bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of pericytes on melanoma development.
Authors: Trevino-Villarreal Jose Humberto , Cotanche Douglas A. , Sepulveda Rosalinda , Rogers Rick A. 
Published: February 2017

83 Background: Melanoma-associated stroma cells regulate tumor establishment, invasion, and dissemination through paracrine and heterotypic cell-cell interactions with cancer cells. Pericytes constitute a major noninflammatory component of the melanoma-associated stroma. Our study is designed to evaluate the role of pericytes in melanoma development. Methods: Tumors induced in GFP+/SCID mice with GFP-B16 cells were harvested after 14 days, enzyme digested, labeled against mesenchymal markers, and analyzed by flow cytometry (FC). The distribution of stromal subpopulations in tumors was investigated by immunofluorescence microscopy (IFM). Stromal pericytes from tumors and adipose tissue were FACS sorted, mixed with B16 cells at a 3:1 ratio, and injected into SCID mice. Tumor diameters were taken periodically with a scientific caliper, and used to determine tumor volumes using the ellipsoid formula. Results: FC analysis showed that the melanoma stroma was composed of CD45+ inflammatory cells, CD31+ endothelial cells, FAP+ myofibroblasts and CD146+ cells. IFM analysis showed that the CD146+ cells are perivascular CD31-/CD34-/α-SMA+ stromal pericytes that associated with TGF-β immunoreactive CD271+/CD146+B16 cells in perivascular tumor niches. Co-induction experiments were performed to investigate the effect of pericytes on melanoma development. We observed faster growth rates in the size of tumors co-induced with pericytes, compared with tumors induced with B16 cells alone. These co-induced tumors had bigger masses, more volume, were hypercellular, and had increase vascularization compared with control tumors. In addition, pericytes increased the B16 cell proliferation rate, as determined by higher expression of Ki-67 in the tumor fraction of co-induced tumors. Conclusions: Pericytes promote melanoma development by inducing angiogenesis and melanoma cell proliferation. Our results suggest that pericytes could be utilized as a therapeutic target for melanoma treatment.
The LIVESTRONG essential elements of survivorship care: Advancing quality survivorship care in clinical care settings.
Authors: Arvey Sarah R. , Rechis Ruth 
Published: February 2017

155 Background: The American College of Surgeons Commission on Cancer (COC) has set a 2015 deadline for oncology practices to comply with new patient-centered standards of care to maintain accreditation. Despite this mandate, there is not a strong evidence base on best practices, or guidance on how to implement quality survivorship care services. In September 2011, the Lance Armstrong Foundation (LAF) and the LIVESTRONG Survivorship Center of Excellence Network (Network) convened researchers, providers, advocates, and cancer survivors who identified and prioritized a list of 20 Essential Elements of survivorship care. LAF and the Network continued work to refine this list with input from stakeholders with the goal of disseminating a framework for survivorship care delivery and advancing a research agenda to strengthen the evidence base for implementing these elements as standard care. Methods: LAF and the Network have refined definitions of the Essential Elements through an iterative process and in late 2012 will facilitate a technology-mediated consensus-building process among a broad group of stakeholders. Results: Refinement of the Essential Elements included defining each element in such detail that “basic” and “enriched” levels of implementation are described to guide providers in real-world settings. This work outlines a research agenda aimed to strengthen the evidence-base of the Essential Elements’ effectiveness in improving survivors’ outcomes. In October 2012, the refined definitions will be disseminated to a broad stakeholder audience and subject to review. Details of this iterative process, resulting definitions, and open-forum feedback will be reported here. Conclusions: Once complete, the Essential Elements will represent a consensus-driven platform that provides the cancer care community with a blueprint for the development and implementation of high-quality survivorship care and research. Additionally, the finalized Essential Elements will further facilitate the broad adoption of the new COC standards including the provision of a treatment summary and survivorship care plans, palliative care, psychosocial distress screening, and care coordination.
The Canadian partnership for quality radiotherapy: A model for radiation treatment quality and safety.
Authors: Cao Jeffrey Quoc , Bissonnette Jean-Pierre , Brundage Michael Donald , Dunscombe Peter , French John , Gillan Caitlin , Keresteci Margaret , Milosevic Michael , Parliament Matthew , Schella Jason 
Published: February 2017

