tbuckley/cabot-search huggingface dataset:
Relationship between nutritional status and length of hospital stay in oncological surgery.
Authors: Carl Meissner, Ronny Otto, Joerg Fahlke, Mathias Mueller, Karsten Ridwelski
Journal: Journal of Clinical Oncology (2020)

e13591 Background: In Germany, a serious illness is the main cause of malnutrition. Various studies have already shown that the length of time in hospital for various diseases and operations in malnourished patients increases. This leads to a deterioration in the quality of life of the patient and results in considerable costs for the health care system. Methods: In order to investigate the relationship between nutritional status and length of hospital stay, a patient group of 363 patients who had a tumor with the primary tumor in the gastrointestinal tract was first identified. All patients had an NRS score of 3 or greater and a meaningful laboratory with regard to protein and albumin levels and / or results of a bioelectrical impedance analysis. The average length of stay for these patients was determined depending on the various parameters. Results: The present study shows that malnourished patients have to stay in the hospital for between 2 and 11.1 days longer. When evaluating the NRS score, the protein and albumin level as well as the BCM and the ECM / BCM index, a longer hospital stay of malnourished patients compared to those who were not malnourished was demonstrated. The BMI is an insufficient parameter to describe the nutritional status. An extension of the length of hospital stay cannot be demonstrated only on the basis of the BMI. Conclusions: Since an inadequate nutritional status obviously affects the length of hospital stay in oncological patients, they should be examined early for malnutrition. The length of stay can be shortened through nutritional therapy measures, which also leads to a significant reduction in costs.
Treatment outcomes in melanoma with brain metastases in the era of immunotherapy: An analysis of the National Cancer Database.
Authors: Justin Moyers, Esther G Chong, Daniel Sufficool, Gayathri Nagaraj
Journal: Journal of Clinical Oncology (2020)

e14513 Background: Brain metastases (BM) are a major cause of morbidity and mortality in metastatic melanoma. Radiotherapy (RT) and/or surgery are the standard of care for treating brain metastases. The introduction of immune checkpoint inhibitors has drastically improved disease outcomes since approved in 2011 and recent trials have exhibited intracranial activity. We aim to assess the added survival benefit of immuno-oncologic agents (IO) for melanoma with BM in National Cancer Database. Methods: We queried the database from 2011 to 2015 for Stage IV melanoma with BM. RT treatments were divided into stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), or no brain radiation; those with insufficient documentation were excluded. Patients were further divided into receipt of IO or no receipt of IO; those without documentation were excluded. Concurrent (CC) treatment was defined as IO begun before or during RT treatment; sequential (SQ) therapy was defined as IO begun after RT. Survival analyses were performed by Kaplan-Meier method and log-rank test. Results: Among 8,561 metastatic melanoma patients with documentation of metastatic sites, 3,008 (35.1%) had documented BM. Median overall survival (mOS) for all stage IV melanoma was 10.5 months with worse survival for those with BM compared to those without (mOS 6.0 v 14.7 m; p &lt; 0.01). Among 3,008 cases with survival data available, 2,762 met criteria for survival analysis of BM treatments. Table summarizes treatment outcomes between cohorts by RT and IO treatment categories. IO + SRS had improved survival compared to all other treatment groups (mOS 19.9 m; p &lt; 0.01). No difference in survival between SRS and IO alone was observed (mOS 10.9 v 11.5 m; p = 0.56). WBRT as single modality did not appear to improve survival over no therapy (mOS 4.2 v 3.3 m; p = 0.35). 436 cases had documented time course between IO and RT. IO was given SQ with RT in 69% of SRS (n = 158/230) and 67% of WBRT (n = 137/206) treated patients. In SRS + IO cohort, survival was longer for SQ compared to CC treatment (23.5 v 13.1 m; p &lt; 0.01). Survival was similar in WBRT for SQ v CC groups (6.8 v 7.9 m; p = 0.62). Conclusions: Superior survival is realized for those who receive IO in addition to SRS for BM. IO and SRS as single modality have similar outcomes, while WBRT seems to add little survival benefit to IO or no therapy. [Table: see text]
<i>NTRK</i> gene fusions in bilio-pancreatic cancers.
Authors: Anne Demols, Luis Perez-Casanova, Laureen Rocq, Manon Charry, Nancy De Nève, Audrey Verrellen, Ali Ramadhan, Claude Van Campenhout, Sarah De Clercq, Calliope Maris, Jean Closset, Valerio Lucidi, Isabelle Salmon, Nicky D'Haene
Journal: Journal of Clinical Oncology (2020)

