bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic role of programmed cell death protein 1 expression in surgically treated patients with upper tract urothelial carcinoma.
Authors: Hayakawa Nozomi , Kikuchi Eiji , Mizuno Ryuichi , Fukumoto Keishiro , Kosaka Takeo , Mikami Shuji , Miyajima Akira , Oya Mototsugu 
Published: February 2017

402 Background: Programmed cell death protein (PD-1) expressed on active T cells, and its ligand PD-L1 expressed on the surface of cancer cells, complementarily down-regulate T cell activation and are related to immune tolerance. A close association between PD-1 expression and poor prognosis has been reported in several cancers, however, in upper tract urothelial carcinoma (UTUC) the role of PD-1 expression on clinical outcome has not been investigated. Methods: The protein expression of PD-1 was evaluated by immunohistochemistry and the relationship with clinicopathological features was investigated in surgical specimens obtained from 100 patients who had been surgically treated for UTUC. At a magnification of 200x, PD-1 protein expression was estimated and the positive cells were graded as no (negative), moderate (1-10 cells), and strong ( > 10 cells). Results: Twenty-four patients (24.0%) had strong PD-1 staining, 32 patients (32.0%) had moderate PD-1 staining, and 44 patients (44.0%) had no PD-1 staining. PD-1 staining was associated with pathological T stage (p = 0.023), tumor grade (p = 0.005), and lymphovascular invasion (p = 0.033). Lymphovascular invasion (p < 0.001) and PD-1 staining (p = 0.02) were independent factors for predicting disease metastasis. The 5-year matastatic free survival rate in patients with strong PD-1 staining was 57.3 %, which was significantly lower than that with no PD-1 staining (87.3%, p=0.001) and that with moderate PD-1 staining (74.3%, p = 0.05). In a sub-group analysis of patients with ≥pT2 (N = 59), a significant difference in disease metastasis was observed between patients with strong PD-1 staining and no PD-1 staining (p = 0.018), but was not observed between strong and moderate PD-1 staining (p = 0.146). Conclusions: PD-1 expression may be a useful indicator for a worse prognosis in UTUC patients who undergo radical nephroureterectomy. Targeting therapy against PD-1 might be a promising therapeutic modality for UTUC.
Long-term effects of Bacilles Calmette-Guerin perfusion therapy for elderly patients with upper urinary tract urothelial carcinoma in situ.
Authors: Yoneyama Takahiro , Mikami Jotaro , Fujita Naoki , Sato Tendo , Kojima Yuta , Iwamura Hiromichi , Tobisawa Yuki , Yoneyama Tohru , Mori Kazuyuki , Imai Atsushi , Hatakeyama Shingo , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

404 Background: According to several guidelines, the standard therapy for carcinoma in situ (CIS) of the upper urinary tract is total nephroureterectomy. However, it is difficult to determine a treatment strategy for elderly patients. Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for non-muscle invasive bladder cancer. However, although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract CIS, it has not been established yet. We conducted a retrospective study to assess the long-term effects of BCG perfusion therapy for the upper urinary tract CIS for elderly patients. Methods: We treated 34 patients with upper urinary tract CIS at our clinic between August 2004 and March 2015. 29 patients (22 men and 7 women) with the age of 65 years or older were enrolled. 11 subjects had the entire urinary tract CIS, 8 had bilateral, 10 had unilateral CIS of the upper urinary tract. The average period of observation was 45.5 months ( 5 to 151 ), and the average subject age was 76.5 years (66 to 90 ). We used a double-J catheter for 22 cases, a transvesical single-J catheter whose curl was positions in an upper calyx for 6 cases, and a straight ureteral catheter inserted for ureterocutaneostomy for 1 case. We used 80 mg of BCG for the first 4 cases, 40 mg for the late 25 cases. The BCG treatment was given once a week for consecutive 6 weeks. Urine cytology was performed to assess the treatment validity. Results: Urine cytology tests became negative in 22 of the 29 subjects (75.9%) who underwent upper urinary tract perfusion therapy. Among these 22 subjects who had negative tests, 6 subjects had a recurrence in their upper urinary tracts. Side effects were observed in 28 subjects (89.7%), 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 safe and effective for elderly patients. Results also suggested that this could be one of the effective treatment options. However, we have to be careful for severe side effects.
Consolidative radiotherapy in metastatic urothelial cancer (MUC).
Authors: Srinivas Sandhya , Narayanan Sujata , Fan Alice C. , Hancock Steven Lee , Skinner Eila C. 
Published: February 2017

