tbuckley/cabot-search huggingface dataset:
Visualization of Fibroblast Activation After Myocardial Infarction Using 68Ga-FAPI PET
Authors: Lukas Kessler, Jana Kupusovic, Justin Ferdinandus, Nader Hirmas, Lale Umutlu, Fadi Zarrad, Michael Nader, Wolfgang P. Fendler, Matthias Totzeck, Reza Wakili, Thomas Schlosser, Tienush Rassaf, Christoph Rischpler, Johannes Siebermair
Journal: Clinical Nuclear Medicine (2021)

The aim of this retrospective analysis was to examine the pattern of cardiac 68Ga-fibroblast-activation protein-α inhibitor (FAPI) uptake in patients after acute myocardial infarction (AMI) using PET and to investigate its association with results of coronary angiography. We correlated FAPI uptake with biomarkers of myocardial damage including left ventricular function.A cohort of 10 patients with no history of coronary artery disease underwent PET 18 ± 20.6 days after AMI (ST-segment elevation myocardial infarction [n = 5] and non-ST-segment elevation infarction [n = 5]), respectively. SUVmax, SUVmean, and SUVpeak of localized tracer uptake were calculated; tracer uptake volume was reported as fibroblast activation volume (FAV), with imaging data being correlated with clinical parameters. Focal FAPI uptake was observed in all patients. Average uptake at 10 minutes postinjection was 8.9 ± 4.4 (SUVmax), 7.6 ± 4.0 (SUVpeak), and 5.3 ± 2.8 (SUVmean), respectively. Affected myocardium showed a partial to complete match between tracer uptake and confirmed culprit lesion by coronary angiography in 44.4% and 55.6% of patients, respectively. A strong correlation between FAV and peak creatine kinase level (r = 0.90, P < 0.01) and inverse correlation of FAV with left ventricular function (r = -0.69, P < 0.05) was observed.This analysis demonstrates in vivo visualization of fibroblast activation after AMI. The uptake area showed a very good agreement with the affected coronary territory. A strong correlation of the de novo established parameter FAV with left ventricular function and peak creatine kinase was observed. This imaging modality may provide important insights into mechanisms of structural remodeling after AMI at an early stage.
A dual target sequencing solution to assess genomic and epigenomic alterations in cell-free DNA with no sample splitting.
Authors: Grace Q. Zhao, Yun Bao, Heng Wang, Wanping Hu, John Coller, Shengrong Lin
Journal: Journal of Clinical Oncology (2021)

3043 Background: Assessing the genomic and epigenomic changes on plasma cell-free DNA (cfDNA) using next-generation sequencing (NGS) has become increasingly important for cancer detection and treatment selection guidance. However, two major hurdles of existing targeted NGS methods make them impractical for the clinical setting. First, there is no comprehensive, end to end, kit solution available for targeted methylation sequencing (TMS), let alone one that analyzes both mutation and methylation information in one assay. Second, the low yield of cfDNA from clinical blood samples presents a major challenge for conducting multi-omic analysis. Thus, an assay that is capable of both genomic and epigenomic analysis would be advantageous for clinical research and future diagnostic assays. Methods: Here, we report the performance of Point-n-SeqTM dual analysis, a kit solution that can provide in-depth DNA analysis with highly flexible and customizable focused panels to enable both genomic and epigenomic analysis without sample splitting. With custom panels of tens to thousands of markers designed with &gt; 99% first-pass success rate, we conducted both performance validation and multi-center, multi-operator, reproducibility studies. Using spike-in titration of cancer cell-line gDNA with known mutation and methylation profiles, Point-n-Seq assay achieved a reliable detection level down to 0.003% of tumor DNA with a linear relationship between the measured and expected fractions. Benchmarked with conventional targeted sequencing and methylation sequencing, Point-n-Seq solution also demonstrated improved performance, speed and shortened hands-on time. Results: In a pilot clinical study, a colorectal cancer (CRC) TMS panel covering 560 methylation markers and a mutation panel with &gt; 350 hotspot mutations in 22 genes were used in the dual assay. Using 1ml of plasma from late-stage CRC patients, cancer-specific methylation signals were detected in all samples tested, and oncogenic mutations. In an early-stage cohort (33 stage I/II CRC patient ), comparison of the analysis between tumor-informed, personalized-mutation panels (̃100 private SNVs) for each patient and the tumor-independent CRC methylation panels were conducted. The initial results showed that tumor-independent TMS assay achieved a comparable detection compared to the personalized tumor-informed approach. Moreover, cfDNA size information (fragmentome) is also integrated into the analysis of the same Point-n-Seq workflow to improve the assay sensitivity. Conclusions: Point-n-Seq dual analysis is poised to advance both research and clinical applications of early cancer detection, minimal residual disease (MRD), and monitoring.
Evaluation of GM-CSF and AS01<sub>B</sub> adjuvants in a phase I/IIa trial of a therapeutic CMV vaccine (VBI-1901) against recurrent glioblastoma (GBM).
Authors: Patrick Y. Wen, David A. Reardon, Deborah Anne Forst, Eudocia Quant Lee, Fabio Massaiti Iwamoto, Francisco Diaz-Mitoma, David E Anderson, Andrew B. Lassman
Journal: Journal of Clinical Oncology (2021)

