tbuckley/cabot-search huggingface dataset:
P01.104 Evaluation of high signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted images after administration of Dotarem vs. Gadavist in brain tumor patients who undergo multiple MRI evaluations
Authors: S Rozenblatt, J Luckman, S Yust-Katz, T Siegal
Journal: Neuro-Oncology (2018)

Gadolinium-based contrast agents (GBCAs) are routinely used in MRI studies performed for evaluation of brain tumors. Recent studies have demonstrated, progressively increased signal intensity in the globus pallidus (GP) and dentate nucleus (DN) on T1-weighted brain images obtained in patients undergoing repeated MR studies. Linear GBCAs result in more retention and longer time of retention than macrocyclic GBCAs. The aim of this study is to evaluate changes in signal intensity ratios of the GP and the DN on unenhanced T1-weighted images after multiple administrations of macrocyclic GBCAs in brain tumor patients. The study included 37 patients with primary brain tumors who had more than 3 MRI evaluations (range: 4–10 studies). Ten of them (27%) have not receive radiation therapy. Patients were divided into two groups: Group 1 included 24 patients who had Gadoterate meglumine (Dotarem®) enhanced MRI and group 2 included 13 patients who had Gadobutrol (Gadavist®) enhanced MRI. Median age of group 1 patients was 46 (24–69) years and of group 2 it was 56 (32–67). Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The difference in mean GP-to-thalamus (GP\TH) signal intensity ratio, DN-to-middle cerebellar peduncle (DN\MCP) signal intensity ratio between the first and last examinations for each patient were calculated. In both groups GP \TH Ratio difference was greater than 0 (Gadavist 0.08 ± 0.06, Dotarem 0.02 ± 0.08 [P=0.035]) following multiple MRI examinations. There was no significant change in DN\MCP ratio in both groups (Gadavist 0.02 ± 0.07, Dotarem -0.01 ± 0.08 [P=0.230]). A significant increased GP\Thal ratio is associated with multiple administrations of both macrocyclic agents, but to a greater extent with administration of Gadavist possibly reflecting the difference in elimination and stability of both contrast agents. Further studies are needed to identify clinical implications, if any, of these findings.
Presentation at diagnosis and intensity of interventions in people with lung cancer.
Authors: Adam C Powell, Amin J Mirhadi, Bryan A. Loy, James W Long, Erin M Kren, Amit K Gupta
Journal: Journal of Clinical Oncology (2016)

e20052 Background: In 2015, lung cancer screening using computed tomography (CT) became a covered benefit for certain at-risk people with Medicare insurance. Candidates may have difficulty deciding whether to be screened due to the numerous false positives and indolent cancers detected by screening, and newly diagnosed people may wonder about the interventions that they are likely to receive. This study characterizes the interventions people with a CT positive for lung cancer received, stratified by presentation at the time of diagnosis. Methods: People included in the study had a diagnostic lung CT with positive lung cancer diagnosis in 2013, no mention of lung cancer in the prior 12 months of claims, and 12+ months of survival following diagnosis. All people (n = 1,261) had Medicare Advantage insurance from one carrier, were aged 55-80, and did not have metastatic cancer. People were classified into groups based on presentation at diagnosis: morbidities unrelated to lung cancer (n = 621), classic lung cancer symptoms (n = 413), and cancer syndromes (Pancoast or SVC, n = 91). People with none of these factors were categorized into the no diagnoses/symptoms group (n = 136). The frequency of early treatment (including brachytherapy, lobectomy, radiofrequency ablation, stereotactic body radiation therapy, and wedge resection), advanced treatment (chemotherapy or radiotherapy), and palliative care in each group was reported. Results: Early treatment was most common in the group with morbidities unrelated to lung cancer (14%) and least common in the cancer syndromes group (7%). Advanced treatment was used by 47% of the cancer syndromes group versus 24% of the no diagnoses/symptoms group; and palliative care was provided for 29% of the cancer syndromes group and 13% of the no diagnoses/symptoms group. Frequencies of advanced and palliative care in the morbidities and classic symptoms groups fell between the no diagnoses/symptoms and cancer syndromes groups. Conclusions: People with no symptoms or morbidities at lung cancer diagnosis less frequently received advanced interventions and palliative care. As such, screening asymptomatic at-risk people could result in less intensive interventions and lower costs.
A population-based comparison of cancer and non-cancer related healthcare costs.
Authors: Davis Sam, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2018)