406 Background: Although rarely curative, chemotherapy remains the mainstay for the treatment of MUC. In patients with MUC who achieve either partial or complete response to chemotherapy, the role of consolidative radiation remains unknown Methods: From our single institution database of 2597 patients with urothelial carcinoma (UC) treated since 1997, we identified 22 patients with MUC who underwent consolidative radiotherapy after a partial response to chemotherapy with the intent of rendering them disease free. All patients had undergone primary surgical therapy with either cystectomy or nephroureterectomy. We excluded patients who received radiation for a palliative intent. Progression Free survival (PFS) was defined as time from completion of RT to relapse or last follow up. Overall Survival (OS) was defined as time from start of chemotherapy to death or last follow up. Results: The median age of the patients was 67 years; 64% were men and 59% had received prior cisplatin based chemotherapy. The most common sites radiated were the regional lymph nodes (64%). Other radiated sites included the lung, adrenal glands and omental metastases. Median time from cystectomy to relapse was 22 months. Median survival from diagnosis of cystectomy was 48 months. Median PFS was 13 months and median OS was 29 months. Nine patients (41%)were alive and disease free 6 years after radiation. Conclusions: In this highly selective cohort of patients with MUC treated with consolidative radiation after chemotherapy, 41% were rendered disease free. Patients who were rendered disease free were those with nodal metastases and needing radiation to a single site of metastases. This suggests that radiation is feasible and may contribute to long-term disease control. Further prospective studies should be undertaken to better characterize who would best benefit from this combined consolidative modality treatment strategy.
High throughput screening to assess urothelial cancer lines and their metastatic derivatives for assessing changes in sensitivity in therapeutics.
Authors: Krane Louis Spencer , Railkar Reema , Hsu Iawan , Vocke Cathy , Meltzer Paul S. , Thomas Craig , Ferrer Marc , Agarwal Piyush K. 
Published: February 2017

407 Background: Chemotherapy for urothelial cancer (UC) is less effective in patients with large volume metastatic disease, likely due to acquired driver mutations. Driver mutation may lead to differences in sensitivity between primary cell lines and metastatic clones. Quantitative high throughput screening (qHTS) assesses large drug libraries to evaluate in vitro effectiveness. We utilized this modality to compare effectiveness of cell inhibition in two bladder cancer cell lines with their metastatic lines. Methods: We screened T24 and UMUC-3 bladder cancer cell lines against 1,912 oncology-focused drugs using a 48 hr cell proliferation assay with an ATP-based readout (CellTiterGlo), and determined the activity and potency of the compounds in a dose response manner. We compared the results of their activity with known metastatic lines for reach of these primary lines: T24T, SLT3 and FL3 for T24 and LUL2 UMUC3 and UMUC3-luc (LUC3). We identified candidate drugs based on two parameters: 1) more than 70% inhibition at 48 hours and 2) a curve class of -1.1 or -1.2 indicating curve class with good fit (r2 > 0.9). We used a custom capture next generation DNA sequencing chip for exonic regions of 229 known cancer related genes to compare primary and metastatic tumor cell lines. Results: The qHTS compounds, are demonstrated in figure 1a for T24 cell lines and figure 1b for UMUC cell lines. Amongst 1912 drugs tested, only 141 (7.4%) met inclusion criteria for T24. However, only 79 of these drugs (56%) met criteria for all cell lines derived from T24. 160 (8.4%) compounds were found to be active in the UMUC line. Only 32 (20%) of the UMUC3 detected compounds remained active in all UMUC3 derived cell lines. Genomic comparison between cell lines identified several mutations which were found only in the derived cell lines (RAC1 and CDH1 in UMUC3) and (AR, CDK12, GATA1, GUCY1A2 in T24). Conclusions: qHTS of a library of potential therapeutic interventions can produce a list of targets and therapies for bladder cancer. This data reinforces the differences between primary and metastatic tumors as compounds identified active in the primary cell lines were inactive in known metastatic cancer cell lines .
Recovery after surgery and care coordination pathway at City of Hope: Length of stay, readmissions, and complications.
Authors: Kardos Steven V. , Chan Kevin G. , Yuh Bertram E. , Yamzon Jonathan , Ruel Nora , Zachariah Finly , Lau Clayton S. , Crocitto Laura E. 
Published: February 2017

