tbuckley/cabot-search huggingface dataset:
Global perspectives on clinical cancer research: A comparison of randomized controlled trial (RCT) design and outcomes across high income and low-middle income countries.
Authors: Connor Wells, Shubham Sharma, Joey C. Del Paggio, Wilma M. Hopman, Bishal Gyawali, CS Pramesh, Richard Sullivan, Christopher M. Booth
Journal: Journal of Clinical Oncology (2020)

7021 Background: Cancer clinical trials have become increasingly international in scope. There are limited data regarding trial variation based on the economic status of the country in which they are conducted. Here we describe trial characteristics, design, and results of all RCTs published globally during 2014-2017. Methods: A structured literature search was designed using PUBMED to identify all RCTs evaluating anti-cancer therapies published during 2014-2017. Data captured included authorship, participants, study characteristics, design, and results. RCTs were classified based on the World Bank country-level economic classification of the first author [low-middle/upper-middle income countries (LMIC) and high-income countries (HIC)]. Among superiority RCTs that met the primary endpoint (i.e. statistically “positive”), we calculated the ESMO-MCBS to identify trials with substantial clinical benefit (MCBS scores 4/5 or A/B). Outcomes were compared with Chi Square or Fisher’s Exact tests. Results: The study cohort included 694 RCTs; 636 (92%) were led by HIC and 58 (8%) were led by LMIC. Compared to LMIC, RCTs in HICs were more likely to be funded by industry [73% vs 41%, p&lt;0.001] and more likely to test novel systemic therapies [87% vs 78%, p=0.027]. LMIC studies were typically smaller (median N=220 vs N=474 participants, p&lt;0.001) and more likely to meet their primary endpoints [66% vs 44%, p=0.002]. In “positive” superiority trials, the effect size was larger in LMICs compared to HICs (median HR 0.62 vs HR 0.84, p&lt;0.001). The proportion of trials identifying treatments with substantial clinical benefit (ESMO MCBS 4/5/A/B) was 45% (LMIC) and 31% (HIC, p=0.291). Studies from LMIC were published in journals with lower impact factors (IF) (median IF 7 vs 21, p&lt;0.001); a publication bias persisted when adjusted for whether a trial was positive or negative: median IF LMIC negative trial=5 vs HIC negative trial=18 (p&lt;0.001); median IF LMIC positive trial=9 vs HIC positive trial= 26 (p&lt;0.001). Conclusions: Only a small minority of oncology RCTs are led by investigators in LMIC; these trials are less likely to be funded by industry and more likely to meet their primary endpoint. “Positive” RCTs from LMIC identify therapies with a substantially larger effect size than HIC. These data identify a substantial publication bias against RCTs conducted in LMIC.
Safety and efficacy of Tirofiban in patients with acute coronary syndrome
Authors: Bin Yuan, Sheng-hu He, Jing Zhang, Jian-feng Yan, Shu Chen, Yong Xie
Journal: BMJ (2009)

A total of 159 patients with acute coronary syndrome(ACS)were enrolled from December 2006 to June 2008 and divided into the percutaneous coronary intervention(PCI)group and the internal medicine treatment group.The participants in the two groups were further assigned to the Tirofiban or the placebo control group.The change in electrocardiograph within 48 hours,major adverse cardiac events (MACE)during hospital stay and 30 days' follow-up,and bleeding were compared between the sub-groups.As a result,in comparison with the placebo control groups,the Tirofiban sub-groups showed significant improvement in electrocardiography(P＜0.01).In the internal medicine treatment group,the rate of MACE during 30 days' follow-up was significantly decreased in patients treated with Tirofiban(P＜0.05),although no significant difference in bleeding rate was found.Our data suggest that Tirofiban may be safe and effective in the treatment of ACS.

Key words: 
Acute coronary syndromes; Therapy
A simulation study of loss to follow up: The impact on time to event and prevention.
Authors: Donna Elise Levy, Bingyan Wu, Daniel Quinn, Sophie Jentzsch, Christine Lusk, Jane Kristina Bentley
Journal: Journal of Clinical Oncology (2020)

