tbuckley/cabot-search huggingface dataset:
Safety and tolerability of MEDI0562 in combination with durvalumab or tremelimumab in patients with advanced solid tumors.
Authors: Jonathan Wade Goldman, Sarina Anne Piha-Paul, Brendan D. Curti, Katrina Pedersen, Todd Michael Bauer, Stefanie L. Groenland, Richard D. Carvajal, Vaishali Chhaya, Scott A Hammond, Katie Streicher, Danielle Michelle Townsley, Young Kwang Chae, Jens Voortman, Aurelien Marabelle, John D. Powderly
Journal: Journal of Clinical Oncology (2020)

3003 Background: We report safety and tolerability of MEDI0562, a humanized IgG1 κ OX40 monoclonal antibody (mAb), in combination with durvalumab (durva; anti-PD-L1 mAb) or tremelimumab (treme; anti-CTLA-4 mAb) in patients (pts) with previously treated advanced solid tumors. Methods: In this phase 1, open-label study (NCT02705482), adult pts received escalating doses of MEDI0562 (2.25, 7.5 or 22.5 mg/kg) every 2 wks (Q2W) in combination with durva (1500 mg/kg) or treme (75 or 225 mg/kg) Q4W, until confirmed disease progression or unacceptable toxicity. Tumor assessments were performed Q8W with immune-related Response Evaluation Criteria in Solid Tumors. Results: In total, 27 and 31 pts received MEDI0562 + durva or treme, across 5 dose combination cohorts (3 + 3 design), with a maximum tolerated dose of 7.5 mg MEDI0652 + 1500 mg durva and maximum administered dose of 10 mg MEDI0562 + 225 mg treme. Median duration of exposure was 12.0 (range 2.0–80.9) and 8.0 (range 2.0–42.0) wks, respectively. Two (22.5 mg MEDI10562 + durva) and 3 (2.25 mg MEDI0652 + 225 mg treme, 22.5 mg MEDI0562 + 75 and 225 mg treme) dose limiting toxicities were observed. For MEDI0562 + durva and MEDI0562 + treme groups respectively, treatment-emergent adverse events (TEAEs) were reported in 96.3% and 100% of pts; most common TEAEs were fatigue (55.6%) and pruritus (45.2%), Gr 3/4 TEAEs occurred in 74.1% and 67.7%; and MEDI0562-related AEs were reported in 20 (74.1%) and 24 (77.4%) pts. Six TEAEs in each group led to MEDI0562 discontinuation (22.2% and 19.4%, respectively), 2 led to death (renal failure [7.5 mg MEDI0562 + durva], multiple organ dysfunction syndrome [22.5 mg MEDI0562 + 225 mg treme]). Three response evaluable pts had PR (11.5% [7.5 and 22.5 mg MEDI0562 + durva, n = 26]). Median overall survival was 17.4 and 11.9 mos for MEDI0562 + durva and MEDI0562 + treme, with stable disease seen in 9 pts from each group, 34.6% vs 29.0%, respectively. Serum exposure of MEDI0562 increased dose proportionally. Post treatment serum antidrug antibody (ADA) was detected in 20 pts from MEDI0562 + durva and MEDI0562 + treme (74.1% and 71.4%, respectively). The impact of ADA on MEDI0562 pharmacokinetics was seen at all doses. Mean percentage of Ki67+CD4+ and Ki67+CD8+ memory T cells increased, while mean percentage of OX40+CD4+ memory T cells decreased following the first dose of MEDI0562 + durva or treme. Conclusions: The safety profile of MEDI0562 in combination with durva or treme was similar between groups. Clinical activity was observed with MEDI0562 + durva in pts with advanced solid tumors. Clinical trial information: NCT02705482 .
Factors related to the incidence of esophageal stenosis after treatment of advanced esophagus cancer.
Authors: Carla Simone Moreira de Freitas, Tiago Magalhães Bastos, Luiz Ronaldo Alberti, Lívia Maria Nicoletti Ariano Bastos, Aleida Nazareth Soares
Journal: Journal of Clinical Oncology (2020)

