bluuebunny/crossref_metadata_2025 huggingface dataset:
GRILAGENS DE TERRA E CONFLITOS RURAIS: O LADO PERVERSO DA COLONIZAÇÃO NO PARANÁ
Authors: Serra Elpidio
Published: March 2019

Resumo: Grilagem de terras, quer através da falsificação de títulos de propriedade, quer através de outros mecanismos ilícitos, se constituiu em tarefa de fácil execução no Paraná, principalmente na fase da ocupação pioneira, ou seja, até o final da marcha colonizadora, nos anos 1960. No presente trabalho, um objetivo é destacar a facilidade com que os desvios de terras ocorreram, contribuindo para isso a estreita relação dos grileiros com o comando administrativo e com as lideranças políticas do Estado. Outro objetivo é associar as grilagens com os conflitos rurais, envolvendo o extermínio de camponeses, antigos ocupantes das terras griladas. Desvios de terras e conflitos vão caminhar lado a lado com a ocupação planejada do território, e no contexto da história agrária do Paraná, vão marcar o que pode ser chamado de o lado perverso da colonização. Em síntese o trabalho, sustentado em referenciais bibliográficos, em documentos oficiais e em informações extraídas de registros históricos, procura evidenciar o quadro de fraudes e de violência que marcou a ocupação e a apropriação das terras, tendo como recortes históricos o ano da emancipação política (1853) e o período em que se esgota o estoque de terras devolutas (década de 1960).
A GEOGRAFIA E A ARTE NO PROCESSO DE AUTOCONSCIÊNCIA DA HUMANIDADE: PRINCÍPIOS METODOLÓGICOS PARA A CONSTRUÇÃO DAS INSTALAÇÕES GEOGRÁFICAS
Authors: RIBEIRO EMERSON
Published: March 2019

O trabalho proposto versa sobre o ensino, a arte e a geografia e como a filosofia de Hegel e Lukács como precursores da estética podem contribuir com a Geografia. Hegel em sua obra fenomenologia do espirito na análise da estética concebe a arte como produtos humanos, já para Lukács na sua leitura entende que a arte promove a elevação da consciência da humanidade. Assim sendo, inserimos a geografia e a arte na formação de professores, tendo como metodologia para a relação de ensino e aprendizagem as instalações geográficas, essas pautadas sobre o aporte teórico desses dois autores entre outros. A proposta desse ensaio teórico/prático é de mostrar como a arte e a geografia por meio desses teóricos pode trazer ao professor e aluno uma ressignificação dos conteúdos da geografia cooperando na transformação sala de aula.
MAPEAMENTO DA DISTRIBUIÇÃO DO USO DA TERRA URBANA NO MUNICÍPIO DE SANTOS (SP)
Authors: Martins Maria Isabel Figueiredo Pereira de Oliveira , Matias Lindon Fonseca
Published: March 2019

O espaço urbano é [re]produzido pela sociedade por meio de acúmulos de processos socioeconômicos que se materializam e se tornam visíveis na distribuição dos usos da terra urbana no interior das cidades. Essa distribuição expressa as contradições, as exclusões e as particularidades de cada zona do espaço urbano. O município de Santos possui um espaço urbano adensado e concentrado na área insular, o que gera um processo constante de refuncionalização urbana, uma supervalorização de localidades específicas e uma supressão das poucas áreas com vegetação. A esse respeito, o artigo teve como principal objetivo compreender como que o uso da terra urbana se distribui no município de Santos (SP), Brasil.  Para isso, foi mapeada a distribuição dos principais tipos de atividades encontradas no espaço urbano do município. No mapeamento foram empregadas técnicas de geotecnologias de classificação manual de polígonos e o estimador de intensidade Kernel. Estão presentes usos misto (24,36%), residenciais (24,09%), zona portuária (12,83%), serviços (12,57%), espaços livres (1,75%), comerciais (1,35%), vazios urbanos (0,77%), industriais (0,26%) e 15,89% de áreas com algum tipo de vegetação. Os usos mistos se distribuem em diversas zonas da cidade, enquanto que os demais se concentram em zonas específicas, tais como a zona portuária e as atividades de serviço. Os produtos cartográficos gerados evidenciaram que as metodologias cartográficas são técnicas que permitem a interpretação de como os usos da terra urbanas estão distribuídos e, assim, contribuir com instrumentos de gestão socioambientais urbanas.
Luzes e sombras: a natureza na peregrinação a Santiago de Compostela segundo o Codex Calixtinus (século XII)
Authors: Vargas Lorena Da Silva
Published: March 2019

No sacrifício da peregrinação medieval, os fiéis encontram um meio de alcance espiritual consigo e com Deus. Pelo caminho, a natureza revela-se escudeira e desafiadora dos limites humanos, carregada de atributos religiosos em um momento de advento da Filosofia Natural. Neste artigo, analisaremos a atuação do ambiente natural na peregrinação a Santiago de Compostela no século XII a partir do Codex Calixtinus, especificamente a partir de seu livro V, o Guia do Peregrino. Enquanto um dos primordiais guias medievais, o Guia do Peregrino não apenas faz uma descrição da natureza no caminho, mas apresenta o conteúdo simbólico que a mesma revela no período.
Knowledge and health promoting lifestyle behaviors about menopause among perimenopausal female teachers
Authors: Alotaibi Samar , Yakout Sahar Mohammed Hassan , Moawad Salma M.
Published: March 2019

