tbuckley/cabot-search huggingface dataset:
Long-term prospective health related quality of life (HRQoL) outcomes: Impact of active surveillance before treatment of low risk prostate cancer (PCa).
Authors: Nathan Jung, Jason Frankel, Galen Conti, Christopher Porter, John Paul Flores
Journal: Journal of Clinical Oncology (2020)

e17518 Background: The treatment options for low risk PCa are active surveillance (AS), radiation therapy (RT), and radical prostatectomy (RP). HRQoL studies with long term follow up are lacking. We evaluated HRQoL of initial active surveillance vs initial treatment. Methods: The Center for Prostate Disease Research (CPDR) database was used. HRQoL data was collected for 5 years with the Expanded Prostate Cancer Index Composite (EPIC) and the 36-item Medical Outcomes Study Short Form (SF-36). Patients had low risk PCa, age less than 75, and follow up data of at least 1 year. AS was defined as no definitive treatment within 12 months of diagnosis and repeat biopsy or PSA within 18 months of diagnosis. Results: Patient characteristics are located in the table. Baseline HRQoL scores were comparable across treatment groups for all HRQoL domains, except for sexual function and bother, and physical health where RT were worse than RP. Of the 68 patients classified as AS, 4 had brachytherapy, 9 had hormone therapy, 38 had RP, and 17 had XRT as a first treatment after terminating their AS. In the Generalized Estimating Equations (GEE) model, the HRQoL scores were compared. Multivariate analysis was done accounting for baseline differences. Urinary function (p = 0.0017), urinary bother (p = 0.0028), hormone function (p = 0.035), bowel bother (p = 0.0122), sexual function (p &lt; 0.01), sexual bother (p &lt; 0.01), and physical health (p = 0.0457) were significantly different. For urinary function and bother, XRT had the best HRQoL scores at most time points, with AS getting worse over time as patients went on to receive treatment. AS had worse scores with hormone function and sexual function. RP had the best scores for bowel bother over the course of the study, but had the worst initial scores in sexual bother, which got better over time. Hormone bother (p = 0.5574), Bowel function (p = 0.098), mental health (p = 0.7231) were not statistically different between groups. Conclusions: Initially AS results in improved HRQoL. For those patients who undergo treatment after AS, HRQoL is no worse than those who got treatment initially. [Table: see text]
Evaluation of clinical competence by computer-based case simulation and objective structured clinical examinations for general practitioners
Authors: 李鲁, 李勤, 耿晓北, 丁盟琪
Journal: BMJ (2007)

目的 探讨运用全科医师计算机模拟病例考试和客观结构化临床考试(OSCE)在全科医师实践技能评价中的应用价值.方法 对已完成全科医师规范化培训的18名学员分别进行计算机模拟病例考试和OSCE,对考试成绩分别进行Pearson相关性检验和多元线性回归分析.结果 计算机模拟病例考试成绩与OSCE总评分及临床技能评分具有相关性(r=0.475,P=0.047;r=0.568,P=0.014;F=7.622,P=0.014).结论 计算机模拟病例考试方法可替代OSCE的部分考试项目测试全科医师实践能力。
Follow-up of graduates of general practice standardized training program
Authors: Jian Wang, Shan-zhu Zhu
Journal: BMJ (2012)

Objective To evaluate the outcomes of the standardized general practice training program in Shanghai Zhongshan Hospital,Fudan University.Methods Total 183 graduates of 11cohorts completed general practice standardized training in Shanghai Zhongshan Hospital,Fudan University since 2000.A questionnaire survey on the career status was conducted and 173 graduates were responded successfully with a respond rate of 95％.Results Among 173 responded graduates,55 were males and 118 females with an average age of 33.8 y.One hundred and sixty nine graduates (98％) were still engaged in general practice,including 148 working in Shanghai and 21working in other cities.For professional ranks,3 of them were chief physicians,17 vice-chief physicians,81attending physicians and 72 residents (34 of them would be soon promoted to attending physician).Among the 173 graduates,39 were heads of GP teams and 49 held administrative positions.Up to February 2011,81graduates had published 184 papers as firstauthor,32 were successful in grant application and 33 research grants were awarded with a total fund of 2.487 million Yuan.Thirteen graduates obtained the chance for further study of general practice in Hong Kong,Taiwan or abroad.Conclusion The follow-up study shows that the outcomes of general practice standardized training program in Shanghai Zhongshan Hospital are satisfactory.

