tbuckley/cabot-search huggingface dataset:
Investigating potential disparities in clinical trial eligibility, offers and enrollment at an NCI-designated comprehensive cancer center.
Authors: Monica Arun Patel, F. John Brinley, Jennifer Lobo Shah, Paul Abrahamse, Christine M Veenstra, Anne F. Schott
Journal: Journal of Clinical Oncology (2020)

e19076 Background: Although many prior studies have demonstrated the existence of disparities in cancer clinical trial enrollment, few studies have explored clinical trial eligibility criteria and offers as potential drivers of disparities in enrollment. Methods: We identified patients age 18-96 with gastrointestinal (GI) cancers who were seen as new patients at the University of Michigan in 2016. Primary outcomes were: 1) Eligibility for; 2) Offer of; and 3) Enrollment in, a clinical trial. All 28 clinical trials available in 2016 for patients with GI cancers were considered. We assessed individual patient eligibility for any trial by exhaustive review of the electronic medical record (EMR). We determined trial offers and patient enrollment in a trial by EMR review, including notes by clinicians and research coordinators. Independent variables included clinical and non-clinical patient-related factors (such as age, race, and gender) as well as provider-related factors. We assessed associations between patient- and provider-related factors and our primary outcomes, using multivariable regression. Results: Of 827 patients, 40% were female, 18% were age ≥75, 7% were Black, and 2% were Asian. 155 (19%) patients were potentially eligible for an open clinical trial. Among patients potentially eligible for a trial, 83 (54%) had documentation of a trial being offered and 46 (30%) enrolled. After adjustment, age &lt; 75, lower Charlson comorbidity index, not having a second primary cancer, hepatobiliary primary, and higher disease stage were associated with a higher odds of clinical trial eligibility (all P &lt; 0.05). Having ≥1 child, lower Charlson comorbidity index, hepatobiliary primary, and higher disease stage were associated with a higher odds of being offered a clinical trial (all P &lt; 0.05). Hepatobiliary primary and higher disease stage were associated with a higher odds of enrollment (all P &lt; 0.05). Conclusions: We found that patients age 75 or over were less likely to be eligible for a clinical trial, but did not find significant disparities in eligibility by other non-clinical factors such as gender and race. Only 54% of patients potentially eligible for a trial had documentation of a trial being offered; this varied by number of children, but not by any other non-clinical factors. We found no significant associations between non-clinical factors and enrollment. Future work is needed to ensure that eligibility criteria for clinical trials reflect the overall patient population, and that trials are offered to eligible patients.
The microbial characteristics of esophageal squamous cell carcinoma (ESCC) and healthy subjects.
Authors: Wenjing Lv, Jing Zuo, Yudong Wang, Zhisong Fan, Li Feng, Long Wang, Xue Zhang, Qi Zhang, Da Jiang
Journal: Journal of Clinical Oncology (2020)

e16546 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive human malignancies. Investigation of the esophageal microbiome is a relatively new field. Recently, we discovered the microbial characteristics among the healthy subjects and patients with ESCC. Methods: DNA was extracted from blood, oral mucosa, saliva, urine, faeces samples from 28 healthy and 26 ESCC cases. Pfu high fidelity DNA polymerase was used for PCR amplification. The PCR amplification products were quantified. Then the sequencing library was prepared. The V3V4 region of the 16S ribosomal RNA gene was sequenced with Novaseq-PE250. In order to comprehensively evaluate the α diversity of microbial communities, we used Chao1 and Observed Species indices to characterize the richness, Shannon and Simpson indices to characterize the diversity. PCoA, NMDS and Distance Matrix were used to analyze differences in β diversity. Results: At the phylum level, the top 5 microbes in both ESCC and healthy samples are Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria. At the genus level, the microbial composition of patients with ESCC and healthy samples was significantly different. However, the bacteria composition in blood samples was the same as the urine samples not only in patients with ESCC but also in healthy samples. Blood and urine samples of patients with ESCC contained Cupriavidus, Vogesella, Acinetobacter, Sphingomonas, Ochrobactrum, Sediminibacterium and the healthy samples contained Ochrobactrum, Sediminibacterium, Acinetobacter. The same rule occurred in oral mucosa and saliva samples. Faeces samples of esophageal cancer patients included Streptococcus, Lactobacillus, Bifidobacterium, Gemmiger, Blautia, Coprococcus. However, the healthy samples included Gemmiger, Roseburia, Faecalibacterium, Bacteroides, Dialister, Bifidobacterium. A comparison of esophageal cancer patients and healthy samples showed that α diversity was significantly different both in blood samples and urine samples. No statistically significant differences were detected within oral mucosa, saliva, faeces samples of esophageal cancer patients and healthy samples. β diversity was different in urine samples. Conclusions: Further understanding of the changes in the esophageal microbiome may help us understand the pathogenesis and the natural history of disease and present potential therapeutic approaches.
Phase I/II study of SAR439859, an oral selective estrogen receptor degrader (SERD), in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).
Authors: Mario Campone, Aditya Bardia, Gary A. Ulaner, Sarat Chandarlapaty, Alice Gosselin, Séverine Doroumian, Vasiliki Pelekanou, Marina Celanovic, Hannah M. Linden
Journal: Journal of Clinical Oncology (2020)