410 Background: Bladder cancer is the second most common urologic malignancy with over 73,350 new cases diagnosed annually of which the incidence is increasing in the elderly. Radical cystectomy (RC), the gold standard for muscle invasive disease, carries a particularly high risk of morbidity and mortality, as well as a protracted length of stay (LOS) and increased readmission rates when compared with other major urologic procedures. Furthermore, in 2013, the Institute of Medicine (IOM) declared cancer care in the US a national crisis with a priority to improve quality of care through care coordination (CC). Simultaneously, enhanced recovery after surgery (ERAS) protocols have surfaced as coordinated, evidence-based models designed to standardize medical care, improve outcomes, and lower healthcare costs. At City of Hope (COH), we evaluated our ERAS and CC pathway. Methods: In April of 2014, an ERAS and CC pathway for bladder cancer was launched at COH with an emphasis on the perioperative care of patients (pts) from a multi-disciplinary team perspective. Preoperatively, pts undergo orientation on stoma education, goals of care, and treatment expectations. The pathway clinically focuses on avoidance of bowel preparation, early feeding, minimizing narcotics, and u-opioid antagonists. On discharge, pts are closely monitored via scheduled phone calls as well as clinic visits. Quality metrics including LOS, complications, and readmissions are reported as median and interquartile range along with descriptive statistics including chi-square and Wilcoxon rank-sum tests. Results: Since implementation, the median LOS was statistically significant between cohorts with 6 days for pts on pathway compared to 8 days for those preceding the pathway (p = 0.0007). Furthermore, the complication and readmission rates have decreased from 67.5% to 50% and from 35% to 30%, respectively. Dehydration and urinary tract infection (UTI) accounted for 17.9% and 21.4% of readmissions for those prior to the pathway, while UTI occurred in 5% of pts readmitted after adhering to the pathway. Conclusions: Our ERAS and CC pathway has reduced LOS without an increase in complication nor readmission rates.
Vector analysis of bladder cancer patient setup utilizing a magnetic resonance image-guided radiation therapy (MR-IGRT) system.
Authors: Fischer-Valuck Benjamin Walker , Green Olga L , Gay Hiram Alberto , Mutic Sasa , Michalski Jeff M. 
Published: February 2017

412 Background: Inter and intra-fraction anatomy changes in patients undergoing radiation therapy (RT) for bladder cancer (BC) are common but have thus far been studied with implanted fiducial markers, limited quality 2-D orthogonal films and computed tomography (CT). The adverse impact of daily set-up variation could be more significant than appreciated. Our goal was to employ the soft tissue imaging capabilities of an integrated magnetic resonance image-guided RT (MR-IGRT) system to analyze daily positioning. Methods: Fourteen patients with BC were treated on a MR-IGRT system. Patient setup was performed via volumetric MR imaging with a resolution of 0.15 x 0.15 cm. Alignment was performed according to skin marks then shifts assessed by comparing the treatment volume from the planning CT to the daily MR image. 240 pretreatment MR images were analyzed and 3 shifts were recorded for each image. A vector shift was calculated by combining the square root of the combined sum of the shifts squared. Number of times that the vector of combined shifts would have exceeded the planning tumor volume (PTV) was recorded. Results: Daily volumetric MR imaging allowed for accurate alignment and daily monitoring of bladder volume and normal tissue anatomy. Recorded shifts of the treated volume were 0.9±0.5 cm in the right/left direction, 0.7±0.3 cm in the anterior/posterior direction, and 0.7±0.4 cm in the cranio-caudal direction. In 66 (28%) of cases the vector shift was initially greater than the PTV margin. For 2 patients, pre-treatment MR imaging revealed the tumor reduced in size and dose to the bowel would have exceeded constraints, and treatment adaptation was performed to reduce normal tissue toxicity. Using CTCAE criteria, no grade 3 or higher toxicities have been reported. Conclusions: Accurate and reproducible treatment delivery is required to avoid marginal misses to the target volume as well as excess dose to normal tissue. MR-IGRT allows for excellent soft tissue visualization which enables for the avoidance of potential setups errors by allowing daily alignment changes to ensure the target is included in the PTV. It also allows the ability to make treatment changes based on anatomy variations.
Chemotherapy treatment patterns and survival outcomes in patients with visceral metastatic upper tract urothelial cell carcinoma.
Authors: Sevillano Elena , Werner Lillian , de Velasco Guillermo , Mullane Stephanie A. , Terrasa Josefa , Gonzalez del Alba Aranzazu , Bellmunt Joaquim 
Published: February 2017

