tbuckley/cabot-search huggingface dataset:
The efficacy and toxicity of osimertinib in T790M-positive NSCLC with acquired resistance to EGFR-TKI in clinical practice.
Authors: Tomoaki Sonoda, Noriko Yanagitani, Masafumi Saiki, Ryo Ariyasu, Junji Koyama, Natsuki Takano, Yosuke Kawashima, Tomoyo Oguri, Shingo Nishikawa, Satoru Kitazono, Fumiyoshi Ohyanagi, Atsushi Horiike, Makoto Nishio
Journal: Journal of Clinical Oncology (2017)

e20575 Background: A Phase III study (AURA3) demonstrated that osimertinib prolonged PFS compared to platinum doublet in patients with T790M-positive non-small-cell lung cancer (NSCLC) exhibiting acquired resistance to epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI). Although the patients in the study had good PS and only one prior EGFR-TKI treatment, most practical patients had multiple prior EGFR-TKI and poor PS. Moreover, several patients exhibited symptomatic central nervous system (CNS) metastasis in clinical practice. In this study, we evaluated the efficacy and toxicity of osimertinib in clinical practice. Methods: We retrospectively analyzed 30 patients who were treated with osimertinib at our hospital from April 11th 2016 to September 30th 2016. The efficacy and toxicity was compared between the patients with matched and unmatched AURA3 eligibility criteria. Efficacy was evaluated according to RECIST ver.1.1 and toxicity was evaluated using CTCAE ver.4.0. Results: A total of 9 out of 30 patients matched the AURA3 eligibility criteria (PS ≤ 1 and one prior EGFT-TKI) and 21 patients were unmatched (PS ≥ 2 or two or more EGFR-TKI or symptomatic CNS metastasis). The overall response rate(ORR) of osimertinib was 78% and 67% for the matched and unmatched patients, respectively. The disease control rate (DCR) was 100% and 90% for the matched and unmatched patients, respectively. In addition, the response rate of symptomatic CNS metastasis was 67%. Regarding toxicity, grade 3/4 toxicities were observed in 22% of the matched patients and 33% of the unmatched patients. In the matched patients, the most frequent AE was a rash (89%) and the frequent grade 3/4 toxicities were a rash (22%) and pneumonitis (11%). In unmatched patients, the most frequent AE was also a rash (57%), but the frequent grade 3/4 toxicities were pneumonitis (14%), rash (10%), and neutropenia (10%). Conclusions: Both the ORR and DCR in the unmatched patients were slightly lower than the matched patients; however, osimertinib was still found to be beneficial in clinical practice.
TCT-422 The impact of weight loss on cardiovascular outcomes following percutaneous coronary revascularization – a contemporary, real world experience
Authors: Trevor Simard, Richard Jung, Pietro Di Santo, Francisco Ramirez, Alisha Labinaz, Ian Pitcher, Pouya Motazedian, Rebecca Rochman, Robert Moreland, Jeffrey Marbach, Paul Boland, Kiran Sarathy, Saleh Alghofaili, Juan Russo, Etienne Couture, Alexander Dick, Michael Froeschl, Michel Le May, Benjamin Hibbert
Journal: Journal of the American College of Cardiology (2018)
Nivolumab-induced interstitial lung disease (ILD) in Japanese patients with non-small cell lung cancer: A study on risk factors for fatal outcome.
