tbuckley/cabot-search huggingface dataset:
Epidemiology and distribution of hepatitis C virus genotype among HIV positive former blood donors and transfusion recipients in Hubei province
Authors: Li-ping Deng, Xi-en Gui, Shi-cheng Gao, Yong Xiong, Rong-rong Yang, Ming-qi Luo
Journal: BMJ (2012)

Objective To explore the epidemiologic features and distribution pattems of hepatitis C virus (HCV) genotype infection among HIV positive former blood donors (FBDs) and transfusion recipients in Hubei province.Methods 597 serum samples from HIV-positive patients in Hubei were collected and examined for anti-HCV by enzyme-linked immunosorbent assay ( ELISA ).Reverse transcription nested polymerase chain reaction (RT-nested PCR) amplification and DNA sequencing were used to evaluate the HCV core regions.Results The prevalence rates of HCV in HIV positive FBDs and transfusion recipients were 76.5％ (205/268) and 57.4％ (189/329) respectively.HCV genotypes 1b (92.8％,90/97) and 2a (7.2％,7/97 ) were detected.Conclusions Blood donation and blood transfusion are the major modes of HIV-HCV co-infection in Hubei province.The prevalence of HCV in HIV positive transfusion recipients is lower than that in HIV positive FBDs.HCV genotypes 1b and 2a are the predominant strains among HIV-positive FBDs and transfusion recipients.

Key words: 
Human immunodeficiency virus(HIV); Hepatitis C virus(HCV); Genotype
Upfront DPYD genotyping and toxicity associated with fluoropyrimidine-based concurrent chemoradiotherapy for oropharyngeal carcinomas.
Authors: Antoine Desilets, Francine Aubin, Houda Bahig, Olivier Ballivy, Danielle Charpentier, Edith Filion, Rahima Jamal, Louise Lambert, Charles Vadnais, Xiaoduan Weng, Denis Soulieres
Journal: Journal of Clinical Oncology (2020)

6580 Background: The combination of carboplatin and 5-fluorouracil (5-FU) is effective when used concurrently with radiotherapy for locoregionally advanced oropharyngeal carcinomas (Calais et al. 1999). DPYD polymorphisms can be associated with an increased risk of severe toxicity to fluoropyrimidines (Deenen et al. 2016). Upfront screening for the DPYD*2A allele is available in the province of Québec, Canada since March 2017. This study aimed to determine the effect of upfront genotyping on grade ≥3 toxicities. Methods: The studied population included all consecutive cases of oropharyngeal carcinomas treated with 5-FU based chemoradiotherapy one year before and after the implementation of upfront DPYD*2A genotyping. All patients were treated at the Centre Hospitalier de l’Université de Montréal (CHUM) between March 2016 and April 2018. Clinical data were extracted from chart review. Extended screening for 3 supplemental at-risk DPYD variants was also retrospectively performed in August 2019. Results: 181 patients were included in the analysis (87 patients before and 94 patients after DPYD*2A screening implementation). 91% of patients (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Those two patients received cisplatin-based treatment and thus avoided 5-FU toxicities. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of 6 additional patients with alternative DPYD variants (two c.2846A &gt; T and four c.1236G &gt; A allele mutations). Conclusions: The DPYD*2A, c.2846A &gt; T and c.1236G &gt; A polymorphisms are associated with an increased risk of G3-4 toxicity to 5-FU, as well as higher hospitalization rates. Upfront DPYD genotyping can identify patients in whom fluoropyrimidine-related toxicity should be avoided. This represents an interesting addition in terms of pharmacovigilance. [Table: see text]
Application of endobronchial blocker in thoracoscopic-laparoscopic resection for patients with esophageal cancer
Authors: Aixiang Li, Chuangen Ma, Wenqi Xin, Haitao Wei
Journal: BMJ (2016)

