tbuckley/cabot-search huggingface dataset:
A meta-analysis comparing therapeutic outcomes for anti-EGFR monotherapy to targeted therapy combinations for non-small cell lung cancer.
Authors: Sonali Kurup, Qian Ding, Felix Amissah, Kaitlin Assaad, Soniya Chandrasekhara
Journal: Journal of Clinical Oncology (2020)

e21570 Background: Small molecule inhibitors of epidermal growth factor receptor kinase (EGFR) are approved for EGFR-positive non-small cell lung cancer (NSCLC). Targeted therapies include agents that block tumor-specific molecular targets and thereby interfere with tumor growth and metastasis. This study focuses on a meta-analysis of therapeutic outcomes from phase II and III clinical trials for anti-EGFR monotherapy compared to anti-EGFR therapy in combination with targeted agents. Methods: A literature search was conducted using EMBASE, Pubmed, Scifinder Scholar, clinicaltrials.gov and the Cochrane library for the following terms: “epidermal growth factor receptor kinase”, “combination therapy”, “non-small cell lung cancer”. Eligible studies included patients of advanced stage IV NSCLC and any mutation status that met the predefined inclusion criteria. Data was extracted on trial demographics and therapeutic outcomes including progression-free survival (PFS), survival post progression (SPP), overall survival (OS) and adverse events (AE). Sub-group analysis based on patient mutation status of wild-type (wt) EGFR, mutant EGFR, wt KRAS and mutant KRAS and a correlation analysis between OS, PFS and SPP was conducted. Results: A total of 34 studies were identified that fit the inclusion criteria from 2009-2019. The pooled OS hazard ratio (HR) was 0.94 (95% Confidence Interval (CI): 0.87-1.01); the pooled PFS HR was 0.8 (95% CI: 0.74-0.87). Median OS correlated more closely with median SPP (r 2 = 0.97 for monotherapy; r 2 = 0.88 for combination therapy) than to median PFS (r 2 = 0.90 for monotherapy; r 2 = 0.82 for combination therapy), although the linear association between log-HR OS and log-HR PFS had a positive slope (β = 0.31± 0.19). A greater incidence of rash and diarrhea was observed in the combination arm compared to monotherapy. A significant improvement was observed for PFS in wt EGFR patients for combination therapy, pooled PFS HR 0.8 (95% CI: 0.67-0.95). Conclusions: A statistically significant improvement in PFS was observed for anti-EGFR combination regimens compared to anti-EGFR monotherapy. The improvement in OS was not statistically significant for anti-EGFR combination regimens compared to monotherapy.
The mutation profile of genes related to primary resistance to EGFR-TKI in early NSCLC.
Authors: Jiangang Ye, Qi Zhang, Xing Zhang, Huijuan Qin, Minqi Tian
Journal: Journal of Clinical Oncology (2020)

e21014 Background: In targeted therapy for patients with advanced non-small cell lung cancer (NSCLC), approximately 30% of NSCLC patients with EGFR mutations develop primary resistance at the beginning of treatment with TKIs. However, the knowledge of primary resistance in early-stage NSCLC patients with EGFR positve remains poorly understood. Methods: Mutations of nine genes that may be related to primary resistance EGFR TKIs in advanced non-small cell lung cancer were chosen through pubmed and other databases including EGFR T790M, EGFR 20ins, PIK3CA, KRAS, BRAF, ERBB2 amplification, MET amplification, PTEN deletion and BCL2L11 deletion. Gene mutations related to primary resistance in patients with early-stage lung cancer (I-IIIA) from the TCGA database were analyzed. Results: According to TCGA database, there were 1089 patients with NSCLC of which 585 were lung adenocarcinoma and 504 lung were squamous cell carcinoma. A number of 46 EGFR-sensitive (19del / L858R) mutations were observed in adenocarcinoma, of which the clinical information of which 44 cases harbored competed clinical information including 39 patients with early stage could be identified as follows,1 patient in stage I, 11 patients in stage IA, 8 patients in stage IB, 7 patients in stage IIA, 4 patients in stage IIB, 8 patients in stage IIIA, 1 patient in stage IIIB and 4 patients in stage IV, respectively. Among the 39 cases of early non-small cell lung cancer with EGFR-sensitive mutations, 2 case of EGFR T790M mutations (5.12%), 2 case of PIK3CA (5.12%), 2 case of BRAF (5.12%), 11 case of MET (DUP) (28.2 %), 8 case of ERBB2 (DUP) (20.5%) and 5 case of PTEN (Del) (12.8%) mutations were observed respectively. Meanwhile, none of primary resistance gene mutations could be found in non-small cell lung squamous cell cancer(0/1). Conclusions: The presence of different mutation frequency in the primary resistance genes associated with EGFR TKIs in patients with early NSCLC was proved. Our study suggested it was necessary for patients to test mutations in primary resistance genes before accepted the adjuvant and neoadjuvant therapy using TKIs. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
全身炎症反应综合征患者血甲状腺激素和皮质醇水平的变化
Authors: 许丽, 李春盛
Journal: BMJ (2006)

