tbuckley/cabot-search huggingface dataset:
Methylation status of eight tumor suppressors in neuroendocrine pancreatic tumors.
Authors: Oleg I. Kit, Vladimir S. Trifanov, Natalya N. Timoshkina, Dmitry Yu. Gvaldin, Milana Yu. Mesheryakova, Evgeniy N. Kolesnikov, Mikhail A. Kozhushko, Mikhail A. Averkin, Stanislav S. Mezentsev, Petr N. Gabrichidze
Journal: Journal of Clinical Oncology (2021)

e16197 Background: Aberrant DNA methylation is a characteristic feature of cancer, affecting gene expression and tumor phenotype. In this study, we quantified the methylation of promoters of eight tumor suppressor genes in pancreatic neuroendocrine tumors (Pan-NET). Methods: The method of pyrosequencing was used to quantity level (Met,%) of methylation of gene promoters - tumor suppressors AHRR, APC1A, DAPK, MGMT, MLH1, P16, RASSF1A, RUNX3 in tumor samples from 55 patients with pancreatic NET (G1-G3) and in the blood of 10 healthy donors. Met for each sample was calculated as the median methylation of CpG sites in triplicate. Results: Hypermethylation was observed for AHRR (75%), APC1A (25%), RASSF1A (30%). In contrast, DAPK, MGMT, MLH1, P16, RUNX3 had low methylation levels ( &lt; 20%). The median of methylation in the blood of healthy donors for AHRR was 91% (76-98); for all other loci it did not exceed 6%. A high incidence of methylation in excess of blood levels in healthy donors was identified for RASSF1A (0.96); AHRR (0.75); MGMT (0.65); RUNX3 (0.41), APC1A (0.25). For tumor suppressor P16, only one case of increased methylation was recorded (Met = 15%), despite the fact that this phenomenon is not uncommon for NETs of other localizations. In 66% of pancreatic NET cases, hypermethylation of more than two promoters of tumor suppressor genes was noted. An association tendency was found between the presence of MEN1 mutations and the RASSF1A methylation level (p = 0.08). Correlation analysis revealed a significant level of negative association between changes in methylation of MLH1 and AHRR (p &lt; 0.01); for the latter, the prognostic value of a high methylation status and a better prognosis for many malignant neoplasms were described. Conclusions: In the present study, significant methylation of the promoters of the APC1A, DAPK, MGMT, RASSF1A, and RUNX3 genes in well-differentiated pancreatic NETs was identified with a high frequency. At the same time, isolated cases of hypermethylation were noted for the well-known tumor suppressors MLH1 and P16.
ENGOT-ov54/Swiss-GO-2/MATAO including LOGOS (Low-Grade Ovarian cancer Sub-study): MAintenance Therapy with Aromatase inhibitor in epithelial Ovarian cancer—A randomized, double-blinded, placebo-controlled, multicenter phase III Trial.
Authors: Viola A. Heinzelmann-Schwarz, Christian Kurzeder, Seraina Schmid, Natalie Gabriel, Andreas Mueller, Mathias Konrad Fehr, Christian Marth, Andreas Du Bois, Maximillian Klar
Journal: Journal of Clinical Oncology (2021)

TPS5598 Background: The prognosis of advanced epithelial ovarian cancer (OC) is poor with a relapse rate of 75% at 5 years. Some 80% of OC express estrogen receptor (ER). This is the first trial that wants to capitalize on this and prospectively evaluates letrozole, a potent aromatase inhibitor, as initial maintenance treatment for high and low grade OC. Methods: Eligible pts have primary OC, FIGO Stage II-IV with low or high grade serous or endometrioid histology, with (interval) debulking surgery, ECOG-status 0-2, Positivity (≥ 1%) for ER expression, and at least 4 cycles of platinum-based chemotherapy (neoadjuvant allowed). Pts are allowed to undergo concurrent maintenance treatment with bevacizumab and PARP inhibitors. Extensive quality of life (QoL) questionnaires via an App and physical activity measurements by a tracking device as well as G8 geriatric score, ESGO surgery questionnaire, and Charleson Comorbidity Index are routinely assessed. Primary objective is to evaluate the efficacy of letrozole maintenance therapy after standard surgical and chemotherapy treatment as measured by Progression Free Survival (PFS) compared to no maintenance therapy (placebo). Primary outcome is PFS, defined as time from date of first letrozole/placebo administration until date of progression or death by any cause. Stratification for high and low grade histologies and ER measurement is performed via a digital centralized pathology review process. Final analysis will be performed for the whole cohort and for the subgroup of low grade ovarian cancers (LOGOS subprotocol). Secondary objectives and outcomes are overall survival (OS), quality adjusted progression free survival (QAPFS), time to first subsequent treatment (TFST), quality adjusted time without symptoms (TWiST), and health related QoL. Study is designed as international, randomized (1:1 ratio), two-arm, multi-centric, double-blinded, placebo-controlled superiority phase III trial. In total, 528 pts will be randomly assigned to letrozole or placebo for 5 yrs or until unacceptable toxicity, progression of underlying disease, or study discontinuation. Final analysis is planned after 5 years without interval analysis and follow-up is collected for up to 10yr and for the low-grade cohort for up to 12yr. Clinical trial information: NCT04111978.
LGG-05. GENERATION OF NOVEL MOUSE MODELS FOR BRAF V600E MUTANT GLIOMAGENESIS TO GAIN MECHANISTIC INSIGHTS INTO TUMOR FORMATION AND PROGRESSION
Authors: Claudia K. Petritsch, Anne Marie Barrette, Jong-Whi Park
Journal: Neuro-Oncology (2021)

