tbuckley/cabot-search huggingface dataset:
Disparities in use of immunotherapy for stage III and IV melanoma patients.
Authors: Richard L. White, Sally Jeanne Trufan, Nicole Lee Gower, Brittany Neelands, Asim Amin
Journal: Journal of Clinical Oncology (2020)

e19087 Background: Approval of immune checkpoint inhibitors (ICIs), ipilimumab (ipi), nivolumab and pembrolizumab has significantly changed the outcome for patients with stage III and IV melanoma. Adoption of ICI based immunotherapy (IT) and utilization has not been studied. We sought to assess the utilization of ICI therapy and identify barriers that limit access. Methods: The National Cancer Database (2004-2016) was used to analyze stage III and IV melanoma patients separately using descriptive statistics, univariable and multivariable models to compare use of IT (yes/no) with sex, race, age, Charlson-Deyo score, insurance status, census median income, census education, distance to treating facility, year of diagnosis and facility type. Results: Of 15,373 stage III patients 2,555 (16.6%) received IT. Since approval of ipi for resected stage III disease, 20.8% received adjuvant treatment in 2015 and 28.2% in 2016 (Table). Multivariable analysis showed that older patients (OR 0.96 (0.96-0.97)), those treated at non-academic programs (community cancer (CC) (OR 0.69 (0.55-0.86)), comprehensive CC (OR 0.55 (0.49-0.70)), or integrated network cancer program (INCP) (OR 0.58 (0.49-0.70))), have government insurance (OR 0.80 (0.70-0.90)) or no insurance (OR 0.78 (0.64-0.94)) vs private insurance were significantly less likely to receive adjuvant IT. Of 21,718 stage IV patients, 3,098 (14.3%) received IT. Using multivariable analysis, patients with fewer co-morbidities (OR 1.4 (1.05-1.86)) diagnosed in 2011 or later (Table) were more likely to receive IT. Disparities were noted in older patients (OR 0.98 (0.97-0.98)), those treated at non-academic programs (CC program, OR 0.34 (0.28-0.41)), comprehensive CC program (OR 0.34 (0.30-0.38)), or INCP (OR 0.40 (0.34-0.46)), and low vs high education level (OR 0.75 (0.62-0.90)) as less likely to receive IT. Conclusions: Despite approval and significant impact of ICIs, many patients did not receive approved therapy. Variations in care depended on where patients received treatment, age, and education level. [Table: see text]
The effect of cardiovascular disease on the association between immune-related adverse events and overall survival.
Authors: Ohad Oren, Julian R. Molina
Journal: Journal of Clinical Oncology (2020)

7059 Background: Preliminary data suggests that immune-related adverse events (irAEs) are associated with lower all-cause mortality, presumably due to improved anti-tumor responses. Investigations of large cohorts are needed to establish better understanding of that association. Methods: We reviewed the Mayo Clinic database for all patients who received an immune checkpoint inhibitor (ICI). The primary outcome was all-cause mortality. Descriptive and uni-variate analyses were generated. Results: Between March, 2010 and July, 2019, 3,326 patients received an ICI. The most common irAEs were colitis (287, 8.6%), pneumonitis (238, 7.2%) and hepatitis (227, 6.9%). A total of 933 (28.1%) patients developed at least 1 irAE and 176 (5.3%) patients experienced 2 or more irAEs. Survival analysis demonstrated an association between the number of irAEs and all-cause mortality (log-rank, P &lt; 0.0001), a relationship which was maintained for the 3 most common cancer types (lung, melanoma, renal) and for the individual ICI agents. In patients with lung cancer, colitis (P = 0.04) but not pneumonitis (P = 0.83) was associated with improved overall survival. No association between irEA and all-cause mortality was demonstrated in patients with history of stroke (log-rank, P = 0.12), peripheral artery disease (PAD) (log-rank, P = 0.68) and obesity (log-rank, P = 0.18). In an analysis of pre-ICI body-mass index (BMI), an association between irAE and lower overall mortality was shown in patients with BMI &lt; 30 (log-rank, P &lt; 0.001) and not in those with higher BMIs (log-rank, P = 0.09). The presence of stroke, PAD and obesity were associated with higher all-cause mortality in a survival analysis (P &lt; 0.001). The irAE-mortality association was not modulated by the presence hypertension (log-rank, P &lt; 0.0001), diabetes mellitus (log-rank, P &lt; 0.0001), or heart failure (log-rank, P = 0.006). Conclusions: The development of any irAE is associated with higher overall survival. The presence of numerous cardiovascular disease states neutralizes that association, likely a result of competing causes of mortality although interaction with immune or inflammatory pathways is possible. In addition, pneumonitis is not associated with better overall survival in patients with lung cancer presumably due to compromise of already-tenuous respiratory status.
Concealed auto-immune diabetes in adults
Authors: 张丽, 张曼华
Journal: BMJ (2004)