Sixty patients with esophageal carcinoma undergoing thoracoscopic-laparoscopic resection were randomly divided into two groups with 30 cases in each group: endobronchial blocker was used during operation in group E and double-lumen tube(DLT)was used in group D. The results showed that compare to group D, intubation time was shorter and the incidence of postoperative hoarseness and sore throat was lower in group E [(27.4±8.6) vs.(37.2±10.3)s, 1 and 9 cases, 5 and 14 cases, all P 0.05]. The study indicates that application of endobronchial blocker can reduce the incidence of postoperative hoarseness and sore throat and shorten the intubation time; especially, it is easy to operate and there is no need to replace the tube after surgery.


Key words: 
Esophageal neoplasms; Intubation, intratracheal
Assessing the value of cemiplimab for adults with advanced cutaneous squamous cell carcinoma (CSCC): A cost-effectiveness analysis.
Authors: Eleanor Paul, Andreas Kuznik, Sam Keeping, Chieh-I Chen, Medha Sasane, Yingxin Xu, Gerasimos Konidaris, Kokuvi Atsou, Dieter Ayers, Emily S Ruiz, Nikhil I. Khushalani, Shannon Cope
Journal: Journal of Clinical Oncology (2020)

e19397 Background: Cemiplimab is a high-affinity, human, hinge-stabilized, monoclonal antibody that potently blocks the interactions of programmed cell death-1 (PD-1) with programmed cell death ligand-1 (PD-L1) and PD-L2. In September 2018, cemiplimab-rwlc became the first systemic therapy approved by the US Food and Drug Administration for the treatment of patients with advanced CSCC ineligible for curative surgery or radiotherapy. In a single-arm Phase II study (NCT02760498), cemiplimab demonstrated substantial antitumor activity, durable responses, and acceptable safety profile in patients with advanced CSCC. The aim of this analysis was to evaluate the cost-effectiveness of cemiplimab in patients with advanced CSCC from a US payer perspective. Methods: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review (SLR), which was supplemented by expert opinion where necessary. The clinical inputs for cemiplimab were based on the individual patient data from the cemiplimab Phase II trial, whereas for SOC, the analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via the SLR (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon using parametric functions consistent with guidance from the National Institute for Health and Care Excellence Decision Support Unit. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. Results: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio (ICER) of $99,024 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372,425 and 3.76, respectively. At a willingness-to-pay threshold of USD $150,000 per QALY, the probabilistic sensitivity analysis suggests a 91% probability that cemiplimab is cost-effective when compared to SOC. Scenario analyses resulted in ICERs ranging from $90,326 to $147,944. Conclusions: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.
Individual prediction of non-adherence to oral mercaptopurine (6MP) in children with acute lymphoblastic leukemia (ALL): Results from COG AALL03N1 study.
Authors: Anna Lynn Hoppmann, Yanjun Chen, Wendy Landier, Lindsey Hageman, Mary V. Relling, F. Lennie Wong, Smita Bhatia
Journal: Journal of Clinical Oncology (2020)

