tbuckley/cabot-search huggingface dataset:
Exome sequencing of metastatic medullary thyroid cancer.
Authors: Deirdre Kelly, Sudipto Das, Bruce Moran, Kathleen Han, Geoffrey Alan Watson, Emily Harrold, Jack Gleeson, Connor Gerard O'Leary, Lisa Mary Prior, Killian Nugent, Marvin Chang Jui Lim, Niall Mulligan, Desmond N. Carney, John McCaffrey, Catherine Margaret Kelly
Journal: Journal of Clinical Oncology (2016)

e23000 Background: Exome sequencing was undertaken on a patient with a novel presentation of metastatic medullary thyroid cancer to bone marrow presenting with disseminated intravascular coagulation. Methods: Sequencing libraries were generated using DNA from tumor, adjacent tissue and bone marrow .Exome capture encompassed all known exonic regions as well as 3’ and 5—UTR. Paired-end 125 bp sequence data from an Illumina HiSeq 2000 (v4) were aligned using the BWA-mem algorithm, with duplicates removed by Picard Tools. Alignment files were realigned, recalibrated and genotyped by the HaplotypeCaller algorithm in GATK v3.3. Germline, loss-of-heterozygosity and somatic mutations were called per sample using VarScan2, with MuTect used to call further somatic mutations. Somatic mutations were defined as being MAF < 0.05. Copy-number variation was identified using the CopywriteR package in the R statistical environment. Visualisation was conducted using Circos under the OmicCircos R package. Results: A non-synonymous missense mutation in CDKN2C was found exclusive to the primary tumour located on chromosome 1:51439685 in exon 4. This mutation has not previously been identified in patients with metastatic medullary thyroid carcinoma. Copy number loss was evident on ten chromosomes, with full chromosome loss in five instances. This manifests as loss of heterozygosity which was identified in 6 of 46 genes known to be invloved in MTC; ALK, ATM, CSF1R, GNAS, SMARCB1 and NOTCH1. In the bone marrow there was evidence of a chromothripsis-like event .This phenomenon has not previously been recorded in medullary thyroid cancer. Conclusions: Molecular analysis provides increased insight into the pathogenesis and potential therapeutic targets of metastatic medullary thyroid cancer. Mutations of CDKN2C have the potential to provide a therapeutic target and require further study. Given the increasing evidence suggesting the involvement of copy number variation, and chromothripsis in disease progression and pathogenesis, further work in this area would allow improved understanding of the clinical applicability of theses events.
Nanogel Tectonics for Tissue Engineering: Protein Delivery Systems with Nanogel Chaperones
Authors: Yoshihide Hashimoto, Sada‐atsu Mukai, Yoshihiro Sasaki, Kazunari Akiyoshi
Journal: Advanced Healthcare Materials (2018)

Abstract Amphiphilic polysaccharide self‐assembled (SA) nanogels are promising protein carriers owing to their chaperone‐like activity that allows them to nanoencapsulate proteins within their polymer networks. The chaperoning function is an important concept that has led to breakthroughs in the development of effective protein drug delivery systems by stabilizing formulations and controlling the quality of unstable proteins. Recently, nanogel‐tectonic materials that integrate SA nanogels as building blocks have been designed as new hydrogel biomaterials. This article describes recent progress and applications of SA nanogel tectonic materials as protein delivery systems for tissue engineering.
Abstract 14763: Implications of Coronary Artery Calcium on Risk Stratification of Subjects With Indication for Lipid Lowering Therapy According to the European Society of Cardiology Recommendations - The Mesa Study
Authors: Marcio S Bittencourt, Ron Blankstein, Michael J Blaha, Veit Sandfort, Arthur Agatston, Matthew Budoff, Roger S Blumenthal, Harlan Krumholz, Khurram Nasir
Journal: Circulation (2016)

Introduction: The European guidelines for statin recommendation are based on different risk estimation and drug prescription strategies than the U.S. guidelines, and they currently do not recommend...