糖尿病是一组由遗传和环境相互作用所致的临床综合征.有些糖尿病患者发病时年龄较大,胰岛功能呈渐进性破坏,开始时不发生酮症酸中毒,也不依赖胰岛素治疗,而被诊断为2型糖尿病,但随着病程进展,口服降糖药继发性失效,最终将依赖胰岛素生存,并且有发生酮症酸中毒的危险.1993年Toumi等[1]把这类称为成人隐匿性自身免疫性糖尿病(latent autoimmune diabetes in adults,LADA),近年来将其纳入1型糖尿病的范畴[2,3].LADA并非少见,据欧美资料,LADA患者占2型糖尿病者的15%～20%,非肥胖者占50%.我国目前虽无确切统计数字,但实际患者不会少.全科医师是初级医疗保健的专业人员,对此应有充分认识。
Clinical analysis of 19 cases of giant cell arteritis
Authors: Xiao-lin Wang, Sheng-yuan Yu
Journal: BMJ (2010)

The clinical data of 19 cases of giant cell arteritis (GCA) including 8 males and 11 females aged 21-92 y (average 62.2 y) from July 2002 to September 2008 were retrospectively reviewed.Among 19 patients,15 first visited the neurology department and 4 the rheumatism department;8 had fever and 16 had headache as primary symptom;the ESR ranged from 20 to 130 mm/1 h (average 71.1 mm/1 h).Fourteen patients were diagnosed as GCA at admission and 18 were treated with steroids hormone and all got remission except 1 death and 2 recurrences.If temporal artery biopsy is not acceptable,integrated analysis of signs,symptoms,laboratory tests,treatment effectiveness and follow-up is important for the correct diagnosis of GCA.

Key words: 
Temporal arteritis;  Diagnosis
老年高血压患者抗高血压药物的选择
Authors: 李俭春
Journal: BMJ (2010)

60岁以上的原发性高血压患者均属老年高血压,往往有多种危险因素群集,靶器官损害及并存症也比较多,其治疗率(32.2%)、控制率(7.6%)都很低.对老年高血压患者,应根据其高血压特点,综合评估并存的危险因素和疾病、靶器官损害程度的危险分层,进行个体化治疗[1-2]。
Evaluation of tumor growth inhibition activity of a novel multi-TRK inhibitor ABP-1130 on glioblastoma xenograft model.
Authors: Zheng-Yun James Zhan, Wanlong Pan, Hao Zhang
Journal: Journal of Clinical Oncology (2020)