对100例全身炎症反应综合征(SIRS)患者(54例存活、46例死亡)、30例非SIRS患者及30例正常对照者,测定血清甲状腺激素和皮质醇水平.研究结果:SIRS患者及SIRS死亡患者急性生理与慢性健康评分(APACHEⅡ评分)、多器官功能不全综合征评分(MODS评分)分别较非SIRS患者及SIRS存活患者明显升高(P＜0.01);SIRS患者较非SIRS患者和正常对照者血甲状腺激素水平降低,而皮质醇升高(P＜0.05);甲状腺素及皮质醇水平与患者预后有关(P＜0.01,P＜0.05),甲状腺素水平愈低,皮质醇水平愈高,则患者预后愈差.表明SIRS患者甲状腺激素水平降低,而皮质醇水平则升高,病情愈重,变化愈显著;血皮质醇≥328μg/L可作为评价危重病预后的参考指标。
First-in-human phase I study of BVAC-B cell therapy in HER2-positive advanced gastric cancer.
Authors: Jii Bum Lee, Woo Sun Kwon, Hyo Song Kim, Minkyu Jung, Sinyoung Kim, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Hyun Cheol Chung, Sun Young Rha
Journal: Journal of Clinical Oncology (2020)

4534 Background: BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HER2/neu gene and loaded with alpha-galactosyl ceramide, a natural killer T cell ligand. It may have activity against HER2/neu positive cancer. Preclinical data in mouse models have shown promising anti-tumor activity by eliciting broad spectrum of immune responses against HER2/neu positive tumor cells. We report here the results of phase 1 study of BVAC-B in HER2 positive advanced gastric cancer. Methods: Metastatic gastric cancer with IHC &gt; 1+ of HER2/neu were eligible for enrollment. Two weeks before treatment, subjects were admitted to hospital for collection of PBMC and plasma by lymphapheresis. The PBMC were sent to Cellid for vaccine manufacturing which took a day. BVAC-B was given intravenously at 0, 4, 8, and 12 weeks. Subjects received low (2.5X 10 7 cells/dose), medium (5.0X 10 7 cells/dose) or high dose (1.0X 10 8 cells/dose). Endpoints included safety, tolerability and MTD for phase 2 trial. Exploratory outcomes included immune responses after BVAC-B administration. Results: As of January 29, 2020, 8 subjects were treated with BVAC-B at doses of 2.5X 10 7 cells/dose (n=1), 5.0X 10 7 cells/dose (n=1) and 1.0X 10 8 cells/dose (n=6). Median line of therapy at which BVAC-B was administered was 4 (range, 2-9). Mean duration treatment was 1.8 (range 1-4) cycles. The most common treatment related adverse events were fever (n=4, 50%). One subject enrolled in medium dose experienced cytokine release syndrome (G2) with high fever (39.3℃) and hypotension 8 hours after first administration, but was manageable with hydration and supportive management. Other adverse events included increase of AST and ALT (G1, n=1 and G2, n=2), and hypotension (G1, n=1). There were no adverse events which led to treatment discontinuation. Immunologic response analysis showed that BVAC-B induced activation of natural killer T cells, natural killer cells, HER2/neu specific T cells, and release of HER2/neu specific antibody upon vaccinations in few patients who were evaluated. Conclusions: BVAC B is feasible and has acceptable toxicity profile. We considered all dose evaluated in this study available for phase 2 study, given that the maximum tolerated dose is expected to exceed the maximum dose administered in this study. For clinically relevant effect, further studies are warranted, including earlier line of exposure to BVAC-B as well as combination treatments. Clinical trial information: NCT03425773 .
Selpercatinib (LOXO-292) in patients with <i>RET-</i>fusion+ non-small cell lung cancer.
Authors: Koichi Goto, Geoffrey R. Oxnard, Daniel Shao-Weng Tan, Herbert H. F. Loong, Todd Michael Bauer, Justin F. Gainor, Caroline Elizabeth McCoach, Oliver Gautschi, Benjamin Besse, Byoung Chul Cho, Nir Peled, Jared Weiss, YuJung Kim, Yuichiro Ohe, Atsushi Horiike, Keunchil Park, Xin Huang, Elizabeth Olek, Vivek Subbiah, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2020)

