tbuckley/cabot-search huggingface dataset:
A discrete choice experiment (DCE) study evaluating preferences of Asian adults for inherited cancer risk testing.
Authors: Ru Jin Tay, Pan Zhao, Hao Chen, Min-Han Tan, Josephine Shuk Ching Chong
Journal: Journal of Clinical Oncology (2020)

e13550 Background: Inherited cancer genetic testing (CGT) is increasingly recommended in a wide range of settings to better evaluate and manage personal and/or family cancer risks. For individuals at risk, identification of monogenic risk factors by inherited CGT allows more appropriate advice, surveillance and targeted prevention. For cancer patients, inherited CGT provides guidance for the selection of targeted therapy treatment options. Little is known about the views of non-Western global communities, which can impact cancer prevention. We designed a DCE study to evaluate four key attributes to better target educational and policy interventions in an urban Asian community. Methods: We recruited healthy adults in the community aged between 21-60 in Singapore. Participants received basic information about cancer and cancer genetic testing, then completed a 16-task DCE survey that examined preferences for four attributes of cancer genetic testing for targeted prevention including: accuracy, waiting time for result, out-of-pocket cost and insurance claims. A conditional logit regression model was used to examine the main effect parameter, assuming all attributes have an independent influence on the participants’ preferences. Results: 93 adults were enrolled (71% female, 29% male). Attributes influencing decision to undergo inherited CGT in decreasing order of concern were accuracy (37%), out-of-pocket costs (22%), insurance claim (21%) and waiting time for result (20%). Increased out-of-pocket cost reduces the likelihood of people to go for testing (coef: -6.579e −04 , p &lt; 0.01). The impact of financial cost is less important for participants with increased monthly household income (coef: 1.791e −04 , p &lt; 0.01). Conclusions: With inherited cancer genetic testing becoming more common and relevant in terms of personal and/or family risk managements and guiding treatment options, this DCE study is helpful to guide clinicians tailor of individualized genetic counseling for non-Western communities, who may have different concerns from Western populations. Targeted policy intervention and education on these concerns may lead to greater accessibility for inherited CGT.
Association between chronological age and geriatric assessment (GA) to identify deficits in elderly adults with cancer: Findings from the Care Registry.
Authors: Grant Richard Williams, Mustafa Al Obaidi, Alice Weaver, Kelly Kenzik, Andrew Michael McDonald, Mackenzi Pergolotti, Crystal Young Smith, Olumide B. Gbolahan, Ravi Kumar Paluri, Smita Bhatia, Smith Giri
Journal: Journal of Clinical Oncology (2020)

12048 Background: Although ASCO and NCCN guidelines recommend that adults with cancer diagnosed at age ≥65y undergo a GA, the association between chronologic age and GA identified deficits remains understudied, and thus, the appropriate age cut-off for employing GA in clinical settings remains unknown. We addressed this gap by examining the association between chronologic age and GA deficits in older adults with cancer. Methods: The Cancer and Aging Resilience Evaluation (CARE) is an ongoing prospective registry of older adults (≥60y) with cancer at a single site. Eligible patients underwent a patient-reported GA adapted from the Cancer and Aging Research Group. The association between age categories (10y increments) and presence of GA deficits was tested using chi-squared tests of trend. Linear association between age and GA deficits was examined using Pearson correlation. Results: The median age at enrollment was 70y (60-96) for 08 participants; 58% were male. Most common cancer types were colorectal (27%), pancreatic (17%), and hepatobiliary (12%). No significant correlation was found between chronologic age and the number of GA deficits (r = 0.03). There was no association between the youngest (60-70y) vs. the oldest age groups (≥80y) with respect to the prevalence of GA deficits: frailty (33% vs. 33%, p= 0.97); impairment of activities of daily living (ADL) (20% vs. 16%, p= 0.7);impairment of instrumental ADL (50% vs 60%, p= 0.3); malnutrition (42% vs. 33%, p =0.4), cognitive impairment (8% vs. 6%, p= 0.6), falls (19% vs. 30%, p 0.1), anxiety (19% vs. 11%, p= 0.1) and depression (13.4% vs. 13.7%, p= 0.2) (Table). Prevalence of 3+ comorbidities was higher in the older patients (45% vs. 59%, p= 0.03). Conclusions: In our cohort of older adults with mostly gastrointestinal malignancies, age was not associated with GA identified deficits and the prevalence of most impairments was similar across age-groups. The use of chronologic age alone to identify which patients may benefit from GA is problematic, and adults 60yrs and above, or perhaps even younger, may derive benefits from a GA. [Table: see text]
Learning guideline to improve diagnosis, treatment and management abilities of hyperthyroidism for primary doctors
Authors: Xing Xiaoyan
Journal: BMJ (2019)