e16561 Background: Esophageal stenosis after curative treatment of esophageal cancer (CE) by radiochemotherapy has a high incidence, causing great impact to the patient’s health. Identifying risk factors for this type of pathology may provide earlier diagnosis and more effective follow-up for patients with CE undergoing curative radiotherapy. The objective of this study was to determine the risk factors for esophageal stenosis in patients with complete regression of the tumor lesion after advanced CE treatment with radiotherapy associated or not with chemotherapy. The choice of the theme is justified because there are no studies on esophageal stenosis after radiotherapy associated or not with chemotherapy in esophageal cancer in the west. Methods: Retrospective observational study with 103 patients of both sexes who presented total regression of esophageal squamous cancer, confirmed by endoscopy and biopsies, after treatment with or without chemotherapy. The relationship between the sexes, age, tumor staging, involvement of the esophageal circumference, tumor location, isolated use of radiotherapy or associated chemotherapy, and tumor extension with or without stenosis and its degree after treatment with total regression of the tumor. Results: Most patients are male (58.3%). There was a direct relationship between the degree of circumference involvement and the degree of stenosis and a significant association between tumor location and degrees of stenosis (p &lt; 0.001). The higher the degree of posttreatment stenosis, the higher the percentage of more advanced tumors (p &lt; 0.001). Regarding tumor extension, the greater the degree of stenosis after treatment, the greater the proportion of tumors larger than 60 mm (p &lt; 0.001). T3 tumors increase in 23.77 chance of post-treatment stenosis compared to T2 tumors. T4 tumors, increase the chance of presenting post-treatment stenosis 23.94 times compared to T2 tumors. Conclusions: Our data show that impaired esophageal circunference, tumor extension, advanced stages, and pretreatment tumor stenosis are factors related to esophageal stenosis following treatment with advanced radiochemotherapy for esophageal cancer.
Adjuvant lenvatinib in combination with TACE for hepatocellular carcinoma patients with high risk of postoperative relapse (LANCE): Interim results from a muticenter prospective cohort study.
Authors: Jin-hong Chen, Lu Lu, Tian-Fu Wen, Zhi-Yong Huang, Ti Zhang, Yong-Yi Zeng, Xiang-Cheng Li, Bang-De Xiang, Cai-de Lu, Xiao Xu, Lun-xiu Qin
Journal: Journal of Clinical Oncology (2020)

4580 Background: Surgical resection was the main treatment for hepatocellular carcinoma (HCC) in China. Multiple clinical studies had demonstrated that the overall survival (OS) of the surgical resection group was significantly better than the transcatheter arterial chemoembolization (TACE) or radiotherapy group even for HCC patients with BCLC stage B or C. There was no standard adjuvant therapy for HCC patients to decrease the post-operative tumor relapse. For HCC patients with high recurrence risk, TACE significantly reduced tumor recurrence, prolonged the disease free survival (DFS) and OS, and was recommended as the adjuvant therapy. However, its effect is not very satisfactory. The purpose of this study was to assess the efficacy and safety of lenvatinib in combination with TACE versus TACE alone as adjuvant therapy in HCC patients with high recurrence risk after resection. Methods: This is a muti-center prospective cohort study. The criteria of HCC patients with high postoperative recurrence risk included: accompanied with gross vascular or bile duct invasion (tumor thrombi in portal vein, hepatic vein or bile duct); or tumor rupture or invasion of adjacent organs; or grade 2 of microvascular invasion (MVI) (M2) along with the tumor number more than 3 or the maximum diameter of tumor larger than 8cm or tumor showed invasive growth with unclear boundaries and imcomplete capsules. The patients were divided into two groups, the lenvatinb (8mg qd for weights &lt; 60kg and 12mg qd for weights≥60kg) in combination with TACE (Len+TACE) group and the TACE group. Results: A total of 90 patients were enrolled into the study, while 45 patients in the Len+TACE group and 45 in TACE group. The media age was 52 years (range from 23 to 73 years). Most patients were males (82.2%) and 66 patients had HBV background (73.3%). There were no significant differences between the two groups in the baseline clinicopathological characteristics including gender, age, HBV background, liver cirrhosis, liver function, tumor characteristic and AFP level. The media DFS was 12.0 months (95% CI 8.0-NA) in the Len+ TACE group, which was longer than that of TACE group (8.0 months, 95% CI 6.0-12.0, P = 0.0359; HR 0.5, 95% CI 0.3-1.0). The most common grade 3 or 4 adverse events were hypertension (11.1%) and diarrhea (7.7%) in the Len+TACE group. Conclusions: Lenvatinib in combination with TACE was effective and safe as adjuvant therapy, which can prolong the DFS of HCC patients with high recurrence risk after resection. Clinical trial information: NCT03838796 .
Prescription Fill Patterns for Commonly Used Drugs During the COVID-19 Pandemic in the United States
Authors: Muthiah Vaduganathan, Jeroen van Meijgaard, Mandeep R. Mehra, Jacob Joseph, Christopher J. O’Donnell, Haider J. Warraich
Journal: JAMA (2020)

