tbuckley/cabot-search huggingface dataset:
Changes in the proportion of patients presenting with early stage colon cancer over time among Medicaid expansion and nonexpansion states.
Authors: Scarlett Hao, Rebecca A Snyder, William Irish, Alexander A. Parikh
Journal: Journal of Clinical Oncology (2020)

251 Background: In 2010, the Affordable Care Act required insurance plans to cover preventative screening, and the Medicaid expansion provision enabled participating states to increase Medicaid coverage of uninsured individuals. The aim of this study was to determine whether the proportion of patients diagnosed with early vs. late stage colon cancer (CC) at Commission on Cancer (CoC) facilities differed over time within states that expanded Medicaid in January 2014 (MES) vs. non-Medicaid expansion states (NMES). Methods: A hospital-based cohort study of patients diagnosed with CC from 2006-2016 was performed using the National Cancer Database. Uninsured and Medicaid-insured patients in MES were compared with patients in NMES. Patients with Medicare, private, or government insurance were excluded. The observed proportions of patients with early (AJCC I-II) vs late (III-IV) stage within each cohort were compared over time. Propensity score adjusted probability of early stage at presentation was determined among patients residing in MES and NMES. Results: The study cohort included 10,289 patients in MES and 15,173 patients in NMES. Compared to MES, a greater proportion of patients in NMES were black (33.4% vs 24.0%), had a median income &lt; $38,000 (39.7% vs 28.2%), and resided in a state with ≥21% of the population without a high school degree (37.4% vs 28.1%). The proportions of early stage CC in both cohorts in 2006 were similar. In NMES, this proportion remained constant over time until 2014 and declined by 0.8% per year after 2014. Within MES, the proportion of early stage CC increased by 0.6% per year until 2014 and 0.9% per year after 2014. By 2016, the absolute difference in the propensity adjusted proportion of early stage CC between cohorts was 8.8% (39.7% vs 30.9%, p &lt; 0.001). Conclusions: Following Medicaid expansion in 2014, the proportion of patients presenting to a CoC facility with early stage CC increased over time within MES and declined in NMES. Further investigation, including population-based research, is warranted to determine if enrollment in Medicaid improves access to colorectal cancer screening and leads to earlier stage at diagnosis.
Pertuzumab plus trastuzumab (P+T) in patients (Pts) with colorectal cancer (CRC) with <i>ERBB2</i> amplification or overexpression: Results from the TAPUR Study.
Authors: Ranju Gupta, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Stacy D. D'Andre, Eyal Meiri, Sagun Shrestha, Sasha L. Warren, Shamika Ranasinghe, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2020)

132 Background: TAPUR is a phase II basket trial evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with ERBB2 overexpression or amplification treated with P+T are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had ERBB2 overexpression or amplification, or certain ERBB2 mutations. Recommended dosing after initial dosing was P, 420 mg IV over 30-60 mins every 3 weeks (wks) and T, 6 mg/kg over 30-60 mins every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks per RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from November 2016 to September 2018 were evaluable for efficacy and safety. Demographics and outcomes are summarized in Table. All pts had ERBB2 amplification; 1 also had an ERBB2 mutation. 79% of pts had at least 3 prior txs. Four PR and 10 SD16+ were observed for DC and OR rates of 50% (90% CI, 36% to 60%) and 14% (95% CI, 4% to 33%), respectively. Two pts had at least one grade 3 AE or SAE at least possibly related to P+T including anemia, infusion reaction, and left ventricular dysfunction. Conclusions: The combination of P+T showed anti-tumor activity in heavily pre-treated CRC pts with ERBB2 amplification . Additional analyses by RAS mutation status are pending. Further study is warranted to confirm efficacy of P+T in this population. Clinical trial information: NCT02693535. [Table: see text]
Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients
Authors: Julie Rodriguez, Sophie Hiel, Audrey M Neyrinck, Tiphaine Le Roy, Sarah A Pötgens, Quentin Leyrolle, Barbara D Pachikian, Marco A Gianfrancesco, Patrice D Cani, Nicolas Paquot, Miriam Cnop, Nicolas Lanthier, Jean-Paul Thissen, Laure B Bindels, Nathalie M Delzenne
Journal: Gut (2020)

