tbuckley/cabot-search huggingface dataset:
Major pathologic response of EGFR mutated non-small cell lung cancer (NSCLC) on 1-3 G TKI.
Authors: Fedor Vladimirovich Moiseenko, Kirill Kryukov, Alexander Myslik, Nikita Levchenko, Alexander Ivantsov, Svetlana Aleksakhina, Nikita Volkov, Albina Gabina, Ksenia Shelekhova, Elizaveta Artem'eva, Vladimir Moiseyenko
Journal: Journal of Clinical Oncology (2020)

e21528 Background: Despite impressive clinical efficacy in response rate, increase in PFS and sometimes in OS EGFR TKI rarely cure cancer patients, as all of them inevitably develop resistance. Small fractions of residual cells appear to be a reservoir of further clones with acquired resistance. For this moment morphological characteristics of “persister” population are not well defined. Methods: We screened hospital data-base containing &gt; 200 pts for EGFRmut NSCLC who underwent cytoreductive surgical treatment during treatment with either TKI and before radiographic disease progression. We obtained 18 pairs of pretreatment biopsy and surgical specimen. 7/18 were male, median age 60.5 yo (45-79). 15/18 had ex19del; 3/18 – L858R. 12/3/2/1 received gefitinib/erlotinib/afatinib/osimertinib before surgery. Median time from treatment initiation to surgery was 8.9 mon (0.7 – 24.3). None of the pts had evidence of increase in any dimension of tumor lesions before surgery. According to RECIST 6/18 pts had SD, 12/18 – PR. 6/18 pts had complete cytoreduction, 4/18 – partial, 8/17 – metastasectomy. All pathologic responses (MPR) were graded according to Hellmann MD et al., 2014. Results: Pathologic response with &gt; 50% of residual tumor – 2/18; 10-50% – 7/18; &lt; 10% – 4/18; pCR – 3/18. Median observation time is 15.4 mon (8.4 – 37.2+). Disease progression after surgery was registered in 6/18 pts. No significant correlations between PFS, MPR, RR, TKI generation, time to surgery were seen. Conclusions: In our serie MPR rate ( &lt; 10% of viable tumor cells according to Hellmann MD et al, 2014) for NSCLC treated with various TKI was 38%, that is higher than in other reports (10.2% in CTONG 1103 for example). Further characterization of the “persister” tumor cells may help to determine mechanisms of intrinsic resistance and direct more efficient antitumor activity.
Risk of cancer-specific death for patients diagnosed with neuroendocrine tumors: A population-based analysis.
Authors: Julie Hallet, Calvin Law, Simron Singh, Alyson Mahar, Sten Myrehaug, Victoria Zuk, Haoyu Zhao, Angela Assal, Natalie Coburn
Journal: Journal of Clinical Oncology (2020)

4605 Background: While patients with neuroendocrine tumours (NETs) are known to experience prolonged overall survival, the contribution of cancer-specific and non-cancer deaths is undefined. We examined cancer-specific and non-cancer death after NET diagnosis. Methods: We conducted a population-based retrospective cohort study of adult patients with NETs from 2001-2015 by linking administrative healthcare datasets. Using competing-risks methods, we estimated the cumulative incidence of cancer-specific and non-cancer death and stratified by primary NET site and metastatic status. Sub-distribution hazard models examined prognostic factors. Results: Among 8,607 included patients, median follow-up was 42 months (interquartile range: 17-82). The risk of cancer-specific was higher than that of non-cancer death, with 27.3% (95%CI: 26.3-28.4%) and 5.6% (95%CI: 5.1-6.1%) at 5 years. Cancer-specific deaths largely exceeded non-cancer deaths in synchronous and metachronous metastatic NETs. Patterns varied by primary tumour site, with highest risks of cancer-specific death in broncho-pulmonary and pancreatic NETs. For non-metastatic gastric, small intestine, colonic, and rectal NETs, the risk of non-cancer death exceeded that of cancer-specific deaths. Advancing age, higher material deprivation, and metastases were independently associated with higher hazards, and female sex and high comorbidity burden with lower hazards of cancer-specific death. Conclusions: Among all NETs, the risk of dying from cancer is higher than that of dying from other causes. Heterogeneity exists by primary NET site. Some patients with non-metastatic NETs are more likely to die from non-cancer than from cancer causes. This information is important for counselling, decision-making, and design of future trials. Cancer-specific mortality should be included in outcomes when assessing treatment strategies.
治疗失眠药物的选择和使用原则
Authors: 潘集阳, 黄俏庭
Journal: BMJ (2008)