e18900 Background: Costs associated with cancer care are increasing. Evaluating costs in the context of common comorbidities has not been extensively studied in a population-based setting. Knowledge from such analyses can better inform healthcare resource allocation and highlight strategies to reduce overall costs. Methods: Using data from a population-based administrative database comprised of health insurance claims, physician billing, and hospital discharge abstracts, we calculated healthcare costs (in CAD) for common comorbidities among the pediatric and adult population of a Canadian province for the 2014/15 fiscal year. We calculated incidence-adjusted healthcare costs for common cancers and comorbidities such as cardiovascular disease. Subgroup analysis was also performed for provincial administrative regions. Results: Total costs related to cancer care amounted to $522M for the province, of which $74M (14%) were attributed to radiation and chemotherapy. Among different cancer subtypes, hematologic malignancies were most costly at $78M, accounting for 15% of the total cancer budget, followed by colon cancer at $51M (10%) and lung cancer at $45M (9%). Cancer costs both with and without accounting for radiation and chemotherapy surpassed those of cardiovascular diseases, diabetes mellitus, mental health, and trauma, but were exceeded by the costs of liver disease (Table 1). Cancer costs varied by provincial administrative region. Conclusions: Cancer costs were greater than those of other common comorbidities, both with and without the costs of radiation and chemotherapy. Using provincial datasets to establish cost trends can help inform healthcare allocation and budget decision-making. Table 1. Incidence-adjusted costs (in CAD) per person per year for cancer and comorbidities. R&C = radiation and chemotherapy. Total Costs Cancer, with R&C 1951 Cancer, without R&C 1917 Cardiovascular disease 806 Diabetes mellitus 663 Liver disease 5208 Musculoskeletal disease 656 Mental health issues 487 Trauma 613
Quantitative multiplex immune fluorescence to reveal the impact of chemoradiation therapy on modulation of the immune micro-environment of pancreatic ductal adenocarcinoma.
Authors: Thomas Enzler, Robyn D Gartrell, Ladan Fazlollahi, Helen Elaine Remotti, Thomas D Hart, Douglas Kanter Marks, Alexander Raufi, Yan Lu, Subha Perni, Pan Kim, Christian Monsalve, Susan Elaine Bates, Yvonne M. Saenger, David Paul Horowitz
Journal: Journal of Clinical Oncology (2018)

4122 Background: Patients with advanced pancreatic ductal adenocarcinoma (PDA) continue to have median survival under one year and to date immunotherapy has largely been unsuccessful. Radiation or chemoradiation can cause the release of tumor antigens and pro-inflammatory cytokines leading to stimulation of anti-tumor immunity. We sought to quantify this effect by comparing immune cell infiltrations of PDAs treated with chemoradiation or not treated prior to surgical resection. Methods: Slides obtained from surgical specimens were stained using opal fluorophores for CD3, CD8, CD4, FOXP3, CD68, Ki-67, and DAPI for nuclear staining. This method allowed simultaneous evaluation of different markers using quantitative multiplex immunofluorescence (qmIF). Images were taken with automated imaging system VECTRA and analyzed for cell densities in tumor and stromal compartments. We included 20 patients who underwent chemoradiation and 12 patients without neoadjuvant treatment. Results: When comparing treated vs. non-treated tumors, total CD3+ densities were significantly higher in stromal tissue of treated tumors (P = 0.0002). There was also a significant increase in CD3+CD8+ T cell densities (P = 0.0006) and CD3+CD4+FOXP3- T cell densities (P = 0.0037) in the stromal tissue of treated tumors. Conversely, CD4+FOXP3+ T cells were significantly increased in the tumor microenvironment (TME) of non-treated tumors when compared to treated tumors (P = 0.0003). No clear differences in infiltrating CD68+ macrophages were observed between the groups. Conclusions: To our knowledge this is the first time that immune cell infiltrates of PDA either treated with neoadjuvant chemoradiation or not treated were compared using qmIF. The higher counts of T helper cells and cytotoxic T cells found in treated tumors can be explained by the increased immunogenicity caused by chemoradiation-therapy. The higher densities of CD4+FOXP3+ cells in non-treated tumors likely reflect the immunosuppressive TME. We will try to identify biomarkers predictive of outcome and, hopefully, our findings will provide rationale for the development of new treatment strategies.
Novel resistance mechanisms to first-generation EGFR tyrosine kinase inhibitors: A perspective study in NSCLC patients using targeted next generation sequencing.
Authors: Ying Jin, Jianjun Zhang, Ming Chen, Yang Shao, Xun Shi, Jun Zhao, Xue Wu, Xinmin Yu
Journal: Journal of Clinical Oncology (2017)