Objective The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin. Design The stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice ( hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3 months. Results We show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansi a, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin. Conclusion These findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders.
Comparison of the frequency of adverse events requiring interventions determined by telephone follow up in hepatocellular carcinoma patients treated with sorafenib and lenvatinib.
Authors: Koki Morishita, Hidetaka Suzuki, Junko Tauchi, Misaki K Takeno, Kohei Hayashi, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2020)

507 Background: The REFLECT trial demonstrated that lenvatinib is non-inferior to sorafenib for first-line treatment of unresectable hepatocellular carcinoma (uHCC). However, no comparison of the frequency of adverse events (AEs) requiring interventions has been reported yet between uHCC patients receiving sorafenib and those receiving lenvatinib. At the National Cancer Center Hospital East, Japan, pharmacists conduct telephone follow-up (TF) during the first month after the start of treatment with sorafenib or lenvatinib in uHCC patients, for the purpose of detecting and treating AEs early. The aim of this study was to reveal the frequency of AEs requiring interventions between patients receiving sorafenib and those receiving lenvatinib, based on TF. Methods: The characteristics, AEs and contents of intervention by TF of 56 uHCC patients who had been started on treatment with sorafenib and lenvatinib were reviewed retrospectively. The study subjects were 33 patients initiated on sorafenib treatment and monitored by TF from March 2017 to March 2018 (Group S) and 23 patients initiated on lenvatinib treatment and monitored by TF from March 2018 to March 2019 (Group L). Results: The total numbers of TFs in Group S and Group L were 91 and 48, respectively. The rate of AEs requiring interventions was significantly higher in Group S as compared to Group L (Group S, 17.6% (16/91); Group L, 4.2% (2/48); p = 0.032). The frequencies of the interventions, including use of supportive treatments (A), withdrawal of sorafenib or lenvatinib (B), and medical examination (C), differed between the two groups (A/B/C: Group S, 8/5/3 times vs. Group L, 2/0/0 times). The most frequently observed AE that necessitated intervention in Group S was the hand-foot syndrome (HFS) (75.0%, 12/16). Conclusions: The frequency of interventions for AEs appears to be higher in uHCC patients receiving sorafenib than in those receiving lenvatinib. Although a great number of patients taking sorafenib had symptomatic AEs, such as HFS, early detection of the symptoms through TF contributed to prevention of treatment withdrawal on account of AEs.
Coronavirus: doctor who faced backlash from police after warning of outbreak dies
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Li Wenliang—a doctor from Wuhan, China, who said he was reprimanded by police for warning other doctors about novel coronavirus at the start of the outbreak—has died after being infected with 2019-nCoV.

When the first cases of a pneumonia-like condition appeared in a local hospital, Li sent messages to his medical school alumni group on the Chinese messaging app WeChat, warning that, from the test results he had seen, it appeared to be a coronavirus. Coronaviruses are a family of viruses that includes …
Serial CT analysis in idiopathic pulmonary fibrosis: comparison of visual features that determine patient outcome
Authors: Joseph Jacob, Leon Aksman, Nesrin Mogulkoc, Alex J Procter, Bahareh Gholipour, Gary Cross, Joseph Barnett, Christopher J Brereton, Mark G Jones, Coline H van Moorsel, Wouter van Es, Frouke van Beek, Marcel Veltkamp, Sujal R Desai, Eoin Judge, Teresa Burd, Maria Kokosi, Recep Savas, Selen Bayraktaroglu, Andre Altmann, Athol U Wells
Journal: Thorax (2020)

Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients with non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range of measurement variation (5.0%-9.9%). We examined whether change in visual CT variables could help confirm whether marginal FVC declines represented genuine clinical deterioration rather than measurement noise.In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs of radiologists scored paired volumetric CTs (acquired between 6 and 24 months from baseline). Change in interstitial lung disease, honeycombing, reticulation, ground-glass opacity extents and traction bronchiectasis severity was evaluated using a 5-point scale, with mortality prediction analysed using univariable and multivariable Cox regression analyses. Both IPF populations were then combined to determine whether change in CT variables could predict mortality in patients with marginal FVC declines.On univariate analysis, change in all CT variables except ground-glass opacity predicted mortality in both cohorts. On multivariate analysis adjusted for patient age, gender, antifibrotic use and baseline disease severity (diffusing capacity for carbon monoxide), change in traction bronchiectasis severity predicted mortality independent of FVC decline. Change in traction bronchiectasis severity demonstrated good interobserver agreement among both scorer pairs. Across all study patients with marginal FVC declines, change in traction bronchiectasis severity independently predicted mortality and identified more patients with deterioration than change in honeycombing extent.Change in traction bronchiectasis severity is a measure of disease progression that could be used to help resolve the clinical importance of marginal FVC declines.
Baseline features predicting receipt of chemotherapy in metastatic esophageal cancer: A National Cancer Database analysis of 12,370 patients.
Authors: Nicholas Manguso, Sungjin Kim, Andrew Eugene Hendifar, Samuel J. Klempner, Joseph Chao, Michelle Guan, Veronica Placencio-Hickok, Haesoo Kim, Jar-Yee Liu, Miguel Burch, Alexandra Gangi, Katelyn Mae Atkins, Mitchell Kamrava, Jun Gong
Journal: Journal of Clinical Oncology (2020)

316 Background: We investigated predictors for chemotherapy (CTX) and prognostic variables in a large metastatic esophageal cancer (mEC) patient data set. Methods: We interrogated the National Cancer Database between 2004-2015 and included patients (pts) with M1 disease who had known CTX status (received or did not receive CTX). Univariable and multivariable analyses were performed, and a logistic regression model was used to estimate the effect of CTX with adjustment for potential confounders. Results: We included 12,370 mEC patients with available CTX status for multivariable analyses. Predictors for CTX treatment included year of diagnosis 2010-2014 (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.17-1.43), median income &gt; $46,000 (OR 1.49, 1.27-1.75), and node-positivity (OR 1.35, 1.20-1.52; all p &lt; 0.05), while female gender (OR 0.86, 0.76-0.98), black race (OR 0.76, 0.67-0.93), uninsured (OR 0.41, 0.33-0.52), and Charlson Comorbidity Index (CCI) ≥2 (OR 0.61, 0.50-0.74) predicted for lower odds of receiving CTX (all p &lt; 0.05). Median OS for pts receiving CTX was 9.53 mos (9.33-9.72) vs. 2.43 mos (2.27-2.60) with no CTX (p &lt; 0.001). Modeling the effect of CTX to OS using a time-dependent coefficient showed that CTX was associated with improved OS up to 10 months, after which there is no significant effect on OS. Independent predictors of OS included treatment at an academic center (hazard ratio (HR) 0.91, 0.87-0.94), CCI ≥2 (HR 1.16, 1.07-1.26), and uninsured status (HR 1.20, 1.09-1.31). Conclusions: We identified several predictors for receipt of CTX and OS in pts with mEC. The benefit of CTX on OS is time-dependent and favors early initiation. Focused outreach in lower income and underinsured patients is critical as receipt of CTX is associated with improved OS.
A randomized study evaluating tailoring of advanced/metastatic colorectal cancer (mCRC) therapy using circulating cell-free tumor DNA (ctDNA) (TACT-D).
Authors: Kanwal Pratap Singh Raghav, Xin Shelley Wang, Lianchun Xiao, Arvind Dasari, Van K. Morris, Benny Johnson, John Paul Y.C. Shen, Christine Megerdichian Parseghian, Bryan K. Kee, Imad Shureiqi, David R. Fogelman, Robert A. Wolff, Victoria M. Raymond, Justin I. Odegaard, Richard B. Lanman, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2020)

