bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of distinct EGFR downstream pathways on resistance to dual EGFR/ErbB2 combined targeted therapy of lapatinib (LPT) and cetuximab (CTX).
Authors: Deeken John F. , Ramos Corinne , Barcus Mary , Hwang Jimmy J. , Marshall John , Subramaniam Deepa Suresh , He Aiwu Ruth , Zhuang Tingting , Hardesty Rosemarie A. , Pishvaian Michael J. 
Published: February 2017

91 Background: Resistance to EGFR therapy is poorly understood. We performed a phase I study in which pre- and post-treatment biopsies were profiled to assess the impact of CTX and LPT on downstream pathways that drive cancer progression. Methods: Between 10/2010 and 5/2012, 16 patients (pts) were enrolled in a 3+3 dose escalation trial, including: colon (7), lung (4), head and neck (3), and anal cancers (2). Prior EGFR therapy was allowed. CTX was 400mg/m2 on D1, then 250 mg/m2 weekly. LPT dose levels were 750 mg, 1000 mg, and 1250 mg daily. Cycles were 21 days in length; pts were assessed for response every 2 cycles. Pts underwent pre- and post-cycle 1 tumor biopsies. Biopsies were evaluated with a Reverse Phase MicroArray (RPMA) platform. Protein lysates were robotically immobilized in defined spots on nitrocellulose-coated slides; each printed array was then interrogated with a highly specific antibody. A total of 36 different proteins were analyzed, including total and phosphorylated EGFR, ErbB2, ErbB3, MET, IGF, MAPK, PI3K, Jak-Stat, and other subpathways. Relative baseline expression levels were determined, as were percent change in matched samples. Results: Of 12 pts evaluable for response, 2 had a partial response (PR), 5 had stable disease (SD), and 5 had disease progression (DP). Baseline tumor measurements of total ERK, p90RSK, and p38MAPK correlated with response (p<0.05), with a trend towards significance between response and expression of pEGFR, pMEK, pNFKB, and p4EBP1 (p<0.10). Nine patients had paired pre- and post-treatment biopsies. In tumors from pts with PR and SD, consistent down regulation of the EGFR pathway was detected. In the four patients with DP, up-regulation of distinct pathway components was detected, including of IGF (1 pt), Mek1/Erk (2 pts), mTOR (2 pts), and STAT3 (3 pts). Conclusions: A tumor profile was defined that correlated with clinical benefit to LPT+CTX. Resistance to this combination was due to upregulation of EGFR pathway components, components that are druggable. This analysis highlights the potential of personalizing therapy with combined EGFR therapies, and for adding additional targeted therapies to patients with resistant tumors.
Establishment of esophagogastric xenografts: A model for characterizing disease heterogeneity.
Authors: Janjigian Yelena Yuriy , Gromisch Christopher M. , Carbonetti Gregory , Tang Laura H. , Kelsen David Paul , Coit Daniel G. , Vakiani Efsevia , de Stanchina Elisa , Strong Vivian E. 
Published: February 2017

95 Background: Gastric cancer is a heterogeneous disease that may be subdivided into distinct subtypes—proximal/gastroesophageal (GE) junction, diffuse/signet ring type, and distal gastric cancer/intestinal type—based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology and gene expression. Human epidermal growth factor receptor (HER2) is a validated treatment target in gastric cancer. For patients with metastatic disease, the available cytotoxic agents are applied indiscriminately to all disease subtypes, and with only modest success. The purpose of this study is to establish xenograft models from gastric cancer subtypes to improve our understanding of disease heterogeneity and develop therapies geared for each subtype of gastric cancer. Methods: Fresh specimens obtained from resected primary or metastatic tumors under aseptic conditions. 1 g tumor samples injected SQ into flanks of NSG mice. Xenografts established after 5 passages and maintained by serial transplantation into new mice. Cell cultures established after 5 in vitro passages; cell lines after 15 passages Results: To date, 66 tumor samples have been implanted from which 16 xenografts have been established. The table below summarizes the results. Single-agent afatinib (pan-ErbB inhibitor) demonstrated antitumor activity in an HER2-positive xenograft established from MSKCC patient’s tumor harvested from a skin metastasis. Conclusions: We have established xenograft models of gastric cancer. In vivo testing of afatinib showed a reduction of tumor growth of HER2-positive gastric cancer. These models provide a platform to study potential therapeutics for esophagogastric cancer to further validate difference in their biology and guide rational design of clinical trials. [Table: see text]
Drug resistance induced by paclitaxel and carboplatin plasmatic concentrations in lung cancer cell lines.
Authors: Luque Raquel , González Vicente Aranzazu , Soberino Jesús , Prados Jose Carlos , Melguizo Consolación , González Rivas Cynthia S. , Ruiz Vozmediano Julia , Conde Veronica , Garcia Garcia Javier , Aránega Antonia 
Published: February 2017