睡眠障碍是一种常见且常伴有明显精神、机体和社会活动障碍的疾病,WHO开展的研究表明,睡眠障碍在世界上是一个未得到充分重视和很好解决的公共卫生问题,全球约有27%的人受其困扰[1].2005年美国睡眠医学会发布的国际睡眠疾病分类第二版(ICSD-2)将睡眠疾病分为8类[2]:即失眠、睡眠相关呼吸障碍、非呼吸相关睡眠障碍所致的白天过度嗜睡、昼夜节律失调性睡眠障碍、异态睡眠、运动相关睡眠障碍、独立的睡眠症状以及其他睡眠障碍(未作出特异诊断).其中失眠最常见.
Establishment of the first international large-scale, genomic screening platform to identify patients with rare oncogene drivers in non-small cell lung cancer (NSCLC) in East Asia.
Authors: Shingo Matsumoto, Caicun Zhou, Chih-Hsi Kuo, Kiyotaka Yoh, Terufumi Kato, Kazumi Nishino, Naoki Furuya, Shucai Zhang, Dongmei Lin, Yuchen Han, Chin-Chou Wang, Takaya Ikeda, Yoshitaka Zenke, Koichi Goto
Journal: Journal of Clinical Oncology (2020)

9605 Background: A rapidly increasing number of oncogenic drivers have been identified in non-small cell lung cancer (NSCLC), and most of them occur in less than 5% of patients. Large-scale genomic screening to identify patients with rare driver alterations is thus necessary to enable precision medicine and to support the development of novel targeted therapies and companion diagnostics (CDx). Methods: A lung cancer genomic screening project (LC-SCRUM-Asia) capturing clinical outcome was established in 2013 with 206 institutions in Japan and 5 in Taiwan currently participating. A separate genomic screening project with similar structure was established in China (LC-IRICA-China) in collaboration with LC-SCRUM-Asia in 2019 (3 institutions enrolling, 17 about to open, 63 undergoing review). Samples are analyzed by a multi-gene PCR panel and targeted next-generation sequencing. The target is to enroll 70000 NSCLC patients (20000 from LC-SCRUM-Asia and 50000 from LC-IRICA-China) by 2022. Results: From March 2013, a total of 9383 lung cancer patients were enrolled in LC-SCRUM-Asia, and from October 2019, 1649 pts were included in LC-IRICA-China (January 2020). The rates of genomic alterations in LC-SCRUM-Asia: EGFR (17%) of which ex20ins (2%), KRAS (13%) of which G12C (4%), ALK fusions (2%), ROS1 fusions (2%), RET fusions (2%), HER 2 ex20ins (3%), MET ex14skip (2%), BRAF V600E (1%), NRG1 fusions (0.2%) and NTRK3 fusions (0.03%). Corresponding rates in the initial 243 pts in LC-IRICA China: EGFR (45%) of which ex20ins (2%), KRAS (8%), ALK (5%), ROS1 (2%), RET (1%), HER2 (2%), MET ex14skip (1%), BRAFV600E (1%). Through the screening, 266 patients from Japan and Taiwan were enrolled into genotype-matched clinical trials of unapproved targeted drugs. In Japan, ROS1-, BRAF- and TRK-targeted therapies were successfully approved based on these clinical trials, and a NGS-based multi-gene CDx for EGFR/ALK/ROS1/BRAF targeted-therapies was approved based a concordance study using archival samples from the project. Conclusions: An East Asian international genomic screening platform has been established to enable precision medicine for patients, accelerate drug and diagnostic development in patients with very rare alterations and to help provide a deeper understanding of the underlying biology of NSCLC in East Asian patients. The screening network will be further expanded to other countries in East Asia in the near future.
Survey on knowledge of chronic kidney disease among medical staff in suburbs of Shanghai
Authors: Jianfang Xie, Jianzhen Yu
Journal: BMJ (2017)