e16664 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( NTRK) have been identified in approximately 1% of solid tumors and inhibitors of TRK have been shown to have anti-tumor activity regardless of tumor type. NTRK gene fusions have been previously reported in bilio-pancreatic tumors. It is of interest therefore to determine incidence and molecular characteristics of NTRK gene fusions in these patients. Methods: Formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies or cytological samples of biliary tract tumors (BTC) including intra-hepatic (IH), extra-hepatic (EH), perihilar cholangiocarcinoma (PH) and gallbladder tumors (G), and pancreatic adenocarcinoma (PA) were retrieved from the tumor bank of CUB Hôpital Erasme between JAN 2010 and OCT 2019. A two-step diagnostic method incorporating immunohistochemistry (IHC) screening followed by NGS analysis was used. Pan–TRK IHC (monoclonal antibody clone EPR17341 [AbCam, Cambridge, MA]) was used for the screening method. Staining intensity (negative, weak, moderate or strong) pattern (diffuse, focal or rare positive cells), and localization (cytoplasmic or nuclear) were evaluated. The presence of at least weak staining tumor cells led to testing by a RNA-based NGS panel (Oncomine Focus Assay ThermoFisher Scientific). Results: For BTC, 162 archival tumors samples have been selected. 149 samples were suitable to perform IHC.17 samples were IHC positive including 9 IH, 3 PH, 2 EH and 3 G tumor samples. Intensity of staining was weak in 16 samples and moderate in one. Staining location was cytoplasmic (14/17), nuclear (2/17), and nuclear+cytoplasmic (1/17). Pattern of staining was rare positive cells (2/17), focal (4/17) and diffuse (11/17). NGS testing of the 17 IHC positive samples revealed a single NTRK3 gene fusion ( ETV6(4)- NTRK3(14)). In this PH tumor, IHC had a weak focal cytoplasmic and nuclear staining. Overall in the patients screened by IHC and confirmed by NGS, percentage of NTRK fusions was 0.67 %. For PA, 319 archival tumor samples have been selected and 297 were suitable for IHC. 19 samples were IHC positive. Intensity of staining was weak in 18 samples and moderate in one. Staining location was cytoplasmic (18/19) and nuclear (1/19). Pattern of staining was focal in 2 cases and diffuse in 17 cases. No fusion was detected by NGS. Conclusions: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to the emergence of possible treatment with specific TRK inhibitors. These results support the use of NGS to confirm positive IHC results during diagnostic screening.
Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status: Analysis of untreated RAS-wildtype mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109).
Authors: Annika Kurreck, Michael Geissler, Uwe Marc Martens, Jorge Riera-Knorrenschild, Jobst Greeve, Axel Florschütz, Swen Wessendorf, Thomas Jens Ettrich, Stephan Kanzler, Nörenberg Dominik, Max Seidensticker, Swantje Held, Petra Buechner-Steudel, Jens Atzpodien, Volker Heinemann, Sebastian Stintzing, Thomas Seufferlein, Andrea Tannapfel, Anke Reinacher, Dominik Paul Modest
Journal: Journal of Clinical Oncology (2020)