e14097 Background: Patient attrition during study follow up is a concern in all clinical trials, although its impact on study results has rarely been assessed. In oncology, in particular, where studies are lengthier and may be extended into longitudinal studies, there is an increased likelihood of loss to follow up (LTFU) (Gill et al., 2018). This creates a heightened need to understand how it affects the trial’s validity. The loss of data from patients who have been LTFU can reduce a study’s precision and power. This imprecision not only impacts the results of the current study but can also affect future research as well as future patient treatment options. Studies have found that participant characteristics differ in individuals LTFU as compared to those who remain in follow up (Childs et al., 2011; Geng et al., 2008; Hochheimer et al., 2016). This further emphasizes how attrition can skew study results and their interpretation and supports the need to minimize patient attrition during follow up in order to reduce bias and generate robust study estimates. Methods: This study assessed the impact of LTFU rates on the study estimates through simulations using SAS software. While all endpoints can be affected by LTFU, this study assessed time-to-event endpoints. Exponential distribution was assumed with varying rates of LTFU. In addition, the work covered suggestions for reducing LTFU. Results: Even for low rates of LTFU, biases are introduced in time-to event endpoints. Conclusions: Researchers should make every effort to minimize the extent of LTFU in the design and of and conduct of their trials.
Mechanisms of pulmonary embolism and/or deep vein thrombosis secondary to chronic obstructive pulmonary disease exacerbation in elders
Authors: Jiuwu Bai, Beilan Gao, Jinfu Xu, Huiping Li, Weijun Cao, Shuo Liang, Kebin Cheng, Haiwen Lu
Journal: BMJ (2014)

Objective
To explore the inflammatory mechanisms of pulmonary embolism (PTE) and/or deep venous thrombosis (DVT) in elders secondary to chronic obstructive pulmonary disease (COPD) exacerbation.


Methods
A total of 26 elders with acute exacerbation of high-risk COPD secondary PTE and/or DVT and 26 patients with low-risk COPD during stable phase diagnosed during the period of January 2008 to December 2012 were enrolled. The relevant parameters of routine blood examination, blood viscosity, D-dimer, fibrinogen (FIB), arterial blood gas, blood cytokine, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were retrospectively analyzed.


Results
The major nonspecific symptoms were cough, sputum and dyspnea. The mean of neutrophile percentage (N%), D-dimer, FIB, interleukin-6 (IL-6), tumor necrosis factor (TNF), C-reactive protein (CRP), low and high shear blood viscosity in blood samples of patients with acute exacerbation of high-risk COPD secondary PTE and (or) DVT were higher than those of the control group (t=3.339, 2.700, 2.207, 2.431, 2.257, 2.143, 2.223, 2.797, all P<0.05). However arterial partial pressure of oxygen (PaO2) was lower than that of lower-risk COPD patients (t=4.312, P<0.05). IL-6 in blood of patients with acute exacerbation of high-risk COPD secondary PTE and (or) DVT was positively correlated with low-shear blood viscosity, D-dimer and FIB (r=0.437, 0.624, 0.429, all P<0.05). TNF in blood of patients with acute exacerbation of high-risk COPD secondary PTE and (or) DVT was positively correlated to FIB, low and high cut blood viscosity (r=0.624, 0.519, 0.513, all P<0.05). Plasma CRP in blood of patients with acute exacerbation of high-risk COPD secondary PTE and/or DVT was positively correlated with D-dimer, FIB, IL-6 and TNF (r=0.478, 0.541, 0.533, 0.491, all P<0.05).


Conclusions
Inflammation may exist in elders with acute exacerbation of high-risk COPD secondary thrombotic disease. IL-6 and TNF may promote thrombosis secondary to acute exacerbation of COPD disease. Early screening and/or prophylactic anticoagulation are necessary for prevention.


Key words: 
Pulmonary disease, chronic obstructive; Pulmonary embolism; Venous thrombosis
Neoantigen screening identifies <i><i>EGFR</i></i> L858R mutation immunogenicity in 1862 Chinese NSCLC patients.
Authors: Jin Lin, Yu Chen, Gang Chen, Liu Jun, Shiguang Hao, Jia-ni Xiong, Bin Lan, Yaping Xu, Yan-Fang Guan, Zengqing Guo, Lin Chen, Li-zhu Chen, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

