bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of eSyM: An ePRO-based symptom management tool fully integrated in the electronic health record (Epic) to foster patient/clinician engagement, sustainability, and clinical impact.
Authors: Hassett Michael J. , Hazard Hannah , Osarogiagbon Raymond U. , Wong Sandra L. , Bian Jessica J , Dizon Don S. , Wedge Jason , Basch Ethan M. , Mallow Jennifer , McCleary Nadine Jackson , Dougherty David W. , Remick Scot C. , Brooks Gabriel A. , Mecchella John , Solberg Peter , Tasker Laura , Faris Nicholas Ryan , Pacheco Alicia , Cronin Christine , Schrag Deborah ,   eSyM Project Managers
Published: May 2020

e14120 Background: Chemotherapy and surgery can cause distressing symptoms, which can be a burden for health system to address. Programs that directly engage patients, including electronic tracking of patient-reported outcomes (ePROs), can improve symptom control and decrease the need for acute care. Previous ePRO programs have relied on third party vendors with limited EHR integration, constraining their clinical utility and scalability. An integrated solution could offer distinct advantages. Methods: As part of NCI’s Moonshot-funded IMPACT consortium, 6 health systems and Epic built an electronic symptom management program (eSyM) based on the PRO-CTCAE questionnaire that is fully integrated into the EHR. The agile, user-centered design process engaged patients, clinicians, and institutions. The core functional components include: 1) symptom surveys in the postoperative period or between chemotherapy visits, 2) self-management tip sheets, 3) clinician alerts, and 4) dashboards for population management. Critical points of integration with supporting EHR functions and workflow impacts were identified; and major challenges of integration and implementation were described. Results: eSyM, which was implemented at two health systems (Baptist Memorial in Tennessee and Mississippi and West Virginia University Health) in the fall of 2019, required multiple supporting EHR functions: 1) access a secure, HIPPA-compliant patient portal/messaging system (MyChart); 2) record diagnosis, procedure and chemotherapy treatment plan data; 3) identify target populations and track metrics/events; 4) define and execute autonomous logic-based workflow rules; 5) generate reports for clinicians/patients; and 6) documentation. Major challenges included: 1) working within pre-existing EHR system standards and capabilities, which limited the ability to customize interfaces and workflows specifically for the eSyM use case; and 2) adapting to different EHR configurations and polices across multiple health systems. Conclusions: The eSyM build leveraged many existing EHR capabilities and addressed regulatory hurdles; but it required design and workflow compromise. Integration of ePRO-based symptom management programs into the EHR could help overcome barriers, consolidate clinical workflows, and foster scalability/sustainability. Ongoing efforts include launching eSyM at four more sites and evaluating its adoption, usability, and impact on clinical outcomes.
Sickness absence and disability pension among Swedish women before breast cancer relapse.
Authors: Elham Hedayati , Gernaat Sofie a.m. , Johnsson Aina , Wilking Ulla m , Altena Renske 
Published: May 2020

e14121 Background: Sickness absence (SA) and disability pension (DP) from diagnosis of primary breast cancer (BC) among patients who in a later stage will develop a recurrence or metastatic disease is unknown. This study explores the prevalence and risk factors of SA and DP in this study population before and after primary breast cancer diagnosis. Methods: Longitudinal register data on 1,310 female patients living in Sweden (age 20 to 63 years) diagnosed with primary BC between 1996 to 2011, were analyzed for annual prevalence of SA days and DP starting 2 years pre- to 5 years postdiagnosis. Logistic regressions were used to explore associations between primary BC characteristics and future SA. Results: 579 (44.2%) had loco-regional recurrence after a median of 2.5 years (interquartile range (IQR) = 1.3-4.3) and 731 (55.8%) had a metastatic disease after a median of 2.3 years (IQR = 1.3-4.1). 320 (24.4%) of 1,310 were still relapse-free 5 years postdiagnosis. SA was high during year 1 postdiagnosis but decreased steadily through year 5 (67.9%, 40.3%, 29.0%, 23.9%, 19.4%, respectively), while DP steadily increased during this time period (16.4%, 17.5%, 19.7%, 24.9%, 28.7%, respectively). The annual prevalence of SA over 180 days among patients who later were diagnosed with metastatic disease was constantly higher compared to patients who later were diagnosis of loco-regional recurrence. Pre-diagnosis SA, age < 50 years at the time of diagnosis, higher tumor stage, chemotherapy and future metastatic disease were associated with higher odds ratios for SA (odds ratio range, 1.56 to 4.42) Conclusions: In conclusion, longitudinal rates of SA and DP in a cohort of women with early BC, of whom a part developed disease relapse during follow-up were higher compared to previous studies. These are unique findings as previously published studies excluded patients with disease relapse. Patients at increased risk for SA, should be assessed and triaged to optimize chances for a smooth transition to return to work after oncological treatment.
Medicaid expansion and trends in cancer stage at diagnosis.
Authors: Withington John , Tramontano Angela , Schrag Deborah 
Published: May 2020