Menopause is a critical period in a woman's life that not only marks the end of reproductive ability, but it also associated with multiple physical, vasomotor, psychological, and sexual complaints Many of the serious complications that women face during menopause are caused by their own poor lifestyles and their lack of knowledge about self-care. The objective of this study was to assess knowledge and health promoting behavior at menopause among perimenopausal female teachers in Dawadmi City. The study applied cross sectional descriptive design with stratified random sampling used to obtain (348) female teachers statistically calculated from the total 3,708 teachers.  A structured closed ended questionnaire was used to collect data consisting of three parts: demographic information, questions to assess knowledge of female teachers about the pre-menopausal symptoms and The Health-Promoting Lifestyle Profile II to measures health-promoting behaviors. 58.9% of the subjects had poor knowledge, 30.7% had moderate knowledge and only 10.3% of teachers had Good and Excellent knowledge levels. Total mean score related to Health Promoting Behaviors was 130.05 ± 27.555 which considered medium in general. In general, socio-demographic variable of female teachers did not show significant correlations by using Pearson Chi-Square test and ANOVA test, also, did not show significant correlations for total knowledge level. Total Behaviors level, which also showed significant correlation with age (F = 1.358, p = .028) and weight during last year (F = 1.303, p = .049) categories. In conclusion, iidentifying the knowledge of women about menopause has an essential role in the development of women’s health during menopausal years. Results suggest that participants do not consistently include health-promoting behaviors into their lifestyle, especially physical activity. Therefore, certain policies should be designed and conducted to promote health behavior. Develop a process to promote worksite wellness programs, and to support behavioral changes intended to promote healthy lifestyles.
Investigation of Friction Coefficients of Veneers as a Function of Fibre Direction and Moisture Content
Authors: Buchelt Beate , Wagenführ André
Published: March 2019

During the manufacture of veneer based moulded parts, veneers move against one another. Friction is caused due to this movement. Different conditions, such as gluing or fibre direction, could influence the friction coefficients and thus the moulding process. For a better understanding of the manufacturing process of veneer based moulded parts, it is important to know which parameters influence friction and friction coefficients. In this paper, results of friction investigations are presented. Thereby the moisture content of the used veneers was varied as well as the fibre direction. Considering the manufacture conditions, the investigations were also conducted with glue-coated veneers. The results prove an influence of fibre direction but this influence depends on moisture content.
Finite Element Analysis of Heat Treated Wood Filled Styrene Maleic Anhydride (SMA) Copolymer Composites
Authors: Zor Mustafa , Kartal Murat , Gardner Douglas J.
Published: March 2019

The computer aided three dimensional static analyses of the specimens was done by using the Finite Element Method (FEM) and obtained data was compared with actual test data. The aim of this study is to compare the deformation/stress analyses with FEM analysis results of styrene maleic anhydride (SMA) copolymer composites. The heat treated wood/SMA copolymer composites were produced from different loadings (from 10 to 30 wt. %) of heat treated and untreated eastern white pine wood flours (Pinus strobus L.). All formulations of wood flour/SMA copolymer composites were produced by melt compounding through injection molding. The deformation/stress results obtained from the experimental solutions are very close to the results obtained from the numerical solutions (SAP2000 V17). As a result, it can be said that it is beneficial to use the FEM in the engineering design approach after the data obtained by the experimental solutions as meaningful values after application of the FEM.
Advocating for Libraries’ Government Information Services
Authors: Baker Gavin
Published: March 2019

I was pleased to accept editor Laura Sare’s invitation to introduce myself and to encourage everyone to join in our continued advocacy for libraries’ government information services. I am assistant director of government relations on ALA’s Public Policy and Advocacy unit, based in ALA’s Washington, DC, office. I have lead ALA’s work on government information policy since starting in that role in 2017.
MTMS Favorites: “It's All in the Cards”
Authors: Rumack Aaron
Published: March 2019

Members of the Editorial Panel are spotlighting articles from the twenty-three-year history of MTMS. In this offering, the takeaways include student thinking, student voicing, and making math social.
CGE19-065: Number of Somatic Mutations Is an Independent Predictor of Overall Survival in Acute Myeloid Leukemia
Authors: Myint Zin W. , Jayswal Rani , Arora Ranjana , Monohan Gregory P. , Goldberg Amit , Fleischman Roger , Herzig Roger , Saeed Hayder , Hildebrandt Gerhard C. , Ramlal Reshma
Published: March 2019

