bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of trimodal chemoradiotherapy with gemcitabine and cisplatin as a bladder-preserving strategy for the treatment of muscle invasive bladder cancer: A single-arm prospective study.
Authors: Matsumoto Hiroaki , Nagao Kazuhiro , Ozawa Sho , Samoto Masahiro , Mori Junichi , Inoue Ryo , Yamamoto Yoshiaki , Yano Seiji , Hirata Hiroshi , Shimabukuro Tomoyuki , Matsuyama Hideyasu 
Published: February 2020

516 Background: Radical cystectomy is still the standard treatment for muscle-invasive bladder cancer (MIBC), while the patients with MIBC are not always appropriate candidates due to multiple comorbidities. We establish novel treatment strategy by trimodal treatment. Methods: The regimen was gemcitabine 300 mg/m2, and cisplatin 30mg/m2 in day 1 and concomitant irradiation 2Gy/Fr, 5 fraction per week. Irradiation was administered to whole pelvis up to 30Gy, then boost to true pelvis until total 48Gy to 54Gy. Extensive transurethral resection (TURBT) was performed and we confirmed pathological stage ≥T2. TURBT was also performed after chemoradiotherapy to evaluate the pathological response to treatment. This study was approved in our institutional review board (ID: H23-89) and the information was opened on UMIN (ID: UMIN000006363). We analyzed their treatment efficacy and survival. Results: The patients were 29 men and 9 women, median age was 76.5 y.o. and median follow up was 23 months (1 - 112). Clinical stage T2, T3, T4, N1 and N2 were 23, 10, 5, 4, 2 cases, respectively. The 2- and 5-year metastatic-free survival (MFS), bladder-recurrence free survival (bRFS), cancer-specific survival (CSS), and overall survival (OS) rates after treatment were 91.7 and 84.0%, 59.7 and 42.6%, 87.3 and 87.3%, and 87.3 and 81.8%, respectively. Salvage cystectomy was performed 3 patients and they were still alive. CR rate was 78.9% and overall response rate was 92.1%. cT stage and valiant histology was not associated with treatment response. The patients achieved CR had significant good prognosis in CSS (p=0.0149) and OS (p=0.0149) compared with non-responders. In cox hazard model, CR achievement was significant prognostic factors for OS (p =0.0015, HR 6.804e+26, 95% CI 56.94-1.631e+86). Patients were able to receive 3 to 5 cycle GC radiation and any grade 3 or more adverse event was 7 (18.4%) cases. no treatment related death was recorded. Conclusions: In selected patients, GC radiation for MIBC may provide good oncological outcomes as bladder preservation strategy.
Neoadjuvant cisplatin-based chemotherapy in patients with ureteral obstruction secondary to muscle invasive bladder cancer.
Authors: Strother Marshall , Kutikov Alexander , Lewis Bianca , Deng Mengying , Handorf Elizabeth A. , Epstein Matthew , Ghatalia Pooja , Greenberg Richard E. , Chen David , Viterbo Rosalia , Anari Fern , Smaldone Marc C. , Zibelman Matthew R. , Uzzo Robert Guy , Plimack Elizabeth R. , Geynisman Daniel M. 
Published: February 2020

523 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by cystectomy is the standard of care for muscle-invasive urothelial bladder cancer (MIBC). 15-35% of MIBC patients present with ureteral obstruction. Poor renal function increases cisplatin toxicity. It is unknown whether patients with ureteral obstruction which has been relieved (whether by nephrostomy tube or nephroureteral stent) have the same risk of toxicity as patients without ureteral obstruction. Methods: We retrospectively reviewed an institutional database of all patients undergoing NAC for MIBC with either dose dense MVAC (ddMVAC) or gemcitabine and cisplatin (GC) from January 2004 through May 2017. Patients without ureteral obstruction prior to initiation of NAC (Group A) were compared to those who had ureteral obstruction which was relieved prior to undergoing NAC (Group B). Continuous variables were compared using the Wilcoxon rank-sum test and categorical variables were compared using Fisher’s exact test. The primary outcome was premature discontinuation of NAC, which was defined as failure to complete all planned cycles. Logistic regression was used to test for differences between the groups in this outcome adjusting for age, ECOG performance status, and baseline glomerular filtration rate (GFR). Results: 160 patients in Group A and 59 patients in Group B were identified. Baseline age, Charlson Comorbidity Index, race, smoking status, and ECOG performance status were similar. Patients in Group B had lower GFR (99.2% vs 78.8% p <0.001) and were more likely to be female (21.9% vs 27.3% p <0.025) and to receive ddMVAC (65.0% vs. 83.1% p =0.012). There was no significant difference between groups in rates of premature NAC discontinuation (15.8% vs 22.0% p = 0.284) or grade ≥3 adverse events (23.4% vs 30.5% p = 0.285). Adjusted analysis showed no significant difference between the groups in frequency of premature NAC discontinuation (OR 1.96, 95% CI 0.84-4.57 p=0.12). Conclusions: We detected no difference in frequency of premature discontinuation of NAC in patients with relieved malignant ureteral obstruction relative to patients without obstruction. NAC for MIBC is likely safe in this population.
Utility of a general molecular screening program in patients with GU malignancies: The ProfiLER trial experience.
Authors: Vinceneux Armelle , Moriceau Guillaume , Lorcet Marianne , Carbonnaux Mélodie , Cassier Philippe Alexandre , Terret Catherine , Baudet Christian , Attignon Valéry , Pissaloux Daniel , Chabaud Sylvie , Wang Qing , Pérol David , Tredan Olivier , Blay Jean-Yves , Negrier Sylvie , Boyle Helen Jane , Flechon Aude 
Published: February 2020

