bluuebunny/crossref_metadata_2025_split huggingface dataset:
PARADIGM study: A multicenter, randomized, phase III study of 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus panitumumab or bevacizumab as first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer.
Authors: Yoshino Takayuki , Uetake Hiroyuki , Tsuchihara Katsuya , Shitara Kohei , Yamazaki Kentaro , Oki Eiji , Sato Takeo , Naitoh Takeshi , Komatsu Yoshito , Kato Takeshi , Iwasaki Kouji , Soeda Junpei , Hihara Masamitsu , Yamanaka Takeharu , Ochiai Atsushi , Muro Kei 
Published: February 2017

TPS776 Background: Optimal combination of monoclonal antibody (anti-VEGF vs. anti-EGFR antibody) with standard chemotherapy as first-line treatment in patients (pts) with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC) remains controversial. FIRE-3 study demonstrated a significant improvement in overall survival (OS) with anti-EGFR over bevacizumab in pts with KRAS exon 2 wild type mCRC, while CALGB 80405 study did not. PARADIGM study is designed to compare panitumumab vs. bevacizumab combined with mFOLFOX6 in pts with RAS wild-type chemotherapy-naive mCRC. Methods: Eligible pts are aged 20-79 years with ECOG performance status (PS) 0-1 and histologically/cytologically confirmed RAS wild-type mCRC. 800 pts will be randomly assigned in a 1:1 ratio to mFOLFOX6 plus panitumumab or bevacizumab, and stratified according to institution, age (20-64 vs. 65-79 years), and liver metastases (present vs. absent). Each treatment regimen includes oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, 5-fluorouracil (5-FU) iv 400 mg/m2 at day 1, 5-FU civ 2400 mg/m2 at day 1-3, and either panitumumab 6 mg/kg or bevacizumab 5 mg/kg at day 1 every two weeks. The primary endpoint is the OS; the study was designed to detect the OS hazard ratio of 0.76, with a one-sided type I error of 0.025 and 80% power. Secondary efficacy endpoints include progression-free survival, response rate, duration of response, and curative resection rate. One interim analysis is planned for the OS when approximately 70% of the targeted 570 events has been observed. Exploratory endpoint is to investigate possible biomarkers including oncogenic mutations using tumor tissue and circulating tumor DNA (Study ID: NCT02394834). As of August 2015, 21 pts have been randomized and recruitment is ongoing. Clinical trial information: NCT02394795.
RX-5902: A phosphorylated p68 targeting agent to treat subjects with advanced solid tumors.
Authors: Gutierrez Martin , Eckhardt S. Gail , Gluck W Larry , Benaim Ely 
Published: February 2017

TPS778 Background: Phosphorylated p68 may play a vital role in cell proliferation and tumor/cancer progression. RX-5902 is a novel compound that targets phosphorylated p68 RNA helicase (also known as DDX5), a member of the DEAD box family of RNA helicases. As a single agent, RX-5902 inhibits tumor growth and enhances survival in a variety of xenograft tumor models (e.g., pancreatic, renal, ovarian, melanoma). Methods: This Phase 1, open-label, multicenter study evaluates the efficacy and safety of RX-5902 in subjects with solid tumors. RX-5902 is administered orally 1, 3 or 5 times per week for 3 weeks with 1 week of rest in each 4 week cycle. Dose escalation starts with an accelerated design treating 1 subject per dose followed by a standard 3 + 3 design using a modified Fibonacci sequence after the occurrence of a single Grade 2 or greater adverse event that is considered at related to RX-5902. The primary endpoint is the overall safety profile characterized by the type, frequency, severity, timing of onset, duration and relationship to study therapy of any adverse events, or abnormalities of laboratory tests or electrocardiograms as well as the description of any dose limiting toxicities that occur during Cycle 1, serious adverse events, or adverse events leading to discontinuation of study treatment. Secondary endpoints include pharmacokinetic parameters (e.g., time to maximum observed concentration [Tmax], maximum observed plasma concentration [Cmax], trough concentration [Ctrough], area under the concentration-time curve [AUC]) and Indices of anti-tumor activity (e.g., overall response rate, time to response, duration of response, and progression-free survival during treatment. Exploratory endpoints are biochemical levels of drug targets in blood and tumor samples. Eligible subjects must have confirmed histologic or cytologic evidence of metastatic or locally advanced solid neoplasm that has failed to respond to standard therapy, progressed despite standard therapy or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens. Clinical trial information: NCT02003092.
Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial.
Authors: van der Stok Eric P , Verhoef Cornelis , Grunhagen Dirk J. ,   CHARISMA Study Group
Published: February 2017