1070 Background: SERDs competitively antagonize and degrade the ER and can block signaling in ER-dependent tumors resistant to standard endocrine therapy (ET). This study (NCT03284957) investigates SAR439859, a potent oral SERD, in ER+/HER2- mBC. We present pooled dose escalation/expansion (Part A/B) data for SAR439859. Methods: Postmenopausal patients (pts) with ER+/HER2- mBC treated for ≥ 6 mos with prior ET received SAR439859 ≥ 150 mg QD (Part A) or 400 mg QD (Part B). Chemotherapy and targeted therapy in the advanced setting were allowed. Objective response rate (ORR; RECIST v1.1), clinical benefit rate (CBR; complete or partial response [PR] or stable disease [SD] ≥ 24 weeks), safety, and pharmacokinetics (PK) were assessed. Results: Pts (n = 62; Part A, 13; Part B, 49) had a median age of 63 yrs (range 37–88) and ECOG PS 0 (59.7%) or 1 (40.3%); 93.5% had visceral disease. All had prior ET, 74.2% had prior targeted therapy and 48.4% had ≥ 3 prior lines in the advanced setting. 61.3% of pts had treatment-related adverse events (TRAEs), all grade 1–2. Most frequent: hot flush (16.1%), constipation, arthralgia (both 9.7%), decreased appetite, vomiting, diarrhea, nausea (all 8.1%), fatigue (6.5%). No pts discontinued due to AEs. CBR was 35.6% overall, with antitumor activity irrespective of ESR1 mutation status (Table). In pts with no prior SERD, CDK4/6 or mTOR inhibitors (n = 14), ORR was 21.4% and CBR 64.3%. PK data for Part B and ESR1 mutation data will be provided. Conclusions: SAR439859 had a favorable safety profile with limited TRAEs. In these heavily pre-treated pts (prior targeted therapy in 74.2%), ORR and CBR were similar to historical fulvestrant performance in pts with no prior targeted therapy. Encouraging ORR and CBR in pts with no prior SERD, CDK4/6 or mTOR inhibitors (n = 14; ORR 21.4%; CBR 64.3%) supports SAR439859 development in earlier lines of therapy. Clinical trial information: NCT03284957 . [Table: see text]
Incidence patterns and survival outcomes in primary small intestine B-cell lymphoma (PSIBCL) and the effect of Rituximab.
Authors: Apoorva Jayarangaiah, Shuai Wang, Mariuxi Alexandra Viteri Malone, Tarek N. Elrafei, Lewis Steinberg, Abhishek Kumar
Journal: Journal of Clinical Oncology (2020)

