tbuckley/cabot-search huggingface dataset:
New frontiers ahead focal therapy postoperative follow-up: What is the real role of MRI in this setting?
Authors: Igor Nunes-Silva, Eric Barret, Mohammed Baghdadi, Victor Srougi, Silvia Garcia Barreras, Arie Carneiro, Paolo Capogrosso, Gregory Rembeyo, Rafael Sanchez-Salas, François Rozet, Marc Galiano, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

e539 Background: Magnetic resonance imaging (MRI) plays an important role as a treatment-monitoring tool along focal therapy (FT) follow-up. This is the first study to assess MRI ability to correctly predict prostate cancer (PCa) local T-stage in the FT postoperative scenario. We aimed to describe MRI effectiveness in predicting upstaging in two groups of men: 1) men who failure after primary FT and then underwent salvage robotic-assisted radical prostatectomy (S-RARP) and 2) men who underwent RARP as primary treatment (P-RARP). Methods: Prospective data of 2775 men underwent RARP for localized PCa from 2000 to 2016 were reviewed. Twenty-two men underwent S-RARP after FT failure (S-RARP group). Total 2750 underwent RARP as first treatment. Matched-pair 1:2 selection of 44 out of 2750 patients by age defined primary RARP group (P-RARP). All patients underwent MRI immediately before RARP. MRI findings were confronted with final surgical pathology. Primary endpoint: sensitivity, specificity, positive and negative predictive values; positive (+LR) and negative (-LR) likelihood ratio regarding upstaging analysis on S-RARP. Secondary endpoint: same effectiveness analysis on P-RARP. Results: Preoperative MRI failed in predicting upstaging in 80% versus 91.7% of patients (p = 0.515) that presented final pathological status ≥ pT3a on S-RARP and P-RARP groups, respectively. On the other hand, when final pathology described a localized disease T2a-T2c, MRI correctly predicted the final pathological status in 81.8% versus 95.2% of patients (p = 0.27) on S-RARP and P-RARP groups, respectively. Between-group analysis, showed sensitivity and specificity rates of 20% versus 8.33% and 81.8% versus 95.23%, respectively; Positive and negative predictive values of 33.33% versus 50% and 69.23% versus 64.51%, respectively; Positive (+LR) and negative (-LR) likelihood ratio of 1.1 versus 1.74 and 0.98 versus 0.96, respectively. Conclusions: MRI has shown to be a weak diagnostic tool for predicting extra-prostatic disease along FT follow-up. Urologists may be warned about the risk of underdiagnosis and undertreatment in patients presenting failure after FT.
Monitoring oral anti-cancer therapy adherence in cancer patients using web based application guided communication compared with nurse counseling in a community cancer center.
Authors: Milana V. Dolezal, Vivian Leong, Rajesh Behl
Journal: Journal of Clinical Oncology (2017)

88 Background: Smart phone web based applications (apps) can be effective communication tools for monitoring compliance and increasing adherence to oral anti-cancer therapy in the outpatient setting. Methods: Cancer patients age 18-90 treated with various oral anti-cancer therapies were recruited to this prospective, 3 month observational trial at our large community cancer center to determine feasibility of using an app for oral anti-cancer therapy compliance. Enrolled patients are randomized to either Arm 1 App arm and nurse counseling or Arm 2 nurse counseling only. The free apps MyMeds and Medisafe incorporate medication reminders and record doses. Patients complete the validated RAND 36- item quality of life (QOL) questionnaire and a free text feedback. Results: 91 patients were screened between 11/2015 to 9/2016 (45 declined enrollment due to various factors). 46 patients were randomized with 25 to Arm 1 and 21 to Arm 2. Demographics included 10 men (various tumor types but mostly multiple myeloma) and 36 women; 22 with breast cancer. MyMeds app lacked the necessary real-time communication so patients were switched to the MediSafe app which features email alerts. 15 patients have completed the study through Month 3. Four patients on Arm 1 missing their monthly visit or were non-compliant with the app. 23 patients remain active in the study. Differences are a higher QOL score in Arm 1 vs Arm 2 in measured domains of Energy/Fatigue (56% in Arm 1 compared to 44% for Arm 2) and Pain (72% in Arm 1 compared to 58% in Arm 2). Patients randomized to the app found the electronic alerts very helpful. Conclusions: Our limited pilot study demonstrated the potential of smart device apps as effective communication tools for improving patients’ adherence to oral anti-cancer therapy and QOL. Ultimately, convenient ways to monitor patients’ compliance with anti-cancer therapy will impact survival and facilitate provider-patient communication.
Prolonged survival and disease control in the academic phase II trial of regorafenib in GIST: Response based on genotype.
Authors: Suzanne George, Yang Feng, Margaret von Mehren, Edwin Choy, Christopher L. Corless, Jason L. Hornick, James E. Butrynski, Andrew J. Wagner, Sarah Solomon, Jeffrey A. Morgan, Michael C. Heinrich, George D. Demetri
Journal: Journal of Clinical Oncology (2013)

