bluuebunny/crossref_metadata_2025_split huggingface dataset:
KOC (K homology domain containing protein overexpressed in cancer) overexpression and progression-free survival after curative intent resection of pancreatic ductal adenocarcinoma.
Authors: Johnson Benny , Khalil Maged F. , Lin Fan , Zhu Shaobo , Kirchner Lester 
Published: February 2017

48 Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the United States. Unfortunately, effective screening and early detection mechanisms are currently unavailable, thereby 80% of patients present with distant metastasis. Of the subset of patients eligible for curative intent surgery, the 5-year survival rate is only 20%. Negative surgical margins, tumor size, stage, and node negative disease are traditional prognostic indicators. However, these can be limited in their ability to predict patient specific prognosis. KOC is an oncofetal RNA-binding protein involved in RNA stabilization and cell growth during embryogenesis. Previous studies have revealed that KOC mRNA is inappropriately overexpressed in pancreatic cancer and that increased expression correlates with tumor stage. In this study, we attempt to identify whether KOC expression in patients who undergo curative intent surgery correlates with progression free survival. Methods: Tissue microarrays prepared from formalin-fixed, paraffin-embedded specimens of patients with PDAC who underwent curative intent surgery were assessed by immunohistochemistry. Results: A total of 35 patients were included. Comparisons between groups on progression free survival are estimated using the Kaplan-Meier method and the log-rank test. KOC was overexpressed in 23.6% of tumors. It was found that there were zero patients with a high KOC expression and no distant metastasis. Patients with a high KOC expression were more than 3 times more likely to progress compared to those with a low KOC expression (HR=3.54, 95% CI: 1.34, 9.36, p=0.011). Conclusions: KOC is a useful prognostic biomarker for predicting those patients with PDAC who have a high risk for early progression and distant metastasis. Identifying patients with high KOC expression upon initial diagnosis can serve as a way to risk stratify patients to aggressive treatment regimens upfront and early exposure to clinical trials.
A comparative study of a monoclonal antibody against EGFR (nimotuzumab) used in combination with chemoradiation versus chemoradiation alone in the treatment of locally advanced inoperable squamous cell carcinoma of the head and neck.
Authors: Bhatnagar Aseem Rai , Singh Dharam Pal 
Published: February 2017

51 Background: To determine the efficacy, safety and tolerability of concurrent nimotuzumab (monoclonal antibody against epidermal growth factor receptor) used in combination with chemoradiation versus chemoradiation (CRT) alone in advanced inoperable squamous cell carcinoma of the head and neck (SCCHN). Methods: 56 patients were randomly assigned to either of the two treatment arms, nimotuzumab + CRT arm and CRT alone arm. Both arms received concurrent Cisplatin 30 mg/m2 repeated weekly for 6-7 cycles along with external beam radiotherapy 64-70 Gy (200cGy/day for 5 days a week for 6-7 weeks). Nimotuzumab arm additionally received nimotuzumab 200 mg weekly for 6-7 cycles. The patients were followed for 6 months after completion of CRT. The study end points were tumor response evaluation according to the RECIST Criteria version 1.1 and safety analysis using RTOG Acute Radiation Morbidity Scoring Criteria. Patients were evaluated weekly with hematologic tests and for adverse events like mucositis and dermatitis during the CRT. Tumor assessment was performed with clinical and endoscopic methods regularly during the CRT and then at 1 month, 3 months, and 6 months intervals after CRT. One MR imaging was done before starting the CRT to evaluate the baseline tumor characteristics, and another was done after the completion of CRT either at 3 months or 6 months or at both the intervals. Results: 25 patients each were evaluable in both the arms who completed the 6-month study. The overall response rate (complete response + partial response) was 96% in nimotuzumab + CRT arm, whereas it was only 72% in CRT alone arm after 6 months of completion of CRT, which is statistically significant (p value = 0.0206 by Chi Square test). Additionally, nimotuzumab did not potentiate toxicities of CRT, and there was no significant difference in the acute radiation mucositis, dermatitis, or hematological toxicities in both the groups (p value>>0.05). Conclusions: Nimotuzumab can be safely added to the standard CRT treatment for advanced inoperable SCCHN, to achieve better tumor response without potentiating toxicity.
Methylation of MGMT in paired primary and recurrent GBMs.
Authors: Bie Li , Zhang Feng Xian 
Published: February 2017