TPS790 Background: Colorectal carcinoma is a leading cause of cancer death worldwide, mostly as a consequence of metastatic disease. If metastases are confined to the liver, surgical resection is the only therapy providing potential for cure. Efforts to improve the outcome of hepatectomy for colorectal liver metastases (CRLM) by combining surgery with chemotherapy have failed to demonstrate overall survival (OS) benefit. This may partly be explained by the fact that previous trials on this subject involved strict inclusion criteria. Consequently, patients with a high oncological risk profile - who might benefit the most from chemotherapy – might have been underrepresented in previous trials. Several Clinical Risk Scores (CRS) have been developed predicting patients’ prognosis after resection of CRLM. The most widely used and validated CRS was described by Fong et al., which characterizes 2 risk groups (high versus low) based on 5 independent clinicopathologic prognostic variables. Each variable is assigned 1 point. Multiple retrospective observations showed that neo-/adjuvant chemotherapy induced significant OS benefit in patients with a high-risk profile (CRS of 3 to 5 points). The CHARISMA trial evaluates the impact of neo-adjuvant chemotherapy in patients with high-risk, primarily resectable liver-only colorectal metastases. We hypothesize that adding neo-adjuvant chemotherapy to surgery improves OS in this high-risk patient group. Methods: The CHARISMA trial is a randomized (1:1) phase III trial. Patients receive either surgery only for CRLM (arm A) or 6 cycles of neo-adjuvant Oxaliplatin + Capecitabine, followed by surgery (arm B). The primary endpoint is OS. On basis of retrospective data, the expected hazard ratio for arm B is 0.60. With an expected 5-year OS of 25% in arm A, a two-sided significance level α = 0.05 and power 1 - β = 0.8, 224 patients have to be recruited. Major eligibility criteria are: liver-only metastases, primarily resectable CRLM, high-risk patients (CRS 3-5). The trial is currently accruing in 10 Dutch liver centers and is registered in the “Dutch Trial Register”: NTR4893 ( www.trialregister.nl ). Clinical trial information: NTR4893.
Effect on clinical trial participation by integration of a clinical pathway program into an electronic health record (EHR).
Authors: Shamah Corey J. , Saphner Thomas James 
Published: February 2017

167 Background: Patient enrollment to clinical trials is lower than desired. Even large organizations with extensive research support services have many barriers to recruitment and poor rates of enrollment. Barriers to clinical trial participation can be physician related, system related, or patient related. Physician related issues are the largest barrier to patient accrual. Physicians are often not aware that a trial may be available for a patient. While all initial patients are manually screened in our system, screening for subsequent lines of therapy are not. Provider awareness and appropriate patient identification are areas of potential improvement in a large, multisite, hospital affiliated, community oncology setting. Methods: Our oncology group recently implemented Via Oncology (Via), an EHR-integrated clinical pathway decision support tool. Information about the patient, their disease, and goals of care generate a recommended treatment algorithm. The pathways are expected to speed the integration of new treatments into practice and improve accrual to clinical trials. Use of Via is required for all new therapy changes. Within the decision algorithm, an appropriate available clinical trial is suggested as the first option when available. Clinical trial enrollment statistics are being tracked to determine if this method of potential patient identification results in increased enrollments. Results: After 11 months of Via implementation and 103,515 visits, the visit capture rate was 82.7% suggesting that providers adapted to the pathways quickly. With 3,844 decisions made, 83.9% of all treatment decisions were on pathway. Clinical trial enrollment was 122 patients in the 459 days prior to Via implementation, and 102 patients in the 271 days afterwards. This increase in accrual rate was significant (p = 0.00174.) Conclusions: Early results suggest that Via implementation has resulted in a significant increase in clinical trial accrual. The system will eventually be able to track how often a trial is offered and how often it is accepted. We are hopeful that with complete visit capture of all patients, there will be continued improvement in our rate of clinical trial enrollment.
Breast cancer specific mortality in patients with early-stage hormone receptor–positive invasive breast cancer and oncotype DX recurrence score results in the SEER database.
Authors: Shak Steven , Petkov Valentina , Miller Dave P , Howlader Nadia , Gliner Nathan , Howe Will , Schussler Nicola C. , Cronin Kathleen , Baehner Frederick L. , Penberthy Lynne 
Published: February 2017