Prescription Fill Patterns for Commonly Used Drugs During the COVID-19 Pandemic in the United StatesConflicting information regarding the benefits of hydroxychloroquine/chloroquine and azithromycin in coronavirus disease 2019 (COVID-19) treatment and hypothetical concerns for drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have challenged care during the pandemic. 1However, limited data are available about how prescription of these therapies has changed.The objective of this exploratory analysis was to evaluate prescription patterns of these therapies, along with other commonly used drugs for reference, in the United States during the COVID-19 pandemic.We hypothesized that the prescription of hydroxychloroquine/chloroquine and azithromycin would exceed historical estimates while ACE inhibitor/ ARB use would be reduced.
Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.
Authors: Lucy Xiaolu Ma, Kirsty Taylor, Osvaldo Espin-Garcia, Chihiro Suzuki, Reut Anconina, Michael J Allen, Marta Honório, Yvonne Bach, Frances Allison, Eric Xueyu Chen, Jonathan Yeung, Gail Elizabeth Darling, Rebecca Wong, Sangeetha Kalimuthu, Raymond Woo-Jun Jang, Patrick Veit-Haibach, Elena Elimova
Journal: Journal of Clinical Oncology (2020)

4557 Background: Malnutrition and sarcopenia (defined as low skeletal muscle mass) are recognized as poor prognostic factors in many cancers. Studies to date in gastroesophageal cancer have largely focused on patients (pts) undergoing curative intent surgery. This study aims to evaluate the prognostic utility of nutritional markers and sarcopenia in pts with de novo metastatic gastric and esophageal adenocarcinoma (GEA). Methods: Pts with de novo metastatic GEA seen at the Princess Margaret Cancer Centre from 2010-2016 with available pre-treatment abdominal computed tomography imaging were identified from an institutional database. Nutritional index (NRI) was calculated using weight and albumin, with moderate/severe malnutrition defined as NRI &lt; 97.5. Skeletal muscle index (SMI) normalized by height was calculated at the L3 level using Slice-O-Matic software. Sarcopenia was defined as SMI &lt; 34.4cm 2 /m 2 in women and &lt; 45.4cm 2 /m 2 in men based on previously established consensus. Results: Of 175 consecutive pts, median age was 61, 69% were male, 79% had ECOG performance status 0-1, and 71% received chemotherapy. Median BMI was 24.2 (range 15.7-39.8), 70% of pts had &gt; 5% weight loss in the preceding 3 months, and 29% had moderate/severe malnutrition. 68 pts (39%) were sarcopenic, of whom 46% were malnourished. Median overall survival (OS) was 9.3 months (95% CI 7.3-11.4) for all pts. OS was significantly worse in malnourished pts (5.5 vs 10.9 months, p = 0.000475) and displayed a non-significant trend in sarcopenic pts (7.8 vs 10.6 months, p = 0.186). On univariable Cox proportional hazards (PH) analysis, ECOG (p &lt; 0.001), number of metastatic sites (p = 0.029) and NRI (p &lt; 0.001) were significant prognostic factors, while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable Cox PH analysis, ECOG (p &lt; 0.001) and NRI (p = 0.025) remained significant as poor prognostic factors for OS. Conclusions: This study demonstrates in a large cohort of de novo metastatic GEA pts that ECOG and NRI were significantly associated with poor OS. NRI was superior to BMI alone. Early identification of malnourished pts using NRI may allow for supportive interventions to optimize nutritional status. Further study is needed to determine whether these factors can be modified to improve prognosis in these pts.
INMUNOSUN-SOGUG trial: A prospective phase II study to assess the efficacy and safety of sunitinib as second-line (2L) treatment in patients (pts) with metastatic renal cell cancer (RCC) who received immunotherapy-based combination upfront.
Authors: Enrique Grande, Teresa Alonso Gordoa, Oscar Reig Torras, Emilio Esteban, Daniel Castellano, Xavier Garcia del Muro, María José Mendez Vidal, Jesús García-Donas, Jose Angel Arranz, Cristina Suarez Rodriguez
Journal: Journal of Clinical Oncology (2020)