3584 Background: Selpercatinib (LOXO-292) is a highly selective and potent small molecule RET kinase inhibitor. Here we report an update on the efficacy and safety of selpercatinib in RET-fusion+ non-small-cell lung cancer (NSCLC). Methods: Patients with RET-fusion+ NSCLC were enrolled to the Phase 1/2 LIBRETTO-001 trial (NCT03157128), a global, multicenter trial (16 countries, 89 sites). Following the Phase 1 dose escalation portion of the trial, patients received the recommended dose of 160 mg orally twice daily. Each cycle was 28 days. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included duration of response (DoR) and safety. Per health authority agreement, the primary analysis set was defined as the first 105 consecutively enrolled patients previously treated with platinum-based chemotherapy. Treatment-naïve patients were analyzed separately. All analyses were based on a 16-Dec-2019 data cutoff date. Results: In the primary analysis set of platinum-treated patients (median of 3 prior systemic regimens; range 1-15), the ORR by investigator assessment was 70% (95% CI 59.8–78.1, n = 73/105). Responses did not differ by fusion partner or number or type of prior therapies, including anti-PD-1/PD-L1 agents and off-label multikinase inhibitor use. The median DoR was 20.3 months (95% CI 15.6–24.0) with 45 of 73 (62%) responders censored at a median follow-up of 14.8 months. Among 39 treatment-naïve patients, the ORR by investigator assessment was 90% (95% CI 75.8–97.1, n = 35/39, including 2 responses pending confirmation). Median DoR was not reached with 27 of 33 (82%) confirmed responses ongoing at a median follow-up of 7.4 months. In the safety analysis set consisting of all selpercatinib dosed patients (N = 702), the most common treatment-related adverse events (TRAEs) that occurred in ≥15% of patients were dry mouth (33.3%), increased AST (24.5%), increased ALT (23.8%), hypertension (23.2%), diarrhea (19.7%), and fatigue (16.8%). Only 2% (14 of 702) of patients discontinued selpercatinib for TRAEs. Conclusions: Selpercatinib achieved marked and durable antitumor activity in patients with RET-fusion+ NSCLC. Selpercatinib was well tolerated. Efficacy data assessed by independent review committee based on the 16-Dec-2019 data cutoff date will be presented. Clinical trial information: NCT03157128 .
Impact of age on racial disparity in early stage breast cancer in the United States.
Authors: Shruti Bhandari, Rohit Kumar, Phuong Ngo, Sarah Mudra, Drew Carl Drennan Murray, Elizabeth Carloss Riley, Stephanie D. Boone
Journal: Journal of Clinical Oncology (2020)

