bluuebunny/crossref_metadata_2025_split huggingface dataset:
UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice
Authors: Hussain Sajjad , Bedekovics Tibor , Liu Qiuying , Hu Wenqian , Jeon Haeseung , Johnson Sarah H. , Vasmatzis George , May Danielle G. , Roux Kyle J. , Galardy Paul J. 
Published: September 2018

Abstract
The mechanistic target of rapamycin (mTOR) is a central regulator of cellular proliferation and metabolism. Depending on its binding partners, mTOR is at the core of 2 complexes that either promote protein biosynthesis (mTOR complex 1; mTORC1) or provide survival and proliferation signals (mTORC2). Protein biosynthesis downstream of mTORC1 plays an important role in MYC-driven oncogenesis with translation inhibitors garnering increasing therapeutic attention. The germinal center B-cell oncogene UCHL1 encodes a deubiquitinating enzyme that regulates the balance between mTOR complexes by disrupting mTORC1 and promoting mTORC2 assembly. While supporting mTORC2-dependent growth and survival signals may contribute to its role in cancer, the suppression of mTORC1 activity is enigmatic, as its phosphorylation of its substrate 4EBP1 promotes protein biosynthesis. To address this, we used proximity-based proteomics to identify molecular complexes with which UCH-L1 associates in malignant B cells. We identified a novel association of UCH-L1 with the translation initiation complex eIF4F, the target of 4EBP1. UCH-L1 associates with and promotes the assembly of eIF4F and stimulates protein synthesis through a mechanism that requires its catalytic activity. Because of the importance of mTOR in MYC-driven oncogenesis, we used novel mutant Uchl1 transgenic mice and found that catalytic activity is required for its acceleration of lymphoma in the Eμ-myc model. Further, we demonstrate that mice lacking UCH-L1 are resistant to MYC-induced lymphomas. We conclude that UCH-L1 bypasses the need for mTORC1-dependent protein synthesis by directly promoting translation initiation, and that this mechanism may be essential for MYC in B-cell malignancy.
Cost-effectiveness analysis of pembrolizumab in cancer therapy: A systematic review.
Authors: Donatien Claudette , Foster Lori-Ann , Loh F. Ellen 
Published: September 2018

109 Background: Cancer treatment is very costly and is further complexed by barriers to healthcare such as the lack of health insurance. Cancer detected at a later stage is more expensive to treat and the outcome can be less successful. Pembrolizumab is an immunotherapy that can be given alone or with chemotherapy. Pembrolizumab, a monoclonal antibody, may be considered first-line treatment in cancer therapy with its increase in life expectancy and successful treatment rates. Methods: A systematic review was conducted to identify relevant studies of the cost-effectiveness of Pembrolizumab treatment in cancer patients. We included studies that compared pembrolizumab to previous treatments, treatment-naive patients, advance melanoma, and metastatic non-small-cell lung cancer. Results: Most of the studies reviewed concluded that pembrolizumab was more cost-effective despite its high drug acquisition cost and disease management costs. Treatment with pembrolizumab was most effective when it was limited to 2 years, however, costs increased when treatment went beyond the two years and disease progression did not cease in most trials. In fact, disease progression occurred in many of the trials and patients had to discontinue treatment with pembrolizumab or other treatment regimens for several reasons not limited to adverse event. Regardless, pembrolizumab, if used as first-line treatment, would reduce the chances of disease progression or costs in drug therapy. Conclusions: Improving a patient’s quality of life is important when choosing the right course of treatment for any type of disease. In these studies, the quality-adjusted life years (QALY) were continuously increased when using pembrolizumab as compared to standard of care treatments and other immunotherapies. In the US healthcare system, the main factors to consider are the Healthcare Budget and the Payers willingness to pay. The US has legislated against the explicit use of cost per QALY thresholds but the $50,000 mark is commonly referred to. More studies should be conducted in the US to further conclude the cost-effectiveness of pembrolizumab in the treatment of cancer.
Sustaining positive outcomes with a progressive upright mobility program protocol in cancer patients.
Authors: Gehringer Paul 
Published: September 2018

