tbuckley/cabot-search huggingface dataset:
P04.58 A new computational method for comprehensive estimation of anti tumor efficacy of tumor treating fields (TTFields). Accounting for field intensity, exposure time and unwanted spatial field correlation.
Authors: A R Korshoej, A Thielscher
Journal: Neuro-Oncology (2018)

The non-invasive glioblastoma treatment, tumor treating fields (TTFields, Optune®), uses alternating electrical fields (200 kHz) to inhibit cancer cell division. TTFields are induced by two sequentially active pairs of transducer arrays placed on the patient’s scalp. Finite element (FE) methods are used to estimate the field intensity of TTFields. To date, calculations have focused entirely on field intensity, neglecting field angle and exposure time that also influence efficacy. Based on principal component analysis, this study derives a novel approach to quantify mean intensity of TTFields together with unwanted effects from spatial field correlation, indexed as fractional anisotropy (FA). Distributions of the two sequential TTFields (50% duty cycle, 2 s total duration) were calculated using FE methods on a realistic glioblastoma head-model (calculated based on images before and after resection) using four different array layouts. In each element of the model, the combined fields were decomposed into principle components. For each element, intensity, and directional correlation of the average field were calculated as the square root of the electrical energy (Frobenius norm) and the FA, respectively. Significant unwanted FA was observed within several regions of the brain, particularly at resection borders. These effects may potentially reduce therapeutic efficacy of TTFields. FA varied between different layouts, suggesting a different array performance than predicted from conventional intensity calculations. Resection of a tumor increased FA and removed differences between layouts. This study questions the rationale for the general use of macroscopically orthogonal layouts to reduce field correlation. The results indicate that in some cases, arrays should be placed differently to maximize pathology coverage and field intensity. We present a new and comprehensive framework for TTFields characterization that potentially could improve treatment planning, technology development, and accurate prognostication models. Further studies are required to validate the method.
TCT-632 Mechanisms of Myocardial Infarction in Patients With Nonobstructive Coronary Artery Disease: Results from the Optical Coherence Tomography Study
Authors: Maksymilian Opolski, Mateusz Spiewak, Magdalena Marczak, Artur Debski, Kajetan Grodecki, Zbigniew Chmielak, Pawel Tyczynski, Adam Witkowski
Journal: Journal of the American College of Cardiology (2018)
Improving patient wait-time and patient/provider wait-time satisfaction by the room pooling model.
Authors: Shawn J Janarthanan, Xiao Zhou, Mary Daniel, Colleen Jernigan, Shreyaskumar Patel, Laura Kaufman, Doris Quinn, Saroj Vadhan-Raj
Journal: Journal of Clinical Oncology (2016)

6595 Background: The growth in patient (pt) volume and limited clinic capacity can lead to long wait times and pt/provider dissatisfaction. The room allocation model (RAM), where fixed rooms are allocated to physicians (MD) based on volume, often underutilizes the clinic rooms. The primary objective of this initiative was to reduce the pt wait time in the exam room and to improve the room utilization in the Sarcoma Center by replacing the current model, RAM, with the room pooling model (RPM), where rooms are not pre-allocated but available to any provider-team when ready to see the pt. Methods: The time studies and the pt/provider wait-time satisfaction surveys were carried out over two weeks prior to (baseline studies during RAM) and after 8-weeks of the implementation (post studies during RPM) of the new model. All times of when pts, mid-level providers, and MD entered and exited the exam rooms were collected for a total sample size of 609 pts that were seen during the clinic hours and analyzed using JMP and SAS. Results: The proportion of pts seen within 30 minutes by MD from the time pts roomed into an exam room improved by about 30% [from 41% (119/293) to 53% (148/280), p = 0.003] with the RPM. The median time for pts in the exam room waiting for MD improved (p = 0.0002) from 36 min. (range: 3-115 min.) to 30 min. (range: 0-126 min.). Pt satisfaction also improved (p = 0.03) with a decrease from 14% (40/287) to 8% (23/278) in the number of pts that were not satisfied to little-satisfied, and an increase from 86% (247/287) to 92% (255/278) in the number of pts that were moderately to very satisfied. In the provider survey, the number of times MD did not have to wait for an open exam room also improved from 79% (54/68) to 92% (60/65, p = 0.03). Conclusions: The RPM was successful in reducing the pt wait-time in the exam room and wait-time satisfaction for both pts and providers. The RPM could improve room utilization and operational efficiency in the clinic.
TCT-521 Long Term Cardiovascular Outcomes with Drug-Eluting Stents vs. Bare-Metal Stents in Saphenous Vein Graft Interventions: Insights from an Updated Meta-Analysis of Randomized Controlled Trials
Authors: Amartya Kundu, Partha Sardar, Saurav Chatterjee, Chirag Bavishi, Nikolaos Kakouros, Herbert Aronow, Jeffrey Rade
Journal: Journal of the American College of Cardiology (2018)
Abstract 13280: Prevalence and Location of Cardiovascular Disease in Familial Hypercholesterolemia and Unaffected Relatives. SAFEHEART (Spanish Familial Hypercholesterolemia Longitudinal Cohort Study) Results
Authors: Adriana Saltijeral Cerezo, Leopoldo Perez de Isla, Rodrigo Alonso, Raimundo de Andres, Pablo Miramontes, Daniel Zambon, Juan F Sanchez Muñoz-Torrero, Teresa Padro, Fatima Almagro, Pedro Mata
Journal: Circulation (2015)