2047 Background: Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4 + and CD8 + T cells are most frequently directed against the gB and pp65 antigens, respectively, and are immunogenic targets in a CMV-based GBM vaccine. Methods: We enrolled a total of 20 patients with KPS at least 70 and first recurrence of GBM into 2 arms of the Phase IIa extension of gB/pp65 enveloped virus-like particles (eVLPs) adjuvanted with either GM-CSF given intradermally or with AS01 B given intramuscularly (NCT03382977). Patients were vaccinated with VBI-1901 every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Results: 10 patients (6 women, 4 men) with a median age of 58 (33-67 yrs) were enrolled into the GM-CSF arm and 10 patients (3 women, 7 men) with a median age of 65 (40-67) enrolled into the AS01 B arm. Disease control rates of 40% and 50% were observed in the GM-CSF and AS01 B arms, respectively, with 2 sustained PRs in the GM-CSF arm. The 6-month OS rate for the GM-CSF arm is 80% and is estimated to be comparable for the AS01 B arm. CMV-specific CD4+ effector memory T cells may correlate with tumor responses in both arms of the study, with AS01 B boosting higher frequencies of these cells regardless of baseline CD4/CD8 ratio. Conclusions: These encouraging results from both arms of the trial justify further clinical evaluation in a randomized, controlled trial expected to begin later in 2021. Clinical trial information: NCT03382977.
Abstract 13416: Natural and Surgical Menopause Before Age 40 Are Associated With Long-Term Incident Cardiovascular Disease Risk
Authors: Michael Honigberg, Seyedeh M Zekavat, Krishna Aragam, Derek Klarin, Nandita Scott, Pradeep Natarajan
Journal: Circulation (2019)

Introduction: Recent guidelines endorse using history of premature menopause (i.e., < age 40 years) to refine atherosclerotic cardiovascular disease risk assessments among middle-aged women, though...
2型糖尿病患者におけるヘモグロビン A 1c レベルについてのエアロビクスおよびレジスタンストレーニングの影響 無作為化対照試験
Authors: S Church Timothy, N Blair Steven, Cocreham Shannon, Johannsen Neil, Johnson William, Kramer Kimberly, R Mikus Catherine, Myers Valerie, Nauta Melissa, Q Rodarte Ruben, Sparks Lauren, Thompson Angela, P Earnest Conrad
Journal: JAMA (2010)
Integrated genomic and transcriptomic analysis identified <i>KRT18</i> mutation and <i>MTAP</i> loss as key genetic alterations related to the prognosis of astrocytoma and glioblastoma.
Authors: Zhiyong Li, Yinghui Jin, Qingping Zou, Xiaofeng Shi, Kaishu Li, Qun He, Zhiying Lin, Xiran Wang, Sidi Xie, Lei Gao, Bowen Ni, Yunxiao Zhang, Ziyu Wang, Rui Liu, Yawei Liu, Guanglong Huang, Songtao Qi
Journal: Journal of Clinical Oncology (2021)