528 Background: Advances in comprehensive tumor molecular pathology in genito-urinary (GU) tumors have driven development of targeted agents since ten years and changed the landscape of GU tumors treatment. We describe our experience with the institutional molecular trial ProfiLER. Methods: Retrospective review of patients with advanced genitourinary malignancies included in the prospective molecular profiling trial ProfiLER (NCT01774409) Tumor samples were analyzed by sequencing a 69 gene panel by next generation sequencing (NGS, Ion torrent PGM system) and whole genome array comparative genomic hybridization (Agilent platform). Clinical data were collected retrospectively. Cases were presented in a molecular board to drive prescription of molecular targeted therapy (MTT) according to the molecular abnormalities observed. Results: Between February 2013 and December 2018 156 adult patients were included, 42 had kidney cancer (including 32 clear cell carcinoma, 5 papillary type 2); 38 prostate cancer, 52 urothelial carcinoma including (16 upper tract), 12 cisplatin-refractory testicular germ cell tumor, 4 penile cancer, 3 adenocarcinoma of the urachus, 2 urethral carcinoma and 3 Leydig cell tumor. Median age at inclusion was 62 years (range 19, 80). Overall NGS and CGH failed in 11.5% of cases, and in 24% of prostate cancer cases.28.8% patients had at least one actionable target (n=45) with a recommended MTT. Only 17.8 % (n=8) patients actually received MTT corresponding to 5.1% of the total screened population. Only one patient had a clinical benefit from MTT. The most frequently initiated MTT were PIK3/AKT/mTOR pathway inhibitors (44,4%), FGRF/EGFR pathway inhibitors (13.3%) PARP inhibitors (8.7%) or cyclin kinase inhibitors (8.7%). The most frequent reasons for lack of MTT initiation were early death, ineligibility for clinical trials due to general condition. Conclusions: Non tumor-specific molecular profiling is feasible in GU cancers. However the use of targeted sequencing with a tumor type specific panel and at an earlier clinical stage may improve the proportion of MTT recommendations.
Comparative response of bladder cancer models to interferon alpha: Recombinant protein versus adenoviral delivery.
Authors: Green Jennifer , Osterhout Robin , McDonnell Scott , Klova Amy , Kamal Adeela 
Published: February 2020

531 Background: Adenoviral delivery of the IFNα2b gene to the bladder urothelium enables prolonged exposure to high levels of IFNα2b protein, relative to intravesically-instilled IFNα protein treatments where short bladder dwell time limits exposure. As such, adenoviral-delivered IFNα2b has demonstrated clinical efficacy in patients with BCG-unresponsive NMIBC. The pleiotropic anti-tumor effects of IFNα include both stimulation of the host immune system and direct cytotoxicity of tumor cells. As clinical efficacy of adenoviral-delivered IFNα2b in the context of bladder cancer could be driven by immune-mediated or direct effects, or both, characterizing the cellular and molecular mechanisms of these activities is warranted. Methods: Here, we investigate the molecular mechanisms of tumor-intrinsic resistance to adenoviral-delivered or recombinant IFNα2b in a panel of bladder cancer cell line and patient-derived bladder cancer organoid models. Adenoviral vectors were constructed that express IFNα2b together with a GFP reporter (Ad-IFNα2b) or GFP alone (Ad-GFP), validated, and benchmarked against in vivo data from the literature. Bladder cancer cells and organoids were treated in vitro with rhIFNα2b, Ad-IFNα2b or conditioned media produced by Ad-IFNα2b infected cells, followed by measurements of cytotoxicity and gene expression in response to treatment. Results: Some bladder cancer models exhibited dose-dependent cytotoxicity in response to IFNα2b treatments, while others were resistant to these effects. Genomic and mRNA features associated with IFNα2b sensitivity/resistance are being evaluated and may inform future investigation of the mechanism of anti-tumor activity in patients. Additional studies to evaluate immune-mediated mechanisms are being conducted. Conclusions: Together, these studies will help to define the molecular mechanisms of response and resistance to IFNa2b treatment in bladder cancer patients.
Impact of histology and toxicities on outcomes of patients with muscle invasive bladder cancer receiving neoadjuvant chemotherapy.
Authors: Curran Catherine , Pond Gregory Russell , Acosta Andres , Nassar Amin , Abou Alaiwi Sarah , Ingham Matthew D. , Preston Mark A. , Steele Graeme S. , Kilbridge Kerry L. , McGregor Bradley Alexander , Mossanen Matthew , Sonpavde Guru 
Published: February 2020