Key words: 
General Practitioner; Questionnaires; Standardized training
Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment targeting the cytokine storm in COVID-19
Authors: Maria Dalamaga, Irene Karampela, Christos S. Mantzoros
Journal: Metabolism (2020)

The most severe presentation of COVID-19 is characterized by a hyperinflammatory state attributed to the massive pro-inflammatory cytokine release, called "cytokine storm". Several specific anti-inflammatory/immunosuppressive agents are being evaluated by ongoing clinical trials; however, there is currently insufficient evidence for their efficacy and safety in COVID-19 treatment. Given the role of phosphodiesterase 4 (PDE) 4 and cyclic adenosine monophosphate in the inflammatory response, we hypothesize that selective PDE4 inhibition may attenuate the cytokine storm in COVID-19, through the upstream inhibition of pro-inflammatory molecules, particularly TNF-α, and the regulation of the pro-inflammatory/anti-inflammatory balance. Conversely, other anti-cytokine agents lead to the downstream inhibition of specific targets, such as IL-1, IL-6 or TNF-α, and may not be efficient in blocking the cytokine storm, once it has been triggered. Due to their mechanism of action targeting an early stage of the inflammatory response and ameliorating lung inflammation, we believe that selective PDE4 inhibitors may represent a promising treatment option for the early phase of COVID-19 pneumonia before the cytokine storm and severe multiorgan dysfunction take place. Furthermore, PDE4 inhibitors present several advantages including an excellent safety profile; the oral route of administration; the convenient dosing; and beneficial metabolic properties. Interestingly, obesity and diabetes mellitus type 2 have been reported to be risk factors for the severity of COVID-19. Therefore, randomized clinical trials of PDE4 inhibitors are necessary to explore their potential therapeutic effect as an adjunct to supportive measures and other therapeutic regiments.
Use of clinical classification software to differentiate good versus poor prognostic patients with ovarian cancer: A SEER-Medicare database analysis from the viera study.
Authors: Gboyega Adeboyeje, Kaushal Desai, Shahed Iqbal, Jinghua He, Matthew J. Monberg
Journal: Journal of Clinical Oncology (2020)

e18069 Background: Historically, recurrence in ovarian cancer (OC) following first-line (1L) chemotherapy (CT) occurs in up to 80% of patients within 2 years. The Clinical Classification Software (CCS) systematically classifies thousands of ICD-9 codes into a smaller number of clinically meaningful categories. We sought to use CCS and other routinely collected variables to differentiate the clinical and demographic profiles of patients with good prognosis (GP) versus poor prognosis (PP) in the United States (US). Methods: This was a retrospective cohort study of newly diagnosed (FIGO stage II - IV), treatment-naïve patients, ≥ 66 years, who received 4-10 cycles of platinum-based 1L CT between Jan 2009 - Dec 2015 using the SEER-Medicare database, a nationally representative cancer registry. Patient were assumed to have progressed to a subsequent line of therapy following a gap between consecutive CT cycles ≥ 63 days. Patients were classified as GP if alive ≥4 years with no further treatment following 1L CT; PP was defined as receipt of ≥2L CT within 12 months of initial 1L CT. Demographic and prognostic characteristics were assessed during a 6-month baseline period prior to initiation of 1L CT. We assessed clinically meaningful differences in baseline characteristics with absolute standardized differences (ASD) using a threshold of 0.1 (indicating negligible difference between two cohorts). Results: There were a total of 2,262 patients (mean age: 74.6 ±6.2 years) including 251 GP (11%) and 209 PP (9%) patients (table below). PP patients were significantly more likely to be older than 70 years, and present at stage IV, liver disease and ascites, and anemia at diagnosis. PP patients were also less likely to have primary debulking surgery. Conclusions: Approximately one tenth of OC patients received no further treatment 4 years after the initial treatment with contemporary standard of care. GP may be differentiated from PP on the basis of commonly used clinical characteristics such as stage and also specific comorbidities such as liver disease and ascites. [Table: see text]
Outcomes of Burkitt lymphoma (BL) managed in academic (Acad) or community (Comm) centers: real-world evidence (RWE) from 30 US sites.
Authors: Adam J. Olszewski, Izidore S. Lossos, Andrzej Stadnik, Stephen Douglas Smith, Deepa Jagadeesh, Seo-Hyun Kim, Tycel Jovelle Phillips, Seema Naik, Tatyana Feldman, Nishitha Reddy, Suchitra Sundaram, Seth Maliske, Vaishalee Padgaonkar Kenkre, Narendranath Epperla, Malvi Savani, Craig Portell, Neil Palmisiano, Andreas Kirschmer Klein, Andrew M. Evens
Journal: Journal of Clinical Oncology (2020)

