tbuckley/cabot-search huggingface dataset:
Baseline blood parameters as predictive biomarkers of immunotherapy efficacy in solid tumors.
Authors: Antonio Marra, Carmen Criscitiello, Stefania Morganti, Giulia Viale, Paola Zagami, Eleonora Nicolò, Emanuela Ferraro, Matteo Repetto, Paolo Tarantino, Paolo D'amico, Dario Trapani, Marzia Adelia Locatelli, Angela Esposito, Giuseppe Curigliano
Journal: Journal of Clinical Oncology (2020)

e15147 Background: Peripheral blood parameters, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and LDH level, have been correlated to immunotherapy (IO) benefit in melanoma and lung cancer. We investigated if peripheral blood parameters could have the same predictive role in a variety of solid tumors treated with either single-agent IO or IO combinations. Methods: Baseline (0 to 14 days from treatment start) blood parameters, including NLR, dNLR, PLR, LMR and LDH, were collected in patients (pts) with metastatic solid tumors treated in phase I trials testing anti-PD-1/PD-L1 single agent (N = 59) and anti-PD-1/PD-L1-based combinations (N = 94), including combinations with immune checkpoint inhibitors/agonists or other agents. IO benefit was assessed for overall survival (OS), progression free survival (PFS), overall response rate (ORR), disease control rate (DCR), and 90-day mortality rate. Logistic regression, Kaplan-Meier method, and Cox regression were carried out to evaluate the impact of clinical and baseline blood parameters on IO efficacy. Results: From Aug2014 to May2019, 153 pts were included [median age 58 (32-80)]. Female/male ratio was 1.47:1 (91 females/62 males). The most common tumors were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Sixty pts (39.2%) had received more than two lines of therapy. Overall, ORR, DCR, and 90-day mortality were 11.8%, 34.9%, and 15.7%, respectively. At multivariate analysis, LDH higher than upper limit of normal (ULN) was associated with reduced DCR (LDH ≤ULN vs &gt; ULN: 50.8% vs 20.8%, OR 0.25, 95%CI 0.1-0.62, p = .003) and increased 90-day mortality (LDH ≤ULN vs &gt; ULN: 7.9% vs 24.5%, OR 3.59, 95%CI 1.18-10.9, p = .025). At a median follow-up of 25.9 months (22.3-29.6), 138 pts (90.2%) experienced tumor progression and 117 (77.0%) had died. At multivariate Cox regression analysis, LDH &gt; ULN and dNLR &gt; 3 were independently associated with reduced PFS (LDH &gt; ULN: HR 1.97, 95%CI 1.30-2.99, p &lt; .001; dNLR &gt; 3: HR 2.29, 95%CI 1.39-3.77, p &lt; .001) and reduced OS (LDH &gt; ULN: HR 2.04, 95%CI 1.26-3.28, p = .004; dNLR &gt; 3: HR 2.06, 95%CI 1.12-3.79, p = .02). Conclusions: Our analysis confirms that baseline LDH &gt; ULN and dNLR &gt; 3 are predictive biomarkers for IO efficacy, regardless of tumor type and combinations with other drugs, representing an easy tool that deserves prospective validation in IO-based clinical trials.
Clinical outcomes of the combination of bevacizumab and ttfields in patients with recurrent glioblastoma: Results of a phase II clinical trial.
Authors: Jaleh Fallah, Rekha T. Chaudhary, Lisa R. Rogers, Wei Wei, Cathy J. Brewer, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2020)