e14039 Background: Astrocytoma and glioblastoma (GBM) are two main subtypes of glioma classified by WHO guide of center nervous system (CNS) tumors to different grades. GBM is the most malignant among all CNS tumors with a 5-year survival rate of less than 5%. Although the prognosis of patients with astrocytoma is better than that of GBM in general, astrocytoma patients with IDH wild-type have a similar prognosis as GBM. Exploring the molecular driving force behind the malignant phenotype of astrocytoma and GBM will help explain the diversity of glioma and discover new drug targets. Methods: We enrolled 12 patients with astrocytoma and 12 patients with GBM and performed whole-exome sequencing (WES) and RNA-seq analysis on tumor samples from the patients. Comparative analysis of somatic mutation, copy number variation, cytoband alteration and differently expressed genes were performed between astrocytoma and GBM. Immune cells infiltration was analyzed by CIBERSORT Algorithm with LM22 immune subsets. Results: This study includes 14 male patients and 10 female patients, and the median age was 45.5 (range, 18-68) years old. Seven patients had IDH1 mutation, including 6 patients with astrocytoma and 1 patient with GBM. Somatic mutation of KRT18, which is associated with cell apoptosis and adhesion by interacting with TRADD and Pinin , was significantly enriched in astrocytoma, but rare in GBM. Copy number loss of MTAP, which is a potential drug target and closely related to a poor prognosis of glioma, was found significantly enriched in GBM. Pathway enrichment analysis found that GBM was mainly enriched in tumor-related pathways, such as cell adhesion, cell division, and angiogenesis, but astrocytoma was mainly enriched in pathways with ion transport, cell-cell signaling and neurogenesis. Immune cells infiltration analysis showed that macrophages M0 was significantly enriched in GBM, and activated mast cells, monocytes and plasma cells were significantly enriched in astrocytoma. Conclusions: This study revealed the distinct characteristics of astrocytoma and GBM at the DNA and RNA levels. Somatic mutation of KRT18, which was first reported in glioma, may be closely related to the malignant phenotype of astrocytoma. Copy number loss of MTAP, which was associated with the susceptibility to purine starvation and specific chemotherapy, was a key genetic alterative gene in GBM and had the potential to become the therapeutic target of GBM.
Province-wide analysis of patient reported outcomes for stage IV non-small cell lung cancer.
Authors: Michael Chandra Tjong, Mark Doherty, Hendrick Tan, Wing Chan, Haoyu Zhao, Julie Hallet, Gail Elizabeth Darling, Biniam Kidane, Frances Catriona Wright, Alyson Mahar, Laura E Davis, Victoria Delibasic, Ambika Parmar, Nicole Mittmann, Natalie G. Coburn, Alexander V Louie
Journal: Journal of Clinical Oncology (2021)