TPS277 Background: Identifying non-responders to expensive salvage therapies with modest benefits and substantial treatment related adverse events (TRAEs) (e.g. regorafenib/TAS102 in mCRC) is necessary to maximize benefits and limit toxicities. Serial ctDNA sequencing is reliable for tracking tumor dynamics and appears to predict resistance to therapy earlier than radiographic progression. Methods: TACT-D is a randomized study (N = 100) to validate the ability of changes in ctDNA (ΔctDNA) to predict resistance early and in limiting toxicities. We hypothesize that increase in ctDNA (measured by variant allele fraction) at 2 weeks (wk) into treatment can predict resistance earlier than standard radiographic means [at 8-12 wk] and detecting resistance early can enable prompt change in therapy resulting in reduction of TRAEs. Pts with mCRC eligible for either regorafenib/TAS102 are randomized 2:1 to either standard of care (SOC) or ctDNA arm. On SOC arm, treatment is given as per current paradigm i.e. for 8 wk and then restaging. On ctDNA arm, decision to continue therapy is based on ctDNA change between baseline and 2 weeks [ΔctDNA = ctDNA (C1D15 – C1D1)]. Increase in ctDNA triggers early radiographic staging (4 wk). Treatment is continued for disease stability/regression and discontinued for progression. Study has 2 co-primary endpoints: 1) Association of Δ ctDNA and radiographic progression [62 pts on SOC arm, have 94% power (2-sided α 0.05) to detect difference of 95% vs. 58% in progressive disease between pts with increase vs decrease in ctDNA] and 2) Compare proportion of pts experiencing TRAEs within 4 months between study arms [67 in SOC arm and 33 in ctDNA arm have 82% power (2-sided α 0.05) to detect a 30% decrease in toxicity]. Key secondary endpoints include: patient-reported outcomes (MD Anderson Symptom Inventory and PRO-CTCAE), OS, clinical events of special interest (hospitalizations/ER visits/medical interventions such as blood transfusions/IV hydration), clinical trial referral and cost effectiveness. Study is now actively accruing pts (NCT03844620). Funding: MD Anderson Cancer Center, Houston, TX &amp; Guardant Health Inc., Redwood City, CA. Clinical trial information: NCT03844620.
Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis
Authors: Lisette F. van Dam, Charlotte E. A. Dronkers, Gargi Gautam, Åsa Eckerbom, Waleed Ghanima, Jostein Gleditsch, Anders von Heijne, Herman M. A. Hofstee, Marcel M. C. Hovens, Menno V. Huisman, Stan Kolman, Albert T. A. Mairuhu, Mathilde Nijkeuter, Marcel A. van de Ree, Cornelis J. van Rooden, Robin E. Westerbeek, Jan Westerink, Eli Westerlund, Lucia J. M. Kroft, Frederikus A. Klok
Journal: Blood (2020)
Safety and efficacy of radiofrequency ablation for pulmonary metastases in metastatic colorectal cancer patients: A single center experience.
Authors: Dong-Hoe Koo, Hyun Pyo Hong, Sukjoong Oh, Yun-Gyoo Lee, Kyung A. Kang, Heon-Ju Kwon, Mi Sung Kim, Soo Youn Ham, Hyebin Lee, Kyung Uk Jung, Hyung Ook Kim, Hungdai Kim, Ho-Kyung Chun, Du-Young Kang, Tae Yun Oh
Journal: Journal of Clinical Oncology (2020)