2537 Background: Clinical trials of bevacizumab monotherapy and TTFields monotherapy have shown activity but limited clinical benefit in patients (pts) with recurrent glioblastoma (GBM), with median progression-free survival (PFS) of 2-4 months and median overall survival (OS) of 6-9 months with either treatment modality. In a single-arm phase II clinical trial, the efficacy of the combination of bevacizumab and TTFields in pts with recurrent GBM was investigated. Methods: Pts with histologically confirmed GBM or other grade IV gliomas, who had disease progression after chemoradiation were enrolled in a phase II trial of the combination of bevacizumab and TTFields. Bevacizumab was given at a dose of 10 mg/Kg intravenously every 2 weeks and TTFields was worn by the pts continuously for more than 18 hours per day. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoints were PFS at 6 months and OS at 12 months. Survival outcomes were assessed using the Kaplan-Meier method and compared by log rank test. Treatment-related adverse events were reported according to CTCAE, v4.0 criteria. Results: From April 2013 to December 2017, 25 pts were enrolled and 23 were evaluable: 18 (78%) men and 5 (22%) women, median age 60 years (range 17–78). 21 pts were Caucasian, 1 was African American and 1 of unknown race. After a median follow up of 31.6 months (range: 4.1-59.0 months), 21 out of 23 pts died (4 women and 17 men). The median PFS was 4.1 months (95%CI, 3.6-9.5) and the median OS was 10.5 months (95% CI, 8.2-14.9). The PFS rate at 6 and 12 months were 33% and 19%, respectively. The OS rate at 6 and 12 months were 82% and 46%, respectively. Women had better OS and PFS compared to men, however, the difference was not statistically significant which can be due to the small study population (table). Grade 3 and 4 toxicities considered definitely or probably related to the treatment included hypertension (n = 1) and cerebral infarction (n = 1). Other reported grade 3-4 toxicities (n = 7) included cough, dysphagia, muscle weakness, hyperglycemia, psychosis, seizure, lymphopenia, transaminitis, and muscle weakness considered unlikely to be treatment-related. Conclusions: The combination of bevacizumab and TTFields in is safe and feasible and has clinical efficacy in pts with recurrent GBM. Clinical trial information: NCT01894061 . [Table: see text]
Real-world outcomes of patients with BRAF-mutated mCRC treated in the United States.
Authors: Matthew Braithwaite, Christopher Duane Nevala-Plagemann, Kelsey Baron, Benjamin Haaland, Lisa M. Pappas, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2020)

4030 Background: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Recent trials have hypothesized that using more aggressive triplet-based chemotherapy regimens such as FOLFOXIRI in the frontline setting may improve outcomes in this patient population. In this study, we utilized real-world data to assess whether FOLFOXIRI is being used in the United States (US) and compared survival outcomes in BRAF mutated (BRAFmt) mCRC stratified by first line (1L) therapy. Methods: The nationwide Flatiron Health EHR-derived de-identified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Patients who had documented BRAF mutation testing and received a standard 1L therapy were included for analysis. Patients who did not have a visit or medication order within 90 days of metastatic diagnosis were excluded to ensure patients were engaged with care at the data-providing institution. Kaplan-Meier and Cox proportional hazard modeling were used to compare survival outcomes stratified by BRAF mutation status and 1L therapy received. Results: A total of 4,454 patients with documented BRAF mutational status were included, of which 3,988 (89.5%) were BRAF wild type (BRAFwt) and 466 (10.5%) were BRAFmt. Median OS was 15.4 months (mo) in the BRAFmt group compared to 28.1 mo in the BRAFwt group (HR 0.48, 95% CI 0.41- 0.56, p &lt; 0.001). Only 3% (n = 16) of BRAFmt patients received 1L FOLFOXIRI +/- bevacizumab with a median OS of 13.8 mo compared to 15.5 mo in patients receiving a chemotherapy doublet (FOLFOX, CAPEOX, or FOLFIRI) +/- bevacizumab (95% CI 4.9 – not reached vs 14.3 – 19.0, p = 0.38). In BRAFmt patients, multivariate analysis (MVA) did not detect a significant improvement in OS with the use of FOLFIRI plus bevacizumab (HR 0.88, 95% CI 0.50-1.56, p = 0.67) or FOLFOX/CAPEOX plus bevacizumab (HR 0.89, 95% CI 0.59 – 1.34, p = 0.58) when compared to chemotherapy doublet alone. A MVA comparing 1L therapies in the BRAFwt group did not detect a significant improvement in OS with bevacizumab plus chemotherapy doublet compared to chemotherapy doublet alone. When stratified by 1L treatment regimen, similar proportions of BRAFmt patients received second line therapy. Conclusions: This analysis of real-world data confirms the negative prognostic impact of BRAF mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the management of these patients in the US. We were unable to demonstrate any significant difference in OS of patients with BRAFmt mCRC based on type of 1L therapy received.
帕罗西汀联合松龄血脉康治疗脑卒中后抑郁气郁化火证者
Authors: 朱黎明, 贺东辉, 王翔宇
Journal: BMJ (2011)