126 Background: Critical illness associated with immobility leads to significant morbidity including increased intensive care unit (ICU) days, hospital lengths of stay (LOS), and prolonged deconditioning. Several prior studies have demonstrated improvements in LOS and ventilator days when early institution of mobility programs are utilized; however, malignancy and a short expected life span have been exclusions from all prior studies. The purpose of this retrospective investigation was to examine the safety and effectiveness of a progressive upright mobility program (PUM) in critically ill ventilated cancer patients. Methods: After twelve months of baseline data was collected investigating ventilator days, ICU LOS and hospital LOS, a stepwise multidisciplinary PUM protocol was developed and followed in all mechanically ventilated patients admitted to a single subspecialty cancer hospital ICU. Exclusions to protocol included hemodynamic instability, the need for continuous sedation, and neuromuscular blockade. Data from control period (pre) was compared to twelve-month post-intervention (post) data. To determine sustainability, an additional twelve months of data was collected and compared to the pre and post intervention groups. Compared data included demographics, severity of illness, ventilator days, and LOS. Results: Statistical analysis of the data included comparison of means and analysis of variance (ANOVA). The post protocol implementation group demonstrated statistically significant outcomes in the three areas measured; ventilator days reduced from 6.3 to 3.7 (p = 0.001755), ICU LOS 10.2 to 7.5 (p = 0.011016), and hospital LOS 20.9 to 14.1 (p = 0.000364). Conclusions: Despite oncology patients having a high severity of illness and likely functional decline, the patients continue to benefit from early mobilization as previously studied groups. The results reflect consistencies with current literature supporting the absence of complications in early mobilization of patients in the ICU. To our knowledge, this has been the first mobilization study conducted in an oncology critical care setting.
Flu fighters: Flu vaccine administrations in pediatric hematology oncology patients.
Authors: Beverley Mehgan , Lorenz Patricia , Kaplan Joel , Turner Nicole 
Published: September 2018

131 Background: Influenza is a serious virus that affects millions of people every year. The CDC and AAP recommend all people starting 6 months of age get a yearly flu vaccine, especially the immunocompromised. Children receiving chemotherapy for cancer treatment are at heightened risk of severe influenza infection and resulting complications. (Goossen et al., 2013). Methods: An interdisciplinary team used the Model for Improvement with an aim statement, current and ideal process flow maps, and annotated run charts to monitor the impact of changes. Change ideas were tested via small-cycle PDSAs. Successful strategies included development of a flu form, targeting patients with pre-visit planning and phone calls, and escalation to physician intervention. Results: A p shewhart chart analyzed the percentage of target population receiving vaccines weekly. The goal was to vaccinate 95% of patients with leukemia or neuro-oncology on active chemotherapy who were older than 6 months of age without medical contraindications. At baseline, upper control limit (UCL) was 6%, mean was 2% and lower control limit (LCL) was 0%. After testing changes, the percentage of flu vaccines improved (special cause variation) to UCL 100%, mean 95%, LCL 87%. The goal was met and sustained through the end of 2018 flu season. This QI project also improved flu vaccinations given to all our patients as compared to the 2016/2017 flu season. During the 2016/2017 flu season, 295 flu vaccines were given. During the 2017/2018 flu season, 457 flu vaccines were given in a similar time frame, i.e. an increase of 155%. In addition to improving care delivered to our target population, this work facilitated greater distribution of flu vaccine to all at-risk populations in our clinic. Conclusions: This project shows a comprehensive and effective approach to reducing the risk of a serious health threat for some of our most vulnerable patients. By developing a well-defined process, standardizing messaging, and using data to inform next steps, our team surpassed benchmarks established by some of the best cancer care specialists in the country. The processes established here can be applied widely, offering hope that future flu seasons could be less devastating to vulnerable populations.
Creation and implementation of a chief fellow of quality improvement in an oncology fellowship program.
Authors: Jones Amy Little , Gulvin Joshua Michael , Butler-Gunn Catherin , Wolff Robert A. , Rieber Alyssa G. 
Published: September 2018