e21512 Background: Therapeutic vaccines targeting mutation-derived neoantigens prime T-cell responses and deliver long-term clinical benefit to patients. Last year we reported EGFR L858R mutation could be a possible target for individual-independent vaccine in 799 Chinese patients with non-small cell lung cancer (NSCLC). Here we verified the findings and explored possible immunological mechanisms in a larger sample size of 1862 Chinese NSCLC. Peripheral blood or normal tissue was used as control. Methods: DNA sequencing data was acquired using our targeted 1021-gene panel and HLA-I genotyping was determined based on DNA sequencing by OptiType v1.0. The peptide-HLA binding affinity was predicted with netMHCpan v4.0. Neoantigen was identified if the IC50 MT &lt; 500 nM and IC50 WT &gt; 500 nM, furthermore, IC50 MT &lt; 50 nM was considered as strong-binders. Results: EGFR (50.05%) was the most prevalent mutated gene, with 22.61% and 13.16% harboring L858R mutations and E746_A750del respectively. HLA typing showed HLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. The combination of EGFR L858R and HLA-A*33:03 had both relatively strongest binding affinity (IC50 MT = 22.9 nM and IC50 WT = 12734.0 nM, 2.93%) and highest shared frequency (2.93%). In terms of mechanism, we examined 7 of 1862 (0.37%) B2M gene mutation and 1092 of 1731 (63.1%) HLA-I LOH (loss of heterozygosity) in our population, but didn’t see any statistical difference between L858R subtype and other position mutations in EGFR. We also calculated 26 immune cell types’ signature scores from Chinese CHOICE study and found L858R subtype was associated with elevated level of pDC (KW-test p = 0.02) and lower level of neutrophils signature(KW-test p = 0.07) compared with exon 19 deletion and other uncommon mutations of EGFR. Conclusions: (1) Targeting EGFR L858R mutation in patients with HLA-A*33:03 allele appeared to be valuable for the neoantigen-based vaccine designed for Chinese NSCLC patients. (2) The specific immunogenicity of L858R seemed to be little influenced by B2M mutation and HLA-I LOH which were important factors for neoantigen presentation. (3) High pDC and low neutrophils infiltration might contribute to the inhibitive microenvironment associated with L858R mutation.
Serum IgA, IgM, and IgG responses in COVID-19
Authors: Huan Ma, Weihong Zeng, Hongliang He, Dan Zhao, Dehua Jiang, Peigen Zhou, Linzhao Cheng, Yajuan Li, Xiaoling Ma, Tengchuan Jin
Journal: Cellular and Molecular Immunology (2020)

Currently, detecting SARS-CoV-2 RNAs is a standard approach for COVID-19 diagnosis.However, there is an urgent need for reliable and rapid serological diagnostic methods to screen SARS-CoV-2infected people including those who do not have overt symptoms.][3][4] Although detection of SARS-CoV-2-specific IgA in serum has been reported in few papers, 5,6 analyses of IgA levels in a larger number of COVID-19 patients are still lacking.
Lenvatinib plus hepatic arterial infusion of modified FOLFOX regime in patients with advanced hepatocellular carcinoma.
Authors: Qicong Mai, Zhiqiang Mo, Feng Shi, Xiaoming Chen
Journal: Journal of Clinical Oncology (2020)

e16603 Background: Recently, Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of modified FOLFOX regime has shown promising results for patients with advanced hepatocellular carcinoma. Lenvatinib is also the first-line treatment for advanced hepatocellular carcinoma, it has shown the better objective response rate (ORR) and longer progression free survival (PFS) than sorafenib. This retrospective study evaluated the combination of lenvatinib plus HAIC of modified FOLFOX regime in patients with advanced hepatocellular carcinoma. Methods: This study retrospectively enrolled and analyzed 24 patients from Nov 2018 to May 2019 from Guangdong provincial people’s hospital. Patients with advanced hepatocellular carcinoma were treated with 8 mg(≤60kg) or 12mg( &gt; 60kg) lenvatinib once daily plus HAIC of modified FOLFOX regime (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Best response according to the RECIST 1.1 and mRECIST criteria. PFS, overall survival (OS) and treatment-related adverse events(TRAE) were also evaluated. Results: 24 patients(median age: 49.2 years) underwent a total of 91 cycles of HAIC therapy (mean: 3.79; range: 2-8). 22 (91.7%) patients had cirrhosis caused by HBV infection.17(70.8%) patients were diagnosed with vascular invasion and 7 (29.2%) were both vascular invasion and extrahepatic spread. 20 (83.3%) patients were classified as Child-pugh A class and 4 (16.7%) patients were Child-pugh B class. The ORR were 58.3% (RECIST) and 66.7% (mRECIST), the disease control rate (DCR) was 79.2% (RECIST/mRECIST). With a median follow-up period of 11.3 months, the median PFS was 8.1 months. 6-, 9-, and 12-months OS rates were 91.7, 83.3%, and 75%, respectively. TRAE occurred in 20 of 24 patients (83.3%), most common TRAE were hypertension (41.7%) and hand-foot skin reaction(25%). No grade 3/4 TRAE was observed. Conclusions: Lenvatinib plus HAIC of modified FOLFOX regime was well tolerated and had shown promising ORR, PFS and 6-, 9-, and 12-months OS rates in advanced hepatocellular carcinoma. A prospective large-scale trial is needed to justify these results. [Table: see text]
Disparities by race, socioeconomic status, and insurance type in the receipt of NCCN guideline concordant care for select cancer types in California.
Authors: Kiran Clair, Jenny Chang, Argyrios Ziogas, Sora Park Tanjasiri, Kari Joanne Kansal, Greg E Gin, Jason A. Zell, Robert E. Bristow
Journal: Journal of Clinical Oncology (2020)