e20025 Background: PSIBCL is a rare manifestation of primary extra-nodal B-cell Non-Hodgkin’s lymphoma and is underreported in literature. We assessed the incidence patterns, and clinicopathologic features and their impact on survival in this population. Methods: Using the SEER database, we identified patients with PSIBCL who were ≥ 18 years old from 1975-2016. Patients were identified using ICD-O-3 and histology codes. Age-adjusted incidence rates were calculated using SEER*Stat 8.36. Using SPSS 26, overall survival (OS) was analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model was used to determine the prognostic factors. Results: We identified 4810 patients with PSIBCL. PSIBCL accounts for 0.8% of all B-cell Non-Hodgkin’s lymphoma. Age adjusted incidence rose from 0.2 to 0.4 per 100,000 during the study period. Annual percentage change of age adjusted incidence was +2.0 (95% CI 1.4-2.6). Incidence was highest among males, age &gt; 80 years, white &amp; Asian race. The median age of diagnosis was 63 yrs (51-75). 83% presented with either Diffuse large B-cell lymphoma (54%) or Follicular lymphoma (29%). The site of disease was specified in 65%; of those, duodenum (24%), jejunum (15%) and ileum (23%). Staging was reported in 88%; early stage disease (stage I/II) was found in 67%. Median OS for the entire cohort was 27 years (95% CI 23-32) and 5-year OS was 72.6%. Although the incidence was lower in black patients, the 10 year OS was worse (61% black vs 67.4% white). Survival was improved after 1997 (10-year OS rate 71.3% vs 52.0%). These results may correlate to Rituximab approval in 1997. In the multivariate analysis, age &gt; 65, male sex, black race, late stage (stage III/IV), DLBCL and Burkitt lymphoma subtypes were associated with unfavorable OS. Conclusions: Analysis of four decades of data show an upward trend in incidence. PSIBCL has a favorable outcome with a clear survival advantage in patients diagnosed after 1997; this is likely attributable to Rituximab approval.
Predictors of adjuvant radiation therapy in the treatment of male breast cancer and its impact on outcomes: A propensity matched analysis.
Authors: Veli Bakalov, Thejus Thayyil Jayakrishnan, Stephen Abel, Christie Hilton, Bindu Rusia, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2020)

e12516 Background: Male breast cancer (MBC) accounts for 1% of all breast cancers and there is a paucity of data on factors impacting the treatment strategies and outcomes. We hypothesized that adjuvant radiation therapy (Adj-RT) may improve survival outcomes and sought to examine predictive factors for Adj-RT receipt. Methods: We queried the National Cancer Database (NCDB) for patients with stages I-III MBC treated with surgery (breast conservation surgery- BCS or mastectomy-MS) within 180 days of diagnosis (years 2004-2015). Multivariable logistic regression identified predictors of adjuvant radiation therapy receipt. Multivariable Cox regression evaluated predictors of survival. Propensity matching for adj-RT accounted for indication biases. Results: We identified 6,217 patients meeting the eligibility criteria (1457 BCS vs. 4760 MS). The majority of patients were white (85%) and within the age range of 50-80 years (74%). Although Adj-RT was omitted for 30% of BCS patients, the utilization was higher compared to MS (OR=26, p-value=0.001). The predictors of Adj-RT use were – African American race, higher stage, higher grade, presence of lymphovascular invasion and ER/Her-2 positivity for the entire cohort and higher age, urban location and higher income for BCS. Adj-RT was associated with lower mortality in the propensity matched model (overall HR for BCS=0.28, p-value&lt;0.001; overall HR for MS=0.62,p-value=0.001) and is shown in the table. Conclusions: This study demonstrates there may be an association between decreased mortality and Adj-RT in MBC undergoing BCS. Although this implies that Adj-RT should be routinely delivered, it appears to be omitted frequently and its use requires further investigation. The study also suggests a benefit to Adj-Rt after MS for stage-III MBC. [Table: see text]
罕见的"大面积心肌梗死"
Authors: 曾昭耆
Journal: BMJ (2005)

心内科病房收了一个56岁的男病人,因发作性心悸憋气2天,门诊检查有心力衰竭体征.心电图示2∶ 1房性扑动,伴有ST-T改变,胸部透视见心影普遍增大,搏动弱,肺淤血.收入病房后,按常规查血清酶.发现肌酸激酶(CK)高达2 000 U/L以上.因不能除外急性心肌梗死,故连日复查.在其后1周内,每天的CK值都保持在2 000 U/L左右。
Targeted DNA sequencing analysis to reveal genetic diversity and androgen-receptor alteration in advanced EGFR mutant lung adenocarcinoma.
Authors: Wei Wu, Ross A. Okimoto, Collin Michael Blakely, James Fraser, Trever G. Bivona
Journal: Journal of Clinical Oncology (2020)