12092 Background: Stage IV NSCLC patients have significant disease and treatment-related morbidity. In Ontario, Canada, cancer patients complete Edmonton Symptom Assessment System (ESAS) questionnaires, a tool that elicits patients’ self-reported severity of common cancer-associated symptoms at clinical encounters. ESAS domains are: anxiety, depression, drowsiness, appetite, nausea, pain, shortness of breath, tiredness and well-being. The purpose of this study is to examine moderate-to-severe symptom burden in the 12 months following a diagnosis of stage IV NSCLC. Methods: Using administrative databases and unique encoded identifiers, stage IV NSCLC diagnosed between January 2007 and September 2018 were evaluated for symptom screening with ESAS in the 12 months following diagnosis. Proportion of patients reporting moderate-to-severe score (i.e. ESAS ≥4) in each domain within 12 months were calculated. Patients reporting moderate-to-severe within the different ESAS domains of were plotted over time. Multivariable (MV) Poisson regression models with potential covariates such as age, sex, Elixhauser comorbidity index, income quintiles, and lung cancer treatments received were constructed to identify factors associated with moderate-to-severe symptoms. Results: Of 22,799 stage IV NSCLC patients, 13,289 (58.3%) had completed ESAS (84,373 unique assessments) in the year following diagnosis. Patients with older age, high comorbidity, and not receiving active cancer therapy were less likely to complete ESAS. Most (94.4%) reported at least 1 moderate-to-severe score. Most prevalent moderate-to-severe ESAS symptoms within 12 months after diagnosis were tiredness (84.1%), lack of wellbeing (80.7%), low appetite (71.7%), and shortness of breath (67.8%); nausea was the least prevalent (34.6%). Most symptoms peaked at diagnosis and persisted in the year after diagnosis. On adjusted MV analyses, patients with high comorbidity, low income, and urban residency were associated with increased moderate-to-severe symptoms. Moderate-to-severe scores in all ESAS symptoms were associated with delivery of radiotherapy within 2 weeks prior, while moderate-to-severe nausea, drowsiness, tiredness, low appetite, and lack of wellbeing were associated with delivery of systemic therapy within preceding 2 weeks. Conclusions: In this population-based analysis of stage IV NSCLC PROs in the year following diagnosis, moderate-to-severe symptoms were highly prevalent and persistently high, underscoring the need to address supportive requirements in this at-risk population.
Aortic Branch Aneurysms and Vascular Risk in Patients With Marfan Syndrome
Authors: Angela Lopez-Sainz, Laia Mila, Jose Rodriguez-Palomares, Javier Limeres, Chiara Granato, Lucia La Mura, Anna Sabate-Rotes, Andrea Guala, Laura Gutiérrez, Laura Galian-Gay, Augusto Sao-Aviles, Sergi Bellmunt, Rafael Rodriguez, Hug Cuellar-Calabria, Albert Roque, Ignacio Ferreira-González, Artur Evangelista, Gisela Teixido-Tura
Journal: Journal of the American College of Cardiology (2021)
Impact of comprehensive geriatric assesment (CGA) in the treatment decision and outcome of older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Authors: Sandra Llop Serna, Clara Ejarque Martinez, Jesús Brenes Castro, Macarena Honorato, M. Esther Vilajosana Altamis, Mireia Melero, Oriol Bermejo, Victoria Gomez Garcia, Marta Fulla, Montse Goma, Isabel Linares, Alicia Lozano, Miren Taberna, Ricard Mesia, Maria Plana, Maite Antonio Rebollo, Marc Oliva Bernal
Journal: Journal of Clinical Oncology (2021)

6057 Background: Up to 24% of patients (pts) newly-diagnosed with LA-HNSCC are 70 years old (yo). NCCN guidelines recommend a geriatric assessment to guide treatment decisions in this pts population. Comprehensive geriatric assessment (CGA) of older HNSCC pts was implemented at our institution in 2018. We evaluated the impact of CGA in treatment decision and outcome and compare it to a control cohort with no CGA treated within the same institution. Methods: Retrospective single-institution analysis of two consecutively-treated cohorts of newly-diagnosed elderly LA-HNSCC pts treated at the Catalan Institute of Oncology: a cohort treated based on CGA between 2018-2020; and a control cohort with no CGA treated based on physician criteria following tumor board decision between 2016-2018. Pts demographics and disease characteristics were obtained from our in-site prospective database. Treatment received (standard, adjusted, palliative-intent, best supportive care [BSC]), treatment completion rate (TCR) an overall response rate (ORR) after conservative treatment were collected and compared for both cohorts using chi-square. Results: A total of 197 pts were included: CGA cohort =81; Control cohort=96. Baseline characteristics were similar between cohorts (Table). Pts in CGA cohort were classified as fit (F) 35 (34.7%), medium-fit (MF) 51 (50.5%) and unfit (UF) 15 (14.9%) according to CGA results. CGA changed final treatment decision following tumor board in 31 % of the cases. Pts were more likely to receive standard treatment in the CGA cohort when compared control (36 vs 21%; p = 0.048), with no differences observed in TCR (84% vs 86%; p = 0.805). In pts who underwent conservative treatment, ORR was similar between CGA and control cohort (73.9% vs 66.7 %; p = 0.082), respectively. Tumor progression was the major cause of death in both groups. Conclusions: Older pts with LA-HNSCC who underwent CGA were more likely to receive standard treatment than those who did not, supporting the relevance of CGA for clinical decision-making in this pt population. No differences were observed in CRR, TCR or death cause. In-deep survival analysis are on-going.[Table: see text]
Population pharmacokinetics (Pop PK) of MYL-1402O (a proposed biosimilar to bevacizumab) and reference product (Avastin) in patients with nonsquamous non-small cell lung cancer (nsNSCLC).
Authors: Joel Owen, Russell J. Rackley, Matthew A. Hummel, Stefan Roepcke, Hannah Huang, Mark S. Liu, Tazeen A. Idris, Sundara Moorthi Nainar Murugesan, Ashwini Vishweswaramurthy, Subramanian Loganathan, Gopinath Ranganna, Abhijit J. Barve, Cornelius Waller, Mark A. Socinski
Journal: Journal of Clinical Oncology (2021)