e14507 Background: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive cancer that begins within the brain. Glioblastoma is a difficult to treat tumor with therapeutics limited by their ability to cross the blood brain barrier. Receptor tyrosine kinases (TRK) inhibitor is reported one of therapies for glioblastoma. ABP-1130 is a novel and potent small molecular multi-TRK Inhibitor for several prime tyrosine kinases (TRKs), such as EGFR, HER2, C-Met, and BTK with potential to treat glioblastoma. Pre-clinical studies with ABP-1130, especially study to evaluate its tumor growth inhibition effect on glioblastoma xenograft model, are planned in progress. Methods: (1) Mobility-Shift Assay used to Analyze the multi-TRK (such as EGFR, HER2, C-Met, and BTK) Inhibition activity of new anti-tumor compounds, (2) CTG Assay used to analyze the inhibition activity of LN-229 Cell Line, (3) Anti-tumor inhibition study of ABP-1130 with the brain cancer nude mice, (4) Safety studies of ABP-1130 for Ames, hERG, and MTD. Results: It was determined that its multi-TRK inhibition activity (IC 50 ) of ABP-1130 was 7nM to EGFR, 3.6nM to HER2, 3.2nM to C-Met, and 3.7nM to BTK, respectively. Its inhibition activity for Cell Line LN-229 was 0.02 µM. In anti-tumor inhibition study with the LN-229 tumor nude mice for 28 days, the anti-tumor inhibition activity of ABP-1130 (40 mg/kg, QD) was significantly observed, and the average volume of brain tumors in nude mice (six mice/each group) was reduced from 122 mm 3 to &lt; 10mm 3 (vs Pazopanib as a positive control, 50mg/kg, tumor volume increased from 123 to 867mm 3 ). Moreover, for other safety issues, its Ames is negative and hERG is &gt; 30 µM, and no test-article related death or adverse events occurred in maximum tolerated dose (MTD) studies with ABP-1130 (100mg/kg, QD) for 14 days. ABP-1130 also had very good metabolic stability in Human (T 1/2 = 193min). Conclusions: Based on our completed preclinical study results, ABP-1130 is a novel and potent multi-TRK Inhibitor, showing excellent enzymatic activity, prominent in-vitro anti-cancer activity, and significant tumor growth inhibition activity with tolerable toxicity in glioblastoma tumor xenograft in nude mice model. It is highly warranted to continue further investigation in glioblastoma.
Rituximab for High-Risk, Mature B-Cell Non-Hodgkin’s Lymphoma in Children
Authors: Véronique Minard-Colin, Anne Aupérin, Marta Pillon, G.A. Amos Burke, Donald A. Barkauskas, Keith Wheatley, Rafael F. Delgado, Sarah Alexander, Anne Uyttebroeck, Catherine M. Bollard, József Zsiros, Monika Csoka, Bernarda Kazanowska, Alan K. Chiang, Rodney R. Miles, Andrew Wotherspoon, Peter C. Adamson, Gilles Vassal, Catherine Patte, Thomas G. Gross
Journal: New England Journal of Medicine (2020)

Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited.
The dark side of thinking through other minds
Authors: Sander Van de Cruys, Francis Heylighen
Journal: Behavioral and Brain Sciences (2020)

Abstract We show that TTOM has a lot to offer for the study of the evolution of cultures, but that this also brings to the fore the dark implications of TTOM, unexposed in Veissière et al. Those implications lead us to move beyond meme-centered or an organism-centered concept of fitness based on free-energy minimization, toward a social system-centered view.
The impact of tumor NGS testing on hereditary cancer risk assessment and population management in an integrated community health care system.
Authors: Sachdev P. Thomas, Jennifer Marie Suga, Thach-Giao Truong, Tilak Kumar Sundaresan, Minggui Pan, Won Kim, Chen Jiang, Elizabeth Hoodfar, Elaine Chung, Pamela Tse, Ninah Achacoso, Lirong Cheng, Laurel A. Habel
Journal: Journal of Clinical Oncology (2020)

