tbuckley/cabot-search huggingface dataset:
Neutrophil to lymphocyte ratio, PD-L1 expression, and survival in patients with advanced non-small cell lung cancer receiving first-line immune checkpoint inhibitor therapy.
Authors: Mingjia Li, Songzhu Zhao, Daniel Spakowicz, Jarred Thomas Burkart, Sandip H. Patel, Marium Husain, Kai He, Erin Marie Bertino, Peter G. Shields, Lai Wei, Carolyn J Presley, Gregory Alan Otterson, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2020)

46 Background: Neutrophil to lymphocyte ratio (NLR) is known to be prognostic for patients with various types of cancer, including those who are treated with immune checkpoint inhibitors (ICI). We evaluated NLR at baseline and during early phase of treatment for patients with advanced non-small cell lung cancer (NSCLC) who received ICI to evaluate its prognostic value in first line ICI therapy and its relationship to programmed death-ligand 1 (PD-L1) expression. Methods: We retrospectively evaluated patients with advanced NSCLC who received ICI as first line therapy from 2016 to 2018. NLR was calculated as ratio of absolute neutrophil/lymphocyte counts and was consider elevated if ≥5. PD-L1 expression by immunohistochemistry was performed as standard of care with 22C3 antibody. Kaplan Meier analysis was used for survival. Wilcoxon-Mann-Whitney test was used to evaluate PD-L1 expression between groups. All Calculation was performed using SAS V9.4. Results: A total of 78 patients were included in this study; 28 received pembrolizumab monotherapy, 45 received pembrolizumab, carboplatin, and pemetrexed, and 5 received other pembrolizumab combinations. Patients with baseline NLR &lt; 5 before initiating ICI had median estimated OS of 46.1 months (79.4% patient still alive and 95% CI not reached) compare to median OS of 10.7 months (95% CI lower limit 6.4 and upper limit not reached) for patients with NLR ≥5, P &lt; 0.001. Similar association between NLR and OS can be seen when NLR were repeated immediate before the cycle 2 with P = 0.001. We observed an association between baseline NLR and PD-L1 expression. The median PD-L1 tumor proportion score (TPS) was 60% (Interquartile Range 1-80) for patients with baseline NLR &lt; 5 vs 20% (IQR 0-60) for patients with NLR ≥5, P = 0.037. Conclusions: We confirmed the prognostic value of NLR for patients with advanced NSCLC at baseline and during early treatment in patients with NSCLC receiving first line ICI treatment. We also found an association between elevated NLR and lower PD-L1 expression. Future study with larger cohort is still needed to further delineate these relationships.
Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
Authors: Robert A. Figlin, Nizar M. Tannir, Robert G. Uzzo, Scott S. Tykodi, David Y.T. Chen, Viraj Master, Anil Kapoor, Daniel Vaena, William Lowrance, Gennady Bratslavsky, Mark DeBenedette, Alicia Gamble, Ana Plachco, Marcus S. Norris, Joe Horvatinovich, Irina Y. Tcherepanova, Charles A. Nicolette, Christopher G. Wood
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS. Results: Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0–35.9] and 32.4 months (95% CI, 22.5–) in the SOC group HR of 1.10 (95% CI, 0.83–1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92–1.44)]. The ORR was 42.7% (95% CI, 37.1–48.4) for the combination group and 39.4% (95% CI, 31.6–47.5) for the SOC group. Median follow up was 29 months (0.4–47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC-treated patients, but are associated with poor outcomes in patients receiving SOC treatment. No serious adverse events attributed to the study medication have been reported to date. Conclusions: Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.
Noninvasive comprehensive genomic profiling from plasma ctDNA in pancreatic cancer patients.
Authors: Danielle Sara Bitterman, Kristin Sedgwick Price, Emily E. Van Seventer, Jeffrey William Clark, Jill N. Allen, Lawrence Scott Blaszkowsky, David P. Ryan, Christine Elissa Eyler, Jennifer Yon-Li Wo, Theodore S. Hong, Ryan David Nipp, Eric Roeland, Janet E. Murphy, Ryan Bruce Corcoran, Colin D. Weekes, Aparna Raj Parikh
Journal: Journal of Clinical Oncology (2020)