Longitudinal trajectory of cancer-related cognitive impairment up to six-months post-chemotherapy: A nationwide NCORP study in 839 breast cancer patients and non-cancer controls.
Authors: Michelle Christine Janelsins, Luke Joseph Peppone, Charles E. Heckler, Charles Stewart Kamen, Supriya Gupta Mohile, Allison Magnuson, Karen Michelle Mustian, Ian Kleckner, Kelly R. Young, Alison Katherine Conlin, Lora Rose Weiselberg, Jerry W. Mitchell, Tim Ahles, Gary R. Morrow
Journal: Journal of Clinical Oncology (2016)

10139 Background: Cancer-related cognitive impairment (CI) is an important problem for breast cancer patients yet the long-term trajectory of CI and factors that confer CI risk are not fully understood. We investigated the impact of chemotherapy on perceived CI in the largest and most definitive prospective, longitudinal nationwide study in community oncology clinics to date as well as whether psychological, clinical and demographic factors predict long-term CI. Methods: Breast cancer patients and age-matched non-cancer controls completed the FACT-Cog at pre- and post-chemotherapy, and six months follow-up. Baseline (pre-chemotherapy) values for age, education, reading ability (cognitive reserve), race, anxiety, depression, and treatment regimen were assessed for their contribution to CI. Results: 505 breast patients (mean age = 54; 48% with anthracycline-based regimens) and 334 controls (mean age = 53) were assessed. Patients reported significant declines on the Fact-Cog total score, perceived CI (PCI), perceived cognitive abilities (PCA), impact of CI on QOL, and perceived CI by others from pre- to post-chemotherapy (all p < 0.05). CI improved slightly from post-chemotherapy to six months follow-up but was still significantly less than baseline (all p < 0.05). When compared to controls, longitudinal mixed-model regressions, controlling for all covariates, revealed patients performed significantly worse on all Fact-Cog domains from pre- to post-chemotherapy (all p < 0.05) and from post-chemotherapy to six month follow-up (all p < 0.05 except the PCA scale). Anxiety, depression, and cognitive reserve significantly predict FACT-Cog changes over time. Breast cancer patients had higher rates of CI than controls from pre- to post-chemotherapy (47% vs 11%) and from pre-chemotherapy to six-month follow-up (38% vs 15%). Conclusions: This definitive study shows that breast cancer patients have significantly more perceived CI up to six-months following chemotherapy compared to controls. Anxiety, depression, and cognitive reserve are important factors influencing long-term CI. Funding: UG1CA189961/K07CA168886.
Prognostic value of microscopic evaluation of organ infiltration and visceral resection margins (VRM) in patients with retroperitoneal sarcomas (RPS).
Authors: Salvatore Lorenzo Renne, Marta Tagliabue, Sandro Pasquali, Paola Collini, Marta Barisella, Dario Callegaro, Chiara Colombo, Alessandro Gronchi, Marco Fiore
Journal: Journal of Clinical Oncology (2017)

11074 Background: Surgery with gross margin clearance (R0 and R1) is the standard treatment for RPS and visceral resection has been proposed even in the absence of macroscopic visceral infiltration. Formal definition and margin sampling procedures for pathological evaluation are lacking for RPS. This study investigated VRM as well as viscera infiltration and their association with patient survival. Methods: Consecutive patients operated on for primary RPS (2009-2014) were extracted from a prospectively maintained database. VRM were sampled for each resected organ and classified as negative and positive. Also, tumor infiltration of resected organs was classified as follow: absence of infiltration, infiltration of perivisceral fat, early infiltration (i.e., renal/adrenal capsule, muscular fascia, contact with muscular tunica of hollow viscera), and infiltration of the viscera. Results: In 207 patients VRM were negative in 182 (88%) and positive 25 (12%). Organ infiltration was absent, perivisceral, early, and visceral in 37 (18%), 13 (6%), 17 (8%), and 140 (68%), respectively. Overall survival analysis showed that patients with negative VRM plus organ infiltration (HR = 3.56; 95%CI 1.15-11.00, P = 0.028) and those with positive VRM irrespective of organ infiltration (HR = 7.76; 95%CI 2.18-27.65, P = 0.002) did worse that patients with negative VRM plus no organ infiltration, after adjustment from known prognostic features. Conclusions: After liberal multivisceral resection for primary RPS, up to 80% of patients have infiltrated organs at some extent, while VRM are positive in up to 10% of cases. Visceral resection is justified even in the absence of macroscopic infiltration. Systematic evaluation of microscopic involvement of adjacent viscera may stratify prognosis.
