tbuckley/cabot-search huggingface dataset:
PIER trial: Neoadjuvant therapy with panitumumab (P) and mFOLFOX-6 in an enriched population of patients with T3 rectal adenocarcinoma of the middle third with clear mesorectal fascia.
Authors: Carlos Fernandez-Martos, Jorge Aparicio, Juan Ayuso, Jaume Capdevila, Javier Gallego, Ferran Losa, Monique Maas, Joan Maurel, Carles Pericay, Nuria Rodriguez Salas, Maria Jose Safont, Maria Tobeña, Manuel Valladares, Ruth Vera
Journal: Journal of Clinical Oncology (2018)

TPS875 Background: Retrospective data suggest that patients with advanced colorectal carcinoma wild-type (WT) for RAS, BRAF or Pi3K achieve increased response rates from anti-EGFR therapy as compared with mutated tumors. Neoadjuvant chemotherapy with oxaliplatin/fluoropyrimidine combination has shown to induce encouraging pathological complete response (pCR) in clinically staged T3 rectal cancer tumours (Schragg et al, JCO 2014 and Fernandez-Martos et al, The Oncologist 2014). We hypothesize this efficacy could be improved in a selected population (quadruple WT [4WT]) combining chemotherapy and anti-EGFR therapy. The objective is to assess the feasibility, efficacy and safety of neoadjuvant therapy with mFOLFOX-6 + P in rectal adenocarcinoma patients of intermediate risk and 4WT. Methods: PIER is a prospective, phase II, single-arm, multicentre, open-label clinical trial (NCT03000374). Key eligibility criteria include patients &lt; 75 years with rectal adenocarcinoma in the middle third , clear mesorectal fascia, candidate for R0 resection with sphincter preservation surgery and absence of mutations in KRAS (exon 2 [codons 12/13], exon 3 [codons 59/61] and exon 4 [codon 117/146]), NRAS ( exon 2 [codons 12/13], exon 3 [codons 59/61] and exon 4 [codons 117/146]), BRAF (exon 15 [codon 600]) and PI3KCA in exons 9 and 20. All pre- and post-treatment MRI scans are centrally reviewed. Treatment: 6 induction cycles of mFOLFOX6 + P every 14 days. After the last cycle, a CT-scan, MRI and rectal endoscopy will be performed and patients will undergo TME surgery within 4 weeks +/- 1 week after the last dose. In case of progression patients will receive standard preoperative chemoradiation. The primary end point is pCR; key secondary end points include R0 resection rate, and clinical complete response. Statistical design: 42 evaluable patients (assuming a P0 of 16% and a P1 35%, with 0.1 alfa and 0.1 beta); 2-stage Simon’s optimal design. Enrolment in PIER is ongoing. Clinical trial information: NCT03000374.
Abstract 18800: Nationwide Analysis on the Impact of Drug and Alcohol Abuse on Inpatient Outcomes of Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention
Authors: Saman Setareh-Shenas, Di Pan, Sung Lee, Nader Ishak Gabra, Felix Thomas, Eyal Herzog
Journal: Circulation (2017)

Background: Drug and alcohol abuse are highly prevalent in the U.S. and associated with significant number of hospital admissions and emergency department visits. The aim of this study is to evalua...
Use of aprepitant in uncontrolled delayed nausea and vomiting associated with preparative regimens in stem cell transplantation: A retrospective analysis.
Authors: Linh Tran, Samit Patel, Eun-Jeong Kim, Dat Thanh Ngo, Jonathan Eliot Benjamin
Journal: Journal of Clinical Oncology (2014)