753 Background: The use of comprehensive genomic profiling (CGP) is increasing in pancreatic ductal adenocarcinoma (PDAC) as knowledge improves regarding molecular drivers of tumorigenesis and effective targeted therapies emerge. However, adequate tissue sampling is often limited. Plasma-based CGP offers a non-invasive approach to assess biomarkers that may impact treatment decisions. Methods: We retrospectively evaluated genomic and clinical data from 97 PDAC patients with circulating tumor DNA (ctDNA) testing from 9/2016-8/2019 (Guardant Health, Inc.). ctDNA analysis included single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 74 genes. ctDNA results were assessed across clinical variables. We evaluated for actionable alterations. Results: A total of 114 samples were obtained from 97 patients for ctDNA testing. ctDNA alterations were detected in 82% (93/114) of all samples, including 90% (18/20) at diagnosis, 88% (59/67) at progression, and 56% (10/18) while on stable therapy. ctDNA alterations were found at each stage of PDAC: in 25% (1/4) of samples with resectable disease, 75% (3/4) with borderline resectable disease, 82% (9/11) with locally advanced disease, and 85% (81/95) with metastatic disease. One or more KRAS alterations were detected in 55% (51/93) of patients with alterations present. The median maximum mutant allele frequency was similar between the cohort of patients with KRAS detected (0.55%) versus not detected (0.70%). 8% (8/97) of patients had potentially actionable alterations (2 activating BRAF SNVs, 1 ERBB2 CNV, 1 ERBB2 activating SNV, 1 KRAS G12C, and 3 indels in Homologous Recombination Deficiency genes). Median turnaround time was 8 days. 51% (49/97) of patients had both plasma-based CGP and tissue-based CGP. Of these patients, tissue-based CGP showed ≥ 1 alterations detected in 82% (40/49), test failure in 14% (7/49), and no alterations detected in 4% (2/49). Conclusions: Plasma-based CGP detected ctDNA alterations in 90% of samples tested at diagnosis and 82% of all samples. Potentially actionable mutations were found in 8% of patients, with prompt processing time allowing for rapid decision making.
WITHDRAWN: Characterization of Patterns of Immune Cell Infiltration in NSCLC
Authors: Max Backman, Linnéa La Fleur, Pinja Kurppa, Dijana Djureinovic, Hedvig Elfving, Hans Brunnström, Johanna S.M. Mattsson, Victor Pontén, Mohamed Eltahir, Sara Mangsbo, Johan Isaksson, Karin Jirström, Klas Kärre, Ennio Carbone, Karin Leandersson, Artur Mezheyeuski, Fredrik Pontén, Cecilia Lindskog, Johan Botling, Patrick Micke
Journal: Journal of Thoracic Oncology (2020)
一项探讨称不同类型重度皮疹(急性皮疹)的研究
Authors: O. Deschamps, N. Ortonne, S. Hüe, C. Rodriguez, C. Deschodt, G. Hirsch, A. Colin, L. Grégoire, M.‐H. Delfau‐Larue, O. Chosidow, P. Wolkenstein, S. Ingen‐Housz‐Oro
Journal: British Journal of Dermatology (2020)

摘要 重度皮疹,也称为急性皮疹 (AE),常见于医院。最常见的类型称为斑丘疹 (MPE),另一种类型为玫瑰糠疹。 AE(尤其是 MPE)的主要原因是药物(迟发超敏反应)和病毒(如艾滋病毒、人疱疹病毒 6 - HHV6 和麻疹病毒),但某些病因尚未确定,称为特发性。 目前没有任何指南提供有关需要进行哪些检测(病毒检测)的指导。研究人员进行了这项研究,以更好地描述 AE,并探讨对 AE 原因进行检查(细胞因子和宏基因组学分析)的价值。 研究纳入了法国 Henri Mondor 医院诊治的 98 例患者。患者接受了医生检查和病毒检测,并进行皮肤活检(组织样本)。 患者分为五组:病毒组(18 例)、药物诱发组(33 例)、药物诱发和病毒(5 例)、特发性(32 例)和玫瑰糠疹(10 例)。 HHV6 是发现的最常见病毒 (74%)。 针对细胞因子蛋白质水平的分析发现,特发性皮疹(即原因不明的皮疹)中白介素-33 的细胞因子水平较高。这可能表明环境因素是触发因素。 这项研究首次证明在皮肤上进行宏基因组学分析(研究遗传物质)的可行性,研究结果对一些常规使用的病毒检测是否总是有用提出了质疑。 本研究摘要: 急性皮炎: 在 98 例成年患者中进行的以细胞因子和宏基因组学为研究重点的前瞻性研究
Phase II study of copanlisib in combination with gemcitabine and cisplatin in advanced cholangiocarcinoma.
Authors: Elaine Tan, Dae Won Kim, Rutika Mehta, Biwei Cao, Jongphil Kim, Angel Meroni, Barbara Centeno, Richard D. Kim
Journal: Journal of Clinical Oncology (2020)