141 Background: Radiofrequency ablation (RFA) has been increasingly used for the treatment of pulmonary metastases from several types of malignancies. Methods: A retrospective analysis was performed for the safety and efficacy of percutaneous RFA in patients with metastatic colorectal cancer between October 2016 and June 2019 as well as assessing prognostic factors of local tumor control. Results: RFA was carried out for 48 lung metastases in 31 consecutive colorectal cancer patients. Male was 17 patients (55%), and the median age at RFA was 61 years (range, 42-81). The mean diameter of metastases targeted for RFA was 12 mm (range, 4-32), and 17 tumors (35%) were located in a sub-pleural or deep position. Although five cases (10%) were failed due to immediate complications, there was no procedure-related death. In terms of immediate complication, a total of 12 cases (25%) had events including nine pneumothorax (percutaneous drain in four), one pleural effusion, and two hemoptysis (ICU care in one). Delayed complications were lung abscess and diaphragm injury in each one patient, respectively. At the time of analysis, the median follow-up duration from RFA was 12.0 months (interquartile range, 6.5-23.1). Only two patients (6%) died of disease progression, and 3-year overall survival rate was 85.5% (95% CI, 75.5-95.5). RFA site progression was observed in 11 patients (23%), and 1-year and 2-year progression-free survival rates were 71.5% (95% CI, 58.7-84.3) and 56.6% (95% CI, 42.6-70.6), respectively. Multivariate analysis showed that extra-pulmonary progression (hazard ratio 17.49; p = 0.023) was only one independent prognostic factor associated with RFA site progression after adjusting for confounding factors including sex, age, performance, tumor size, location, contact with the vessel, last chemotherapy response, and duration. Conclusions: RFA is a comparatively safe and effective option for the treatment of small-sized lung metastases; however, the control of extra-pulmonary metastases should be accompanied for effective local control.
Aspartyl (asparaginyl) β-hydroxylase (AABH), a serum biomarker for lung cancer.
Authors: Kiarash Moshiri
Journal: Journal of Clinical Oncology (2020)

45 Background: There are no serum biomarkers currently approved for the detection of lung cancer, a leading cause of cancer associated mortality world wide. More than 180,000 cases of lung cancer will be diagnosed in the United States in 2020 by other means such as by X-ray and CT scanning methods, which have inherently lower sensitivity and higher cost when compared generally to serological methods. While the five year survival for lung cancer is 15%, a survival rate of 50% can be achieved when detection is made early in individuals with localized cancer. Current detection methods, however, enable such detection in only about 18% of cases overall. Methods: A prospective serum biomarker Aspartyl (Asparaginyl) ß Hydroxylase (AABH), has been previously found to be elevated by immunohistochemical staining (IHC) in a broad range of cancers, including lung cancer. AABH was detected in &gt; 99% of tumor specimens tested (n &gt; 1000) but absent in adjacent tissue. The present study introduces a double monoclonal sandwich ELISA which provides detection and comparative quantification of AABH in serum of lung cancer patients vs. normal, and high-risk controls such as cigarette smokers without cancer. This is relevant since 87% of lung cancers are attributable to cigarette smoking, and associative parallels can be seen with recent reductions in rates of smoking. Results: Increased levels of serum AABH were found in 99% of patients with lung cancer (n = 192). Serum AABH was found to be undetectable in individuals not known to have cancer (n = 129, specificity = 93%). In patients with lung cancer, AABH was detectable at all stages. In a population of 50 smokers not known to have cancer, the mean serum AABH level was 0 ng/ml with 90% specificity. Conclusions: The AABH serum ELISA therefore has great promise as an additional diagnostic tool for lung cancer having the practicality and cost effectiveness of conventional serological screening. Elevated serum AABH in conjunction with CT scanning may greatly facilitate earlier diagnosis of lung cancer at a stage in which cure rates are significantly higher and thus may contribute to increased patient survival.
Gender Difference in Behavioral and Psychological Symptoms of Alzheimer's Disease
Authors: Nan MU, Huawang WU, Ping MA, Dongping RAO, Junchang YU, Qiaoting Huang, Mouni TANG, Ruoxi ZHANG, Jiyang PAN
Journal: Alzheimers Disease & Dementia (2019)

Behavioral and psychological symptoms of dementia (BPSD) are important clinical manifestations of Alzheimer's Disease (AD), which may occur at the early stage or throughout the entire course of dementia. They can predict the progression of dementia and serve as the major causes for long-term hospitalization and reduction in caregiver's life quality. Current studies on gender difference of AD are only limited to the epidemiological aspect, but rarely on the clinical and neuropathology aspect.