10530 Background: Poor adherence to 6MP (measured electronically [MEMS]) increases relapse risk in children with ALL (Bhatia et al. JAMA Oncol 2015). Adherence is difficult to assess clinically and non-adherers are more likely to over-report 6MP intake (Landier et al. Blood 2017). Key sociodemographic/clinical factors (Bhatia et al. JCO 2012) and red cell methyl-mercaptopurine (MMP, a 6MP metabolite) levels (Hoppmann et al. ASCO 2017) are associated with non-adherence and could potentially identify non-adherers. Methods: We developed a prediction model for 6MP non-adherence (MEMS adherence rate &lt; 90%), using receiver operating characteristic (ROC) analyses in 407 children with ALL receiving 6MP (mean age 7.7±4.4y; 68% males; 35% Caucasians, 34% Hispanics, 16% African Americans, 15% Asians). The cohort was divided into a training set (n = 250) and test set (n = 157) using stratified random sampling (stratified by race/ethnicity, gender, age and 6MP non-adherence). We used logistic regression with backward variable elimination, guided by change in area under ROC (AUC), to create a prediction model in the training set, using only clinical and sociodemographic variables (Clinical Model). We then generated a model that added 6MP dose-intensity (6MPDI)-adjusted red cell MMP levels to the Clinical Model (Final Model). All models were validated in the test set. Results: Predictors retained in the Training Clinical Model included: age, race/ethnicity, absolute neutrophil count, 6MPDI, family structure, and taking 6MP at the same vs varied time of day (AUC = 0.79; 95%CI 0.72-0.85). The Training Final Model (adding 6MPDI-adjusted MMP to the Clinical Model) yielded an AUC = 0.79 (95%CI 0.72-0.86). The Test Final Model (AUC = 0.79, 95%CI 0.69-0.88) showed significantly superior discrimination compared to the Test Clinical Model (AUC = 0.74, 95%CI 0.63-0.85; P = 0.002). Using a binary classifier with predicted probability of non-adherence ≥0.5, the Test Final Model had an accuracy of 79%, and positive and negative predictive values of 71% and 80%, respectively. Conclusions: We created, validated, and compared 2 risk-prediction models for 6MP non-adherence in children undergoing maintenance chemotherapy. While inclusion of red cell MMP levels provided superior discrimination in identifying non-adherent patients, the Clinical Model (without MMP levels) performed adequately well, and could be used in the clinical setting.
A retrospective analysis of CDK4/6 inhibitors among adult female patients with metastatic breast cancer.
Authors: Silvia Comis, Thenmozhi Kandasamy, Alysa J Perrin, Kelley Kent, Mahendra Dulawat, Arun Chhikara, Nitish Ranjan
Journal: Journal of Clinical Oncology (2020)

e13028 Background: The aim of this study is to examine the behavior pattern of cyclin-dependent kinase (CDK4/6) inhibitor combinations in adult females with de novo metastatic breast cancer as first therapy or following adjuvant hormonal therapy. Methods: Using United States open health claims and prescription data we analyzed metastatic breast cancer from 2015 Q1 to 2019 Q4, adult female patients (age ≥18). Patients were classified into 3 groups based on their first therapy: Group 1-Hormonal, Group 2-CDK4/6 Inhibitor Combinations, and Group 3-Everolimus Combination. Analysis was completed using the Chi-Squared goodness of fit test assessing the patients moving to next therapy by time period. We also compared the overall CDK4/6 group as a base for probability distribution to study the pattern of therapy change in individual groups. Results: Of 37,351 patients on CDK4/6 inhibitors as first therapy or following adjuvant hormonal therapy for advanced/metastatic diseases, the percentage of patients who moved to next therapy was 3.2% (1,200 patients). For most patients, change in therapy occurred within a 2-year period (87%) and those who remained on their first therapy continued for an extended duration. In both Groups 1 and 2 no statistically significant difference was found in the treatment pattern compared to the overall CDK4/6 inhibitor patient population. However, most patients in Group 3 (90%) compared to the overall patient population on CDK4/6 inhibitors moved to Chemotherapy within the first year of treatment (statistically significant at p-value = 0.02). Further analysis of granularity in individual patient pathways showed about 90% of patients with CDK4/6 inhibitors remained on therapy for about 1 year and, interestingly, about 2% extended beyond 2 years up to 4.5 years. Conclusions: The results show most patients on CDK4/6 inhibitors (95%) had progression free survival (PFS) for the period we analyzed. Overall, patients on CDK4/6 inhibitors behaved similarly when used as first therapy or following adjuvant hormonal therapy.
Out-of-pocket cost of screening with breast MRI for women at high risk for breast cancer.
Authors: I-Wen Pan, Kevin C. Oeffinger, Ya-Chen T. Shih
Journal: Journal of Clinical Oncology (2020)

