tbuckley/cabot-search huggingface dataset:
Improving cancer clinical trial accrual in Ontario, Canada: The clinical trials infrastructure fund (CTIF) experience.
Authors: Lesleigh S. Abbott, Joseph L Pater, Kay T. Friel, Diana Kato, Janet Dancey
Journal: Journal of Clinical Oncology (2014)

6602 Background: Participation in clinical trials is essential to evaluating safety and efficacy of emerging cancer therapies. To improve trial activities in the province of Ontario, Canada, the CTIF was established in 2002 and operationalized from 2004-2008 by the Ontario Cancer Research Network (OCRN), Ontario Institute for Cancer Research's (OICR) predecessor and funded by the Ontario government. The goals were to double trial recruitment from the baseline of 2001 and have self-sustaining trial units over 4 years. Methods: Beginning in 2004, the CTIF awards were issued in 3 phases – phase 1: 14 adult cancer centers, phase 2: 9 community hospitals, phase 3: 5 pediatric cancer centers. Per case funding (PCF) provided was $3300/patient; $4000/patient to community hospitals. The total program cost was $12.9 Million/3 years. Participating sites reported recruitment to academic and industry trials and shared 11% of additional industry trial funding over 5 years back to OCRN/OICR. The number of patients accrued was divided by the number of patients treated at sites to calculate the percentage of cancer patients accrued to clinical trials. Results: Trial recruitment and personnel increased during the years of the CTIF peaking in 2007. Trial increase was most marked for larger adult cancer centers. Successful sites maintained an average of 40% industry trials within their clinical trials portfolio and had a clinical trials manager with business experience. Conclusions: Providing additional PCF improved clinical trials accrual in Ontario, particularly in larger cancer centers that could rapidly expand their trial activities and personnel, but the effect was not sustained. Defining the best business model(s) and trial portfolio for trial units requires further elucidation. Year Cancer centers Patient accrual % Change accrual from baseline %Overall accrued to trials Patient accrual % Change accrual from baseline %Overall accrued to trials Community hospitals Baseline 2797 N/A 173 N/A 2004 4126 48 9 2005 4948 77 11 - 2006 5167 85 12 161 -7 N/A 2007 5572 100 13 187 8 4 2008 4428 58 9 76 -56 2 2009 4321 54 8 190 10 4 2010 3757 34 7 83 -52 2
Leukemia Stem Cells Are Characterized By CLEC12A Expression and Chemotherapy Refractoriness That Can be Overcome By Targeting with Chimeric Antigen Receptor T Cells
Authors: Saad S Kenderian, Marco Ruella, Olga Shestova, Michael Klichinsky, Miriam Y Kim, Craig Soderquist, Adam Bagg, Reshma Singh, Celeste Richardson, Regina M Young, Carl H June, Saar I. Gill
Journal: Blood (2016)
Case 7-2017
Authors: Robert L. Fogerty, Jeffrey L. Greenwald, Shaunagh McDermott, Angela E. Lin, James R. Stone
Journal: New England Journal of Medicine (2017)

A 73-year-old man with a history of heart failure, pulmonary hypertension, and a hepatic venovenous malformation presented with confusion. CT of the abdomen revealed pneumatosis of the ascending colon to the level of the hepatic flexure. Diagnostic tests were performed.
Abstract 17328: Ultrasmall Supraparamagnetic Particles of Iron Oxide-enhanced Magnetic Resonance Imaging in the Assessment of Cellular Inflammation after Myocardial Infarction
Authors: Colin G Stirrat, Shirjel R Alam, Tom J MacGillivray, Marc R Dweck, Peter A Henriksen, David E Newby, Scott Semple
Journal: Circulation (2014)