9613 Background: Aprepitant, a well tolerated antiemetic, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy in combination with other antiemetic agents. Aprepitant has not been studied for the treatment of established or refractory nausea and vomiting. We report the experience of an academic medical center in the treatment of uncontrolled delayed nausea and vomiting in the stem cell transplant (SCT) population. Methods: Between 2008-2013, 110 patients were identified retrospectively to have been treated with a 3-day course of oral aprepitant for uncontrolled delayed nausea and/or vomiting after receiving preparative regimen for SCT. Primary outcome was to determine the rate of complete response (CRNV, defined as no vomiting with grade 0-1 nausea, using CTCAE 4.02 at 5 days) and partial response (PRNV, defined as a reduction in grade of nausea and vomiting without achieving CR at 5 days). Further analysis to assess CR, PR and time to control (reduction in the grade) for nausea (CRN, defined as grade 0-1 nausea at day 5; PRN, defined as a reduction in grade of nausea without achieving CR at day 5) and vomiting (CRV, defined as no vomiting at day 5; PRV, defined as a reduction in grade of vomiting without achieving CR at day 5) was also performed. Results: Of 110 patients, 37% were female, average age was 46.9 years (range, 21-75 years), 46.4% received alloSCT (25.5% FTBI), 52.7% autoSCT, and 0.9% syngeneic SCT. After receiving aprepitant, CRNV was achieved by 23.6%, with 50% CRN and 51.8% CRV. 14.5% achieved a PRNV with 24.5% PRN and 1.8% PRV. Median time to control nausea was 2 days (range, 1-5 days) and vomiting was 1 day (range, 1-2 days). All but 2 patients received ondansetron and dexamethasone prior to aprepitant administration. Of 21 patients who received at least one agent from a new class of antiemetic after administration of aprepitant, 6 (29%) of those patients achieved CRNV and 2 (10%) achieved PRNV. Conclusions: The use of aprepitant shows efficacy in the treatment of uncontrolled delayed nausea and vomiting associated with preparative regimens in SCT.
A fluorescence based GEF exchange assay in a high throughput screen format
Authors: Li Cheng, Ashley S. Davis, Kim M. Middleton
Journal: Cancer Research (2005)

5912  The Ras superfamily of small GTPases serves as binary switches cycling between GDP-bound inactive and GTP-bound active state, which process is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine nucleotide dissociation inhibitors (GDIs). GEFs catalyze the exchange of GDP for GTP to generate the active state of small GTPases in response to extracellular signals. The GEF family is composed of more than 70 members in human, constituting the largest family that regulates small GTPases. Many GEF proteins have been identified as oncogenes and more and more GEFs have been found involved in human disease such as cancer, thus attracting more attentions for potential therapies in cancer treatment. Recently developed fluorescence analogs of guanine nucleotides have greatly improved the technical ability to define the real time exchange reaction of GEFs, including kinetic and thermodynamic properties, eliminating the need for traditional radioactive labeling method. This fluorescence based assay takes advantage of the spectroscopic difference between bound and unbound fluorescent analogs to guanine nucleotides and thus is able to monitor the states of small GTPases. One of most widely used fluorescent analogs is mant (N-methylanthraniloyl) fluorophores. Once bound to GTPases, this fluorophore emission intensity increases dramatically. Therefore, the enhancement of fluorescent intensity will reflect the activities of known or unknown GEF proteins. Since conventional fluorescence based assays are mostly performed in a cuvette (2 ml volume) and not suitable for high throughput screen, we developed a mant fluorophore based GEF assay suitable for both 96-well and 384-well format. For example, human Dbs protein exhibited exchange activity towards Cdc42, RhoA in both 96-well and 384-well format, with similar kinetic parameters as 2 ml volume reaction. This assay can be applied to multiple research purposes such as characterizing the known or unknown GEFs and discovering GEF inhibitors in a high throughput screen format.
Abstract 15395: Dose Coronary Artery Calcification Morphology Predict Plaque Rupture and Successful Coronary Revascularization in ST-Elevation Myocardial Infarction?: An Optical Coherence Tomography Study
Authors: Shunsuke Miyauchi, Masaya Kato, Keigo Dote, Shota Sasaki, Noboru Oda, Eisuke Kagawa, Michiaki Nagai
Journal: Circulation (2017)

Introduction: Recent pathological and computed tomography studies have revealed that vulnerable plaques exhibit a high frequency of spotty calcification. On the other hand, optical coherence tomogr...
Abstract 13609: A Novel Wearable Cardioverter Defibrillator Algorithm With Reduced False Alarm Rate
Authors: Joseph Sullivan, Kelley Branch, Laura Gustavson, Angela Stewart, Pamela Breske, Ron Rowbotham, Jaeho Kim, Jeanne Poole
Journal: Circulation (2017)

Background: Wearable Cardioverter Defibrillators (WCDs) provide temporary protection from ventricular arrhythmias, but commonly experience false arrhythmia alarms. For the only commercially availab...
Racial differences and pancreatic cancer: A 5-year retrospective review of stage at diagnosis, insurance status, and choice for hospice care versus aggressive treatment at an inner city university program.
Authors: Khurram Bilal Tariq
Journal: Journal of Clinical Oncology (2014)

