bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cell (CTC) counts and CTC telomerase activity (TA) as prognotic markers of overall survival (OS) in SWOG S0421: Docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Goldkorn Amir , Vogelzang Nicholas J. , Fink Louis M. , Ely Benjamin , Quinn David I. , Tangen Catherine M. , Tai Yu-Chong , Twardowski Przemyslaw , Van Veldhuizen Peter J. , Agarwal Neeraj , Carducci Michael Anthony , Monk J. P. , Garzotto Mark , Mack Philip C. , Lara Primo , Higano Celestia S. , Hussain Maha , Cote Richard J. , Thompson Ian Murchie ,   Southwest Oncology Group
Published: February 2017

1 Background: CTCs are promising biomarkers in mCRPC, and telomerase activity (TA) is a recognized cancer marker. In this phase III trial we analyzed CTCs using 2 methods: CellSearch for fixed cell enumeration, and a novel Parylene-C slot filter for live CTC capture and TA measurement. Methods: Blood samples (7.5 ml) were drawn at baseline (d1) and pre-cycle 2 (d21) of Rx and shipped overnight for central processing. For CellSearch enumeration, Cox regression was used to evaluate the association between OS, baseline CTC counts, and CTC dynamics (d1 to d21). For TA, filter-trapped cells were lysed and assayed for TA using qPCR-based telomeric repeat amplification. Cox regression evaluated the association between OS and TA overall and within subgroups characterized by good vs. poor (<5 vs. >=5) prognosis baseline CTC counts. For all measurements, receiver operator characteristic (ROC) analysis and characteristics and regression trees (CART) were used to explore further prognostic cutpoints. Results: Samples were obtained from 263 men. Median d1 CTC count was 5, and there was a significant difference in OS for d1 CTC < vs. >=5, hazard ratio (HR) 2.92 (p<0.001) after adjustment for other factors. D1 CTC and OS had ROC AUC of 0.781. In men with low d1 CTC (< 5), an increase in CTC was associated with shorter OS, HR 4.04 (p=0.004); in men with high d1 CTC (>=5), a >=2-fold decrease in CTC was associated with longer OS, HR 0.45 (p=0.012); adjusting for risk factors. For TA, men with baseline CTC >=5 (41% of cohort) who had high CTC TA had HR 1.14 (p<0.005) for OS after adjustment for other factors including CTC counts. CART identified additional risk subgroups based on CTC counts and TA. Conclusions: In this phase III trial, d1 CTC and d1 to d21 CTC dynamics were prognostic of OS after risk factor adjustment, comprising the largest docetaxel-based prospective cohort to date which validates a 5 CTC prognostic threshold and identifies new potentially useful enumeration subgroups. In men with CTCs >=5, TA from cells live-captured on a new slot filter constitutes the first CTC-derived biomarker prognostic of OS in a prospective clinical trial.
Use of epiregulin (EREG) and amphiregulin (AREG) gene expression to predict response to cetuximab (cet) in combination with oxaliplatin (Ox) and 5FU in the first-line treatment of advanced colorectal cancer (aCRC).
Authors: Adams Richard A. , Fisher David , Farragher Susan , Jasani Bharat , Smith Christopher G. , James Michelle D. , Cheadle Jeremy , Nichols Laura L. , Meade Angela M. , Kaplan Richard S. , Wilson Richard H. , Wasan Harpreet , Maughan Tim 
Published: February 2017