e20576 Background:Patients with non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Identification of actionable mutations conferring drug-resistance can be helpful for guiding the subsequent treatment decision. Currently, the known mechanisms of acquired resistance includes: the secondary gatekeeper EGFR-T790M mutation, activation of members of downstream signaling pathways such as PI3K/AKT/mTOR pathway, activation of bypass signaling such as MET, and changes in tumor histology. However, the mechanisms in the remaining patients are still unknown. Methods:In this prospective study, thirty-one advanced NSCLC patients initially carrying sensitive EGFR mutations and subsequently developing acquired resistance to the first-generation EGFR-TKIs were enrolled. Pre-treatment tumor samples as well as re-biopsies of tumor and plasma when the patients were diagnosed with EGFR-TKI resistance were acquired, followed by mutation profiling using targeted next generation sequencing (NGS) on 416 cancer-related genes. Results: In total, 55% of patients were identified to carry acquired secondary EGFR-T790M mutation. Three patients (~10%) harbor EGFR-T854A mutation, which has been reported as another TKI resistant mutation. 26% and 19% of cases accumulated TP53 and RB1 mutations, respectively. In T790M/T854A-negative cases, 30% of patients acquired MET amplification. Other potential acquired resistance mechanisms includes single nucleotide variants (SNVs) in genes such as SMAD4, DNMT3A, GNAS, ATM, KRAS, PIK3CA and TET2, and copy number variations (CNVs) in genes such as CDK4, MDM2, MYC, RICTOR and ERBB2. Conclusions:The study depicted the genetic landscapes comprehensively in matched pre- and post-EGFR-TKIs samples of NSCLC population resistant to first generation TKI treatments. Our analysis demonstrates new perspectives for further study of resistance and putting forward corresponding relevant tactics against the challenge of disease progression. Clinical trial information: NCT02804217.
Prognostic factors in oligometastatic non-small-cell lung cancer (OM-NSCLC) patients treated with ablative therapy.
Authors: Juan Antonio Mendez, Domingo Benjamín, David Lorente, Corina Escoin, Carmen Salvador, Edwin Navarro, Marcos Melian, Nuria Mancheño, Jose Gómez-Codina, Oscar Juan Vidal
Journal: Journal of Clinical Oncology (2018)

e21089 Background: OM-NSCLC represents a distinct prognostic group within stage IV lung cancer. Prognostic factors influencing outcome in these patients are not well-known. Methods: We analyzed 84 OM-NSCLC pts (defined as ≤3 metastatic lesions in a PET-CT scan performed at diagnosis) diagnosed between Jan-2012 and Dec-2016 at the Hospital UiP La Fe. Median OS was calculated with the Kaplan-Meier method. The association between clinical and pathological factors and OS was determined using uni- (UV) and multivariable (MV)Cox regression models. Variables with a p-value < 0.01 in UV analysis were included in the MV model. Results: 25 pts squamous histology (29.8%), 58 adenocarcinoma (58%) and 1 (1.2%) undifferentiated carcinoma. 11 pts (13%) were EGFR-mutation positive. Most patients presented with one (78.3%) or two (20.5%) metastatic sites: CNS (39.2%), bone (29.8%), lung (17.9%), adrenal (11.9%) and liver (10.7%). 57 pts (67.9%) underwent local treatment (8.8% surgery, 70.2% radiotherapy, both 21.2%). Median follow-up was 10.5 months with a median OS of 15.8 months (95CI%:8.9-22.7). In MV OS analysis, only T-stage (p = 0.012) and histology (p = 0.006) were significantly associated with OS (Table). Conclusions: Lower initial T-stage in the primary tumor and adenocarcinoma histology may be associate to a favorable prognosis. The optimal management of NSC-OM patients will require robust data from well-designed prospective clinical trials. Table: UV and MV Cox-regression Models. Variable Univariate Multivariate HR (CI95%) p-valor HR (CI95%) p-value Histology 0,32 (0.18-0.58) < 0.001* 0.42 (0.23-0.78) 0.006 Sex 0,44 (0.19-1.03) 0.059* 0.52 (0.22-1.25) 0.142 Smoking 1,27 (0.79-2.05) 0.320 T stage 1,47 (1.16-1.89) 0.002* 1.44 (1.09-1.92) 0.012 N stage 1,01 (0.99-1.02) 0.496 Nº of metastasis 1,32 (0.72-2.41) 0.366 Site of metastasis Lung 0.80 (0.41-1.58) 0.522 Adrenal gland 0.91 (0.49-1.69) 0.767 CNS 0.89 (0.55-1.45) 0.647 Liver 1.36 (0.76-2.44) 0.302 Bone 1.45 (0.91-2.33) 0.118 1.05 (0.42-2.63) 0.916 Local treatment (yes/no) 0.42 (0.24-0.76) 0.004* 0.61 (0.33-1.12) 0.115
CD19 targeted chimeric antigen receptor T (CAR-T) cell immunotherapy has demonstrated significant anti-leukemia activity in pediatric patients with relapsed/refractory acute lymphocytic leukemia: A multicentre study in China.
Authors: Lei Xiao, Yongmin Tang, Xiaofan Zhu, Jing Chen, Zhao Wu
Journal: Journal of Clinical Oncology (2017)