Introduction: Heterozygous familial hypercholesterolemia (HeFH) increases the risk of cardiovascular disease. Traditionally it has been reported that the most affected territory is the coronary arteries tree. However, there are very few data from large cohorts of HeFH and even fewer data comparing them with a control population. Hypotesis: To analyse the prevalence and location of cardiovascular disease in individuals with HeFH and their families with negative genetic diagnosis in a large study. Methods: Data from the study, which recruited 3745 individuals aged 18 and olderbetween January 2004 and November 2013 were analysed. Out of them, 2752 were genetically diagnosesof HeFH and 993 were family members without the mutation. Results: Median age of individuals with HeFH was 44 years (18-89) and 40 (18-87) in unaffected relatives. One thousand, two hundred and sixty four (45.90%) HeFH and 463 (46.60%) controls were male. Table and figure show atherothrombotic disease prevalence in different locations. Conclusions: The prevalence of atherothrombotic disease is higher in individuals with HeFH than in their unaffected relatives. In HeFH patients, the predominant involvement is at the level of the coronary tree.
Outcomes of metastatic chromophobe renal cell carcinoma (chrRCC) in the targeted therapy era: Results from the International Metastatic Renal Cell Cancer Database Consortium.
Authors: Steven Yip, Jose Manuel Ruiz Morales, Frede Donskov, Anna Paola Fraccon, Umberto Basso, Brian I. Rini, Jae-Lyun Lee, Georg A. Bjarnason, Jennifer J. Knox, Benoit Beuselinck, Ravindran Kanesvaran, James Brugarolas, Konstantinos Koutsoukos, Simon Yuen Fai Fu, Takeshi Yuasa, Carmel Jo Pezaro, Ajjai Shivaram Alva, Christian K. Kollmannsberger, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2016)

4570 Background: Treatment outcomes are poorly characterized in patients with metastatic chromophobe renal cell cancer (chrRCC), a subtype of renal cell carcinoma. Methods: A retrospective data analysis was performed using the IMDC dataset to determine metastatic chrRCC treatment outcomes in the targeted therapy era. All 5621 patients received one or more lines of targeted therapy for their metastatic renal cell cancer (mRCC). Kaplan-Meier and summary statistics were used. Overall survival rates and overall response rates were calculated. Results: Out of all 5621 IMDC database patients, 114 (2%) patients were identified to have metastatic chrRCC. Baseline characteristics and risk factors are outlined in table 1. Metastatic chrRCC patients with IMDC favorable (20%), intermediate (57%) and poor risk (23%) had median overall survivals of 31.4, 27.3 and 6.5 months, respectively. Patients with metastatic chrRCC had a similar overall survival compared to patients with clear cell mRCC (20.8 months (95% CI 19.9 - 21.7) vs 21.8 months (95% CI 20.9 - 22.9), respectively). The overall response rate of targeted therapy was 20% (4% CR, 16% PR, 49% SD, 31% PD). 52/114 (46%) metastatic chrRCC received second line systemic therapy. Conclusions: Outcomes in metastatic chrRCC and clear cell mRCC are similar when treated with conventional targeted therapies. To the authors’ knowledge this is the largest series of metastatic chrRCC patients and these results set new benchmarks for clinical trial design and patient counseling. Baseline characteristics & first-line therapy in metastatic chrRCC. Baseline Characteristics & First-Line Therapy Metastatic chrRCC Patient Group (N= 114) Gender 56% Male, 44% Female Anemia 51/104 Thrombocytosis 15/105 Neutrophilia 14/104 Karnofsky Performance Status < 80 19/106 Less than 1 year from time of diagnosis to first-line therapy 48/114 First-line therapy Sunitinib 68/113 Sorafenib 16/113 Bevacizumab 1/113 Temsirolimus 11/113 Pazopanib 12/113 Everolimus 5/113
Correlation of peripheral T cell receptor repertoire with response to neoadjuvant chemotherapy plus trastuzumab in early-stage HER2-positive breast cancer.
Authors: Wenna Wang, Fei Ma, Wenting Chen, Ying Fan, Zongbi Yi, Dengkun Xiong, Yuqi Wang, Yan-Fang Guan, Xiuwen Guan, Xuefeng Xia, Ling Yang, Xin Yi, Binghe Xu
Journal: Journal of Clinical Oncology (2018)