266 Background: Innovative, overarching national, and international strategies for the assurance of safe and high quality radiation treatment (RT) are needed, given the rate of technologic innovation and shifts in traditional roles associated with RT planning and delivery. Methods: The Canadian Partnership for Quality Radiotherapy (CPQR) was created as an interprofessional alliance of the Canadian Association of Radiation Oncology (CARO), Canadian Organization of Medical Physicists (COMP), Canadian Association of Medical Radiation Technologists (CAMRT) and Canadian Partnership Against Cancer (CPAC), aimed at developing and promoting coordinated national strategies for high quality and safe RT. Results: A steering committee of national leaders from each profession and content experts in RT quality and safety was created, with financial and strategic backing provided by the federal government through CPAC. The vision and strategy were communicated broadly to the RT treatment community and to other stakeholders provincially, nationally, and internationally. ‘Quality Assurance Guidance for Canadian Radiation Treatment Programs’ was published online in April 2011 and empowered programs across the country to evaluate their internal procedures against these indicators. This document was downloaded over 875 times in the first 6 months, a measure of the demand and broad uptake in Canada and internationally. This early success has fostered other foci of activity, including engagement by the Canadian medical physics community around synthesis of detailed quality control guidelines for equipment, a dialogue about national incident reporting, and support from international partners in relation to collaborative programs. The goal is to incorporate RT quality and safety indicators into national accreditation programs for cancer care to assure long-term sustainability. Conclusions: CPQR has established a model for quality and safety that is fostering the evolution of a new national quality culture. This model is applicable to other jurisdictions, recognizing that a coordinated international approach to setting guidelines and standards will ultimately lead to higher quality and safer RT on a global scale.
An electronic chemotherapy administration safety checklist: The safe transition from paper to computer.
Authors: Olsen MiKaela M. , Wilt Monica , Van de castle Barbara , Mooney Kathy , Cohen Melanie , Taffe Elizabeth , Swisher Marie , McCready Jackie , Daniel Denise , Krumm Sharon , Chen Allen Ray Sing 
Published: February 2017

303 Background: This abstract describes the successful implementation of an electronic chemotherapy administration safety checklist and the outcomes that led to further enhancement of safe chemotherapy administration. The purpose of this abstract is to give an overview of the processes in transitioning from a paper checklist to an electronic version. Following the implementation of a paper chemotherapy administration safety checklist in 2002, this cancer center realized a significant reduction in chemotherapy errors reaching patients. The checklist became a model for many practitioners across the U.S. Our implementation of the Sunrise computerized provider order entry (CPOE) system in oncology inpatient units in 10/2009 included support for all of the 2009 ASCO/ONS chemotherapy ordering standards, and featured a two-way interface with the pharmacy system, and an electronic medication administration record. In the 12 months following its deployment, the rate of chemotherapy errors that reached the patient fell from 2.71 per 100 chemotherapy admissions using our paper system to 1.11 per 100 chemotherapy admissions using CPOE. With the advent of electronic documentation it became apparent that the paper checklist was outdated. Methods: An electronic chemotherapy checklist was implemented, replacing a paper version that had been in use for almost a decade. The proper design and implementation of the electronic version were essential to ensure that the safety achieved with the paper checklist was not compromised. After pilot testing, the checklist was implemented. Results: The electronic chemotherapy checklist was accepted by staff and resulted in a decrease in errors reaching the patient. Conclusions: The safe administration of chemotherapy is the number one priority at our cancer center. To our surprise the electronic checklist has been a welcomed addition to our armamentarium against chemotherapy errors. The checklist has enhanced independent safety checks due to required independent sign-on of the electronic system. The checklist also heightened awareness of chemotherapy safety checks, which were unchanged, leading us to believe that the paper version had become somewhat ineffective.
Use of iPad technology to determine cancer patient-reported preferences for and understanding of pharmacogenetic testing (PGT).
Authors: Martin Petra , Brown Catherine , Cuffe Sinead , Pringle Dan , Mahler Mary , Villeneuve Jodie , Niu Chongya , Charow Rebecca , Lam Christine , Shani Ravi M. , Hon Henrique , Otsuka Memori , Epsin-Garcia Osvaldo , Xu Wei , Alibbhai Shabbir , Jenkinson Jodie , Liu Geoffrey 
Published: February 2017