脑卒中后抑郁的发病率国内外文献报道为22％～79％[1-2].2009年11月至2010年11月笔者运用帕罗西汀联合松龄血脉康治疗脑卒中后抑郁气郁化火证98例,报道如下.1.对象与方法:98例患者均来自洛阳市机车医院中西医结合科、郑州市惠济区人民医院和洛阳市第一中医院内科.均为脑卒中后抑郁气郁化火证.脑卒中的诊断参照《中国脑血管病防治指南(试行版)》[3],抑郁诊断参照WHO国际疾病分类手册[4].参照高等中医药院校教材《中西医结合内科学》,全部患者均中医辨证为气郁化火证.按随机表法分为两组,治疗组50例,男26例,女24例;年龄45～75岁,平均(64±12)岁;抑郁病程70～80 d,平均(71 ±9)d;其中缺血型32例,出血型16例,混合型2例;发病时意识清楚41例,意识不清9例. 关键词：抑郁
骨软化症与佝偻病诊疗指南(讨论稿)
Authors: 中华医学会骨质疏松和骨矿盐疾病分会
Journal: BMJ (2006)

骨软化症和佝偻病是指新形成的骨基质不能正常矿化的一种代谢性骨病.发生在成人骨骺生长板闭合以后者称为骨软化症,发生在婴幼儿和儿童骨骺生长板闭合以前者称为佝偻病,两者的病因和发病机制基本相同。
Factors affecting time to treatment in hepatocellular cancer.
Authors: Karan Seegobin, Umair Majeed, Ashton Ritter, Natasha Wylie, Jason Scott Starr, Jeremy Clifton Jones, Kabir Mody
Journal: Journal of Clinical Oncology (2020)

e19088 Background: Significant disparities in the stage at diagnosis and survival outcomes exist between various groups diagnosed with hepatocellular carcinoma (HCC) based on sex, race, insurance coverage, and marital status. Previously published data shows disparities more in patients who are African-American, Asian and low income. Little data has been published on factors that influence timeliness to treatment initiation in patients diagnosed with HCC. Methods: Retrospective analysis was performed on 96,586 patients diagnosed with HCC from 2004-2014 using data in the National Cancer Database (NCDB). Time to treatment was divided into two categories: ≤40 days (early, n = 66322) and &gt; 40 days (late, n = 30264). We carried out univariate and multivariate analyses to compare demographic, clinical, treatment, and facility-related factors influencing the timeliness of treatment initiation in HCC. Results: Univariate analysis revealed a significant difference in time to treatment initiation based on age, race, income, insurance status, type of area, geographic region, type of facility, and cancer stage (P &lt; 0.001). Multivariate analysis showed that household income &lt; $30,000/year, Pacific region, urban area of residence, black race, age 70-79 years old or ≥80 years old, academic centers, stage II disease and medicaid insurance were all factors with longer time to treatment initiation. Discussion: HCC is the sixth most common cancer and the second leading cause of cancer mortality worldwide. The 5-year relative survival for localized, regional, and distant stages are 32.6%, 10.8% and 2.4% respectively. In our results we noted significant disparities in time to treatment with respect to various socioeconomic factors. These results are comparable to that reported in other cancer types. Further subgroup analysis of our data shows 2581 patients who received their first treatment after 200 days. In a similar study done in Taiwan, those treated more than 181 days and 61–180 days after diagnosis had a 1.68 and a 1.39 increased risk of death respectively, which were statistically significant. Many factors contribute to delayed treatment, some of which are difficult to circumvent, however where possible efforts should be made to overcome these. Conclusions: Various socioeconomic factors were found to affect the time to treatment initiation in HCC patients. The next step would be to strategically implement policies and practices to address these factors.
Clinical benefit of luspatercept in patients (pts) with lower-risk MDS (LR-MDS) and high transfusion burden in the phase III MEDALIST study.
Authors: Amer Methqal Zeidan, Guillermo Garcia-Manero, Amy Elizabeth Dezern, Pierre Fenaux, Peter L. Greenberg, Michael R. Savona, Joseph G. Jurcic, Amit Verma, Ghulam J. Mufti, Rena Buckstein, Valeria Santini, Abderrahmane Laadem, Jennie Zhang, Anita Rampersad, Daniel Sinsimer, Chrystal Ursula Louis, Peter G. Linde, Alan F. List, Mikkael A. Sekeres
Journal: Journal of Clinical Oncology (2020)