415 Background: Upper tract carcinoma (UTUC) is a poorly studied location amongst urothelial tumors. Treatment strategies are often extrapolated from bladder cancer and are not well defined. We aimed to retrospectively evaluate the chemotherapy (CT) treatment patterns and prognostic factors associated with outcome in patients (pts) with visceral metastatic UTUC. Methods: We collected clinical data on 102 UTUC pts treated at Dana-Farber Cancer Institute between Jan 2001 and Dec 2014. We focused our analysis on pts who recurred with visceral metastasis after radical nephroureterectomy and were subsequently treated with CT. Patients with lymph node only recurrence were excluded. Of 102 pts, 74 developed visceral metastasis from which 45 were treated. Overall survival (OS) was defined from date of first line CT for metastatic disease to date of death or censored at last follow up. Kaplan Meier method was used to estimate median OS. Cox regression model was used to summarize the association of OS and potential prognostic factors. Results: Overall, 45 pts received CT. The most common sites of metastases were lung (60%, n = 27), liver (49%, n = 22) and bone (36%, n = 16). 36 % of the pts (n = 16) received first line CT with cisplatin-based combinations. With a median follow up of 29.8 mo the median OS was 14.7 mo, with 32 pts having died at the time of analysis. PS, Hb ≤ 11 and other described known factors were analyzed as well as the impact on OS of the type of CT given cisplatin vs non cisplatin. 81% of the pts (n = 37) had PS < 2. PS 0-1 vs > 1 was included as an exploratory analysis being the number of pts small for grouping. Lower Hb was associated with shorter OS (p = 0.04). Cisplatin vs non cisplatin regimens had a trend on survival benefit in the analysis done in 11 pts (19,3 vs 13,2 mo). Further analysis is ongoing. Conclusions: Although only one third of patients were eligible, this study supports the use of cisplatin regimen to optimize survival in patients with UTUC and visceral metastasis. A significant correlation between Hb ≤11 and OS were observed. The exploratory analysis of PS 0-1 vs > 1 did not have an impact on survival. [Table: see text]
Extended analysis of a validated urine-exosome signature to predict high grade prostate cancer on initial biopsy: Performance across multiple sub-groups.
Authors: Donovan Michael , Bentink Stefan , Noerholm Mikkel , O'Neill Vince , Skog Johan 
Published: February 2017

42 Background: We recently completed a prospective observational clinical trial of a first-catch urine exosome gene expression signature (ExoIntelliScore Prostate) to predict high-grade prostate cancer, HGPCA (>/=GS7) on initial biopsy. The assay accurately predicted HGPCA with an NPV>90% for an intended use popuation: men >/= 50 years with an equivocal PSA of 2-10 ng/mL presenting for their first biopsy. Given the current high prostate biopsy rate and potential impact of race, we sought to further understand performance of the assay by constructing sub-cohorts from the validation study. Methods: Utilizing the ExoIntelliScore Prostate result and clinical data from the 519 patient intended use clinical validation cohort (IU), we constructed several subgroups including: i. prior negative (A, n=149), ii. combined prior negative + initial biopsy (B, n=668) and African Americans, AA (C, n=87). Area under the curve (AUC), NPV, PPV, sensitivity and specificity with validated cut-point assess performance. Results: There was demographic comparability between the initial intended use (IU) and various subgroups, i.e., prior negative (A), combined prior negative and initial biopsy (B) and African Americans (C) with some exceptions observed (bold) for AA patients; family history (IU, 23%; A: 27%, B: 24%, C: 30%; positive biopsy rate (IU, 48%; A: 34%, B: 45%, C:52%; and >/= GS7 (IU, 28%; A: 13%, B: 27%; C: 34%). The AUC range for ExoIntelliscore Prostate + standard of care (i.e., age, race, PSA and family history) between IU and A, B subgroups was 0.72-0.74; AUC for AA was 0.62, except for prior negative biopsy AA patients, AUC 0.80; supporting importance of prior negative biopsy. Of note, applying the ExoIntelliscore Prostate cut-point, A, B yielded an NPV of 91%; including NPV of 89% for AA (initial biopsy) and NPV of 91% for AA with initial + prior negative biopsy. Conclusions: The ExoIntelliScore Prostate performed equally well in men with or without a prior negative biopsy with comparable results also seen for African Americans. Additional confirmatory studies with more patients is necessary to confirm initial observations.
Comparative effectiveness of a patient centered pathology report for bladder cancer care.
Authors: Mossanen Matthew , Macleod Liam Connor , Chu Alice , Wright Jonathan L. , Lin Daniel W. , Dalkin Bruce L. , True Lawrence D. , Gore John L. 
Published: February 2017