e15230 Background: Pancreatic cancer is the tenth most common malignancy and fourth leading cause of cancer related deaths in the US. To our knowledge studies have looked into hospice in terminal cancer patients in general, but not in pancreatic cancer in specific. The present study looks into the ethnic differences in stage and insurance status of pancreatic cancer patients and their choice for hospice service versus aggressive therapies. Methods: A retrospective chart review of all pancreatic cancer patients in Tumor Registry at UF Hospital, Jacksonville from Jan 2000 to Dec 2005. Results: We found82 patients, with mean age at diagnosis = 66.4 years. Male: female ratio =1.1:1.0. African-Americans (65%) and Caucasians (35%). 41% patients were smokers. 17% patients had diabetes at the time of diagnosis. Most common presentation: Obstructive jaundice (43%), fatigue, abdominal and back pain combined= 40%. 60% presented at Stage 4, 17% Stage 3, 16% stage 2 and 7% at Stage 1. 65% had unresectable disease at the time of diagnosis. 57% patients had Charlson Co-morbidity index(CMI) of 0-1. 3% had CMI of greater than one. 84% patients had ECOG Performance status of 0-1 and 16% had ECOG status greater than 1. 52% patients elected hospice care over aggressive chemoradiation or surgery including 37 (60%) African Americans and 7 (24%) Caucasian patients. 33 (40.2%) had no medical insurance including 24 (72.2%) blacks and 9(27.27%) white males. On analysis African Americans were more likely to elect for hospice over aggressive therapy compared to Caucasians (p<0.008, OR- 5.6, 95% CI- 1.9-16.1). Using a multivariate probability model; higher age (p-0.02, OR-1.011, 95% CI – 1.11-1.135), Stage at presentation (p<0.001, OR-63, 95% CI- 9.2-400) and lower socioeconomic status (p<0.002, OR- 9.3, 95% CI- 2.2-39) were associated with choice of hospice care over aggressive therapy. Conclusions: African Americans are more likely to present with no medical insurance, higher stage at presentation and elect for hospice care over more aggressive therapy compared to white patients.
The relationship between perceived severity of stressful life events and preoperative anxiety in women undergoing surgery for suspected endometrial malignancy.
Authors: Elizabeth Lauren Kacel, Linda S Morgan, Deidre B Pereira
Journal: Journal of Clinical Oncology (2014)

e20563 Background: Anxiety is a prominent symptom in the cancer experience. Researchers have examined the relationship between anxiety and life stress, highlighting coping style, social support, or locus of control as the underlying mechanism. Many of these studies focused on the relationship between total number of events experienced by an individual and an additional psychosocial factor to predict anxiety. Few studies have investigated how individuals’ average severity rating across stressful life events in a given period of time is related to anxiety, particularly in the context of a potential cancer diagnosis. The current study examined the relationship between average perceived severity of stressful life events and preoperative anxiety in women undergoing surgery for suspected endometrial malignancy. Methods: Participants were 98 women (M age [years] = 61, SD = 9.06) who underwent surgical resection of suspected endometrial cancer. Stressful life events were captured by a modified version of the Life Experiences Survey (Sarason et al, 1978) which asks respondents to select stressful life events that have occurred in the last six months and assign a severity rating to each event. Participants' perceptions of stressful life events were calculated by creating an average severity rating across total number of events. Preoperative anxiety was assessed by the Structured Interview Guide for the Hamilton Anxiety and Depression Scales (Williams, 1988). Results: Linear regression analyses revealed that greater average perceived severity of stressful life events in the six months prior to surgery was associated with greater preoperative anxiety (β = .21, p = .04). Conclusions: These findings suggest that regardless of the total number of negative life events women experience in the six months prior to surgery for suspected endometrial cancer, the way in which they perceive the severity of these stressful events may be a risk factor for increased preoperative anxiety. Future research should further explore how individual differences in responses to different types of life stress may impact preoperative anxiety in women with suspected endometrial cancer.
Quality of life of patients with locally advanced head and neck cancer (LAHNC) treated with docetaxel/cisplatin/5-fluorouracil (TPF) followed by cisplatin-containing chemoradiotherapy (CRT).
Authors: Chantal Driessen, Hans Groenewoud, J. P. De Boer, Hans Gelderblom, Margot Et Tesselaar, Winette T.A. Van Der Graaf, J. H. Kaanders, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2014)