32 Background: Previous data suggests the EGF ligands EREG/AREG may predict outcome of KRAS wt patients (pts) treated with cet in the chemo-refractory setting but this finding has not been previously reported from first line randomised trials. Methods: FFPE samples from primary tumours of pts in Arms A&B of the COIN trial of Ox fluoropyrimidine (Fp) +/- cet were analysed for EGFR IHC, KRAS/NRAS/BRAF mutation and EREG/AREG expression by RT-PCR. Ligand levels were assessed against baseline data, prognostic markers as uni/multivariate analyses and as predictive markers in wild type (wt) and mutant (mt) cohorts and separately by Fp backbone [capecitabine (CapOx) or 5FU (FOLFOX)]. Tests for interaction were performed with EREG/AREG continuous, using Flexible Parametric survival analysis. Results: 952/1630 (57%) of pts were evaluable for all parameters. High EREG/AREG levels were associated with KRAS wt (p<0.005), BRAF wt, absence of MSI and with primary tumour in left colon/rectum, presence of liver metastases, post randomisation radical surgery, high CEA (p<0.05) and ALKP. In the control arm, high EREG/AREG conferred a better prognosis among KRAS wt pts in a multivariate analysis. High EREG predicted for OS benefit from cet. treatment in KRAS wt pts, (n=525, p=0.017) and, separately, in pts treated with FOLFOX (n=310, p=0.021), with greatest effect in the “combined” subgroup (KRAS wt + FOLFOX, n=176, p=0.0042). Conversely a trend towards disbenefit was observed in KRAS wt pts treated with XELOX (n=349, p=0.14). Conclusions: The data suggest a prognostic effect of EREG/AREG in aCRC. The original hypothesis, that KRAS wt patients with high EREG expression have improved outcome with cet, is limited to patients treated with FOLFOX in the first-line setting. This data further suggests that capecitabine in combination with oxaliplatin and cetuximab produces a sub-optimal outcome.
Mutational load distribution analysis of colorectal and pancreatic carcinoma by next generation sequencing platform.
Authors: Lopez-Doriga Adriana , Azuara Daniel , Morell Mireia , de Oca Javier , Rodriguez-Moranta Francisco , Fabregat Joan , Boadas Jaume , Larochelle William , Capella Gabriel , Costa Jose 
Published: February 2017

57 Background: It has been suggested that the sequential analysis of the mutational spectra at loci involved in the pathogenesis of tumors (mutational load distribution analysis [MLDA]) may reflect the biology of the tumor and/or the risk of cancer before the tumor emerges. Metrics derived from MLDA could assist quantifying risk, in early diagnosis, and in monitoring response to therapy. The aim of this study was to assess the efficacy of the NGS platform to obtain clinically relevant metrics derived from MLDA. Methods: Two sets of DNA samples were assessed: (i) 6 paired tumor/normal colorectal carcinomas and 8 colorectal adenomas; and (ii) 21 pancreatic carcinoma and 6 non-matched normal pancreas. Thirty amplicons from 6 genes (KRAS, BRAF, EGFR, CDKN2A, TP53, and PI3KCA) were sequenced using the Roche 454 GS FLX-TI platform. Data analysis was carried out by Variant Identification Pipeline (VIP) software and R (computing environment) commands. Total mutational load (TML) was calculated as the sum of all variants frequency for each sample. Results: In all, 18,626 variants were identified. Optimal filters applied to discard false positives were: (1) variants with an absolute frequency < 10x, (2) variants in homopolymer (HP) ≥ 6 nucleotides, (3) insertions and deletions (INDELs) in HP ≥ 5 nucleotides, and (4) INDELs in only one strand. Filtering yielded 870 variants from all samples remained as valid, 92 being unique. After discarding polymorphisms, variants classified as neutral by the Condel software and variants preferentially detected in normal tissues, 46 variants were used to compute TML. TML in colonic carcinomas and adenomas was higher than normal mucosa (0.83 vs. 0.607 vs. 0.128, p = 0.01). In pancreatic disease, TML for pancreatic carcinoma was higher than normal pancreas (0.716 vs. 0.135, p = 0.01). KRAS and TP53 analysis provide most of the information in both tumors, while PI3KCA adds information for colorectal carcinomas exclusively and CDKNA2 is informative in pancreatic samples. Conclusions: NGS provides a robust and quantitative measure of genetic alterations in tumor samples. MLDA is an effective tool for the classification of GI tumors.
Detection of low-frequency FGFR3 mutations in the urine of patients with bladder cancer using next-generation deep sequencing.
Authors: Millholland John M. , Li Shuqiang , Fernandez Cecilia A. , Shuber Anthony P. 
Published: February 2017

