tbuckley/cabot-search huggingface dataset:
Predictors of immunotherapy (IO) response and subsequent tyrosine kinase inhibitor (TKI) response in hepatocellular carcinoma (HCC).
Authors: Samantha Ann Armstrong, Bhavana Pendurthi Singh, Monika Kulasekaran, Petra Prins, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2020)

e16642 Background: Despite advances in understanding the molecular pathways of HCC, therapeutic options are limited and patient survival is dismal. IO is a promising HCC treatment and predicted to become first line therapy. Little is known about indicators predicting a prolonged response to IO or the effects of IO on subsequent TKI treatment. Methods: In this single-institutional retrospective analysis, pts received one of five IO containing regimens with nivolumab, pembrolizumab, atezolizumab plus bevacizumab, durvalumab or cemiplimab until disease progression (PD) or unacceptable toxicity. Relevant clinical factors including, but not limited to: stage, viral etiology, vascular invasion, tumor thrombus, multifocal disease, toxicity grade and additional therapies, were correlated to clinical outcome: progression free survival (PFS), overall survival (OS), response rate (RR), using Pearson’s chi-square test or student's t-test. Responses were assessed using RECIST v 1.1 criteria for stable disease (SD), partial response (PR) and PD were correlated with best response and PFS. OS was calculated by the Kaplan-Meier method. Results: Cohort demographics (n = 76) were: 72% male; 38% African American, 30% Caucasian and 16% Asian; 29% of pts had HBV, 41% had HCV, 1% had both HBV/HCV and 13% had no viral etiology (n = 64). The majority of pts were stage III (43%) or IV (38%). Best response to IO was SD in 65.7% of pts, PR in 25.7% and PD in 8.6%. Median OS was 13m (95% CI 7.9-18.1) from the start of IO and median PFS (n = 65) was 14m (95% CI 6.8-21.2). Median OS and PFS were significantly improved in pts with PR compared to PD (45 vs 8m, p &lt; 0.0005, PFS 15 vs 3m p = 0.007). Both OS and PFS showed benefits for SD of ≥2 months compared to those with PD (11 vs 8m, p &lt; .0005, PFS 5 vs 3m p = .007). Abnormal TSH anytime during IO treatment tended toward prolonged mOS (20 vs 9m p = 0.126). Thirty-five pts received additional lines of therapy after IO, 57% (N = 20) received a TKI and 14.2% (N = 5) received additional IO agents. Those who received TKI upon completion of IO had a significantly improved OS (p = 0.014) versus those who did not; median OS 22 m (95%CI 12.7-31.3) versus 10m (95%CI 5.4-14.6). Conclusions: PR and SD are independent predictors for prolonged PFS and OS in HCC pts receiving IO therapy. Abnormal TSH during IO treatment tended toward improved mOS. In addition data strongly indicates subsequent TKI therapy improves patient outcomes after IO.
Consideration and status quo of the training of GP teachers in Shanghai
Authors: Jian Wang, Shan-zhu Zhu
Journal: BMJ (2009)

To introduce the achievements and experiences made by the Training Center of GP teachers.since its establishment,in training hospital-based GP teachers and community-based GP teachers,and to discuss problems occurred in the course of teacher training and resolutions for them.It suggests establishing encouragement mechanism for GP teaching and authentication system of GP teachers and enhancing the teaching capability of GP teachers.

Key words: 
Teaching; Teacher's training
Tumor-infiltrating lymphocytes and tumor budding refine prognostication in patients with low- and high-risk stage III colon cancers (NCCTG N0147)[Alliance].
Authors: Dan Sha, Hee Eun Lee, Nathan R. Foster, Qian Shi, Steven R Alberts, Thomas C. Smyrk, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2020)