7554 Background: Anemic pts with LR-MDS and high baseline RBC transfusion burden (HTB) have very few treatment options and constitute a pt population with significant clinical unmet need. In this secondary analysis of the MEDALIST trial (NCT02631070), we sought to evaluate the clinical benefit of luspatercept in this pt population. Methods: MEDALIST is a randomized, placebo (PBO)-controlled, phase 3 study evaluating the efficacy and safety of luspatercept in pts with anemia due to LR-MDS with ring sideroblasts (RS) (Fenaux &amp; Platzbecker et al. NEJM. 2020;382:140-51). Pts were aged ≥ 18 years; had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS; were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents (serum erythropoietin &gt; 200 U/L); and had anemia requiring regular RBC transfusions (≥ 2 units/8 weeks in the 16 weeks prior to randomization). 229 pts were randomized 2:1 to luspatercept (starting dose 1.0 mg/kg; titration up to 1.75 mg/kg allowed) or PBO subcutaneously every 3 weeks. HTB was defined as ≥ 6 RBC units transfused/8 weeks. Results: 153 pts were randomized to luspatercept and 76 to PBO. As of July 1, 2019, 23/66 (34.8%) and 12/66 (18.2%) HTB pts receiving luspatercept achieved a ≥ 50% and ≥ 75% reduction from baseline in RBC transfusion burden over ≥ 24 weeks, respectively, vs 3/33 (9.1%; P = 0.0063) and 1/33 (3.0%; P = 0.0363) pts receiving PBO. 6/66 (9.1%) luspatercept-treated HTB pts and 1/33 (3.0%) PBO-treated HTB pt achieved RBC-transfusion independence (TI) ≥ 8 weeks in Weeks 1–24 ( P = 0.2699). The median (range) time to achieve RBC-TI with luspatercept was 50.0 days (1.0–100.0) and median (range) duration of RBC-TI in the luspatercept arm was 42.6 weeks (8.4–81.1). Mean number of transfusion events in Weeks 1–24 was 9.2 in the luspatercept arm vs 12.4 in the PBO arm (hazard ratio [95% confidence interval] 0.794 [0.660–0.956]). 65/66 (98.5%) luspatercept- and 29/33 (87.9%) PBO-treated HTB pts reported ≥ 1 treatment-emergent adverse event (TEAE); 11/66 (16.7%) and 3/33 (9.1%) pts, respectively, reported ≥ 1 TEAE leading to discontinuation. 28/66 (42.4%) luspatercept- and 15/33 (45.5%) PBO-treated pts reported ≥ 1 serious AE. Incidence of grade 3–4 TEAEs in HTB pts was similar between arms (53.0% luspatercept vs 54.5% PBO). Conclusions: Luspatercept treatment resulted in clinically significant reductions in transfusion burden and reduced number of transfusion events in HTB pts with LR-MDS with RS, with an acceptable safety profile consistent with the overall population. Clinical trial information: NCT02631070 .
Genomic-directed personalized matched targeted therapy approach may improve clinical outcomes among patients with advanced pancreatic cancer.
Authors: Justin Shaya, Shumei Kato, Hitendra Patel, Paul T. Fanta, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2020)

