tbuckley/cabot-search huggingface dataset:
Receipt of palliative care (PC) in acute myeloid leukemia (AML) using data from the National Cancer Database (NCDB).
Authors: Bryan Lee Chan, Allison O. Taylor, Kimberley Doucette, Jaeil Ahn, Xioyang Ma, Catherine Lai
Journal: Journal of Clinical Oncology (2021)

12087 Background: AML is an aggressive disease with high mortality and significant impact on quality of life. Palliative care (PC) services have become integral in managing patient’s symptoms during treatment as well as at the end of life. We hypothesize that socioeconomic factors such as achieving higher levels of education, and higher incomes, increases the odds of receiving PC. Methods: This is a retrospective analysis using NCDB data of 124,988 newly diagnosed non-M3 AML patients over 18 yrs from 2004-2016. Unadjusted and multivariate adjusted logistic regression analysis (MVA) evaluated the impact of socioeconomic variables on the receipt of PC. In the MVA, we adjusted for demographic variables and facility characteristics including facility type, facility volume, age, sex, race, Hispanic origin, income, education, urban/rural residence, Charlson-Deyo score, great circle distance, Medicaid expansion status state group, and insurance status. Patients with Medicaid expansion &lt; 39yrs were excluded due to low patient numbers. Results: For the 124,988 patients, median age was 63 years (range 18-90) with 54% males and 86% White. 25% of patients lived in regions with the highest education level defined as &lt; 6.3% of adults over 25 without a high school diploma. 35% of patients had a household income bracket of ≥ $63,333. A total of 3% of patients received PC. MVA showed that patients within the highest income bracket of ≥ $63,333 were less likely to have used PC services (OR 0.82, p &lt; 0.01). More educated patients residing in regions with &lt; 6.3% of adults without a high school diploma had higher odds of receiving PC treatment compared with patients with less education (OR 1.23, p &lt; 0.01). Residence in states with Medicaid expansion in January 2014 or later was associated with greater utilization of PC services (Jan 2014 expansion states: OR 1.33 and late expansion states/after Jan 2014: OR 1.43, p &lt; 0.01) compared to residence in non-expansion states. No difference was seen across races; except Hispanics with decreased use of PC services(OR 0.8, p = 0.022). Conclusions: In this large cohort, a small percentage of patients received PC. Higher education was associated with higher likelihood of using PC, while, surprisingly, higher income was associated with a lower likelihood of PC. Additionally, the higher use of PC services with Medicaid expansion suggests a broad impact of public health insurance in providing increased access to PC services.
Duality of the association between COVID-19 and acute pancreatitis
Authors: Xiu-He Lv, Kai Deng, Jin-Lin Yang
Journal: Gut (2021)

<h3>Abstract</h3> External direct current (DC) cardioversion is a commonly used method of terminating atrial arrhythmias. The chance of procedural success is inversely related to the duration of the arrhythmia. In many hospitals, the procedure is carried out under general anaesthesia, necessitating the presence of anaesthetic as well as medical staff. Frequently, it may be difficult to coordinate the availability of the two teams, causing delays to each patient, waste of staff time, an inefficient service and increased costs. The primary aim of the study was to determine the safety and tolerability of conscious sedation using intravenous midazolam in elective external DC cardioversion of patients with atrial flutter or atrial fibrillation attending University Hospital Limerick, Ireland. Patients who were electively admitted for DC cardioversion for atrial fibrillation or atrial flutter were recruited. A pre-defined sedation protocol using intravenous midazolam was used. The midazolam was given by the cardiology registrar without the presence of an anaesthetist. DC cardioversion was then performed according to the hospital protocol. Any complications arising during the procedure were noted. Prior to discharge, patients were given a questionnaire to determine their awareness of the procedure and if they would have the procedure done again in the future if needed. A total of 100 patients were recruited. The median number of shocks was one (highest number of shocks being four). The median dose of midazolam was 7.5 mg, with the highest dose being 20 mg. All of patients surveyed were not aware of the shock that was administered to them. All of the patients surveyed were happy with the service and would be happy to return for a repeat cardioversion in the future if required. The use of conscious sedation for DC cardioversion of patients with atrial fibrillation / atrial flutter was found to be safe and tolerable.
Clinical application of next-generation sequencing in cancer patients.
Authors: Valentina Shamrikova, Polina Shilo, Maria Stepanova, Ksenia Dekhanova, Evgeny Ledin
Journal: Journal of Clinical Oncology (2021)

