tbuckley/cabot-search huggingface dataset:
Abstract NT-121: AN ANTI-AMPHIREGULIN ANTIBODY AS POTENTIAL TREATMENT FOR OVARIAN CANCER
Authors: Einav Zmora, Moshit Lindzen, Yosef Yarden
Journal: Clinical Cancer Research (2019)

Abstract The ErbB family of receptors consists of four receptors, which bind with eleven ligands. These EGF-like ligands can be classified according to their affinity to EGFR: EGF, TGFα, HB-EGF and betacellulin are considered high affinity ligands, whereas AREG, EREG and EPGN are considered low affinity ligands. The literature reports that AREG is a type II cytokine which plays a role in inflammation, its expression is known to contribute to tissue repair and regeneration due to its ability to promote cell survival and proliferation. Furthermore, AREG is expressed by activated Th2 cells, mast cells, eosinophils, basophils and M1 macrophages. Profiling the repertoire of EGF-like ligands in ascites fluids collected from 43 ovarian cancer patients, we found that 86% expressed high levels of AREG. These findings lead us to generate an anti-AREG antibody active against both human and murine AREG. Efficacy of this antibody was tested in several in vivo experiments using anti-AERG alone or in combination with chemotherapy (cisplatin). A murine anti-EGFR antibody was used as a positive control. Our results showed a significant prolongation of the lifespan of mice treated with an anti-AREG antibody, postponing the advancement of the disease compared to the control untreated group, or the groups treated with an anti-EGFR antibody or with chemotherapy only. One of our next goals is to establish a model that is completely murine. We are using immunocompetent C57 black female mice, the ID8 cell line which is an ovarian cancer mouse cell line and our antibody, which blocks the murine form of AREG. We hope that in this way we would be able to evaluate the involvement of the immune system. The knowledge we will gain about the efficacy and toxicity of an anti-AREG approach may not be available from humanized models. Citation Format: Einav Zmora, Moshit Lindzen, Yosef Yarden. AN ANTI-AMPHIREGULIN ANTIBODY AS POTENTIAL TREATMENT FOR OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-121.
HGG-22. EVALUATING THE REGULATION OF BLOOD-BRAIN BARRIER INTEGRITY IN DIPG MOUSE MODELS
Authors: Xin Wei, Timothy Phoenix
Journal: Neuro-Oncology (2021)

Abstract Diffuse intrinsic pontine gliomas (DIPGs) are considered to maintain a fairly intact blood-brain barrier (BBB) based on patient imaging tumor histology. In characterizing recently developed DIPG and HGG mouse models, we identified differences in BBB function and increased Angiopoietin1 (Angpt1) in H3 K27M DIPG models. We hypothesize that H3 K27M mutations promote the maintenance of DIPG BBB integrity through upregulation of Angpt1. To determine DIPG and HGG BBB phenotypes we performed an intergrative analysis of vascular histology and endothelial transcriptomes Ongoing studies using electroporation based DIPG mouse models are being performed examine the regulation and function of Angpt1 in DIPG BBB integrity. We have initiated studies comparing H3 K27M DIPG mouse models to H3 WT and G34R cortical HGG mouse models, demonstrating that DIPG models show minimal changes in vascular phenotype, including vessel density, branching, and diameter compared to cortical HGG models. Comparing DIPG and HGG purified endothelial transcriptomes, HGG ECs displayed enrichments of inflammatory signals and proliferation gene sets, and increased expression of tip cell identity genes. We identified Angpt1 as selectively upregulated in H3 K27M mouse models and derived cell lines. Preliminary data suggests Angpt1 supports the maintenance of BBB integrity in DIPG models. BBB phenotype differences are present in DIPG and HGG mouse models. Uncovering mutation specific mechanisms that regulate BBB function in brain tumors will be critical to advance our understanding of brain tumor pathogenesis and treatment response.
Trends in the incidence of endometrial cancer among young women in the United States, 2001 to 2017.
Authors: Fangjian Guo, Lyuba Levine, Abbey Berenson
Journal: Journal of Clinical Oncology (2021)