65 Background: Epigenetic sliencing of the MGMT gene promoter in primary glioblastomas of patients subsequently treated with TMZ is associated with prolonged survival. Further, several studies have observed a change in MGMT silencing in paired primary and recurrent glioblastoma. However, the relationship between this “MGMT switch” and patients outcome is largely unknown. Methods: The study involved primary and recurrent tumor tissue samples from 53 glioblastoma patients diagnosed and treated within the First Hospital of Jilin University from January 2003 to November 2010. After surgical treatment, all patients were subjected to radiotherapy with concomitant administration of TMZ. Patients that experienced recurrent tumors received TMZ. 53 patients underwent 58 further operations after recurrence (5 pats received a third surgery). MGMT promoter methylation levels were determined using qMSP. The relationship between “MGMT switch” and clinical outcome was investigated. Results: 53 (M/F=33/20; median age: 49.2±3.6, 19.5-72.3 ys) underwent a first operation for GBM. qMSP analysis revealed MGMT promoter methylation in 19 pats (35.8%, A, OS 31.5 ms); no methylation in 34 pats (64.2%, B, OS 7.9 ms). In the recurrent tumors, MGMT promoter methylation was detected in 25 pats (47.2%); and no methylation in 28 pats (52.8%). Comparison of individual pairs of primary and recurrent GBMs revealed a changed methylation status in 10 (18.9%), including 8 changed from unmethylated to methylated tumors (15.1%, C, OS 29.4 ms), 2 changed from methylated to unmethylated tumors (3.8%, D, OS 10.5 ms). Median overall survival (OS) was 12.1 months. MGMT promoter methylation was significantly associated with a favorable clinical outcome (A vs B, p=0.0027). The outcome of patients were not significant different between group A and group C (p>0.01). Conclusions: The methylation status of the MGMT promoter was altered in 10 (18.9%) of 53 recurrent GBM after chemoradiotherapy. 8 patients the promoter changed from unmethylated to methylated and these patients had a median overall survival similar to the better prognosis of patients who had a methylated promoter in their primary tumor. 2 pats where a change from methylated to unmethylated was observed had a poorer outcome.
Biopsy-driven study to identify biomarkers of drug resistance in patients with triple-negative breast cancer.
Authors: Aguilar-Mahecha Adriana , Lafleur Josiane , Ahmadzadeh Elaheh , Przybytkowski Ewa , Seguin Carole , Mihalcioiu Catalin Liviu Dragos , Roy Josee-Anne , Desbiens Christine , Robidoux Andre , Marcus Elizabeth A. , Diaz Zuanel , Pelmus Manuela , Batist Gerald , Basik Mark ,   Quebec Clinical Research Organization in Cancer
Published: February 2017