8043 Background: Prior analyses have suggested better overall survival (OS) of cancer patients (pts) treated in Acad rather than Comm hospitals, but these disparities may reflect different patient characteristics. We examined outcomes of pts with BL in a large RWE cohort from 30 US healthcare systems (Evens, ASH 2019) with a mix of Acad and affiliated Comm sites. Methods: We collected clinical data on adults with BL diagnosed in 2009-2018, individually assigned to Acad or Comm principal setting of care. We compared duration of chemotherapy (CTx, incl. standard CODOX-M/IVAC, hCVAD/MA, DA-EPOCH), rates of complete response (CR), progression-free survival (PFS), and OS adjusting for age, sex, HIV, performance status (PS), stage, LDH &gt; 3x upper limit of normal (ULN), involvement of bone marrow or cerebrospinal fluid (CSF), reporting adjusted risk (RR) or hazard ratio (HR) with 95% CI. Results: Among 641 BL pts, 77 (12%) were managed in Comm setting. Comm pts had lower median age (45 vs 48 in Acad, P= .049), less frequent HIV (13% vs 23%, P= .039), less marrow (21% vs 36%, P= .009) or detected CSF involvement (8% vs 15%, P= .11), and less LDH &gt; 3xULN (21% vs 41%, P= .013), with no significant differences in sex, PS, stage, hemoglobin, or receipt of CTx (97% vs 99%). Acad sites more often applied standard intensive CTx regimens (93% vs 85%, P= .03) and rituximab (92% vs 79%, P= .001), without significant difference in median time to CTx ( P= .69) or treatment-related mortality (TRM, P= .16). Pts managed in Comm (vs Acad) sites were less likely to achieve CR (61% vs 75%, P= .03; RR = 0.79 [0.65-0.95]) and had worse 3-year PFS (46% vs 67%, log-rank P= .003; HR = 2.17 [1.51-3.14]) and OS (53% vs 72%, P= .006; HR = 2.20 [1.48-3.25]). There was no significant interaction with age, sex, HIV, PS, or CSF involvement. Excess mortality concentrated in the 1 st year of follow-up. CR, PFS, and OS appeared similar between Acad and Comm settings for pts receiving hCVAD or DA-EPOCH, but outcomes were significantly worse in Comm setting for pts receiving CODOX-M/IVAC. Median number of cycles did not differ between Comm or Acad sites, but median duration of CODOX-M/IVAC delivery was significantly longer in Comm setting (113 vs 101 days, P= .023). Conclusions: In this large RWE analysis, superior outcomes of adults with BL in Acad setting were not explained by baseline patient characteristics or TRM. Differences in the use of standard CTx regimens, rituximab, duration of Ctx, and CR rates suggest need for further research on potential barriers to delivery of intensive CTx for BL in a broader Comm setting.
以咯血为首诊症状会厌癌一例
Authors: 李凯述, 左凯, 张颖, 于立萍, 王新安, 甘红梅
Journal: BMJ (2011)

患者男,59岁.因无明显诱因咯血10余天于2010年8月9日入院,多为痰中带血,偶有咯血.无发热、胸痛,无心悸及心前区不适,无全身皮疹及疱疹,无鼻衄及牙龈出血,无呕血及黑便.患者饮食和睡眠、二便如常。
Immune toxicity and flow cytometry of circulating blood cells in cancer patients receiving immune therapy.
Authors: Saad A. Khan, Noah Sorrelle, Rolf A. Brekken, Rong Lu, Mitchell S. von Itzstein, Donglu Xie, David Hsieh, Yvonne Gloria-McCutchen, Jessica Saltarski, Mary Watters, Benjamin Aaron Bleiberg, Vinita Popat, Murtaza Ahmed, Yuqing Zhang, Farjana Fattah, Shaheen Khan, Jason Park, David E. Gerber
Journal: Journal of Clinical Oncology (2020)