176 Background: NCI’s SEER Program provides cancer incidence and survival statistics for ~28% of the US. New research models are needed to characterize the use and impact of genomic tests on patient outcomes. Genomic Health and SEER collaborated to electronically supplement SEER registries with Recurrence Score (RS) results, and have evaluated breast cancer specific mortality (BCSM) in early stage hormone receptor (HR)+ HER2- invasive breast cancer. Methods: Pts were eligible for pre-specified node negative (N-) disease analysis if HR+, HER2- (by RT-PCR), no prior malignancy, 40-85 years of age, and diagnosed between Jan 2004 (Oncotype DX available Jan 2004) and Dec 2011 (SEER survival analysis complete through 2012). BCSM was defined as previously described (Howlader et al, JNCI 2010). Additional analyses of BCSM were performed for pts with N+ disease. Results: Of 169,158 eligible N- pts, 38,568 (23%) had a RS, increasing from 2% in 2004 to 35% in 2011. Pts with RS had median age of 57yr, were 99.4% female, 84% white, 29% grade 1 & 54% grade 2, 25% < 1cm & 53% 1-2cm. Median FU was 39mo. 8,239 pts had > 5yrs follow-up. Among RS < 18 (N = 21,023), RS 18-30 (N = 14,494) and RS ≥ 31 (N = 3,051) pts, chemotherapy use was reported in 7%, 34%, & 69%, respectively, and 5yr N- BCSM was 0.4% (95% CI, 0.3-0.6), 1.4% (95% CI, 1.1-1.7) and 4.4% (95% CI,3.4-5.6), respectively. Multivariate showed that RS was significantly associated with BCSM after adjusting for age, grade, and tumor size (p < 0.001), and when stratified by treatment (p < 0.001). BCSM results in additional N- subgroups (e.g., socioeconomic), and in > 60,000 N+ pts will be presented. Conclusions: 5yr survival outcomes are excellent in the over 21,000 N- pts with RS < 18 disease. RS ≥ 31 disease is associated with greater 5yr mortality despite addition of chemotherapy. The large sample size of this population-based observational study provides important information on prospective outcomes in subsets of pts that are often underrepresented in randomized clinical trials.
Cost-effectiveness of brentuximab vedotin in relapsed or refractory systemic anaplastic large cell lymphoma.
Authors: Hux Margaret , Zou Denise , Ma Esprit , Sajosi Peter , Engstrom Andreas , Selby Ross , Benson Eugene , Teasell Jeremy , Richhariya Akshara , Briggs Andrew , Bonthapally Vijayveer 
Published: February 2017

18 Background: Systemic anaplastic large cell lymphoma (sALCL) is a rare T-cell lymphoma. For patients who fail front-line therapy, outcomes are poor and there is no current defined standard of care. Brentuximab vedotin has demonstrated high objective response rates and is approved for patients with relapsed or refractory (R/R) sALCL. However, the cost-effectiveness of brentuximab vedotin compared with conventional chemotherapy has not been explored. Methods: A lifetime Excel-based partitioned survival model was used to compare survival outcomes from the pivotal phase-2 single-arm brentuximab vedotin trial of 58 R/R sALCL patients with good Eastern Corporative Oncology Group (ECOG) performance status after one or more prior therapies (SG035-0004); with 40 sALCL patients from a Canadian cancer registry receiving first-line conventional salvage chemotherapy (65% with ECOG 0 or 1) between 1980 and 2012 and followed for up to 20 years. Extrapolation of brentuximab vedotin survival after the trial period assumed the same rate of change as for conventional chemotherapy. A United Kingdom National Health Service perspective was adopted. Costs included drug acquisition and administration, and medical care for adverse events and pre- and post-progression. Utility values elicited by response and by progression, and disutilities associated with adverse events were applied to estimate quality-adjusted life years (QALYs). Results: The incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £35,390 per QALY gained versus conventional chemotherapy. ICERs were between £28,112 and £61,921 across a range of alternative model assumptions. Comparing only first-line salvage patients in both groups reduced the ICER to £26,766. Conversely, considering only patients with good ECOG performance status increased the ICER to £38,186. Using probabilistic sensitivity analysis, at willingness-to-pay of £38,000, the probability that brentuximab vedotin is cost-effective was > 50%. Conclusions: Brentuximab vedotin may represent a cost-effective intervention compared to conventional chemotherapy for this patient population with limited therapeutic options.
Improving anti-emetics in chemotherapy induced nausea and vomiting.
Authors: Toutounji Sandra , Fung Ron , Enright Katherine 
Published: February 2017