甲状腺功能亢进症（甲亢）是内分泌系统常见疾病，其疾病谱广，临床表现具有异质性，如不能早期诊断和治疗，将对患者的健康造成很大危害。《甲状腺功能亢进症基层诊疗指南（2019年）》是国内第一个为基层医生量身定制的甲亢指南，内容涵盖甲亢的识别、诊断、治疗、双向转诊、管理等方面，旨在提高基层医生诊治、管理甲亢的能力，并在甲亢分级诊疗中发挥重要作用。
Toxicity burden in older patients with chronic lymphocytic leukemia (CLL) receiving bendamustine with rituximab (BR) or ibrutinib (IB) regimens: Alliance A041202.
Authors: Amy S. Ruppert, Sumithra J. Mandrekar, Allison M. Booth, Wei Ding, Nancy L. Bartlett, Danielle M. Brander, Steve E. Coutre, Jennifer R. Brown, Sreenivasa R. Nattam, Richard A. Larson, Harry Paul Erba, Mark Robert Litzow, Carolyn Owen, Charles S. Kuzma, Jeremy S. Abramson, Richard F. Little, Scott E. Smith, Richard M. Stone, John C. Byrd, Jennifer Ann Woyach
Journal: Journal of Clinical Oncology (2020)

e20004 Background: IB is a Bruton’s tyrosine kinase inhibitor that showed superior progression-free survival compared with BR in CLL patients (pts) 65 years or older in a randomized phase 3 trial (Woyach et al, NEJM 2018). Pts receiving IB had higher rates of atrial fibrillation (AFIB) and hypertension (HTN); BR pts had higher rates of hematologic toxicity. Differences in treatment duration for BR (6 cycles) and IB (until progression) complicated adverse event (AE) comparisons. Here we use an exploratory approach to compare toxicity burden between arms and provide assessment of AFIB, HTN and infections (INF). Methods: AEs were reported for each of cycles 1-6 and then every 3 cycles until progression or nonprotocol CLL therapy. Only grade (gr) 3-4 AEs were reported thereafter until death. A simple global AE score was calculated for each pt by summing grades of all gr 1-4 AEs and dividing by the number of cycles over which AEs were submitted. Results: 537 pts began therapy (176 BR, 361 IB). 68% on BR completed all 6 cycles. At a median follow-up of 38 months, 64% remained on IB. Treatment discontinuation for AE occurred in 10% and 14% of BR and IB pts. Overall, median AE score was 1.8 (interquartile range (IQR) 0.9-3.3) and 3.8 (IQR 2.3-5.9) in BR and IB arms (p &lt; 0.01). For cycles 1-6, median AE score was 6.2 (IQR 3.8-9.0) and 4.8 (IQR 3.0-7.2) in BR and IB arms (p &lt; 0.01). In the IB arm, median AE score post 6 cycles decreased significantly to 3.4 (IQR 1.9-5.6) (p &lt; 0.01). Gr 3 or higher cumulative rates of AFIB, HTN, and INF over time appear in the table. 100 pts (26/176 BR, 74/361 IB) had 137 severe INF (39% respiratory: 16 BR, 37 IB; 25% skin: 3 BR, 31 IB; 12% GU: 3 BR, 13 IB; 25% other: 12 BR, 22 IB). There were 7 gr 5 INF (3 BR, 4 IB), none confirmed fungal. Conclusions: There was no difference in treatment discontinuation rates for AE. Overall toxicity burden was significantly higher for IB, although IB toxicity burden decreased after 6 cycles. Toxicity burden was significantly higher in cycles 1-6 for pts receiving BR. Risk of severe AFIB, HTN, and INF is highest in the first year of IB. A simple AE score provides valuable information, especially when evaluating regimens of varying length. Clinical trial information: NCT01886872 . Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org ; Pharmacyclics; ClinicalTrials.gov Identifier: NCT01886872. [Table: see text]
在女性各生理阶段如何预防尿失禁
Authors: 韩劲松
Journal: BMJ (2005)

在国内外已有的关于女性尿失禁的流行病学调查资料中,虽然所采用的尿失禁定义、目标人群、调查方式和内容有所不同,结果有一定差异, 但多数调查结果显示,影响尿失禁发病的危险因素与年龄、分娩、肥胖、独居、缺乏帮助有关,便秘、慢性咳嗽、卒中、帕金森病、糖尿病也与尿失禁发病有一定的相关性.针对导致发病的高危因素,在女性各生理阶段采取相应的预防措施,以减少尿失禁的发生非常重要。
Serum cardiac troponin I and lactic acid in neonatal patients with hypoxic-ischemic encephalopathy
Authors: Dong-jie Guo, Guo-rui An, Yu-fen Wang, Hai-bin Liu
Journal: BMJ (2008)

Serum Cardiac troponin Ⅰ (cTn Ⅰ) and lactic acid were measured in 128 neonatal patients with hypoxic-ischemic encephalopathy and 38 healthy neonates (control group). Serum cTn Ⅰ and lactic acid levels were higher in neonates with hypoxic-ischemic encephalopathy than those in healthy neonates (P < 0. 05 ); and the differences of these values were also statistically significant between the serious patients and the mild patients (P<0.05). Serum cTn Ⅰ and lactic acid are two sensitive markers for degree of myocardial injury and hypoxia in neonatal patients with hypoxic-ischemic encephalopathy.