Abstract Background The BRAF V600E mutation occurs in ~ twenty percent of histologically diverse pediatric gliomas and is the second most common mutation in pediatric low-grade gliomas (LGG). BRAF V600E expression in LGG with balanced CDKN2A is associated with a higher rate for progression than for BRAF V600E wildtype tumors, and despite adjuvant therapy, consisting of resection, radiation and chemotherapy. Progression invariably occurs in BRAF V600E mutant CDKN2A deleted gliomas, marking a high-risk group. Here, we aim to overcome the lack BRAF V600E mutant glioma models that allow for studies of stem and progenitor cells and the immune system ability to understand progression. Methods We develop novel immunocompetent, stem and progenitor cell-based mouse models for BRAF mutant gliomas, including genetically engineered mouse models (GEMMs), orthotopic glioma models derived from gliomas in GEMMs as well as in vitro models of those tumors. BRAF mutant mouse brains and cells were analyzed by immunofluorescence staining, flow cytometry, mass cytometry and RNA sequencing. Results Ongoing model development studies indicate that BRAF V600E mutant gliomas in murine brain exhibit very similar neuroanatomical preferences to human gliomas. The BRAF V600E mutation exacerbates the heterogenous cell cycling pattern of normal neural stem and progenitors and expands a symmetrically dividing progenitor population. Cellular plasticity rather than cellular lineage hierarchy drives the generation of a therapy resistant stem cell pool. Transcriptomic analyses of neuroglial stem cells with induced BRAF V600E expression provide insights into mechanisms for neoplastic transformation and progression. Conclusion Analyses of two independent BRAF V600E mutant mouse models provide novel insights into the role for tumor intrinsic factors, such as plasticity and stemness, and the tumor microenvironment in progression.
Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia
Authors: Alex Bourguignon, Donald M. Arnold, Theodore E. Warkentin, James W. Smith, Tania Pannu, Jeffrey M. Shrum, Zainab A.A. Al Maqrashi, Anjali Shroff, Marie-Claude Lessard, Normand Blais, John G. Kelton, Ishac Nazy
Journal: New England Journal of Medicine (2021)

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).
Ectopic Pulmonary Goiter Simulating Malignant Tumor Detected on SPECT/CT
Authors: Xiangyue Liang, Junhong Li, Yi Huang, Shengmei Peng, Zhixiao Wei
Journal: Clinical Nuclear Medicine (2021)

A 46-year-old asymptomatic woman with a newly detected large pulmonary mass was admitted to our hospital. An ultrasonography-guided needle biopsy was performed based on a suspicion of malignancy, and an ectopic goiter was confirmed pathologically. Laboratory findings were unremarkable, except that thyroid function tests suggested subclinical hyperthyroidism. A 131I whole-body scintigraphy and SPECT/CT were further performed and revealed intense radioiodine uptake in the pulmonary mass, the mediastinal nodule, and thyroid gland. A diagnosis of ectopic pulmonary goiter with normally located thyroid was finally made.
Abstract 11407: Systematic Screening for Cardiovascular Disease in Young Sports Participants
Authors: Rasha Aurshiya, Kunal Bhagatwala, Archana Sinha, Jasmine Singh, Sudip Nanda, Jamshid Shirani
Journal: Circulation (2019)