59 Background: FGFR3 mutations have been identified in ~60-70% of low-stage, non-invasive tumors. Our group and others have developed assays to detect FGFR3 mutations in the urine of bladder cancer patients. However, urine-based assays have been limited by the technical ability to detect rare events in a dilute medium where there is a high background of normal DNA. In these assays, FGFR3 mutations are generally found in ~30% of the urine samples, which is < 50% concordance with the expected detection in tissue. We have now developed an ultra-deep amplicon sequencing technique that increases FGFR3 mutation detection in urine to ~67%, close to the expected detection frequency if every mutation found in tissue could be detected in urine. Methods: Amplicons were designed against FGFR3 exons 7, 10, and 15 using PCR primers containing the adapter sequences for unidirectional sequencing. Primary amplification was performed from DNA isolated from 4 ml of urine. The resulting PCR products were used as template for emulsion PCR and these were then sequenced using the Roche 454 GS Junior. Samples were analyzed for total DNA reads per sample and number of mutant sequencing reads to determine percent mutation. Results: Urine samples from 43 patients with bladder cancer were analyzed by both our previously described qPCR method and the new ultra-deep sequencing approach. Using ultra-deep amplicon sequencing, 24 out of 43 (55.8%) were positive for FGFR3 mutations, while only 5 out of 43 (11.6%) were positive for mutations by qPCR. The urine samples from the 15 newly identified mutations using deep sequencing contained FGFR3 mutations as low as 0.05% mutant DNA. The sensitivity achieved using deep sequencing was 91% concordant with the FGFR3 mutations observed in tissue. Conclusions: We have developed a highly sensitive non-invasive urine based assay that can detect FGFR3 mutant DNA when present at < 1% of the sample and is > 90% concordance with the mutations found in tumor tissues. To our knowledge, this is the first practical application of next generation sequencing technology for diagnostic use.
Attitudes toward and use of cancer management guidelines in a national sample of medical oncologists and surgeons.
Authors: Huang Grace , Hawley Sarah T. , Zikmund-Fisher Brian , Janz Nancy K. , Griffith Kent A. , Griggs Jennifer J. , Katz Steven J. , Jagsi Reshma 
Published: February 2017

163 Background: Previous studies have assessed physician perceptions of practice guidelines and identified barriers to adherence, including lack of knowledge, attitudes, and other factors. Little is known about attitudes toward and use of cancer management guidelines specifically. Methods: We surveyed a random sample of 750 medical oncologists and 750 surgeons drawn from the AMA Masterfile between January and June 2012. 896 responded; 130 of these reported that they had not seen breast cancer patients in the previous year and were asked not to complete the remainder of the survey. We analyzed responses from the remaining 766 (403 surgeons and 363 medical oncologists). Results: Mean participant age was 52; 36% worked in a practice with an academic affiliation. Attitudes towards clinical practice guidelines were generally favorable. Few (<3%) disagreed that guidelines were good educational tools or convenient, and only 12% felt that they were biased, although 24% felt they were oversimplified, 20% found them too rigid, and 20% perceived them as a challenge to physician autonomy. Most agreed that guidelines were intended to improve the quality of care (98%) but opinion split about whether they were intended to decrease costs (51% felt they were). NCCN guidelines were reported to influence the cancer management decisions of 96% of medical oncologists and 70% of surgeons (p<0.001), and ASCO guidelines influenced 65% of medical oncologists and 45% of surgeons (p<0.001). Many respondents looked at the NCCN guidelines at least every few months (93% of medical oncologists, 48% of surgeons, p<0.001). Most respondents reported they made guideline-concordant decisions in the majority of their cancer cases. Yet most respondents reported that they rarely refer patients to the patient versions of the NCCN guidelines (76% refer ¼ or fewer of their patients). When making a guideline-inconsistent recommendation, 17% do not routinely discuss the inconsistency with patients. Conclusions: Attitudes toward physician-directed cancer management guidelines are generally positive, and they are frequently used. However, physicians infrequently advise use of patient versions.
Quality of care among breast cancer (BC) survivors in the University of California (UC) Athena Breast Health Network.
Authors: Ganz Patricia A. , Hahn Erin E. , Petersen Laura , Melisko Michelle E. , Pierce John P. , Von Friederichs-Fitzwater Marlene Marie , Lane Karen , Hiatt Robert A. 
Published: February 2017