e15090 Background: Next-generation sequencing (NGS) has been moving rapidly from pure cancer genomics research towards clinical oncology to provide a rigorous personalized approach to treating cancer. Still there is a number of limitations to overcome before we are ready to fully introduce NGS into everyday clinical decision-making. Here we are sharing our experience with using targeted NGS platforms in clinical practice. Methods: We retrospectively evaluated the NGS results and the treatments, provided to the patients after NGS testing between Marсh 2019 and January 2021. The patients’ clinical characteristics, response to treatment and genomic mutation profiles were reviewed. Coprimary endpoints were the percentage of patients with NGS revealed targeted therapy options and the percentage of patients who received mutation-driven therapy. Results: Samples from 95 patients were tested, most frequently GI tumors (n=25, 26%), hepatobiliary tumors (n=11, 12%), breast cancer (n=10, 11%) gynecological tumors (n=10, 11%), central nervous system tumors (n=7, 7%) and others (n=32, 33%). An average of two gene alterations were identified per patient (range 0-15). The 95% (n=90) of samples had at least one detected mutation, and in 42% (n=40) of cases gene mutations happened to be targetable with existing drugs, including off-label prescriptions. Mutation-driven therapy was performed in 9,5% cases (n=10) with clinically meaningful response in 5 patients (2 patients with ovarian cancer, 2 patients with colon cancer and 1 melanoma). Conclusion: Mutational profiling using a targeted NGS panel has identified potentially targetable alterations in a vast majority of advanced cancer patients. The assay has revealed additional therapeutic options in 42% of patients. However, due to the short-term follow-up, just a small number of patients have received mutation-driven therapy. Further study will be required to determine if the mutation-driven therapy will prove to be clinically meaningful in these patients.
Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease
Authors: Stephan Urban, Christoph Neumann-Haefelin, Pietro Lampertico
Journal: Gut (2021)

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5-10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.
The incidence of occult endocrinopathies in patients with cancer undergoing immunotherapy in community practice.
Authors: Ahmed Abdalla, Aditi Singh, Hussein Gharib, Benjamin Huber, Sindhu Janarthanam Malapati, Tarik H. Hadid, Zyad Kafri
Journal: Journal of Clinical Oncology (2021)

e14571 Background: Immune checkpoint blockade (IO) can induce inflammation of the pituitary, thyroid or adrenal glands. This usually results in non-specific symptoms such as headache, low-energy, nausea and vomiting, which can be difficult to differentiate from symptoms associated with cancer and therapy-related symptoms. Therefore, the exact incidence of endocrinopathies is exceedingly difficult to estimate in community practices. Also, the variable methods of assessment, diagnosis, and monitoring used in different clinical trials make it challenging to precisely measure the incidence of endocrinopathies. Methods: This is a single-center retrospective chart review of patients diagnosed with cancer receiving immunotherapy for cancer treatment who had routine hormone levels checked during their treatment. Data collected includes tumor types and the types of IO agents used. Laboratory data collected included thyroid-stimulating hormone (TSH), testosterone level, follicular stimulating hormone (FSH), luteinizing hormone (LH), cortisol levels. Results: In total, 75 patients were included in the study. The primary indication for IO was lung cancer in 43 patients (57%), genitourinary tumors (12%), melanoma (12%) and head &amp; neck cancers (5.3%). Single-agent nivolumab (39 patients) was the most common IO agent used followed by single-agent pembrolizumab (22 patients), ipilimumab (11 patients), atezolizumab (3 patients), avelumab (1 patient) (There was one patient who got nivolumab initially and then pembrolizumab). Nine patients were treated with ipilimumab/nivolumab combination. The mean number of cycles received was 9.1. The total number of patients who developed at least one abnormal hormone level was 57(76%), with 33 out of 74 (45%) patients had at least one abnormal TSH, 29 out of 44 (66%) patients had at least one abnormal testosterone level, 10 out of 49 (20.4%) patients had at least one abnormal FSH and/or LH level, 36 out of 52 (69%) patients had at least one abnormal cortisol level. The mean number of days from starting IO to develop the first abnormal laboratory result was 106 days. Conclusions: The incidence of endocrinopathy was significantly high in patients receiving IO in this study, which is higher than what is reported in previous clinical trials. This could be due to frequent testing in asymptomatic patients and strict laboratory cut-off values which is not always clinically meaningful. This finding may highlight the importance of routine monitoring of the endocrine function during IO treatment. Routine measurement of hormone levels can detect asymptomatic endocrinopathy which may warrant further work-up and treatment. These findings should be validated in a larger prospective study.
An exploratory clinical study of gefitinib combined with anlotinib in the first-line treatment of stage ⅢB-Ⅳ EGFR gene mutant non-small cell lung cancer patients with slow progress.
Authors: Pengyuan Wang
Journal: Journal of Clinical Oncology (2021)