87 Background: Resistance to chemotherapy is the underlying cause of death in most patients dying of breast cancer. Patients with early stages of breast cancer whose tumor is or becomes resistant to chemotherapy have a poor prognosis, while women with advanced breast cancer live as long as their tumors respond to chemotherapy. Because of the great difficulty of obtaining clinical samples from drug resistant tumors in patients, there is scant information about molecular factors from actual drug resistant tumors. This project aims to systematically profile resistant triple negative breast cancers (TNBCs) in order to discover molecular “resistance” genes/proteins as a first step to develop strategies to overcome drug resistance. Methods: Paired biopsies are collected from TNBC patients (NCT01276899). Four needle core biopsies are collected before the initiation of treatment and 2 weeks before surgery or at the time of progression in the neoadjuvant and metastatic settings respectively. Paired biopsies will undergo Next Gen Sequencing, flow sorted aCGH analysis, gene expression and miRNA profiling as well as phosphoproteomic profiling using reverse phase protein arrays. Results: We have currently enrolled 28 patients in the neoadjuvant setting and 3 metastatic patients. We have standardized the methods of collection and processing of tissue and blood specimens to ensure their molecular integrity and compatibility with different genomic and proteomic molecular platforms. Analysis of tumor cellularity has been incorporated into our quality control and we have optimized the extraction of nucleic acids to obtain high yields and optimal quality. In parallel, we have generated acquired resistance to paclitaxel in a panel of TNBC cell lines. These cell lines will also undergo genomic profiling and exome sequencing to identify molecular markers of resistance that will be correlated with the markers found in patient samples. Conclusions: This project will allow us to identify the molecular factors responsible for drug resistance in TNBCs and enable the elaboration of strategies to overcome resistance.
Eradication of experimental brain metastases of human non-small cell lung cancer by macitentan, a dual antagonist of the endothelin A and B receptor, combined with paclitaxel.
Authors: Hanibuchi Masaki , Kim Sun-Jin , Otsuka Kenji , Tabata Sho , Kuramoto Takuya , Goto Hisatsugu , Nishioka Yasuhiko , Fidler Isaiah Josh 
Published: February 2017

92 Background: Treatment of patients with lung cancer brain metastases remains a major challenge because of the limited availability of standard therapy. Thus, the development of successful treatment options for these patients is mandatory. Recently, the endothelin axis was reported to be involved in cancer progression through its pleiotropic biological effects on cell survival, proliferation, invasion, and metastasis. Methods: In this study, we evaluated both the in vitro and in vivoeffects of macitentan, an orally bioavailable, dual endothelin A receptor and endothelin B receptor antagonist, as monotherapy, and in combination with paclitaxel. Results: In human non-small cell lung cancer PC-14 cells, macitentan treatment inhibited cell proliferation, corresponding with inhibition of Akt and p42/44 mitogen-activated protein kinase phosphorylation, and increased apoptosis. The combination of macitentan and paclitaxel resulted in the potentiation of all of these effects, suggesting that macitentan could enhance sensitivity to paclitaxel. Moreover, macitentan completely abrogated astrocyte-mediated protection of tumor cells against paclitaxel. In an experimental brain metastasis model of human lung cancer, the combination of macitentan and paclitaxel significantly inhibited the growth of brain metastasis and produced a striking survival prolongation of tumor-bearing mice. Conclusions: The endothelin A and B receptor blockade by macitentan could be a promising therapeutic strategy for brain metastases of non-small cell lung cancer.
Clinical assay development program.
Authors: Conley Barbara A. , Cavenagh Margaret M. , Rohan JoyAnn Phillips , Lively Tracy G. , Lih Chih-Jian , Williams P. Mickey 
Published: February 2017

98 Background: Discoverers of predictive or prognostic molecular features often do not have the resources to analytically validate findings into a “locked down” assay. Methods: The Clinical Assay Development Program (CADP) was created to provide resources to transition promising markers/signatures into validated assays for use in clinical trials. The CADP is composed of the Clinical Assay Development Network of 8 contracted CLIA-accredited labs and research lab soon to be CLIA accredited (at Frederick National Laboratory for Clinical Research), and Tissue Resources. Applicants from industry, academia, and government are eligible to apply. Applicants must specify one intended clinical use, a prototype assay that performs in human tissues, and relevant prevalence information. Applicants must also describe the clinical need, the current state of the assay and future plans for assay development (such as use in clinical trial) and request the services required for analytical validation (e.g. platform migration, etc.). The applications are evaluated by outside experts. Recommended applications are reviewed internally to ensure availability of appropriate resources and consistency of the application with NCI strategic directions. The successful application is then overseen by a project management team: project manager, subject matter experts from NCI, expertise from contracted resources, and the assay submitter. Intellectual Property remains with the submitter. After validation, the specifics of assay performance and standard operating procedures are returned to the assay submitter. Results: Of 16 applications in year 1, 2 projects are near completion and 2 are beginning. Common problems of the applications were lack of definition of single intended use, specimen availability, and marker still in discovery. Several applicants have used the advice of the CADP team to improve development strategy. Conclusions: Continued education on assay development strategy, particularly intended use and clinical context, is necessary to encourage development of potential molecular assays from the research lab into clinical use. Creativity is needed in finding appropriate specimens. Initial results of CADP are promising; interest from potential applicants is increasing. http://cadp.cancer.gov .
Differential receipt of sentinel lymph node biopsy within practice-based research networks.
Authors: Meyer Anne-Marie , Reeder-Hayes Katherine Elizabeth , Liu Huan , Wheeler Stephanie B. , Penn Dolly , Weiner Bryan , Stitzenberg Karyn Beth , Carpenter William Ruffin 
Published: February 2017