7031 Background: There are a limited number of studies that have evaluated the association between National Comprehensive Cancer Network (NCCN) guideline adherence and survival across different cancers. We aim to assess the relationship between race/ethnicity, socioeconomic status (SES), insurance type and the receipt of NCCN guideline concordant cancer care and survival. Methods: This is a retrospective population-based cohort study of patients with 7 types of invasive cancer using the California Cancer Registry. Adherence with NCCN guidelines was defined by appropriate surgical, radiation, and chemo- or hormonal therapies. Multivariate logistic regression was used to evaluate the relationship between the patient, insurance type, tumor, and guideline adherence. Disease-specific survival analysis was performed using multivariate proportional hazards model. Results: A total of 543,198 patients were identified with invasive cancer between 2004-2017 (cases by disease type: breast 189,311, prostate 156,502, colon 80,102, liver 25,857, gastric 22,066, ovary 22,551, and cervix 16,691). The proportion of patients receiving NCCN guideline-concordant care varied by disease type. Non-concordant guideline treatment was associated with increased disease-specific mortality across all cancer types: breast (HR 1.28, 95%CI 1.23-1.33), prostate (HR 1.31, 95%CI 1.22-1.41), colon (HR 1.73, 95%CI 1.67-1.78), liver (HR 2.52, 95%CI 2.42-2.63), gastric (HR 2.38, 2.28-2.49), ovary (HR 1.32, 95%CI 1.26-1.38), and cervical cancer (HR 1.17, 95%CI 1.08-1.26). In multivariate models, compared to White, black patients were less likely to receive guideline concordant care for breast (OR 0.88, 95%CI 0.84-0.92), prostate (OR 0.90, 95%CI 0.86-0.93), colon (OR 0.85, 95%CI 0.79-0.92), and ovarian cancer (OR 0.71, 95%CI 0.62-0.82). Compared to Managed care insurance patients, Medicaid payer status was also associated with lower guideline concordant care for breast (OR 0.81, 95%CI 0.78-0.84), prostate (OR 0.91, 95%CI 0.86-0.97), colon (OR 0.70, 95%CI 0.65-0.75), gastric (OR 0.69, 95%CI 0.63-0.75), and liver cancer (OR 0.66, 95%CI 0.61-0.72). Conclusions: Less than half of cancer patients received NCCN guideline concordant care. There was an incremental relationship observed between SES and the likelihood of receiving guideline concordant care. Patients receiving non-guideline concordant care had worse disease-specific survival.
Clinical analysis for 12 cases of severe vulvar intraepithelial neoplasm
Authors: Hui-fang Huang, Ling-ya Pan, Jia-xin Yang, Mei Yu, Keng Shen, Jing-he Lang
Journal: BMJ (2008)

Objective To study the clinical characteristics, diagnosis, treatment and its effectiveness of vulvar intraepithelial neoplasm Ⅲ(VIN Ⅲ).Methods Clinical data, including age of the patients, mode of surgical operation, pathological features, results of post-operation follow-up, of 12 cases of VIN Ⅲ admitted to the Peking Union Medical College Hospital(PUMCH)during January 1984 to December2006 were retrospectively analyzed.Results Mean age of the 12 cases was 40.3(ranging from 23 to 56)years.All the patients had symptoms of vulvar itching, three with VUlVar ulcer and one with vulvar pain.There was single neoplasm focus in two cases and multiple focuses in 10 cases, five cases with neoplasm in other sites and five with human papilloma virus(HPV)infection.All the 12 patients received surgical operation, three with simple vulvectomy(one with some residue at perianal incisal edge)and other nine with lumpectomy(four with some residue at incisal edge).Eight cases were followed-up for 9.0 months in average(ranging 1～22 months)after surgical operation, including three with some residue at incisal edge.Relapse was found in two cases three and 11 months after operation, respectively, who received re-operation, including one with residue at incisal edge and one without residue.Conclusions It is necessary to attach more importance to biopsy for the cases of suspected VIN Ⅲ, as well as colposcopic diagnosis for those with vaginal or vulvar neoplasm and testing for HPV infection.Surgical operation, including simple vulvectomy and lumpectomy with or without adjunctive measures, are main treatment for patients of VIN Ⅲ and follow-up is also important for all those with VIN Ⅲ.