1517 Background: Next-generation sequencing (NGS) for tumor molecular profiling is used in Oncology to identify ‘actionable alterations’ for clinical trials or on/ off-label therapy. Tumor NGS can also reveal potentially heritable germline mutations. The frequency of such incidental germline mutations has been estimated to be 4-15%. The 2015 ASCO Statement supports communication of medically relevant incidental germline findings from somatic mutation profiling to patients (PTS). The impact of tumor NGS testing on hereditary cancer risk assessment programs in the context of a wider population management strategy is unknown. We sought to evaluate this within our Kaiser Permanente Northern California (KPNC) population with ready access to tumor NGS and an ongoing hereditary cancer risk assessment program. Methods: Kaiser Permanente Northern California (KPNC) is part of a large, integrated health care system. NGS at KPNC is performed in collaboration with STRATA Oncology, a precision oncology partnership. All NGS results are reviewed by a multidisciplinary KPNC Genomic Oncology Committee (GOC)which also includes genetic counselors and pathologists. We examined all NGS reports between November 2017 through December 2019 to determine the types of cancers tested, number with a possible germline mutation and number referred for genetic counseling and testing (GCT). Results: 4,825 PTS with advanced cancer underwent STRATA NGS testing. A total of 207 PTS (4.3%) were identified as potential germline mutation carriers, all 207 were recommended for GCT referral. Of these, 92 (45.0%) separately met 2020 NCCN Criteria for Genetic/Familial High-Risk Assessment (2020NG/FA), prior to tumor NGS; 115 (53.6%) did not and 3 (1.4%) had insufficient information. The cancers most frequently meeting NCCN criteria were pancreatic, breast and colon. Of the 92 PTS who met 2020NG/FA, 60 (65%) underwent GCT and 34 (57%) were confirmed to have a germline mutation. Of the 115 PTS that did not meet 2020NG/FA, 47 (41%) underwent GCT and 19 (40%) were confirmed to have a germline mutation. Overall germline mutations were confirmed in 16.5% of patients who did not meet 2020NG/FA and 37% who did. Conclusions: In our community-based integrated healthcare system, systematic review of next-generation sequencing results by an expert GOC led to more robust identification of germline mutation carriers and navigated them to appropriate GCT. Ongoing work will clarify data on cascade testing. We are currently developing automated workflows for GCT.
Lung-MAP (SWOG S1400): Design, implementation, and lessons learned from a biomarker-driven master protocol (BDMP) for previously-treated squamous lung cancer (sqNSCLC).
Authors: Mary Weber Redman, Vassiliki Papadimitrakopoulou, Katherine Minichiello, David R. Gandara, Fred R. Hirsch, Philip C. Mack, Lawrence Howard Schwartz, Everett E. Vokes, Suresh S. Ramalingam, Natasha B. Leighl, Jeffrey Bradley, Michael Leo LeBlanc, Shakuntala Malik, Vincent A. Miller, Ellen V. Sigal, Stacey Adam, Charles David Blanke, Karen Kelly, Roy S. Herbst
Journal: Journal of Clinical Oncology (2020)

9576 Background: S1400, a BDMP, was designed to address an unmet need in sqNSCLC, run within the National Clinical Trials Network of the National Cancer Institute using a public-private partnership (PPP). The goal of was to establish an infrastructure for biomarker-screening and rapid evaluation of targeted therapies in biomarker-defined groups leading to regulatory approval. Methods: S1400 included a screening part using the FoundationOne assay and a clinical trial part with biomarker-driven studies (BDS) and “non-match” studies (NMS) for patients not eligible for any BDS. Patients could be screened (SaP) at progression or pre-screened (PreS). Results: Between June 2014 and January 2019, 1864 patients enrolled (711 PreS, 1079 SaP), 1674 with biomarker results, and 653 registered to a study with 217 to BDS and 436 to NMS. Six BDS and 3 NMS were initiated in small subsets with all BDS and 2 NMS completed within 2-3 years (see Table). Completed BDS have not demonstrated activity with 0-2 responses. On S1400I, Nivolumab and ipilimumab did not improve survival. Response with durvalumab (S1400A) was 16%. Conclusions: Lung-MAP met its goal to quickly answer targeted and other novel therapy questions in rare sqNSCLC subpopulations, answering questions that likely would not have been otherwise feasible, thereby demonstrating value. Activated just prior to the success of PD-(L)1 therapies in sqNSCLC, the trial had to undergo major design changes. Lessons learned include the need to update based on new science and that the PPP collaboration was essential to success. Lung-MAP continues now with new BDS and NMS in all NSCLC as of January 2019. Clinical trial information: NCT02154490 . [Table: see text]
Risk factors and pathogenesis of posttransplantation diabetes mellitus
Authors: 陈琳, 盛正妍, 王煜非
Journal: BMJ (2007)

