bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application-based perioperative management of the radical cystectomy patient.
Authors: Metcalf Meredith , Hamilton-Reeves Jill , DeRuyter Martin , Bishop David , Hand Lauren , Holzbeierlein Jeffrey M. , Lee Eugene 
Published: February 2018

480 Background: Radical cystectomy patients are a vulnerable population, with up to 65% suffering complications and 26% readmitted within 90 days. Perioperative education, early identification of patients at risk, and discharge transitions remain central to improving outcomes. This project aimed to examine the feasibility of using LifeScience Technologies tablet-based application (LST app) for perioperative patient education, transition care communications, and post-discharge monitoring. Methods: We initiated a prospective feasibility pilot trial (NCT NCT02942121) in 20 patients undergoing radical cystectomy. Participants were provided an iPad preloaded with the LST app and equipment to measure vital signs during the study. Patient education videos tailored to each individual based on gender and diversion type were sent via the app for viewing preoperatively. Postoperatively participants were asked to log medication compliance and vital signs. Vital equipment was wirelessly transmittable, and the study team was alerted to any abnormal patient data. Compliance with watching videos and recording vital signs was the primary aim of the study. Results: Twenty patients were enrolled between 2/2017 and 10/2017. Two patients discontinued due to difficulty with electronics, two due to oncologic restaging, and two await surgery. Patients watched 155/235 (66%) of assigned education videos. On average, each video was viewed 2.1 times (range 0-3.7), and 16/18 (89%) of all videos were watched more than once. Excluding the patients who did not complete the trial, compliance in video watching was 143/193 (74%). Complete vital signs were logged on 181/227 (70%) of patient study days. Excluding patients who did not complete the trial, compliance in vital sign recording was 175/216 (81%). Conclusions: Tablet-based applications are emerging as adjuncts to traditional clinical practice. This protocol demonstrates patient compliance with assigned tasks and was feasible for extending educational content beyond the office while allowing for repetition of viewing, vital for improving comprehension and recall. Additionally, patients were compliant with recording vitals while at home, demonstrating feasibility of this novel technology. Clinical trial information: NCT02942121.
Association of stromal lymphocyte infiltration with tumor invasion depth and high-grade T1 bladder cancer.
Authors: Rouanne Mathieu , Betari Reem , Radulescu Camélia , Signolle Nicolas , Allory Yves , Marabelle Aurelien , Adam Julien , Lebret Thierry 
Published: February 2018

488 Background: Morphological assessment of tumor-infiltrating lymphocytes (TIL) has been shown to provide prognostic and potentially predictive significance in many different tumor types. Large studies investigating TIL in urothelial carcinoma are lacking. We investigated in a homogenous population of patients with high-grade T1 (HGT1) bladder cancer the association of TIL with clinico-pathological parameters and clinical outcomes. Methods: Pretreatment index tumors were collected between 2000 and 2015 from 147 patients with primary high-grade cT1N0M0 bladder cancer. The density of stromal TIL was evaluated using hematoxylin and eosin (H&E)-based staining on whole tissue sections. Stromal TIL density was scored as percentage of stromal area infiltrated by mononuclear cells. Inter-reader assessment and stromal TIL correlation with a subset of CD3+ stained sections were evaluated. The main endpoint was correlation with overall survival (OS). Hazard ratios (HRs) and 95% CIs associated with stromal TIL were estimated through a multivariable Cox model. Results: Median follow-up was 8.2 years (6.1-9.5). Induction BCG therapy was followed by 126 patients (86%). Recurrence and progression were respectively observed in 67 patients (46%) and 40 patients (27%). Stromal TIL density was high (≥10%) in 82 tumors (56%). The overall agreement was good between the two readers (κ = 0.75). Correlation between stromal TIL density analyzed on H&E-sections and CD3+ IHC staining was high (ρ = 0.71, p < 1.10-5). Stromal TIL were positively associated with variant histology (p = 0.01) and tumor invasion depth (p = 0.03). For the OS analysis, intense (≥10%) vs. non-intense ( < 10%) stromal TIL unadjusted HR (95% CI, p) was 1.30 (0.75-2.24, p = 0.34) and adjusted HR was 1.25 (0.72-2.16, p = 0.43). Conclusions: Density of stromal TIL was associated with tumor invasion depth and variant histology, but not with prognosis of patients with HGT1 bladder cancer. These data suggest that tumor progression is associated with an increased adaptive immune response but other factors may influence outcome of patients. Characterization of TIL subpopulations may be required to identify immune-related prognostic factors.
Is radical radiotherapy effective for elderly patients with muscle invasive bladder cancer?
Authors: Price James , Sivanandan Mayuran , Elmusharaf Rania , Chakraborti Prabir R , Smith-Howell Mike , Das Prantik 
Published: February 2018