152 Background: Educating oncology trainees in methods and practical applications of quality improvement (QI) is essential. QI is a key component of the ACGME core competency of systems based practice. Formal QI training helps oncologists deliver safe and effective cancer care. Creating a QI chief fellow position allows for patient safety and QI initiatives to be fellow-driven and focused on building lifelong, oncology specific, QI skills. Methods: Feedback was solicited from the fellowship’s executive committee and divisional leadership to establish the job description and funding. Nominations were sought from peer fellows, focusing on a fellow who has expressed interest in QI, patient safety, and/or value based healthcare. The chief fellow was tasked with implementing a QI educational curriculum, developing a fellowship-wide QI project, and representing the fellowship on institution-wide QI and patient safety committees. Results: 100% (14/14) graduating fellows completed the requirements for an institutional clinical QI certificate by the end of the second year of the QI chief implementation, compared to 0% before the start of the implementation. 100% (27/27) of 1st and 2nd year fellows completed online training modules in QI. Biannual root cause analyses for patient safety events were initiated as a standard part of educational curriculum. 4 separate fellow-initiated QI projects were completed: oral chemotherapy patient education, opioid use and documentation, survivorship care plans, and infusion center usage. Fellows’ selection to the institutional clinical safety and effectiveness course increased from 4.8% (2/42) to 9.8% (4/41) in since implementation of the QI chief fellow. Fellowship representation on institution-wide patient safety committee increased from 0 to 2. Conclusions: Implementing a QI chief fellow role in an oncology fellowship is a feasible way to integrate a QI curriculum and provide structure for fellows to obtain further certification in QI or patient safety during fellowship. Ongoing challenges include encouraging enthusiasm from the entire fellowship for QI projects, finding appropriate QI mentorship from faculty, and translating QI initiatives into academic products.
Sleep quality in hematopoietic stem cell transplant recipients and caregivers.
Authors: Badia Alonso Priscila , Hickey Victoria , Flesch Laura , Byerly Megan , Sensibaugh Chelsea , Potts Katherine , Michel Celia , Drozd Alisha , Dandoy Christopher Eugene 
Published: September 2018

165 Background: Sleep is an essential biological function vital for physiological rest, healing and emotional well-being. Sleep disruption, defined as alterations to the normal sleeping patterns, is commonly seen in patients and caregivers with lengthy hospital stays. Sleep disruption in caregivers can lead to increased stress and fatigue, decrease quality of life and ultimately affect the caregiver ability to support their loved one. Methods: We studied through a longitudinal observational cohort study, the quality and quantity of sleep in pediatric patients undergoing hematopoietic stem cell transplant (HSCT) and their caregivers; we identified a high level of sleep disturbance utilizing actigraphy and recounted poor sleep through qualitative assessments. We then performed a cross sectional focus group analysis of patients/caregivers and medical staff to identify the factors associated with poor sleep. The global aim of our quality improvement initiative was to improve sleep quality in HSCT patients and caregivers through a reduction of the nighttime noise (9pm-7am) in the bone marrow transplant unit, from 46 decibels (dB) (mean baseline data) to 38dB (WHO recommends night outside noise of less than 40dB) in a 6 month period. Results: We identified the factors associated with sleep disruption; noisy room entries, overnight trash pulls, loud hallway noise and hospital staff. A simplified failure mode analysis identified four main key drivers; reliable nighttime awareness system, quiet nighttime nursing system, unobtrusive nighttime cleaning process and awareness maintenance system. Several PDSA (plan, do, study, and act) interventions took place and were adopted. After four months the overnight mean dB have decreased to 42dB (9% reduction). Overnight noise spikes above 60dB have decreased from a mean of 271 spikes to a mean of 151 spikes (44% reduction). By September 2018 we expect further decrease in spikes and overnight dB and follow up quantitative and qualitative sleep assessments. Conclusions: With a quality improvement initiative, we identified factors that negatively impact sleep and performed interventions that successfully mitigate these factors, leading to improve quality of sleep in HSCT patients and caregivers.
Promoting patient engagement in bladder cancer (BC) care through education.
Authors: Jaganathan Hamsa , Roc Anne , Turell Wendy , Chisolm Stephanie , Mohamed Nihal , Galsky Matthew 
Published: September 2018