556 Background: First line therapy for advanced cholangiocarcinoma (CCA) is currently gemcitabine and cisplatin. However, survival rarely exceeds one year with this regimen. PI3K/AKT activation has been shown to increase resistance to chemotherapy in CCA; therefore, inhibiting this pathway may improve chemotherapy’s efficacy. This phase II study evaluated the safety and efficacy of copanlisib, a potent and reversible pan-class I PI3K inhibitor, with gemcitabine and cisplatin in advanced CCA. Methods: Between July 2016 and April 2019, pts with histologically confirmed advanced/unresectable CCA received cisplatin (25 mg/m 2 ), gemcitabine (1000mg/m 2 ), and copanlisib 60mg on day 1 and 8, every 21 days as first line treatment. The primary endpoint was PFS at 6 months. Secondary endpoints were RR, median OS and PFS, and safety profile. A single-arm Simon’s two-stage minimax design with one-sided 10% type I error and 80% power was used. Based on ABC-01 and ABC-02 studies, PFS6 for gemcitabine and cisplatin were 57.1% and 59.3%, respectively. Therefore, PFS6 of 57% was considered not to warrant further study and ≥72% to warrant further investigation. Results: Twenty-four pts received at least one dose of the study drug (62.5% female, median age 64 years), with 70.8% intrahepatic, 16.7% extrahepatic, and 12.5% gallbladder cancer. For all pts, median OS was 13.9 months (95% CI: 6.8-17.9) and median PFS was 6.2 months (95% CI: 1.3-11.1). PFS at 6 and 12 months was 57.0% and 42.2%, and 6 and 12-month OS was 73.9% and 53.2%, respectively. Only 19 pts were considered evaluable for RR. Five pts were either lost to follow up, withdrew consent, or died before a second scan was done. Six pts achieved PR (31.5%) and 11 (57.9%) had SD. Grade 3 or higher adverse events (AE) occurred in 75% of pts. The most common grade 3/4 AEs were decreased neutrophil count (40%) and increased lipase (20%). Treated related AEs led to drug discontinuation for 3 pts (12.5%) and dose modification for 7 pts (29.2%). Conclusions: Gemcitabine, cisplatin, and copanlisib in combination did not meet the primary endpoint of 6-month PFS. However, additional correlative work is ongoing to identify a possible biomarker for copanlisib. Clinical trial information: NCT02631590.
Shortened medical training for physiotherapists and pharmacists must not reduce standards, doctors warn
Authors: Abi Rimmer
Journal: BMJ (2020)

The government has announced proposals for existing healthcare professionals, such as physiotherapists or pharmacists, to train as doctors in less than five years.

The Department of Health and Social Care (DHSC) said that now that the UK has left the European Union, people who were already working as healthcare professionals could train to become doctors and nurses more quickly.1 Currently, medical training standards set by the EU mean that doctors have to train for a minimum of five years.

Under the potential new system, however, a physiotherapist who has been in the job for 10 years could complete training based on their experience and qualifications, rather …
Reply to Mehmood: Asthma and Obstructive Sleep Apnea: Taking It to Heart
Authors: Mihaela Teodorescu, Sharmilee M. Nyenhuis, Bharati Prasad
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