PrE0204: A multi-institutional, single arm, two-stage phase II trial of nab-paclitaxel and gemcitabine for first-line treatment of patients with advanced or metastatic cholangiocarcinoma—A PrECOG LLC study.
Authors: Vaibhav Sahai, Paul J. Catalano, Sam Joseph Lubner, Mark R. Menge, Hidayatullah G. Munshi, Halla Sayed Nimeiri, Al Bowen Benson, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2017)

4072 Background: Pts with advanced or metastatic cholangiocarcinoma (CCA) have limited response to current chemotherapy regimens and poor overall survival (OS). Nab-Paclitaxel (nabPAC) can increase the intra-cellular concentration of gemcitabine (GEM) through depletion of its metabolizing enzyme, cytidine deaminase (CDA). We investigated the nabPAC+GEM combination in a ph II single arm trial in advanced or metastatic CCA pts with exploratory biomarker evaluation, including CDA, hENT1, SPARC and circulating tumor cells (CTCs). Methods: Key eligibility criteria: advanced or metastatic CCA with no prior systemic chemotherapy, age &gt; 18, ECOG PS 0-1 and Child-Pugh &lt; 8. Pts received nabPAC (125 mg/m2 IV) and GEM (1000 mg/m2 IV) days 1, 8 and 15 Q4 weeks until progression. Primary endpoint: progression-free survival (PFS) rate at 6 months. Secondary endpoints: safety, time to progression (TTP), objective response (ORR) and disease control rates (DCR), median PFS and OS, as well as correlation of change in CA 19-9 to clinical efficacy. The study required &gt; 43 of 67 evaluable patients alive and progression-free at 6 months to conclude the 6-month PFS rate is at least 70% against a null hypothesis of 55% based on historical data. Results: 73 eligible patients (41.1% male, 91.8% Caucasian, 45.2% ECOG PS 0) were enrolled across 22 sites with a median age of 62 (range 36-87) years and received a median of 6 (range 1-18) cycles. The primary endpoint of PFS rate at 6 months was 54.7% on intention to treat analysis. Response evaluation is underway and will be reported at the meeting. The median PFS and OS were 6.5 (95% CI, 5.1-7.7) and 10.3 (95% CI, 9.1-14.6) months, respectively. The safety profile of nabPAC+GEM was similar to that reported in ph III MPACT trial. The most common treatment-related G3/4 toxicities were neutropenia (24.3%), fatigue (13.5%) and anemia (12.2%). Five patients remain on the trial. Exploratory analyses are pending. Conclusions: The observed PFS rate at 6 months with nabPAC+GEM in CCA is insufficient to reject the null hypothesis of 55% PFS at 6 months, and appears to be as effective as the historical control. Clinical trial information: NCT02181634.
Copy number variation of <i>MDM2</i> and <i>p53</i> genes in extracellular DNA as potential marker for lung adenocarcinoma diagnostics.