4065 Background: Tumor infiltrating lymphocytes (TILs) and tumor budding (linked to epithelial mesenchymal transition) may influence metastatic potential and patient prognosis. We analyzed these features and their relative contribution to survival among low (T 1-3 N 1 ) and high (T 4 and/or N 2 ) risk groups, defined by the IDEA study, used to inform the duration of adjuvant chemotherapy in stage III colon cancer. Methods: Among 1,532 patients (low risk n=804; high risk n=728) treated in a phase III adjuvant trial of FOLFOX + cetuximab (x 6 months), intraepithelial TIL densities and tumor budding were quantified at microscopy in routine histologic sections. Optimal cutpoints were determined in association with 5-yr disease-free survival (DFS). Relative contribution of variables to DFS was calculated using χ2 from Harrell’s rms R package based on multivariable Cox regression models. Results: In the overall cohort, the tumor budding/TILs combined variable was more robust for predition of DFS than either alone. Budding/TILs was significantly associated with DFS in both low (HR adj , 1.59; 95% CI, 1.02-2.48; p=.0273) and high (HR adj , 2.82; 95% CI, 1.72-4.63; p&lt;.0001) risk patients. We then determined its relative contribution (%) to DFS (Table). Among low risk, budding/TILs ranked second (24.4%) behind KRAS status (45.5%) and ahead of treatment arm (7.2%) and mismatch repair (MMR) status (6.1%). Among high risk, budding/TILs contributed the most to DFS (45.4%) followed by primary tumor sidedness (13.0%), performance status (12.0%), and MMR (10.4%). Conclusions: Tumor budding/TILs provides robust prognostic stratification by risk group to improve anatomic tumor staging. The relative contribution of budding/TILs to DFS was second only to KRAS status in low risk patients, and was the most important predictor of DFS in high risk patients. Evaluation in patients treated with 3 vs 6 mos of adjuvant chemotherapy is warranted. [Table: see text]
Prospective study comparing self-administered geriatric assessment to provider’s routine clinical assessment of older patients with metastatic breast cancer treated at community oncology practices.
Authors: Rino S. Seedor, Caitlin R. Meeker, Bianca Lewis, Elizabeth A. Handorf, Kelly A. Filchner, Jennifer S. Winn, Lori J. Goldstein, Efrat Dotan
Journal: Journal of Clinical Oncology (2020)

12029 Background: Geriatric Assessment (GA) is recommended for evaluating an older cancer patient’s (pt) fitness for treatment. We conducted a prospective study evaluating the current gaps that exist in the assessment of older pts with metastatic breast cancer (MBC) in community practices (CP). Methods: Self-administered validated GA was compared to provider assessment (PA) of MBC pts ≥ 65-years-old treated at CP in the US. Providers were blinded to the GA results until their evaluation was completed. Differences in PA vs GA detected abnormalities were assessed using McNemar’s test. The effect of patient/provider factors on the rate of abnormalities not identified was assessed using regression models, clustering by provider and adjusting for the number of prior pts seen. Results: 100 pts were enrolled across 9 CP (median age 73.9, (65-90)). GA detected a total of 356 abnormalities in 96/100 (96%) pts, of which 223 required immediate interventions. African American and widowed/single pts were more likely to have abnormalities identified by GA. On average PA did not identify abnormalities detected by validated GA in 2 of 8 domains. 73% of functional status, 86% of social support, 44% of nutritional, and 96% of cognitive abnormalities detected by GA were not identified by PA (all P &lt; 0.0001). Providers with more years of clinical experience were more likely to identify abnormalities (compared to &lt; 5 years (y) in practice: 5-10 y in practice, p = 0.149; 11-15 y in practice, p = 0.028; &gt; 15 y in practice, p = 0.017). GA had the most significant impact on pts with decreased ECOG PS (p = 0.045). Pts found to have an abnormal Timed Up and Go (TUG) test were more likely to have additional abnormalities in other domains (mean 4.3 vs 2.1, Wilcoxon p &lt; 0.001), and more abnormalities not identified by the PA (p &lt; 0.001). Providers were “surprised” by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 40% of pts based on GA findings. Conclusions: Including a GA in the care of older pts with MBC in CP is beneficial as validated GA has a high detection rate of abnormalities not detected by PA.
Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (CE) alone or in combination with nivolumab as frontline therapy for extensive-stage small cell lung cancer (ES-SCLC): ECOG-ACRIN EA5161.
Authors: Ticiana Leal, Yating Wang, Afshin Dowlati, DeQuincy Andrew Lewis, Yuanbin Chen, Amit Ramesh Mohindra, Mohammad Razaq, Harish G. Ahuja, Jijun Liu, David M. King, Christopher Joseph Sumey, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2020)