97 Background: Multidrug resistance (MDR) phenotype is the major cause of chemotherapy failure. It has been related to several proteins expression: P-glycoprotein (PgP), MRP family, LRP, and BCRP. We study the resistance pattern induced after paclitaxel and carboplatin in non-small cell lung cancer (NSCLC). Methods: We used 5 different cell lines. A549 and A427 cell lines were derived from lung epithelial carcinoma. NODO line was obtained from lung carcinoma metastases, and 3 cell lines derived from other tumours: gastric cancer (GAS), seminoma (SEM), breast cancer (MCF7). The cell lines were exposed to paclitaxel, carboplatin, and the combination of both drugs. The concentrations we used were similar to the plasma concentrations observed in patients treated previously. Results: A549 cell line did not show basal expression of MDR1, but a weak basal expression of MRP3 was observed. After chemotherapy, we observed that paclitaxel induced MDR1 and carboplatin induced MRP3. The combination of both drugs induced MDR1 and MRP3 expression, however, when paclitaxel is associated to carboplatin, MRP3 expression did not increase significantly. A427 cell line did not show basal expression of MDR1 and MRP3. Paclitaxel induced MDR1 and carboplatin induced MRP3. The association of both drugs increased significantly the expression of MDR1, and very few the expression of MRP3. NODO cell line did not show any basal expression. Paclitaxel induced MDR1 and carboplatin induced MRP3. Cell lines derived from other tumours not show any basal expression. Paclitaxel induced MDR1 in all cell lines. Carboplatin did not induce MDR1, nor MRP3 in GAS cell line. Conclusions: Plasma concentrations of paclitaxel induced MDR1 expression but not MRP3 in lung cancer and other tumours derived cell lines. Carboplatin produced overexpression of MRP3 but not MDR1 in the same cell lines. The combination of both drugs at plasma concentrations was not able to activate a new resistance mechanism in the studied cell lines, but improve the resistance mechanism induced by each one of the drugs individually.
Evaluating a preference-tailored decision tool for increasing colorectal cancer screening.
Authors: Hawley Sarah T. , Ling Bruce , Fagerlin Angela , Vernon Sally W. , Vijan Sandeep 
Published: February 2017

10 Background: Incorporating patient preferences into CRC screening decisions has been identified as one method for improving informed decision making and increasing screening adherence, yet the impact of tailoring screening recommendations to patients’ preferences on these outcomes has not been evaluated. Methods: We compared the effect of a web-based preference-tailored decision tool (intervention) to a standard information decision tool (control) through an RCT at two VA sites. Eligible subjects were age 50-77, due for CRC screening, with a scheduled primary care visit. Participants arrived 45 minutes early to complete consent and were randomized online. Telephone surveys were conducted 3-5 days post-enrollment and CRC screening adherence was collected from medical charts 6 months later. We evaluated the effect of the tool on adherence and compared stated test preferences to test recevived through Chi-square tests and regression. Results: 468 subjects were enrolled from two VAs. CRC screening adherence 6-months post-enrollment was 38.6% and was not significantly different between groups (37.4% intervention, 39.7% control). Most were adherent with fecal occult blood test (FOBT) (22.4%), followed by colonoscopy (COL) (16.7%). The most commonly recommended test by physicians was COL (59.2% of tests recommended), though veterans most commonly stated a preference for FOBT (60.1%). The features of tests most important to veterans were nature of the test (32.8%), effectiveness (27.1%), and risk of complications (17%). Participants significantly more often adhered to the test that they stated they preferred after the intervention than with a non-preferred test (30.4% adhered to preferred test vs. 7.6% adhered to non-preferred test, P<0.001). Conclusions: CRC screening adherence in this population of veterans was low and the preference-tailored intervention did not significantly improve adherence relative to standard information. Veterans preferred a non-invasive test (FOBT) despite higher rates of recommendation for COL by their physicians. Improving concordance between physician recommendations and patients’ preference may be one method for improving CRC screening adherence in this population.
Feasibility and savings of a suspicion of cancer clinic at a large county hospital.
Authors: Mougalian Sarah Schellhorn , Wang Jennifer , Zarzour Maria Alejandra , Quinn Doris , Rieber Alyssa G. 
Published: February 2017