102 Background: Sentinel lymph node biopsy (SLNB) is a quality indicator for breast cancer care. Provider-based research networks (PBRNs) promote diffusion of innovations like SLNB into clinical practice; however, evidence is limited. We examined the diffusion of SLNB for early-stage breast cancer through the Community Clinical Oncology Program (CCOP), a community-based PBRN and its interaction with medical school affiliation. Methods: We identified women undergoing breast conserving surgery with axillary staging for stage I or II breast cancer between January 2000 and December 2003 using Surveillance Epidemiology and End Results-Medicare data (n=6,226). The primary outcome was receipt of SLNB vs. ALND. Exposure was constructed by combining information on the CCOP affiliation of the preforming physician with the medical school affiliation of the hospital. Covariates included race, age, marital status, education, Medicaid eligibility, comorbidity, tumor grade, stage, estrogen receptor status, year of diagnosis, SEER region, and NCI cancer center designation. Multivariable generalized linear modeling with generalized estimating equations was used to measure association between CCOP exposure and receipt of SLNB. Results: Women who saw a CCOP physician at a hospital affiliated with a medical school had a three-fold increase in odds of receiving SLNB compared to non-CCOP women. In contrast, the odds of SLNB were equivalent when looking in women who were seen by a CCOP physician but differed only by their hospital affiliation. Conclusions: Women seen by CCOP-affiliated physicians were more likely to receive SLNB; while medical school affiliation did appear to significantly impact receipt. Innovative, high-quality cancer care can be facilitated PBRNs such as the NCI CCOP program. There must be mechanisms by which providers are exposed to advances in clinical practice outside of organizational affiliations. [Table: see text]
Quality oversight for specialized cancer services.
Authors: Hertz Sherrie , Ross Jillian , Kaizer Leonard , Sawka Carol Anne 
Published: February 2017

103 Background: Cancer Care Ontario (CCO), a provincial agency responsible for continually improving cancer services in Ontario, Canada, reviews selected services with a view to understanding and resolving issues of access, quality, innovation, and funding. Specialized cancer services are low-volume, high-complexity, high-cost, and are not available in every region. They tend to be high-risk, involve a rapidly evolving scientific knowledge base, and a high degree of specialization. A specialized services oversight (SSO) approach has been implemented to address the challenge for optimization of service delivery while providing equitable access to safe, high-quality, best practice care. Methods: The SSO approach involves 1) establishing a provincial forum for expert clinical advice; 2) A regular and systematic process for literature and jurisdictional reviews; 3) provincial-level demand and capacity forecasting; 4) provincial funding linked to evidenced-based eligibility/quality criteria; 5) communication/awareness strategies for appropriate and equitable access. Enablers are CCO structures for performance management, stakeholder engagement, service planning, data management, and CCO’s guiding principles of "transparency, equity, evidence, performance-oriented, active engagement, and value for money." Results: The SSO approach has been implemented in full for PET scanning services, and in part for stem cell transplant (SCT), sarcoma, molecular oncology, prostate brachytherapy, and selected neuroendocrine cancer care. Stakeholder acceptance of the approach has been high. Outputs include provincial guidelines on indications for SCT, performance metrics and benchmarks, multicentre sharing of information, and inter-regional referral processes. Conclusions: Implementation of the SSO approach has introduced provincial-level system planning, formal evidence scanning, sharing of best practices, and performance measurement for high-complexity services where there was no such oversight in the past. The approach is anticipated to avoid access crises and support timely and equitable access to services of high quality, which make optimal use of resources.
Use of predictive models (PMs) in colorectal cancer (CRC) for diagnosis of Lynch syndrome (LS): A process measure for quality of care.
Authors: Sadeghi Sarmad , Barzi Afsaneh , Kattan Michael W. , Meropol Neal J. 
Published: February 2017