e16055 Background: In patients with mCRC, dynamics of response and disease progression may play a critical role in the understanding of long-term outcome. Depth of response (DpR), time to DpR and post-DpR survival represent innovative endpoints to evaluate response and disease dynamics. Methods: We evaluated DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR image to tumor progression or death), and post-DpR overall survival (pOS = DpR image to death) with special focus on BRAF mutational status in 66 patients. Results: BRAF wildtype (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (-57.6% vs. -40.8%, p = 0.013) with a comparable time to DpR (BRAF-WT 4.0 (95% CI 3.1-4.4) months vs. BRAF-MT 3.9 months (95% CI 2.5-5.5), p = 0.8852). pPFS was 6.5 (95% CI 4.7-8.4) versus 2.6 (95% CI 1.0-3.9) months in favor of BRAF-WT patients (HR: 0.24 (95% CI 0.11-0.53; p &lt; 0.001). This also transferred into a significant difference in pOS (33.6 (95% CI 30.0-42.1) versus 5.4 (95% CI 4.7-16.1) months, HR: 0.27 (95% CI 0.13- 0.55); p &lt; 0.001). Further data including primary tumor site will be presented at the meeting. Conclusions: BRAF-MT patients treated within the VOLFI-trial derive a less profound response to treatment as compared to BRAF-WT patients. The substantial difference in outcome according to BRAF status is evident after achievement of deepest response with BRAF-MT patients hardly deriving any further disease control beyond DpR. This is reflected by pPFS and pOS. Our observations hint towards aggressive tumor evolution in patients with BRAF-MT-tumors which may already be molecularly detectable at time of DpR. These findings somehow challenge the currently practiced aggressive treatment strategy of FOLFOXIRI-based 1 st -line regimens as they may stimulate treatment resistance and suggest that close monitoring of BRAF-MT patients may include the continuous monitoring of clonal evolution.
Changes of serum cytokeratin 19 fragment in postoperative patients with non-small cell lung cancer
Authors: 周永新, 王永武, 梅运清, 冯靖, 蔡建志, 孙益峰, 季强, 李大文
Journal: BMJ (2007)

目的 探讨血清角蛋白19片段(CYFRA21-1)在非小细胞肺癌术后患者预后判断及随访监测中的价值.方法 回顾性分析我院207例非小细胞肺癌患者手术前后的CYFRA21-1结果,分析其与患者预后、复发和转移之间的关系.CYFRA21-1测定采用放射免疫分析方法.结果 所有患者平均随访37个月,治疗前总的阳性率为42.0%(87/207),其中腺癌34.6%(27/78),鳞癌为48.8%(60/123),两者间差异有统计学意义(χ2=3.901,P＜0.05).全组、Ⅱ期和Ⅲ期术前阳性患者的生存率均较阴性患者差(P＜0.05).术后27个月随访中患者再次出现阳性或持续阳性对诊断是否有转移或复发的敏感性为52.9%(54/102),特异性为91.4%(96/105),而对于术前阳性的患者,则敏感性为81.3%(39/48),特异性84.6%(33/39).结论 术前CYFRA21-1阳性非小细胞肺癌患者的预后差于阴性患者,CYFRA21-1可作为监测肿瘤是否有复发或转移的指标。
Burden of genetic testing in an academic biobank by pathological and family history-based criteria in prostate cancer (PCa).
Authors: James Ding, Emily Feld, Anh Le, Pauleen Sanchez, Jacquelyn Powers, Abigail Doucette, Peter Edward Gabriel, Michael McLaughlin, Rachel Kember, Joellen Weaver, Renae Judy, Daniel Rader, Scott Damrauer, Daniel Lee, Vivek Narayan, Susan M. Domchek, Lauren Schwartz, Kara Noelle Maxwell
Journal: Journal of Clinical Oncology (2020)

