tbuckley/cabot-search huggingface dataset:
Patient's characteristics and outcome of small bowel adenocarcinoma in Saudi Arabia.
Authors: Bader I Alshamsan, Ahmed ali Badran, Mohamed Aseafan, Amgad Shaheen, Mahmoud Abdelsatar Elshenawy, Ali H Aljubran
Journal: Journal of Clinical Oncology (2021)

e16277 Background: Small bowel adenocarcinoma (SBA) is a rare disease. We aim to describe patient's characteristics and clinical outcomes among Saudi patients. Methods: All patients with SBA diagnosed between 2007 - 2020 were reviewed. Logistic regression was used to assess variables associated with metastasis at diagnosis, and a log-rank test was used to compare factors associated with survival. Results: Forty-three patients were eligible for analysis, and (76.7%) were males. The median age at diagnosis was 53 years. History was significant for colon cancer in two patients, celiac disease in three patients, Lynch syndrome, Familial adenomatous polyposis (FAP), Non-APC in one patient, and cholecystectomy in seven patients. The common initial presenting symptoms were abdominal pain (58.8%), bowel obstruction (30.2%), Overt gastrointestinal bleeding (9.3%). Tumor markers were elevated in 21 patients. EGD was used for diagnosis in 60.5%, while CT scan in 23.3%. The most common primary site was duodenum 60.5%, jejunum 27.9%, ilium 7%. Stage IV was (41.9%). The most common site for metastases was the liver in 10 patients. Patients' ECOG performance status was 0/1 in 51% at diagnosis. Univariate analysis did not reveal that patients with high Neutrophil-lymphocyte Ratio (NLR) (≥0.85) are more likely to be metastatic; P = 009. There was no association of sex, presenting complaints, tumor markers with the stage at diagnosis. Surgery was performed for 53.4% of patients (RO, 73%), and the median DFS was 49 vs. 8 months in R0 vs. R1 group, respectively (p = 0.01). FOLFOX Chemotherapy regimen was given for 10 patients as adjuvant treatment and for 8 patients for metastatic sitting. The median duration of follow-up was 12 months. The median overall survival (OS) for localized stages was not reached, and for the metastatic stage was 10 months. The 3 years OS based on stages were 100% (I), 85% (II), 53% (III) and 35% for (IV), p = 0.001. Other factors associated with survival were ECOG Performance status (p &lt; 0.001), NLR ( &lt; 0.001), CA19-9 (p = 0.04), and receiving chemotherapy in a metastatic setting (p = 0.02). Conclusions: SBA is diagnosed at a younger age in Saudi patients and more in males. The advanced stage, lower performance status score, high CA19-9, and high NLR at diagnosis are associated with poor OS. NLR could be a prognostic factor for a metastatic stage at diagnosis.
Association of antibiotic exposure with the mortality in bevacizumab-treated metastatic colorectal cancer: A secondary analysis from Dryad database.