12035 Background: The immune microenvironment of tumor is now emerging as an indicator of responses to anticancer treatment in HER2-positive breast cancer. However, the peripheral blood (PB) TCR repertoire and its interaction with early-stage HER2-positive breast cancer patients treated with chemotherapy plus trastuzumab have not been systemically studied. Methods: We investigated the TCR repertoire using next-generation deep sequencing of the complementarity determining region 3 (CDR3) of the TCR β chain in the PB samples from 26 treatment-naïve hormonal receptor (HR)-negative HER2-positive breast cancer patients before and after 2 cycles of chemotherapy plus trastuzumab and 26 age- and gender-matched healthy volunteers. The patient population was obtained from a single-center prospective study between January 2014 and June 2017 (ClinicalTrials.gov, NCT02041338). Results: The TCR repertoire in the pre-treatment PB of patients was markedly different from that of healthy volunteers, exhibiting higher TCR density (P = 0.0001) and lower evenness (P = 0.01). Patients who achieved a pCR (n = 11) had a lower TCR density in their pre-treatment PB (P = 0.0147) and a higher degree of overlap between the pre- and post-treatment PB TCR repertoires (P = 0.0488) than patients who achieved a non-pCR (n = 15). The sequences of V segments of the TCR β chain demonstrated significantly lower frequencies of TCR β variable (TRBV) 3-1, TRBV4-2, TRBV12-3, TRBV12-5, TRBV15, TRBV6-2, and TRBV7-7 genes in the pre-treatment PB samples of the pCR group than in the non-pCR group. There were no significant differences in TCR density, diversity, clonality or evenness between pre- and post-treatment PB samples. Conclusions: Based on the current study, the TCR repertoire in pre-treatment PB may be used as a predictor of response to neoadjuvant chemotherapy plus trastuzumab in HR-negative HER2-positive breast cancer patients and as a new approach to select patients who will benefit from neoadjuvant therapy.
General proteolysis as factor of postoperative anastomotic bleeding in cancer of the head of the pancreas.
Authors: Larisa Kozlova, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Evgeniy N. Kolesnikov, Umar Muhmadovich Gaziev, Vladimir Trifanov, Leonid V. Kharin
Journal: Journal of Clinical Oncology (2016)

e15681 Background: Anastomotic leakage with arrosive bleeding (AB) develops in 4-29%% of the cases after surgery for pancreatic cancer. AB is mediated by destruction of vascular wall resulting from the local activation of proteolysis. The purpose of the study was to determine general proteolysis in the blood plasma (BP) of patients with pancreatic cancer (T3 N0 M0 ) before and after the surgery. Methods: Pancreatodigestive anastomosis was performed in 26 patients, pancreatoenteroanastomosis – 49, bypass gastroenteroanastomosis and cholecystoenteroanastomosis – 4. Kinetics of general proteolysis in BP was determined by spectrophotometric method before the surgery and 1-3 days after it; the results were compared with the norm (N) of 39 donors. Results: General proteolysis in 4 (5.1%) of 79 patients before the surgery was 10.1 times higher than N, after the surgery – by 14.3 times; AB was observed on day 3-4. General proteolysis in these patients after the surgery was 9.9-18.3 times higher than N and 41.9% higher than the value before surgery. AB was not observed in 75 patients; general proteolysis before the surgery exceeded N by 2.9-5.0 times. After the surgery: general proteolysis twice increased the value before surgery and was 3-9 times higher than N. The results demonstrated that general proteolysis in patients with and without AB before the surgery was expressed to varying degrees, and after the surgery it increased in comparable range but with significant differences. Conclusions: AB was not associated with anastomotic locations as it was observed in 1 patient with pancreatodigestive anastomosis (3.9%), 2 patients with pancreatoenteroanastomosis (4.1%) and 1 patient with bypass. The data on general proteolysis before the surgery can be used in detection of a patient’s individual predisposition to AB. Prognosis effectiveness was shown in 94.9% of cases with AB and in 100% without AB.
Abstract 19566: Transactivation Domain of P53 Regulates DNA Integrity in Human Cardiac Fibroblast Derived iPS Cells
Authors: Ramaswamy Kannappan, Saidulu Mattapally, Wugiang Zhu, Jianyi Zhang
Journal: Circulation (2016)