9526 Background: Lung cancer remains the leading cause of death from cancer around the world. Several oncogenic drivers have been identified from large cancer genome projects focused mainly on profiling early-stage lung cancers. Targeted therapies have been developed for specific activated driver gene mutations and are used in advanced-stage patients. For instance, advanced EGFR mutant lung cancer is primarily treated with EGFR tyrosine receptor inhibitors (TKIs). However, resistance remains an obstacle to durable anti-tumor control. We hypothesize that concurrent genetic alterations co-exiting with EGFR driver mutations contribute to the failure of EGFR TKI therapy. Methods: To understand the complexity and diversity of genetic alterations present in EGFR mutant advanced lung cancers, we utilized 660 EGFR mutant advanced lung adenocarcinomas samples with targeted DNA sequencing from Foundation Medicine, 394 cases from MSK-IMPACT dataset, along with TCGA lung cancer data. We performed systematic co-mutation analysis, molecular simulation, functional annotation and pathway enrichment analysis. Results: We updated mutational profiling on EGFR gene with hotspots at exon 18, 19, 20 and 21. Among them, EGFR L858R, exon19 deletion, T790M and G719A are top ranking alleles among EGFR mutations. Interestingly, a subset (n = 26 cases) of EGFR T790M mutations parallel with other EGFR mutations, which could affect the TKI binding pocket as inferred by molecular simulations. Furthermore, in advanced lung cancer EGFR mutations co-occurred with known oncogenic mutations in KRAS, MET, NF-1, MAP2K1, ERBB2, and ALK/ROS-1/RET fusions. Functional annotation suggests that concurrent mutated genes and copy number alterations in advanced EGFR mutant lung cancer were enriched in signatures of epigenetic modifiers, genome instability, WNT signaling, and RNA splicing. Compared to early stage TCGA-lung adenocarcinomas, Cell cycle, DNA repair, WNT signaling and androgen receptor-mediated signaling pathways are predominantly altered in advanced EGFR mutant lung cancers. Conclusions: We characterized the genetic landscape of advanced EGFR-mutant lung adenocarcinomas and further dissected concurrent mutated genes with EGFR driver mutations. Our findings provide a rational for polytherapy roadmap for testing in advanced EGFR-mutant lung cancer.
Uptake of targeted therapy in clinical practice among US patients with ovarian cancer.
Authors: John K. Chan, Larissa Meyer, Patricia Luhn, Carlos Flores, Lydie Bastiere-Truchot, Mary K Downer, Yvonne Gail Lin, Jason Dennis Wright
Journal: Journal of Clinical Oncology (2020)

e18049 Background: Since first approvals for targeted therapies (TTs) in ovarian cancer (OC) patients (pts) in 2014, FDA approvals for TTs including bevacizumab (bev) and PARP inhibitors (PARPis) continue to expand. Approval of front line (1L) indications for bevacizumab (all-comers) and maintenance olaparib (BRCA-mutated) occurred in 2018. Here we describe real-world trends in the use of these TTs. Methods: Data were analyzed from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of patient-level data, curated via technology-enabled abstraction. We used descriptive statistics and significance tests to describe TT use in pts with OC. Results: We included 2975 treated OC pts diagnosed from 2011-18, with treatment data through 2019. Median follow-up was 32 months. 47% of OC pts received TT during follow-up, 12% of whom received TT during 1L. TTs were given as maintenance therapy in 54% of 1L and 37% of recurrent (2L+) OC pts. 40% of OC pts received bevacizumab anytime, 24% of whom received bevacizumab during 1L. Bevacizumab was given as maintenance therapy in 43% of 1L and 26% of recurrent OC pts. 20% of 2L and 17% of 3L bevacizumab-treated pts were platinum sensitive. From 2012-19, bevacizumab use changed biennially from 10% to 10% to 8% to 18% in FL (p &lt; 0.001), 24% to 35% to 34% to 38% in 2L (p = 0.008), and 21% to 34% to 35% to 36% in 3L (p = 0.06). Corresponding changes in PARPis use were 0% to 0% to 5% to 13% in FL (p = 0.03), 0% to 1% to 11% to 23% in 2L (p = 0.09), and 0% to 3% to 10% to 20% in 3L (p = 0.02). TT use (ever vs. never during follow-up) was more common among pts with stage III-IV tumors (81% vs. 55%), serous histology (90% vs. 75%), history of BRCA (82% vs. 61%) or NGS (38% vs. 13%) testing, and BRCA mutations (21% vs. 33%) (p &lt; 0.001 for all). Conclusions: Bevacizumab and PARPi use is expanding in 1L and 2L treatment; in 1L bevacizumab was more common than PARPis in 2019 (31% vs. 19%). These data reflect the evolving treatment landscape in 1L OC, which is expected to further evolve based on recent evidence from maintenance PARPi monotherapy and PARPi + bevacizumab combination studies. [Table: see text]
原发性纤维蛋白溶解症一例救治体会
Authors: 苗其云
Journal: BMJ (2005)