A questionnaire survey on knowledge of chronic kidney disease (CKD) was conducted among 168 medical staff in suburban Shanghai on March 2016.The results showed that the average score was 53.53±13.35, with the lowest score of 17.5 and the highest score of 82.5; the score of 118 participants (70.2%) was  0.05).


Key words: 
Kidney disease, chronic; Medical staff; Cognition
CDC20 is a novel potential therapeutic target in NF1-mutant melanoma.
Authors: Douglas M. Donnelly, Keith M. Giles, Eleazar Vega-Saenz de Miera, Rebecca Betensky, Carolyn Winskill, Yu hsin Yeh, Iman Osman, George Jour
Journal: Journal of Clinical Oncology (2020)

e22075 Background: NF1-mutant melanoma (NF1-MT) is a distinct molecular subtype with worse overall prognosis than NF1-wild melanoma (NF1-WT). Despite its prevalence in 20% of patients and associated clinical disadvantage, there is no specific targeted therapy available to treat NF1-MT as its biological impact remains understudied. We tested the hypothesis that NF1-MT possess distinct genomic and transcriptomic characteristics from NF1-WT, which can potentially inform therapeutic innovation. Methods: Tumor DNA from metastatic melanoma (MM) patients treated with checkpoint inhibition at NYU was genotyped using exome sequencing. Microenvironment-related transcripts (n = 770) were then compared in NF1-MT versus NF1-WT using unsupervised clustering, differential gene expression, and gene set enrichment analyses. Verification of genomic and transcriptional findings was performed using qPCR and immunohistochemistry (IHC). TCGA melanoma (SKCM) data were analyzed as an independent cohort. Results: Pathogenic NF1 mutations were detected in 31/121 (27%) cases and were significantly associated with higher tumor mutational burden (P = 0.02). NF1-MT showed recurrent homozygous deletion in the membrane regulatory gene SYT1 and amplifications in oncogenes including CCND1 and MDM2, verified by qPCR. NF1-MT showed upregulation of proliferation with significantly increased expression of Ki-67 and cell division cycle protein 20 CDC20 (P = 0.03) validated by IHC (P = 0.03). Cell cycle was the top enriched pathway in NF1-MT (P = 0.003, FDR = 0.04). Analysis of TCGA melanoma data (n = 440) corroborated upregulation of MKI67 and CDC20 in NF1-MT melanoma (P = 0.01, P = 0.03). Conclusions: NF1-MT is associated with a hyper-proliferative tumor phenotype that cannot be only attributed to MAP kinase activation. Our data suggest that NF1-MT may be vulnerable to pharmacological inhibitors of cell cycle progression and proliferation, such as those targeting CDC20 or CDK4/6.
Functions of pancreatic islet α-cells and β-cells in different disease courses of type 2 diabetes mellitus
Authors: Hang Guo, Bao-cheng Chang, Ju-hong Yang, Chun-yan Shan, Miao-yan Zheng, Jie-yu Liu
Journal: BMJ (2013)

Objective
To evaluate the functions of pancreatic islet α-cells and β-cells in different disease courses of type 2 diabetes mellitus.