319 Background: PGT in oncology can be used to predict the efficacy and toxicity of a particular treatment in an individual. Previous work by our group has demonstrated that among cancer patients willing to undergo chemotherapy, >98% wanted PGT testing if it could identify patients who would respond to chemo. However, in the original study using a paper questionnaire, 22% of patients did not understand the concept of PGT and its clinical implications. Therefore, we have devised a simpler, more visual questionnaire in electronic format using iPad technology and simple animations. We are assessing if patient understanding using this format is increased and also if patients prefer completing the survey with this novel technology. Methods: An interim analysis of a broad cross-section of cancer patients using an iPad was performed. PGT questions related to hypothetical efficacy, toxicity, time to test results, willingness to pay as well as understanding of PGT scenarios were assessed. Results: 135 cancer patients (87% adjuvant, 12% metastatic; 27% breast, 25% colon, 22% heme malignancy, 23% other) attending Princess Margaret Hosptial participated. 85% of patients accepted chemo that had a 5% absolute improvement in survival and <10% chance of side effects. 94% of patients chose to have PGT if it could identify subsets of patients who would benefit from chemo. The median that patients were willing to pay for PGT was $250 (range $0-$5,000), however the median that patients felt was a reasonable price was $100 ($0-$5,000). 11% of patients admitted that they did not understand the concept of PGT and its clinical implications. Conclusions: Almost all patients who were willing to undergo chemo were also willing to accept PGT. Fewer patients in this study compared with our original paper directed questionnaire described themselves as lacking an understanding of PGT (11% versus 22% respectively), suggesting that survey administration on an iPad with a visual characterization of question scenarios improved understanding. Final data from over 300 patients will be analyzed in the fall, which would include data on patient attitudes on use of such technology for communication and decision making.
Oral chemotherapy: A focus on interventions and access.
Authors: Mancini Robert , Wilson David , Modlin Jessie , Zuckerman Dan Sayam , Powell Colleen , Rapp Delisa , Collins Jill , Hutchinson Thea 
Published: February 2017

44 Background: Oral chemotherapies are becoming more predominant with 40% of the currently available oral agents being approved in the last 7 years. Patient self-administration and the costs of these medications raise concerns about monitoring and access. As a result, nonfulfillment rates in the literature have been reported to range from 10-24% with rates directly correlated with cost of the medication. Methods: Patients who utilized the pharmacist-managed oral chemotherapy program were included for evaluation. Patients were excluded if they utilized external mail order pharmacies. Patient charts were audited for documented pharmacist-initiated interventions such as drug-interactions, lab monitoring, and dose adjustments. Patient nonfulfillment rates were evaluated by evaluating percentage of patients referred to number of prescriptions filled. Patients were classified as either filled, mail order, financial assistance or never started. Financial assistance patients were divided into free drug or co-pay assistance. Total amount of free drug obtained was assessed by multiplying the average number of cycles obtained by patients by the average wholesale price (AWP). Results: A total of 702 patients were served by the Oral Chemotherapy program between August 2009 and October 2011. In those patients, 82 drug-drug interactions and 24 patients required dose adjustments up front, mostly due to renal dysfunction. Compared to the 10-24% nonfulfillment rates in the literature, this program was able to keep rates less than 1% for patients who were unable to obtain medication for financial reasons. In this time period, underinsured patients were able to obtain >$1 million in free drug and >$200,000 in co-pay assistance funds thanks to our financial advocates. Conclusions: Collaboration within one health system between oncologists, pharmacists, nurses and social workers/financial advocates was able to ensure better quality of care by helping address medication issues upfront with minimal delays in access. In addition, this program was able to ensure that most patients were able to obtain their medication within a reasonable time period at a reasonable cost, reducing non-fulfillment rates compared to what has previously been reported in the literature.
aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer.
Authors: Gray Richard G. , Rea Daniel , Handley Kelly , Bowden Sarah Jane , Perry Philip , Earl Helena Margaret , Poole Christopher John , Bates Tom , Chetiyawardana Shan , Dewar John A. , Fernando Indrajit Nalinika , Grieve Robert , Nicoll Jonathan , Rayter Zenor , Robinson Anne , Salman Asad , Yarnold John , Bathers Sarah , Marshall Andrea , Lee Martin ,   on behalf of the aTTom Collaborative Group
Published: February 2017