Purpose: Acute myeloid leukemia (AML) is characterized by multiple somatically acquired mutations that affect genes of different functional categories. It has been well established in myelodysplastic syndrome (MDS) that the cumulative number of somatic mutations has an impact on overall survival. However, no such data exist for AML. In this study, we sought to determine the number of clinically significant somatic mutations for each cytogenetically defined risk group of AML and to determine whether this had an impact on overall survival (OS). Methods: In this retrospective, single-center study, all adult patients diagnosed with AML from August 2016–December 2017 were reviewed. Baseline characteristics, somatic mutations in the diagnostic bone marrow as detected by Next Generation Sequencing (NGS), and survival outcomes were analyzed. NGS panel was done in-house and could identify 94 genes. Patients were divided into favorable, intermediate, and poor risk groups based on cytogenetics, and molecular abnormalities using NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML, version 1.2018. Kaplan-Meier plots and Cox regression analyses were utilized. Results: A total of 105 AML patients were included; baseline characteristics and frequency of identified clinically significant (CS) mutations are described in the presentation. The FLT3 mutation occurred in the highest frequency (22%) followed by DNMT3A & ASXL1 (15%). 17 (16%) patients were favorable risk, 33 (31%) intermediate risk, and 55 (52%) were poor risk. 67.6% of patients were male, and the median age was 64 (20–79) years. There was a difference in the number of CS mutations between the intermediate risk group and favorable risk group (P=.007), but not between the favorable risk and poor risk groups (P=.221) or between the intermediate risk group and poor risk group (P=.093). Increased number of CS mutations (≥ 5) was seen with equal frequency across risk groups and predicted for shorter overall survival in both univariate (HR=2.80; P=.039) and by multivariate Cox regression analysis (P=.001) independently from assigned risk group. There were no differences in age, gender, smoke, geographic, and different risk groups by multivariate analyses. Conclusion: Our study shows that ≥ 5clinically significant somatic mutations were associated with adverse outcomes and decreased survival, independent of risk groups and induction regimen. Thus, it may be a useful prognostic factor. This finding needs to be validated using a larger sample size.
HSR19-076: A Prospective Study of the Usage of Pain Medication, Cost, Alternative Medication Use, and Outcome by Cancer Patients in Real World
Authors: Adusumilli Praveen , Viswanath Vidya , Digumarthi Raghunadha Rao
Published: March 2019

Introduction: Perception of pain and the need to treat it is highly variable, even amongst oncologists. Availability of pain specialists is an added advantage. This is an analysis of prescription patterns of pain medication and its outcome in cancer patients. Materials and Methods: The center has 8 oncologists and a pain and palliative care specialist. All the patients presenting to the outpatient department of our institute with a diagnosis of cancer were prospectively analyzed for usage of pain medication using a structured questionnaire. Data on diagnosis, stage, treatment given, and outcomes were analyzed. Pain intensity was recorded on visual analogue scale, types of pain medicines used, and their side effects were noted. The average cost of the pain medication purchased in our pharmacy was calculated. Use of alternative medicines was also noted. Results: A total of 1,098 cancer patients were evaluated. Pain was a prominent complaint in 64.6% of patients. Of these, only 89.5% received pain medication. Mild, moderate, and severe pain was seen in 52.1%, 26.7%, and 21.2% respectively. The 3 most common diagnoses were breast cancer in 19.7%, gastrointestinal cancer in 14%, and 12.1% with head and neck cancers. Weak opioids and NSAIDS were most commonly prescribed analgesics in 44.2% and 42.1%, respectively. Morphine was prescribed for 13.7% of patients. The average cost of pain medicines is Re 148 (US $2.25 a month). Side effects from medication were seen in 13.5% of patients, with constipation being the most common. Alternative forms of medicine were reportedly used by 148 patients: Ayurveda by 20.8%, and homeopathy by 12.9%, native medication by 6.1%, Unani by 1.8%. Good relief of pain was reported by 66%, fair relief by 27%, no relief by 6.1%, and worsening by <1%. Conclusion: Pain management is near ideal with the availability of services of pain and palliative care specialist in a cancer center.
QIM19-119: Validity of the French-Language Mammography Satisfaction Instrument Evaluating Women’s Satisfaction With an Organized Breast Cancer Screening Program: A Confirmatory Study
Authors: Bairati Isabelle , Julien Anne-Sophie , Chiquette Jocelyne
Published: March 2019

Background: To evaluate the quality of an organized mammography screening program based on the perception of screened women, we developed and validated the French-language Mammography Satisfaction Instrument (MSI). The study objective was to confirm the validity and reliability of the MSI. Methods: A confirmatory study was conducted among 529 women who had had a recent screening mammography under the Quebec Breast Cancer Screening Program (PQDCS). Eligible women from the Quebec City region completed the online MSI between January 14 and May 23, 2016. The MSI originally included 14 items evaluating 4 factors: satisfaction with (1) the technician’s skills; (2) the physical environment; (3) the staff’s communication skills; and (4) the information provided under the program. A fifth factor with 2 items, evaluating mammography accessibility, was added. A confirmatory factor analysis (CFA) was done and goodness of fit indices were generated (SRMR, CFI, RMSEA with its 90% CI). Item reliability and composite reliability were estimated. Variance extract estimates (VEEs) were generated to assess the amount of variance explained by the factors. Multivariate logistic regressions were done to test the sensitivity of each scale to identify subgroups of unsatisfied women. Odds ratios (OR) and their 95% CI were estimated. Results: Most women (62.0%) were aged 55–64, and 32.9% had university level education. The CFA demonstrated that the 5 factors fitted the data well (SRMR=0.044; CFI=0.969; RMSEA=0.055 with its 90% CI: 0.047–0.063). Item reliabilities (≥0.55) and composite reliabilities (≥0.87) were high. All VEEs were also high (≥0.70). Pain during compression, anxiety before the mammography, perception of not having an excellent health, and the radiologic centers were the factors the most consistently and significantly associated with the 5 scales of satisfaction. In addition, women with university level education were less satisfied with the staff’s communication skills (OR=0.64; 95% CI: 0.43–0.97) and those having had less than 10 lifetime mammograms were less satisfied with the physical environment (OR=0.52; 95% CI: 0.33–0.83) and the accessibility (OR=0.53; 95% CI: 0.31–0.92). Conclusions: This confirmatory study showed the good reliability and validity of the construct of the 16-item MSI with 5 factors. The MSI is useful to detect unsatisfied women and to improve the quality of organized breast cancer screening programs.
QIM19-124: Does Virtual Navigation Improve Care Continuity and Compliance in Patients With Early Stage Colon Cancer?
Authors: Crawford Dayna , Blackmore Brook , Ortega Jeremy , Williams Erica
Published: March 2019