e15126 Background: The mechanisms by which immune checkpoint inhibitors (ICI) cause immune related adverse events (irAE) are not clear. No current blood tests predict which patients will suffer irAEs. Methods: 70 cancer patients had blood drawn prior to ICI and then 4-6 weeks later. 63 had lung cancer; median age was 69 yrs; 21 were female and median ICI treatment duration was 142 days. Patient blood samples were analyzed using flow cytometry for over 50 lymphoid and myeloid markers to determine levels of circulating white blood cells, as well as their changes over time. Medical records were reviewed for irAE’s grades in 8 groups: rash, colitis, hypothyroidism, hyperthyroidism, hypophysitis, hepatitis, adrenal insufficiency, and pneumonitis. To determine association between toxicity and cell counts we used logistic regression and random forest for the univariate and multivariate analysis. We included a random permutation of the baseline age (which is associated with higher toxicity rates) as the analytical control in the random forest model to help identify the threshold of association strength of a random noise and to identify only those cell subsets that were statistically significant (reported below). Results: Patients with elevated baseline levels of specific subsets of T-cells were more likely to develop irAE’s, and elderly patients were more likely to develop Grade 2 irAE’s. T-cell populations associated with any toxicity included CD3+CD8+PD1+; CD3+CD8+; CD25+CD127lowFoxP3+ and CD3+CD8+Ki-67+. Also, patients who developed any irAE’s demonstrated changes in the following cell types after 2 doses of immune therapy compared to their baseline readings. These included changes in the percentage of circulating cells that were CD3+CD8+PD1+; CD3+CD8+HLA-DR+; CD3+CD4+HLA-DR+; CD3+CD8+CCR7-; CD56+; CD3-CD19-; CD3+CD8+; CD16+CD56dim. Patients with grade ≥2 toxicities, or organ specific toxicities demonstrated statistically significant differing levels of T-cells subsets, though the number of patients in each group was limited. Patients with &gt; median baseline expression of CD3+ CD8+ PD1+ cells had greater survival compared with those that had &lt; median levels. Conclusions: Flow cytometry analysis of patients receiving immune therapy at baseline and 6 weeks after initiating therapy may predict which patients are at greater likelihood of any/organ specific irAEs, potentially leading to an improved understanding their mechanisms. Responding to leukocyte changes by substitution of drugs or shortening of treatment duration may reduce irAEs.
Efficacy of immune checkpoint blockade alone or combined with chemotherapy and smoking status in NSCLC: A systematic review and meta-analysis.
Authors: Shanshan Wang, You-En Lin, Dan Yang, Guoqiang Wang, Shangli Cai, Jun Qian, Chuan Chen, Jianping Xiong, Yu Xu
Journal: Journal of Clinical Oncology (2020)

e21661 Background: Tobacco smoking is a critical cause of mutational burden and immuno-microenvironmental alteration in non-small cell lung cancer (NSCLC). However, the association between tobacco consumption and the synergetic effect of chemotherapy on single-agent immunotherapy remains controversial. Methods: We systematically searched PubMed, the Cochrane Central library and Embase, for the RCTs of ICI in NSCLC with HR for both PFS and OS according to smoking status. Random-effects model were used to pool estimates of survival HR and 95%CI. Subgroup analysis and meta-regression were implemented to investigate the source of heterogeneity. Results: In total, 13 eligible RCTs of 8154 NSCLC patients (6800 ever-smokers and 1354 never-smokers) were included. PFS benefit from immunotherapy comparing standard treatment remarkably differed between ever-smokers and never-smokers (P = 0.005), where significant PFS benefit was observed in ever-smokers (pooled HR = 0.72, 95%CI 0.63-0.81, P &lt; 0.001) instead of never-smokers (pooled HR = 0.98, 95%CI 0.73-1.31, P = 0.90). In never-smokers, the choice of regimen (monotherapy vs. combination therapy) considerably impacted the benefit of PFS (HR = 2.21, 95%CI 1.35-3.61, P = 0.005) and OS (HR = 1.99, 95%CI 1.03-3.82, P = 0.041). Compared to standard treatment, monotherapy worsened PFS (HR = 1.39, 95%CI 1.01-1.90, P = 0.046) and did not improve OS (HR = 0.91, 95%CI 0.72-1.14) in never-smokers, while combination therapy dramatically delayed both progression (HR = 0.63, 95%CI 0.49-0.81, P &lt; 0.001) and death (HR = 0.45, 95%CI 0.25-0.82, P = 0.010). Conclusions: Tobacco smoke was associated with larger PFS, but not OS benefit from immunotherapy. In never-smokers, not ever-smokers, combination with chemotherapy compared to single-agent ICI might confer significantly greater delays of both progression and death. [Table: see text]
Elucidating resistance mechanism to PARP inhibitors for the development of novel therapeutic approaches in high-grade serous ovarian cancer.
Authors: Hagen Kulbe, Wanja Nikolai Kassuhn, Frauke Ringel, Gabriele Welsch, Peggy Treffkorn, Eliane T Taube, David Horst, Jalid Sehouli, Ioana Braicu
Journal: Journal of Clinical Oncology (2020)