Background: Although rare (1:80,000-1:200,000), sudden cardiac death (SCD) is a tragic even for young athletes. Comprehensive initial pre-participation physical evaluation (CIPPE) is mandated for j...
Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage
Authors: Jung-Hoon Park, Jieun Park, Yejong Park, Jeon Min Kang, Dae Sung Ryu, Jeongsu Kyung, Jong Keon Jang, Changmo Hwang, In Kyong Shim, Ho-Young Song, Su-Geun Yang, Song Cheol Kim
Journal: Journal of Controlled Release (2021)
Etiology and prevalence of ESBLs in adult community-onset urinary tract infections in East China: A prospective multicenter study
Authors: Jingjing Quan, Honglei Dai, Weichao Liao, Dongdong Zhao, Qiucheng Shi, Linghong Zhang, Keren Shi, Murat Akova, Yunsong Yu
Journal: Journal of Infection (2021)

ObjectivesCommunity onset urinary tract infections (COUTIs) drew attention recently owing to their increased prevalence and associations with resistant pathogens. The study is aimed at investigating the etiology of COUTIs as well as prevalence and the related risk factors of extended-spectrum β-lactamase (ESBL) in COUTIs in China.MethodsThe prospective study was performed in nineteen hospitals during November 1, 2017 and August 31, 2019. Non-duplicated isolates from COUTIs were included. The ESBL phenotypic confirmation test was performed and whole genomes were sequenced for all the ESBL-positive bacteria for further analysis. The risk factors for ESBL-producing bacterial infections were analyzed using binary logistic regression.ResultsA total of 1760 COUTI cases were included in this study. Escherichia coli (1332, 75.7%), Klebsiella pneumoniae (110, 6.3%) and Enterococcus faecalis (52, 3.0%) were the top three common pathogens of COUTIs in China. The overall positive rate of ESBLs in Enterobacterales was 37.2% (562/1512). The age (OR=1.007, P = 0.041), solid malignant tumor (OR=1.668, P = 0.016), prostate diseases (OR=2.035, P = 0.010), history of lithotripsy for urinary calculi (OR=2.009, P = 0.030), history of urological surgery (OR=1.869, P = 0.009) and cephalosporin use within 3 months (OR=1.503, P = 0.025) were independent risk factors for ESBL-producing organisms causing COUTIs. The predominant ESBL types were CTX-Ms, among which CTX-M-14, CTX-M-55 and CTX-M-27 were the most common subtypes. ST131 and ST1193 were the predominant sequence types of ESBL-producing E. coli (ESBL-EC). Most of the tested antimicrobial agents showed significantly higher non-susceptible rates in the ESBL positive group as compared with ESBL-negative group (P < 0.05).ConclusionsEnterobacterales, especially E. coli, is the most common pathogen in COUTIs in China and ESBL-producers are highly prevalent. Thus, early prediction depending on risk factors seems to be crucial to determine the appropriate empirical therapy for infections caused by ESBL-producing pathogens.
CD8+ T-cell lymphocyte infiltration predict clinical outcomes Wilms’ tumor.
Authors: Mahtab Rahbar, Keykhosro Mardanpour, Sourena Mardanpour
Journal: Journal of Clinical Oncology (2021)

e22001 Background: The abundance and location of CD8+ tumor-infiltrating lymphocytes demonstrate important facets of the anticancer immune response. CD8-expressing lymphocytes have been used in immunotherapy for multiple cancers. This study aims to determine the association between the abundance and localization of CD8+ tumor-infiltrating lymphocytes and clinical outcomes Wilms’ tumor. Methods: This retrospective study employed 42 pediatric patients diagnosed with Wilms’ tumor. CD8+ tumor-infiltrating lymphocyte counts were calculated based on the mean percentage of stroma occupied by CD8+ lymphocytes at the center and the invasive border of the tumor using immunohistochemistry. Results: CD8+ tumor-infiltrating lymphocyte counts were significantly higher in the center and the invasive border of the early-stage tumor samples. CD8+ tumor-infiltrating lymphocytes in the invasive border and tumor center positively correlated with tumor invasion, regional lymph node invasion, histological type, metastasis, and stage of the tumor. A high CD8+ tumor-infiltrating lymphocyte scores at the invasive margin of the tumor correlated with low tumor recurrence. Low CD8+ tumor-infiltrating lymphocyte scores in the two tumor regions correlated with poor prognosis and shorter disease-free survival. Conclusions: Overall, these findings show that patients with high CD8+ tumor-infiltrating lymphocytes are associated with better clinical outcomes. Therefore, measuring the abundance of CD8+ tumor-infiltrating lymphocytes may be useful in predicting response to cancer immunotherapies.
Atezolizumab in combination with bevacizumab in patients with unresectable locally advanced or metastatic mucosal melanoma: Interim analysis of an open-label phase II trial.
Authors: Lu Si, Meiyu Fang, Yu Chen, Lili Mao, Peng Zhang, Jing Lin, Xue Bai, Xiao Cao, Yi Chen, Jun Guo
Journal: Journal of Clinical Oncology (2021)