6053 Background: The CONDOR study, a randomized phase II trial, investigated feasibility of TPF followed by conventional CRT with cisplatin 100 mg/m2 on days 1,22,43 (cis100+RT) versus CRT with accelerated RT with weekly cisplatin 40 mg/m2(cis40+ART) in LAHNC pts, PS 0-1, age 18-65. Here we report the analysis of health-related quality-of-life (HRQOL) and symptoms. Methods: HRQOL was assessed at baseline (BL), after 2 TPF, before start and at the end of CRT, and 1, 4, 8, and 12 months after completion of CRT using the EORTC QLQ-C30 and QLQ-H&N35. A change of >10 points on mean scores was considered clinically significant. BL scores were compared to EORTC reference values of LAHNC pts. Results: 62 pts started with TPF; 56 pts were randomized to cis100+RT (n=27) and cis40+ART (n=29). The study was terminated prematurely due to toxicity and inability to get the full dose of cisplatin: 22% (cis100+RT) and 41% (cis40+ART) of the pts could receive the planned cisplatin during CRT, respectively. The planned radiotherapy was given to 96% of the pts. Despite high toxicity rates, especially mucositis in cis40+ART, and not full dosed cisplatin 2-years overall and progression free survival were 72% and 65%, respectively. Compliance with the QOL questionnaires was 94% (59/62) at BL, and dropped to 61% (30/49) at 12 months. Mean global health score (GHS) at BL was 75.3 (SD 19.7) compared to the reference value of 63.1 (SD 22.4). GHS decreased after TPF, even more during CRT to 46.8 (SD 19.7) in both arms equally, but restored to BL level after approximately 12 months. Pain and swallowing dysfunction improved significantly during TPF, but deteriorated below BL levels during CRT, more in cis40+ART than in cis100+RT (p<0.05). Speech ameliorated not significantly during TPF, worsened during CRT below BL level, more in cis40+ART (p<0.05). All symptoms restored to BL within a year in both arms. Conclusions: The BL GHS appeared to be high in this population reflecting the good condition of these pts. After TPF, cis40+ART had a more negative impact on symptoms than cis100+RT, probably due to the ART. GHS and symptoms restored to BL levels within one year in both arms. Clinical trial information: NCT00774319.
LIHNCS trial: Lugol's iodine in head and neck cancer surgery.
Authors: Janet A Dunn, Raghav Kulkarni, David Gouldesbrough, Hisham Mehanna, Jeremy McMahon McMahon, Richard Shaw, James Anthony McCaul
Journal: Journal of Clinical Oncology (2012)

e16042 Background: Residual dysplasia at margins of mucosal tumour resection is a cause of disease failure. While risk of transformation of dysplasia is difficult to assess, malignant cells within a field of dysplastic change indicate high transformation potential of this dysplastic field. Lugol's iodine assists in the assessment of surgical margins at tumour resection to ensure removal of margin dysplasia where present and resectable using the surrogate biomarker of glycogen storage. This multicenter RCT assesses efficacy of this technique in head and neck cancer surgery and is recruiting over the next two years. Methods: Patients undergoing primary surgery for oral cavity and oropharynx squamous carcinoma are randomised to gold standard surgical resection or to resection guided by Lugol's iodine application. Mucosal surfaces are irrigated with saline, carbocisteine solution applied to remove surface mucus and then irrigated with Lugol's iodine solution. Where present, adjacent visible surface dyplasia is resected with the tumour specimen. Histopathologists are blinded to the technique used. Histopathology is repeated centrally for quality control. Margin status is assessed for involved, close and clear for carcinoma and for presence of dysplasia at margins. Quality of life data are collected at baseline, six weeks, six, twelve and 24 months. Results: Our cohort study of 100 cases showed a reduction in margin dyplasia from 32% to 4% p&lt;0.001. A feasibility pilot trial recruited 98 patients with 100% consent and data collection rates. Recruitment is progressing on schedule and at time of writing two sites are open. Forty six patients have consented in four sites and are included in the trial to date. A further 12 sites are in the trial set up process. We will report our interim data regarding sites open, screened and consented rates and outcomes so far. Conclusions: To date recruitment is on schedule. We have demonstrated the acceptability of the trial and techniques therein to both patients and surgeons. This is a promising technique which may modify head and neck cancer surgery by targeting dysplasia for inclusion at time of resection of primary cancer. Thus locoregional recurrence may be reduced in a proportion of patients undergoing curative surgical resection.
Everolimus in bevacizumab-refractory metastatic renal cell carcinoma patients.
Authors: Anton Snegovoy, Liudmila V. Manzyuk, Sergey Varlamov, Sufia Safina, Ludmila Gurina, Ilya Tsimafeyeu
Journal: Journal of Clinical Oncology (2014)