104 Background: The Lyndon B. Johnson General Hospital (LBJGH) is part of the Harris County Hospital District (HCHD), serving the third largest county in the United States. Many patients are admitted to the hospital for expedited workup when cancer is suspected to avoid outpatient delays. We sought to establish the main contributors to delays in cancer diagnosis and to calculate the potential savings, both in terms of time and expense, of an ambulatory Suspicion of Cancer Clinic. Methods: The charts of 327 consecutive new patients to the LBJGH medical oncology clinic between June 2011 and November 2011 were reviewed. Only patients whose cancer was diagnosed within HCHD (n=165) were included in the analysis. Dates of initial presentation, emergency department (ED) visits, abnormal imaging, admissions, diagnosis, and initial oncology visit were collected, along with the method of diagnosis. Additional chart review was performed to determine which admissions were solely for expedited work up based on the documentation provided. The project was approved by the MD Anderson Quality Improvement Assessment Board. Results: 60% of cancer diagnoses were made in the ambulatory setting, whereas 40% of patients were diagnosed inpatient. Breast cancer was the most frequent cancer diagnosis. The mean time from presentation to diagnosis in the inpatient setting was 3.9 days for breast cancer, 12.9 days for colon cancer, and 5.5 days for lung cancer. For patients diagnosed in the ambulatory setting, the times were 77.1 days, 65.4 days, and 70.8 days respectively. 15.6% of patients were admitted to the hospital for expedited work up, accounting for 130 hospital days. Based on the average costs in HCHD, elimination of hospitalizations and multiple ED visits using an ambulatory suspicion of cancer clinic could save more than $300,000 annually. Conclusions: We propose a Suspicion of Cancer Clinic to expedite outpatient diagnostic workup, in collaboration with diagnostic imaging, surgical specialties, and pathology. The establishment of a Suspicion of Cancer Clinic could reduce ambulatory diagnostic times, decrease the frequency of admissions, and potentially improve patient outcomes. Piloting of this clinic is underway.
Increasing genetics referrals: The National Cancer Institute Community Cancer Centers Program (NCCCP) network performance improvement project.
Authors: Cohn Jeffrey , Carrigan Angela , Palaniappan Selvi , Rivero Silvana , Castro Kathleen M. 
Published: February 2017

111 Background: A NCCCP goal is to improve quality of care through increasing guideline adherence at participating community cancer centers. 14 NCCCP sites participated in a performance improvement project to (1) increase genetics referral and counseling services by 10% in accordance with established guidelines for breast or colorectal cancer. The project hypothesized that data collection and feedback improves referral rates by better targeting eligible populations for improvement interventions. Methods: Sites recorded the source and outcome of each breast/colon referral using a tool developed by the NCCCP. Aggregate data were shared on monthly project calls where site staff shared best practices/issues with peers and received feedback. Results: Data were collected Jul 2011-Apr 2012 and analyzed at 2-week intervals. The number of colorectal and breast patients referred for genetics counseling remained stable through the 9-month period. Despite no change in the rates of referrals the data were hypotheses generating. Colorectal cases of all ages were being correctly referred in accordance with established guidelines; project calls demonstrated sites’ efforts to improve referral processes, such as including genetics counselors in the multidisciplinary team discussions, implementing universal screening for Lynch syndrome, and developing new linkages with referring staff. Conclusions: The project was a successful proof of concept study showing the feasibility of pooling genetic counseling data across diverse community cancer centers. Robust data collection is inadequate to drive sustainable improvement; specific process changes are also required. Future NCCCP collaborative initiatives are needed to ensure all eligible patients have access to genetic counseling referral services as there remain a significant group of patients eligible for genetic counseling who are not being seen. Funded by HHSN261200800001E.
Unanticipated hospital admissions in patients undergoing radiotherapy with or without concurrent chemotherapy: Incidence and predictive factors.
Authors: Arastu Nabeel H. , Chen Ronald C. , Jackson Marianne , Green Rebecca L. , Qaqish Bahjat F. , Xu Zijie S. , Camporeale Jayne , Collichio Frances A. , Marks Lawrence Bruce 
Published: February 2017