Introduction: Retaining DNA integrity is essential to induced-pluripotent stem cells. p53 regulates a wide range of cellular processes including cell death and cell cycle progression, cell metabolism and DNA damage and repair. p53 is composed of transactivation domain (TAD), proline-rich region, DNA-binding domain, tetramerization domain and extreme carboxyl domain. The role of p53 in DNA damage and repair mechanisms has been studied extensively in various somatic cells. However, the role of p53 TAD, a multifunctional and dynamic domain, on DNA damage repair and retaining DNA integrity in human cardiac fibroblast derived induced-pluripotent stem cells (hiPS) cells has not been studied. Methods: The transactivation domain of p53 was knocked out using CRISPR/Cas9 system. Both, hiPS cells expressing wild type p53 (p53WT) and p53 TAD knockout (p53TADKO) were exposed to low dose of doxorubicin to induce oxidative stress and DNA damage. DNA damage was assessed by comet assay utilizing OxiSelect Comet Assay kit ...
Incidence rate and clinical-pathological features of hereditary diffuse gastric cancer patients in China.
Authors: Miaozhen Qiu, Rui-hua Xu, Yi-xin Zhou, Ying Jin, Zi-Xian Wang
Journal: Journal of Clinical Oncology (2017)

4065 Background: Familial clustering is seen in 10 % of gastric cancer cases and approximately 1-3 % of gastric cancer arises in the setting of hereditary diffuse gastric cancer (HDGC). Little is known about the incidence rate and clinical-pathologic features of HDGC in Chinese patients. Methods: We retrospectively collected gastric adenocarcinoma patients who were diagnosed in Sun Yat-sen University Cancer Center between January 2002 and December 2014. All the patients had detailed record of family history and Lauren classification. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). Results: 7431 patients were enrolled for analysis. The incidence rate of HDGC was 3.97% (295/7431). There were 124 (42.03%) male and 171 (57.97%) female patients. The median age was 35 (Mean ±SD: 35.23±7.50). The most common sites were gastric body (49.47%) and fundus (35.09%) . The distribution of AJCC 7 th TNM stage was 47 (16.32%) stage I, 59 (20.49%) stage II, 88 (30.55%) stage III and 94 (32.64%) stage IV. Only 92 patients received the HER2 immunohistochemistry test. 4 (4.35%) patients were HER2 IHC +++ and 8 (8.70%) patients were ++. The median survival was 80 months for the whole population and 15 months for stage IV patients. Conclusions: The incidence rate of HDGC was 3.97% in China. About one third of the patients were diagnosed at stage IV. Early detection of HDGC was warranted in China.
A phase I trial of PD-1 deficient engineered T cells with CRISPR/Cas9 in patients with advanced non-small cell lung cancer.
Authors: You Lu, Jianxin Xue, Tao Deng, Xiaojuan Zhou, Kun Yu, Meijuan Huang, Maozhi Liang, Lei Deng, Jingwen Huang, Zhenyu Ding, Youling Gong, Jiang Zhu, Yongsheng Wang, Ruizhan Tong, Li Li, Yanying Li, Bingwen Zou, Min Yu, Yuquan Wei, Weimin Li
Journal: Journal of Clinical Oncology (2018)