220 Background: Chemotherapy induced nausea and vomiting (CINV) remains one of the most feared treatment-related toxicities in cancer patients. CINV has been shown to decrease quality of life and to increase dose modifications and unplanned hospital visits. Cancer Care Ontario (CCO) and the American Society of Clinical Oncology (ASCO) updated their CINV guidelines in 2013. These changes included a reclassification of many regimens from moderate (MEC) to highly emetogenic (HEC) and a decrease in the duration of serotonin inhibitors (5HT3i). Uptake of the new guidelines at Trillium Health Partners has been slow. We aimed to improve CINV by increasing the percentage of patients who received guideline concordant anti-emetics with their first cycle of HEC/MEC chemotherapy. Methods: The first 25 patients started on MEC/HEC chemotherapy during 3 time periods (pre-guidelines, 6 months post guidelines, 1.5 years post guidelines) were identified. The primary measure of interest was the percentage of patients receiving MEC/HEC who were treated in concordance with the updated CINV guidelines. Secondary measures included the percentage of MEC/HEC patients who experienced grade 2+ CINV. The collected data was used with quality improvement techniques to guide the development of interventions to improve guideline concordance. Results: The concordance of anti-emetics on the day of chemotherapy improved over time, but post-chemotherapy concordance remained at 0% (table). The primary driver for concordance was the use of NK1inhibitors on chemotherapy day, and the duration of 5HT3i post-chemotherapy. Using quality improvement methodology, the highest impact intervention was identified as changing the default settings in the computerized order entry system (CPOE) to reflect the updated guidelines. These changes are currently in progress and a test of this change will be presented. Conclusions: Concordance with CINV guidelines improved over time resulting in lower CINV and less need for reactive CINV interventions. Further work to target duration of 5HT3i is ongoing. [Table: see text]
Assessing patient experience in an outpatient multidisciplinary clinic setting.
Authors: Denny Diane , Hartman Scott 
Published: February 2017

224 Background: Cancer Treatment Centers of America (CTCA), a national network of five hospitals, implemented a new survey instrument and methodology to gather patient experience data in the outpatient setting. While borrowing many questions from its vendors’ client base, the network also added questions considered pivotal to understanding the critical dimensions of care deemed most relevant to the oncology patient. Surveying includes 100% of all patients first contacted via the U.S. mail and subsequently using e-surveys. Methods: Data is collected, with the ability to be segmented by cancer type; for medical, surgical and radiation oncologists with respect to confidence and likelihood of recommending. For each specialty, an open ended question has been added for the patient to elaborate upon his/her rating. Further, several questions have been added to reflect key dimensions of care specific to the oncology such as emotional needs, family involvement and information, sensitivity to personal difficulties associated with treatment, drawing blood and IV discomfort, and involvement in care decisions, to name a few. Results: The revised approach has resulted in greater than a 200% increase in responses, at a cost reduction, cognizant of the growing sophistication of the population served in using technology as part of the patient experience feedback process. Results at three months post-implementation have yielded the findings in the Table. Conclusions: Since implementation, not only have completed surveys increased with respect to easily accessible discrete quantitative data, qualitative information has grown exponentially. This has resulted in more meaningful and robust data around which to focus, including specialty data at the disease and provider levels. The revisions also substantially support CTCA centers’ Magnet journey, including question dimensions and unit level reporting. [Table: see text]
Utilization of an innovative tool to improve oncology patient outcomes.
Authors: McNeil Dana , O'Driscoll Jessica , Patel Jaimika , Decker Marie , McGovern Joanne 
Published: February 2017