114 Background: Unanticipated admissions are burdensome for patients and the healthcare system. An improved understanding of their frequency and predictive factors can inform initiatives to prevent such admissions and mitigate their associated human and financial costs. Methods: Electronic medical records of all patients (n=1144) undergoing external beam radiotherapy (RT) at our center in 2010 were reviewed in this retrospective study. Unanticipated admission within 90 days of initiating RT, and associated clinical factors, were recorded. Chi-squared and uni- and multivariate logistic regression was used to examine factors associated with admission. Results: Unanticipated admissions occurred in 19% (213/1144) of patients, median length of stay was 3 days (range 1-22), and the mean interval between the start of RT till admission was 28 days (1-89 days). The most common indications for admissions were pain (19% of admissions), GI toxicity (18%), and respiratory distress (15%). On univariate analysis, admission rates were higher in patients treated with palliative vs. curative intent (30% vs. 14%, p<0.001), with concurrent chemotherapy (23% vs. 18% RT alone, p=0.047), in those who had a recent admission prior to RT initiation (37% vs. 14% with no prior admission, p<0.001), and patients on their second or third course of RT (27% vs. 16% first treatment course, p<0.001). Multivariable analysis showed treatment intent, chemotherapy, and prior admissions to be associated with unplanned admissions (Table). Conclusions: Rates of unanticipated admissions are ≈20% in patients undergoing RT. Slightly less than 1/3 of patients receiving palliative RT, and nearly 1/4 receiving concurrent chemoradiation, experienced an unplanned admission. Prophylactic measures should be studied in these high-risk patients to reduce admission rates, as unplanned admission may be an important quality of care indicator in oncology. [Table: see text]
Time to antibiotic.
Authors: Equila Everett John , So Tonette , Leon-Guerrero Velma , Moller Keriann , Cooper Robert Michael 
Published: February 2017

115 Background: The aim of this quality improvement (QI) project is to identify the interdisciplinary factors that cause delay of antibiotic administration to febrile Hematology/Oncology patients directly admitted to Pediatric department. Pediatric oncology research has shown that there is significant lower mortality associated with antibiotics given within one hour vs. delayed or no treatment (Adderson, Flynn, and Hoffmann, 2011). Methods: This QI project is conducted at a 32 bed pediatric unit at Kaiser Permanente Los Angeles Medical Center. Hematology/oncology patients admitted to the pediatric floor with fever were included in the study. A six month audit (n=22) showed that current workflow was inadequate and did not meet the time to antibiotic (TA) goal. A three-point workflow was designed to improve the TA outcome. The workflow includes initial documentation of actual time patient arrived to pediatric floor to the time admitted patient is entered in the electronic medical record (EMR) system. This is followed by auditing actual time patient is admitted to EMR to the actual time computerized physician order entry (CPOE) for time to antibiotic protocol is entered. Lastly, CPOE to actual time antibiotic was administered was audited. An ongoing six month audit has begun with the implementation of changes to workflow. Results: Audit prior to TA workflow: Patients (n=22) who met the criteria showed that (22.7%) received initial antibiotics within 1 to 2 hours. Eight patients (36.4%) received the antibiotics within 2 to 3 hours of admission. Four patients (18.2%) received initial antibiotics at 3 to 4 hours of admission. Notably, none (0%) of these patients received antibiotic within the goal of one hour. Audit after implementation of TA workflow: A three month audit (n=14) showed that (57.1%) received antibiotic less than 1 hour from time of admission. Two patients (14.2%) received antibiotic less than 2 hours of admission. Two patients (14.2%) received antibiotic less than 3 hours of admission. Two patients (14.2%) of these patients received antibiotics 3 to 4 hours of admission. Conclusions: Based on current data, the TA protocol showed marked improvement in the delivery and administration of antibiotic received by hematology/oncology patients.
The incidence of acute kidney injury among children treated for fever and neutropenia after elimination of empiric gentamycin use.
Authors: Heczey Andras , McCarthy Kathy , Wu Meng-Fen , Kennedy Curtis , Hockenberry Marilyn 
Published: February 2017