e21089 Background: Anlotinib is a new type of small molecule anti-angiogenic drug that can inhibit the activity of a variety of tyrosine kinase receptors. Based on the initial efficacy of the combination of anti-angiogenic drugs and EGFR-TKIs and a clearer definition of people who are sensitive to EGFR-TKIs treatment, this study explores the slow progress of first-line use of gefitinib in patients with non-small cell lung cancer slowly progress, the efficacy and safety of combined Anlotinib. Methods: Fifteen patients with first-line non-small cell lung cancer who received gefitinib treatment and slowly progressed after enrolled in Xuchang Central Hospital, 15 received anlotinib(12mg/d from day 1 to day 14 in a 21-day cycle) combined with gefitinib（250mg /d） treatment until the disease progressed or died or was intolerable Adverse events. The primary endpoint was the progression-free survival(PFS), and the secondary endpoints were objective response rate (ORR), disease control rate( DCR) and safety. Results: As of January 4, 2021, a total of 15 patients have been enrolled and 14 patients can be evaluated. 0CR, 5PR, 8SD, 1PD. The median progression-free survival was 13.3 months (95% Cl, 3.71-4.89), and the most common adverse reactions were Grade 1, including hypertension (42.86%) and fatigue (21.42%). No higher-grade adverse reactions. Conclusions: Gefitinib combined with Anlotinib Hydrochloride Capsules is safe, effective and well tolerated when the first-line treatment of EGFR gene mutant non-small cell lung cancer patients progresses slowly.
HGG-09. TARGETING FACILITATES CHROMATIN TRANSCRIPTION (FACT) AS A NOVEL STRATEGY THAT ENHANCES RESPONSE TO HISTONE DEACETYLASE (HDAC) INHIBITION IN DIPG
Authors: Anahid Ehteda, Sandy Simon, Laura Franshaw, Federico M Giorgi, Jie Liu, Elisha Hayden, Jourdin Rouaen, Chi Nam Ignatius Pang, Ruby Pandher, Chelsea Mayoh, Yujie Tang, Aaminah Khan, Caitlin Ung, Anne Kankean, Rebecca Lehmann, Sylvie Shen, Anjana Gopalakrishnan, Peter Trebilcock, Katerina Gurova, Andrei Gudkov, Murray D Norris, Michelle Haber, Orazio Vittorio, Maria Tsoli, David S Ziegler
Journal: Neuro-Oncology (2021)