5 Background: In estrogen-receptor-positive (ER+) early breast cancer, 5 years of tamoxifen reduces breast cancer death rates by about a third throughout years 0-14. It has been uncertain how 10 years of tamoxifen compares with this. Methods: During 1991-2005, 6,953 women with ER+ (n=2755), or ER untested (4198, estimated 80% ER+ if status known) invasive breast cancer from 176 UK centres were, after 5 years of tamoxifen, randomized to stop tamoxifen or continue to year 10. Annual follow-up recorded compliance, recurrence, mortality, and hospital admissions. Results: Allocation to continue tamoxifen reduced breast cancer recurrence (580/3468 vs 672/3485, p=0.003). This reduction was time dependent: rate ratio 0.99 during years 5-6 [95%CI 0.86-1.15], 0.84 [0.73-0.95] during years 7-9, and 0.75 [0.66-0.86] later. Longer treatment also reduced breast cancer mortality (392 vs 443 deaths after recurrence, p=0.05), rate ratio 1.03 [0.84-1.27] during years 5-9 and 0.77 [0.64-0.92] later; and overall mortality (849 vs 910 deaths, p=0.1), rate ratio 1.05 [0.90-1.22] during years 5-9 and 0.86 [0.75-0.97] later. Non-breast-cancer mortality was little affected (457 vs 467 deaths, rate ratio 0.94 [0.82-1.07]). There were 102 vs 45 endometrial cancers RR=2.20 (1.31-2.34, p<0.0001) with 37 (1.1%) vs 20 (0.6%) deaths (absolute hazard 0.5%, p=0.02). Combining the similar results of aTTom and its international counterpart ATLAS (Lancet 2013) enhances statistical significance of recurrence (p<0.0001), breast cancer mortality (p=0.002) and overall survival (p=0.005) benefits. Conclusions: aTTom confirms that, in ER+ disease, continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence, from year 7 onward, and breast cancer mortality after year 10. Taken together with the reduction in breast cancer deaths seen in trials of 5 years of tamoxifen vs none, these results indicate that 10 years of adjuvant tamoxifen, compared to no tamoxifen, reduces breast cancer mortality by about one third in the first 10 years following diagnosis and by a half subsequently. Clinical trial information: ISRCTN17222211.
Oral HPV infection in HPV-positive oropharyngeal cancer cases and their spouses.
Authors: D'Souza Gypsyamber , Gross Neil D. , Pai Sara I. , Haddad Robert I. , Gillison Maura L. , Posner Marshall R. 
Published: February 2017