10511 Background: Regorafenib (REGO) is a broad spectrum tyrosine kinase inhibitor with activity against KIT, PDGFR, VEGFR, and FGFR. Phase II and III trials demonstrated significant activity in patients (pts) with advanced GIST following failure of at least imatinib and sunitinib. Pts have continued on the Phase II trial, and we now report longer-term follow-up as related to primary and secondary tumor genotype (KIT, PDGFRA) and SDH expression. Methods: This multicenter Phase II study of RE in GIST enrolled 33 pts with metastatic GIST. REGO was started at a dose of 160mg per day, d1-21 of each 28d cycle. Anatomic restaging was performed every 2 cycles. Clinical benefit rate (CBR) was defined as CR, PR or prolonged SD (&gt;16 wks) per RECIST 1.1. KIT genotype was determined for tumors with adequate tissue available. SDHB staining was performed on a subset of patients whose tumors lacked activating mutations in KIT or PDGFRA. Response, progression free survival (PFS), and overall survival (OS) were determined for the entire cohort and for subsets based on KIT genotype and SDHB immunohistochemical status. Results: Median followup as of 20Jan2013 was 20 mos. Four pts remain on REGO without progression. CBR for the entire cohort was 81%, with 9% PR (n=3). Median PFS for the entire cohort was 13 mos (95%CI 9-18). Median OS was 27 mos (95%CI 16-NR). Tumor primary KIT mutations and associated median PFS are as follows: exon 11(n=19), 13 mos (95%CI 10-21); exon 9(n=3), 6 mos (95%CI 2-NR) (log-rank p-value=0.93). 6 pts had SDH-deficient GIST, 2 of whom experienced PR. Median PFS of pts with SDH-deficient GIST was 12 mos (95%CI 7-NR). Secondary KITmutations in a GIST lesion were identified prior to enrollment in 9 pts : exon 17 (n=7); one each in exon 13 and exon 18. Median PFS for pts with a documented exon 17 mutation was 18 mos (95%CI 6-NR). Conclusions: REGO is an active agent in advanced GIST. Prolonged disease control and OS is demonstrated in heavily pre-treated pts with KIT exon 11-mutant GIST; although with small sample size, there is no statistical significance in outcomes between genotypes. Objective responses were seen in 2 of 6 of pts with SDHB-deficient GIST. Other biomarkers of response and benefit are under active investigation. Clinical trial information: NCT01068769.
Anti-AML activity of a novel beta-catenin antagonist BC2059.
Authors: Kapil N. Bhalla, Warren Fiskus, Sunil Sharma, Stephen Horrigan, Uma Mudunuru, Ruben Reyes, Sunil H. Abhyankar, Joseph McGuirk, Omar Salah Aljitawi, Siddhartha Ganguly
Journal: Journal of Clinical Oncology (2012)