Introduction: Excessive inflammation after myocardial infarction (MI) can be detrimental to the recovery of cardiac function. Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect myocardial cellular inflammation after MI. We aimed to determine the time course and duration of USPIO-enhancement following acute MI. Methods: Twenty-one patients with acute MI were studied in the 3-month period following acute MI. Repeated T2*-weighted 3T MRI was performed throughout and 24 h after USPIO (ferumoxytol, 4 mg/kg) administration at 4±3, 12±2, 21±4 and 90±9 days. Myocardial regions of interest (ROIs) were drawn and categorised into infarct and non-infarct regions by the presence or absence of late gadolinium enhancement (LGE). R2* values within ROIs were determined to assess the time course and duration of uptake and clearance of USPIO. Results: Following single-dose USPIO administration 2-7 days after acute MI, USPIO uptake is demonstrable at 24 h (p&lt;0.0001) and is cleared within 4-8 days (Figure 1a). Increased USPIO uptake is seen in the infarct region at days 2-7 (p&lt;0.0001), and days 10-14 (p&lt;0.05) compared to non-infarcted myocardium (Figure 1b). Conclusions: For the first time, we have shown USPIO-enhanced MRI can detect and quantify infarct-related cellular inflammation in the first 2 weeks following acute MI.
Abstract P2-04-26: Identifying patient-specific neoepitopes for cell-based and vaccine immunotherapy across breast cancer classifications reveals rarely shared recurrent neoepitopes
Authors: A Nguyen, JZ Sanborn, CJ Vaske, S Rabizadeh, K Niazi, P Soon-Shiong, SC Benz
Journal: Cancer Research (2017)

Abstract Introduction: Targeted therapies for breast cancers such as trastuzumab and everolimus have durable clinical benefits for patients that express the relevant biomarkers (HER2 and mTOR respectively). Triple negative breast cancer patients lack these biomarkers and are left with few options. Recent advances in immunotherapy agents against PD-1/CTLA4 for patients with melanoma have yielded amazing clinical benefits for a subset of patients and may have similar results in breast cancer patients, but again the vast majority of patients still undergo disease progression. We analyzed whole genome sequencing (WGS) and RNA sequencing data from The Cancer Genome Atlas (TCGA) to identify neoepitopes among breast cancer patients that could be used to develop next-generation, patient-specific cancer immunotherapies. Neoepitopes are tumor specific markers that arise from mutations acquired from cancer and may represent a path to targeted therapies even in triple negative breast cancers. Results: We analyzed 99 breast cancer patients from TCGA, containing a mixture of PR+/HER2+/ER+ and TNBC classifications. These breast cancer patient samples were selected by the availability of whole genome sequencing (WGS) data, RNA-sequencing data as well as clinical outcome data. We identified an average of 680 potential neoepitopes per patient based solely on WGS data. To further refine and select high quality neoepitopes we restricted these neoepitopes based on gene expression yielding an average of 304 expressed neoepitopes per patient. We predicted each patient's HLA typing using only omics data, which we then used to predict HLA-expressed neoepitope binding analysis resulting in an average of 11 high-quality tumor specific neoepitopes per patient. We identified few recurrent neoepitopes that were bound and expressed, indicating the need for a personalized medicine approach. Conclusions: Within the TCGA dataset, the majority of neoepitopes among patients with breast cancer were unique to each patient. Rarely within subsets of breast cancers such as HER2+, we identify neoepitopes that are shared between patients. For breast cancer patients who do not respond to targeted therapies, high-throughput identification of neoepitopes could serve as the basis for the development of next-generation, patient-specific immunotherapies. Citation Format: Nguyen A, Sanborn JZ, Vaske CJ, Rabizadeh S, Niazi K, Soon-Shiong P, Benz SC. Identifying patient-specific neoepitopes for cell-based and vaccine immunotherapy across breast cancer classifications reveals rarely shared recurrent neoepitopes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-26.
Did balloon catheter have superior efficacy to the basket catheter?
Authors: Feng Shao, Chen Wang, Qiang Huang, Lujun Qiu
Journal: Endoscopy (2017)