540 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) extends survival in muscle invasive bladder cancer (MIBC) patients (pts). Pathologic complete response (pCR) is associated with survival. We conducted a retrospective study to examine the prognostic impact of other variables including histologic subtype, location, multifocality, margins, size of tumor and toxicities. Methods: Pts who underwent RC at Dana-Farber for MIBC stage T2-T4N0-1 were studied. Data were collected for demographics, clinical and pathologic variables. Descriptive stats were reported, and Cox proportional hazards regression analyses were conducted to examine the association with recurrence-free survival (RFS) and overall survival (OS). Results: From 2002 to 2018, 150 patients were available. The median age was 66 (range 36-89) and 102 (68%) were male. MVAC/dose dense MVAC, GC and other non-standard regimens were given in 42 (28%), 85 (56.7%) and 23 (15.3%) pts, respectively. The 2-yr RFS was 63.6%, the 5-yr OS was 68.7% and pCR occurred in 38 pts (25.3%). Multivariable analysis identified pure urothelial carcinoma in the residual tumor and absence of pathologic response to be associated with poor RFS and OS. Positive margins were associated with poor RFS, while grade ≥3 toxicities were associated with poor OS. Conclusions: Pure urothelial carcinoma histology was associated with worse RFS and OS following RC after NAC for MIBC, suggesting molecular studies may be useful in these cases. The association of severe toxicities with poor OS suggests that optimal pt selection for NAC and early recognition of toxicities is important.[Table: see text]
MHCI and FOXP3 predicting outcome to neoadjuvant atezolizumab in sequential urothelial cancer tissue.
Authors: Szabados Bernadett , Kockx Mark , Van Dam Pieter-Jan , Rodriguez-Vida Alejo , Duran Ignacio , Crabb Simon J. , Van Der Heijden Michiel Simon , Font Albert , Gravis Gwenaelle , Prendergast Aaron , Perdicchio Maurizio , Stanoeva Diana , Daelemans Sofie , Mariathasan Sanjeev , Tea Joy S. , Mousa Kelly , Banchereau Romain , Castellano Daniel , Powles Thomas 
Published: February 2020

541 Background: Biomarker analysis predicting outcome with neoadjuvant atezolizumab in muscle invasive bladder cancer (MIBC) was performed. This includes previously unreported findings with FOXP3 and MHC1. Methods: Sequential tissue obtained from 95 patients in the ABACUSstudy (NCT02662309) which investigated two cycles of atezolizumab prior to cystectomy in MIBC patients. Multiplex immunohistochemistry staining, Foundation One analysis and RNA sequencing was performed on paired pre- and post- treatment samples. CD8+ T cells, fibroblast activation protein (FAP), granzyme – B (GZMB), FOXP3, MHC1, PD-L1 expressions were analyzed and correlated with outcome. Results: After a median follow up of 13.1 months, 31% had a pathological complete response (pCR) and 18% have relapsed. 40% were PD-L1 positive at baseline and 73%, 19% and 8%had inflamed, excluded and desert phenotype respectively. CD8/GZMB and CD8/MHC1 expression prior to therapy was significantly associated with response in inflamed tumors. CD8, PDL1, GZMB and MHC1 expression all increased with treatment in this group of patients. Immune desert phenotype at baseline, showed low and static expression of immune biomarker. TGFb correlated with relapse in excluded phenotypes. Treatment was associated with increase in cell cycle genes and FAP, both of which were associated with relapse. FOXP3 expression correlated with CD8 and increased with therapy in responding tumors. Combining FAP (high) to CD8 (low) and MHC1 (low) increased the positive predictive value for relapse. TMB did not correlate with outcome or increase with therapy. FGF DNA alterations were associated with response. Conclusions: MIBCs have high T effector immune expression, which may account for high pCR rates. Biomarkers at baseline and after treatment can predict outcome. Assessment of multiple biomarker within algorithms improves accuracy in predicting outcome. FOXP3 expression correlates with activated T cell expression, potentially accounting for the counterintuitive findings. Clinical trial information: NCT02662309.
Molecular characterization of neuroendocrine bladder cancer.
Authors: Choi Woonyoung , Hoffman-Censits Jean H. , Fong Megan , Hahn Noah M. , Comperat Eva , McConkey David James 
Published: February 2020