Authors: Terufumi Kato, Fumikazu Sakai, Tomohisa Baba, Masahiko Kusumoto, Hirotsugu Kenmotsu, Hiroaki Sugiura, Junya Tominaga, Katsunori Oikado, Masafumi Sata, Masahiro Endo, Noriyo Yanagawa, Shinichi Sasaki, Tae Iwasawa, Yoshinobu Saito, Yutaka Fujiwara, Yuichiro Ohe, Yoshihiko Ito, Yasuhiro Tahara, Kazuyoshi Kuwano
Journal: Journal of Clinical Oncology (2017)

9077 Background: We investigated case reports of nivolumab-induced ILD in patients with non-small cell lung cancer to identify risk factors for poor prognosis of ILD. Methods: Among data obtained during post-marketing surveillance of nivolumab, case reports of ILD with detailed clinical course and chest imaging (CT) findings were assessed by the ILD Expert Review Committee, which consists of respiratory medicine specialists and expert chest radiologists. The imaging findings were examined and classified into those with typical or atypical patterns. Atypical patterns included shadows limited to surrounding tumors designated as “peritumoral infiltration”, relapse of radiation pneumonitis, worsening of underlying infection, and predominant shadow in diseased side. CT pattern was classified as DAD (diffuse alveolar damage) or non-DAD. Data were analyzed using a multivariate stepwise logistic regression analysis. Results: Among 160 reported cases of ILD, 140 cases were considered to be induced by nivolumab. Imaging findings showed typical patterns in 92 patients, and 23 (25.0%) died of ILD. Atypical patterns were noted in 48 patients, and 5 (10.4%) died of ILD. The following table summarizes the results of univariate and multivariate analyses of risk factors for poor prognosis of ILD. See table. DAD pattern was observed in 20, 14 (70%) among them showed fatal outcome, whereas non-DAD pattern showed it in 14/120 (11.7%). Male and pretreatment CRP level were significant risk factors for fatal outcome. Conclusions: Nivolumab-induced ILD may show some atypical pattern that was not seen in conventional chemotherapy or EGFR-TKI. Outcome of patients with atypical patterns was better than those with typical patterns. DAD pattern at CT, male, and pretreatment level of CRP were identified as risk factors of fatal outcome. [Table: see text]
Single cell analysis of multiple myeloma.
Authors: Guy Ledergor, Assaf Weiner, Mor Zada, Yael Chava Cohen, Moshe E Gatt, Nimrod Snir, Hila Magen, Maya Koren-Michowitz, Hadas Keren-Shaul, Venkata Yellapantula, Bruno Paiva, Arnon Nagler, Jesus San-Miguel, Dina Ben-Yehuda, Elli Papaemmanuil, Irit Avivi, Gabriel I Barbash, Amos Tanay, Ido Amit
Journal: Journal of Clinical Oncology (2018)

8026 Background: Multiple myeloma (MM) remains mostly incurable despite advances in treatments in the last decade. Major clinical challenges include: capturing inter- and intra- patient heterogeneity, stratification of asymptomatic patients, sensitive and functional identification of residual disease to tailor therapeutic strategies, as well as performing accurate liquid biopsies to mitigate the need for recurrent bone marrow (BM) sampling. Methods: To capture BM and circulating plasma cells (PC), we performed single cell RNA-seq (scRNA-seq). Index sorting enabled to link cell surface markers intensity on each cell with its expression profile. Analysis of the transcriptome together with the specific B cell receptor (BCR) using k-nearest-neighbor graphs characterizes the inter and intra tumor heterogeneity of myeloma patients in both the BM and blood at single cell resolution. Results: Analysis of more than 30,000 PC sorted from 35 patients and 12 control subjects, created a detailed map of 43 transcriptionally homogeneous subpopulations. These were based on cluster-specific expression patterns of more than 1500 genes. PC from healthy donors clustered together and displayed 4 states representing either long-lived PC or cycling short-lived PC. In contrast, each patient presented a unique PC transcriptional state, with a specific BCR clonotype. We uncover novel overexpressed genes, previously unimplicated in MM, such as LAMP5. We identify intra-tumor heterogeneity in 10/35 patients, for example, a patient with a FRZB and SMAD1 gene signature in 68% of PCs and an antimicrobial gene DEFB1 in the rest of the PC, which share the same BCR clonotype. We define new markers to differentiate normal circulating PC from tumor cells (CTC) in the blood and show that CTC mirror the BM state. Further, we accurately characterize the heterogeneity within MGUS patients into PC with a normal transcriptional state in contrast to small clones with a defined malignant program. Finally, we identify small cancer clones in the setting of minimal residual disease (MRD) following high-dose therapy. Conclusions: We show the power of scRNA-seq as a new, high resolution tool, to identify new pathways and potential targets in myeloma, stratify patients based on unique molecular programs, and identify residual disease in both the BM and blood.