6078 Background: PARP inhibitors (PARPi) have been established as a targeted therapeutic approach not only in patients with high-grade serous ovarian cancer (HGSOC) that have genetic loss of function of BRCA1/2-associated DNA repair. However, treatment efficacy varies and neither BRCA mutation, nor homolog recombination deficiency (HRD) status seem to be optimal predictors. Moreover, mechanisms of treatment resistance are poorly understood and novel approaches are urgently required. Methods: Here we created gene expression data of HGSOC patients (n = 52) before PARPi treatment to elucidate key signaling pathways of resistance to increase their efficacy in combinatorial therapeutic strategies. We performed a comprehensive bioinformatics analysis of the differentially expressed genes between the 25% extreme responders (n = 26; 13 each group), including gene set enrichment analysis (GSEA) and causal inference analysis with the CARNIVAL pipeline to elucidate the underlying molecular and regulatory mechanisms governing treatment efficacy and resistance. Results: In accordance with recent publications, we found higher levels of MYC activity in non-responders and deregulation of the Wnt/ß-catenin signaling pathway resulting in PARPi treatment resistance. The pathway enrichment analysis also revealed specific pathways especially PDGFR, FGFR, PI3K/mTOR and MAPK signaling pathway associated with resistant phenotype. Furthermore, we have identified key kinases, particularly JAK1/2 and SRC that might mediate resistance to PARP inhibition. In addition, differential gene expression analysis revealed folate receptor 1 (FOLR1) to be significantly higher expressed in non-responders (logFC = 2.66; p &lt; 0.0026) with the potential as a serum-based biomarker not only for ovarian cancer, as it correlates closely with CA125, but also PARPi treatment efficacy. Conclusions: In conclusion, these findings define a network of pathways, that are crucial to mediate mechanism of PARPi resistance and identified key signaling kinases as therapeutic targets in ovarian cancer.
Diagnostic yield of germline genetic testing following tumor testing in prostate cancer patients.
Authors: Kingshuk Das, Stephen E Lincoln, Nhu Ngo, Daniel Esteban Pineda Alvarez, Shan Yang, Scott T. Michalski, Sarah M. Nielsen, Edward D. Esplin, Robert Luke Nussbaum
Journal: Journal of Clinical Oncology (2020)

1591 Background: NCCN guidelines recommend germline testing for patients with localized or advanced prostate cancer meeting family history or clinical/pathologic criteria. However, the guidelines for somatic molecular analysis generally consider advanced disease only, primarily to inform therapy. As the analytical and clinical specifications of both testing modalities differ accordingly, we examined the results of germline testing following prior somatic testing. Methods: We reviewed somatic and germline variants in an otherwise unselected consecutive series of patients who: (a) had a current or previous diagnosis of prostate cancer; (b) had undergone tumor sequencing; and (c) were referred for germline testing. Indications for germline testing included: potential germline origin of somatic test result, treatment or surgical planning, personal or family history, and patient concern. Results: 208 patients met study criteria of whom 81 (39%) harbored a pathogenic germline variant (PGV) in a cancer predisposition gene. Certain genes were more likely to harbor germline variants, and 98% (81) of PGVs were potentially actionable (Table). 9.6% of PGVs were not reported by somatic testing, reflecting analytical limitations of the somatic testing. Of note, 11 patients (14%) had PGVs identified after diagnosis of a subsequent primary malignancy. Conclusions: The high PGV rate of 39% was unexpected, given reported rates of 11.8% in patients with metastatic prostate cancer and 6% in high-risk localized disease (NCCN)--even considering potential clinician ascertainment bias. This finding, the potential clinical utility of 98% of PGVs identified, the significant proportion unreported by somatic testing, and the fraction of patients diagnosed with a PGV after a subsequent malignancy all suggest that germline testing is an underutilized tool in the care of prostate cancer patients and their families. [Table: see text]