e19058 Background: Racial disparities persists in women with early stage breast cancer and is most pronounced in Black (B) compared to White (W) women even when controlled for stage and biological subtype. Little is known about the impact of age on racial disparities. Our study evaluates the magnitude of a racial disparity in mortality across age strata in a real-world population. Methods: We identified stage I-III female breast cancer patients between 2010 – 2015 from the National Cancer Database. Hazard ratios (HR) and 95% Confidence Intervals (CI) for all-cause mortality were estimated using multivariable Cox Proportional Hazards regression, adjusted for clinical and demographic factors. The mortality risk for B and Other (O) race was compared to W across four age groups. To determine the significance in excess risk of mortality, the magnitude of disparity of each age group was compared to the &gt; 60y age group. Results: A total of 679,327 patients were included. W comprised the largest percentage across all age groups. However, the percentage of W increased with age, while the percentage of B decreased with age (p &lt; 0.001). The risk of mortality was significantly higher for B relative to W across all age groups ≤60y. When compared to &gt; 60y, the magnitude of effect of age on risk of dying was significantly different (p &lt; 0.0001) (Table). Conversely, the risk of mortality was significantly reduced for O race compared to W, with similar magnitude of effect across all ages. Conclusions: Even after adjusting for known risk factors of racial disparity such as insurance, biologic subtype and stage, the B to W racial disparity in mortality decreased with age (most pronounced in younger age) and appeared to diminish among women &gt; 60 years of age. In contrast, the risk of dying in O race remained constant. Reasons are unclear and may be due to unmeasured socioecomomic or biologic factors that cannot be controlled for in this dataset. Regardless, identifying factors associated with worsened outcomes in younger age groups in B women should be the direction of future studies. [Table: see text]
Pomalidomide, bortezomib, and dexamethasone (PVd) in lenalidomide (LEN)-pretreated relapsed refractory multiple myeloma: Subanalysis of patients with renal impairment in OPTIMISMM.
Authors: Fredrik Schjesvold, Meletios A. Dimopoulos, Meral Beksac, Albert Oriol, Jindriska Lindsay, Anna Marina Liberati, Monica Galli, Pawel Robak, Katja Weisel, Alessandra Larocca, Münci Yagci, Filiz Vural, Larry D. Anderson, Jr, Abraham Sebastian Kanate, Eva Casal Mendez, Ruiyun Jiang, Shankar Srinivasan, Lara Grote, Tsvetan Nikolov Biyukov, Paul G. Richardson
Journal: Journal of Clinical Oncology (2020)

e20562 Background: Upfront LEN until disease progression is a standard treatment (Tx) in multiple myeloma (MM). Data are limited on optimal Tx after first-line LEN, especially in LEN-refractory patients (pts), a growing population. In OPTIMISMM (phase 3, NCT01734928), PVd significantly improved median PFS at first relapse in relapsed refractory MM (RRMM) pts, of whom 100% were LEN pretreated and 57% were LEN refractory (median, 20.7 vs 11.6 mos; HR = 0.54 [95% CI, 0.36-0.82]; P = .0027) vs Vd (Richardson, 2019). Pd has shown efficacy and safety in RRMM pts with moderate or severe renal impairment (RI), including those on dialysis (Dimopoulos, 2018). However, outcomes with second-line PVd in RRMM pts with RI have not been assessed. Here we report efficacy and safety of PVd vs Vd at first relapse by renal status (CrCl &lt; 60 vs ≥ 60 mL/min). Methods: Pts received PVd or Vd (1:1) in 21-day (D) cycles (C); POM 4 mg/D on D1-14 (PVd arm only); BORT 1.3 mg/m 2 on D1, 4, 8, 11 of C1-8 and on D1, 8 of C9+; and DEX 20 mg/D (10 mg/D for pts aged &gt; 75 yrs) on days of and after BORT. Pts on dialysis were excluded. Results: Of 559 pts enrolled, 226 (40%) had 1 prior line of therapy; of whom 28% had CrCl &lt; 60 mL/min and 4% had severe RI (CrCl &lt; 30 mL/min). In pts with CrCl &lt; 60 mL/min (PVd vs Vd), median age was 74 vs 73 yrs. In pts with CrCl ≥ 60 mL/min (PVd vs Vd), median age was 62 vs 64 yrs. A higher proportion of pts with baseline CrCl &lt; 60 (23% vs 43%) than ≥ 60 mL/min (7% vs 8%) had ISS stage III at study entry. Data cutoff was Oct 26, 2017. Median PFS was improved with PVd in both renal groups (Table). ORR significantly improved regardless of renal status. Depth of response also improved with PVd vs Vd; ≥ VGPR occurred in 54% vs 21% in the CrCl &lt; 60 mL/min group and 64% vs 23% in the CrCl ≥ 60 mL/min group. Myelosuppression was the most common grade 3/4 TEAE (Table). Conclusions: Second-line PVd led to improved vs Vd in pts with RRMM and RI; however, the PFS difference was not statistically significant. Safety was consistent for PVd with no new signals in pts with RI. These findings further support the earlier use of POM-based Tx in RRMM pts, including those with mild to moderate RI. Clinical trial information: NCT01734928. [Table: see text]
误吸引起慢性阻塞性肺疾病急性发作19例
Authors: 孙逊, 蒋超英
Journal: BMJ (2007)