Utilization of telemedicine at two high-volume cancer care organizations.
Authors: Rob Williams, Michelle Aspden, Peter D. Stetson, Christian Otto
Journal: Journal of Clinical Oncology (2018)

6604 Background: The Ontario Telemedicine Network (OTN) in Support of Cancer Care Ontario (CCO), and Memorial Sloan Kettering (MSK) are leveraging telemedicine and digital health care to improve patient/provider satisfaction, care coordination, and clinical outcomes, while decreasing costs. Methods: Data on patient telemedicine services and provider activity was reviewed, in addition to implementation challenges and lessons learned. New virtual services were outlined regarding their ability to enhance patient accessibility and clinical effectiveness. Results: OTN has enabled 268 CCO sites across the 14 Ontario Regional cancer centers which have generated 20,138 cancer telemedicine sessions in 2016/17. Prostate, lung, breast, and colorectal cancers had the highest telemedicine utilization. Telemedicine sessions were employed by 20% (N = 40) of provincial radiation oncologists, and 20% (N = 34) of medical oncologists. In 2015, telemedicine supported the delivery of oral and intravenous chemotherapy in 1,269 cases and facilitated 368 palliative care visits. Telemedicine saved patients: 6.4 million km of driving, 64K hours of travel time, and over $4.7 million in travel and accommodation costs. MSK sees 19K new actively treated patients annually, 76% access the patient portal to view appointment notifications, complete patient assessments, review lab results, retrieve learning materials, send and receive secure messages from providers, and review billing. Patient assessments include PRO-CTCAE daily symptom surveys, with symptom alerts, to track recovery in post-surgical patients. TeleGenetics at MSK has delivered 3416 virtual visits to patients and family members at four regional locations, telepsychiatry has supported 160 sessions to 3 regional sites; and an inpatient fall prevention program using video monitoring of a patient’s movements has decreased falls 42% in GI and 34% in neurology cancer inpatients while decreasing patient attendant costs $393K. Conclusions: Utilization of telemedicine and digital care platforms among cancer patients and providers is steadily increasing due to convenience, significant cost savings, high satisfaction rates, increased care coordination, and improved clinical outcomes.
Advanced support for quality of life in oncology: Brazilian private and public health insurance cancer patients' point of view.
Authors: Gustavo Fernandes Godoy Almeida, Mauricio Assuero Lima de Freitas, Marcela Silva Costa, Rafaela Batista da Silva Cordeiro, Evandro Lopes de Barros Filho, Gabriela Pereira Barreto dos Reis, Juliana Oliveira Santos, Luisa Conceicao Violet Jatoba, Estevao Michel Santana de Luna, Lauro Vinicius Machado da Silva, Alexandro Machado, Gabriel Brito Barbosa, Thais Milla Franco de Freitas, Luiz Alberto Reis Mattos
Journal: Journal of Clinical Oncology (2017)

e18229 Background: Cancer patients suffer from burden symptoms and adverse events which compromise quality-of-life. Early palliative care involvement of metastatic non-small cell lung cancer patients has demonstrated increased overall survival. Advanced Support for Quality-of-Life in Oncology - ASQO - addresses cancer and its treatment complications aiming a safe cure or symptom control and dignified death. Measure cancer patients' background and interest about their disease is critical for planning care. To study the point of view of cancer patients about ASQO and compare private and public Brazilian health insurance cancer patients. Methods: An interview was performed and SPSS was used to find means and rates. The protocol was approved by Federal University of Pernambuco ethics committee and all patients signed informed consent Results: 48 patients were interviewed, 28 at Hospital das Clinicas Federal University of Pernambuco and 20 at ÓNKOS Oncology. Attached tables show demographic data and patients’ background, interest and opinion. The topics on which more and less patients’ background were “Chances of cure” (85%) and “Fertility” (25%); Fertility (59%) and participation in clinical research (40%) were the subjects for which more and less patients wanted additional information; Among those patients who wanted additional information about any topic, the theme on which more and less comments were made were “Pain” (100%) and individualization of treatment (10%); Goals of treatment (89%) and fertility (41%) were the subjects that more and less patients were satisfied with the information received Conclusions: In Brazil, the majority of cancer patients don’t have the opportunity to discuss treatment goals and fertility is not widely discussed with them. This translated into highest percentage of interest in the subject and a higher degree of dissatisfaction with the information received, despite median age of 58 years in the study population. The high prevalence of uncontrolled pain reflected in 100% of responders have made additional comments, indicating a need for health professionals education to adequately manage this symptom. Clinical trial information: CAAE 50921215.8.0000.5208.