5578 Background: Endometrial cancer at this time is predominantly being looked at as a disease of postmenopausal population. Increased obesity has been identified as an important risk factor for endometrial cancer. An overall increase incidence of endometrial hyperplasia and endometrial carcinoma in obese premenopausal women has been reported. A close examination of the relationship between trends in endometrial cancer incidence and obesity prevalence in young women will provide important information for prevention and early screening of the disease and its precursors. This study was to assess current trends in endometrial cancer incidence in women ages 20-29 and 30-39 years in relationship to obesity in the US. Methods: We used data on US adult women 20-39 years old from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence–U.S. Cancer Statistics 2001–2017 database. This database covered essentially all young female population between 2001 and 2017 in the US (Puerto Rico not included). Incidence was age adjusted to the 2020 U.S. standard population. We also examined the trends in obesity prevalence among females 18-34 years old using data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Results: There were 24,446 cases of endometrial cancer among young adult women aged 20-39 years during 2001-2017. Endometrial cancer incidence increased from 0.6 per 100,000 in 2001 to 1.2 per 100,000 in 2017 (APC 3.6, 95% CI 2.9-4.4) among young women 20-29 years old, and increased from 4.6 per 100,000 in 2001 to 7.5 per 100,000 in 2017 (APC 3.0, 95% CI 2.7-3.3) among women 30-39 years old. Obesity prevalence also increased significantly from 1988-2014 among females 18-34 years old. Incidence of endometrial cancer and obesity prevalence were both higher in Hispanics than in other racial/ethnic groups. Conclusions: The significant increasing incidence in endometrial cancer among young adult women is in accordance with the concurrent increasing prevalence in obesity in young girls and women in the US. This indicates that endometrial cancer screening might need to be considered at much earlier age among patients with abnormal bleeding and certain ethnic populations.
KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma
Authors: Sundar Jagannath, Yi Lin, Hartmut Goldschmidt, Donna Reece, Ajay Nooka, Alicia Senin, Paula Rodriguez-Otero, Ray Powles, Kosei Matsue, Nina Shah, Larry D. Anderson, Matthew Streetly, Kimberly Wilson, Hoa Van Le, Arlene S. Swern, Amit Agarwal, David S. Siegel
Journal: Blood Cancer Journal (2021)

Abstract Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P &lt; 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM.
Pooled Analysis of Day +100 Survival for Defibrotide-Treated Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) and Ventilator or Dialysis Dependence Following Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Paul G Richardson, Angela R. Smith, Nancy A. Kernan, Joseph H. Antin, Leslie Lehmann, Robert J. Ryan, Robin L. Hume, William Martin Tappe, Stephan A Grupp
Journal: Blood (2017)
BRAF testing timelines and impact on the starting of systemic treatment.
Authors: Diana Paola Arteaga, Zaid Saeed Kamil, Thiago Pimentel Muniz, Diane Liu, Ian King, Tracy Stockley, Diana Gray, Samuel Saibil, David Hogg, Anna Spreafico, Marcus O. Butler
Journal: Journal of Clinical Oncology (2021)

e21575 Background: Targeted therapy with BRAF and MEK inhibitors constitute part of the standard treatment for BRAF V600 mutated melanoma. Timely detection of BRAF mutation is necessary for clinicians and patients to make treatment decisions. We aimed to map the BRAF testing timelines from the time of request until the reported result in order to assess obstacles to timely BRAF reporting in our community, and its impact on the initiation of systemic therapy. Methods: In this single-center retrospective study, we included adult patients referred to the Medical Oncology Department at the Princess Margaret Cancer Centre (PM) from January 2019 to August 2019 with histologically confirmed cutaneous or mucosal melanoma and BRAF molecular testing performed in 2019. The Log-Rank method was applied to detect differences in BRAF turnaround time and time to treatment initiation in specified subgroups. A p value &lt; 0.05 was considered statistically significant. Results: Sixty-six cases were identified. The median age was 64 (24-88), and 42 (64%) were male. At the time of BRAF request, 10 (15%) patients had stage II, 33 (50%) had stage III, and 23 (35%) had stage IV disease. Twenty-eight (43%) were positive for the BRAF V600E/K mutation by ARMS assay and 4 (6%) for other variants by NGS test. Thirty-three (50%) patients had the BRAF test available at their first PM Medical Oncology visit. Median time between BRAF request and result was 17 days; when a reflex BRAF test was ordered by the Pathology Department, the median turnaround time was 12 days (95% CI 8-15), compared to 20 days (95% CI 16-23) if the order was requested by another specialist ( p &lt; 0.001). Median time to transfer samples between institutions was 6 days. If the BRAF test was processed within the institution where the biopsy was performed, the BRAF median turnaround time was 13 days (95% CI 6-19) compared to 19 days (95% CI 16-21) if a sample was transferred to another institution ( p = 0.02). In total, 49 patients had systemic therapy. Median time between the first visit with Medical Oncology and treatment initiation was 29 days and was not statistically different if the BRAF result was available or not (28 vs. 34 days; p = 0.09). In the subgroup with stage IV disease (Table), 20 patients received systemic therapy; the median time to treatment initiation was 24 days and differed with BRAF result availability (20 vs. 31 days, p = 0.03). Conclusions: The current BRAF testing timeline at the PM varies from days to weeks. A major factor impacting this timeline is transfer time, which can be streamlined by pathology reflex testing. Delays in turnaround time appears to impact subsequent timing and type of therapeutic interventions, especially in patients with stage IV disease.[Table: see text]
Multifunctional microcapsules: A theranostic agent for US/MR/PAT multi-modality imaging and synergistic chemo-photothermal osteosarcoma therapy
Authors: Hufei Wang, Sijia Xu, Daoyang Fan, Xiaowen Geng, Guang Zhi, Decheng Wu, Hong Shen, Fei Yang, Xiao Zhou, Xing Wang
Journal: Bioactive Materials (2021)