9511 Background: Mucosal melanoma is a rare malignant melanoma in Caucasians but ranks the second most common subtype in the Asian population. It is more often diagnosed at an advanced stage and responds poorly to current PD-1/PD-L1 inhibitors. Here we report the interim analysis results of ML41186, an open-label, multicenter, single-arm phase II study, aiming to evaluate the efficacy and safety of atezolizumab in combination with bevacizumab in patients (pts) with advanced mucosal melanoma. Methods: Eligible pts aged 18 to 75 years with histologically confirmed unresectable locally advanced or metastatic mucosal melanoma had at least one measurable lesion per RECIST version 1.1 at baseline, with an ECOG PS 0 or 1 and adequate hematologic and organ function. ML41186 is a Simon two-stage design study, if 22 pts completed ORR evaluation and more than 3 pts respond in stage I, the study then continue to Stage II. Atezolizumab and bevacizumab were administered at a fixed dose of 1200 mg and 7.5 mg/kg Q3W respectively (on day 1 of each 21-day cycle) until unacceptable toxicity or loss of clinical benefit. The primary endpoint is the objective response rate (ORR). The secondary endpoints include progression-free survival (PFS), duration of objective response (DoR), disease control rate (DCR), and safety. Results: By the cut-off date of 9 th September 2020, 35 pts has been enrolled, among whom 22 pts in the stage I analysis set has completed two efficacy evaluation, while 28 pts (full analysis set) has completed at least one efficacy evaluation. In ITT populations (n=35), mean age was 58.9 years with 10 (28%) pts had ECOG PS of 1. LDH level elevated in 9 (25.7%) pts. More than half pts (19, 54.3%) had metastatic mucosal melanoma, of whom 3 (15.8%) pts had more than 3 metastasis sites and 4 (21.1%) pts had liver metastasis. In stage I analysis set (n=22), the best confirmed ORR was 36.4% (95% CI, 17.0%-59.3%). Median progression-free survival was 5.32 months (95% CI, 1.58-not reached), and the best confirmed DCR was 59.1% (95%CI, 36.4%-79.3%). The median confirmed DoR was not reached (95% CI, 2.76-NR). In the full analysis set (n=28), the unconfirmed ORR was 42.9% (95%CI, 24.5%-62.8%). In ITT populations (n=35), 28 pts (80%) experienced at least one adverse event (AE) and 5 pts (14.3%) experienced at least one grade 3-4 AEs. Only one patient experienced AE leading to treatment discontinuation. One patient died of autoimmune lung disease. Conclusions: The combination of atezolizumab plus bevacizumab showed promising benefit and was tolerable in pts with advanced mucosal melanoma. At the time of this interim analysis, the primary endpoint did not cross the futility boundary, thus the study will run into Stage II. Clinical trial information: NCT04091217.
Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine
Authors: Jiyoon Park, An K. Le, Tai-Chung Tseng, Ming-Lun Yeh, Dae Won Jun, Huy Trinh, Grace L.H. Wong, Chien-Hung Chen, Cheng-Yuan Peng, Sung Eun Kim, Hyunwoo Oh, Min-Sun Kwak, Ka Shing Cheung, Hidenori Toyoda, Yao-Chun Hsu, Jae Yoon Jeong, Eileen L. Yoon, Teerapat Ungtrakul, Jian Zhang, Qing Xie, Sang Bong Ahn, Masaru Enomoto, Jae-Jun Shim, Chris Cunningham, Soung Won Jeong, Yong Kyun Cho, Eiichi Ogawa, Rui Huang, Dong-Hyun Lee, Hirokazu Takahashi, Pei-Chien Tsai, Chung-Feng Huang, Chia-Yen Dai, Cheng-Hao Tseng, Satoshi Yasuda, Ritsuzo Kozuka, Jiayi Li, Christopher Wong, Clifford C. Wong, Changqing Zhao, Joseph Hoang, Yuichiro Eguchi, Chao Wu, Yasuhito Tanaka, Ed Gane, Tawesak Tanwandee, Ramsey Cheung, Man-Fung Yuen, Hyo-Suk Lee, Ming-Lung Yu, Jia-Horng Kao, Hwai-I Yang, Mindie H. Nguyen
Journal: Clinical Gastroenterology and Hepatology (2021)
Predictors of receiving survivorship care plans and visits.
Authors: Christine M. Duffy, Harish Saiganesh, Stavroula Chrysanthopoulou, Camille Higel-Mcgovern, Don S. Dizon
Journal: Journal of Clinical Oncology (2021)