9000 Background: Immune checkpoint inhibition is now given in combination with chemotherapy for first line (1L) therapy of extensive stage small cell lung cancer (ES-SCLC). We conducted a randomized phase II study of nivolumab (anti-PD1) in combination with platinum-etoposide (CE) as 1L treatment for patients with ES-SCLC (EA5161, NCT03382561). Methods: Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. Patients were randomized 1:1 to nivolumab 360 mg + CE every 21 days for 4 cycles followed by maintenance nivolumab 240 mg every 2 weeks until progression or up to 2 years (arm A) or CE every 21 days for 4 cycles followed by observation (arm B). Prophylactic cranial irradiation (PCI) was permitted at the investigator’s discretion. Investigator’s choice of cisplatin or carboplatin was allowed across both arms. The primary endpoint was PFS in eligible and treated patients. Secondary endpoints included OS, ORR, and safety. Adverse events (AEs) were graded per NCI-CTCAE v4.0. Results: This study was activated in May 2018 and completed accrual in December 2018. 160 patients were enrolled. Baseline characteristics were well balanced between arms. In the ITT population (n = 160), nivolumab + CE significantly improved the PFS compared to CE with HR 0.65 (95% CI, 0.46, 0.91; p = 0.012); mPFS 5.5 versus 4.6 months, respectively. Secondary endpoint of OS was also improved with nivolumab + CE versus CE with HR 0.67 (95% CI, 0.46, 0.98; p = 0.038); mOS 11.3 versus 8.5 months. Among patients who initiated study therapy, nivolumab + CE significantly improved the PFS compared to CE with HR 0.68 (95% CI, 0.48, 1.00; p = 0.047); mPFS 5.5 versus 4.7 months, respectively; in this population, OS was also improved with nivolumab + CE versus CE with HR 0.73 (95% CI, 0.49, 1.11; p = 0.14); mOS 11.3 versus 9.3 months. The ORR was 52.29% versus 47.71%. The incidence of treatment-related grade 3/4 AEs was 77% versus 62% and AEs leading to discontinuation 6.21% versus 2.07%. Ten patients remain on maintenance nivolumab. Lethal adverse events independent of treatment were similar between the two arms (9 in arm A; 7 in arm B). Conclusions: The addition of nivolumab to CE as 1L treatment for ES-SCLC significantly improved PFS and OS. No new safety signals were observed. Clinical trial information: NCT03382561.
农民工尘肺七例
Authors: 武传梅
Journal: BMJ (2009)

2007年3月至2008年3月,我院接诊农民工尘肺患者7例. 一、临床资料 1.一般资料:7例男性患者均由于胸闷、气短、气喘等呼吸系统症状前来就诊,年龄34～45岁,平均37岁,工龄1.5～10.0年,平均5年.工作在煤矿6例,金矿1例,均为采掘工.来院后行血常规、血红细胞沉降率、肺功能、心电图检查和拍摄高千伏胸片,职业病诊断组专家阅片临床诊断:尘肺Ⅰ期3例,Ⅱ期2例,Ⅲ期2例.均系外地打工者,无法提供详细职业史证明。
An investigation on use of sedative and hypnotic agents in urban community residents aged 60 years and over in Shanghai
Authors: Sun-fang Jiang, jie Gu, Shan-zhu Zhu, Jian-lin Ji
Journal: BMJ (2008)