176 Background: BC is the 6th leading cause of cancer in the US and it is estimated that 81,190 Americans will be diagnosed this year. Promoting patient knowledge and involvement in BC care have led to successful management strategies. We offered 1 hour of online education to patients and their caregivers to provide clinical and supportive information that lends a sense of control, supports effective self-management, and promotes patient-physician communication. Methods: PlatformQ Health Education, in partnership with the Bladder Cancer Advocacy Network, developed and executed an interactive education program for patients with BC and their caregivers, which was broadcast live online on cancercoachlive.com on September 29, 2017 and on-demand through March 29, 2018. The program was viewed on cancercoachlive.com by 587 learners and attracted 533 additional learners through social media channels (e.g. Facebook). Education focused on treatment options and the accessibility of resources and support. Self-reported surveys, distributed to patients and caregivers 8 weeks after the program, were analyzed for improvements in perceived engagement in their cancer care. Results: After participating in the education, a majority of the learners reported they felt knowledgeable on treatment options to discuss with their HCPs (92%, n = 60) and resources and information they can use for self-care strategies (88%, n = 58). Follow-up survey results (n = 60) also indicated that the education helped 50% of learners enhance their communication with their HCP. Moreover, 54% of learners (n = 48) felt more in control of health care decisions, and 36% of learners (n = 59) reported improvements in their health-related behaviors. Write-in examples focused on staying informed of treatments and side effects, seeking support, and proactively asking questions to their HCPs. Conclusions: As ASCO guidelines note, providing patients with preoperative information and encouraging them to take an active part in the decision-making process are essential elements to achieving positive outcomes in BC. Results from the patient survey indicate that participating in an interactive, online education program enhanced knowledge and promoted patient engagement in BC care.
Evaluation of the implementation of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) across the province of Ontario.
Authors: Haji Farzana , Barbera Lisa Catherine , Amernic Heidi , Evans Jenna , Ismail Zahra , Brundage Michael Donald 
Published: September 2018

188 Background: EPIC-CP, a prostate cancer Patient-Reported Outcome Measure (PROM), was implemented across Ontario’s 14 Regional Cancer Centres (RCCs) using a phased roll-out approach. This approach enabled implementation and evaluation in enrolled centres, with the aim of using the results to improve implementation in both the enrolled regions and those preparing to implement. The objective was to analyze formative evaluation results and identify opportunities for improvement in implementation. Methods: Surveys were developed for patients and providers to capture attitudes and experiences regarding EPIC-CP. Data collection was initiated approximately three months post-implementation, with three RCCs evaluated concurrently in ‘waves’. Descriptive analyses were performed to summarize the survey data. Results: To date, nine RCC’s have completed the formative evaluation with 104 providers and 517 patients responding to the surveys. Providers reported challenges with data flow (44% always or mostly received EPIC-CP results in a timely manner) and with responding to specific symptoms (27% and 29% reported that they are very confident in treating/managing sexual function and emotional issues respectively). Although 54% of providers acknowledged that using EPIC-CP should be part of their role, 46% indicated that it has added little or no value to their practice. In contrast, 75% of patients reported that EPIC-CP made it easier to communicate symptoms to their care team, which suggests that patients find EPIC adds value. Patient comments identified gaps such as educational resources for symptom management and additional support when completing the PROM. Conclusions: Opportunities to improve the patient and provider experience with EPIC-CP include: developing educational resources, addressing issues with technology and data flow, and identifying factors that influence provider uptake. These results will be used to design resources and support to improve the process for implementing EPIC-CP in later waves.
Feasibility of cancer clinical trial enrollment goals based on cancer incidence.
Authors: Tran George Nhat , Harker Matthew , Chiswell Karen , Unger Joseph M. , Fleury Mark , Hirsch Bradford Richard , Miller Kimberly , D'Almada Philip , Tibbs Sheri , Zafar Yousuf 
Published: September 2018