164 Background: Post-treatment cancer care needs improvement (IOM 2006), including use of treatment summaries (TS) and survivorship care plans (SCP). ASCO BC surveillance guidelines (2006) suggest only 1 provider needs to see patients 3 to 4 times a year in first 2 years, and every 6 to 12 months thereafter. Athena is a collaborative project designed to drive innovation in BC care among the five UC cancer centers. Interviews with Athena MDs and RNs noted visit redundancy and poor guideline adherence (Hahn ASCO Breast 2011). Methods: BC patients diagnosed in 2008-09 were recruited from UC hospital tumor registries. With UC-wide IRB approval, patients were invited to participate in a mailed survey on post-treatment care starting September 2011. A 30-page survey collected information on post treatment care including number and type of provider visits, discussion of key topics, satisfaction with care, and quality of life. We targeted 100 completed questionnaires from each site. Results: Data from the first 194 respondents are reported. Most were white, college graduates, with mean age 61 yrs, and mean time from diagnosis 3.2 ± 0.6 years. Treatments: surgery (S) only=33; S and radiation (XRT)=66; S and chemotherapy (C)=25; S, C, XRT=70. Mean number of BC follow-up care providers (2.3±1) was not related to treatment received (p=0.3). S-only treatment resulted in fewer BC specific clinic visits than C-treatment (33% vs. 45% to 58%). Of 80% who attended UC clinics, most received follow-up care every 3 to 4 months. The providers seen were: oncologists (66%), surgeon (38%), radiation oncologist (47%), primary care (40%). There were no differences in visit frequency by <3 or >=3 years since diagnosis. 68% had copies of medical records; 40% had received a TS; 57% had a SCP (61% at UC vs. 41% not at UC, p=0.03). The presentation will update data with a larger sample and multivariable models. Conclusions: Patient reports confirm that multiple providers are delivering BC specific follow-up care. Visit frequency may exceed guideline recommendations, and does not reflect risk of recurrence or treatment intensity. Less than half of patients received TS, but more than half had SCP. There is room to improve the coordination of post-treatment BC care.
Retrospective assessment of quality of cancer care in last 6 months of life.
Authors: Cassel Brian , Skoro Nevena , Kerr Kathleen , Shickle Lisa , Coyne Patrick J. , Del Fabbro Egidio 
Published: February 2017

234 Background: National organizations such as the Centers for Medicare and Medicaid Services (CMS) and the National Quality Forum (NQF) have developed metrics that assess the quality of cancer care. These metrics include consensus standards by the NQF for management of symptoms and end-of-life-care. Cancer centers need feasible methods for self-evaluating their performance on such metrics. Methods: Claims for our cancer patients were matched to Social Security Death Index data to determine date of death.3,128 adult cancer patients died between January 2009 and July 2011 and had at least 1 contact with our center in their last six month of life. All inpatient and outpatient claims data generated in the last six months of life at our hospital were analyzed. Results: 32% of patients had an admission in their last 30 days of life, with 15% dying in the hospital. 19% had at least one 30-day readmission in their last six months of life. 6.7% had chemotherapy in the 2 weeks prior to death, and 11.4% in the last month. 27.5% had some contact with the specialist palliative care (SPC) team. Solid tumor patients with SPC earlier than 1 month until death had fewer in-hospital deaths (15.6%) versus those with later or no SPC (19.5%), p=.041. There was no SPC difference for 30-day mortality, or 14- or 30-day chemotherapy metrics. Conclusions: Hospitals can self-evaluate their own performance on NQF endorsed measures, and CMS outcome measures. These data provide additional impetus for earlier integration of specialist palliative care teams. SPC in the last 1-3 weeks of life did not improve most utilization metrics.[Table: see text]
Developing an IT infrastructure for the National Radiation Oncology Registry.
Authors: McNutt Todd , Palta Jatinder , Bogardus Carl , Bosch Walter , Carlin Jeffrey , Chou Henry , Curran Bruce , Goldwein Joel , Hotz Ken , Kapoor Rishabh , Kessler Marc , Mayo Charles , Mutic Sasa , Tulskie William , Gabriel Peter 
Published: February 2017