Authors: Chenyu Sun, Xianwei Guo, Kelly Kozma, Chandur Bhan, Na Hyun Kim
Journal: Journal of Clinical Oncology (2021)

e15609 Background: Colorectal cancer (CRC) is one of the most diagnosed cancers and the second leading cause of cancer-related death worldwide. Globally, more than 1.8 million people are diagnosed of colorectal cancer (CRC) in 2018. In advanced CRC patients, bevacizumab plus 5-fluorouracil-based or platinum-based therapy has become one of the standard first-line chemotherapy regimen. A recent study also found that antibiotic exposure could be inversely associated with the mortality in metastatic colorectal cancer (mCRC) patients treated with bevacizumab. However, subgroup analysis of this study was no sufficient. Therefore, we conducted a secondary analysis based on the data of this study from Dryad database. Methods: In this retrospective cohort study, 147 mCRC patients treated with bevacizumab were included. All data was obtained from Dryad database (https://doi.org/10.5061/dryad.ft5sk66). Patients were divided into follow subgroups: (1) left colon vs right colon; (2) BMI &lt; 18.5 vs BMI 18.5-24 vs BMI≥24;(3) Age &lt; 45 vs Age≥45, (4) no surgery vs palliative surgery vs radical surgery, (5) bevacizumab plus FOLFIRI vs bevacizumab plus capeOX/FOLFOX vs bevacizumab plus other chemotherapy regimen. Specific survival of each subgroup was analyzed through the Kaplan-Meier curve, and the survival curves of the variables were compared using the log-rank test. Results: Survival analysis found no statistically significant differences of the cumulative survival rates between left colon cancer and right colon cancer, (58.9% vs 62.5%, respectively; χ2 = 0.043, P = 0.836), groups of different BMI (57.9% of BMI &lt; 18.5 vs 55.2% of 18.5≤BMI &lt; 24 vs 70.7% of BMI ≥24，χ2 = 3.026, P = 0.220), Age &lt; 45 group and Age≥45 group (54.8% vs 61.2%, respectively; χ2 = 0.001, P = 0.976), surgical treatments (No surgery 59.0% vs Palliative surgery 57.6% vs Radical Surgery 61.3%; χ2 = 1.885, P = 0.390), as well as groups of different chemotherapy regimens (66.7% of FLOFIRI vs 52.0% of CapeOX/FOLFOX vs 59.9% of others; χ2 = 1.572, P = 0.456). Conclusions: Based on the data from this study, we found that different sites of colon cancer, age, BMI, different surgical treatments, and different chemotherapy regimens did not affect the survival outcome of patients with mCRC treated with bevacizumab after antibiotic exposure. Subsequent studies with larger sample size are still needed to further elaborate the effects of different antibiotics on survival outcomes.
Key Characteristics of Human Hepatotoxicants as a Basis for Identification and Characterization of the Causes of Liver Toxicity
Authors: Ivan Rusyn, Xabier Arzuaga, Russell C. Cattley, J. Christopher Corton, Stephen S. Ferguson, Patricio Godoy, Kathryn Z. Guyton, Neil Kaplowitz, Salman R. Khetani, Ruth A. Roberts, Robert A. Roth, Martyn T. Smith
Journal: Hepatology (2021)

Hazard identification regarding adverse effects on the liver is a critical step in safety evaluations of drugs and other chemicals. Current testing paradigms for hepatotoxicity rely heavily on preclinical studies in animals and human data (epidemiology and clinical trials). Mechanistic understanding of the molecular and cellular pathways that may cause or exacerbate hepatotoxicity is well advanced and holds promise for identification of hepatotoxicants. One of the challenges in translating mechanistic evidence into robust decisions about potential hepatotoxicity is the lack of a systematic approach to integrate these data to help identify liver toxicity hazards. Recently, marked improvements were achieved in the practice of hazard identification of carcinogens, female and male reproductive toxicants, and endocrine disrupting chemicals using the key characteristics approach. Here, we describe the methods by which key characteristics of human hepatotoxicants were identified and provide examples for how they could be used to systematically identify, organize, and use mechanistic data when identifying hepatotoxicants.
Retroflexion in the duodenal bulb combined with tunnel and double-clip traction: the key to successful endoscopic submucosal dissection of a malignant gastric adenoma protruding through the pylorus
Authors: Marion Schaefer, Thomas Lambin, Benjamin Hamel, Clémentine Gandilhon, Jérémie Jacques, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2021)

An 81-year-old man was referred for resection of a prepyloric lesion, described as a large pseudopolypoid gastric fold, with low grade dysplasia adenoma on biopsies. Examination showed a flat, centrally depressed lesion without ulceration, protruding completely through the pylorus ([Video 1]). The distal side of the lesion could not be assessed in forward view, despite the use of a transparent cap. A careful retroflexion in the bulb, with underwater examination (gastroscope GIF-H190; Olympus, Tokyo, Japan), allowed perfect visualization of the distal margin ([Fig. 1 a]). After submucosal injection of glycerol solution with indigo carmine, distal incision was carefully made in retroflexion in the duodenum, with a DualKnife J 1.5 mm (Olympus) ([Fig. 1 b]). Then, we proceeded to the proximal incision and submucosal dissection in a tunnel with visualization of the pylorus muscle arch ([Fig. 1 c]). Counter-traction was applied with two clips (Resolution 360°; Boston Scientific, Marlborough, Massachusetts, USA) and rubber band to expose the posterior edges ([Fig.1 d]). During the procedure, the axis of the counter-traction was modified to allow good exposure of the superior and anterior parts of the lesion. En bloc resection was achieved ([Fig. 2 a]). Histological examination confirmed complete resection of intestinal-type pyloric adenoma with intramucosal adenocarcinoma ([Fig. 2 b]).