231 Background: Introduction of an electronic board can improve interdisciplinary communication to ensure early intervention and improve patient outcomes. Early detection and prevention is key. The early stages of physiologic demise may be demonstrated by subtle changes in the patient’s vital signs. The purpose of this study was to implement a visual tool to indicate and update the acuity of patients on the oncology unit. The parameters displayed included vital signs, Hendrich, and Braden scale. The goal of the electronic board was to create a continuously accessible resource for the interdisciplinary team for rapid assessment of the patient’s condition throughout rounds and all shifts. Methods: This electronic board produces a color-coded alarm for abnormal parameters. Vital signs highlighted in red indicate the urgency for assessment and intervention. The Hendrich score displayed in yellow alerts all disciplines of fall risk patients. The Braden scale, color-coded purple, identifies patients at risk for skin breakdown. Improvement in early and rapid identification of patient deterioration and risk was analyzed using two months of post implementation data from the electronic health record. A survey was sent to all disciplines to qualitatively measure the value of this tool. Results: Abnormal vital signs identified from the facility board led to clinician interventions impacting 27% of admitted patients in the first two months. Falls decreased by 33% after the first month of implementation. The number of specialty beds ordered increased by 32% for patients identified at risk for skin breakdown. Twenty-five survey responses illustrated 71% of the interdisciplinary team that replied used the facility board and 68% confirmed improvement in interdepartmental communication. Conclusions: There is a significant association between early intervention and decreased mortality rate in acutely ill cancer patients. The continuous display of pertinent patient data on an electronic board holds clinicians accountable to recognize and provide early intervention thus impacting oncology patient outcomes. This innovative tool will further enhance outcomes as we move to interfacing our vital signs monitor into our electronic health record.
Characterization of unplanned 30-day medical oncology readmissions after discharge at an academic medical center with a comprehensive cancer center.
Authors: Lennes Inga Tolin , Eusebio Justin , Bohlen Nie , Ruddy Margaret , Ryan David P. 
Published: February 2017

269 Background: Hospital readmission rate is increasingly suggested as a quality care metric. Currently there are no standard criteria for an avoidable readmission in oncology. Although patients with cancer have been identified as being at increased risk of readmission, there has been little to examine the reasons for the oncology patient readmission. The aim was to examine the profiles of patients with an unplanned readmission within 30 days after discharge by an oncology provider and to measure the unplanned 30-day readmission rate. Methods: A retrospective review of oncology provider discharge encounters resulting in a 30-day unplanned readmission during the 2012 calendar year at a tertiary hospital with a comprehensive cancer center was conducted. Planned readmissions for chemotherapy, radiation therapy, hematopoietic stem cell transplantation, dialysis, and surgical procedures, as well as readmissions for rehabilitation, hospice, and psychiatry were excluded. Medical oncologists analyzed medical records for the primary reason of readmission and if the readmission was possibly preventable. Results: Of the 2,944 admissions, a final cohort of 441 unplanned readmissions from 321 unique patients for an unplanned 30-day readmission rate of 14.9% was observed. The average age at admission was 59 (SD 15.9). The cohort was mostly male (56.9%) and White/Caucasian (84.4%). Gastrointestinal (24.0%), lymphoma (18.6%), and leukemia (17.5%) were the most common cancer types. Of those with solid tumors types (n = 225), approximately 70% had metastatic disease. The median time to readmission was 10 days and 10.7% died within 30 days of readmission. Oncology reviewers most commonly assessed that readmission was primarily due to treatment-related effects (46.7%) and the progression of disease (42.2%). Approximately 20% of 30-day readmissions were determined to be possibly preventable, representing 3% of all admissions for the year. Conclusions: Oncology patients readmitted within 30-days frequently present with complicated, advanced disease. A review by medical oncologists suggests there is margin for intervention to reduce 30-day unplanned admissions.