300 Background: The National Radiation Oncology Registry (NROR) is developing an IT infrastructure to support the efficient collection, aggregation, and analysis of data concerning cancer patients treated with radiotherapy across the United States. Methods: Detailed requirements were developed to emphasize the following distinguishing goals for the system: 1) streamline the process of data collection by minimizing manual data entry; 2) support the collection of patient-reported outcomes (PROs) and their linkage with clinician-observed outcomes; 3) facilitate data integration within the NROR and between the NROR and other registries; 4) allow for evolution of the system in response to new learning; and 5) promote sustainability and ongoing improvement through an open standard of interoperability. Results: An innovative technical architecture has been designed to meet the goals described. The system maximizes efficiency through automated extraction and electronic transfer of data from radiation oncology information systems. PROs are collected directly from patients via a web-based portal and linked to data submitted from participating institutions. A data dictionary has been developed based on national standards and controlled vocabularies to facilitate data integration. Contemporary forms-based database technology is used in combination with traditional relational technology to permit both flexible evolution of the system and efficient data analysis. A unique “gateway” architecture and open transmission standard makes it possible for commercial products to interoperate with the registry in the future. Conclusions: The NROR prototype system will be launched later this year to collect data for a pilot registry of prostate cancer patients. Its performance and usability will be important factors in the success of the pilot. If effective, the platform will support the expansion of the NROR to benefit patients, clinicians, researchers, payors, device manufacturers, and policy-makers by capturing reliable, population-based information on radiation treatment delivery and health outcomes.
Radiation oncology whiteboard: Data and workflow manager for enhanced communication and task management.
Authors: Wolfgang John A. , Hong Theodore S. 
Published: February 2017

304 Background: Patient care within the radiation oncology clinic consists of several interdependent data driven procedures which must be executed in concert to ensure the best possible patient care. State of the art treatment in radiation oncology is largely computer driven, where patient care relies on the use of a typically vendor dependent, heterogeneous server environment. Traditional, peer-to-peer communication in such an environment introduces a fault intolerant workflow, where failed communication and data inconsistency issues may result in delayed or inappropriate patient treatment. Methods: The MGH Radiation Oncology Whiteboard is an intranet based application allowing for live monitoring of these patient care tasks available across the entire radiation oncology clinical domain. Patient events are recorded through interaction from various care-givers and data sources within the department, changing state as well as collecting event data from the accomplished task. Personnel may be alerted of state changes through automatic, customizable paging, email and live monitoring notification, triggering subsequent steps in the workflow chain. Currently the Whiteboard leverages data from multiple points in the clinic including: CT Simulation and data (4D), treatment planning written directive, dvh plan results, imrt and sbrt plan QA, daily and monthly linac QA, IORT coordination and calculation check, linear accelerator engineering log, patient treatment wait time (linac), remote treatment plan review. Results: Since introduction of the Whiteboard into the MGH clinic in 2008, task compliance in key areas, such as contour definition, radiation dose prescription, imrt QA measurement completion and pre-treatment plan checking has risen to levels well above 95%. Conclusions: Monitoring of patient care events improves QA by eliminating peer-to-peer communication and introducing complete transparency to the workflow communication chain. This approach enables all members of the staff to become active participants in the quality control process, every individual, through interaction with the Whiteboard, acting as an additional QC filter to improve patient care.
Quality-of-care implications of improving physician communication through a Web-based tool (Teamwork).
Authors: Silva Alex Pimenta , Bertoni Vanessa Dybal , Mulvey Therese M. , Sampaio Carlos 
Published: February 2017

310 Background: Our practice is a community-based multidisciplinary oncology-hematology outpatient clinic located in Northeastern Brazil serving a population of three million. Hospitalizations are frequent events for treatment of complications and for palliative care. Patients are distributed in several different units across five hospitals. A team of oncologists, hematologists and other clinicians is organized in daily shifts for ambulatory consults and hospital visits. The group meets every Monday morning in rounds for case discussion and planning. The number of patients, physicians and hospitals involved poses a communication challenge. Methods: In order to improve communication and quality of care, we created a internet application (Teamwork) which provides a patient table sorted by hospital, room number, assistant physician, last visiting doctor, diagnosis and treatment plan. This information is easily accessible from any internet connected computer, tablet or smartphone with a friendly graphic interface. The doctor who admits or consults with the patient is responsible for daily updates. All the multidisciplinary teams may consult and add information. Results: Data from our program between March 2011 and June 2012 demonstrated that on average 7 physicians visited a mean of 21.8 patients daily in 5 different hospitals. With the use of the online application (Teamwork) improvements in quality of care were noticed, including: 1) Admitted patient information was rapidly available for the team, anywhere; 2) Doctors could immediately identify the physician responsible for the most recent visit, improving communication, optimizing time and reducing uneccessary phone calls to make decisions; 3) Doctors out of town could obtain updated information about their patients and contribute to their care; 4) Statistical information was readily available, providing data for improvement of team organization. Conclusions: The use of a simple online database, easily accessible and updatable represents a major step forward in the quality of care as measured by enhanced communication among providers, making it possible to assist patients in several hospitals, in a large city, with minimal communication stress.