e16794 Background: Despite advances in pancreatic cancer management, 2-year overall survival (OS) remains to be less than 10% in patients with metastatic disease. Given this, novel therapeutic approaches are urgently needed. We hypothesize that a matched combination targeted therapy approach, which is customized based on patient’s cancer genomics, may have clinical efficacy among advanced pancreatic cancer patients. Methods: This is a single center retrospective analysis of advanced pancreatic adenocarcinoma patients treated at UC San Diego. All patients (N = 26) received matched targeted therapy based on genomic alterations detected by tissue NGS and/or blood cell-free DNA assays. This study followed the guidelines of the IRB-approved UCSD PREDICT study (NCT02478931). Results: In the cohort, median age was 67 and 62% (N = 16) were female. 27% (N = 7) received matched therapy front line and 73.1% (N = 19) received matched therapy in the second line or later. The median number of targeted agents administered was 3 (range 1-4). There was a significant improvement in progression-free survival (PFS) when matched therapy was administered in the first line when compared to second line or greater (7.0 vs 2.8 months, hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.19-0.90, P = 0.031) and there was a difference in OS (1 st line vs 2 nd line or greater: 9.2 vs 4.4 months, HR: 0.58, 95% CI: 0.24-1.42, P =0.23). When stratified by Matching Score of ≥50% (high) and &lt; 50% (low) (Matching Score is roughly equivalent to the number of alterations targeted by therapy divided by the total number of characterized alterations), patients who were treated with a high Matching Score demonstrated significantly prolonged PFS and OS when compared to those with a low Matching Score (PFS: 3.8 vs 2.0 months, HR: 0.34, 95% CI: 0.13-0.91, P =0.031, OS: 5.6 vs 3.3 months, HR: 0.33, 95% CI: 0.13-0.85, P =0.022). In patients with a Matching Score of ≥50%, the disease control rate (DCR) (defined as complete response, partial response, and stable disease ≥ 6 months) was 36.8% and among patients who received matched therapy first line, DCR was 71.3%. Representative cases who were successfully treated with matched targeted therapy will be presented. Conclusions: Combination matched targeted therapy, particularly in patients with a high degree of matching, showed improved clinical outcomes. While the sample size here is small and these data warrant further prospective investigation, matched combinatorial targeted therapy may offer patients a novel option for therapy.
A model comparing the value of broad next-gen sequencing (NGS)-based testing to single gene testing (SGT) in patients with nonsquamous non-small cell lung cancer (NSCLC) in the United States.
Authors: Nathan A. Pennell, Jie Zhou, Brian Hobbs
Journal: Journal of Clinical Oncology (2020)