Differences of US-FNA BSRTC class, postoperative pathology, and mutation landscape of thyroid nodules between China and other countries.
Authors: Yuntao Song, Jie Liu, Weiran Wang, Tonghui Ma
Journal: Journal of Clinical Oncology (2021)

3055 Background: Ultrasound and ultrasound-guided fine needle aspiration (US-FNA) are the first choice for judging benign and malignant thyroid nodules. This study will report on the differences of US-FNA BSRTC class, postoperative pathology and mutation landscape of thyroid nodules between China and other countries. Methods: We conducted a prospective study containing 383 FNA samples of thyroid nodules. For most of these FNA samples, genomic DNA and RNA were extracted and sequenced with FSZ-Thyroid NGS Panel V1, and postoperative pathology were followed up. Moreover, we also compared results of this study with those of West China Hospital in China, Yamashita Thyroid Hospital in Japan, and Cleveland Clinic in the United States. Results: Among the 383 FNA samples, the proportions of BSRTC class I to VI were 10.7%, 6.3%, 18.8%, 3.7%, 12.3%, and 48.3% respectively. Compared with study in other countries, the proportion of class II was significantly lower than that in Japan and the United States. Meanwhile, the proportion of class V and VI were significantly higher than the above two countries. Subsequently, 232 thyroid nodules were surgically removed. Postoperative pathology showed that the proportion of malignant tumors (85.3%) was also significantly higher than reported in Japan and the United States. But compared with other studies in China, there was no significant difference. Most of the malignant tumors were papillary thyroid cancer (PTC, 96%), accompanied with 2 follicular thyroid cancer (FTC), 3 medullary cancer (MTC) and 3 anaplastic thyroid cancer (ATC). Compared with study in the United States, the proportion of PTC and FTC were elevated (96% vs. 85.3%) and reduced (1% vs. 9.3%) respectively. At last, we also analysis the mutation landscape of 180 malignant tumors. Compared with TCGA study, the frequency of BRAF V600E in PTC in our study was significantly higher than that of TCGA (73.3% vs. 58%), and the frequency of RAS mutation was significantly lower (1.2% vs. 12.6%). And compared with an institutional experience of ThyroSeq v3 for Bethesda III and IV at the University of Pittsburgh Medical Center, the frequency of BRAF V600E and RAS mutation in Bethesda III-IV malignant tumors was also significantly higher (45.8% vs. 1.4%) and lower (8.3% vs. 47.1%). Conclusions: There were significant differences in BSRTC class and postoperative pathology between China and other countries, such as Japan and the United States. The possible reasons included that the indications for FNA in China were different. For example, most of patients who underwent FNA in this study had suspicious clinical/ultrasound features. So the proportion of BSRTC class V and VI as well as the malignant rate were elevated. On the other hand, more BRAF V600E and less RAS mutations were detected in malignant tumors in this study which might result from racial differentiation and discrepancy in proportion of PTC and FTC.
Brief relaxation training effects on long-term endocrine therapy adherence among women with breast cancer.