Development of versatile theranostic agents that simultaneously integrate therapeutic and diagnostic features remains a clinical urgent. Herein, we aimed to prepare uniform PEGylated (lactic-co-glycolic acid) (PLGA) microcapsules (PB@(Fe
Cerebral Venous Sinus Thrombosis in the U.S. Population, After Adenovirus-Based SARS-CoV-2 Vaccination, and After COVID-19
Authors: Behnood Bikdeli, Saurav Chatterjee, Shilpkumar Arora, Manuel Monreal, David Jimenez, Harlan M. Krumholz, Samuel Z. Goldhaber, Mitchell S.V. Elkind, Gregory Piazza
Journal: Journal of the American College of Cardiology (2021)
Interventions for Patients With Secondary Mitral Regurgitation
Authors: Sameer Hirji, Adam S. Cifu, Tsuyoshi Kaneko
Journal: JAMA (2021)

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A multicenter, open-label, uncontrolled phase II study of ONO-4538 for cutaneous angiosarcoma (Angio Check study).
Authors: Yasuhiro Fujisawa, Koji Yoshino, Taiki Isei, Kenjiro Namikawa, Taku Fujimura, Masahito Yasuda, Yuki Yamamoto, Hiroshi Uchi, Teruki Yanagi, Hiroshi Kato, Atsushi Otsuka
Journal: Journal of Clinical Oncology (2021)

TPS11579 Background: Cutaneous angiosarcoma (CAS) is a rare sarcoma and advanced cases face a complex treatment regimen and dismal prognosis. Several cytotoxic agents (anthracycline, taxane, and gemcitabine) and targeted therapies (bevacizumab and sorafenib) have been tested for advanced disease in clinical trials with poor results. Since CAS commonly develops in elderly patients, high-grade adverse events from treatment may not be ideal and thus therapies featuring durable response and low comorbidity are in great demand. Recent studies suggest that CAS has a distinct genomic profile, including higher tumor mutational burden (TMB), compared to angiosarcomas developed in other sites. Moreover, we have shown that CAS with higher PD-1/L1 in the tumor microenvironment had statistically better overall survival compared with those without, indicating CAS susceptibility to immune checkpoint blockade therapy. However, to date, reports of immune checkpoint inhibitors for CAS are nonexistent. Methods: The present study is a phase 2, multicenter, single-arm clinical trial of ONO-4538 (nivolumab, 480 mg IV every 4 weeks) for patients with unresectable or metastatic CAS refractory to first-line paclitaxel. Twenty-three patients with advanced CAS will be enrolled at 11 sites in Japan with a primary objective to assess the confirmed response rate (H0 p &lt; 5%, H1: p &gt; 20%) to nivolumab. Secondary endpoints include PFS, OS, time to response, and adverse events. A correlative aim includes assessing tissue biomarkers using whole-genome sequencing (1023 genes including interferon-gamma associated genes and other known factors associated with response to immune checkpoint inhibitors) for association with response to nivolumab. The study started in April 2020 and remains open with 7 patients enrolled at time of Clinical trial information: UMIN000043039.
Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data
Authors: Munawar Anwar, Qitong Chen, Dengjie Ouyang, Shouman Wang, Ning Xie, Quchang Ouyang, Peizhi Fan, Liyuan Qian, Gannong Chen, Enxiang Zhou, Lei Guo, Xiaowen Gu, Boning Ding, Xiaohong Yang, Liping Liu, Chao Deng, Zhi Xiao, Jing Li, Yunqi Wang, Shan Zeng, Jinhui Hu, Wei Zhou, Bo Qiu, Zhongming Wang, Jie Weng, Mingwen Liu, Yi Li, Tiegang Tang, Jianguo Wang, Hui Zhang, Bin Dai, Wuping Tang, Tao Wu, Maoliang Xiao, Xiantao Li, Hailong Liu, Lai Li, Wenjun Yi
Journal: Clinical Cancer Research (2021)

Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce.This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR), and overall response rate (ORR) were analyzed.Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR).Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.
Changes in ctDNA levels after MIBG therapy in patients with relapsed or refractory neuroblastoma.
Authors: Kevin M. Campbell, Kelly S. Klega, David Stephen Shulman, Denice D. Tsao-Wei, Susan G. Groshen, Fariba Goodarzian, Rachel Berkovich, Hiroyuki Shimada, Araz Marachelian, Judith Villablanca, Julie R. Park, Meaghan Granger, Katherine K. Matthay, Brian D. Crompton, Steven G. DuBois
Journal: Journal of Clinical Oncology (2021)

10012 Background: Circulating tumor DNA (ctDNA) is detectable in children with neuroblastoma. Less is known about how levels change during treatment and the implications of these changes. We evaluated ctDNA pre- and post- 131I-metaiodobenzylguanidine (MIBG) therapy. Methods: We utilized plasma samples from NANT11-01 (NCT02035137), a multi-center, open label, randomized phase II clinical trial evaluating MIBG with or without radiation sensitizers for patients with relapsed or refractory neuroblastoma. Plasma was collected at Baseline prior to MIBG, 72 hours (Hr72), 96 hours (Hr96), 15 days after MIBG (D15), and prior to a second course among patients without progression who received a second course (C2). Samples were analyzed for percent ctDNA levels using ultra-low passage whole genome sequencing. We evaluated associations between ctDNA findings with baseline disease measures of percent involvement in bone marrow, Curie score, and RECIST disease sum of diameters as well as overall response by NANT Response Criteria v1.2 (complete response or partial response coded as responders). Results: Eighty-four patients had a baseline sample and were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32% (range 3.9-91%). Baseline ctDNA levels showed a significant positive correlation with percent involvement in bone marrow (r=0.37; p=0.0004) and Curie score (r=0.26; p = 0.018), but not RECIST sum of diameters for soft tissue sites (r=0.065; p=0.56). Following therapy, the proportions of patients with detectable ctDNA were: Hr72 47% (34/73; median level 28%); Hr96 50% (26/52; median 28%); D15 33% (7/21; median 4%); and C2 14% (3/21; median 50%). Rate of ctDNA detection was similar between responders and non-responders at baseline, Hr72, and Hr96, but lower among responders at D15 and C2 (Table). Among the 21 patients with C2 data, ctDNA levels were either undetectable (n=18) or lower than Cycle 1 Baseline (n=3). Among patients with detectable baseline ctDNA, the median relative ctDNA level at Hr72 (Hr72 ctDNA/baseline ctDNA) for non-responders was 0.87 (n=24) vs. 1.16 for responders (n=7). In contrast, the median relative ctDNA level at C2 for non-responders was 0.56 (n=4) vs. 0 for responders (n=4). Conclusions: ctDNA is detectable in a substantial proportion of patients with relapsed / refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints (Hr72 and Hr96) are less informative, whereas ctDNA becomes undetectable at D15 and C2 more commonly in patients with clinical response.[Table: see text]
Impact of the COVID-19 pandemic on tuberculosis national reference laboratory services in the WHO European Region, March to November 2020
Authors: Florian P Maurer, Natalia Shubladze, Gulmira Kalmambetova, Irina Felker, Giorgi Kuchukhidze, Francis Drobniewski, Askar Yedilbayev*, Soudeh Ehsani
Journal: Eurosurveillance (2021)

We assessed the impact of COVID-19 on diagnostic services for tuberculosis (TB) by national reference laboratories in the WHO European Region. Of 35 laboratories, 30 reported declines in TB sample numbers, amounting up to &gt; 50% of the pre-COVID-19 volumes. Sixteen reported reagent or consumable shortages. Nineteen reallocated ressources to SARS-CoV-2 testing, resulting in an overall increase in workload, largely without a concomitant increase in personnel (n = 14). This poses a risk to meeting the 2025 milestones of the End TB Strategy.