e18512 Background: Patients with relapsed/refractory B-ALL are difficult to be treated. Autologous CD19 CAR-T may overcome many limitations of conventional therapies and induce remission in patients with relapsed/refractory disease. We explored treatment of 11 pediatric cases (come from Multicenter) with r/r B-ALL and assessed the clinical safety and efficacy. Methods: We infused autologous CD19 CAR-T in patients at doses of 0.45 × 10 6 to 10.51 × 10 6 cells per kilogram of body weight. Between Oct. 23 2015 and Jan. 12 2017, a total of 11 children from 3 clinical centers (in China) cases were treated with CAR-T cells (Table1). Patients were monitored for a response, toxic effects, and remission rate. Statistical analysis involving categorical or continuous covariates, univariates, or multivariates analyses. Results: 73% (8/11) of the patients achieved complete remission (CR) and MRD negative between Day7-14 after CD19 CART cell infusion. 4 patients received a repeat infusions following initial ones since they have endured the Cytokine release syndrome (CRS) and have no safety concerns. Cytokine release syndrome (CRS) was seen in 73% (8/11) of patients and severe CRS occurred in 18% (2/11) of patients. Severe CRS was relieved gradually when the anti-IL6R agent tocilizumab and Methylprednisolone were administrated. 1 patients performed bone marrow transplant after they achieved MRD negative. The median CR maintenance is 121 day. Conclusions: This effort provides the first large set of pediatrics data that describes the potential for CART19 therapy to benefit Chinese population. Autologous CD19 CAR-T was effective in treating relapsed/refractory B-ALL not only low leukemia burden, but also high-burden leukemia patients. The method also can associated with a high remission rate. Importantly, While the multicenter trial involves 3 clinical centers in China, the variable clinical settings do not seem to impact patient outcomes due to the highly standardized CAR T cell preparation protocol and manageable CRS in most. (NCT 02813837) Clinical trial information: NCT 02813837.
TCT-465 Diagnostic Accuracy of Microcatheter Derived Fractional Flow Reserve: Systematic Review with Lesion Level Analysis
Authors: Ozan Demir, Satoru Mitomo, Antonio Mangieri, Marco Ancona, Damiano Regazzoli, Giuseppe Lanzillo, Francesco Giannini, Luca Testa, William Wijns, Antonio Colombo, Azeem Latib
Journal: Journal of the American College of Cardiology (2018)
Abstract 16411: Impact of Prediabetic Status on Coronary Atherosclerosis: A Multi-Vessel Angioscopic Study
Authors: Osamu Kurihara, Masamichi Takano, Masanori Yamamoto, Seiji Kanou, Tetsurou Shimura, Nakahisa Kimata, Toru Inami, Nobuaki Kobayashi, Ryo Munakata, Daisuke Murakami, Takayoshi Ohba, Chikao Ibuki, Yoshihiko Seino, Kyoichi Mizuno
Journal: Circulation (2012)

Background: Although diabetes mellitus is a major risk factor of coronary artery disease (CAD), there is no evidence that pre-diabetes including impaired fasting glucose and impaired glucose tolera...
Computational integrative analysis of identification of potential therapeutic genes and networks in breast cancer
Authors: M. Peer Mohammed, V. Parthasarathy
Journal: Annals of Oncology (2018)