2017 Background: The prevention provision of Affordable Care Act (ACA) mandates private insurance to waive cost sharing for preventive services with grade A or B recommendations from the US Preventive Services Task Force. Although several professional societies have recommended augmenting screening mammography with MRI for women at high risk for breast cancer, the ACA prevention provision does not apply to screening MRI. This study examined the proportion of high-risk women having zero cost sharing associated with breast MRI for screening purposes and estimated out of pocket (OOP) costs as well as sources of variations. Methods: We identified women who underwent MRI and mammography for breast cancer screening from Marketscan database, 2009-2017. We quantified OOP costs as the sum of copayment, coinsurance, and deductible and defined zero cost sharing as having no OOP cost. We calculated the proportion of zero cost sharing for mammography and that for MRI and compared the time trend of each before and after ACA (enacted in 2010). We used multivariable logistic regression to examine factors associated with zero cost sharing for MRI use. We estimated OOP costs of MRI and examined cost variations by geographic regions or whether a woman had high deductible plans. Results: 25,232 women were included in the analysis. For screening mammography, the rate of zero cost sharing increased from 81% in 2009 to 91% in 2011 (post ACA) then 97% in 2017. For MRI, the rate was 41%, 37%, and 25%, respectively. The odds ratio (OR) of zero cost sharing for MRI screening was significantly lower for women with high deductible plans (OR = 0.65, 95% CI: 0.59-0.72) and for those resided in South (vs. Northeast) region (OR = 0.50, 95% CI: 0.46-0.53), after controlling for age, MSA, family breast cancer history, and year. OOP costs of MRI varied by region and insurance plan (Table); the mean OOP cost for women with high deductible plan were more than twice the mean cost for those in other plan types. Conclusions: With the financial protection under the ACA prevention provision applying to only screening mammography, many women at high risk for breast cancer are subject to high OOP costs for MRI screening. Those enrolled in high deductible plans and resided in the South are especially vulnerable financially. [Table: see text]
Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma
Authors: Dipongkor Saha, Samuel D Rabkin, Robert L Martuza
Journal: Journal for ImmunoTherapy of Cancer (2020)

Temozolomide (TMZ) chemotherapy is a current standard of care for glioblastoma (GBM), however it has only extended overall survival by a few months. Because it also modulates the immune system, both beneficially and negatively, understanding how TMZ interacts with immunotherapeutics is important. Oncolytic herpes simplex virus (oHSV) is a new class of cancer therapeutic with both cytotoxic and immunostimulatory activities. Here, we examine the combination of TMZ and an oHSV encoding murine interleukin 12, G47Δ-mIL12, in a mouse immunocompetent GBM model generated from non-immunogenic 005 GBM stem-like cells (GSCs.We first investigated the cytotoxic effects of TMZ and/or G47Δ-IL12 treatments in vitro, and then the antitumor effects of combination therapy in vivo in orthotopically implanted 005 GSC-derived brain tumors. To improve TMZ sensitivity, O6-methylguanine DNA methyltransferase (MGMT) was inhibited. The effects of TMZ on immune cells were evaluated by flow cytometery and immunohistochemistry.The combination of TMZ+G47Δ-IL12 kills 005 GSCs in vitro better than single treatments. However, TMZ does not improve the survival of orthotopic tumor-bearing mice treated with G47Δ-IL12, but rather can abrogate the beneficial effects of G47Δ-IL12 when the two are given concurrently. TMZ negatively affects intratumor T cells and macrophages and splenocytes. Addition of MGMT inhibitor O6-benzylguanine (O6-BG), an inactivating pseudosubstrate of MGMT, to TMZ improved survival, but the combination with G47Δ-IL12 did not overcome the antagonistic effects of TMZ treatment on oHSV therapy.These results illustrate that chemotherapy can adversely affect oHSV immunovirotherapy. As TMZ is the standard of care for GBM, the timing of these combined therapies should be taken into consideration when planning oHSV clinical trials with chemotherapy for GBM.
Different response to ALK inhibitors in EML4-ALK positive mediastinal cancer of unknown primary.
Authors: Chunhong Hu, Lishu Zhao, Fang Wu
Journal: Journal of Clinical Oncology (2020)