1576 Background: Approximately 5% of localized PCa and 12% of metastatic PCa are associated with germline mutations in DNA repair genes. The National Comprehensive Cancer Network (NCCN) issued genetic testing guidelines to identify PCa patients (pts) likely to harbor a germline DNA repair mutation. The overall burden of this guideline-based, resource-intensive genetic testing is unknown. Using supervised phenotype-genotype information extraction algorithms, we determined the projected genetic testing burden at a single institution adhering to NCCN PCa genetic testing guidelines. Methods: A PCa cohort of 2127 pts was identified from the Penn Medicine BioBank via ICD 9/10 codes. Phenotypic data were extracted from the Penn Medicine Cancer Registry and electronic health record systems via natural language processing and manual chart review. Pts were classified based on 9 germline genetic testing criteria outlined in the NCCN PCa guidelines (Version 4.2019). Results: 895/2127 pts met at least 1 of the 9 NCCN genetic testing criteria, corresponding to a 42.1% overall genetic testing burden. 35.2% qualified for testing via high-risk localized PCa and 6.4% qualified via metastatic disease. Of the pts with localized PCa (n=2014), 15.1% qualified for genetic testing via high Gleason score, 5.1% via high-risk family history, 3.7% via PSA&gt;20ng/mL, 8.7% via Ashkenazi Jewish descent, and 0.8% via intraductal/ductal histology. Conclusions: In this single-center PCa cohort, germline genetic testing was NCCN-guideline recommended for a larger proportion of pts than would otherwise be expected based on previously published reports. Future studies are needed to validate the sensitivity and specificity of these criteria for identifying germline mutations. Our study also highlights a need for novel methods to improve the efficiency of genetic testing for a large cohort. [Table: see text]
Epidemiology and patterns of care of intrahepatic cholangiocarcinoma (iCCA) in France: Real-life data from the French National Hospital‐Discharge Summaries Database System (PMSI).
Authors: Cindy Neuzillet, Corinne Emery, Clément Teissier, Stéphane Bouée, Astrid Lièvre
Journal: Journal of Clinical Oncology (2020)

e16624 Background: Little is known about epidemiology and patterns of care of iCCA in daily clinical practice. The aims of this study were to estimate from real-life data the incidence of iCCA in France and to describe the healthcare pathways of these patients (pts). Methods: A retrospective analysis was carried out using the nationwide prospective French PMSI database. All pts with a new diagnosis of "carcinoma of the intrahepatic bile duct" who had a 1 st hospital stay in Medicine, Surgery and Obstetrics departments (MSO) between 2014 and 2015 with a 2-year follow-up were included. Data related to the 1 st identified stay (S1) in MSO and on all subsequent stays in MSO, Aftercare and Rehabilitation (SSR) or Home Hospitalizations (HAD) were analyzed. Results: A total of 3,650 new iCCA cases were identified. At S1 (admission via emergency room [ER] in 28%), median age of pts was 73y, 57% were male and 35% had metastases. Jaundice/anemia/ascites/cholangitis were reported in 17%/16%/12%/7%, respectively. Pts care at S1 was mainly provided in general hospitals (CHG, 60%), rather than university hospitals (CHU, 15%), private (20%) or cancer centers (CLCC, 6%). 896 (24%) pts died during S1: they were more frequently hospitalized via ER (48% vs 23%), metastatic (52% vs 35%) and symptomatic. Subsequent stays were identified for 2,507 pts (69%). Similarly to S1, most pts were managed in CHG during their follow-up (70% vs 20% in CHU and 12% in CLCC). Based on the number of pts treated over the study period, centers were classified as low (≤5 pts, 68%), intermediate (5-20 pts, 26%) and high volume ( &gt; 20 pts, 6%). 47% of the high-volume centers were CHU/CLCC. Three healthcare pathways were defined: surgery (n = 519; 14%), chemotherapy (CT) without surgery (n = 812; 22%) and best supportive care (BSC) (n = 2,319; 63%). CT, surgery and BSC were most frequently performed in CLCC, CHU and CHG, respectively. Pts who received CT (mean time between S1 and start of CT: 1.9 months) were younger, less frequently hospitalized via ER and less symptomatic at S1. A palliative care code was associated with S1 in 25% of pts and with a subsequent MSO/SSR/HAD stay in 60%. Conclusions: This real-life, medico-administrative study, covering all hospitalized patients in France, reveals a higher incidence of iCCA than that previously reported by cancer registries. It also highlights the severity of this disease, the central role of CHG in the management of pts and the expertise of CHU and CLCC for surgery and CT, respectively.
FIH phase I dose escalation study of FN1501, an investigational FLT-3 inhibitor with multiple targets in patients with relapsed or refractory solid tumors and acute myeloid leukemia.
Authors: Gary Edward Richardson, Ulka N. Vaishampayan, Viviana Bozon, Ai-Min Hui, Stephen K. Williamson
Journal: Journal of Clinical Oncology (2020)