由各种原因引起的误吸对于慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)急性发作来说是个重要的促发因素,如何预防和救治值得重视.现回顾性分析我院2000年10月至2005年10月采取综合治疗措施救治因误吸引起的COPD急性发作患者19例情况。
Demands of tobacco control service among male smoking patients in community health service centers in Shanghai
Authors: Haiyan Lei, Shijie Fu, Sunfang Jiang, Yao Liu
Journal: BMJ (2020)

Objective
To survey the demands of tobacco control service among male smoking patients in primary health care settings in Shanghai.


Methods
Eight community health service centers in Shanghai were selected through stratified cluster sampling method. A total of 1 458 male patients, who visited their doctors in community health centers in January 2017, completed the questionnaire and were eligible for our study. The contents of questionnaire included demographic information, smoking history, knowledge of tobacco smoking, attitudes toward tobacco control; and the questions regarding smoking cessation service were only for the smokers.


Results
Of the 1 458 male patients, there were 679 current smokers (46.6%, 679/1 458), among whom 358 (52.7%, 358/679) intended to quit. The demand rate for the knowledge regarding tobacco and health, smoking cessation plan, overcoming barriers were 58.9% (211/358), 56.4% (202/358) and 53.1%(190/358), respectfully. The rate of demand for smoking cessation hotline was 38.5% (138/358). Those who were under 45 years of age, retirees, suffering from chronic disease (s), having knowledge of tobacco, having knowledge of smoking cessation pathway (s), smoking cessation recommendation from medical staff were more willing to accept tobacco control services.


Conclusions
The demand for tobacco control services and utilization rate are relatively low among male smoking patients in primary health care settings in Shanghai. Based on the results acquired from the survey the appropriate measures should be taken.


Key words: 
Community health center; Tobacco use cessation; Health services needs and demand; Questionnaires
Preclinical evaluation of TQB3602, a small molecule proteasome inhibitor clinical candidate.
Authors: Xiquan Zhang, Ling Yang, Xin Tian, Lihua He, Jian Xiong, Xiaoxia Niu, Yuanfeng Xia, Jian Li, Shuhui Chen, Kevin Chen
Journal: Journal of Clinical Oncology (2020)