between asthma and obstructive sleep apnea (OSA) (1).However, to develop a personalized approach toward the treatment of comorbid pulmonary diseases with systemic spillover of inflammation (1), we have to appreciate their cardiovascular interactions (2).Because the cardiovascular impact of OSA and chronic obstructive pulmonary disease is relatively well described (2), a brief discussion with regard to asthma and cardiovascular disease (CVD) is warranted.A recent large retrospective cohort of patients admitted to National Health Service hospitals in the United Kingdom reported a strong and independent association of asthma, chronic obstructive pulmonary disease, and interstitial lung disease with CVD (3).Asthma was independently associated with ischemic heart disease, and heart failure (hazard ratio, 1.81; 95% confidence interval, 1.75-1.87)and ischemic heart disease (hazard ratio, 1.04; 95% confidence interval, 1.01-1.07)were among the variables that were independently associated with mortality in patients with asthma (3).In another large study, late-onset asthma, diagnosed at age >18 years, was associated with an increased risk of incident CVD events after adjustment for age, sex, and CVD risk factors (4).In a biracial, community-based, long-term investigation of risk factors and natural history of CVD, young adults with a history of asthma were found to have a significantly greater risk of increased left ventricular mass index independently of other major cardiovascular risk factors (5).Many similarities exist between the biochemical and cellular pathways of cardiac and pulmonary fibrosis (6).As we read the article by Prasad and colleagues and appreciate the multifaceted overlap between asthma and OSA, we have to remind ourselves of the current evidence and knowledge gaps regarding cardiopulmonary interactions in asthma to help improve risk stratification, devise precise management strategies, and identify novel therapeutic targets.
No man is an island: e-cigarette, or vaping, associated lung injury in Europe
Authors: Denitza P. Blagev
Journal: European Respiratory Journal (2020)

<b>The first case of e-cigarette, or vaping, associated lung injury (EVALI) diagnosed and treated in Europe reminds us to remain vigilant for this diagnosis, and importantly, that we are still learning about the full spectrum of risks of e-cigarette use</b>http://bit.ly/2TauItr
Trends in Racial and Ethnic Diversity in Internal Medicine Subspecialty Fellowships From 2006 to 2018
Authors: Lekshmi Santhosh, Jennifer M. Babik
Journal: JAMA Network Open (2020)

ResultsA total of 298 820 IM residents and 124 382 subspecialty fellows were included in our sample; 2184 residents (0.7%) and 1001 fellows (0.8%) who identified as multiracial and 42 377 residents (14.2%) and 8222 fellows (6.6%) whose race/ethnicity was other or unknown were excluded.Between 2006 and 2018, the annual number of IM residents and subspecialty fellows increased (from 21 855 to 26 228 residents and 8144 to 10 578 fellows) (Table ).Over time, the percentage of UIM trainees was unchanged in IM residencies (2688 [12.3%; 95% CI, 11.9%-12.7%]to 3599 [13.7%; 95% CI, 13.3%-14.1%];P = .28)but increased in all subspecialty fellowships (874 [10.7%; 95% CI, 10.1%-11.4%] to 1299 [12.3%; 95% CI, 11.7%-12.9%];P < .001)(Table; Figure, A).However, there were substantial
Blood-based-inflammation-markers, body mass index, and survival of nonmetastatic esophageal cancer.
Authors: Wanning Wang, Joelle Soriano, Tyler Soberano, Katrina Hueniken, M. Catherine Brown, Kirsty Taylor, Jaspreet K. Bajwa, George Dong, Eric Xueyu Chen, Jennifer J. Knox, Raymond Woo-Jun Jang, Rebecca Wong, Gail Elizabeth Darling, Wei Xu, Micheal McInnis, Geoffrey Liu, Dmitry Rozenberg, Elena Elimova, Aline Fusco Fares
Journal: Journal of Clinical Oncology (2020)