420 Background: We compared the effectiveness of a patient-centered (PC) version of bladder biopsy pathology reports derived from PC outcomes research methods with standard pathology reports. Methods: Local bladder cancer experts provided consensus on the important elements of a bladder biopsy pathology. Patient focus groups reviewed these elements and identified PC formats and language. Candidate reports were iterated with patients to arrive at a pilot PC bladder biopsy report. We enrolled 40 patients undergoing bladder biopsy for suspicion of initial or recurrent bladder cancer. Block randomization was performed to the standard report or the standard report and the pilot patient-centered pathology report (PCPR). Through web-based surveys, we assessed self-efficacy with the PEPPI (Perceived Efficacy in Patient-Physician Interactions), physician communication with the CAT (Communication Assessment Tool), knowledge based on comprehension of report elements prioritized by experts, and format preferences at pathology disclosure and one month later. We compared study groups with descriptive statistics. Results: The 26-member expert clinician panel identified stage, grade, and histology as the most important elements of a pathology report. Patients prioritized data expressed in a narrative format, an illustration of tumor stage, and risk stratification for future recurrence. From July 2014 to 2015, 39 patients completed initial and follow-up assessments. Patients that received the PCPR had an improved ability to identify their cancer stage (initial 58% vs 20%, p = 0.02; follow-up 47% vs 15%, p = 0.03) and trended toward improved identification of cancer grade (initial 74% vs 50%, p = 0.12) compared with patients that only received standard reports. Ratings of patient self-efficacy did not differ by report format and communication trended toward improved communication for patients exposed to PCPR. Conclusions: PCPR are associated with greater patient knowledge about their new cancer diagnosis and may aid patient-provider communication around a new cancer diagnosis. While these results require validation in larger cohorts, this pilot may serve as a model for the development of PCPR for other cancers.
Sequential chemotherapy with gemcitabine+carboplatin followed by gemcitabine+carboplatin+docetaxel for advanced upper-tract urothelial cancer.
Authors: Yoneyama Takahiro , Sato Tendo , Mikami Jotaro , Kojima Yuta , Fujita Naoki , Iwamura Hiromichi , Tobisawa Yuki , Yoneyama Tohru , Mori Kazuyuki , Imai Atsushi , Hatakeyama Shingo , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

428 Background: Chemotherapy for advanced upper-tract urothelial cancer (UC) has not yet been established. Gemcitabine+cisplatin may be a promising regimen for advanced upper-tract UC as well as for advanced bladder cancer. However, cases with renal dysfunction are common in advanced upper-tract UC, and cisplatin often unfits for those patients. We retrospectively evaluated the effectiveness and adverse events (AEs) of a sequential chemotherapy with gemcitabine+carboplatin(GCarbo) followed by GCarbo+ docetaxel (GCarboD) for advanced upper-tract UC. Methods: We treated 74 patients (52 men and 22 women) with advanced upper-tract UC from September 2004 to December 2014. Mean age was 69.3 (43–89), and mean Ccr was 50.5 (11.6–99.3) ml/minute. Mean observation period was 24.0 (3–96) months. The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (70mg/m2) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR. GCarboD treatment was administered in 21 cases, and yielded two (9.5%) PR. The median survival period was 18.3 months with GCarbo/GCarboD regimens. Adverse events (AE) of grade 3 or higher occurred in 48 of those who had undergone the GCarbo therapy (64.9%). In GCarboD regimen, there were 20 (95.2 %) of G3/4 AEs. Conclusions: GCarbo and GCarboD chemotherapy can be administered safely to advanced upper-tract UC cancer, many of whom have renal dysfunctions. GCarbo regimen achieved high response rate (50.0%) in advanced upper-tract UC. However, GCarboD had limited effectiveness for non-responder of GCarbo.