随着器官移植技术的不断进步和免疫抑制剂的使用,移植患者的生存率大大提高.然而,移植后糖尿病(posttransplant diabetes mellitus,PTDM)却对患者和移植物存活产生了不容忽视的负面影响,包括移植物功能下降、患者生存期缩短以及移植物功能丧失.Benhamou和Penfornis[1]报道移植后前2年的急性排斥反应发生率和死亡率在PTDM患者中显著升高.PTDM发病率较高,不同研究报道PTDM发病率从2%～53%不等[2],多数患者在移植后60 d内新发糖尿病[3]。
盐酸右美托咪啶预防小儿七氟醚全身麻醉苏醒期躁动的临床效果观察
Authors: 曹丙玉
Journal: BMJ (2012)

将60例七氟醚全身麻醉(全麻)小儿分为3组(各20例),分别予右美托咪啶0.5μg/kg、0.7μg/kg和生理盐水缓慢静脉注射,行分组对照研究.0.5μg/kg右美托咪啶可明显降低小儿七氟醚全麻苏醒期躁动发生率,维持苏醒期血流动力学稳定,未见不良反应。
Molecular characterization of patients with advanced lung adenocarcinoma at diagnosis with next generation sequencing by liquid biopsy in the Mexican population.
Authors: José Fabián Martínez-Herrera, Luis Martinez-Barrera, Jeronimo Rafael Rafael Rodriguez Cid, Carla Paola Sánchez-Ríos, Mario Alberto Sanchez-Prieto, Rodrigo Rodrigo Flores-Mariñelarena, Raul Alejandro Andrade Moreno, Julia Angelina Saenz-Frias, Jorge Alatorre-Alexander
Journal: Journal of Clinical Oncology (2020)

e21511 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tumor biopsy represents the standard for molecular diagnosis, nevertheless it is not always feasible to obtain. Liquid Biopsy (LB) may offer an alternative in the first line setting. Methods: Retrospective review of case files and next generation sequencing report (NGS) from LB from patients in a Validation Trial, performed from January 2018 to September 2019. We present the molecular alterations and clinical characteristics of the population. Results: 147 records and LB reports of patients 18 years and older with metastatic lung adenocarcinoma without prior treatment were included. 40% of the population had been selected based on a commercial local PCR test for EGFR (Idylla). 49% of them were female with Mean age of 60.9 ± 12.7. 56% had a history of smoking with an average packs/year of 20.5 (1-156) and 39% had exposure to wood smoke, 92% had an ECOG 0-1. 65 % of the Patients were diagnosed in Clinical Stage (8 th Edition) IVA and 22% in IVB. 13% had SNC metastasis. The LB detected genomic alterations in 85.5% of the cases. 78% represent pathogenic mutations and 7.5% variants of uncertain significance (VUS).14.5% of the biopsies could not detect any ctDNA. The most frequent aberrations reported were TP53 in 51.7%, KRAS 16%, EGFR 16%, ALK 9%, PIK3CA 4%, RET 4%, BRAF 3%, BRCA 3, and HER2 3%. In addition, 20% had bTMB ≥10. Only 20% of the patients could receive a targeted therapy or immunotherapy of the potential ≈50%. Most cases had co-mutations (1-6 x case). Looking for factors associated with the presence of bTMB by a logistic regression model, it was possible to identify the presence of CNS metastases and smoking as identified with an OR of 3,688 (p = 0. 0.042) and 3.952 (p = 0. 024) respectively. Conclusions: It is feasible to have tumor molecular analysis through liquid biopsy in most cases, with genetic alterations previously reported in tumor tissue in the first line setting. [Table: see text]
Test identifies ovarian cancer patients with hyperactive c-Met and ErbB signaling tumors who may benefit from c-Met and pan-HER combination therapy.
Authors: Lance G. Laing, Stefano Rossetti, Catherine Kuzmicki, Aaron Broege, Joanna Sabat, Salmaan Khan, Ian A. MacNeil, Brian Sullivan
Journal: Journal of Clinical Oncology (2020)