e14129 Background: Cancer stage distribution offers an early window into the effect of the ACA’s 2014 Medicaid expansion. If Medicaid expansion enabled uninsured adults to access preventive care, then the proportion of cancers diagnosed at early stage should be higher in states that adopted it. Methods: Patient level data were retrieved from SEER-18, New York and Texas cancer registries from January 2010 to December 2015, for eight common tumor types; including N = 2,493,589 (breast, cervical, colorectal, prostate, lung) screen detectable and N = 369,203 (testis, kidney and uterine corpus) not detected by routine screening. Patients were categorized by residence in states that were: 1) Non-expanders; 2) Expanders - income eligibility thresholds increased from 0% to 138% of the federal poverty level (FPL) in 2014; and 3) Pre-Expanders, with pre-2014 eligibility thresholds > 70% of FPL. Stage distributions were compared before and after January 2014, categorized by AJCC stage and using ordinal stage equivalent (OSE) which assigns a numeric score based on AJCC stage. Difference in difference in difference (D3) methods compared patients ≥65 versus < 65, and screen-detectable versus not. Multivariable logistic regression was used to adjust for variation in age, sex, race, ethnicity and tumor site across states. Results: No differences in stage distribution were observed across the three categories of state. (Table). D3 analysis revealed no difference between trends in the over 65s, or for screen-detectable cancers. Adjustment for age, sex, race, ethnicity and tumor site made no significant difference to these results. Conclusions: States’ Medicaid expansion status in 2014 was not associated with a significant difference in early stage diagnoses for adults with cancer diagnosed before age 65. Obstacles to early cancer detection other than financial access must be addressed to improve population-level outcomes. [Table: see text]
How to better anticipate innovative anticancer drugs and their potential challenges: A European survey from the iPAAC WP9.
Authors: Denis Hélène , Bermudez Elisabeth , Aurélie Krol , Duperray Marianne , Negellen Sophie , Breton Thierry , Ifrah Norbert 
Published: May 2020

e14134 Background: The European joint action iPAAC, funded by the European Commission, aims to develop innovative approaches to advances in cancer control. The field of anticancer drugs has strongly evolved over the past years and the clinical development remains very important. Horizon scanning systems (HSS) help policy makers and healthcare professionals to anticipate new medicines and their main impacts before their marketing authorization. The Work package 9 (WP9) of iPAAC, dedicated to innovative therapies in cancer, wanted to evaluate the need for more finesse in the anticipation of innovative therapies in the oncology field. Methods: A survey among organizations in charge of an HSS was conducted to point out methodologic features needed to enable a better anticipation of anticancer drugs, gene and cell therapies, biomarkers and pediatric indications. In addition, a retrospective analysis of the efficiency of HSS was conducted based on the review of 11 approved indications of checkpoint inhibitors and CAR-T cells. For each indication, organizations indicated if it was anticipated via their HSS and provided eventual challenges encountered. Results: Eleven main organizations in charge of HSS were identified in Europe, from which 9 participated to the iPAAC WP9 study. Time frames of these HSS ranged from 3 years to only a few months prior marketing authorizations. While most of the organizations included all innovative drugs in their scope, 2 were focusing only on oncology drugs and had developed specific methods to prioritize innovative medicines. To enable a good anticipation of biomarkers and gene & cell therapies, it appeared important to screen earlier phases clinical trials and to collect additional data. The retrospective analysis showed that biomarker expression threshold and centers authorized to provide gene and cell therapies or biomarker tests were some of the hardest parameters to anticipate. Having a structured database in the HSS process was seen as helpful, as it allowed the generation of ad hoc queries. Involving the expertise of practicing clinicians for prioritizing and assessing the innovative therapies was seen as an important asset for predicting clinically impacting drugs. Conclusions: Anticipating innovative drugs in oncology requires specific characteristics, especially given the variety of drugs, the earliness of data supporting marketing authorization and the dynamics of this therapeutic area. HSS is a valuable resource for the proper introduction and diffusion of innovative drugs.
The impact of patients’ and physicians’ characteristics on surgery decision for head and neck cancer: Results of a national survey.
Authors: Dupret-Bories Agnès , Grosclaude Pascale , Lamy Sebastien , Nebout Antoine , Bories Pierre , Cros Fanny 
Published: May 2020