561 Background: Neuroendocrine bladder cancer (NEBC) is a rare and aggressive variant that is associated with poor survival outcomes. Because NEBC is rare, the molecular features of NEBC remain poorly characterized. Therefore, we characterized NEBC at the molecular level to understand the underlying biology and identify novel therapeutic targets. Methods: Whole transcriptome RNAseq was performed on FFPE cores from 24 NEBCs and 51 conventional muscle-invasive bladder cancers (MIBCs) from Tenon Hospital in Paris. Results: Unsupervised cluster analysis of 75 tumors generated 2 distinct clusters that separated NEBCs from MIBCs. The NEBC tumors were strongly enriched with biomarkers for the characteristic of neuroendocrine or small cell malignancies, including DLL3, SOX2, and EZH2. In addition, E2F1 pathway is significantly enriched due to the impair of RB/p53 pathways. Further, the NEBCs were enriched with the TCGA’s neuronal differentiation genes that were associated with high response rates in patients treated in atezolizumab (anti-PDL1) within the context of the ImVigor 210 trial. Nevertheless, the NEBCs were characterized by suppressed immune pathway gene expression signatures, such as the Th1 pathway, effector T cell lymphocyte, and IFNg that are usually highly enriched in tumors that are sensitive to immune checkpoint blockade. Of candidate mechanisms, the suppressed TGFbpathway activity observed in the NEBCs was the most obvious explanation for sensitivity to checkpoint blockade. Conclusions: NEBCs are distinct from conventional MIBCs by gene expression signature. They are also characterized by overexpression of canonical neuroendocrine markers and inhibition of TGFb pathway activity.
Health care team and treatment decision-making experiences among prostate cancer patients.
Authors: Nicksic Nicole E. , Miller Melissa F. , Clark Kelly , Zaleta Alexandra Katherine 
Published: February 2020

57 Background: Treatment by a multidisciplinary healthcare team can improve patient outcomes, but not all prostate cancer (PC) patients may access multiple providers. This study explored whether differences in healthcare team at treatment were associated with PC treatment type and decision-making. Methods: Of 311 PC patients enrolled in the Cancer Support Community’s Cancer Experience Registry online, 160 (32% ever metastatic, 28% had recurrence, median 3 years since diagnosis) indicated which specialists comprised their healthcare team during treatment (urologist versus a specialist team including 2-5 doctors, 70% of which included urologists). We examined PC treatment decision-making using chi-square tests, independent sample t-tests, and linear regression. Results: The majority were not experiencing symptoms of PC at diagnosis (69%); 58% were diagnosed after a routine check-up. More PC patients with advanced disease at diagnosis had a team of specialists, whereas those diagnosed at stages 1 or 2 typically only saw a urologist ( p<0.01). Most first received care at a private urology practice (44%) compared to 27% for current treatment. Treatment discussions varied by treatment for urologist-only (28%) versus a team of specialists (72%): chemotherapy (16% vs 36%, p=.01), surgery (89% vs 65%, p<.01), radiation (82% vs 80%, p=.75), hormones (36% vs 75%, p<.001), and active surveillance (51% vs 23%, p<.001). More patients who had seen only a urologist had surgery (95% vs 43%, p<.001); those seeing a specialty team tended to undergo other treatments, such as chemotherapy (4% vs 30%, p=.001), radiation (12% vs 83%, p<.001), and hormones (27% vs 77%, p<.001). After controlling for stage at diagnosis, those treated only by a urologist had lower treatment regret ( β=0.22, p<.01). Conclusions: Advanced PC patients more often treated by a specialist team and discuss different treatment options vs. those followed by a urologist only. While effects were small, care provider type was associated with treatment regret and confidence. Healthcare teams could improve the patient experience by increasing communication surrounding navigating myriad treatment options. Clinical trial information: NCT02333604.
Long-term outcomes of patients with locally advanced bladder cancer that underwent intra-arterial chemotherapy with/without radiotherapy for organ preservation.
Authors: Matsuo Tomohiro , Miyata Yasuyoshi , Mitsunari Kensuke , Ohba Kojiro , Sakai Hideki 
Published: February 2020