Non-invasive <i>in vivo</i> prediction of tumour grade and <i>IDH</i> mutation status in gliomas using dynamic susceptibility contrast (DSC) perfusion- and diffusion-weighted MRI.
Authors: Sotirios Bisdas, Cristiana Tisca, Carole Sudre, Eser Sanverdi, Diana Roettger, Jorge M Cardoso
Journal: Journal of Clinical Oncology (2018)

e24173 Background: Analysis of perfusion- and diffusion-weighted MRI may enhance tumour grading and IDH phenotyping, improving patient selection for specific treatment options. We investigated the relevance of texture and statistical features extracted from perfusion and diffusion MRI parametric maps (PMs) to discriminate between WHO grades and IDH mutation status in gliomas. Methods: 95 subjects with gliomas underwent treatment-naïve MRI scanning. Apparent diffusion coefficient (ADC) maps and PMs of tumour relative cerebral blood flow (rCBF), leakage-corrected relative cerebral blood volume (rCBV) and permeability (K2) were generated. Distribution and texture features were extracted in the tumour area. Group differences across tumour grades and IDH mutation status were evaluated using Wilcoxon signed-rank test. Results: Significant differences between tumour grades were observed across multiple PMs and the extracted features (Table 1). Most features, particularly the rCBV-related ones, were helpful to differentiate between the mutant and wild-type IDH phenotypes (Table 1). Conclusions: Texture features from PMs and notably rCBV show significant differences between tumour grades and IDH mutation status. Further studies have the potential to further validate this assumption and establish rCBV as surrogate biomarker. Table 1. Diagnostic performance of different features extracted from perfusion- and diffusion-weighted maps for glioma grading and non-invasive IDH phenotyping. Parametric map Skewness Kurtosis Min Max Standard Deviation 25% percentile Median 75% percentile Contrast Correlation Sum Square Sum Average Difference Variance Sum Variance Information Measure of Correlation WHO grade 2 vs 3 rCBV * rCBF K2 ADC * WHO grade 2 vs 4 rCBV ¶ ¶ ^ ^ ^ ¶ ^ ^ ^ rCBF * * * ^ * K2 * ^ * * ADC * ¶ ¶ ^ * ¶ ¶ * ¶ WHO grade 3 vs 4 rCBV ^ * * * ^ ¶ * * * * rCBF ^ * K2 ^ * ADC ^ ^ Wild type vs mutant IDH rCBV ¶ ¶ * * ^ ¶ ¶ ¶ ¶ ¶ ¶ rCBF * ^ ^ * ^ K2 ^ * * ^ ¶ ¶ ¶ ¶ ¶ ADC ¶ ¶ ¶ ^ ^ ^ ^ *: p < 0.05 ^: p < 0.01 ¶: p < 0.001.
Abstract 14370: Randomized Trial of Short vs Ultra Short Radial Artery Clamp Time Post Trans-radial Cardiac Catheterization
Authors: Shahar Lavi, Andrew Yadegari, Asim Cheema, Rodrigo Bagur, Nour AbuRomeh, Yaniv Levi, Yasir Parviz, Zeev Israeli, Kokab Awan, Mistre Alemayehu, Dorian Murariu, Sabrina Wall, Terry McPherson, Jaffer Syed
Journal: Circulation (2016)

Introduction: Radial artery occlusion (RAO) is a known complication following transradial cardiac catheterization. A shorter duration of radial clamp time post procedure may reduce this risk. Howev...