20 Background: More than 20% of US clinical trials fail to accrue sufficient patients and terminate prematurely, impeding innovation and negating the valuable contributions of participating patients. The aim of this study is to estimate availability of patients for each trial opening in the national oncology clinical research portfolio to provide a benchmark for better understanding feasibility of clinical trial enrollment goals. Methods: The Database for Aggregate Analysis of ClinicalTrials.gov, up-to-date as of September 3, 2017, was used to identify actively-recruiting, interventional oncology trials at US sites. Observational studies were excluded as not all are registered. Trials were categorized via Medical Subject Headings or free text condition terms and sorted by cancer diagnosis. Trial slot availability was estimated between September 1, 2017, to August 31, 2018. Availability was estimated from total anticipated enrollment, assuming a constant recruitment rate. Estimates for studies with both foreign and US sites were pro-rated to calculate available enrollment in the US alone. The 2017 American Cancer Society cancer incidence estimates were used to approximate total US cancer diagnoses. Results: 4598 oncology trials were identified. Overall, an estimated 12.6 cancer patients are available for each clinical trial slot. The estimates by cancer diagnosis were: colorectal: 24.7 patients per trial slot; lung & bronchus: 20.1; prostate: 17.6; breast (female): 13.8; leukemia 11.6; and brain & other nervous system: 6.0. Conclusions: Across all diagnoses, 1 in 13 patients must enroll to meet accrual demands. This ratio varies by diagnosis. If cancer incidence is too low, trials with unrealistic accrual goals may be doomed at inception. In diagnoses with high disease burden, trial failure may be due to poor patient access or suboptimal design. [Table: see text]
Are real-world patient-reported outcomes associated with survival in patients with advanced pancreatic cancer?
Authors: Dai Wei Fang , Beca Jaclyn Marie , Guo Helen , Qiao Lucy , Isaranuwatchai Wanrudee , Schwartz Deborah , Naipaul Rohini , Arias Jessica , Gavura Scott , Barbera Lisa Catherine , Chan Kelvin K. 
Published: September 2018

205 Background: Advanced pancreatic cancer (APC) patients often have a substantial symptom burden. In Ontario, patients visiting cancer clinics routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for 9 symptoms (scale: 0-10). Using ESAS, we explored the association between baseline patient-reported outcomes and overall survival (OS). Methods: APC Patients with ESAS records prior to receiving publicly-funded drugs from November 2008 to March 2016 were identified from Cancer Care Ontario’s New Drug Funding Program and Symptom Management databases. We examined 3 baseline composite ESAS scores: Total Symptom Distress Score (TSDS: all 9 symptoms), Physical Symptom Score (PHS: 6/9 symptoms), and Psychological Symptom Score (PSS: 2/9 symptoms); Composite scores greater than a threshold (defined as number of symptoms in composite score multiplied by clinically relevant score (≥4)) were categorized as High Symptom Burden (TSDS ≥ 36, PHS ≥ 24, PSS ≥ 8). The primary endpoint, OS, was assessed using Kaplan-Meier. Multivariable Cox models were used to adjust for age, gender, income, prior therapies (surgery, adjuvant gemcitabine, radiation), and Charlson's comorbidity. Analysis was repeated in a sub-cohort with identifiable ECOG status and stage. Results: We identified 2,199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving gemcitabine (54%), FOLFIRINOX (40%) or gemcitabine/nab-paclitaxel (6%). Crude median survival was 4.5 and 7.3 months for patients with high and low TSDS burden, respectively (HR = 1.50, 95% CI: 1.36, 1.66). After adjustment with multivariable Cox model, high TSDS burden was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). Similar trends were observed for PHS and PSS. When adjusting for both PHS and PSS in a Cox model, only the effect of PHS remained significant. In the sub-cohort (n = 393), high TSDS burden (HR = 1.34, 95% CI: 1.04, 1.73) was associated with lower OS, after adjusting for ECOG and stage. Conclusions: Among APC patients, a higher burden of patient-reported symptoms, via ESAS, at baseline was associated with reduced OS. The effect was prominent for physical symptoms, even after adjusting for treatment, stage and ECOG.