Objective To investigate use of sedative and hypnotics agents in urban community residents aged 60 years and over in Shanghai. Methods A cross-sectional study on use of sedative and hypnotics agents was conducted in 2248 residents aged 60 years and over in Jing' an community of Shanghai during July to October 2005 with questionnaire. Results Overall prevalence of use of sedative and hypnotics agents was 15.8% (355/2248), 7.3% (165/2248) for consecutive use and 6.2% (140/2248) for long-term consecutive use, respectively, which increased with age (P < 0.05). Prevalence of use of sedative and hypnotics agents, whatever consecutive use or long-term consecutive use was significantly higher in women than that in men [18.7 % (224/1303) vs. 11.7% (111/945), P<0.01; 8.3 % (108/1303) vs. 6.0% (57/945), P < 0.05 ; or 7. 3% (95/1303) vs. 4. 8% (45/945), P < 0.05]. Use of benzodiazepinos accounted for 90. 0 % (126/140) in those with long-term consecutive use. About 93.8 % (333/355) of sedative and hypnotic agents were prescribed by medical doctors. Conclusiong In general, prevalence of sedative and hypnotics agents use in the aged residents of community is higher, mainly with benzodiazepines. There are a few problems about their unreasonable use in women and attention should be paid to it.

Key words: 
Aged;  Sleep initiationan and maintenance disorders;  Hypnotics and sedatives
Clinical outcomes of checkpoint inhibitors in metastatic non-clear cell renal cell carcinoma and clear cell renal cell carcinoma with variant features.
Authors: Guy vin Chang, Moataz Ellithi, Radowan Elnair, Jonathan Bleeker
Journal: Journal of Clinical Oncology (2020)

e17065 Background: Checkpoint inhibitors (CPI) are a well-established treatment option for advanced clear cell renal cell carcinoma (ccRCC); however, there is a paucity of data on efficacy of CPI on advanced non-clear cell renal cell carcinoma (nccRCC) and ccRCC with variant (sarcomatoid or rhabdoid) features. Recently, small series have demonstrated benefit for CPI in these entities. Methods: We performed a retrospective review of patients with metastatic nccRCC or ccRCC with variant features, who received a single agent CPI (nivolumab or pembrolizumab) or combination therapy (nivolumab and ipilimumab) between Feb 2016 – Oct 2019 at our integrated community-based health system. The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). We used Kaplan-Meier survival analysis for PFS and OS. Results: A total of 26 patients met eligibility criteria; 11 patients with nccRCC (papillary n = 6, chromophobe n = 1, unclassified n = 4), 12 patients with sarcomatoid ccRCC, 2 patients with rhabdoid ccRCC, and 1 patient with both sarcomatoid and rhabdoid features. Sixteen patients received nivolumab, 3 received pembrolizumab, and 7 received a combination of nivolumab and ipilimumab. CPI was halted in 4 patients due to adverse effects including arthralgia, hyperthyroidism, hepatitis, and colitis. Among these 26 patients, 5 patients (19.2%) achieved complete response (CR), 3 patients (11.5%) achieved partial response (PR), and 10 patients (38.5%) had stable disease (SD). All patients who achieved CR or PR had a durable response throughout the follow-up period. At the median follow-up of 16.4 months, median PFS was 14.3 months, and median OS was not reached. Conclusions: In this retrospective series, the ORR of CPI in metastatic nccRCC and ccRCC with variant features was 30.7%, and disease control rate was 69.2%. These findings suggest that CPI may provide significant clinical benefit in patients with nccRCC and ccRCC with sarcomatoid and/or rhabdoid features. Sample size may limit inference and additional studies are needed.
Comparing breast cancer characteristics and outcomes between black U.S.-born patients and black immigrant patients from individual Caribbean islands.
Authors: Danielle Cerbon, Matthew Schlumbrecht, Camille Ragin, Priscila Barreto Coelho, Judith Hurley, Sophia George
Journal: Journal of Clinical Oncology (2020)