104 Background: With the development of next-generation sequencing (NGS) and precision medicine, targeted therapy especially molecule-driven therapy irrespective of tumor site may play an important role in cancer patients with druggable targets. Cancer of unknown primary (CUP) especially mediastinal CUP (MCUP) has poor prognosis with empirical chemotherapy but may harbor targetable genetic alterations. In the study, we evaluate the response to ALK inhibitors in ALK-positive MCUP. Methods: We queried the cancer database of the Second Xiangya hospitalfrom 2018.10 to 2019.12 for patients with ALK-positive cancers regardless of tumor site.Then we selected ALK-positive MCUP patients treated with ALK inhibitors, on which both NGS and programmed death-ligand 1 (PD-L1) testing were performed. Results: Forty-eightpatients with ALK-positive cancers were registered in the database. Two MCUP patients were found and showed different response. The first MCUP patient obtaining remarkable response to alectinib harbored ALK/TP53 co-mutation and TERT wild type accompanied by low PD-L1 expression, while the second one showing stable disease with crizotinib carried ALK/TP53/TERT co-mutation and high PD-L1 expression. Conclusions: We reveal for the first time that ALK inhibitors are applied to MCUP as first-line therapy and alectinib is firstly reported to treat MCUP patients. ALK inhibitor alectinib is expected to improve outcomes of patients with ALK-positive MCUP. NGS and PD-L1 testing should be recommended for MCUP to get more information about therapy and efficacy. [Table: see text]
促纤维增生型小圆细胞瘤12例的CT影像特点
Authors: 李刚, 余永波, 张翠莲, 毕纯龙, 钟文昭, 亢玺刚, 杨慧云, 赵大伟, 李学松, 罗文琦, 陈和忠, 柯庆华
Journal: BMJ (2009)

促纤维增生型小圆细胞瘤(desmoplaatic small round celltumor,DSRCT)是一种高度恶性肿瘤,多发生于青少年,绝大多数DSRCT发生在腹部.本研究收集1998年6月至2008年3月诊治的12例DSRCT患者的临床资料,结合其CT特点报告如下。
Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells
Authors: Teresa Manzo, Boone M. Prentice, Kristin G. Anderson, Ayush Raman, Aislyn Schalck, Gabriela S. Codreanu, Carina B. Nava Lauson, Silvia Tiberti, Andrea Raimondi, Marissa A. Jones, Michelle Reyzer, Breanna M. Bates, Jeffrey M. Spraggins, Nathan H. Patterson, John A. McLean, Kunal Rai, Carlo Tacchetti, Sara Tucci, Jennifer A. Wargo, Simona Rodighiero, Karen Clise-Dwyer, Stacy D. Sherrod, Michael Kim, Nicholas E. Navin, Richard M. Caprioli, Philip D. Greenberg, Giulio Draetta, Luigi Nezi
Journal: The Journal of Experimental Medicine (2020)

CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the tumor microenvironment (TME) can dampen their ability to control tumor progression. We describe lipid accumulation in the TME areas of pancreatic ductal adenocarcinoma (PDA) populated by CD8+ T cells infiltrating both murine and human tumors. In this lipid-rich but otherwise nutrient-poor TME, access to using lipid metabolism becomes particularly valuable for sustaining cell functions. Here, we found that intrapancreatic CD8+ T cells progressively accumulate specific long-chain fatty acids (LCFAs), which, rather than provide a fuel source, impair their mitochondrial function and trigger major transcriptional reprogramming of pathways involved in lipid metabolism, with the subsequent reduction of fatty acid catabolism. In particular, intrapancreatic CD8+ T cells specifically exhibit down-regulation of the very-long-chain acyl-CoA dehydrogenase (VLCAD) enzyme, which exacerbates accumulation of LCFAs and very-long-chain fatty acids (VLCFAs) that mediate lipotoxicity. Metabolic reprogramming of tumor-specific T cells through enforced expression of ACADVL enabled enhanced intratumoral T cell survival and persistence in an engineered mouse model of PDA, overcoming one of the major hurdles to immunotherapy for PDA.
PROCLAIM-CX-072: Analysis of patients with advanced solid tumors receiving long-term treatment with CX-072, a PD-L1 probody therapeutic, as a single agent or in combination with ipilimumab.
Authors: Fiona Thistlethwaite, Aung Naing, Marta Gil-Martin, Patricia LoRusso, Manreet Randhawa, Ferry Eskens, Rachel E. Sanborn, Nataliya Volodymyrivna Uboha, Daniel C. Cho, Alexander I. Spira, Igor Bondarenko, Elizabeth Ruth Plummer, Javier Garcia-Corbacho, Iván Victoria, Javier Lavernia, Ignacio Melero, Elisabeth De Vries, William Garner, Hendrik-Tobias Arkenau, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2020)

3005 Background: Monotherapy with immune checkpoint inhibitors (ICIs) has demonstrated efficacy in many cancers. Combining ICIs PD-L1 + CTLA-4 enhanced efficacy but worsened toxicity vs monotherapy; therefore, CTLA-4 dose modifications are often needed, despite a dose-response effect having been shown for efficacy. CX-072 is an investigational PD-L1 PROBODY therapeutic that is preferentially activated in the tumor microenvironment (TME); localized activation may reduce immune-related AEs (irAEs). PROCLAIM-CX-072-001 identified 10 mg/kg Q2W (Mono10) as the recommended monotherapy dose. Here we provide data for Mono10 and for dose escalation of CX-072 in combination with IPI (Combo), with a focus on long-term (≥6 mo) therapy. Methods: Mono10 was evaluated in multiple tumor types. Combo doses evaluated were CX-072 0.3–10 mg/kg and IPI 3–10 mg/kg Q3W. Patients (pts) with ≥6 mo treatment duration (≥6M-TD) were compared to those with &lt; 6 mo of treatment ( &lt; 6M-TD) as of November 30, 2019. Results: Disease control rates (DCR = CR+PR+SD) were 41% for Mono10 (n = 47 of 114; 10 PRs) and 37% for Combo (n = 10 of 27; 1CR + 4 PRs (1CR and 3PRs at 3 mg/kg IPI [IPI3]). Additional results are shown in the table. No treatment-related adverse events (TRAEs) led to death. The most common reason for discontinuation (dc) in all groups was disease progression. Conclusions: CX-072 monotherapy demonstrated durable responses consistent with activation of the PROBODY therapeutic in the TME. The safety profile supports the tolerability of CX-072 as monotherapy and when combined with IPI3. CX-072 + IPI3 demonstrated activity in heavily pretreated pts with various tumors. The safety profile of the combination of CX-072 with IPI3 compares favorably to historical data (grade ≥3 TRAEs 55% and leading to dc in 36%; Larkin J, et al. N Engl J Med. 2015;373:23-34). CX-072 + IPI3 is being explored in a phase 2 study in 2L melanoma Clinical trial information: NCT03993379 . [Table: see text]
Shaping new model of non-communicable disease management and enriching the construction of national chronic disease control zone
Authors: Jianqun Dong
Journal: BMJ (2016)

自2010年启动以来，国家慢性病综合防控示范区建设在十二五期间取得了可喜的进展。在深化医改，大力推行分级诊疗制度的背景下，十三五期间示范区建设工作应进一步探索并推广以慢性病管理结果为导向、以患者为中心、以社区为基础的慢性病管理工作模式，不断提升示范区建设的内涵。