120 Background: The mortality rate of chemotherapy-related fever and neutropenia (F&N) has decreased significantly in recent years with attention shifting to antibiotic regimens with the least side effects. Multiple randomized controlled clinical trials have demonstrated that antibiotic regimens without aminoglycosides are sufficient for successful treatment of F&N and the addition of aminoglycosides significantly increases the risk of acute kidney injury among adults. The institutional F&N Guideline of Texas Children’s Hospital (TCH) mandated the use of gentamycin in combination vancomycin and piperacillin-tazobactam (P-T) for the treatment of hig- risk (HR) patients with F&N. To decrease the incidence of nephrotoxicity while maintaining excellent survival, empiric gentamycin use was stopped. Methods: Bacterial susceptibility and characteristics of patients with positive blood cultures treated at TCH during 2009 were retrospectively analyzed (pre-intervention group). Negligible P-T resistance was confirmed among bacterial isolates and empiric use of gentamycin for HR patients with F&N was stopped. After a 6 month adjustment period, data for all patients treated according to the new HR algorithm were prospectively collected (post-intervention group) for 12 months. The pre- and post-intervention groups were evaluated for differences in treatment success and incidence of nephrotoxicity. Results: Data from 69 patients from the pre-intervention group and 39 patients from the post-intervention group who had bacteremia were analyzed. No statistical difference was found between pre- and post-intervention groups for age, gender, survival, baseline creatinine level and baseline estimated creatinine clearance. However, significant difference was found for change in creatinine levels (0.12 vs. 0.04 mg/dl p=0.01), change in estimated creatinine clearance (24.8 vs. 12.1ml/min/1.73m2, p=0.01) and incidence of acute kidney injury (30.1 vs. 11.1%, p=0.04). Conclusions: Children with high risk F&N episode may be treated effectively and safely with decreased incidence of acute kidney injury without the empiric use of gentamycin.
Improvement of time to develop treatment plan at a specialized sarcoma center.
Authors: Chavez Adriana , Singh Prachee , Anderson Jaime , Aleman Andrea , Jernigan Colleen , Ravi Vinod 
Published: February 2017

127 Background: Treatment of new patients at the MD Anderson Sarcoma Medical Oncology Clinic can take up to 1 to 2 weeks from their initial consultation depending on the information available for review. Treatment delays can result in poor patient outcomes, adversely affecting the quality of care provided. There are numerous processes involved in the development of a treatment plan that could be improved to reduce the time to finalization of treatment plan. Methods: We undertook a quality improvement project involving key clinic and administrative team members. We performed detailed process mapping and developed a cause and effect diagram to identify and prioritize opportunities for improvement. We measured the time in hours from the patient’s initial appointment to finalization of a treatment plan. Baseline data (before process improvement implementation) was collected retrospectively through chart review. Post-implementation data was collected prospectively. For process improvement, we focused on two deficiencies that were regarded as the key causes of delay to develop a finalized treatment plan (1) insufficient data for decision making at the time of new patient visit, and (2) delays in obtaining diagnostic imaging. Results: Due to insufficient data for decision-making available at the time of initial consultation, the median time to develop a treatment plan is 72 hours. After initiating process improvement, the median time to develop a treatment plan decreased to approximately 7 hours. Conclusions: Improving the quality of data available for the medical oncologist prior to initial consultation greatly enhances the rapid development of finalized treatment plan. Availability of an early treatment plan improves patient outcomes, diminishes patient anxiety, and decreases the costs incurred by the patient awaiting a treatment plan at a specialized oncology clinic.