5060 Background: Immunotherapy (IO)-based combinations have replaced tyrosine kinase inhibitors (TKI) as standard upfront treatment of metastatic RCC pts. Selection of 2L treatment after progression to novel combinations in 1st-line (1L) is mostly based on retrospective series or subgroups analysis of randomized trials. We aim to evaluate the activity and safety of sunitinib in advanced RCC after progression on an IO-based 1L approach. Methods: This is a prospective, non-randomized, open-label and multicenter phase II study. Pts with ECOG 0-2 and locally advanced or metastatic RCC after treatment in 1L with a prior PD-1 and/or PD-L1 and/or CTLA-4 inhibitor were included. Sunitinib was administered at 50 mg/day on a 4/2 schedule until disease progression. Primary endpoint was overall response rate (ORR) by RECIST v 1.1 criteria. Results: Twenty pts were enrolled in the study. Median age was 66 yo, 70% had intermediate prognosis by Heng's scale, and 88% ECOG 1. 45% of pts received atezolizumab, 30% pembrolizumab, 20% nivolumab and 15% ipilimumab-based regimens as 1L. ORR to 1L treatment was 45%. Median time from end of 1L to sunitinib onset date was 1.1 months (0.3-22.1). Two (10%) pts had partial response with sunitinib and 11 (55%) stable disease for a total disease control rate of 65%. With a median follow-up of 8.8 months, median PFS was 6.8 months (0.0-13.9) and median OS 13.6 months (10.5-16.6). Median duration of treatment was 4 months (0.9-16-2). Most common treatment-related adverse events, all grades, were asthenia (55%), dysgeusia (35%), diarrhea (30%), hypertension (30%), mucosal inflammation (25%), palmar-plantar erythrodysesthesia (25%), anemia (20%), neutropenia (20%) and nausea (15%); grade 3 were asthenia (15%), hypertension (10%) and neutropenia (10%). Conclusions: To our knowledge, the INMUNOSUN trial is the first study to evaluate prospectively the activity of a single agent TKI in a pure 2L setting of metastatic RCC pts treated with an IO-based approach upfront. ORR and PFS with sunitinib seem lower than expected when used as a 1L. Consistency in toxicity profile was observed. Clinical trial information: NCT03066427 .
Does time from diagnosis to treatment affect the prognosis of patients with newly diagnosed acute myeloid leukemia?
Authors: Christoph Röllig, Michael Kramer, Christoph Schliemann, Jan-Henrik Mikesch, Björn Steffen, Alwin Krämer, Richard Noppeney, Kerstin Schäfer-Eckart, Stefan W. Krause, Mathias Hänel, Regina Herbst, Volker Kunzmann, Hermann Einsele, Edgar Jost, Tim H. Brümmendorf, Sebastian Scholl, Andreas Hochhaus, Andreas Neubauer, Kristina Sohlbach, Lars Fransecky, Martin Kaufmann, Dirk Niemann, Markus Schaich, Norbert Frickhofen, Alexander Kiani, Frank Heits, Ulrich Krümpelmann, Ulrich Kaiser, Johannes Kullmer, Maxi Wass, Friedrich Stölzel, Malte von Bonin, Jan Moritz Middeke, Christian Thiede, Johannes Schetelig, Wolfgang E. Berdel, Gerhard Ehninger, Claudia D. Baldus, Carsten Müller-Tidow, Uwe Platzbecker, Hubert Serve, Martin Bornhäuser
Journal: Blood (2020)
Cut-off value of waist circumference for identifying metabolic syndrome in middle-aged and elder residents in Changfeng community of Shanghai
Authors: Sun-fang Jiang, Xin Gao, Li-min Ren
Journal: BMJ (2008)