Methods
Two hundred and eighty three patients with type 2 diabetes mellitus were divided into 4 groups according to their disease courses: group A (course of disease≤1 years), group B (1 years  10 years). Oral glucose tolerance test (OGTT), insulin releasing test and glucagon releasing test were performed to observe the differences of glucagon, glucagon/insulin, ratio of insulin increment/glucose increment 30 min after glucose-load (ΔI30/ΔG30), area under curve (AUC) of insulin in receiver operational characteristic (ROC) curve of insulin (AUCI) and glucagon among 4 groups and the correlation analysis was performed between glucagon and other indicators.


Results
(1) Glucagon, glucagon/insulin and AUC of glucagon increased significantly with the prolonged course of disease (P 0.05); compared to group A, HOMA of β-cell function (HOMA-β), ΔI30/ΔG30, AUCI in groups B, C and D were significantly lower (F=3.75, 3.77 and 3.07 respectively, all P<0.05).(3) Multiple stepwise regression analysis showed that glucagon was positively correlated with FPG and AUC of glucose (AUCG) (t=6.23 and 3.41, all P<0.05), and negatively correlated with AUCI/AUCG (t=-2.13, P<0.05).


Conclusions
In order to reach the blood glucose control target, in the early stage of diabetes attentions should be given to regulation of glucagon while protect the β-cell function.


Key words: 
Glucagon; Islet α-cell; Islet β-cell; Course of disease; Diabetes mellitus，type 2
Decompressing Stoma vs Stent in Left-Sided Obstructive Colon Cancer
Authors: Åsa Hallqvist-Everhov, Johannes Asplund, Martin Dahlberg
Journal: JAMA Surgery (2020)

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Optimizing the febrile neutropenia care process in cancer patients in a third level Spanish hospital.
Authors: Maria Pilar Solis-Hernandez, Luka Mihic Góngora, Debora Corina Contreras Toledo, Clara Iglesias Gomez, Sara Fernandez Arrojo, Carlos Alvarez Fernandez, Paula Jiménez Fonseca, Marta Izquierdo Manuel, Alfonso Revuelta, David Gómez, Jorge del Río Fernández, Sena Valcárcel González, Maria Muniz Castrillo, Oscar Alfredo Castillo Trujillo, Noemí Villanueva, Juan Luis Garcia Llano, Isabel Palacio Vázquez, Yolanda Fernandez Perez, Emilio Esteban
Journal: Journal of Clinical Oncology (2020)

e14034 Background: Cancer patients under cytotoxic treatment with fever used to have an average time of antibiotics administration of 11h (median 3h43min) when admitted and identified at the Emergency Room Service in the third level Central University Hospital of Asturias. International guidelines recommend antibiotic administration in the first hour: the so called “Golden Hour”. This delay implies an increase in patient morbidity as well as the cost of managing this complication. Methods: Data was collected from our electronic registry after proper authorization and corresponding anonymization. Pareto and fishbone diagrams were built to point out the possible causes and to stratify them in related subgroups. We measured: Number of visits to ER with fever and Number of inpatients with Febrile Neutropenia diagnosis, Time from the admission to antibiotic administration, Average stay of inpatients with Febrile Neutropenia diagnosis. A protocol associated to electronic tools and validated international scores was designed for patients at Febrile Neutropenia risk and launched on March 2019. Results: 66 patients were included since January 2018. Baseline data showed that the median time to antibiotics indication was 3h50min (average 4h38min) with a median delay of 18min to the administration (average 1h06min), a median of 3h54min (average 10h09min) time to antibiotic administration. When the protocol was activated, median time to antibiotic indication was 30min (average (1h08min) with a median 41min (average 40min) delay in administration, and a median of 1h30min (average 1h42min) time to antibiotic administration. Those with activation of the protocol had average length of stay of 1d13h40min vs. 5d11h18min in those to whom this protocol was not applied. Conclusions: A continuous evaluation effort and the design of appropriate protocols and interventions will increase the efficiency of the oncology patient care process with febrile neutropenia, by reducing unnecessary variability and costs.
对中国成人血脂异常防治指南全科医生需要关注的问题
Authors: 叶平, 盛莉
Journal: BMJ (2007)