Authors: Molly Ream, Emily A Walsh, Jamie M. Jacobs, Natasha Schaefer Solle, Steven A. Safren, Michael Antoni
Journal: Journal of Clinical Oncology (2021)

12061 Background: Despite life-saving potential, many women struggle to adhere to adjuvant endocrine therapy (AET) for their early-stage, hormone receptor-positive breast cancer. Prior research has demonstrated that emotional distress is a barrier to AET adherence. The current study aimed to test the long-term effects of two 5-week post-surgical group-based stress management interventions, cognitive behavioral therapy (CBT) and relaxation training (RT), versus an attention-matched health education (HE) control on AET adherence at long-term follow-up. Methods: We conducted long-term follow-up (median = 8 years, range = 7-11 years) of a cohort of women who enrolled in a randomized controlled trial of CBT vs. RT vs. HE shortly after surgery for stage 0-3 breast cancer.We measuredadherence with the Endocrine Therapy Medication Usage Questionnaire (ETMUQ) given at long-term follow-up. First, we established adherence factors on the ETMUQ via confirmatory factor analysis. We then used structural equation modeling to regress these factors on study arm, controlling for patient age, stage of disease, and treatments received (chemotherapy/radiation). Results: The sample was predominately middle-aged ( M= 54.81, SD= 10.19), White (41.5%) and Hispanic (42.2%), partnered (62.2%) with stage 1 (57.0%) or stage 2 (25.9%) disease. Of the women who completed long-term follow-up (N = 59, 44.7% of original sample); more than half (n = 30; 50.8%) reported having at least some problems with adherence. There was an effect of intervention group on adherence, such that women receiving RT (n = 15) had significantly better adherence than those receiving CBT (n = 20) on the factor measuring Forgetfulness/Inconsistency ( B(SE) =.57 (.34), p=.001), and marginally better adherence than those receiving CBT on the factor measuring Intentional Nonadherence ( B(SE) =.60 (.33), p =.062). There was no such effect when comparing RT or CBT to HE (n = 24). Conclusions: Women receiving RT were less likely to forget to take their AET and marginally less likely to intentionally miss doses of AET in the long-term compared to women receiving CBT. Future research could investigate the mechanism by which RT may improve adherence. For example, RT may reduce somatic symptoms related to AET or improve a patients’ self-efficacy to cope with these symptoms thereby reducing intentional non-adherence. In addition, RT may improve patients’ attention and awareness leading to less forgetfulness. Clinical trial information: NCT02103387.
HGG-01. 3D GENOME STRUCTURE IMPACTS GENE EXPRESSION IN PEDIATRIC HIGH-GRADE GLIOMA
Authors: Tina Huang, Juan Wang, Ye Hou, Andrea Piunti, Elizabeth Bartom, Ali Shilatifard, Feng Yue, Amanda Saratsis
Journal: Neuro-Oncology (2021)

Abstract Introduction Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are highly morbid brain tumors. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding Histone H3. To investigate whether the H3K27M mutant protein is associated with distinct chromatin structure affecting transcription regulation, we generated the first high-resolution Hi-C and ATAC-Seq maps of pHGG cell lines, and integrated these with tissue and cell genomic data. Methods We generated sequencing data from patient-derived cell lines (DIPG n=6, GBM n=3, normal n=2) and frozen tissue specimens (DIPG n=1, normal brainstem n=1). Analyses included cell line RNA-Seq, ChIP-Seq (H3K27ac, H3K27me3, H3K27M) and genome-wide chromatin conformation capture (Hi-C), as well as tissue ATAC-Seq. Publicly available pediatric glioma tissue ChIP-Seq data was integrated with cell data. Results We identified tumor-specific enhancers and regulatory networks for known oncogenes in DIPG and GBM. In DIPG, FOX, SOX, STAT and SMAD families were among top H3K27Ac enriched motifs. Significant differences in Topologically Associating Domains (TADs) and DNA looping were observed at OLIG2 and MYCN in H3K27M mutant DIPG, relative to wild-type GBM and normal cells. Pharmacologic treatment targeting H3K27Ac (BET and Bromodomain inhibition) altered these 3D structures. Functional analysis of differentially enriched enhancers in DIPG implicated SOX2, SUZ12, and TRIM24 as top activated upstream regulators. Distinct genomic structural variations leading to enhancer hijacking and gene co-amplification were identified at A2M, JAG2, and FLRT1. Conclusion We show genome structural variations enhancer-promoter interactions that impact gene expression in pHGG in the presence and absence of the H3K27M mutation. Our results imply that tridimensional genome alterations may play a critical role in the pHGG epigenetic landscape and thereby contribute to pediatric gliomagenesis. Further studies examining the impact of the alterations, including CRISPR knock-down of target enhancer regions, is therefore underway.
COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy — Eight Integrated Health Care Organizations, United States, December 14, 2020–May 8, 2021
Authors: Hilda Razzaghi, Mehreen Meghani, Cassandra Pingali, Bradley Crane, Allison Naleway, Eric Weintraub, Tat'Yana A. Kenigsberg, Mark J. Lamias, Stephanie A. Irving, Tia L. Kauffman, Kimberly K. Vesco, Matthew F. Daley, Malini DeSilva, James Donahue, Darios Getahun, Sungching Glenn, Simon J. Hambidge, Lisa Jackson, Heather S. Lipkind, Jennifer Nelson, Ousseny Zerbo, Titilope Oduyebo, James A. Singleton, Suchita A. Patel
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination† and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.
Cabozantinib (C) exposure-response (ER) analysis for the phase 3 CheckMate 9ER (CM 9ER) trial of nivolumab plus cabozantinib (N+C) versus sunitinib (S) in first-line advanced renal cell carcinoma (1L aRCC).
Authors: Amishi Yogesh Shah, Robert J. Motzer, Andrea B. Apolo, Thomas Powles, Bernard Escudier, Joshua Zhang, Christian Scheffold, Sravan Karumanchi, Linh Thuy Nguyen, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2021)

4561 Background: In the phase 3 CM 9ER trial (NCT03141177), N+C significantly improved progression-free survival (PFS; HR 0.51, 95% CI 0.41–0.64; p &lt; 0.0001), overall survival (OS; HR 0.60, 98.89% CI 0.40–0.89; p = 0.0010), and objective response rate (p &lt; 0.0001) vs S in 1L aRCC (Choueiri, 2020). N+C was generally well tolerated with low rates of treatment-related discontinuations, indicating successful adverse event (AE) management with dose modification to maintain tolerability. Here the impact of C exposure on efficacy and safety outcomes in CM 9ER was evaluated using ER analysis. Methods: Patients (pts, N = 320) with previously untreated aRCC received C 40 mg QD in combination with N 240 mg Q2W; dose reductions of C to 20 mg QD or 20 mg Q2D were allowed to manage AEs. Time-to-event Cox proportional hazard ER models were developed to characterize the relationship between predicted C exposure or apparent clearance (CL/F) and specified endpoints, including PFS, dose modification, and select AEs (palmar-plantar erythrodysesthesia [PPE; Gr ≥1], diarrhea [Gr ≥3], hypertension [Gr ≥3], fatigue/asthenia [Gr ≥3], and ALT/AST elevation [Gr ≥3]). C exposure was defined as the overall average concentration from time zero to the time of event or censoring (CAVG) and estimated by population pharmacokinetic modeling for a typical patient. ER analysis for OS was not done due to the low number of events at the database lock date (March 30, 2020). Results: In the ER analysis of PFS, predicted C exposure at 40-mg and 20-mg QD doses was not significantly associated with the rate of progression or death (HR 1.00, 95% CI 0.78–1.27, for 20-mg vs 40-mg dose). In the ER analysis of AEs, lower predicted C exposure was significantly associated with lower rates of PPE (HR 0.63, 95% CI 0.50–0.78, for 20-mg vs 40-mg dose) and diarrhea (HR 0.48, 95% CI 0.29–0.80) but was not significantly associated with the rates of hypertension, fatigue/asthenia, or ALT/AST elevation. Higher predicted C CL/F was associated with a lower rate of C dose modification; however, this association was not statistically significant (HR 0.80, 95% CI 0.57–1.12, for CL/F 3.2 vs 1.2 L/hr). Conclusions: In ER models of pts with 1L aRCC treated with the combination of N+C, C exposure was not significantly associated with PFS; however, higher C exposure was associated with higher rates of PPE and diarrhea. ER modeling predicts that a starting dose of 40 mg QD C in combination with N with appropriate dose modifications to manage C AEs will not adversely affect the efficacy of the combination in 1L aRCC. Clinical trial information: NCT03141177.