Authors: Denis S. Kutilin, Yaroslav S. Enin, Dmitriy I. Vodolazhsky, Vyacheslav A. Sustretov, Tamara G. Ayrapetova, Pavel A. Anistratov, Sergey P. Pyltsin, Igor A. Leyman, Anna V. Chubaryan, Olesia A. Bogdanova, Leonid Kharin, Igor N. Turkin, Maxim N. Dyritsky, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e23094 Background: Today, the problem of early diagnostics of lung cancer remains unsolved as every fourth patient diagnosed with the disease already has distant metastases. Studying gene copy number variation (CNV) in extracellular DNA in the blood plasma can become a basis for a new effective and low invasive method for predictive diagnostics and disease prognosis. The purpose of the study was to examine the copy number of the MDM2 and p53 genes in extracellular DNA of patients with metastatic and non-metastatic lung cancer and healthy donors. Methods: The blood samples of 30 patients with lung adenocarcinoma (collected before surgery) and 30 healthy donors (without cancer) were studied. Each sample was centrifuged to obtain blood plasma. DNA was isolated from plasma using a phenol-chloroform extraction method. Detection of relative copy number of the MDM2 and p53 genes (reference gene - GAPDH) was performed by RT-qPCR using CFX96 thermocycler (Bio-Rad, USA). The groups were compared by the Mann-Whitney U- test. Results: Reduction of the p53 gene copy number by 57% (p &lt; 0.05), as well as increasing of the MDM2 gene copy number by 160% (p &lt; 0.05), were found in the extracellular DNA of patients with lung adenocarcinoma compared with healthy donors. As a result, the ratio of copy number of pro-/anti-apoptotic genes p53:MDM2 in extracellular DNA of patients with lung adenocarcinoma (1:23 ratio) was different from that of healthy donors (1:4 ratio). The MDM2 gene copy number in extracellular DNA of patients with metastases exceeded the value in non-metastatic patients two-fold (p &lt; 0.05). The p53 gene copy number in extracellular DNA of patients with metastatic and non-metastatic cancer did not differ significantly. Conclusions: CNV of the p53 and MDM2 genes in extracellular DNA has a high potential for low invasive diagnostics and prognosis of lung adenocarcinoma.
An open-label, randomized phase III trial of gemcitabine and carboplatin (GC) followed by Epstein-Barr virus-specific autologous cytotoxic t lymphocytes (EBV-CTLs) versus GC as front-line therapy for patients (pts) with advanced nasopharyngeal carcinoma (NPC).
Authors: Han Chong Toh, Josemund Menezes
Journal: Journal of Clinical Oncology (2018)

6082 Background: Median overall survival (OS) and prognosis in patients with advanced EBV-positive NPC remain poor and treatment options are limited. In a small phase II trial (38 Asian pts), EBV-CTLs following chemotherapy (GC) as a first line setting for pts with metastatic and/or recurrent NPC has shown promising efficacy and acceptable toxicity: median OS and overall progression free survival (PFS) was 29.9 and 7.6 months respectively, with 2-year OS rate of 62.9% (Chia et al., Mol Ther., 2014). A Phase III trial has been initiated to evaluate the antitumor efficacy of GC-CTL versus GC in these pts (NCT02578641). Methods: This multicenter, randomized, open-label, two arm study is ongoing across 30 sites in Malaysia, Singapore, Taiwan, Thailand and USA. Eligible pts have a histologically confirmed metastatic or locally recurrent EBV-positive, non-keratinizing and/or undifferentiated NPC (not amenable to curative treatment with surgery and/or chemoradiation therapy), with measurable disease (RECIST v1.1) at screening, ECOG PS≤2 and NCI CTCAE < 2. Pts with CNS metastasis, autoimmune disease or prior immunotherapy are excluded. Prior chemotherapy or radiation with curative intent is allowed. 330 pts will be randomized 1:1 to receive either four cycles of GC followed by six cycles of EBV-CTLs (Arm A) or six cycles of GC alone (Arm B). Stratification factors include country and disease stage (metastatic versus locally recurrent). Analysis of the primary endpoint is based on the hazard ratio calculated using the Cox Proportional Hazard model. Secondary endpoints include PFS, overall response rate, clinical benefit rate and quality of life. Safety assessments will consist of monitoring and recording all adverse events (graded by NCI CTCAE v 4.0). Results: As of 31 Jan 2018, 226 of the planned 330 pts are enrolled. Conclusions: An Independent Data Monitoring Committee has reviewed the trial on 29 Aug 2017 and concluded that trial accrual continue as planned. Clinical trial information: NCT02578641.