Abstract DIPG is an aggressive and incurable childhood brain tumour for which new treatments are needed. A high throughput drug screen of 3500 pharmaceutical compounds identified anti-malarials, including quinacrine as having potent activity against DIPG neurospheres. CBL0137, a compound modelled on quinacrine, is a novel anti-cancer compound which targets Facilitates Chromatin Transcription (FACT), a chromatin remodelling complex involved in transcription, replication, and DNA repair. CBL0137 effectively crosses the blood-brain barrier and has recently completed Phase I testing in adult patients. CBL0137 induced apoptosis in DIPG neurospheres and had profound cytotoxic activity against a panel of DIPG cultures. In a DIPG orthotopic model, treatment with CBL0137 significantly improved survival. We found that treatment with CBL0137 up-regulated TP53 and increased histone H3.3 acetylation and tri-methylation in DIPG cells. We therefore examined the interaction between CBL0137 and the histone deacetylase (HDAC) inhibitor panobinostat. In vitro experiments showed that the two agents had profound synergistic activity against DIPG neurospheres in clonogenic assays and enhanced caspase activation and apoptosis. The FACT subunit SSRP1 was found to directly interact with H3.3K27M and treatment with CBL0137 targeted this epigenetic defect, restoring histone H3.3 trimethylation and leading to tumor cell death. Transcriptomic analysis and immunoblotting indicated that combination treatment activated signalling pathways controlled by Retinoblastoma (RB)/E2F1 and subsequently increased phosphorylation and enzymatic activity of enhancer of zeste homolog 2 (EZH2). Consistent with the in vitro results, the combination of CBL0137 and panobinostat significantly prolonged survival in two independent orthotopic models of DIPG, while histological analysis showed restoration of H3K27me3 and decreased Ki67 positive cells. In addition to panobinostat, CBL0137 has been found to combine synergistically in vitro and in vivo with PARP and BET inhibitors. Given these promising results, a paediatric trial of CBL0137 will open through the Children’s Oncology Group with an expansion cohort for DIPG patients.
Corticosteroids Plus Intravenous Immunoglobulin Compared with Corticosteroids for the Treatment of Immune Thrombocytopenia in Pregnancy: An Observational Multicenter Study in China
Authors: Xiao-Lu Zhu, Jing-Wen Wang, Jian-Liang Shen, Hui Liu, Ru Feng, Cheng-Hong Yin, Ying-Jun Chang, Jiang Qian, Hao Jiang, Jin Lu, Mei-Ying Liang, Xiao-Hong Zhang, Jian-Liu Wang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: Blood (2017)
Multicenter phase I/II trial of encorafenib with and without binimetinib in combination with nivolumab and low-dose ipilimumab in metastatic BRAF-mutant melanoma.
Authors: Max Jameson-Lee, Patrick Alexander Ott, Jason J. Luke, Michael A. Postow, Andrew Stewart Poklepovic
Journal: Journal of Clinical Oncology (2021)