e14151 Background: The choice between surgical or medical treatments in head and neck cancer is a function of many patient-related and disease-related factors. We investigated how physicians' behavioral characteristics and patients’ socioeconomic status could affect medical decision-making. Methods: A nationwide cross-sectional online survey of surgeons and (radiation) oncologists specialized in head and neck oncology collected data on medical decision-making for 7 clinical vignettes involving head and neck squamous cell carcinoma patients that were representative of routine practice. Questionnaires elicited physicians' demographic and occupational characteristics along with their individual behavioral characteristics according to the decision theory framework. Patients’ gender and socioeconomic position were distributed across vignettes using a Latin square design. Results: We obtained 206 assessable answers. A multivariate analysis shows that surgeons suggested surgery more often than other professionals, which is mostly related to vignettes corresponding to clinical cases for which there is no consensus, so oncologists are 68% less likely than surgeons to choose surgery. For clinical vignette with an absence of consensus, physicians with lower risk aversion recommend more often surgery compared to those with higher risk aversion (OR = 1.88, p = 0.052). When the vignette corresponds to a clinical case for which there is a surgical consensus decision the isolated male blue-collar worker has a 75% lower chance of being offered surgery compared to the married male small business owner (OR = 0.25, p = 0.024). We did not observe any differences based on the patient's gender. Conclusions: Patients’ socioeconomic status did affect our clinical management decisions in head and neck oncology. The significant association between medical decision and individual behavioral characteristics of the physician documented still understudied mechanisms that involved nonbiological factor to explain clinical practices variations.
Association of leukocyte count (neutrophilia and lymphopenia) with poor prognosis in patients with high-grade gliomas in a Guatemalan cohort.
Authors: Ramirez Rixci , Rosales Lopez Daniel Estuardo , Dominguez Jennifer , Gramajo Marisol , Camey Carolina 
Published: May 2020

e14500 Background: In previous studies separately, it has already been determined how the inflammatory response measured by it neutrophilia and also lymphopenia s with temozolamide have determined that they are important at the time of initiation of treatment and have a prognostic value in patients with high-grade gliomas, the objective This study was the prognostic value of leukocyte disorders, absolute neutrophil count and absolute lymphocyte count in a retrospective cohort of patients with high-grade glioma who receive concomitant temozolomide and radiation plus maintenance. Methods: Clinical records of patients treated at the Guatemalan Social Security Institute were registered in the Oncology service within the period from January 1, 2013 to December 2018, the treatment consisted of temozolomide (75 mg / m2 per day) and concomitant radiation and subsequent maintenance with temozolomide (150 mg / m2 D1-5) every 28 days for 6 cycles. The prognostic value of neutrophilia and lymphopenia, prior to treatment in survival, was defined as a neutrophil count greater than 7x10 3 / uL and lymphopenia less than 2 x10 3 / uL. The analysis was performed using Kapplan Mayer curves, log rank test and Cox analysis. Results: We identified 64 high-grade patients (grades III and IV according to WHO), all treatments with concomitant chemoradiotherapy based on temozolomide and subsequent maintenance with temozolamide. The initial surgery was lost in the majority (75%), with resection > 90% in 25 patients (34%). 79.4% were treated with radiotherapy plus concomitant chemotherapy followed by adjuvant chemotherapy with temozolamide of these, 69% completed the treatment, thirty-two patients (50%) with pre-treatment neutrophilia. The overall survival at 2 years was 55%. In the univariate analysis, neutrophilia is associated with a worse overall survival (p = 0.019), as well as lymphopenia (p = 0.003), in addition to the age ≥65 years (p = 0.0001), surgical resection < 90% (p = 0.045) and prednisolone consumption ≥50mg / day (p = 0.045). In the multivariate analysis, neutrophilia (p = 0.017), age ≥65 (p = 0.001), lymphopenia (p = 0.0056) were associated with a worse prognosis with reduced survival. Conclusions: In high-grade gliomas treated with temozolomide and concomitant radiation followed by maintenance with temozolamide, neutrophilia and lymphopenia can be a significant prognostic factor for overall survival, with the advantage that it is not an expensive test and is accessible at all times of patient follow-up.
Combination chemotherapy versus temozolomide (TMZ) for patients with MGMT methylated (m-MGMT) glioblastoma (GBM): Results of cellworks omics biosimulation—MyCare-015.
Authors: Castro Michael , Mundkur Nirjhar , Pampana Anusha , Alam Aftab , Alam Aktar , Parashar Rajan , Rajagopalan Swaminathan , Lala Deepak Anil , Ghosh Roy Kunal Ghosh , Basu Sayani , Prakash Annapoorna , Nair Prashant , Christie Jim , Joseph Vishwas , Agarwal Ashish , G Poornachandra , Behura Liptimayee , Kulkarni Shruthi , Choudhary Nikita Ray , Kapoor Shweta 
Published: May 2020