Identification of symptom clusters by occurrence and severity in lung cancer patients receiving chemotherapy.
Authors: Melisa L. Wong, Bruce A. Cooper, Judy Mastick, Steven M. Paul, Christine Miaskowski
Journal: Journal of Clinical Oncology (2016)

e21657 Background: Lung cancer patients experience a high prevalence and severity of symptoms, which often co-occur to form symptom clusters. Symptom clusters can be identified using different measures such as occurrence or severity but the optimal method is not known. We aimed to compare symptom clusters identified using occurrence versus severity among lung cancer patients receiving chemotherapy. Methods: As part of a larger cohort study of cancer patients receiving chemotherapy, lung cancer patients self-reported symptom occurrence and severity 1 week after receipt of chemotherapy using the Memorial Symptom Assessment Scale. We characterized the occurrence and severity of symptoms and performed separate exploratory factor analyses (EFA, unweighted least squares extraction method, geomin oblique rotation) to identify symptom clusters using occurrence versus severity ratings (0 = not present to 4 = very severe). Results: 145 lung cancer patients completed the symptom assessment (57% female; mean age 64 years; 88% non-small cell lung cancer, 12% small cell). Patients experienced a mean of 14 symptoms (SD 7.1). The most prevalent symptoms were lack of energy (79%), feeling drowsy (66%), difficulty sleeping (66%), and pain (61%). Among only patients with each symptom, the most severe symptoms were problems with sexual interest or activity (mean severity rating 2.43), lack of energy (mean 2.38), constipation (mean 2.27), and hair loss (mean 2.21). EFA using symptom occurrence identified 5 symptom clusters: sickness behavior (which included physical symptoms), lung cancer, psychological, nutrition, and epithelial symptoms. EFA using symptom severity identified 5 similar clusters but the sickness behavior cluster included both physical and psychological symptoms. Conclusions: EFA using symptom occurrence versus severity identified the same number of symptom clusters with similar themes. However, the symptoms within each cluster were more comprehensive when symptom severity was used. The presence of physical and psychological symptoms in the sickness behavior cluster identified using symptom severity highlights the importance of addressing these symptoms together.
Disparities in treatment patterns and outcomes between Caucasian and African American patients with multiple myeloma (MM).
Authors: Safiya Abouzaid, Kejal Parikh, Zheng-Yi Zhou, Zhou Zhou, Wenxi Tang, Jipan Xie, Manali I. Patel
Journal: Journal of Clinical Oncology (2016)

8022 Background: Novel treatments (tx) and advancements in autologous stem cell transplant (ASCT) have improved overall survival (OS) for patients (pts) with MM. The present study aimed to assess tx patterns, healthcare costs, and OS for Caucasians (CAU) and African Americans (AA) with MM. Methods: CAU and AA with MM in the SEER-Medicare database (2007-2011) were included. The index date was defined as the first MM diagnosis (dx) date. Pts were required to be continuously enrolled in Medicare Part A, B, and D for 6 months (mos) before (baseline period) and ≥ 6 mos after the index date (study period) unless they died. Tx, costs, and OS were assessed during the study period. Proportions of pts receiving specific MM tx were compared between cohorts using Chi square tests. Time-to-therapy initiation and OS were described using Kaplan Meier analyses and compared using log-rank tests. Costs were compared using Wilcoxon rank sum tests. Results: The study included2,200 CAU and 536 AA. The CAU cohort had a higher proportion of men (51% vs 42%, p < 0.01), were older (mean age 76 vs 73), and married (52% vs 25%, p < 0.01) as compared to AA. AA had lower rates of ASCT (3% vs 6%, p < 0.01) and novel (lenalidomide, thalidomide, or