Sentinel lymph node biopsy in medullary thyroid microcarcinomas after methylene blue dye mapping: A pilot study.
Authors: Radan Dzodic, Nada Santrac, Merima Goran, Marko Buta, Igor Djurisic, Gordana Pupic, Ognjen Zivkovic, Ivan Markovic
Journal: Journal of Clinical Oncology (2016)

e17549 Background: Serum calcitonin level (sCT) is a precise marker for medullary thyroid carcinoma (MTC). However, lymph node (LN) metastases can be found in lower sCT. Further, preoperative ultrasound examination is not reliable enough for assessment of regional LNs. The aim of this pilot study was to analyze usefulness of sentinel lymph node (SLN) biopsy of jugulo-carotid chains, after methylene blue dye mapping procedure, for selection of clinically N0, but true-positive patients with micro-MTC for one-time modified radical neck dissection (MRND). Methods: This pilot study included 14 patients operated in our surgical clinic from 2007 to 2016th due to MTC with sCT lower than 1000pg/ml, tumors ≤ 10mm in size and clinically negative LNs. Patients with sCT > 1000pg/ml, larger tumors and cervical lymphadenopathy were excluded. All patients underwent total thyroidectomy and central neck dissection. SLN mapping was performed with intrathyroid subcapsular injection of 1%-methylene blue dye (0.2-0.5ml). Levels II and III were explored on both sides, blue stained SLNs were removed and examined by frozen section analysis. If SLNs were benign, additional surrounding non-colored LNs were removed for more precise evaluation. If SLNs were malignant, one-time MRND was performed. Results: One patient had hereditary form of MTC, with bilateral subcentimeter tumors and sCT of 200pg/ml, while others had sporadic, unilateral MTC. Sporadic MTCs showed no central or jugulo-carotid LN metastases on bilateral SLN biopsy, with no indication for MRND. Hereditary MTC patient had central LN metastases, with positive SLNs on both sides, thus bilateral MRND was performed. Metastases were found in other dissected jugulo-carotid LNs, as well. Frozen section and definite pathological analysis were 100% match. Conclusions: This pilot study is the first reported experience with SLN biopsy of jugulo-carotid chains in MTC after methylene blue dye injection. This original technique is feasible and can be precisely used for intraoperative assessment of jugulo-carotid LNs. It optimizes surgery for patients with micro MTCs, selecting clinically N0, but true positive patients for one-time MRND.
Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis
Authors: Bjørt K. Kragesteen, Malte Spielmann, Christina Paliou, Verena Heinrich, Robert Schöpflin, Andrea Esposito, Carlo Annunziatella, Simona Bianco, Andrea M. Chiariello, Ivana Jerković, Izabela Harabula, Philine Guckelberger, Michael Pechstein, Lars Wittler, Wing-Lee Chan, Martin Franke, Darío G. Lupiáñez, Katerina Kraft, Bernd Timmermann, Martin Vingron, Axel Visel, Mario Nicodemi, Stefan Mundlos, Guillaume Andrey
Journal: Nature Genetics (2018)
Genome-wide discovery of novel susceptibility loci for treatment-associated hypothyroidism among survivors of pediatric medulloblastoma.