324 Background: Blood-based-inflammation-markers (BBIM) and Body Mass Index (BMI) have been associated with overall survival (OS) in a number of cancers. Inflammation and obesity have biological interactions. We evaluated the role of Neutrophil-to-Lymphocyte-Ratio (NLR), Platelet-to-Lymphocyte-Ratio (PLR) and Systemic-Inflammation-Index (SII) in conjunction with BMI as predictors of OS in localized/locally-advanced-esophageal cancer (LEC/LAEC). Methods: LEC/LAEC patients treated from 2006-2014 had the following variables analyzed both as continuous and categorical: BMI (low &lt;25 kg/m 2 , high ≥25 kg/m 2 ), NLR (low &lt;4, high ≥4), PLR (low &lt;232, high ≥232), and SII (low &lt;1375, high ≥1375), with OS. Univariate (UVA) and Multivariate analysis (MVA) were analyzed using Cox regression (adjusted hazard ratios, aHR; 95% Confidence Intervals, CI). MVA models of OS were built, assessing different categorical combinations of BBIM factors with and without BMI. Results: Of 411 pts, 79% were males, median age was 63.5 years, 67% were adenocarcinomas; Stage I/II/III: 14%, 28%, 59%; Median BMI was 26.5kg/m 2 and BMI distribution was: 3% underweight, 40% normal weight, 37% overweight and 20% obese. After a median follow-up of 87 months, 204 pts recurred, and 257 died. In MVA, BMI alone had no impact on OS (aHR 0.89, CI 0.7-1.1, p=0.15); individually as continuous variables, higher SII (p=0.03) and higher NLR (p=0.006) were inversely associated with OS whereas higher PLR was not (p=0.10). In an MVA of categorical combinations of BMI and BBIM on OS, patients in the high-BMI/low-PLR group were at lower risk of death when compared to all other groups (aHR=0.65, 95%CI:0.5-0.8, p=0.007). Similar non-statistically significant trends were shown when SII and NLR were individually combined with BMI (aHR=0.77, 95%CI:0.6-1.0, p=0.09; aHR=0.74, 95%CI:0.5-1.0, p=0.05, respectively). Conclusions: Our results suggest that in LEC/LAEC pts, high BMI and low PLR together are associated with improved OS when compared to pts with low BMI and/or high PLR. NLR and SII alone were associated with OS. Further studies evaluating the underlying mechanisms of BBMI, in particular PLR and inflammation/obesity are warranted.
A phase Ib/II study of the anti-CD47 antibody magrolimab with cetuximab in solid tumor and colorectal cancer patients.
Authors: George A. Fisher, Nehal J. Lakhani, Cathy Eng, J. Randolph Hecht, Johanna C. Bendell, Philip Agop Philip, Peter J. O'Dwyer, Benny Johnson, Adel Kardosh, Tina M Ippolito, Yan V. Wang, Balaji Agoram, Jens-Peter Volkmer, Roy Maute, Isagani Chico, Mark Chao, Chris H.M. Takimoto, Amita Patnaik
Journal: Journal of Clinical Oncology (2020)

114 Background: Magrolimab (M, Hu5F9-G4) is an antibody targeting CD47, a macrophage “don’t eat me” signal that demonstrates preclinical synergy with cetuximab (C) in refractory KRAS wild type (KRASwt) and KRAS mutant (KRASm) colorectal (CRC) tumors. Methods: Phase (Ph) 1 doses of M+C were escalated in solid tumor patients (pts) and Ph 2 efficacy was explored in previously treated KRASwt and KRASm CRC patients. Day 1 priming with 1 mg/kg of M was used to mitigate on-target anemia followed by maintenance doses ranging from 10 to 45 mg/kg in combination with C. Ph 2 pts were treated with 30 or 45 mg/kg of M and 400/250 mg/m2 of C. Results: In 78 treated pts (32 Ph 1 and 46 Ph 2), the median age was 59 years (range 19-82), and median prior therapies was 5 (range 1-14). No maximum tolerated dose was reached. Treatment-related adverse events (TRAEs) of any Grade (G) included dermatitis acneiform 36%, dry skin 33%, fatigue 32%, infusion reactions 31%, headache 30%, diarrhea 23%, nausea 23%, chills 23%, and anemia 22%. There were no fatal TRAEs and 3/78 (4%) discontinued M treatment due to any adverse events. In the combined Ph 1+2 study, 2 of 30 evaluable KRASwt CRC pts had confirmed PRs for 7.0 and 12.5 months (mo), for a 6.7% objective response rate (ORR). Both had prior C treatment. The median progression-free survival (mPFS) and median overall survival (mOS) was 3.6 mo (95%CI 1.8-5.4) and 10.1 mo (95%CI: 6.9-14.4), respectively. In 40 evaluable KRASm pts, there were no responses but 45% had stable disease (SD) and the mPFS and mOS were 1.9 mo (95%CI: 1.8-3.5) and 10.4 mo (95%CI: 5.7-16.4), respectively. In 28 KRASm pts who were TAS102/regorafenib naïve, preliminary mOS was 12.4 mo (95%CI: 5.9-not reached) which is longer than that reported for historical controls. Tumor biopsies showed treatment-related increases in macrophage immune cell infiltrates in SD pts, and baseline T cell infiltration was associated with longer OS. Pharmacokinetic profiles will be presented. Conclusions: M+C is a novel, well-tolerated combination immunotherapeutic treatment regimen. Responses were observed in two previously treated CRC pts and survival is encouraging in KRASm pts. Funded by Forty Seven and California Institute for Regenerative Medicine. Clinical trial information: NCT02953782.