e21087 Background: MYL-1402O (MYL) is a proposed biosimilar to bevacizumab reference product. A multicenter, double blind randomized, phase 3 study compared the efficacy, safety, PK, and immunogenicity of MYL and Avastin in patients with Stage IV metastatic nsNSCLC. Patients received either MYL or reference product, in combination with carboplatin-paclitaxel up to 18 weeks (6 cycles) followed by monotherapy for up to an additional 24 weeks (8 cycles). The objective was to develop a Pop PK model based on data from a phase 3 study pooled with a single dose healthy volunteer phase 1 study data; to assess PK linearity across the dose levels of 1 mg/kg to 15 mg/kg in 2 clinical studies; to assess the PK similarity of MYL and reference product in patients with nsNSCLC; and to explore potential covariates to account for variability in Pop PK model parameters. Methods: A Pop PK model was developed based on preliminary analyses of MYL phase 1 data and published population analyses of reference product using a 2-compartment linear model (Han K et al., 2016). Individual empiric Bayesian parameter estimates of nsNSCLC patients were used to predict PK measures reflecting exposure to drug and were compared qualitatively between treatments. Results: The data subset used for model development consisted of 8724 records from 771 subjects. Population PK analyses indicated no differences between PK profiles of patients in the MYL and reference product arms. Importantly, treatment was not a significant covariate of clearance ( P = 0.453) or volume of the central compartment ( P = 0.161) using the likelihood ratio χ 2 test. Model-based steady state exposure measures, predicted based on the final model for all patients, were also similar between treatment arms (Table). Conclusions: The model supported linear PK at clinical doses in patients with nsNSCLC; there were no clinically relevant/significant differences between the PK of MYL and reference product; and the findings were consistent with the PK study in normal, healthy volunteers. Bayesian Parameter Clinical trial information: 2015-005141-32. [Table: see text]
Association of parental cancer and school absenteeism, medical financial hardship, healthcare use, and psychological distress among minor children.
Authors: Zhiyuan Zheng, Jingxuan Zhao, Xuesong Han, Leticia Nogueira, Robin Robin Yabroff
Journal: Journal of Clinical Oncology (2021)

6544 Background: A cancer diagnosis can affect the entire family, including minor children. However, little is known about the association of parental cancer on minor children’s school absenteeism, family’s financial ability to afford healthcare for children, as well as healthcare use, psychological distress, and behavioral problems. Methods: The 2015 to 2018 National Health Interview Survey was used to identify minor children (ages 5-17 years) whose parent(s) reported a cancer history (n = 695, representing 1.2 million children) and children whose parent did not report a cancer history (n = 19,122, representing 35.7 million children). Separate multivariable logistic regressions were used to compare school absenteeism, financial hardship, healthcare use, and psychological distress among children with and without parental cancer history. All analyses adjusted for children’s age group (5-11 years, 12-14 years, and 15-17 years), sex, family income as a percentage of the federal poverty line, marital status of their parents, survey year, and region. Results: Children of cancer survivors were more likely to receive annual well-child checkups, experience school absenteeism, take prescription medications for more than 3 months, visit hospital emergency rooms, suffer psychological distress, and have behavioral problems than children of parents without a cancer history (Table). Conclusions: Parental cancer history is associated with disruption in their minor children’s life. The associated psychological distress and physical and emotional health among these children may develop into more severe health issues in adulthood. Special attention to minor children of parents with a cancer history may be required to help prevent development of longer-term physical and mental health problems.[Table: see text]