血脂异常是动脉粥样硬化性心脑血管病的主要危险因素,加强对血脂异常的防治是预防心脑血管疾病发生和发展的关键环节.2007年我国正式发布由多个学科联合制定的《中国成人血脂异常防治指南》(《指南》),既吸收了国际上循证医学的证据和经验,又结合我国人群的特点,在具体要点上有别于国际指南,对适应我国心血管病防治形势的需要,加强心血管病的防治具有十分重要的指导意义.下面对全科医师需要了解的《指南》关键点和如何实施作一介绍。
Contemporary management and associated outcomes of 3,151 patients with stage III non-small cell lung cancer (NSCLC) in a real-world setting: Results of KINDLE, a multicountry observational study.
Authors: Abdul Rahman Jazieh, Huseyin Cem Onal, Daniel Shao-Weng Tan, Ross A. Soo, Kumar Prabhash, Amit Kumar, Reto Huggenberger, Stephen Robb, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2020)

9043 Background: Stage III NSCLC is a heterogeneous disease requiring a multimodality approach. We conducted a global study to characterise the patients (pts), treatment patterns and their associated outcomes for this disease in a real-world setting in the pre-IO era. Methods: KINDLE is a retrospective, multi-country, multi-centre study capturing data on patient and disease characteristics, treatments and outcomes. The study included pts with stage III NSCLC diagnosed between January 1 st , 2013 and December 31 st , 2017 and with at least 9 months of documented follow-up. Descriptive statistics were used to describe patient demographics, disease characteristics and treatment modalities. Inferential statistics was used to correlate various clinical and treatment variables with progression free survival (PFS) and overall survival (OS). Results: 3151 patients were enrolled at 125 centres in three geographical regions; 1046 pts in Middle East and North Africa, 1874 pts in Asia and 231 pts in Latin America. Median age was 63 years (range 21-92); 76.5% were male; 69.2% with a smoking history; 55.9% were staged as IIIA (AJCC 7 th ed.); 53.7% had adenocarcinoma and 36.6% squamous cell, and 31.7% were known to have an EGFR mutation. 21.4% of patients underwent curative surgical resection. First line therapy included more than 25 different regimens, the most common being concurrent chemo-radiotherapy (cCRT) in 29.4%, chemotherapy (CT) alone in 17%, sequential chemo-radiotherapy (sCRT) in 10.4%, and radiotherapy (RT) alone in 8.5%. Median PFS for the whole cohort was 12.5 mos (95% CI; 12.06 – 13.14) and median OS 34.9 mos (95% CI; 32.00 – 38.01). Stage IIIA patients who were eligible for and underwent surgery + CT, had longer OS than patients who did not undergo surgery, receiving other treatments. Non-surgical approaches included CT, RT, and CRT. In stage IIIB, OS was significantly improved for cCRT vs. CT alone (p = 0.0015) or RT alone (p = &lt; 0.0001) or sCRT (p = 0.0216). Improved survival was observed with sCRT compared with RT alone and chemotherapy vs RT alone. Conclusions: KINDLE, a large multi-country observational study, reveals the diversity of treatment practices that exist in stage III NSCLC and provides insights on the outcomes in a real-world setting. The unmet medical need remains high and approaches are required to optimize patient outcomes including implementation of guidelines, physician education and improved access to innovative medicines and quality care.
Age-dependent prognostic value of KRAS mutation in metastatic colon cancer.
Authors: Muhammet Ozer, Suleyman Yasin Goksu, Nina Niu Sanford, Todd Anthony Aguilera, Radhika Kainthla, Amy Little Jones, Aravind Sanjeevaiah, Muhammad Shaalan Beg, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2020)