e14501 Background: UKT-03 evaluated TMZ plus Lomustine in a single arm phase II trial in newly diagnosed GBM patients. An overall survival of 23 months was a substantial improvement over historical experience. Patients with m-MGMT v. unmethylated tumors had a 2-yr survival of 75% and median survival not reached compared to 20% and 12.5 months, respectively. These data formed the basis for NOA-9, a randomized phase III trial in newly diagnosed, m-MGMT GBM which randomized 141 patients to standard therapy or experimental therapy with Lomustine and TMZ every 6 weeks. A superiority for the combination was observed: 48.1 v. 31.4 months for the standard arm in the ITT analysis. Nevertheless, many neurooncologists are reluctant to adopt this approach. The current standard of care uses single biomarker, m-MGMT, in contrast to comprehensive pathway analysis (CPA). We sought to determine if CPA could discriminate more effectively among each patient’s likelihood of benefiting from combination treatment. Methods: Cellworks Singula employs a novel Cellworks Omics Biology Model (CBM) to predict patient-specific biomarker and phenotype response of personalized GBM avatars to drug agents, radiation, and targeted therapies. The CBM was developed and validated using PubMed to generate protein network maps of patient-specific activated and inactivated disease pathways. CBM was used to simulate the TMZ and TMZ-Lomustine therapies for each patient in a TCGA cohort of 368 GBM patients. Omics data including methylation, whole exome sequencing, and copy number alterations were input into CBM. The Singula Composite Inhibition Score (CIS) was calculated based on the measured quantitative drug effects. Results: Though incremental gain from the combination was seen in all patients, CIS varied across the population with relative scores ranging from 32-82, with best responders have more than twice the benefit. Conclusions: CPA shows that m-MGMT is an excellent biomarker for determining the likelihood of benefit from TMZ and lomustine, with the caveat that CBM identifies 18% could be spared from TMZ exposure and would benefit from Lomustine alone. Otherwise, these data lend support for evolving the standard of care with combination therapy for patients with m-MGMT GBM and should help overcome a reluctance to employing combination therapy. Additionally, CBM has utility to individualize clinical decision making. [Table: see text]
Evaluation of tumor growth inhibition activity of a novel multi-TRK inhibitor ABP-1130 on glioblastoma xenograft model.
Authors: Zhan Zheng-Yun James , Pan Wanlong , Zhang Hao 
Published: May 2020