Objective To explore an optimal cut-off value of waist circumference(WC)for identifying metabolic syndrome(MS)in middle-aged and elder residents in an urban community.Methods Database of 1558 residents aged 40-79 years at high-risk in screening for diabetes from Changfeng community,Putuo District,Shanghai during 2005 to 2007 was used to analyze sensitivity and specificity of varied cut-off values of WC for identifying two or more components of MS in men and women,respectively.Receiver operating characteristics(ROC)curve was used to explore the optimal value.Results Optimal cut-off value of WC was 85.0 cm for men and 80.0 cm for women,respectively,for identifying two or more components of MS bv ROC curve,with sensitivity of 72.3%and 74.9%,and specificity of 50.2%and 62.2%,respectively.Based on that optimal cut-off value of WC and definition of International Diabetes Federation(IOF),prevalence of MS was 38.8%in this population,40.7%in men and 37.8%in women,respectively.Conclusion The optimal cut-off value of WC was 85.0 cm in men and 80.0 cm in women,respectively,for identifying MS in the middle-aged and eldedy in an urban community of Shanghai.

Key words: 
Metabolic syndrome X; Waist circumference; Cross-sectional studies
Relationship between vitamin D and inflammatory diseases
Authors: Yang Li, Jianchun Xian, Aiwen Geng
Journal: BMJ (2016)

Traditionally regarded as a vitamin regulating calcium and phosphorus homeostasis, vitamin D is now discovered as a highly versatile molecule involved in immunity, cancer, infectious diseases, fibrosis, fatty liver diseases, and alcoholic liver diseases. In several studies, lower vitamin D status has been found to be associated with increased risk and unfavorable outcome of acute infections. This paper reviews the research progress of the roles played by vitamin D in various inflammatory diseases and its mechanisms.


Key words: 
Vitamin D; Inflammatory diseases
针刺醒神开窍疗法结合康复训练治疗阿尔茨海默病60例
Authors: 赵廷涛
Journal: BMJ (2007)

阿尔茨海默病(Alzheimer disease,AD)是一种痴呆综合征,在我国患者超过300万,约占痴呆患者的67.2%,已经成为严重危害老年人健康的一种疾病.我们2001年以来应用针刺醒神开窍疗法配合康复训练治疗本病,取得了较满意的疗效。
Intrarenal renin-angiotensin system in hypertensive patients with localized kidney cancer.
Authors: Roman Osokin, Ekaterina Komarova, Igor Aboyan, Aleksey Yu. Maksimov, Roman Ischenko, Olga Shatova, Elizaveta Komarova
Journal: Journal of Clinical Oncology (2020)