We read with great interest the recent article by Ishiwatari et al. [1]. The authors concluded that the balloon catheter is recommended as the first-line device in endoscopic treatment of patients with four or more bile duct stones. It is an interesting study. Nevertheless, several issues seem worthy of comment.
NAMPT/PBEF Enzymatic Activity Is Indispensable for Myeloma Cell Growth and Osteoclast Activity
Authors: Sathisha Upparahalli Venkateshaiah, Sharmin Khan, Wen Ling, Rakesh Bam, Xin Li, Bart Barlogie, John D Shaughnessy, Shmuel Yaccoby
Journal: Blood (2011)
Phase 1/2 Study of AMG 531 in Thrombocytopenic Patients (pts) with Low-Risk Myelodysplastic Syndrome (MDS): Update Including Extended Treatment.
Authors: Hagop Kantarjian, Pierre Fenaux, Mikkael A. Sekeres, Pamela Becker, Adam Boruchov, David Bowen, Richard Larson, Roger Lyons, Petra Muus, Jamile Shammo, Michael Ehrman, Kuolung Hu, Janet Nichol
Journal: Blood (2007)
PP42. SINGLE INSTITUTION RECURRENCE PATTERNS OF GLIOBLASTOMA AFTER RECEIVING A RADICAL DOSE OF RADIOTHERAPY
Authors: Dr Aurora Sanz-Torres, Ms Nicola Cornelius, Mr Jonathan Stoddart, Ms Nicola Cantrill, Mrs Vanessa Ohlendorf
Journal: Neuro-Oncology (2017)

PURPOSE: To investigate the patterns of failure in the treatment of glioblastoma (GBM) when using margins according to Radiation Oncology Group Margins (RTOG) or European Organisation for Research and Treatment of Cancer (EORTC) guidelines at consultant discretion. METHODS: Between January 2012 and November 2015, 41 patients with GBM completed a radical course of radiotherapy (54 to 60 Gy) with concurrent temozolomide. Patients were treated with GTV expansions that ranged from 2–3 cm with or without shrinking field technique. The pattern of recurrence was determined by relationships between locations of recurrent tumors and irradiated doses. RESULTS: The median progression-free survival from the time of diagnosis to documented failure was 8 months (range 2–31). 11 patients received doses below 60 Gy in order to meet dose constraints of organs at risk. Of the 38 documented recurrences, 28 patients (73 %) had central recurrence, 3 (8 %) had in-field recurrence, 4 (10 %) had a marginal component, and 3 (8 %) had both in field and distant component with 2 cases of meningeal metastases and 1 case of pathologically confirmed pleural and liver metastasis. CONCLUSIONS: Recurrence patterns of glioblastoma after radical radiotherapy were mainly central. The low rate of marginal or distant recurrence suggests that wide margins would have little impact on the pattern of failure. Further investigation should be carried on to reduce volumes safely and avoid toxicities such as radionecrosis and cognitive decline.
Diagnostic and Prognostic Implications of Prohibitin Overexpression in Normal Karyotype Acute Myeloid Leukemia
Authors: Hye-Ran Kim, Jun Hyung Lee, Min-Gu Kang, Ra-Young Park, Moinul Md Hoque, Sol Jeong, Min-Seo Noh, Seok-Yong Choi, Soo-Hyun Kim, Jong-Hee Shin, Soon-Pal Suh, Myung-Geun Shin
Journal: Blood (2016)
Abstract PL3: Global cost of cancer care
Authors: PB Bach
Journal: Cancer Research (2017)