10605 Background: The canonical WNT-β-catenin pathway is essential for self-renewal, growth and survivalof AML stem and progenitor cells. Deregulated WNT signaling inhibits degradation of β-catenin, causing increased nuclear translocation and interaction of β-catenin with the TCF/LEF transcription factor, which up regulates cyclin D1, Myc and survivin expression in AML progenitor cells. BC2059 (β-Cat Pharmaceuticals) is a potent, small molecule, anthraquinone oxime-analog, which inhibits WNT-β catenin pathway by promoting the degradation and attenuation of β-catenin levels. Methods: We determined the in vitro anti-AML activity of BC2059 (BC) (250 to 1000 nM) against cultured and primary human AML blast progenitors, as well as evaluated the in vivo anti-AML efficacy of BC in NOD-SCID and NOD-SCID-IL2γ receptor deficient (NSG) mice. Results: BC induced cell cycle G1 phase accumulation and apoptosis (40%) of the cultured OCI-AML3, HL-60 and HEL92.1.7 (HEL) AML cells. BC dose-dependently also induced apoptosis of primary AML versus normal progenitors. Treatment with BC resulted in proteasomal degradation and decline in the nuclear levels of β-catenin, which led to decreased activity of the LEF1/TCF4 transcription factor highlighted by reduced TOP-FLASH luciferase activity in the AML cells. This was associated with reduced protein levels of cyclin D1, MYC and survivin. Co-treatment with BC and the histone deacetylase inhibitor panobinostat (PS) (10 to 20 nM) synergistically induced apoptosis of cultured and primary AML blasts. Following tail vein infusion and establishment of AML by OCI-AML3 or HEL cells in NOD-SCID mice, treatment with BC (5, 10 or 15 mg/kg b.i.w, IV) for three weeks demonstrated improved survival, as compared to the control mice (p &lt;0. 001). Survival was further improved upon co-treatment with BC and PS (5 mg/kg IP, MWF). BC treatment (5 or 10 mg/kg IV) also dramatically improved survival of NSG mice with established human AML following tail-vein injection of primary AML blasts expressing FLT3 ITD. Mice did not experience any toxicity or weight loss. Conclusions: These findings highlight the notable pre-clinical in vitro and in vivo activity and warrant further development and in vivo testing of BC against human AML.
Complementary Transplantation with Haploidentical Stem Cells and Unrelated Cord Blood for Leukemia and Thalassemia
Authors: Chunfu Li, Yuelin He, Xuedong Wu, Xiaoqin Feng, Jianyun Liao, Zhiyong Peng, Fuyu Pei, Huaying Liu, Wing Leung
Journal: Blood (2016)
Sorafenib for hepatocellular carcinoma managed by non-oncologists: Impact on drug exposure and survival.
Authors: David Edward Kaplan, Tamar H. Taddei, Rajni Mehta, Kathryn D'Addeo, Ayse Aytaman, Kristel Hunt, Rena Fox, Michelle Baytarian, Adriana Valdarrama
Journal: Journal of Clinical Oncology (2017)

404 Background: Few data exist on practitioner type, initial dosing regimens, and survival for patients with HCC treated with sorafenib in a real-world setting. Methods: HCC patients exposed to sorafenib were identified from the VA CDW using ICD9 codes and pharmacy records. ICD9 codes, CPT codes, AUDIT-C surveys and laboratory tests were utilized to characterize underlying liver disease, calculate Child-Turcotte-Pugh (CTP) and MELD scores. Two abstractors achieved 100% chart verification of tumor number, size, macrovascular invasion and extrahepatic spread on imaging immediately proximate to sorafenib initiation to quantify Barcelona Clinic Liver Cancer (BCLC) stage and to determine the provider specialty initiating sorafenib. Results: 4838 patients prescribed sorafenib for HCC between 2008 and 2015 were included in this interim analysis. Median age was 62; 98.8% were male, 61.8% white/26.0% black; 44% EtOH/54% HCV/5% HBV/29% other; CTP A 58%/B 37%/C 4%; median MELD 11; 96% ECOG &lt; 2; and pre-sorafenib BCLC 0-0%/A-5%/B-37%/C-49%/D-8%. Sorafenib was prescribed by oncologists (92%), GI/hepatologists (7.6%) and other practitioners (0.4%). Patients treated by GI/hepatologists rather than oncologists had similar BCLC distributions, similar treatment durations (median 90 vs. 90 days), received more pills (median 360 vs. 240, p = 0.0016), but had identical survival (median 234 vs. 239 days, p = NS). Hepatologists were more likely than oncologists to uptitrate during the first month (25% vs. 14%, p &lt; 0.0001) whereas oncologists were more likely to uptitrate later (8.9% vs. 3.8%, p &lt; 0.001). Oncologists were more likely to stop sorafenib due to progression (29 vs. 18%), while hepatologists were more likely to continue sorafenib until death (28 v. 18%) with no difference in discontinuation for AEs or functional decline. In multivariable models including CTP, BCLC, and ECOG PS, prescriber specialty had no impact on OS. Conclusions: In the VA, 8% of sorafenib is prescribed by GI/hepatologists. Despite modest differences in prescribing practices, hepatologists and oncologists achieve similar sorafenib exposure and overall median survival rates of 7.8 months in real-world practices.
Approach to Serial Liquid Biopsy: Enrichment of circulating tumor cells (CTC) in breast cancer patients for cancer panel analysis.
Authors: Myoung Shin Kim, Sung Ho Choi, Ga-Yun Kim, Sei-Hyun Ahn, Byung Ho Sohn, Jong Won Lee, Jong Han Yu, Nak-Jung Kwon, Woo Chung Lee, Kap-Seok Yang, Beom Seok Ko, Hee Jeong Kim, Jisun Kim, Cham Han Lee, Soo Jeong Lee, Mi So Choi, Dong-Hyoung Lee, Du Yeol Han, Jinseon Lee, Byung Hee Jeon
Journal: Journal of Clinical Oncology (2015)