e15603 Background: Everolimus (EVE) has shown clinical activity in metastatic renal cell carcinoma (mRCC) patients who had received sunitinib or sorafenib in RECORD-1 study. Efficacy data on EVE in patients with disease progression (PD) on bevacizumab is limited. Methods: Patients with clear cell mRCC who progressed on a bevacizumab ± interferon received EVE (10 mg/day) until PD (RECIST 1.1). A Simon MiniMax 2-stage design determined sample size (stage I: 23 patients (≥13 patients with no evidence of PD for 2 months needed to proceed to stage II; stage II: 14 patients; If in ≥ 24 patients were no evidence of PD for 2 months, treatment was considered effective). Secondary endpoints were response rate, safety, median progression-free survival (PFS) and overall survival (OS). Results: 23 patients were enrolled on the first stage of study. 19 (83%) patients had no PD and additional 14 patients were included on the second stage. From 12/2011 to 10/2013, totally 37 patients (28M, 9F) were enrolled. Median age was 60.5 years (range, 41-66), 11% had ECOG >2, and MSKCC favorable/intermediate risk was 38/62%. 5 (14%) patients had a confirmed partial response and 26 (70%) patients had a stable disease. In 31 (84%) patients no PD was found for 2 months. Median PFS was 11.5 months (95% CI, 8.8-14.2). Median OS was not reached. No grade 3 or 4 treatment-related toxicities were observed. The most common grade 2 adverse events were fatigue (19%) and pneumonitis (8%). Conclusions: EVE demonstrated efficacy in bevacizumab-refractory mRCC patients. Clinical trial information: CRAD001LRU02T.
Molecular profiling of thyroid cancers.
Authors: Alexander Stojadinovic, Sherri Z. Millis, Rebecca Feldman, Itzhak Avital
Journal: Journal of Clinical Oncology (2014)

e17008 Background: Generally considered low-risk tumors, thyroid cancers that progress become difficult to treat. Recent success with targeted agents prompted us to investigate whether a multiplatform profiling approach can identify new treatment options for various thyroid cancers. Methods: 169 thyroid cancers [including follicular (FTC), medullary (MTC), papillary (PTC), Hûrthle cell, anaplastic (ATC), poorly differentiated (PDTC), carcinoma and metastatic subtypes] were evaluated. Theranostic biomarkers were evaluated by a combination of sequencing (Sanger, NGS), protein expression (IHC) and gene amplification (ISH). Results: IHC analysis in 150 patients revealed the potential utility of several agents: anti-hormonal therapies, cMET inhibitors, nab-paclitaxel, platinums, mTOR inhibitors, taxanes and gemcitabine, based on overexpression of hormone receptors (AR 5%, ER 12% and PR 29%), cMET (32%) and SPARC (39%), and low expression of ERCC1(73%), PTEN (39%), TUBB3 (57%) and RRM1 (85%). Amplification of cMET and EGFR were observed in 4% (2/51) and 3% (2/73) of patients, respectively. Sanger sequencing was performed in 90 patients and NGS in 43 patients. Mutations in BRAF were most abundant (39% or 55/141) (54/55 were V600E), and were most frequently observed in PTC (as expected; 43/66), but also observed in FTC (n=2/10), follicular variants of PTC (n=2/5), ATC (n=1/15), PDTC (n=1/6) and thyroid carcinoma, NOS (n=6/11). RAS family mutations occurred in 9% (15/171), across subtypes, and can be targeted with MEK inhibitors such as selumetinib. Additional variants were detected in the following genes: TP53 (16%, 7/43), PTEN/PIK3CA (5%, 5/109), AKT and cMET (5%, 2/43), VHL (3%, 1/38) and ATM, EGFR, RB1, APC and JAK3 (2%, 1/43), which all represent additional opportunities for targeted therapy intervention. Conclusions: This study shows that the combination of protein and sequencing-based profiling can identify additional treatment options for thyroid cancer, including traditional chemotherapies and novel targeted agents. Recent data demonstrating dramatic clinical response to vemurafenib in ATC and the occurrence of BRAF V600E in our series, demonstrates the potential widespread application of vemurafenib and other BRAF inhibitors for thyroid cancer.
A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy
Authors: Hong Cheng, Xue-Yan Jiang, Rong-Rong Zheng, Sheng-Jia Zuo, Lin-Ping Zhao, Gui-Ling Fan, Bo-Ru Xie, Xi-Yong Yu, Shi-Ying Li, Xian-Zheng Zhang
Journal: Biomaterials (2019)
RNA Sequencing-Based Measurement of Fusion-Transcript for Minimal Residual Disease (MRD) Monitoring in Core-Binding Factor Acute Myeloid Leukemia (CBF-AML)
Authors: Taehyung Kim, Joon Ho Moon, Jae-Sook Ahn, Marc S. Tyndel, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Seunghyun Choi, Ja-yeon Lee, Yoojin Lee, Sang Kyun Sohn, Zhaolei Zhang, Hyeoung-Joon Kim, Dennis Dong Hwan Kim
Journal: Blood (2018)