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.
QIM19-123: Addressing Opportunities for Improving Care Cadence by Driving Interdepartmental Collaboration
Authors: Byrwa-Neff Kimberly , Waugh Wendi , Bomkamp Rhondalyn
Published: March 2019

Background: Southern Ohio Medical Center (SOMC) is a community hospital in Portsmouth, Ohio. Review of data pertaining to breast care delivery demonstrated opportunities for improvement. Analysis of the cadence of care processes across departments demonstrated delays in care and outmigration potential. One quality study demonstrated 10% of patients did NOT select SOMC for surgical intervention post biopsy. Method: SOMC reached out to industry for solutions and suggestions to better coordinate care and address barriers within the breast program. A team of clinical, process excellence specialists from Leica Biosystems conducted telephonic interviews and on-site assessments relative to internal processes and methods for care delivery. The SOMC Breast Health Leadership Team (BHLT) in concert with the Leica Biosystems Process Excellence Team identified the following barriers and opportunities: Barriers were (1) Lack of timely data to drive breast care coordination and prioritization; (2) Inefficiencies in patient scheduling; (3) Lack of common goal deployment across departments; and (4) Limitations of resources. Opportunities were to (1) Improve coordination, (2) improve quality and safety of care provided, (3) increase market share, and (4) increase patient loyalty. Results: The SOMC BHLT purposefully initiated interdepartmental communications and emphasized the importance of interdepartmental task interdependence. Data reviewed and collected during the on-site observational analysis provided baselines for opportunities for improvement in care delivery and pointed out where delays and risks for patient safety existed. Patients requiring additional imaging evaluation and/or comparison to prior mammograms (BI-RADS 0) experienced improvement when changes were implemented relative to scheduling; days from screening to diagnostic mammogram in 2017 was 21.8 days versus 6.5 days in 2018. Patients with BI-RADS 4 or 5 experienced improved timelines from diagnostic mammogram to biopsy, 4.5 days in 2017 to 2.5 days in 2018. Finally, 34% of patients received their biopsy within 24 hours in the fourth quarter in 2017 while 76% of the patients received a biopsy within 24 hours in the most recent quarter (July–September 2018). Conclusion: Working together, industry can provide expertise and guidance not always available in community hospital settings to help: identify barriers and opportunities, drive interdepartmental care optimization, reduce opportunity for outmigration, mitigate risks, and strive to improve quality.
HSR19-112: Qualitative Development of a Patient-Reported Outcome Measure of Symptom Burden in Breast Cancer
Authors: Whisenant Meagan S. , Strunk Faith A. , Tripathy Debasish , Williams Loretta A.
Published: March 2019

Background: The use of disease-specific patient-reported outcomes (PROs) is critical for facilitating individualized symptom monitoring and improving cancer patient outcomes. The MD Anderson Symptom Inventory (MDASI) is a PRO measure of symptom burden. The purpose of this study was to describe the patient experience and define the content domain for the MDASI module specific to breast cancer (MDASI-Br). Methods: 36 patients with breast cancer across the disease and treatment continuum described their experience in single qualitative interviews. Content analysis was used to define the symptom burden content domain. An expert panel scored the relevance on a 0–4 scale (4 = relevant) of the symptoms identified from the qualitative interviews. Symptoms were selected for inclusion in the MDASI-Br if they met at least 1 of the following criteria: (1) mean relevance rating of ≥3 by the expert panel, (2) described by ≥20% of patients in qualitative interviews, or (3) core MDASI items. Results: Participants had a mean age of 57.9 years, 86.1% had stage I–III, and 52.8% were on active treatment. 36 symptoms were identified, with 14 reported by ≥20% of participants. Symptoms varied among participants based on disease stage and treatment modality. Fatigue and distress were described by most women regardless of treatment, whereas arm swelling was reported only by women who had undergone surgery, and skin changes were reported primarily by women who received radiation therapy. Patients volunteered ways in which symptoms affected daily functioning. 21 symptoms were included in the MDASI-Br for psychometric testing, including 6 breast cancer-specific symptoms: breast changes, hot flashes, constipation, arm swelling, fingernail or toenail changes, and skin changes. Two additional symptoms, vaginal dryness and decrease in sexual interest or activity, were included because they are common to endocrine therapy. Conclusions: Patients with breast cancer experience numerous but distinct symptoms related to disease and treatment that may result in interference with daily activities, relationships, life plans, treatment adherence, and mood. Various treatments result in unique symptom burden. The content domain for a PRO symptom-burden measure of breast cancer encompasses the diversity, severity, and activity interference of common symptoms of breast cancer and its treatment.
CLO19-052: Incidence of Ribociclib-Associated Cardiac Conduction Abnormalities in Patients With Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer: A Combined Analysis of 3 Phase III Randomized Controlled Trials
Authors: Thein Kyaw Z. , Ball Somedeb , Swarup Sriman , Sultan Anita , Zaw Myo H. , Tijani Lukman , Awasthi Sanjay , Hardwicke Fred , Jones Catherine
Published: March 2019