e22029 Background: Although many effective therapies improve the survival rate in breast cancer patients, a significant number of patients could not avoid recurrence and metastasis. Liquid biopsy using circulating tumor cells (CTC) is a non-invasive method to obtain tumor cells, and can be a substitute for tumor tissue biopsy. This new approach may provide molecular profiling of tumor, which can be useful for determination of personalized cancer therapy according to the molecular profiling of individual patient during the process of tumor diagnosis, recurrence, and metastasis. Methods: Blood samples (10 ml) were collected, and processed through Cytogen protocol to enrich CTCs. In brief, whole blood was incubated with specific antibodies against RBC and WBC, and spun down followed passing through micro fabricated porous filter (CytoGen). Enriched CTCs were divided into two parts, one for counting and one for molecular analysis. For CTC counting, cells were stained for EpCAM, CD45, and DAPI. DNAs were extracted, amplified and analyzed using Ion AmpliSeq Cancer Hot Spot Panel V2 (Life Technologies, NY) and PGM 200 Seq 316 V2 chip (Life Technologies). MCF7 cell line was included as a positive control. Results: The average purity of enriched CTCs was 17.7% (0~100%), and the average amount of amplified DNA was 28.7 μg (4.8~37.8 μg). Reference location coverages were above 98.8% (98.8~99.4%) in all 11 samples, and total 30 COSMIC (catalogue of somatic mutation in cancer) were detected in 10 cases. Two COSMIC (COSM 14253, COSM 33733) were detected in a patient without EpCAM positive cells, which suggesting EpCAM negative CTCs. Highest number of mutations in one patient is 7, most abundant mutations were STK11 (3 cases, COSM21378, COSM25851, COSM21360), IDH2 (3 cases, COSM33733), TP53 (2 cases, COSM 43753, COSM 44547), PTEN (2 cases, COSM 23626, COSM 4994, COSM 4990). PTEN showed high frequency of mutations in different regions in same gene, 3 different mutations in 2 patients. Conclusions: We provide a new approach to obtain enough amounts of CTCs, which can be used for molecular analysis. And this new approach can be an applicable tool of serial liquid biopsy in breast cancer treatment.
ZDHHC11 and ZDHHC11B are critical novel components of the oncogenic MYC-miR-150-MYB network in Burkitt lymphoma
Authors: A Dzikiewicz-Krawczyk, K Kok, I Slezak-Prochazka, J-L Robertus, J Bruining, M M Tayari, B Rutgers, D de Jong, J Koerts, A Seitz, J Li, B Tillema, J E Guikema, I M Nolte, A Diepstra, L Visser, J Kluiver, A van den Berg
Journal: Leukemia (2017)
Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample
Authors: Alfredo Ramos-Miguel, Jesús A. García-Sevilla, Alasdair M. Barr, Thomas A. Bayer, Peter Falkai, Sue E. Leurgans, Julie A. Schneider, David A. Bennett, William G. Honer, M. Julia García-Fuster
Journal: Molecular Neurodegeneration (2017)

FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigated the possible association of FADD forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample.FADD forms were quantified by western blot analysis in dorsolateral prefrontal cortex (DLPFC) samples from a large cohort of participants in a community-based aging study (Memory and Aging Project, MAP), experiencing no-(NCI, n = 51) or mild-(MCI, n = 42) cognitive impairment, or dementia (n = 57).Cortical FADD was lower in subjects with dementia and lower FADD was associated with a greater load of amyloid-β pathology, fewer presynaptic terminal markers, poorer cognitive function and increased odds of dementia. Together with the observations of FADD redistribution into tangles and dystrophic neurites within plaques in Alzheimer's disease brains, and its reduction in APP23 mouse cortex, the results suggest this multifunctional protein might participate in the mechanisms linking amyloid and tau pathologies during the course of the illness.The present data suggests FADD as a putative biomarker for pathological processes associated with the course of clinical dementia.
Impact of an oncology pharmacist attendance at a multidisciplinary lung clinic.
Authors: Sue Kirsa, Clare Walter, Carol Rice, Dan Mellor, Linda R. Mileshkin, Mary Duffy, David Ball
Journal: Journal of Clinical Oncology (2012)

e16538 Background: Medication misadventure contributes to unplanned hospital admissions in patients with cancer. Often, numerous medications are added to existing ones and general practitioners (GP) may lack experience in managing problems involving cancer related medication. A survey exploring the unmet needs of our lung cancer outpatients highlighted the need for more medication information. Inpatient clinical pharmacy services are known to impact on patient care and morbidity. This project aimed to evaluate the effects of extending this service to outpatients. Methods: An oncology pharmacist joined the lung cancer clinic team for 6 months. Consented patients completed assessments of medication adherence (using Morisky tool) and satisfaction with medicines information at baseline and within 30 days of review. Post pharmacist review, a medication list and plan (detailing recommendations/interventions) were provided to patients and community and hospital healthcare providers. Uptake of recommendations was evaluated 7 days after review. Assessment results (pre and post review) were analyzed using the matched pairs Wilcoxon test. Interventions were categorized and graded according to risk avoided. Unplanned admissions and clinic attendance rates were compared to the previous year and analyzed using the Rate Ratio Test assuming Poisson counts.GPs opinion of the service was evaluated via survey. Ethics approval was obtained from HREC. The project was supported by an educational grant from Roche Pharmaceuticals. Results: 48 patients were recruited. Medication adherence (p=0.007) and patient satisfaction (p&lt;0.001) were significantly improved. 154 pharmacist interventions were made: 4.5% extreme risk and 43.5% high risk. Ratios of unplanned admissions and clinic attendances decreased; 0.3 to 0.26 (p= 0.265) and 3.32 to 2.98 (p=0.004) respectively. 31 of 48 general practitioners (GPs) completed the survey, 74% found the service useful. Conclusions: Adding a pharmacist to the outpatient lung team led to significant improvements in patient medication adherence. Both patients and GPs were highly satisfied with the service. Medication misadventure, unplanned admissions and clinic attendances were reduced.
The role of age on dose-limiting toxicities (DLTs) in phase I dose-escalation trials.
Authors: Anita Schwandt, Pamela Jo Harris, Sally Hunsberger, Amélie Deleporte, Gary L Smith, Diana Vulih, Barry Douglas Anderson, S. Percy Ivy
Journal: Journal of Clinical Oncology (2013)

9517 Background: Elderly oncology patients are not enrolled on phase I trials in proportion to the prevalence of cancer in the age-matched population. They are excluded from these trials based on the perception that these patients will have an increased number of and more severe toxicities, per dose level, than younger patients. We hypothesize that if other patient characteristics are accounted for, then age will not be an independent predictor of dose limiting toxicities (DLTs). Methods: We retrospectively reviewed data from 162 single- agent dose-escalation phase I clinical trials performed at the Cancer Therapy Evaluation Program/National Cancer Institute. Several baseline patient characteristics, including age, were collected. Patient dose levels were described as %MTD and an analysis of age, dose and DLTs was performed. Results: Data was obtained from 5,401 patients who were divided into five age groups, with 556 pts &lt; 40 years old, 2,438 between 40-59, 1,481 between 60-69, 836 between 70-79 and 90 pts &gt; 79. Proportion of DLT occurring in each age group and %MTD are described in the Table. Conclusions: This analysis of DLTs occurring in nearly 1000 patients over 70 years of age on phase I dose-escalation trials is the largest reported. A logistic regression model will be performed to determine if age, by itself, predicts for DLTs and what concurrent patient characteristics contribute to their occurrence. [Table: see text]
Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset
Authors: Woonyoung Choi, Andrea Ochoa, David J. McConkey, Mattias Aine, Mattias Höglund, William Y. Kim, Francisco X. Real, Anne E. Kiltie, Ian Milsom, Lars Dyrskjøt, Seth P. Lerner
Journal: European Urology (2017)