e20546 Background: Proteasome inhibitors, selectively inhibit the activity of proteasome in ubiquitin proteasome system , together with immunomodulatory drugs formed the basis of many treatment regimens for multiple myeloma in first-line therapy as well as for the treatment of relapsed disease . Bortezomib (Velcade), the first approved therapeutic proteasome inhibitor with a unique boronic acid as warhead, limited by its requirement for parenteral administration (intravenous or subcutaneous). The 2 nd generation boronic acid – orally bioavailable Ixazomib (Ninlaro) was approved in 2015 by FDA greatly improved patient’s compliance. However, its adverse effect remained an issue in clinical application. The purpose of this study is to investigate the in vitro and in vivo antitumor activity of TQB3602, a novel orally bioavailable small molecule proteasome inhibitor, in preclinical models of multiple myeloma. Methods: The enzyme inhibition and anti-proliferative activity of TQB3602 was evaluated in 20S proteasome and MM.1S cell line. Oral administration of TQB3602 at 3 doses was used to evaluate the in vivo anti-tumor activity in MM.1S multiple myeloma xenograft (CDX) models. Results: TQB3602 displayed potent kinase inhibiting activity for 20S proteasome enzyme with IC 50 15.3 nM. TQB3602 inhibited cell proliferation in MM.1S multiple myeloma cell line with IC 50 10.1 nM. In the MM.1S multiple myeloma CB-17 CDX model, TQB3602 showed antitumor efficacy with TGI &gt; 100% @7 mpk, BIW (tumor can’t be measured from day 17). Conclusions: We have identified a novel potent proteasome inhibitor TQB3602. Preclinical studies showed antitumor efficacy of TQB3602 in MM.1S multiple myeloma model. TQB3602 represents a promising clinical candidate for treating multiple myeloma and the First-in-human trial is expected in the middle of 2020.
BRAF V600E-mutated anaplastic thyroid carcinoma (ATC) and treatment with BRAF-inhibitors: Real-world data from a single-institution, still far from the cure.
Authors: Francesca Platini, Elisa Ortolan, Stefano Cavalieri, Giacomo Massa, Daria Maria Filippini, Salvatore Alfieri, Cristiana Bergamini, Carlo Resteghini, Ester Orlandi, Biagio Paolini, Cesare Piazza, Federica Perrone, Elena Tamborini, Linda Ferrarini, Mara Serena Serafini, Vera Cappelletti, Maria Grazia Daidone, Lisa F. Licitra, Laura Deborah Locati
Journal: Journal of Clinical Oncology (2020)

e18577 Background: ATC is a very aggressive disease. In the last years new insights on molecular profile of ATC have led to novel therapeutic options, primarily BRAF-targeted agents. Methods: From May 2018 to December 2019, data on recurrent/metastatic ATC patients treated at our Institution have been reviewed. BRAF V600E was assessed in each patient. BRAF mutation was tested both on tumor sections and on cell-free DNA (cfDNA). Circulating BRAF V600E was assessed by using Droplet Digital PCR (ddPCR) Technology. BRAF wild-type (WT) patients were treated with standard chemotherapy (adriamicin or taxans or platinum-based regimens). BRAF V600E patients were treated with dabrafenib 300 mg per day and trametinib 2 mg per day (combo regimen) until progression or unacceptable toxicities. Response was assessed by RECIST 1.1; progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier method and compared with log-rank test. Safety was evaluated according to CTCAE version 5.0. Results: 16 ATC patients were included. Male/female 5/11, median age was 68 years (range 43-80). Eight patients (50%) carried BRAF mutation. Best response in BRAF V600E was 4 partial response (PR), 3 stable disease (SD) and response in 1 patient has not been assessed yet. Combo was well tolerated, the most common adverse events (G2) were fatigue (14%), pyrexia (14%), nausea and vomiting (9%). Only one patient experienced drugs interruptions. Best response in BRAF WT patients was SD for 1, progressive disease for 4 and 3 patients received supportive care. Concordance between circulating BRAF status with tumor tissue was 80%. Assessment of circulating BRAF performed at baseline and at best response was available for 3 patients achieving a PR: mean reduction was -99.48% from baseline (range -99.37 – -99.66%). Median follow up was 22.8 weeks (95% CI 12.8-22.8). Median PFS was 13 weeks in BRAF V600E and 7.4 weeks in BRAF wt patients (p=0.1); in the same groups median OS was 18.4 and 7.8 weeks, respectively (p=0.051). Conclusions: Real-life data with combo regimen showed an ORR of 50%, with short PFS and OS. Reduction of circulating BRAF observed during treatment might be an indirect marker of tumor shrinkage, even if more data are needed to correlate circulating BRAF and disease response.