e15656 Background: FN1501 inhibits various tyrosine kinases as CDK4/6, KIT, PDGFR, ALK and RET proteins, particularly potent on FLT3 and EGFR2. A Ph1 FIH trial for patients (pts) with solid tumors and Acute Myeloid Leukemia (AML) is on-going 1 . Preclinical data showed that FN1501 inhibits the phosphorylation of FLT3 and its downstream kinase STAT5 in human acute leukemia cell lines, arrests the cell cycle inducing apoptosis and inhibits growth and proliferation of leukemia cells. It has anti-proliferation activity against other leukemia cell lines bearing FLT3 mutations, and lymphoma cell lines 2, 3 . Methods: 26 pts with advanced solid tumors or AML enrolled in the escalation phase and received IV FN1501 on days 1, 3, 5, 8, 10 and 12 on 21-day cycles. Primary objectives are safety and MTD, secondary objectives include preliminary activity, PK and PD. Plasma PK were assessed at different timepoints pre and post dose in C1 and C2. Results: As of 6FEB20, 26 pts have been treated in 7 ascending doses of 2.5mg, 5mg, 10mg, 15mg, 22.5mg, 30mg and 40mg. A 54 mg dose cohort is on-going. No DLTs, no SAEs or deaths associated to FN1501 have been reported. 12 pts (46%) had one grade 3 or higher TEAE and 7 pts (27%) had dose interruptions due to a TEAE. Administration of FN1501 to pts with metastatic solid tumors has resulted in anti-tumor activity. 9 pts had durable stable disease across 4 doses in renal, endometrial, ovarian, gastric, appendix and thymic malignancies. One pt with serous endometrial carcinoma achieved a cPR after 2 cycles at 40mg with a 47% tumor size reduction (target lesions). As of 26Oct19 preliminary PK data showed a t1/2 of approximately 12.7-19.0 hours post-dose. Mean Cmax and AUC increased proportionally with dose and Clearance is consistent among all doses. Conclusions: This on-going Ph1trial of FN1501 is providing evidence of dose or exposure effects as a single agent in patients with solid tumors. Since FN1501 targets multiple kinases on addition to FLT3, antitumor activity beyond AML is also being observed, suggesting that the potent inhibitory effects of other tyrosine kinases, including EGFR2 may be playing a role in the regulation of cellular functions, cell growth, differentiation and angiogenesis effects. FN1501 has been well tolerated and AEs are manageable. Genomic alterations investigations are underway to identify candidate biomarkers useful for predicting sensitivity to the multiple FN1501 tyrosine kinases. Further development of FN1501 is warranted. Clinical trial information: NCT03690154.
提高全科医师临床实践能力教学的质量
Authors: 李大蓉, 贾建国
Journal: BMJ (2007)

高素质全科医学人才的短缺已成为制约社区卫生服务发展的瓶颈,加大全科医师培训力度,尽快建立起品质高、数量足的全科医师队伍已刻不容缓.20世纪末北京市启动了全科医学培训工程,就是要解决向全科医学服务转轨和并轨中存在的人才缺少问题。
Immune checkpoint inhibitors (ICI) response in metastatic non-small cell lung cancer (NSCLC) patients with WNT pathway mutations (APC/CTNNB1).
Authors: Patricia Iranzo, Ana Callejo, Anna Pedrola, Nuria Pardo Aranda, Alejandro Navarro, Alex Martinez-Marti, Susana Cedres Perez, Javier Ros, Juan David Assaf, Nadia Saoudi, Caterina Carbonell, Ramon Amat, Joan Frigola, Jose Jimenez, Rodrigo Dienstmann, Hector G. Palmer, Ana Vivancos, Enriqueta Felip
Journal: Journal of Clinical Oncology (2020)