e13633 Background: Caribbean-born black immigrants (CBI) represent 57% of all black immigrants in the US; they come mainly from Haiti, Jamaica, Dominican Republic (DR), and Cuba. Breast cancer (BC) is the leading cause of cancer deaths in women living in the Caribbean, however, our previous retrospective cohort of 1131 black women with BC shows that CBI have a better overall survival compared with US-born black (USB). The Caribbean has a majority of African ancestry; nonetheless, different ancestral populations differ in genetic composition, making the Caribbean a distinct population with several health disparities within it. Therefore, we stratified our study by each Caribbean country compared to USB patients with the objective of further studying the difference in BC outcomes between USB patients and CBI. Methods: We identified BC patients through a Safety Net and Private Hospital Tumor Registries. We selected the most populace sites: Haiti, Jamaica, Bahamas, Cuba and DR; and used data from 1,082 patients to estimate hazard rations (HRs) using Cox proportional hazards regression and Kaplan Meier analysis for overall survival; Chi Squared and independent sample t-test to verify associations in categorical variables. Results: The study has 250 Haitian, 89 Jamaican, 43 Bahamian, 38 Dominican, 38 Cuban and 624 USB women. Haitians underwent less surgery (HB 61.2% vs USB 72.9%; P = 0.001) and had less triple negative BC (18% vs USB 27.8%; P = 0.006). Bahamians were the youngest at diagnosis (50.5 years vs. USB 57.6 P &lt; 0.001) and presented at more advanced stages (stage 3/4, 54.3% vs USB 35.3%; P = 0.02). Jamaicans and DR underwent more radiation therapy (43.8%, P = 0.002 and 44.7%, P = 0.028 vs. USB 28%). Jamaican women had a better overall survival compared to USB patients (median of 154.93 months, 95% CI: 114.1-195.5 vs 98.63 months, 95% CI: 76.4-120.8; Log-Rank Mantel Cox P = 0.034). Favorable factors for survival were: radiation therapy in Haitian and USB (aHR = 0.45, 95% 0.27-0.77; P = 0.004); and surgery in USB (aHR = 0.26 (0.19-0.36), p &lt; 0.001), Bahamians (aHR = 0.05 (0.01-0.47), p = 0.008) and Jamaicans (aHR = 0.08 (0.03-0.24), p &lt; 0.001). Conclusions: This study underlines the vast heterogeneity in the Caribbean population and demonstrates that Jamaican immigrants with BC have a higher overall survival compared to USB patients, proposing that genetic and other cancer related factors inherent to country of origin impact survival within Caribbean immigrants and highlighting the need for further studies in this immigrant sub-group.
Association between immune and tumor gene signatures with response or resistance to tislelizumab monotherapy or in combination with chemotherapy in gastroesophageal adenocarcinoma.
Authors: Jianming Xu, Tianshu Liu, Jong-Seok Lee, Yuxian Bai, Yee Chao, Silu Yang, Yun Zhang, Xiaopeng Ma, Pei Zhang, Jianfei Zheng, Yanyan Li, Jin Wang, Lin Shen
Journal: Journal of Clinical Oncology (2020)