TPS9596 Background: Targeted therapy (BRAF + MEK inhibitors) and immunotherapy (anti-PD1 + anti-CTLA4) have improved overall survival for metastatic or unresectable BRAF V600E/K mutant melanoma. Whereas targeted therapy has a high response rate, immunotherapy may deliver longer term disease control for a larger number of patients. Despite these treatments, patients with high risk metastatic melanoma such as those with brain or liver metastases, elevated lactate dehydrogenase (LDH) and bulky disease have inferior treatment outcomes with current therapies. A BRAF+MEK+PDL1 regimen has recently emerged however the role for this treatment remains unclear. Several recent trials combining MEK inhibition and immunotherapy have failed possibly because MEK inhibition can compromise T cell activation. Meanwhile the addition of CTLA4 blockade to PD1 inhibition appears to disproportionately benefit patients with non-T cell-inflamed tumors and potentially high-risk disease. For patients with high risk BRAF-mutant metastatic melanoma, further investigation of BRAF/MEK targeted and PD-1/CTLA-4 directed immunotherapy combination strategies remains a priority. Methods: This is an open label, multi-site, Phase 1/2 study of encorafenib (Enco) +/- binimetinib (Bini) + nivolumab (Nivo) + ipilimumab (Ipi) for the treatment of patients with unresectable or metastatic BRAF-mutated melanoma in high-risk cohorts (NCT04655157). An initial regimen confirming Phase I approach will be pursued on two schedules concurrently, with patients accruing equally to each group. Group 1 will receive 3mg/kg Nivo, and 1 mg/kg Ipi and 300mg Enco (12 participants, triple therapy) and Group 2 will receive 3mg/kg Nivo and 1mg/kg Ipi and 450mg Enco and 45mg Bini, (12 participants, quadruple therapy). Dose limiting toxicity (DLT) will be evaluated weeks 1-6. A recommended Phase II regimen (RP2R) [either triple or quadruple therapy] will be carried forward into two high risk metastatic disease cohort expansions of 30 participants each. Cohort 1 will include patients with symptomatic brain metastases, while cohort 2 will include patients with elevated LDH as well as either liver metastases OR bulky visceral disease (sum of longest diameters &gt; 44mm). Patients meeting criteria for cohorts 1 and 2 will be placed in cohort 1. Patients with symptomatic brain metastases will be included with an ECOG up to 2 and on ≤ 4mg of dexamethasone or equivalent. Continuous Bayesian toxicity monitoring will be used throughout to monitor DLT. Pre and on-treatment tumor biopsies will assess changes in the tumor microenvironment while peripheral blood ctDNA and T cell Ki67% changes will assess early response and immune activation during triplet and quadruplet therapy. Clinical trial information: NCT04655157.
Clinical characteristics, treatment patterns, and overall survival of real-world patients with idiopathic multicentric Castleman disease.
Authors: Aaron B. Cohen, Akshay Swaminathan, Xiaoliang Wang, Stephen Zamora, Michael A Repucci, Jonathan Kelly, Mark D Hannan, Daniel Sepler, Suganya Sridharma, Abigail Orlando, Barry Leybovich, David Fajgenbaum
Journal: Journal of Clinical Oncology (2021)

7048 Background: Castleman disease (CD) has three subtypes: Unicentric (UCD), Human herpesvirus-8 associated multicentric (HHV-8 MCD) and idiopathic multicentric (iMCD). Outcomes for patients with iMCD are poor and treatment options are limited, with only one FDA-approved therapy (siltuximab in April 2014). Further, the lack of CD-specific ICD codes until 2017 has limited real-world evaluation. We identified iMCD patients in an electronic health record (EHR)-derived dataset and described their clinical characteristics, treatment patterns, and real-world overall survival (rwOS). Methods: Patients with a possible diagnosis of CD as of 8/31/20 were identified from the nationwide deidentified Flatiron Health EHR-derived database using patient-level structured data (e.g., ICD-9/10 codes) and unstructured data (e.g., clinician notes), curated via technology-enabled manual abstraction to confirm CD diagnosis and treatments received. Descriptive statistics summarized patient characteristics and treatment patterns. Patients without structured data within 90 days after diagnosis were excluded from treatment patterns analyses. 5-year rwOS rate was estimated from diagnosis date using the Kaplan-Meier estimator. Results: 747 patients with possible CD were identified, of whom 453 were confirmed to have CD by abstraction (172 UCD, 100 iMCD, 36 HHV-8 MCD, and 145 unclassified). IMCD patients were predominantly female (53%), white (58%), and treated at community sites (70%). Of the 52 iMCD patients with evidence of structured data within 90 days after diagnosis and who had at least one documented line of therapy, the most common first-line therapies were siltuximab-based therapy (42.3%), rituximab monotherapy (36.5%), and chemotherapy-based treatment (13.5%). Among 28 iMCD patients with evidence of second-line therapy, the most common treatment was rituximab monotherapy (35.7%). Among 60 iMCD patients diagnosed on or after siltuximab approval in April 2014 (including those without evidence of any treatment), 26 (43%) received siltuximab at some point. 5-year rwOS rate for the 100 iMCD patients was 75% [95% CI: 63-89%]. Conclusions: This is the first study to utilize a large EHR-derived database to describe characteristics, treatment patterns, and overall survival of iMCD patients in real-world practice. Less than half of iMCD patients diagnosed on or after the date of FDA approval for siltuximab received it at some point. Future work should focus on characterizing the drivers of poor patient outcomes.