9529 Background: Patients (pts) with nonsquamous (ns) NSCLC should be tested for actionable driver oncogenes (ADOs), and highly effective treatments (tx) may be available for these pts. Although EGFR and ALK single gene testing (SGT) is relatively common (&gt;80%) in the US, testing for less common ADOs is rare. Unidentified pts with ADOs have survival comparable to pts without alterations. We interrogate plausible testing configurations and discuss their implications for the US population. Methods: Simulation was used to evaluate various levels of testing with SGT or NGS on the basis of life years gained (LYG) as well as cost per LYG. Expected prevalence of ADOs among nsNSCLC pts as well as the survival distribution of pts in the presence versus absence of an ADO tx strategy were calibrated based on current literature. Survival duration for each simulated pt was generated from Weibull distributions fit to statistical estimates of median and 5-year survival. With appropriate match between ADO and targeted tx, the Weibull distribution offered a median additional 2 years of life. ADOs included in NGS: EGFR, ALK, ROS1, BRAF, RET, MET, NTRK. SGT: EGFR and ALK. Results: Each incremental 10% increase in NGS instead of SGT produces 2630 additional LYG and a cost savings per LYG between -$49 to -$109. At the current 80% testing rate, replacing SGT with NGS would result in an additional 21,019 LYG with reduced cost per LYG of -$599. Increasing testing from 80% to 100% of eligible pts would increase LYG by 15,017 over the current state. If 100% of eligible pts were tested with NGS and every identified pt received tx, the cost per LYG of this strategy would be $16,641.57. Conclusions: In a hypothetical model where highly effective tx is available to all identified pts with ADOs, broad NGS testing compared to SGT for EGFR/ALK leads to large gains in life years at reduced cost per LYG compared to SGT, supporting universal NGS testing of all advanced nsNSCLC pts. Conversely, lower levels of testing or only testing for common ADOs (as is the current state) result in large numbers of pts being unidentified and not experiencing these benefits. [Table: see text]
全科医生如何诊疗儿童咳嗽
Authors: 施萍
Journal: BMJ (2010)

施萍:咳嗽是一种常见症状,占儿科就诊主诉的30%左右. 一般来说,咳嗽是反射性的,这种反射由咳嗽感受器引发并受脑干咳嗽中枢调节,但有时可被随意地启动或压抑.咳嗽感受器主要集中分布于气管后壁、隆突、大气道分叉处及咽部、喉、鼻旁窦、外耳道和胃等等,因此诊疗咳嗽时要注意不仅仅要考虑是什么疾病,还要考虑是什么相关感受器所在部位引发的咳嗽.咳嗽町被热的、化学的、机械的或炎性的刺激所诱发,随之而来产生快速呼气,因为快速呼气可排出呼吸道分泌物,所以治疗时常常会想要止咳。
Efficacy and safety of anlotinib combined with transarterial chemoembolization versus transarterial chemoembolization alone in patients with unresectable hepatocellular carcinoma: A retrospective study.
Authors: Wenbo Guo, Song Chen
Journal: Journal of Clinical Oncology (2020)

e16611 Background: HCC is one of the most common cancer among all the malignant tumor, while the efficacy of TACE alone for unresectable HCC patients still remains unsatisfactory. With the development of targeted drug, more and more targeted drugs are applying to the treatment of HCC. Objective: The aim of the stidy is to investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with Anlotinib versus TACE alone in patients with unresectable HCC. Methods: This single-center retrospective study involved 82 patients with unresectable HCC who underwent TACE alone (TA group; n=46) or TACE combined with Anlotinib (TC group; n=36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes included the objective response rate (ORR), the disease control rate (DCR) and main complications. Results: The TC group showed relatively higher PFS than the TA group (7.35months vs. 5.54 months, p=0.035). The 3-month survival rate was not statistically different between the two groups (97.2% vs. 93.5%, p=0.627), while both the 6-month survival rate and 1-year survival rate were significantly higher in the TC group than in the TA group (83.3% vs. 56.5%, p=0.016; 66.7% vs. 19.6%, p&lt;0.01). ORR in the TA group was significantly higher than in the TC group (77.8% vs. 32.6%, p&lt;0.01), while the two groups showed no statistical difference in DCR (94.4% vs. 82.6%, p=0.17). No treatment-related mortality or grade 4 adverse event was observed, but grade 3 adverse events occurred in two patients in the TC group (one suffered with erythra, and another suffered with hand-foot-skin reaction). Both of them disappeared after prompt treatment. Conclusions: TACE combined with Anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. It still needs more further randomized controlled trials to clarify the potential role of Anlotinib in hepatocellular carcinoma. Key words: Hepatocellular carcinoma; Anlotinib; Transarterial chemoembolization