3050 Background: We performed the first phase I clinical trial (NCT02793856) to assess safety of CRISPR/Cas9-mediated knockout of PD-1 gene in autologous T lymphocytes (PD-1-/- T) therapy in patients with metastatic non-small cell lung cancer (NSCLC). Methods: We assigned patients with advanced NSCLC with positive PD-L1 expression who had progressed after 3rd line standard therapeutic regimens. Two patients were enrolled in Pre-A cohort who received PD-1-/- T therapy with 2 x 107 cells/kg for one cycle and were observed for another cycle. Then 3 cohorts (A, B, C) enrolled 3 patients in each group receiving PD-1-/- T cells therapy with 1×107/kg, 2×107/kg, 4×107/kg in each cycle, respectively. Patients received PD-1-/- T therapy until disease progression or study withdrawal. Primary outcome was safety. Secondary end points were 8 weeks disease control rate (DCR) and progression-free survival (PFS). In exploratory analyses, next-generation sequencing was performed on PD-1 editing region of T cells and CDR3 region of T-cell receptor. Results: Nine patients were enrolled and eight patients received totally 17 cycles of PD-1-/- T therapy. Twenty-three adverse events (AEs) related to PD-1-/- T cell infusion occurred (Table 1). No 3-5 AEs were observed. Of note, one patient in Pre-A group suffered grade 1 arrhythmia (premature beat) that lasted for 42.4 weeks. Seven patients were response evaluable. Two patients experienced stable disease (SD) with 17.6 and 22.0 weeks, respectively. Other 5 patients had progression disease (PD). Eight-week DCR was 28.6% and median PFS was 7.6 weeks. In exploratory data, two patients with SD showed higher diversity of T cell repertoire in PBMC than other 5 patients with PD. Conclusions: Patients receiving PD-1-/- T therapy seemed safe. Further larger size studies are warranted to explore effective dose and related immune response. Clinical trial information: NCT02793856. Total Cohort ( N = 8) Pre-A (N = 2) A (N = 3) B (N = 3) Events Grade 1 2 ≥3 1 2 ≥3 1 2 ≥3 1 2 ≥3 Fever 2 2 Hyperhidrosis 3 3 Rash 1 1 Arthralgia 1 1 Fatigue 2 1 1 Infusion related reaction 1 1 Arrhythmia 1 1 Hypertension 1 1 Aminotransferase increased 2 1 1 White blood cell decreased 7 7 Thrombocytopenia 2 2 Total 22 1 0 5 0 0 10 1 0 7 0 0 All level events 23 5 11 7
Clinical characterization of pancreatic ductal adenocarcinomas (PDAC) with mismatch repair (MMR) gene mutations.
Authors: Zishuo Ian Hu, Anna M. Varghese, Jinru Shia, Alice Zervoudakis, Maeve Aine Lowery, Kenneth H. Yu, Sree Bhavani Chalasani, Mark E. Robson, Zsofia Kinga Stadler, Philip Caron, David Paul Kelsen, David Klimstra, Daniel W. Kelly, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2017)

e15791 Background: Tumors with mismatch repair-deficiency (MMRD) have a high mutational burden and have good responses to immunotherapy (Le, NEJM, 2015). We describe the natural course, clinicopathological, and genomic status of MMRD PDAC patients (pts) at Memorial Sloan Kettering Cancer Center (MSKCC). Methods: MSKCC institutional registry and ICD billing database queried from 2006-2016 for PDAC pts with genetically confirmed mutations in mismatch repair (MMR) genes. Mutation # determined via MSK-IMPACT, a targeted tumor next generation sequencing (NGS) test (Cheng, J Mol Diagn, 2015). Results: 5/607 (0.8%) PDAC pts had Lynch syndrome (LS) (confirmed germline mutations) (Table 1). Of the 5 LS pts, all had &gt; 10 mutations in NGS, with 4 of 5 having &gt; 50 mutations. 4 of 5 (80%) are alive at last follow-up (survival 30-314 months). N=4 had extensive personal/family history of cancer. Of N=3 who had resected disease, all 3 had recurrence at 11, 49 and 311 months, and all are alive (survival: 69-314 months). Of N= 2 pts that had unresectable tumors, one passed away at 30 months while the other is on checkpoint inhibitor trial and is alive at 30 months. In contrast, 7/607 (1.1%) PDAC pts had somatic mutations in MMR genes with an average of 5.7 mutations in NGS, with 4/7 having &lt;5 mutations. 4/7 (57%) are deceased at last follow-up (survival: 10-42 months). Conclusions: All cases with germline mutations in the MMR genes, with one exception, had high mutation #. All cases with somatic mutations in the MMR genes had low mutation #. Germline mutations in MMR genes and high mutational burden may predict for a prognostically favorable subgroup of PDAC pts with high susceptibility to immune oncology agents. [Table: see text]
TCT-666 Safety Evaluation of the Biodegradable Polymer-Based Sirolimus-Eluting Stent with Faster Drug Eluting Rate and Polymer Absorption Kinetics in Complex Patient and Lesion Subgroup of the PANDA III Trial
Authors: Sida Jia, Changdong Guan, Jinqing Yuan, Runlin Gao, Martin Leon, Bo Xu
Journal: Journal of the American College of Cardiology (2018)