Abstract According to a 2014 IMS health report, cancer drugs represent 26% of specialty drug spending, more than $32B in the US in 2014, and specialty drug spending is growing faster than any other sector of healthcare. Unsurprisingly, cancer drugs are the largest sub-segment. These price rises are not just an economic curiosity. Because of the structure of many insurance products, the co-insurance on these expensive drugs is crippling, impacting access on a large scale. A recent study reported that more than 10% of Medicare beneficiaries with a cancer diagnosis face out of pocket expenses exceeding their incomes. In a nationally representative survey conducted in 2006, twenty-five percent of patients reported exhausting all or most of their savings. In a recent analysis of discontinuation rates among patients taking Gleevec and other highly effective drugs for Chronic Myeloid Leukemia, patients with high copayments were 42% more likely to be nonadherent. Dr. Bach has researched this problem with a data-driven set of related projects that aim to achieve substantive change to pricing of and access to specialty drugs, beginning with cancer drugs because of established expertise, but expanding to other analogous areas rapidly. In 2009, Dr. Bach's team began tracking the launch prices of new cancer drugs, a project which has shown a 100-fold increase in introductory cancer drug prices, after adjusting for inflation. A follow-on study found that the increase in price is not accompanied in an increase in clinical value, with the cost of a year of life increasing by $8,500 a year. In 2012, on behalf of Memorial Sloan Kettering Cancer Center, Dr. Bach publicly rejected the pricing of the cancer drug, Zaltrap, by announcing the hospital's position in the New York Times. In response, the company lowered its price by 50%, proving that the price is not tied to any specific metric (i.e. R&amp;D costs), but is rather determined by what the market can bear. Dr. Bach launched a project in 2015 called the DrugAbacus (drugabacus.org), an interactive web based tool that allows users to manipulate various metrics to determine the ‘value’ of cancer drugs. DrugAbacus shifted the conversation of value-based pricing from one of theory to one more focused on implementation, and has been cited as a source of pricing for both CVS and Express Scripts. The Zaltrap stance, the DrugAbacus, and much of his work has made MSKCC a leader in using evidence to shift the discussion on drug pricing, a consistent theme of which has been that the price a manufacturer sets is a product of the marketplace, not a product of the costs of their business or something else structural. Citation Format: Bach PB. Global cost of cancer care [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PL3.
The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement
Authors: Vasilios G. Athyros, Theodore K. Alexandrides, Helen Bilianou, Evangelos Cholongitas, Michael Doumas, Emmanuel S. Ganotakis, John Goudevenos, Moses S. Elisaf, Georgios Germanidis, Olga Giouleme, Asterios Karagiannis, Charalambos Karvounis, Niki Katsiki, Vasilios Kotsis, Jannis Kountouras, Evangelos Liberopoulos, Christos Pitsavos, Stergios Polyzos, Loukianos S. Rallidis, Dimitrios Richter, Apostolos G. Tsapas, Alexandros D. Tselepis, Konstantinos Tsioufis, Konstantinos Tziomalos, Themistoklis Tzotzas, Themistoklis G. Vasiliadis, Charalambos Vlachopoulos, Dimitri P. Mikhailidis, Christos Mantzoros
Journal: Metabolism (2017)
Does the addition of molecular targeted therapy to standard treatments lead to better or worse outcomes overall? A systematic review of EGFR-targeted therapies used in combination with standard treatments.
Authors: Jennifer Rauw, Marguerite Ennis, Monika K. Krzyzanowska, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2012)

2572 Background: Combining novel targeted therapies with standard treatment is a common strategy in drug development. The primary aim of this systematic review was to provide a summary of the outcomes from studies combining EGFR targeted therapy (ETT) with standard treatments. Methods: A PubMed (1975-Jan, 2012) and ASCO (2005-2011) abstract database search was performed. Eligible studies were RCTs that compared standard therapies (chemotherapy, radiation therapy, or hormonal therapy) to standard therapy plus an ETT. Efficacy outcomes: overall survival (OS), progression free survival (PFS), objective response rate (ORR) time to progression (TTP), clinical benefit rate (CBR), and toxicity (total and grade 3+) were recorded. If any toxicity was significantly more frequent in one arm it was coded as such. Results: 128 studies (60 manuscripts, 68 abstracts) met criteria. Median study enrolment was 230 patients, with breast, lung, and colorectal cancer as the main tumor sites. ETT, cetuximab (41%), trastuzumab (19%), gefitinib (13%), erlotinib (13%), and lapatinib (16%), was combined with platinums, 5FU, taxanes, nucleoside analogs; hormonal therapy and/or radiation therapy. Refer to the table for efficacy results. Most frequent toxicities (common and grade 3+) in the combined arm were rash, diarrhea, hematological toxicity and fatigue. Conclusions: Despite enthusiasm for combining standard treatments with targeted therapies, we have demonstrated mixed efficacy results, with marginal benefit and worse toxicity. Quality of life (Q of L) was rarely reported. A similar analysis is underway for VEGFR, and mTor inhibitors, but raises the question of how best to approach the question of combination therapy. [Table: see text]
An Open-Label, Dose Escalation, Multi-Center Phase 1 Study of PRLX 93936, an Agent Synthetically Active Against the Activated Ras Pathway, in the Treatment of Relapsed or Relapsed and Refractory Multiple Myeloma
Authors: Peter M Voorhees, Robert L. Schlossman, Cristina J Gasparetto, Jesus G. Berdeja, John Morris, Douglas A Jacobstein, Kenneth C. Anderson, Constantine S Mitsiades, Jacob P. Laubach, Paul G. Richardson
Journal: Blood (2014)
Biomaterial-enabled delivery of SDF-1α at the ventral side of breast cancer cells reveals a crosstalk between cell receptors to promote the invasive phenotype
Authors: Xi Qiu Liu, Laure Fourel, Fabien Dalonneau, Rabia Sadir, Salome Leal, Hugues Lortat-Jacob, Marianne Weidenhaupt, Corinne Albiges-Rizo, Catherine Picart
Journal: Biomaterials (2017)
Abstract PD7-06: SEER study of breast cancer-specific mortality in patients with poorly differentiated tumors treated based on recurrence score results
Authors: VI Petkov, DP Miller, N Howlader, FL Baehner, L Penberthy, S Shak
Journal: Cancer Research (2017)