506 Background: Radical radiotherapy (RT) is a curative option for muscle-invasive bladder cancer (MIBC), and offers the chance of bladder preservation. RT and radical cystectomy have not been compared in an RCT, but landmark trials of RT +/- concurrent systemic therapy have demonstrated outcomes comparable to surgery. In clinical practice, patients are often older and less fit compared to trials, and consequently may not be fit for concurrent chemotherapy which may impact treatment outcomes. Methods: A retrospective review of all patients aged 70 years or older treated with radical RT for MIBC from January 2010 – October 2016. Minimum 12 months follow-up. iSOFT manager for used for clinical data and MOSAIQ for radiotherapy parameters. Statistical analysis performed using Stata version 11.2. Results: 71 patients were identified. Male: female ratio 3:1 and median age 79 (range 71 – 93). Median performance status (PS) 1. 81.7% of patients had pT2 disease or greater, 77.5% of patients underwent TURBT prior to RT and 97.2% had transitional cell-carcinoma histology. 38 patients were treated to 60-64Gy/30-32 fractions and 33 patients to 52.5-55Gy/20 fractions. 6 patients (8.5%) received neoadjuvant chemotherapy and 15 (21.1%) received concurrent chemotherapy. Of the 53 patients who did not receive chemotherapy, all were deemed not suitable. 23 of 71 patients (32.4%) developed a loco-regional relapse, either in the bladder (n = 18), pelvic lymph nodes (n = 4), or on cytology alone (n = 1). 24 patients (33.8%) developed distant metastases, only 7 of these were fit for palliative chemotherapy. The median progression-free survival (PFS) was 17 months (95% C.I. 10 – 34 months). Neoadjuvant and concurrent chemotherapy use was not associated with an increased PFS (p = 0.99 and p = 0.97, log rank). The median overall survival was 18 months (95% C.I. 14 – 27 months). Conclusions: Our data demonstrate RT produces favourable outcomes for elderly patients and reasonably well tolerated without significant toxicities. Use of concurrent systemic therapy did not significantly improve outcomes, but numbers were small.
The impact of neoadjuvant chemotherapy (NAC) on conditional survival (CS) among patients with muscle-invasive bladder cancer (MIBC).
Authors: Waingankar Nikhil , Jia Rachel , Ferket Bart , Audenet François , Mehrazin Reza , Sfakianos John , Mazumdar Madhu , Galsky Matt D. 
Published: February 2018

520 Background: Achieving a pathologic complete response (pCR) with NAC for MIBC is associated with a favorable prognosis. Patients with pathologic residual disease (pRD) generally have poor outcomes. However, prognosis after radical cystectomy (RC) improves with ongoing survivorship. Whether the difference in prognosis of patients with pCR and pRD is sustained over time has not been explored. Methods: We queried the National Cancer Database for patients who received NAC and RC for clinically localized MIBC (cT2-T4aN0M0) between 2002-2010. We identified patients with pCR (</= pTis) and pRD. Using Kaplan-Meier analysis, we assessed CS up to 5 years given survivorship of 0-4 years using log-rank test with multiple comparison adjustment. Results: The cohort comprised 1,554 patients (pCR: 314, pRD: 1,240). The median follow up was 2.38 (0.04-9.60) and 2.76 (0.01-9.97) years for pCR and pRD, respectively. Patients with pCR had lower stage (cT2= 79% vs. 72%; cT3= 14% vs. 18%; cT4= 7% vs. 10%), more recent diagnosis (2010: 31% vs. 19%), and were more often treated at a high-volume center (>15 RC/year: 61% vs. 49%). Patients with pCR had improved CS relative to those with pRD with survivorship up to 3 years, but the benefit associated with pCR becomes attenuated from 4 years post-RC (Table). Conclusions: MIBC patients with pRD after NAC have worse CS up to years 3 post-RC, but this difference diminishes after 4 years. These findings may inform patient counseling, surveillance intensity, and novel adjuvant approaches for patients with pRD, and are subject to confirmation with a forthcoming multivariable analysis. Probability of surviving to X years (95% CI). [Table: see text]
Pre-operative chemotherapy (ctx) in plasmacytoid urothelial carcinoma (PUC).
Authors: Teo Min Yuen , Al-Ahmadie Hikmat , Seier Kenneth , Ostrovnaya Irina , Regazzi Ashley Marie , Dalbagni Guido , Bochner Bernard H. , Funt Samuel , Iyer Gopa , Bajorin Dean F. , Rosenberg Jonathan E. 
Published: February 2018