574 Background: We previously reported efficacy and safety of intra-arterial chemotherapy with/without radiotherapy in patients with locally advanced bladder cancer. However, there was no data on long-term outcomes, such as organ preservation, subsequently metastasis, and survival of such therapy. In this study, we investigated outcomes of intra-arterial chemotherapy with/without radiotherapy in these patients for long term periods. Methods: In this study, we investigated 129 patients who treated with intra-vesical chemotherapy (n = 50) and intra-arterial chemotherapy and radiotherapy (n = 79). There was no significant difference on age at diagnosis, gender, grade, and T stage between these two groups. Mean/median follow up periods in intra-vesical chemotherapy (n = 50) and intra-arterial chemotherapy with radiotherapy was 86.5/101 and 107.7/122 months. Results: Rates of bladder preservation in intra-arterial therapy and intra-arterial therapy with radiotherapy are 66.0 and 82.3%, respectively (P = 0.035), and Kaplan-Meier survival curves showed that intra-arterial therapy with radiotherapy had better than intra-arterial therapy (P = 0.007). On the other hand, subsequently metastasis-free survival rates in intra-arterial therapy with radiotherapy was significantly better than those with intra-arterial therapy (P = 0.037). Regrading cause-specific survival, the survival period in intra-arterial therapy with radiotherapy was significantly better than that in intra-arterial therapy (P < 0.001). In addition, even if radical cystectomy was performed, the survival rates after the operation in intra-arterial therapy with radiotherapy was significantly better than that in intra-arterial therapy (P = 0.002). There was no sever complication at late phase (over 5 years). Conclusions: Our results showed that intra-arterial therapy with radiotherapy showed better outcomes of bladder preservation, subsequently metastasis, and survival. In addition, in patients locally advanced bladder cancer received radical cystectomy, intra-arterial therapy with radiotherapy had better prognosis compared to intra-arterial therapy.
A novel clinical decision aid to support personalized treatment selection for patients with CT1 renal cortical masses: Results from a multi-institutional competing risks analysis including performance status and comorbidity.
Authors: Psutka Sarah P. , Gulati Roman , Jewett Michael A.S. , Fadaak Kamel , Finelli Antonio , Morgan Todd Matthew , Pierorazio Phillip M. , Allaf Mohamad E. , Herrin Jeph , Lohse Christine M. , Thompson R. Houston , Boorjian Stephen A. , Atwell Thomas D. , Schmit Grant , Costello Brian Addis , Legere Laura , Shah Nilay , Leibovich Bradley C. 
Published: February 2020

610 Background: Personalized treatment for clinical T1 renal cortical masses (RCMs) should account for competing risks related to tumor and patient characteristics. Using a contemporary multi-institutional cohort, we developed treatment-specific prediction models for cancer-specific mortality (CSM), other-cause mortality (OCM), and 90-day complication rates for patients managed with surgery, thermal ablation (TA), and active surveillance (AS). Methods: Preoperative clinical and radiological features were collected for eligible patients aged 18-91 years treated at four academic centers from 2000-2016. Prediction models used competing risks regressions for CSM and OCM and logistic regressions for 90-day Clavien >3 complications, adjusting for tumor size as well as patient age, sex, ECOG performance status (PS), and Charlson comorbidity index (CCI). Predictions accounted for missing data using multiple imputation. Results: After excluding 25 patients with no follow-up, the cohort included 4995 patients treated with radical nephrectomy (RN, n=1270), partial nephrectomy (PN, n=2842), thermal ablation (n=479), or active surveillance (n=404). Median follow-up was 5.1 years (IQR 2.5-8.5). Predictions from the fitted model are shown in an online calculator ( https://rgulati.shinyapps.io/rcc-risk-calculator ). To illustrate the use of this calculator for a specific patient, a 70-year-old female with a 5.5 cm RCM, PS of 2, and CCI of 3 has a predicted 5-year CSM of 4-7% across treatments, 5-year OCM of 34-49%, and 90-day risk of Clavien ≥3 complications of 4%, 10%, and 6% for RN, PN, and TA respectively. Conclusions: Personalized treatment selection for cT1 RCM is challenging. We present a competing risk calculator that incorporates pretreatment features to quantify competing causes of mortality and treatment-associated complications. Pending validation, this tool may be used in clinical practice to provide patients with estimated individualized treatment-specific probabilities of competing causes of death and complication risks to facilitate shared decision-making.