患者女,34岁,孕2产1,孕41周.因停经41周,不规律腹痛4 d于2003年5月16日上午10时入院.查体:营养、发育良好,神志清.血压100/60 mm Hg(1 mm Hg=0.133 kPa),呼吸20次/min,心率78次/min,心肺检查未见异常.产科检查:宫高34 cm,腹围106 cm,胎儿心率156次/min,头先露,宫口容指,胎膜未破.实验室检查:尿常规检查无异常,外周血白细胞9×109/L,红细胞5.2×1012/L,血红蛋白129g/L,血小板251×109/L。
Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer (NSCLC) patients with <i>EGFR</i> or <i>HER2</i> exon 20 insertions.
Authors: Kaiyan Chen, Guoqiang Pan, Yanjun Xu, Yun Fan
Journal: Journal of Clinical Oncology (2020)

e21540 Background: This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with insertions in exon 20 (Ex20ins) of EGFR or HER2. Methods: Molecular spectrum, tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were reviewed for NSCLC patients with Ex20ins of EGFR or HER2. Results: Thirty-five patients carrying EGFR Ex20ins and 21 patients harboring HER2 Ex20ins were retrospectively enrolled between April 2016 and September 2018. The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than those with HER2 mutations (48.6% vs. 19.0%, P=0.027). High TMB and PD-L1 expression was independently associated with considerably poor prognosis (P=0.025, P=0.045; respectively). Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins. Conclusions: NSCLC patients with EGFR/ HER2 Ex20ins had distinct immune features. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the underlying reason for the different responses to PD-1/PD-L1 blockage.
Controlled clinical studies on drug-induced liver injury in the elderly Chinese patients: a literature review
Authors: Ying Zhang, Gan-sheng Zhang, Zhi-jun Bao, Song-bai Zheng
Journal: BMJ (2013)

Objective
To review the clinical features of  liver  (DILI) in elderly Chinese patients.


Methods
A literature search was conducted with the key words drug-induced liver injury or drug-induced liver disease and elderly; four Chinese medical databases were used: including Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Wanfang Database and China National Knowledge Infrastructure (CNKI), from when the bases established to December 2011. Data from retrieved literatures of retrospective controlled studies of DILI were analyzed by SPSS 14.0 software.


Results
Five studies met the inclusion criteria, including 275 elderly patients (aged group) and 602 non-elderly patients (non-aged group) with DILI. There was no significant difference in gender between the two groups (P>0.05). Clinical manifestations of jaundice, fatigue, anorexia, and skin itching were more commonly seen in the aged group (P 0.05].


Conclusion
The elderly are more sensitive to the drugs and have a high risk of DILI. Prevention and timely diagnosis and treatment of DILI are particularly important for elderly patients.


Key words: 
Retrospective study; Drug-induced liver injury; Elderly
Intra-aortic balloon counterpulsation for patients with acute myocardial infarction and undergoing percutaneous coronary intervention: a meta-analysis
Authors: Zhiwei Gao, Yingzi Huang, Qingsong Sun, Man Luo, Hong Sun, Hongmei Zhao
Journal: BMJ (2017)

Objective
To evaluate the effects of intra-aortic balloon counterpulsation (IABP) on mortality of patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI).


Methods
Randomized controlled trials (RCTs) of IABP compared with non-IABP control in AMI patients, from January 1970 to May 2015, were searched from MEDLINE, Embase and Web of Science. The data were analyzed with software RevMan 5.0.


Results
Five RCTs involving 1 450 AMI patients, including 722 treated with IABP (IABP group) and 728 without IABP (non-IABP group), were included for analysis. Compared with non-IABP group, IABP did not significantly decrease the hospital mortality or 30-day mortality (OR=0.92, 95%CI: 0.69-1.25, P=0.61). According to the timing of IABP before or after PCI, it was further divided into IABP-before-PCI subgroup and IABP-after-PCI subgroup. Compared with non-IABP group, the 30-day mortality was not decreased in IABP-before-PCI subgroup or in IABP-after-PCI subgroup (OR=0.64, 95%CI: 0.23-1.78, P=0.39; OR=1.25, 95%CI: 0.42-3.77, P=0.69, respectively). According to complicating with cardiogenic shock (CS) or not, patients were divided to AMI with CS subgroup and AMI with no-CS subgroup; the hospital or 30-day mortality were not significantly decreased in both subgroups (OR=0.96, 95%CI: 0.70-1.32, P=0.80; OR=0.68, 95%CI: 0.28-1.70, P=0.27, respectively).


Conclusion
IABP does not decrease the 30-day mortality of AMI patients treated with PCI.


Key words: 
Intra-aortic balloon counterpulsation; Percutaneous coronary intervention; Myocardial infarction; Meta-Analysis