Background: Cancer genomics research aims at investigation of biological pathways affected by mutations of these genes will help us to understand the determinants of cancer initiation, progression, and other biological functions. The sophisticated computational methods have been developed to facilitate the detection of cancer driver mutations and pathways. We made an attempt in this study to identify the potential candidate genes in the breast cancer carcinogenesis by computational integrative analysis. This approach is appropriated for identifying potentially useful diagnostic and prognostic biomarkers for therapeutic intervention of breast cancer. Methods: Breast cancer tissue microarray datasets were retrieved from Gene Expression Omnibus database (GEO) and the upregulated and downregulated genes were analyzed. Gene ontology, pathway analysis and coexpression network patterns identification were performed. Results: A total of 1760 Differential Expressed Genes were identified, including 1083 upregulated and 677 downregulated genes. The Gene Ontology terms for molecular functions, biological processes, and cellular component were protein binding, small molecule metabolic process, and integral to membrane, respectively. The most significant pathway in BIOCARTA was DNA replication & repair and cell division regulation pathways. Protein to protein network analysis indicated that the significant hub genes including ARD1,AURKB, AIK2, AIM1, ARK2, AurB, IPL1, STK5, AIM-1, STK12, PPP1R48, aurkb-sv1, aurkb-sv2, CEP55, CT111, URCC6, C10orf3,MELK , HPK38,FOXA1,HNF3A, TCF3A,ARA, IGDA, IHG1, FKHL7, IRID1, RIEG3, FREAC3,ACKR1, CCBP1, CD234, WBCQ1 , PIR- FIGF and BAI1 associated protein 2(BAIAP2) . Gene coexpression network analysis identified 4 major modules,Ankyrin repeat domains,Forkhead box C1,Forkhead box A1 and Trefoil factor 3. Conclusions: Our study concludes a comprehensive view of integrative analysis of gene expression patterns associated with the breast cancer onset and progression. Legal entity responsible for the study: M. Peer Mohammed. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Evaluating the appropriateness of granulocyte colony-stimulating factor (G-CSF) use in patients (pts) receiving myelosuppressive chemotherapy by febrile neutropenia (FN) risk level.
Authors: Hassam Baig, Zandra Karina Klippel, Melissa A. Pirolli, Barbara Somlo, Melissa Eisen, Scott Stryker, Spiros Tzivelekis, Phuong Khanh H. Morrow
Journal: Journal of Clinical Oncology (2016)

e21691 Background: G-CSF prophylaxis is recommended for pts receiving chemotherapy with a high risk of FN and considered for pts with additional risk factors who receive intermediate-risk (IR) chemotherapy. However, inappropriate G-CSF use has been reported. Using the OSCER EMR database, we investigated prophylactic G-CSF (pegfilgrastim or filgrastim) use in pts with cancer by chemotherapy FN risk level. Methods: Pts had metastatic or nonmetastatic breast, head/neck, colorectal, ovarian/gynecological, or lung cancer or NHL and started/ended a chemotherapy cycle from June 2013 to May 2014. Chemotherapy regimens were defined as high risk (HR), IR, or low risk (LR) for FN per NCCN guidelines; if regimen risk was undefined per NCCN guidelines, regimen risk was adjudicated by two independent clinical reviewers. Analyses included the number of cycles with prophylactic G-CSF use overall and by FN risk level and the number of NCCN risk factors (age ≥65 y, performance status, prior bone marrow involvement, prior neutropenia/infection, renal/liver dysfunction, HIV infection) in a random pt subset (n=400) treated with IR regimens. Results: Of ~4.2 million chemotherapy cycles, 9% were HR, 48% were IR, and 43% were LR. Overall, prophylactic G-CSF was used in 24% of cycles; use was highest in HR cycles in the nonmetastatic setting (Table). In a random subset of 400 pts with metastatic disease who were receiving IR regimens and prophylactic G-CSF, 69% (95% CI, 64.5%–73.5%) of pts had ≥1 NCCN risk factor. Conclusions: G-CSF use was appropriately highest in HR regimens and lowest in LR regimens, consistent with the clinical rationale for FN risk reduction. Largely, prophylactic G-CSF use in pts receiving IR regimens appears to be appropriate when accounting for both regimen risk and pt risk factors for FN. G-CSF use by chemotherapy FN risk level. Cycles With G-CSF Prophylaxis / Total Chemotherapy Cycles (%) HR IR LR Metastatic 128,755/ 255,001 (50) 300,110/ 1,106,845 (27) 183,079/ 1,647,542 (11) Nonmetastatic 87,457/112,090 (78) 277,767/896,479 (31) 9,010/157,615 (6) Overall 216,212/ 367,091 (59) 577,876/ 2,003,324 (29) 192,089/ 1,805,157 (11)