522 Background: PUC is characterized by E-cadherin loss, diffuse growth pattern and aggressive natural history. Management of this entity is controversial. This retrospective study aims to evaluate the impact of PUC histology on clinical outcomes with ctx compared to UC-NOS. Methods: Consecutive cases of nonmetastatic PUC were identified as either (1) localized disease (LD: cT2-3 cN0) or (2) locally-advanced (LA: fixed bladder or radiographic nodal disease). All cases were reviewed by a GU pathologist to confirm PUC histology per WHO classification (2016). A separate cohort of neoadjuvant(NAC)-treated UC-NOS (Tully et al, ASCO GU 2014) served as comparator for clinical outcomes. Kaplan-Meier estimates and logrank test were used for analysis of recurrence free (RFS) and overall survival (OS) defined from date of cystectomy (RC). Results: Between 2000 and 2017, eighty one PUC were identified, with median age of 65 years (range: 22 - 84) and 65% male. Thirty patients (pts) had up-front RC; 51 pts had ctx. In the former group, all pts had LD but upstaging was seen on post-op pathology: 63% pT3, 17% pT4 and 37% pN+. Among ctx pts, 33/51(65%) were LD and had NAC: 70% had ctx doublet and 24% triplet; 82% had 4 cycles and 18% had up to 6 cycles. Response ( < pT2 pN0) was seen in 7/33(22%), four (12%) of which had no residual disease (pCR). Six RC were aborted after NAC for pT4b disease. NAC response was not associated superior RFS (NR vs. 17.3 months; HR 0.52 95% CI 0.18 – 1.47, p = .218) or OS (41.3 vs. 25.5 months; HR 0.65 95% CI 0.23 – 1.87, p = .428). Compared to UC-NOS, PUC responders had significantly inferior outcomes (table). In LA cohort, majority had triplet chemotherapy (72%) and up to 6 cycles (89%). Response was seen in 4/18(22%) pts, with two pCR (11%). Five RC were aborted for pT4b disease. Median RFS and OS were 5.8 and 10.5 months, respectively, with 19% alive at 2-years. Most common sites of recurrence/progression for PUC were peritoneal (42%) and locoregional invasion (26%). Conclusions: Outcomes for PUC are poor with conventional NAC-RC approach. [Table: see text]
An analysis of multiple biomarkers to better predict prostate cancer metastasis and death after radical prostatectomy.
Authors: Zhang Alison Yan , Chiam Karen , Haupt Ygal , Fox Stephen B. , Birch Simone , Tilley Wayne , Butler Lisa , Knudsen Karen E. , Cornstock Christopher , Rasiah Krishan , Grogan Judith , Mahon Kate Lynette , Bianco-Miotto Tina , Bohm Maret , Henshall Susan M. , Delprado Warick , Stricker Phillip , Horvath Lisa , Kench James 
Published: February 2018

54 Background: Identification of potentially lethal disease at the time of diagnosis with localized prostate cancer (PCa) remains a significant clinical issue despite a plethora of candidate biomarkers. This study evaluates a range of biomarkers previously associated with biochemical relapse (BR) in localized PCa to determine whether a combined expression model can improve detection of clinically significant cases. Methods: The Australian PCa Research Centre NSW has completed 23 studies of molecular biomarkers associated with BR in a well-described localized PCa cohort (n=324, median followup 16 years). 12 studies were excluded due to missing data. Each biomarker was analyzed as a marker for metastatic-free survival (MFS) and prostate cancer specific survival (PCSS) and then used to develop a prognostic model for clinical outcomes incorporating clinico-pathological factors. This model is currently being validated in an independent cohort. Results: The PCa cohort experienced 39 metastatic relapses (12%) and 23 PCa deaths (7%). Of 12 biomarkers (AR, AZPG1, C0S, Cyclin D1a, Cyclin D1b, E6AP, H3K18Ac, H3K4me2, Ki67, p53, PML, SGTA) assessed, only AZGP1 and Ki67 were associated with MFS (HR 2.9, 95% CI, 1.4-5.6; P=0.002, and HR 1.2, 95% CI, 1.0-1.4; P=0.03, respectively) and PCSS (HR 4.2, 95% CI, 1.7-10.5; P=0.002; and HR 1.2, 95% CI, 1.0-1.5; P=0.04, respectively). The combined panel of AZGP1 and Ki67 was an independent predictor of MFS (HR 1.9, 95% CI, 1.1-3.2; P=0.01), and PCSS (HR 3.3, 95% CI, 1.5-7.3; P=0.002) when modeled with known clinicopathological variables. The panel was more robust in predicting MFS and PCSS compared to the individual biomarkers alone and superior to other prognostic models (See table). Data from the validation cohort will be available for the meeting. Conclusions: Our novel signature of AZPG1 and Ki67 improves existing prognostication tools in predicting PCa metastasis and death. [Table: see text]
VinCaP: A phase II trial of vinflunine chemotherapy in locally-advanced and metastatic carcinoma of the penis (CRUK/12/021).
Authors: Pickering Lisa M. , Tovey Holly , Elliott Tony , Burnett Stephanie M. , Bahl Amit , Kirkbride Peter , Mitra Anita , Thomson Alastair H , Vasudev Naveen , Slade Rachel , Tregellas Lucy , Morgan Bruno , Hassall Alison , Hall Emma , Nicholson Steve 
Published: February 2018

