+ disease at RC for all age groups: median OS improvement not reached in those under 60; 32 months in those 61−70; 55 months in those 71−80; and 34 months in those over 80 (all p<0.01). Similar improvements in survival were noted after IPTW. Conclusions: Older patients are significantly less likely to receive RC for HG NMIBC, despite a similar risk of upstaging and an improved survival when pathologic NMIBC is found at RC. These data support the use of RC for HG NMIBC in well selected patients across age strata.
Association of chemotherapy regimen with venous thromboembolic risk in patients with urothelial tract cancer.
Authors: Ramos Jorge , Holt Sarah , Schade George , Galsky Matt D. , Wright Jonathan L. , Gore John L. , Yu Evan Y. 
Published: March 2017

314 Background: Cisplatin chemotherapy (CTX) is associated with increased risk of venous thromboembolism (VTE); however, other agents have also been hypothesized to increase risk. We assessed the association of VTE with different CTX regimens in urothelial tract cancer patients. Methods: We identified > 66 year-old patients diagnosed with urothelial tract cancers (excluding renal pelvis) from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database from 1998 to 2011. CTX regimens included gemcitabine/cisplatin (GC), methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), or gemcitabine/carboplatin (GCarbo). We calculated VTE rates within 120 days of CTX initiation and compared VTE by CTX regimen with multivariable logistic regression models adjusted for patient and cancer characteristics. Results: Of 5050 identified patients, VTE occurred in 13.1% (660/5050). VTE rates were 15.3% (265/1737) and highest for GC; 8.8% (23/262) and 12.2% (372/3051) of MVAC and GCarbo patients experienced VTE, respectively. Adjusted for patient demographic and cancer-specific variables, MVAC and GCarbo were associated with lower odds of VTE compared with GC (see Table). Conclusions: Compared with GC, MVAC and GCarbo are associated with a decreased rate of VTE. This finding suggests that gemcitabine may add to the increased thrombosis risk from cisplatin. Patients treated with GC should be counseled about this association. Sensitivity analyses to assess VTE risk of different CTX regimens in the perioperative setting will be presented. [Table: see text]