CRA6031 Background: Incidence of human papillomavirus-positive oropharyngeal cancer (HPV-OPC) is increasing, and spouses of these patients have high anxiety about their own HPV-related cancer risk. Methods: Partner study of 149 HPV-OPC and 81 of their spouse/long-term partners. Data collection included a 30-second rinse and gargle (at diagnosis and again 1 year later for 103 cases and 46 partners), computer-assisted risk factor survey, tumor collection (cases), and visual oral examination (spouses). Oral rinse samples were tested for 36 types of HPV DNA using PGMY09/11 primers and line-blot amplification, and HPV16 copy-number using real-time PCR. Results: Cases were primarily male (89%), white non-Hispanic (92%), had performed oral sex (94%), and never-smokers (51%) with a median age of 56 years. Twelve-month survival was high among never- and ever-smoking HPV-OPC (100% vs 93%, p=0.18). The 81 spouses of HPV-OPC were primarily female (81%), white non-Hispanic (92%), never-smokers (54%), with a median age of 53 years. Spouses were significantly less likely than cases to have >10 lifetime oral sex partners (11% vs 39%, p<0.001). Prevalence of any oral HPV (65%) and oral HPV16 (52%) was high among HPV-OPC at diagnosis. Four (7.7%) of 52 HPV-OPC with HPV16 DNA detectable before therapy, had HPV16 persistently detected one year after diagnosis/therapy. Prevalence of any oral HPV DNA among partners was significantly lower than among HPV-OPC (7.3% vs 65%, p<0.001). Oral HPV prevalence was significantly higher among the 7 male partners than the 74 female partners (29% vs 5%, p=0.025). Oral HPV infections among partners included HPV16 (n=2), HPV62 (n=2), HPV 83 and 51 (1 each). Both partners with oral HPV16 infections were female and no longer had oral HPV16 detected at the one year follow-up. 64% of spouses had a visual oral exam, and no pre-cancers or cancers were identified. However, two (2.5%) enrolled spouses reported a personal history of cervical cancer, and 6 HPV-HNC cases (4.0%) reported a previous spouse who developed cervical or vaginal cancer. Conclusions: Oral HPV16 DNA is common among HPV-OPC, but not among their spouses. Spouses of HPV-OPC may have an elevated risk or history of cervical cancer.
Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM).
Authors: Carvajal Richard D. , Sosman Jeffrey Alan , Quevedo Fernando , Milhem Mohammed M. , Joshua Anthony Michael , Kudchadkar Ragini Reiney , Linette Gerald P. , Gajewski Thomas , Lutzky Jose , Lawson David H. , Lao Christopher D. , Flynn Patrick J. , Albertini Mark R. , Sato Takami , Paucar Daniel , Panageas Katherine S. , Dickson Mark Andrew , Wolchok Jedd D. , Chapman Paul B. , Schwartz Gary K. 
Published: February 2017

CRA9003 Background: Gq/11 mutations are early oncogenic events in UM resulting in MAPK pathway activation. We demonstrated decreased viability in UM cell lines harboring Gq/11 mut with sel, a small molecule inhibitor of MEK1/2 (Ambrosini, CCR 2012). Methods: We conducted a 16 center randomized phase II study of hyd-sulfate sel 75 mg BID vs TMZ 150 mg/m2 daily for 5 days in 28-day cycles (or DTIC 1000 mg/m2 q21 days) for patients (pts) with metastatic UM with a Q209 Gq/11 mut who have not received prior TMZ/DTIC. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall survival (OS) and response rate (RR). Select pts underwent tumor biopsies at baseline and after 14 (+/- 3 days) of sel. Our statistical plan required ≥80 pts randomized and ≥68 events to detect a PFS hazard ratio of 0.6 (p=0.1). Randomization was stratified by mut (Gq vs G11), M stage and number of prior therapies (tx). Tumor assessment occurred every 4 weeks (wks) for 8 wks and then every 8 wks using RECIST 1.1. Pts receiving TMZ who progressed could receive sel (TMZ→sel). Results: 80 pts were randomized. Sel (n=39): median age 66 (range 32-86), 54% male, 54% G11 mut, median ECOG PS 0 (range 0-1), 97% M1c, median prior tx 0 (range 0-2). TMZ (n=41): median age 60 (range 34-81), 63% male, 58% G11 mut, median ECOG PS 0 (range 0-1), 93% M1c, median prior tx 0 (range 0-2). 11/39 (28%) pts on sel experienced grade (gr) 3 toxicity (tox) manageable with dose modification (5 CPK elevation, 3 LFT elevation, 1 rash, 1 lymphopenia, 1 edema). 1/41 (2%) pt on TMZ experienced gr 3 tox (neutropenia). No gr 4/5 tox occurred. 28 pts on sel underwent paired tumor biopsies with inhibition of pERK and cyclinD1 observed by Western blot at day 14. At interim analysis (9/25/12), 55 pts were evaluable with 45 progression events and 16 deaths. Sel (n=27): median PFS 16 wks (95% CI 8-30.9), RR 11%, median OS 11.8 months (95% CI 4.8-not reached). TMZ (n=28): median PFS 4 wks (95% CI 3.7-15), RR 0%, median OS 4.7 months (95% CI 4.3-14.3). TMZ→sel (n=25): median PFS 8.1 wks (95% CI 7-15), RR 0%. Conclusions: Sel is the first drug to ever show improved clinical activity in UM relative to TMZ. Sustained target inhibition is observed with sel. Final results will be presented. Clinical trial information: NCT01143402.