bortezomib) combination therapies (66% vs 74% among pts with pharmacological therapy, p < 0.01) compared to CAU, although the proportions with novel monotherapy was comparable (28% vs 25%). The median times from dx to therapy initiation (2.3 vs 1.7 mos, p < 0.05) and novel therapy initiation (5.3 vs 3.1 mos, p < 0.05) were significantly longer for AA than CAU. OS was comparable between AA and CAU (26.7 vs 30.0 mos, p = 0.27). AA incurred significantly higher monthly all-cause medical costs compared to CAU (mean: $10,395 vs $9,212, p < 0.05), but comparable drug costs ($1,855 vs $2,071) and total (medical + drug + other) costs ($12,250 vs $11,283). Conclusions: AA received less ASCT and novel combination therapies, and at a later time than CAU; however, OS and total healthcare costs were similar across cohorts, although AA had higher hospitalization costs. Differences in disease aggressiveness and other clinical characteristics at baseline between AA and CAU can affect tx outcomes and should be explored in future studies.
TCT-551 Extremely early optical coHerence tOmogRaphy comparative Study among drug Eluting stents with Persistent, absOrbable or Without polymER (HORSEPOWER Study)
Authors: Beatriz Vaquerizo, Raul Millan, Helena Tizon-Marcos, Neus Salvatella, Iris Rodriguez-Costoya, Consol Diaz, Josep Gomez Lara
Journal: Journal of the American College of Cardiology (2018)
P01.127 The impact of first MR in clinical decision making of patients with high grade glioma treated with radio-chemotherapy
Authors: M Cantarella, F Pasqualetti, A Molinari, A Gonnelli, M Cosottini, F Paiar
Journal: Neuro-Oncology (2018)

Standard up-front therapy of high grade glioma (HGG) is focused on the so called Stupp protocol, that includes surgical resection followed by radiotherapy (RT) combined with concomitant and adjuvant chemotherapy with temozolomide (TMZ). As supported by several international guidelines, disease assessment is performed using magnetic resonance (MR) one month since the end of RT and then every 3 months: in case of tumour progression the administration of temozolomide (the most active agent against glioma) is interrupted and salvage therapy or best supportive care are recommended. The aim of this study is to investigate in a retrospective manner the real value of first MR following RT and its relevance in clinical decision making about up-front therapy. Between April 2005 and July 2017, data of 78 patients (pts) with a proven diagnosis of HGG and treated with Stupp protocol at the University Hospital of Pisa were collected. Tumor progression was defined according to Mac-Donald’s Criteria. Considering the potential presence of pseudo-progression (PSP) and the evolutionary pattern of the suspected recurrences, lesions suggestive for tumor progression inside the radiotherapy field were investigate with a new MR after 6–8 weeks. Otherwise, the presence of new lesions outside the radiotherapy field was interpreted as disease progression (PD) and patient’s therapy was changed. Presence or absence of symptoms, extent of surgery and MGMT methylation status were recorded. The first MR after RT-CT evidenced infield progression (interpreted as PSP) in 16 pts (20,5%) and outfield progression in 8 (10.2%).Three out of 8 patients with outfield progression were symptomatic for the tumor growth. The second MRI confirmed the presence of PSP in 10 pts out of 16 pts whereas in 6 patients a true progression (PD) was present since the first MR. In absence of symptoms, the first MR after radio-chemotherapy influenced clinical decision making (sending the patients to further salvage therapy or BSC) only in 5 out of 78 patients (6.4%). In 72 patients, even in presence of radiological signs suggestive for disease progression inside the RT field, clinical decision making did not change. Further studies involving a higher number of patients are required in order to confirm our findings.