547 Background: Platinum-based combination chemotherapy regimens are used in the treatment of carcinoma of the penis, but toxicity limits their value for patients with metastatic disease. This trial aims to define both the toxicity and the rate of disease control for the non-platinum cytotoxic agent Vinflunine. Methods: A phase II single-arm trial was designed to demonstrate a clinical benefit rate of at least 40% and to exclude a rate of less than 15% (p0 = 0.15, p1 = 0.40, α = 0.05, β = 0.80, Fleming-A’hern exact design). 22 evaluable patients were required. Key eligibility criteria included measurable, histologically-proven squamous cell carcinoma of the penis staged as M1; or M0, Tx, N3; or M0, Tx, N2 and deemed inoperable by multidisciplinary team; or M0, T4 any N. Patients were required to have ECOG performance status of 0, 1 or 2 and adequate hepatic and renal function. Treatment comprised four 21-day cycles of vinflunine (320mg/m2) with RECIST v1.1 restaging following cycle 4 (response primary endpoint). Patients deemed to be benefitting from treatment were permitted to continue vinflunine at the discretion of the treating clinician until progression or unacceptable toxicity. Results: 25 patients were recruited from 8 UK centres between June 2014 and May 2017. Median age was 68 years; 19 patients had metastatic (M1) disease. All patients have completed trial treatment and primary endpoint assessment. Data cleaning for the primary analysis is currently in progress, with the snapshot for the primary analysis due in October 2017 and primary analysis to be presented to the trial oversight committees in November 2017. Conclusions: It is hoped that single-agent vinflunine will be associated with a favourable toxicity profile combined with meaningful clinical responses. The results will be available for presentation at the meeting. Clinical trial information: NCT02057913.
Current practice patterns surrounding fertility concerns in stage I seminoma patients: Survey of United States radiation oncologists.
Authors: Post Carl M , Jain Aditya , Degnin Catherine , Chen Yiyi , Craycraft Michael Ellis , Hung Arthur , Jaboin Jerry Jeff , Thomas Charles R. , Mitin Timur 
Published: February 2018

553 Background: Patients with testicular seminoma may face fertility issues because of their underlying disease as well as treatments they undergo. The current patterns of practice among US radiation oncologists aimed at assessing and preserving fertility in patients with Stage I seminoma are unknown. Methods: We surveyed practicing US radiation oncologists via an IRB-approved online questionnaire. Respondents’ characteristics, and perceived patient infertility rates were analyzed for association with treatment recommendations. Results: We received 353 responses, of whom one quarter (23%) consider themselves experts. A vast majority (84%) recommend observation as a default strategy. 52% routinely advise fertility assessment for patients prior to observation or chemotherapy, and 74% routinely do so prior to adjuvant RT. Nearly two-fifths believe that 10% and 30% of patients are infertile following orchiectomy. Thirty-seven and 22% believe infertility rates following para-aortic RT to be 30 and 50%, respectively. 80% routinely use clamshell scrotal shielding. Responders with higher perceived infertility rates are more likely to recommend fertility assessment/sperm banking (Fisher’s exact p<0.0001). Responders who routinely advised fertility assessment were more likely to use clamshell shielding (Cochran-Armitage trend test p = 0.0007). Clamshell use was positively correlated with higher perceived infertility rates following para-aortic RT (Spearman’s correlation coefficient = 0.006). Conclusions: Despite a clear knowledge of fertility issues in men diagnosed with seminoma, there is no universal adoption of fertility assessment among US radiation oncologists.
High-dose chemotherapy (HDC) and stem-cell rescue as salvage treatment for germ cell testicular tumors in second- and third-line, and outside clinical trials.
Authors: Ronchi Fernanda Carneiro , Araujo Daniel Vilarim , Urvanegia Ana Claudia Machado , Rinck José Augusto 
Published: February 2018