e17069 Background: In the last decade, the relationship between arterial hypertension and the risk of developing kidney cancer has been pointed out. Some studies have shown that the metabolic imbalance of the components of the renal renin-angiotensin system (RAS) is associated with the development and progression of kidney cancer. Aim: To study the state of RAS in tumor and peritumoral tissues in hypertensive patients with kidney cancer. Methods: In patients with localized kidney cancer T1N0M0 and grade I-II arterial hypertension without special treatment (n = 40; KC + AH) in the samples of tumor (TT), peritumoral (PTT) and histologically unchanged tissue (HUT), the levels of angiotensin 1 and 2, 1-7 (AT1 and AT2, AT (1-7)) of angiotensin-converting enzymes (ACE and ACE2) were determined by ELISA. The comparison group consisted of patients with RC without impaired blood pressure (n = 55, KC). Results: In patients with KC, the level of AT1 is 1.5 times higher (p &lt; 0.05), and AT2 is 1.6 times higher (p &lt; 0.05) in TT against the background of unchanged content in PTT compared with HUT. The level of ACE is higher than HUT by 2.7 times, ACE2 - by 1.6 times (in all cases p &lt; 0.05), and in PTT it is identical in HUT. In patients with KC + AH, the level of AT1 and AT2 in the TT is 1.8 times higher (p &lt; 0.05) and 2.1 times (p &lt; 0.01), respectively, the content of AT(1-7) is 1.6 times (p &lt; 0.01). In PTT, AT1 is 1.6 times higher (p &lt; 0.01) and AT2 is 1.9 times higher (p &lt; 0.05), significantly lower than only AT2 in the TT (1.2 times at p &lt; 0, 05). The level of AT(1-7) in the PTT is identical to the values in the GNT. The content of ACE and ACE2 in TT is 3.6 and 2.9 times higher, respectively, and in PTT is identical to that in TT. Correlation analysis revealed a reliable direct relationship in the studied groups for all parameters, while in the PTT of hypertensive patients, the relationship between the average blood pressure and the RAS peptide content had a higher tightness. Conclusions: An increase in the levels of angiotensin 1 and 2, angiotensin-converting enzymes ACE and ACE2 in the tumor tissues and peritumoral tissue in patients with localized kidney cancer, regardless of the presence of arterial hypertension at initially higher values in hypertensive patients, was shown. The presence of arterial hypertension in patients with KC changes the metabolism of local RAS in peritumoral tissue and is associated with an increase in the correlation between changes in the components of RAS and arterial hypertension.
Treatment patterns and outcomes by age in metastatic melanoma: A study of the National Cancer Database.
Authors: Justin Moyers, Esther G Chong, Gayathri Nagaraj
Journal: Journal of Clinical Oncology (2020)

12037 Background: Metastatic melanoma carries poor prognosis and traditional chemotherapy has limited efficacy. Immune checkpoint inhibitors (ICI) have drastically improved disease outcomes since first approved in 2011. Elderly patients were underrepresented in landmark early trials of ICI leading to limited clinical trial data on efficacy and treatment patterns in this population. We aimed to examine the real-world IO outcomes and demographics of elderly patients in the National Cancer Database. Methods: We queried the database for patients with stage IV melanoma diagnosed between 2011-2015 with survival data available. Patients were divided into receipt of immunotherapy (IO) or no receipt of IO; those without documentation were excluded. Cases were separated into 3 cohorts of age at diagnosis (60 years-old or younger, 61-74 years-old, and 75 years-old and greater). Descriptive variables were compared by Chi-squared analysis and survival analyses were performed by Kaplan-Meier method and log-rank test. Results: 11,265 cases met inclusion criteria: 4,117 aged 60 or less, 3,940 aged 61-74, and 3,208 aged 75 or older. Those receiving immuno-oncologic agents (IO) in all age groups showed a longer median OS (mOS) than those who did not receive IO (mOS overall 17.28 v 7.49; p &lt;0.01). Survival was longer in all age cohorts when IO was received compared to not received; ages less than 60 (mOS 20.3 v 9.2m; p&lt;0.01), ages 61-74 (mOS 15.5 v 7.8m; p&lt;0.01), and ages 75 or greater (mOS 14.4 v 5.8m; p&lt;0.01). A greater percentage of patients received IO in younger than older cohorts, 20.1% in ≥ 75, 37.6% in 61-74, and 42.3% in ≤ 60; p &lt;0.01. Additional descriptive variables shown in the table were compared between the cohorts include care at academic or integrated cancer network, uninsured, Charlson-Deyo Comorbidity Index (CDCI) of 2 or greater, and documented inclusion of palliative care treatment. Conclusions: Substantial survival benefit is realized with IO in all age cohorts although elderly cohorts did not receive IO as often as younger cohort. Elderly patients experienced lower rates of care at academic/network cancer programs, lower uninsured rate, and higher CDCI. [Table: see text]