Introduction: Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, has improved survival in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER 2)-negative advanced breast cancer. Despite remarkable efficacy, potential cardiac toxicities remain a concern. We undertook a combined analysis of randomized controlled trials (RCT) to estimate the incidence of prolongation of corrected QT interval (QTcF) associated with ribociclib. Methods: We performed systematic search of Embase, MEDLINE, and meeting abstracts till September 30, 2018, to find all phase 3 RCTs comparing ribociclib with other agents or placebo in patients with advanced breast cancer and reporting QTc prolongation as adverse event. Mantel-Haenszel method was used to calculate the pooled risk ratio (RR) and absolute risk difference (RD) with 95% CI. Fixed effects model was applied. Heterogeneity was assessed using I2 statistic. Results: Three phase III studies with 2,062 participants were included. Randomization ratio was 1 to 1 in MONALEESA-2 and 7 studies and 2 to 1 in MONALEESA-3 study. I2 statistic was 0, suggesting homogeneity across studies. Prolongation of QTcF >60 msec from baseline was observed in 72 patients (61 had post-baseline QTcF >480 msec) in ribociclib arm, compared to 7 in control arm. Pooled RR for prolongation of QTcF was 7.956 (95%CI: 3.683–17.187; P<.001) and RD was 0.055 (95%CI: 0.040–0.070; P<.001). The risk of having a post-baseline QTcF >480 msec was significantly higher with ribociclib vs control (pooled RR, 4.002; 95%CI: 2.161–7.412; P<.001; and RD, 0.039; 95%CI: 0.024–0.055; P<.001). A total of 16 (1.38%) patients in the ribociclib arm had dose reduction, interruption, or discontinuation due to QTcF prolongation, as opposed to 3 (0.33%) in control arm. Pooled RR and RD were statistically significant at 4.204 (95%CI: 1.333–3.260; P=.014) and 0.012 (95%CI: 0.004–0.021; P=.006), respectively. Conclusion: Advanced breast cancer patients may have cardiac dysfunction due to prior cardiotoxic chemotherapies. In our meta-analysis, ribociclib was associated with significantly higher risk of QTc prolongation and the resultant dosing inconsistencies and discontinuation. Early detection of this potential adverse event and timely intervention are critical.
EPR19-74: Risk of Cabozantinib-Associated Gastrointestinal and Hepatic Toxicities in Patients With Metastatic Solid Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Sultan Anita , Swarup Sriman , Mogollon-Duffo Francis , Aung Ye , Myat Yin M. , Zaw Myo H. , Yendala Rachana , D’Cunha Nicholas , Thein Kyaw Z.
Published: March 2019

Background: Cabozantinib is an oral inhibitor of multiple tyrosine kinases and is used in treatment of multiple solid tumors, targeting several pathways such as vascular endothelial growth factor signaling pathway and proto-oncogenes MET, KIT, RET. These pathways are implicated in several tumor development and progression. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities among patients with metastatic solid tumors treated with cabozantinib. Methods: MEDLINE, EMBASE databases, and meeting abstracts from inception to September 2018 were queried. Phase 3 RCTs that mention GI and elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: We included 4 phase 3 RCTs with a total of 2,703 patients with various solid tumors. The study arm used cabozantinib while the control arm utilized everolimus or placebo or prednisone. The relative risks of all-grade side effects were as follows: diarrhea, 2.495 (95% CI: 2.149–2.897, P<.0001); nausea, 1.849 (95% CI: 1.649–2.072; P<.0001); vomiting, 2.335 (95% CI: 1.724–3.163; P<.0001); stomatitis, 4.541 (95% CI: 0.908–22.696; P=.065); dysgeusia, 4.428 (95% CI: 2.67–7.343; P<.0001); elevated AST, 2.002 (95% CI: 1.331–3.011; P=.001); and elevated ALT, 1.988 (95% CI: 0.936–4.222; P=.074). The RR of high-grade side effects were as follows: diarrhea, 5.913 (95% CI: 3.655–9.566; P<.0001); nausea, 3.098 (95% CI: 1.266–7.581; P=.013); vomiting, 1.298 (95% CI: 0.395–4.265; P=.668); stomatitis, 3.837 (95% CI: 0.749–19.665; P=.107); dysgeusia, 1.522 (95% CI: 0.159–14.574; P=.716); elevated AST, 1.733 (95% CI: 1.101–2.728; P=.018); and elevated ALT, 2.489 (95% CI: 1.164–5.326; P=.019). Conclusion: The risk of developing all grades of diarrhea, nausea, elevated AST, and any-grade vomiting, dysgeusia as well as high-grade elevated ALT, was high in cabozantinib group. Timely recognition and providing good supportive care will enhance patients’ quality of life.
HSR19-077: Primary Tumor Location (PTL) and Survival Outcomes in a Real World Cohort of KRAS Wild-Type (WT) Metastatic Colorectal Cancer (mCRC) Patients in the United States
Authors: Aggarwal Himani , Sheffield Kristin M. , Li Li , Lenis David , Sorg Rachael , Miksad Rebecca
Published: March 2019