3115 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, has demonstrated clinical benefit as a single agent and in combination with chemotherapy for patients (pts) with gastroesophageal adenocarcinoma (GEA), including gastric, gastroesophageal junction (G/GEJ), and esophageal adenocarcinoma (EAC). Immune- and tumor-transcriptomic features of response and resistance to tislelizumab were assessed from data collected in two monotherapy studies (NCT02407990, CTR20160872) and one tislelizumab plus chemotherapy study (NCT03469557). Methods: Gene expression profiling (GEP), using the 1392-gene HTG EdgeSeq panel, was performed on baseline tumor samples from 103 pts with GEA receiving monotherapy and 13 receiving combination therapy. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures (GS). Differential gene signature (DEG) analysis was performed between responders and nonresponders (NRs) using Wilcoxon rank-sum test; GS associated with survival were evaluated using Cox proportional hazards model. Results: Of the 76 pts with available GEP data, 64 (n=51 G/GEJ; n=13 EAC) had evaluable responses. Across these pts with GEA, tislelizumab demonstrated antitumor activity (Table). In pts treated with monotherapy, DEG showed IFNγ GS ( IFNG, CXCL9, CXCL10, HLA-DRA, IDO1, STAT1) scores were positively correlated with response ( P=0.03) as well as progression-free (HR=0.5, 95% CI: 0.27–0.93) and overall survival (HR=0.44, 95% CI: 0.21–0.89). Monotherapy NRs could be clustered into distinct GEP subgroups. Compared with responders, two NR subgroups had lower IFNγ GS ( P=0.002, 0.047) along with either higher epithelial-mesenchymal transition (EMT; P=0.027), and angiogenesis ( P=0.002) or cell cycle (CC; P=0.097) GS expression. A third NR subgroup showed higher CC GS scores compared with responders ( P=0.015), despite high IFNγ GS levels. Unlike tislelizumab monotherapy, responders to combination therapy showed higher CC GS expression versus NRs ( P=0.089). Conclusions: While higher IFNγ GS was associated with clinical benefit with monotherapy, elevated EMT/angiogenesis and CC GS levels may indicate resistance. The effects of these signatures in pts treated with combination therapy may vary. Both immune- and tumor-intrinsic factors may be considered for validation in a phase 3 study (NCT03777657). [Table: see text]
Clinical experience of ONC201 in patients with recurrent H3 K27M-mutant spinal cord glioma.
Authors: Sylvia Christine Kurz, Rohinton Tarapore, Yazmin Odia, Nicholas A. Butowski, Carl Johannes Koschmann, Dolly Aguilera, Tobey J. MacDonald, Guangrong Lu, Joshua E. Allen, Wolfgang Oster, Minesh P. Mehta, Andrew S. Chi, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2020)

2563 Background: High-grade gliomas of the spinal cord are a rare and understudied entity, representing &lt; 5% of all spinal cord tumors. Reported median survival times range from 10-16 months. Up to 53% of tumors harbor the H3 K27M mutation, which is associated with an unfavorable prognosis. Postsurgical treatment often includes radiation ± temozolomide, although the role of chemotherapy has not been conclusively established. At recurrence, there are no effective therapies and most clinical studies exclude patients with spinal cord tumors. We report our clinical experience with ONC201, a small molecule DRD2 antagonist and caseinolytic protease P agonist, in patients with recurrent H3 K27M-mutant diffuse gliomas of the spinal cord (scDG). Methods: Adults and children with recurrent H3 K27M-mutant scDG received ONC201 in two Phase II clinical trials enrolling adult recurrent H3 K27M-mutant glioma patients (NCT02525692; NCT03295396) and in one Phase I clinical trial enrolling pediatric patients (NCT03416530). Adult patients received ONC201 at the RP2D dose of 625 mg weekly and pediatric patients received the RP2D of 625 mg weekly, scaled by body weight. All patients began ONC201 as a single agent until disease progression. Five patients continued ONC201 combined with bevacizumab beyond progression. Results: As of January 15, 2020, 12 evaluable patients (adult n = 8, pediatric n = 4) received ONC201. The median age was 20.9 (range: 7-72) years. The median follow-up time for the single agent ONC201 group was 5.4 (range 1.3-9.7) months while that of the combination group is 7.4 (range 6.2-25.1) months. The median number of ONC201 doses was 10 (range: 5-39) for the ONC201 single agent group and 34 (range: 21-100) for the combination group. Five of 7 patients remain alive in the ONC201 single agent group while 3 of 5 patients remain alive in the combination group. Three patients in the ONC201 single agent group and 2 patients in the combination group continue on treatment. There were no drug-related toxicities requiring dose reduction or discontinuation. Conclusions: Treatment with ONC201 alone or combined with bevacizumab is well tolerated in patients with recurrent H3 K27M-mutant scDG and a subset of patients experiences prolonged survival that exceeds historical outcomes. Clinical trial information: NCT02525692; NCT03295396; NCT03416530 .