e18038 Background: No sub-groups of ovarian cancer patients with clinically actionable ErbB genetic variants have yet been found. Measurement of ErbB signaling activity rather than genetic variants may identify ovarian cancer patients likely to benefit from ErbB targeted therapies. We have previously reported studies detecting dysregulated ErbB and c-Met signaling activity in 20%-25% of HER2-negative breast cancer patient tumors using the CELx Signaling Function Test. To determine whether ErbB or c-Met signaling dysregulation is involved in ovarian cancer, the CELx Test was adapted to analyze ovarian tumor cells. The current study set out to: 1) characterize c-Met and ErbB family signaling activity in ovarian patient tumor cells and tumor cell lines; 2) evaluate in vivo response to pan-HER and c-Met inhibitors in an ovarian tumor xenograft model. Methods: For the ex vivo studies, a set of fresh tumor specimens from 15 ovarian cancer patients and a set of 12 ovarian cancer cell lines was obtained. Cell samples were cultured from each. Live cell response to ErbB and c-Met agonists (NRG1b, EGF, or HGF) with or without an antagonist (2C4, a HER2 dimerization inhibitor or tepotinib, a c-Met kinase inhibitor) was measured using an xCELLigence impedance biosensor (Agilent Technologies). Signaling activity above a previously established cut-off value was used to identify abnormal levels of EGFR, HER2 and c-Met signaling activity. For the xenograft study, OVCAR-4, an ovarian cancer cell line, determined to have abnormal HER2, EGFR, and c-Met signaling with the CELx Test, was studied. 40 female NSG mice were each injected with two million cells. Mice were randomly assigned to either a control group or a treatment group that received neratinib, tepotinib, or neratinib and tepotinib for 16 days. Results: Of the patient cell and cell lines samples tested ex vivo with the CELx Test, 4 of 27 (15%; 95% CI = 6%-32%) had hyperactive HER2 and c-Met signaling pathways. In the xenograft study, tumor volume change was 40% less in the tepotinib + neratinib treated group than in the control arm change. There was no significant difference in tumor volume between the control and tepotinib or neratinib groups. Conclusions: These findings suggest that a significant sub-group of ovarian cancer patients have abnormal ErbB and c-Met signaling activity that may respond to treatment with a combination of ErbB and c-Met inhibitors. A clinical trial to evaluate treatment response of this patient sub-set to combined c-Met and pan-HER inhibitors is warranted.
食管神经内分泌癌四例临床分析
Authors: 梅波, 赖应龙, 何光杰, 付茂勇, 魏蜀亮, 赵泽良, 王烈
Journal: BMJ (2011)

食管神经内分泌癌(NEC)是一类罕见的食管恶性肿瘤,因其发病率低,临床表现缺乏特异性,对其认识不清,故常不能被正确诊治.本院自2003年至2007年间共收治食管NEC患者4例,现报告如下。
Comparative analyses of advanced gastric cancer on different chemotherapeutic protocols
Authors: Lei Fan
Journal: BMJ (2015)

Objective
A total of 86 cases with advanced gastric cancer were randomly divided into XELOX(capecitabine plus oxaliplatin) and FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin)groups (n=43 each). The immediate efficacies were evaluated by the criteria of Response Evaluation Criteria In Solid Tumors (RECIST). Adverse reactions were compared between two groups. The overall effective rate were 56% and 51% in XELOX and FOLFOX4 groups. And there was no significant inter-group difference (P>0.05). The incidences of myelosuppression and nausea, vomiting in XELOX group were lower than those in FOLFOX4 group (P 0.05). Both chemotherapies were comparable in immediate efficacies for advanced gastric cancer. However, XELOX chemotherapy had a lower incidence of adverse reactions and it is more tolerable and compliant for patients.


Key words: 
Stomach neoplasms; Antineoplastic combined chemotherapy protocols