Background: PTL is a prognostic factor for mCRC. Recent data suggest PTL is also predictive of survival benefit with cetuximab (CET) and bevacizumab (BEV). This study evaluated the prognostic and predictive effect of PTL in patients with KRAS WT mCRC who initiated first-line (1L) therapy with CET vs BEV in the real world. Methods: This retrospective study selected patients with KRAS WT mCRC who initiated 1L therapy with CET or BEV + FOLFIRI or FOLFOX between January 2013 and April 2017 from Flatiron Health’s electronic health record-derived database. PTL was abstracted from patients’ charts. Left-sided PTL (LPTL): splenic flexure to rectum; right-sided PTL (RPTL): cecum to splenic flexure. Propensity score matching was used to balance treatment cohorts on baseline characteristics. Kaplan Meier and Cox regression methods were used for survival analyses. Results: 1,312 patients met the selection criteria. Of 248 CET + FOLFIRI or FOLFOX patients, 164 had LPTL and 84 had RPTL; of 1,064 BEV + FOLFIRI or FOLFOX patients, 679 had LPTL and 385 had RPTL. CET LPTL and RPTL patients were more likely to receive FOLFIRI vs BEV patients (LPTL: 64.0% vs 24.3%; P<.001; RPTL: 76.2% vs 24.9%; P<.001). Stage at initial diagnosis was different between CET RPTL vs BEV RPTL patients (P<.001). CET RPTL patients were more likely to be stage III (44.0% vs 22.6%) while BEV RPTL patients were more likely to be stage IV (48.8% vs 65.7%) at initial diagnosis. CET RPTL patients were more likely to have a history of adjuvant chemotherapy vs BEV RPTL patients (47.6% vs 22.3%; P<.001). In the matched sample, median overall survival (OS) was 29.7 months (95% CI, 26.9–35.2) for LPTL patients vs 18.3 months (95% CI, 15.8–21.3) for RPTL patients (P<.001). Median OS was 29.7 months (95% CI, 27.4–NA) for CET LPTL vs 29.1 months (95% CI, 26.6–35.6) for BEV LPTL patients (HR, 0.87; 95% CI, 0.63–1.19; P=.378), and 17.0 months (95% CI, 12.0–32.6) for CET RPTL vs 18.8 months (95% CI, 15.8–22.3) for BEV RPTL patients (HR, 1.00; 95% CI, 0.68–1.46; P=.996). The interaction of treatment and PTL was not significant in the Cox regression. Conclusions: This study found a prognostic effect of PTL but not a predictive effect. LPTL patients had significantly longer OS vs RPTL patients. However, the treatment effect for CET vs BEV by PTL was not significantly different. Future research is needed to examine differences between real-world and clinical trial populations that may have contributed to divergent results.
YIA19-007: Patient-Derived Tumor Organoids for Drug Discovery of High-Risk Hepatoblastoma
Authors: Zhu Liqin , Li Liyuan , Hamel Laura , Lopez-Terrada Dolores
Published: March 2019

Hepatoblastoma (HB), the most common liver cancer in children, has become the fastest growing pediatric cancer in the United States. The extent of tumor resection remains the most significant prognostic factor for HB, leaving children with unresectable HB limited treatment options and a largely stagnant survival rate below 40%. Due to the rareness and heterogeneity of this pediatric solid tumor, clinically-relevant, patient-derived models are in urgent need in order to develop more effective therapy for individual patients. Recent studies on many adult cancers have proven patient-derived organoids (PDOs) are faithful in vitro models mimicking disease biology and patient drug response. Via the support from a 2017 NCCN Young Investigator Award, our lab tested HB organoid culture using a large cohort of patient-derived xenografts (PDXs). To date, we have grown HB PDOs from PDXs derived from primary, metastatic, and recurrent tumors at 82% (11/14), 100% (7/7), and 100% (2/2) successful rate, respectively. These HB PDOs displayed histopathology consistent with that of their parental tumors. When we tested the first group of 6 PDO lines to the 10 drugs included in recently opened COG AHEP1531 clinical trial for pediatric liver cancer, we found 2 lines whose parental tumors did not respond to HB standard-of-care cisplatin. They showed the same resistance to cisplatin as well as 2 other platinum-based drugs, carboplatin and oxaliplatin. PDOs derived from 2 matched primary and metastatic tumors showed most similar overall response. These results provided encouraging evidence supporting the notion that HB PDOs mimic patient drug response. Intriguingly, in a subset of cisplatin-resistant HB PDOs, vincristine and gemcitabine showed strong antitumor activities, which we will further validate in vivo using a novel neonatal liver xenograft model developed in our lab. To accurately model the unique early developmental tumor microenvironment (TME) of HB, we have successfully engrafted HB cells into the liver of postnatal day 5–7 mice. We found TME of the neonatal liver, indeed, has a strong and unique metastasis-promoting effect compared to that of the adult liver. With this first PDO effort on pediatric HB and our exciting preliminary data, we are confident that we are approaching our long-term goal of building an integrated “HB PDO Clinic” to enable accurate evaluation of disease risk and therapeutic response to facilitate personalized HB patient care.
BPI19-020: A New Protecting Method for the Inferior Parathyroid Gland in situ: The Meticulous Thyrothymic Ligament Dissection Technique
Authors: Si Yan , Cai Jingsheng , Zhang Hao , Fang Haisheng , Shen Meiping
Published: March 2019