116 Background: LS diagnosis (Dx) in CRC patients (probands or Pds) and their first degree relatives (FDRs) impacts the management, outcomes and quality of care. Lack of a uniform approach to screening in academic and community centers is an impediment. Recent studies advocate universal immunohistochemistry (IHC) testing for Pds; however, these analyses exclude clinical criteria e.g., Amsterdam (Ams), Bethesda (Beth), and PMs, e.g., MMRpro (Mpro), MMRpredict (Mpre), and PREMM (PRE) due to concerns for reliability. This comprehensive comparison of all LS screening strategies (STs) aims to identify a cost effective process measure that addresses this need. Methods: We performed a cost effectiveness analysis with a societal viewpoint using TreeAge software. 21 STs for Pd and general population (GP) screening in a population of 100,000 were examined assuming a 3% LS prevalence (Prev) in Pd and 0.23% in GP, 5 FDRs per LS (Dx), 50% LS Prev in FDRs, and 90% germline testing (GT) compliance in Pds and GP and 52% in FDRs. Sensitivity, life years gained (LYG), and incremental cost effectiveness ratios (ICERs) were calculated. Results: See table. Conclusions: This study suggests that Mpro is a cost-effective first step in screening for LS in Pds, and its routine use may be considered as a possible process measure for quality of care in CRC patients. Up-front IHC +/- BRAF, GT could be reserved for Pds where history is incomplete. [Table: see text]
Doctor, what are my options? A prospective cohort study of an individualized care plan for patients with gastrointestinal cancer.
Authors: Hird Amanda E. , Lemke Madeline , Turovsky Miriam , DeAngelis Carlo , Chow Edward , Ko Yoo-Joung 
Published: February 2017

12 Background: For new cancer patients, information about the complexity of the disease, treatment schedule and potential side effects is often delivered during an emotional, stressful visit which can lead to misunderstanding. Appropriate informational support can improve informed decision making, adherence to treatment, and reduce anxiety and cancer morbidity. This is a 3-part clinical study investigating the utility of a patient-centered individualized care plan for patients with gastrointestinal (GI) cancer starting a new treatment. Methods: Part 1: Items identified in a comprehensive literature search were formatted into a questionnaire. For each item, participants ranked its importance. Part 2: MDs and RNs involved in the care of patients with GI cancer provided comments about the content of the care plan. Part 3: A prospective cohort study was conducted. During the first 10-weeks, patients received the standard of care. During the subsequent 10-weeks, patients received the intervention, a written individualized care plan. Outcomes were assessed at baseline and 2-4 weeks: QOL (FACT-G), anxiety and depression (HADS), treatment compliance and patient satisfaction (FACT-TS-PS). Results: Part 1: 73 items were included in the questionnaire. 20 patients completed the interview. Part 2: A long and short version of the care plan were created. The majority of MDs and RNs preferred the long version. Based on the comments, the final version was created. Part 3: 54 and 41 patients have been enrolled in the control and intervention cohorts, respectively. Analysis of the baseline data revealed fewer self-reported anxious (p=0.008) and depressive symptoms (p=0.002) in the intervention group. The nursing satisfaction score was significantly higher in the intervention group (7.09 vs. 4.80, p=0.018). Overall QOL and satisfaction scores were higher in the intervention group, but not statistically significant (81.30 vs. 76.25, 79.70 vs. 76.27). Conclusions: The care plan resulted in fewer anxious and depressive symptoms. There was a trend towards improved QOL and satisfaction in the intervention group, although not significant. We are continuing to enroll patients and analyze follow-up data.