Authors: Austin L Brown, Kevin J. Biclamowicz, Rona Sonabend, Michael E. Scheurer, Philip Lupo, Arnold Paulino, ZoAnn Eckert Dreyer, Anita Mahajan, Murali M. Chintagumpala, M. Fatih Okcu
Journal: Journal of Clinical Oncology (2017)

10571 Background: Pediatric medulloblastoma patients exposed to craniospinal radiation (CSI) are at high risk of developing endocrinopathies, including hypothyroidism. We sought to evaluate the role of genetic variation on hypothyroidism susceptibility among survivors of pediatric medullobastoma. Methods: Records from 61 medulloblastoma survivors treated at Texas Children’s Hospital between 1997 and 2013 were reviewed. All patients completed baseline and yearly follow-up thyroid assessments. Genome-wide genotyping was performed on Illumina HumanOmni1 and HumanOmni2.5 BeadChip single nucleotide polymorphism (SNP) arrays. Following standard quality control measures and exclusion of rare variants (minor allele frequency [MAF] &lt; 5%), 572,562 autosomal SNPs were included in our analyses. The association between each SNP and hypothyroidism was tested using Fisher’s exact test and logistic regression, assuming additive allelic effects. Results: A total of 25 patients (41%) developed hypothyroidism with median follow-up of 8.3 years from diagnosis (range: 1.8-17.2 years). Primary hypothyroidism was identified in 9 (36%) cases, while the remaining 16 (64%) developed central hypothyroidism. Hypothyroidism was detected in 13 of 40 (33%) individuals exposed to &lt; 30 Gy CSI and 12 of 21 (57%) individuals exposed to ≥30 Gy CSI (p = 0.06). Genome-wide association analysis identified several risk loci, including 3 variants associated with hypothyroidism (p-value &lt; 1x10 -5 ) at chromosome 2q11.2 ( NPAS2 gene). The top overall SNP (MAF = 27.5%, p-value = 6.5x10 -7 ) remained strongly associated with hypothyroidism after accounting for possible confounders, including CSI dose, CSI type (proton/photon), age, sex, and genetic ancestry. Conclusions: Our findings suggest susceptibility to treatment-related hypothyroidism is strongly influenced by common genetic variation in NPAS2. The NPAS2 gene, a central component of the circadian rhythm network, is a transcriptional activator and regulator of DNA damage response and DNA repair genes.
Stereotactic comparison study of <sup>18</sup>F-Alfatide and <sup>18</sup>F-FDG PET imaging in LLC tumor-bearing C57BL/6 mice model.
Authors: Yuchun Wei, Yongsheng Gao, Jianbo Zhang, Xudong Hu, Wenhong Hou, Ning Liu, Song Gao, Jinming Yu, Shuanghu Yuan
Journal: Journal of Clinical Oncology (2016)

e20070 Background: Tumor background ratio of 18F-FDG PET in some organs and some diabetic patients is not sufficiently high enough for a diagnosis. New tracers have been developed as supplements. Because Arginine-Glycine-Aspartic (RGD) can specifically bind to integrin αvβ3 which is significantly up-regulated in various types of tumor cells, we use 18F-alfatide as a RGD tracer for PET imaging of αvβ3 in cancer. This study aimed to stereotactically compare the PET imaging performance of 18F-Alfatide and 18F-FDG and immunohistochemistry (IHC) staining in a Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. Methods: Mice (n = 15) were investigated by PET imaging using 18F-Alfatide and 18F-FDG separately. 18F-Alfatide standard uptake value (SUV) and 18F-FDG SUV were measured in normal tissues, organs and the overall tumor at 1 hour after injection. The PET SUV and αvβ3 and GLUT-1 expression on IHC were further measured and correlated with each other stereotactically when the xenografts were divided into outer (SUVRGD-O , SUVFDG-O ), middle (SUVRGD-M , SUVFDG-M ) and inner (SUVRGD-I , SUVFDG-I ) layers. Results: The tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of 18F-Alfatide PET were significantly higher than those of 18F-FDG PET (P < 0.001). The spatial heterogeneity of the tumors was detected, and the tracer accumulation enhanced from the outer layer to the inner layer consistently using the two tracers (SUVFDG-O , SUVFDG-M , and SUVFDG-I were 3.04±0.64, 6.33±1.16, 9.95±1.64, respectively; SUVRGD-O , SUVRGD-M , and SUVRGD-I were 1.46±0.30, 1.96±0.37, 2.36±0.37, respectively; P < 0.001). PET imaging was validated by IHC examination. The parameters of the tumors were significantly correlated with each other between 18F-FDG SUV and GLUT-1 (R=0.895, P<0.001), 18F-Alfatide SUV and αvβ3 (R=0.595, P=0.019), 18F-FDG SUV and 18F-Alfatide SUV (R=0.917, P<0.001), and GLUT-1 and αvβ3 (R=0.637, P=0.011). Conclusions: 18F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to 18F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study.