e14507 Background: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive cancer that begins within the brain. Glioblastoma is a difficult to treat tumor with therapeutics limited by their ability to cross the blood brain barrier. Receptor tyrosine kinases (TRK) inhibitor is reported one of therapies for glioblastoma. ABP-1130 is a novel and potent small molecular multi-TRK Inhibitor for several prime tyrosine kinases (TRKs), such as EGFR, HER2, C-Met, and BTK with potential to treat glioblastoma. Pre-clinical studies with ABP-1130, especially study to evaluate its tumor growth inhibition effect on glioblastoma xenograft model, are planned in progress. Methods: (1) Mobility-Shift Assay used to Analyze the multi-TRK (such as EGFR, HER2, C-Met, and BTK) Inhibition activity of new anti-tumor compounds, (2) CTG Assay used to analyze the inhibition activity of LN-229 Cell Line, (3) Anti-tumor inhibition study of ABP-1130 with the brain cancer nude mice, (4) Safety studies of ABP-1130 for Ames, hERG, and MTD. Results: It was determined that its multi-TRK inhibition activity (IC50) of ABP-1130 was 7nM to EGFR, 3.6nM to HER2, 3.2nM to C-Met, and 3.7nM to BTK, respectively. Its inhibition activity for Cell Line LN-229 was 0.02 µM. In anti-tumor inhibition study with the LN-229 tumor nude mice for 28 days, the anti-tumor inhibition activity of ABP-1130 (40 mg/kg, QD) was significantly observed, and the average volume of brain tumors in nude mice (six mice/each group) was reduced from 122 mm3 to < 10mm3 (vs Pazopanib as a positive control, 50mg/kg, tumor volume increased from 123 to 867mm3). Moreover, for other safety issues, its Ames is negative and hERG is > 30 µM, and no test-article related death or adverse events occurred in maximum tolerated dose (MTD) studies with ABP-1130 (100mg/kg, QD) for 14 days. ABP-1130 also had very good metabolic stability in Human (T1/2 = 193min). Conclusions: Based on our completed preclinical study results, ABP-1130 is a novel and potent multi-TRK Inhibitor, showing excellent enzymatic activity, prominent in-vitro anti-cancer activity, and significant tumor growth inhibition activity with tolerable toxicity in glioblastoma tumor xenograft in nude mice model. It is highly warranted to continue further investigation in glioblastoma.
Treatment outcomes in melanoma with brain metastases in the era of immunotherapy: An analysis of the National Cancer Database.
Authors: Moyers Justin , Chong Esther G , Sufficool Daniel , Nagaraj Gayathri 
Published: May 2020

e14513 Background: Brain metastases (BM) are a major cause of morbidity and mortality in metastatic melanoma. Radiotherapy (RT) and/or surgery are the standard of care for treating brain metastases. The introduction of immune checkpoint inhibitors has drastically improved disease outcomes since approved in 2011 and recent trials have exhibited intracranial activity. We aim to assess the added survival benefit of immuno-oncologic agents (IO) for melanoma with BM in National Cancer Database. Methods: We queried the database from 2011 to 2015 for Stage IV melanoma with BM. RT treatments were divided into stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), or no brain radiation; those with insufficient documentation were excluded. Patients were further divided into receipt of IO or no receipt of IO; those without documentation were excluded. Concurrent (CC) treatment was defined as IO begun before or during RT treatment; sequential (SQ) therapy was defined as IO begun after RT. Survival analyses were performed by Kaplan-Meier method and log-rank test. Results: Among 8,561 metastatic melanoma patients with documentation of metastatic sites, 3,008 (35.1%) had documented BM. Median overall survival (mOS) for all stage IV melanoma was 10.5 months with worse survival for those with BM compared to those without (mOS 6.0 v 14.7 m; p < 0.01). Among 3,008 cases with survival data available, 2,762 met criteria for survival analysis of BM treatments. Table summarizes treatment outcomes between cohorts by RT and IO treatment categories. IO + SRS had improved survival compared to all other treatment groups (mOS 19.9 m; p < 0.01). No difference in survival between SRS and IO alone was observed (mOS 10.9 v 11.5 m; p = 0.56). WBRT as single modality did not appear to improve survival over no therapy (mOS 4.2 v 3.3 m; p = 0.35). 436 cases had documented time course between IO and RT. IO was given SQ with RT in 69% of SRS (n = 158/230) and 67% of WBRT (n = 137/206) treated patients. In SRS + IO cohort, survival was longer for SQ compared to CC treatment (23.5 v 13.1 m; p < 0.01). Survival was similar in WBRT for SQ v CC groups (6.8 v 7.9 m; p = 0.62). Conclusions: Superior survival is realized for those who receive IO in addition to SRS for BM. IO and SRS as single modality have similar outcomes, while WBRT seems to add little survival benefit to IO or no therapy. [Table: see text]