12055 Background: While the Commission on Cancer has eliminated strict quotas for accreditation, Survivorship Care Plans (SCPs) and/or Survivorship Care Visits (SCV) at treatment completion are encouraged. However, who receives a SCP or SCV, whether it impacts care, and impact of distress on care is unknown. We examined the provision of survivorship care at the Lifespan Cancer Institute (LCI) to determine (1) clinical and distress thermometer scores (DTS) association with SCPs and SCVs; (2) impact of SCV visits on specialty referrals, and (3) demographic and clinical predictors of receipt of SCP and SCV. Methods: We retrospectively reviewed EMR records on 1,960 patients at LCI between 2014-2017 for SCPs and SCVs and extracted demographics, treatment variables, and distress scores. We used T-test or Wilcoxon rank test and Chi-square tests for evaluating the bivariate associations of SCP and SCV with continuous and categorical factors respectively. We fit logistic regression models to assess the adjusted effect of these factors on receipt of SCP and SCV independently. All analyses were performed in R v4.0.2. Results: The mean age was 63.9 (SD=11.8), 67% were female, 51.2% were married or partnered. Breast (38.8%), lung (17.6%), and prostate (13.7%) were the most common cancers. DTS were recorded in 64% with mean of 3.88(SD=3.05): distress was higher in women (4.36, SD=3.01), breast cancer pts (4.53, SD=3.07), gyn (4.22, SD=3.07), pancreatic (4.12, SD=3.41) and anal cancers (4.52, SD=3.47) and in those with Stage IV disease (5.33, SD=3.43). SCPs were completed in 740 (37.8%) patients and of those 65.9% had a SCV. SCV were associated with more specialty referrals for psychiatry, physical therapy, nutrition, and sexual health but not smoking cessation or fiscal services. DTS were associated with increased referral to psychiatry only. The adjusted models (table) showed odds of receiving a SCP were higher in those younger, and having breast cancer v all other cancers, with prostate having lowest odds. For receipt of SCV, odds were higher in those younger, female, and having breast cancer, with prostate and lung having the lowest odds. Conclusions: Gender, age and type of cancer are significant predictors of receipt of SCP and SCV. SCP and SCV patterns may represent patient preferences, but practice patterns and unconscious biases may also play a part suggesting areas for further research and outreach.[Table: see text]
Outcomes for hospitalized cancer patients with COVID-19 during the height of pandemic in New York City.
Authors: Amelia Sawyers, Margaret Chou, Paul Johannet, Nicholas Gulati, Yingzhi Qian, Hua Zhong, Iman Osman
Journal: Journal of Clinical Oncology (2021)

10572 Background: Several reports have suggested that cancer patients are at increased risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suffering worse coronavirus disease 2019 (COVID-19) outcomes. However, little is known about the impact of cancer status on presentation and outcome. Here, we report on the association between cancer status and survival in hospitalized patients who tested positive for SARS-CoV-2 during the height of pandemic in New York City. Methods: Of the 6,724 patients who were hospitalized at NYU Langone Health (3/16/20 - 7/31/20) and tested positive for SARS-CoV-2, 580 had either active cancer (n = 221) or a history of cancer (n = 359). Patients were classified as having active malignancy if they either received treatment within six months of their COVID-19 diagnosis or they had measurable disease documented at the time of their hospitalization. Patients were categorized as having a history of cancer if there was no evidence of measurable disease or there were no treatments administered within six months of their COVID-19 diagnosis. We compared the baseline clinicodemographic characteristics and hospital courses of the two groups, and the relationship between cancer status and the rate of admission to the intensive care unit (ICU), use of invasive mechanical ventilation (IMV), and all-cause mortality. Results: There was no differences between the two groups in their baseline laboratory results associated with COVID-19 infection, incidence of venous thromboembolism, or incidence of severe COVID-19. Active cancer status was not associated with the rate of ICU admission ( P = 0.307) or use of IMV ( P = 0.236), but was significantly associated with worse all-cause mortality in both univariate and multivariate analysis with ORs of 1.48 (95% CI: 1.04-2.09; P = 0.028) and 1.71 (95% CI: 1.12-2.63; P = 0.014), respectively. Conclusions: Active cancer patients had worse survival outcomes compared to patients with a history of cancer despite similar COVID-19 disease characteristics in the two groups. Our data suggest that cancer care should continue with minimal interruptions during the pandemic to bring about response and remission as soon as possible. Additionally, these findings support the growing body of evidence that malignancy portends worse COVID-19 prognosis, and demonstrate that the risk may even apply to those without active disease.