Abstract Introduction: The SEER Program of the NCI is an authoritative source of cancer incidence and survival statistics. Linking the 21-gene assay Recurrence Score® (RS) results to the SEER Registries (N=44,825) demonstrated very low 5-year breast cancer-specific mortality (BCSM) with RS &amp;lt;18 across many key clinical-pathological subgroups, such as age, nodal status, tumor grade, and size (npj Breast Cancer. 2016;2:16017). Given the large sample size and specific interest in outcomes as a function of tumor grade, further stratification of patients with poorly differentiated tumors was performed to determine BCSM when examined by both tumor grade and tumor size. Methods: Patients were eligible if node negative (N0), HR+, HER2-negative (by RT-PCR), had no prior malignancy, had poorly differentiated (G3) tumors, and were diagnosed between Jan 2004 (test available in Jan 2004) and Dec 2011 (SEER survival updated through 2012). BCSM was defined according to pre-existing robust methodology (J Natl Cancer Inst. 2010;102:1584). RS was categorized according to the cutpoints of 18 and 31 established in the NSABP B-14 study. Five-year BCSM was estimated using actuarial methods. Results: Among 6,666 eligible patients with G3 tumors, 4,683 had tumors ≤2 cm and 1,983 had tumors &amp;gt;2 cm. Median age was 57 years; 99.1% were female. Median follow-up was 39 months. The proportion of patients with RS &amp;lt;18 was 29% among those with tumors ≤2 cm and 25% among those with tumors &amp;gt;2 cm, somewhat lower than the overall population. For RS &amp;lt;18, 5-year BCSM was 0.3% (G3; ≤2 cm) and 1.4% (G3; &amp;gt;2 cm); reported chemotherapy use was 10% and 16%, respectively. 5-year BCSM for all groups are provided in Table. An additional year of BCSM follow-up in N0 G3 disease, as well as results for patients with node positive (micrometastases or 1-3 positive nodes) G3 disease, will be available for presentation. N0, G3 tumor, RS &amp;lt;18N0, G3 tumor, RS 18-30N0, G3 tumor, RS ≥31Tumor sizeN5-y BCSM (95% CI)N5-y BCSM (95% CI)N5-y BCSM (95% CI)≤2 cm13620.3% (0.1%, 1.2%)21482.1% (1.3%, 3.3%)11732.9% (1.8%, 4.7%)&amp;gt;2 cm4861.4% (0.4%, 4.6%)8514.6% (2.7%, 7.8%)6469.0% (6.0%, 13.4%) Conclusions: Although patients with poorly differentiated tumors have worse prognosis in general, the RS identifies a sizable proportion of patients who can expect good outcomes without chemotherapy and its associated toxicity. Citation Format: Petkov VI, Miller DP, Howlader N, Baehner FL, Penberthy L, Shak S. SEER study of breast cancer-specific mortality in patients with poorly differentiated tumors treated based on recurrence score results [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-06.
Usefulness of the Glasgow Coma Score in Survivors of Cardiac Arrest
Authors: Zsolt T Stockinger
Journal: JAMA (2004)

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