Key words: 
Vulvar Neoplasms; Gynecologic surgical procedures; Neoplasm,vulvar,intraepithelial; Human papilloma virus
Impact of TKIs post–allogeneic hematopoietic cell transplantation in Philadelphia chromosome–positive ALL
Authors: Neeraj Saini, David Marin, Celina Ledesma, Ruby Delgado, Gabriela Rondon, Uday R. Popat, Qaiser Bashir, Chitra M. Hosing, Yago Nieto, Amin M. Alousi, Muzaffar H. Qazilbash, Stefan Ciurea, Elizabeth Shpall, Issa Khouri, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi, Richard E. Champlin, Partow Kebriaei
Journal: Blood (2020)
由病例分析看轻型系统性红斑狼疮的诊断和治疗
Authors: 侯勇, 张奉春
Journal: BMJ (2006)

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一个累及多系统多器官、临床表现复杂多变、病程迁延反复的自身免疫性疾病.SLE多数呈隐匿起病,开始仅累及1～2个系统,表现为发热、关节炎、皮疹、隐匿性肾炎、自身免疫性溶血性贫血、血小板减少性紫癜等,部分患者长期稳定在轻型狼疮,部分患者可由轻型突然变为狼疮危象,更多的则由轻型逐渐出现多系统损害,逐渐变为重型狼疮;也有一些患者一起病就累及多个系统,甚至表现为狼疮危象.SLE的自然病程多表现为病情的加重与缓解交替.以前病死率较高,随着诊疗水平的提高,预后已大为改观,但仍需进一步提高.以下通过分析一个具体病例来谈轻型SLE的诊疗。
Utilization of adjuvant chemotherapy in “ideal candidates” with stage III colon cancer.
Authors: Mohsin Soleja, Suleyman Yasin Goksu, Nina Niu Sanford, Muhammad Shaalan Beg, Radhika Kainthla, Aravind Sanjeevaiah, Amy Little Jones, Linda Farkas, Udit Verma, David Hsieh, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2020)

4103 Background: Prior studies have observed under-utilization of adjuvant chemotherapy (ACT) in stage III colon cancer. Our aims were to observe the rate of utilization of ACT in very healthy or “ideal candidates”, identify reasons for omission and socioeconomic factors associated with ACT use, and observe patient outcomes. Methods: We queried patients from the National Cancer Database (NCDB) with stage III colon cancer, age&lt;65, and Charlson-Deyo score of 0 who underwent resection in the United States between 2004-2015. Patients who received ACT were compared to patients who had surgery only (SO). We used chi-square test for categorical variables, Kaplan-Meier and Cox regression method for survival analyses. Results: Out of 243,388 stage III colon cancer patients during the study time, a total of 49,046 patients met the specific criteria of “ideal candidate”. Out of these, 88.5% received ACT and 11.5% underwent SO. The primary reason for chemotherapy omission was: no reason given (54.2%), patient/guardian refusal (26.7%), physician recommended against (9.3%), patient died (3%), unknown (6.7%). Patients who received ACT were more likely to be female, non-Hispanic white, have a higher level of education, travel shorter distance for cancer treatment, have private insurance or higher income as compared to counterpart ( all p&lt;.001). Patients who received ACT had significantly better overall survival (5-year survival rate 74% vs. 54%, p&lt;.001). This persisted after multivariable Cox regression analysis [HR:0.48 (CI:0.45-0.50), p&lt;.001]. Conclusions: We observed a high rate of utilization (88.5%) of ACT in patients with stage III colon cancer who were under age 65 and without comorbidities. However, the omission of chemotherapy in this population remains a problem, partially due to patient refusal. Socioeconomic factors associated with lower utilization were primarily related to insurance status (private vs non-private). Patients who received ACT had significantly improved survival as compared to SO group. [Table: see text]