e15137 Background: APC and CTNNB1 mutations (mut) lead to an aberrant activation of the WNT pathway which has been linked to lack of benefit of immunotherapy in patients (pts) with lung cancer. Our aim is to describe the pts’ characteristics of a NSCLC cohort with APC or CTNNB1 mut and their association with outcomes (Overall survival [OS] and Progression-Free-Survival [PFS]) when treated with ICI. Methods: We selected NSCLC pts with mut in APC or CTNNB1 by targeted NGS (tissue), whole exome sequencing (tissue) or Guardant 360(plasma) between January 2014 and October 2019. Functionality of mut and β-catenin protein expression by immunohistochemistry (IHC) were correlated with outcome. Results: We identified a total of 37 patients with 44 mutually-exclusive mutations in APC (31) or CTNNB1 (6), 25 adenocarcinomas (68%). Of APC mut cohort, 16 had pathogenic mut (52%) and 15 of unknown significance (48%). All 6 CTN NB1 mut were known pathogenic. Median OS (mOS) in metastatic setting was 21.6 months (m) (CI95% 14.9-NR), without differences between APC and CTNNB1 groups (HR 1.5, p = 0.4) or when stratified by mut functionality (HR 1.1, p = 0.8). Globally, 21 pts received treatment with ICI (57%, 19 APC, 2 CTNNB1), median PFS (mPFS) was 5.43m (1.8-21.7), with trend for shorter mPFS in CTNNB1 mut (mPFS 1.7m) vs. APC mut (mPFS 6.6m, HR 1.5, p = 0.1). Among patients treated with ICI, 8 (38%) had coexisting driver targetable alterations ( EGFR, ERBB2 or MET) and 13 (62%) other functional mut were found ( TP53, KRAS, STK11, BRCA2, ATM). mPFS was 3.9m (1.8-NR) in the subgroup with driver mut vs. 6.6m (1.4-NR) for remaining pts (HR 1.36, p = 0.5). In 15 pts β-catenin IHC was performed, being positive in 7 cases (47%), 4 of them received ICI with a mPFS 12.1m. Conclusions: In our experience, benefit with ICI is not influenced by the presence of APC mut, and small numbers of CTNNB1 cohort limit conclusive statements. Additional studies are required to assess WNT pathway activation on top of genomics and correlate with the ICI efficacy.
The practice of standardized training of general practitioners in Zhongshan Hospital
Authors: Qian Chen, Zhigang Pan, Tianhao Wang
Journal: BMJ (2015)

Objective
To review the standardized training of General practitioners (GPs) in Zhongshan Hospital since 2010.


Methods
Sixty seven GP trainees were recruited by Zhongshan Hospital since 2010.A retrospective analysis was carried out about the training methods, training content, assessment methods and training management.


Results
The pass rate of hospital examination was 100.0%.Sixteen out of nineteen GP residents of grade 2010 passed both the final examination and medical licensing examination, and completed the training plan; the remaining 3 trainees did not pass the licensing examination, among whom 2 extended the training and passed the exam eventually, and 1 dropped off.Sixteen out of seventeen in grade 2011 passed the medical licensing examination and were preparing for 2014 graduation examination.The training mode of human-centered and competency-based assessment system was established.


Conclusion
Zhongshan Hospital has accumulated rich experience in standardized training of GPs, established a system of training and assessment, and it will be continuously improved in the future.


Key words: 
Training; Education, medical; General practitioner
Mental Health Outcomes Among Frontline and Second-Line Health Care Workers During the Coronavirus Disease 2019 (COVID-19) Pandemic in Italy
Authors: Rodolfo Rossi, Valentina Socci, Francesca Pacitti, Giorgio Di Lorenzo, Antinisca Di Marco, Alberto Siracusano, Alessandro Rossi
Journal: JAMA Network Open (2020)

This cross-sectional study reports on symptoms of posttraumatic stress disorder, depression, anxiety, and insomnia among health care workers in Italy during the coronavirus disease 2019 (COVID-19) pandemic.
Somatic symptoms in patients with depressive disorder :an analysis of 736 cases
Authors: Jie Zhang
Journal: BMJ (2010)

The somatic symptoms of patients with depressive disorder in a general hospital were retrospectively analyzed.From May 2004 to April 2009,736 patients in Psychological Clinic were diagnosed as depressive disorder,among them 723(98.2%)had somatic complains.The somatic symptoms were complex and involving several systems,nervous system,digestive system and cardiovascular system were the most common.It is necessary to recognize the typical somatic symptoms of depressive disorders to avoid misdiagnosis.

Key words: 
Depressive disorder; Somatoform symptom