Objective: To explore the anatomic features and the dissection technique of thyrothymic ligament (TTL) and to explore the clinical significance of protecting the inferior parathyroid gland (IPTG) with this structure. Method: Dissect the TTL of patients who receive initial thyroid surgery in our center, describe the structural features of TTL, and investigate the positional relationship of TTL and IPTG. Results: TTL is a kind of adipose connective tissue that is wide at the bottom and narrow at the top, accompanying with the inferior thyroid vein, from the thymus to the thyroid. Over 70% TTL are attached to the lower pole and the lower one-third dorsal of thyroid, containing fat and vessels. About 121 patients have undergone this dissection, totally dissected 194 sides, 143 sides had TTL (73.7%). About 63.4% IPTGs are located in the thymus-thyrothymic ligament-IPTG complex (TLIC), and nearly 70.6% IPTG can be proactively identified and located by the TTL during the operation. The incidence rate of postsurgical hypoparathyroidism is 14.9%. According to whether the dissection is successful, the IPTG can be described into 2 types, the ligament type (L) and the non-ligament type (N), and each type can be described into different subtypes.
CLO19-047: Jeopardizing the Oncological Safety: Transurethral Resection of Bladder Tumor May Induce Measurable Hematogenous Seeding of Cancer Cells
Authors: Saini Sumit , Nayyar Rishi , Sharma Alpana , Dogra Prem Nath
Published: March 2019

Objectives: Transurethral resection of bladder tumour (TURBT) is a standard procedure for both diagnosis and management of bladder cancer. Intravesical seeding of cells shed during TURBT supposedly plays an important role in tumor recurrences. This may be due to the inherent nature of the procedure, which refutes the basic oncological principle and demands for piecemeal resection. Additionally, high pressure of irrigation fluid during TURBT has the treacherous potential for systemic absorption of tumor cells into circulation and metastatic tumor seeding. By measuring circulating tumor cells (CTC) before and after TURBT, it may be possible to ascertain whether TURBT induces measurable seeding of cancer cells into the circulation. Methods: All consecutive patients undergoing TURBT for newly diagnosed bladder mass were enrolled. Cases with resection time less than 10 min, prior intravesical or radiation therapy, chronic cystitis, neurogenic bladder, metastatic disease at presentation, and final histology other than transitional cell carcinoma were excluded. Peripheral venous blood samples were drawn before and after (within 2 hours) of TURBT, and analyzed using flow-cytometry to ascertain the number of CTC. The peripheral blood mononuclear cells were separated, suspended in FACSTM buffer, stained with specific antibodies to CD-45, EpCam, Cytokeratin 18 & 19, and immediately acquired on a FACSCantoTM II cytometer (BD Biosciences, 4-2 configuration). A cell positive for cytokeratins 18, 19 & EpCam and negative for expression of CD45 was defined as a CTC. The number of CTC in pre and postoperative samples were compared and correlated to the final histopathology. Results: 32 patients were studied. No perforations were encountered. 4/32 (12.5%) patients had raised CTC count following TURBT. All 4 of these patients had high grade and at least T2 (ie, muscle invasive) disease. Overall, rise in CTC count was seen in 4/8 patients (50%) with muscle invasion and 4/13 cases (30.79%) with high-grade disease. There was no significant difference in the average resection time between the group showing rise in CTC versus the other (34 vs 32 .5 minutes, respectively; P=.43). Conclusions: This study provides objective evidence that tumor cells are released into the circulation during TURBT and are detectable in peripheral venous circulation. This occurs predominantly in patients with higher grade and higher stage disease.
HSR19-102: Direct and Indirect Economic Burden of Cervical Cancer (CxCa) in the United States in 2015: A Mixed-Methods Analysis
Authors: Nwankwo Chizoba , Corman Shelby L. , Shah Ruchit , Kwon Youngmin
Published: March 2019

Background: An estimated 12,820 women in the United States will be diagnosed with CxCa in 2018, with 4,210 deaths from the disease. The economic burden of CxCa, both in terms of healthcare costs and lost productivity, has not been adequately studied. Methods: This was a mixed-methods study that evaluated the direct and indirect costs of CxCa using data from the Medical Expenditure Panel Survey (MEPS) for prevalent CxCa cases and the National Center for Health Statistics (NCHS) for deaths due to CxCa. Total healthcare costs and number of work days missed were compared between CxCa cases and controls in MEPS, using propensity scores calculated from baseline demographics and comorbidities. Missed work was converted to costs using the average hourly wage for women in 2015. Per-patient incremental healthcare and lost work productivity costs were then multiplied by the number of prevalent cases of CxCa in 2015 obtained from the Surveillance, Epidemiology, and End Results Program (SEER). NCHS data on the age-stratified number of CxCa deaths per year (1935–2015) and life expectancy data from the Social Security Administration were then used to calcluate the number of women who would be alive in 2015 if they had not died from CxCa and the lost earnings resulting from early mortality. The primary study outcome was the total direct and indirect cost of CxCa in 2015, calculated as the sum of the incremental direct healthcare costs, incremental lost productivity costs due to missed work, and lost productivity costs resulting from early death due to CxCa. Results: An estimated 257,524 women were alive with CxCa in 2015. Total healthcare costs were $4,221 higher, and an additional 0.37 work days were missed in women with CxCa compared to propensity-matched controls. Of the 488,475 women who died of CxCa prior to 2015, 108,832 would be alive in 2015 and 38,540 would be part of the workforce. Lost earnings in 2015 attributable to these deaths totaled $2.19 billion. The total economic burden of CxCa in the United States in 2015 was thus estimated at $3.3 billion (Table 1). Conclusions: CxCa was responsible for nearly $3.3 billion in direct and indirect costs in 2015. Early death among women with CxCa was the biggest driver of total economic burden.
QIM19-130: Quality Improvement Project to Standardize a Prehabilitation Pathway for Patients With Esophageal Cancer Receiving Neoadjuvant Chemoradiation
Authors: Glode Ashley E. , Davis S. Lindsey , Jain Supriya K. , Marsh Megan D. , Wingrove Lisa J. , Schefter Tracey E. , Goodman Karyn , Dewberry Lindel C.K. , McCarter Martin D. , Melton Laura , Bunch Michelle , Purcell William T. , Leong Stephen
Published: March 2019