e16085 Background: KRAS mutation is associated with poor prognosis in metastatic colon cancer (mCC). However, the age-dependent prognostic value of KRAS status is unknown. We aimed to confirm if the prognostic impact of KRAS is dependent on the age of diagnosis in mCC. Methods: We identified adult patients with mCC diagnosed between 2004 and 2016 using the NCDB. We compared patients with KRAS mutation and KRAS wild type, stratified according to age group &lt; 50, 50-70, and ≥70. Categorical variables were compared using the chi-square test. We performed the Kaplan-Meier and Cox regression methods for survival analyses. We adjusted for patient and tumor characteristics (included KRAS status, MSI, 18q loss of heterozygosity, side of the primary tumor). Results: A Total of 19,875 patients had KRAS status reported; 43% had KRAS mutation, and 57% were KRAS wild type. Patients with KRAS mutation were more likely to be female, black, have elevated CEA, and have right-sided tumors (all p &lt; .001). In the overall population, patients with KRAS mutation had significantly worse OS compared to patients with KRAS wild type (20 vs. 22 months, p &lt; .001), and this difference was maintained after multivariable Cox regression analysis ( p &lt; .001) (Table). Young patients ( &lt; 50 years) with KRAS mutation had a worse prognosis than those with KRAS wild type in the tumor (23 vs. 29 months, p &lt; .001). KRAS status did not maintain its prognostic value among older age (≥70 years) patients (14 vs. 14 months, p = NS). Conclusions: In this analysis of a national cancer registry, we confirmed that KRAS mutation was an independent poor prognostic factor for mCC. This effect persisted after adjusting for patient and tumor characteristics, including sidedness and MSI status. However, we identified that this prognostic value of KRAS mutation is significant in young mCC patients &lt; 50 years, as compared to older patients. [Table: see text]
Esophageal cancer: How far is close enough?
Authors: Leighton Andrew Elliott, Joseph Vadakara
Journal: Journal of Clinical Oncology (2020)

e19049 Background: According to Surveillance, Epidemiology, and End Results (SEER) data, 5-year survival of esophageal cancer (EC) improved from 4.1% to almost 20% from 1975 to 2016, however, this is still poor compared to other cancers. Chitti et al describe temporal changes in EC mortality by geographic region across the United States (U.S.) and concluded that disparities exist. Other studies described survival disparities for rural communities specific to small cell lung carcinoma, cervical cancer, and breast cancer. Hung et al determined that 1 in 5 rural Americans lived &gt; 60 miles from a medical oncologist. Studies performed outside of the U.S. described no difference in survival with travel distance. No studies on this topic have focused on gastrointestinal malignancy. Our study aimed to associated travel distance with travel time to a medical oncology treatment center as time can vary greatly with similar distances. We focused specifically on esophageal cancer considering its high mortality rate and significant effect on quality of life. Methods: We performed a descriptive analysis of a retrospective cohort (January 2008 – August 2019) of all individuals diagnosed with esophageal cancer using data from the institutional Oncology Tumor Registry, a regional cancer registry, and the electronic health records (EHR) of patients throughout a rural integrated health system in Pennsylvania. We geocoded home addresses using Google Maps Geocoding application programming interface (API) and the average driving distance and time to the nearest medical oncology treatment center was calculated using the Google Maps Distance Matrix API. Travel time compared to cancer stage was also assessed. Addresses listed over 100 miles were evaluated for documentation accuracy via the EHR. Results: A total of 1157 adult patients diagnosed with esophageal cancer was evaluated; of these, 433 had a documented outpatient chemotherapy infusion site visit. The mean travel distance to a medical oncology treatment center was 19.8 miles with a median of 16 miles; this correlated with a mean travel time of 28.2 minutes. Seventy-five percent of the population lived within 26 miles of an outpatient oncology center. The maximum distance traveled was 139 miles, which was confirmed via EHR chart review. Conclusions: This study shows that a rural population may not necessarily experience disparity in travel distance and time to a medical oncology treatment center. This was an exploratory study and further analysis will be needed to see if there was any statistically significant difference in survival based on distances when stratified by stage, age, treatment modality, etc.