557 Background: Germ-cells testicular tumors are the most common cancer in young males, usually curable in early stages. Therefore, only 25% of relapsed patients are long-term survivors. Previous non-randomized studies showed promising results with HDC, however, the only randomized trial did not support this approach. Here we report our experience in a Brazilian academic center Methods: We conducted a retrospective review of all consecutive patients treated with salvage HDC followed by Stem-Cell transplantation at our service (1996 – 2016). Survival curves were estimated by Kaplan-Maier method. Prognostic factors were determined by Cox regression model. Results: We found 36 eligible patients. The cohort median follow-up was 56 months (m). At 2 years 50.4% of the patients were alive, and 46.7% were disease-free. The median overall survival (OS) was not-reached and the median progression-free survival (PFS) was 21.8 m. The overall response-rate was 61.2% (22% had complete response and 39% had partial response). All patients who achieved complete response were alive at the last follow-up, and only one had progressive disease. Out of the patients who achieved partial response, one third were rescued with surgery (46% teratoma, 23% fibrosis, and 31% residual disease). Approximately 80% were alive in 2 years vs 20% not operated. Complete response (vs. others) and HDC as second line treatment (vs. 3rd and 4th) were good prognostic factors, (HR N/A; p 0,03, HR 0.19; CI: 0.04-0.88, p = 0.01 respectively). In 2 years, the OS in patients treated in 2nd line was approximately 80%, 50% for 3rd line, and 0% of those treated in 4th line. 89% of the patients experienced grade 3 toxicity, and 25% grade 4. The most common were neutropenic fever (69%), mucositis (36%) and diarrhea (25%). There were 3 deaths related to the treatment. Conclusions: Patients with complete response have sustained long-term survival, and represent the subgroup with evident benefit of the treatment. Surgery, when feasible, can rescue 80% of the patients with partial response. According to our data, we do not recommend this modality of treatment in 4th line.
Safety and efficacy of axitinib (axi) in combination with pembrolizumab (pembro) in patients (pts) with advanced renal cell cancer (aRCC).
Authors: Atkins Michael B. , Plimack Elizabeth R. , Puzanov Igor , Fishman Mayer N. , McDermott David F. , Cho Daniel C. , Vaishampayan Ulka N. , George Saby , Olencki Thomas , Tarazi Jamal Christo , Rosbrook Brad , Fernandez Kathrine C. , Lechuga Mariajose , Choueiri Toni K. 
Published: February 2018

579 Background: Prior studies combining programmed death-1 (PD-1) checkpoint inhibitors with tyrosine kinase inhibitors of the vascular endothelial growth factor (VEGF) pathway have been characterized by excess toxicity precluding further development. We hypothesized that a combination of axi, a more selective VEGF-pathway inhibitor, with pembro (anti-PD-1) would be well tolerated and yield antitumour activity in treatment-naïve pts with aRCC. Methods: This ongoing open-label phase Ib study of axi/pembro comprised a dose-finding phase to determine the maximum tolerated dose and dose expansion phase. Axi 5 mg was administered orally twice daily with pembro 2 mg/kg administered intravenously every 3 weeks. Tumors were assessed, using RECIST v1.1, at baseline, week 12, and every 6 weeks thereafter. The primary endpoint was dose-limiting toxicity (DLT) during the first 2 cycles (6 weeks), with secondary endpoints evaluating safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Between 23 Sept 2014 and 13 Oct 2015, 52 treatment-naïve pts with aRCC were enrolled. No unexpected toxicities were observed. Three DLTs were reported among the 11 pts treated in the dose-finding phase: transient ischemic attack (n = 1) and < 75% of planned axi dosage administered due to treatment-related toxicity (n = 2). At cutoff date (March 30, 2017), 25 pts were receiving study treatment. Most common (≥10%) grade ≥3 all-causality AEs included hypertension (23%), diarrhoea (10%) and fatigue (10%). Most common ( > 10%) potentially immune-related AEs included diarrhoea (29%), increased alanine aminotransferase (17%), or aspartate aminotransferase (13%), hypothyroidism (13%), and fatigue (12%). ORR was 73.1% (95% confidence intervals [CIs], 59.0–84.4). Median (95% CI) PFS was 20.9 (15.4–not evaluable) months. OS data were not mature at minimum follow-up period of 17.6 months, with 6 treatment-unrelated deaths reported. Conclusions: The combination axi/pembro is tolerable and exhibits promising antitumour activity in treatment-naïve pts with aRCC. A randomized phase 3 trial comparing the combination to sunitinib monotherapy is underway. Clinical trial information: NCT02133742.