Background: At our institution, the standard treatment recommendation for esophageal cancer patients with stage IB–IIIB disease is for neoadjuvant chemoradiation per the CROSS regimen prior to surgery. This regimen can be difficult for patients to tolerate, and they may be unable to receive full dose therapy without treatment dose reductions and delays. Methods: We conducted a quality improvement (QI) project, STRENGTH (Seeking to Reactivate Esophageal and Gastric Treatment Health), to implement supportive care interventions in the prehabilitation phase of neoadjuvant treatment. Our QI program included a standardized chemotherapy order template with supportive care interventions implemented at specific time points. Following implementation of the STRENGTH pathway, a retrospective QI analysis assessed an equal number of patients in the pre-STRENGTH and STRENGTH group for chemotherapy and radiation therapy dose intensities, as well as treatment outcomes. Results: During the pre-STRENGTH period, patients received an average of 5 chemotherapy treatments (range, 2–6), with an average relative dose intensity of 91.8% for carboplatin and 86.7% for paclitaxel. During the STRENGTH period, patients received an average of 6 (range, 5–8) chemotherapy treatments, with an average relative dose intensity of 111.4% for carboplatin and 112.9% for paclitaxel. In the pre-STRENGTH group, one patient did not complete their planned radiation dose due to nausea, vomiting, and dehydration. All patients in the STRENGTH group received their planned radiation dose. In the STRENGTH group, there is a trend of improved pathologic response, longer progression-free survival, and shortened time to surgery. Conclusion: Implementation of the STRENGTH pathway improved chemotherapy dose intensity, with potentially improved oncologic outcomes in the STRENGTH group. We plan to further optimize the STRENGTH program with implementation of standardized dose reduction and delay protocols for both chemotherapy and radiation, and assess the effects of STRENGTH interventions on patient quality of life.
HSR19-103: Burden of Self-Reported Mental Health Among Women With Cervical Cancer (CC) in the United States
Authors: Nwankwo Chizoba , Doane Michael J.
Published: March 2019

Background: Globally, CC is the fourth most common cancer in women, with 569,847 new cases and 311,365 deaths from CC reported in 2018. Little is known about the burden of living with CC, especially related to mental health. This study examined patient-reported outcomes, including symptoms of depression and anxiety, amongst women with and without a diagnosis of CC. Methods: Data were aggregated from the 2016–2018 U.S. National Health and Wellness Surveys, a nationally representative, self-administered, internet-based survey of adults (N=247,484). Women who reported a physician-diagnosis of CC were matched 1:1 by propensity scores to a sample of women who did not report any cancer diagnoses. Propensity score matching was conducted using the following sociodemographic characteristics: age, race, possession of health insurance, smoking status, comorbidity status, body mass index, income, and year of survey completion. Bivariate analyses (ie, chi-square and t-tests) assessed differences in mental health outcomes between these 2 matched groups of female respondents. Outcomes included the following: (1) depressive severity via the Patient Health Questionnaire (PHQ-9), (2) suicidal ideation via the PHQ-9 (ie, thoughts of being better off dead on several days or more during the past 2 weeks), (3) anxiety severity via the Generalized Anxiety Disorder 7-Item Scale (GAD-7), and (4) healthcare resource use for mental health services (ie, visits to psychologists and psychiatrists during past 6 months). Results: Analyses of the propensity score matched sample of 1,044 women with a CC diagnosis versus 1,044 without a CC diagnosis showed that CC respondents reported significantly more severe scores of both depression (7.3 vs 6.0; P<.001) and anxiety (5.7 vs 4.7; P<.001). Although not statistically significant, a numerically greater proportion of CC respondents reported suicidal ideation during the past 2 weeks (19.0% vs 16.0%; P=.158). Respondents with CC were marginally more likely to visit a psychologist (8.6% vs 6.4%; P=.056) and were significantly more likely to visit a psychiatrist (8.6% vs 6.2%; P=.037) at least once during the prior 6 months than respondents without CC. Conclusions: CC is associated with mental health burden, including more severe symptoms of depression and anxiety as well as greater use of mental health services. This study highlights the likely impact of CC for both patients as well as the healthcare system