Key words: 
Hypoxia-ischemia,brain;  Troponin Ⅰ;  Lactic acid
"三九养阴"在2型糖尿病治疗中的临床观察
Authors: 王家涛, 卢泳
Journal: BMJ (2007)

将64例阴虚型2型糖尿病患者随机分为三九养阴组和对照养阴组,分别于节气中的三九期间和其他时间给予中药玉液汤治疗.从两组患者治疗后空腹血糖值及餐后2 h血糖值控制情况看,总有效率分别为94%和78%(P＜0.05),即在阴虚型2型糖尿病的治疗中,三九期间较非三九期间养阴效果更佳.三伏养阳,三九养阴作为春夏养阳,秋冬养阴理论的引申,可为临床治疗各种阳虚或阴虚型疾病的最佳时机的选择提供思路。
Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: The randomized RAPIDO trial.
Authors: Geke Hospers, Renu R. Bahadoer, Esmee A. Dijkstra, Boudewijn van Etten, Corrie Marijnen, Hein Putter, Elma Meershoek – Klein Kranenbarg, Annet G. Roodvoets, Iris D. Nagtegaal, Regina GH Beets-Tan, Lennart K. Blomqvist, Tone Fokstuen, Albert J. ten Tije, Jaume Capdevila, Mathijs P. Hendriks, Ibrahim Edhemovic, Andres Cervantes, Per J. Nilsson, Bengt Glimelius, Cornelis J. H. Van De Velde
Journal: Journal of Clinical Oncology (2020)

4006 Background: Local control in locally advanced rectal cancer (LARC) has improved. However, systemic relapses remain high even with postoperative chemotherapy, possibly due to low compliance. Short-course radiotherapy (SCRT) followed by delayed surgery with, in the waiting period, chemotherapy, may lead to better compliance, downstaging and fewer distant metastases. The main objective of the international multicenter phase III RAPIDO trial is to decrease Disease-related Treatment Failure (DrTF), defined as locoregional failure, distant metastasis, a new primary colon tumor or treatment-related death, by reducing the risk of systemic relapse without compromising local control. Methods: MRI-diagnosed LARC patients with either cT4a/b, extramural vascular invasion, cN2, involved mesorectal fascia or enlarged lateral lymph nodes considered to be metastatic were randomly assigned to SCRT (5x5 Gy) with subsequent six cycles of CAPOX or nine cycles of FOLFOX4 followed by total mesorectal excision (TME) (experimental arm) or, capecitabine-based chemoradiotherapy (25-28 x 2.0-1.8 Gy) followed by TME and optional, predefined by hospital policy, postoperative eight cycles of CAPOX or twelve cycles of FOLFOX4 (standard arm). Results: Between June 2011 and June 2016, 920 patients were randomized. Pathological complete response rates were 27.7% vs 13.8% (OR 2.40 [1.70 – 3.39]; p &lt; 0.001) in the experimental and standard arms, respectively. At three years, cumulative probability of DrTF was 23.7% in the experimental arm and 30.4% in the standard arm (HR 0.76 [0.60 – 0.96]; p = 0.02). Probability at three years of distant metastasis and locoregional failure were, in the experimental and standard arms, 19.8% vs 26.6% (HR 0.69 [0.53 – 0.89]; p = 0.004) and 8.7% vs 6.0% (HR 1.45 [0.93 – 2.25]; p = 0.10), respectively. No differences in DrTF between hospitals with or without policy for postoperative chemotherapy were found (p = 0.37). Overall health ( p = 0.192), quality of life ( p = 0.125) and low anterior resection syndrome score ( p = 0.136) were comparable between the two treatment arms. Conclusions: A lower rate of DrTF, as a result of a lower rate of distant metastases, in high-risk LARC patients can be achieved with preoperative short-course radiotherapy, followed by chemotherapy and TME than by conventional chemoradiotherapy. In addition, the high pCR rate, achieved with the experimental treatment regimen can contribute to organ preservation. This treatment can be considered as a new standard of care. Clinical trial information: NCT01558921 .
Expression and implications of human interleukin-32 in acute exacerbation with chronic obstructive pulmonary disease
Authors: Xing-qi Deng, Jin-yan Shao, Wei Gu, Mei Liu, De-shah Cheng, Ai-yong Yu
Journal: BMJ (2012)

Objective To measure the levels of human interleukin (IL)-32 in the serum and induced sputum of patients with chronic obstructive pulmonary disease (COPD) and investigate the possible roles of IL-32 in COPD.Methods Sixty patients with acute exacerbation of COPD ( AECOPD),60 patients with stable COPD,and 30 healthy subjects were recruited.The concentrations of IL-8,tumor necrosis factor alpha (TNF-α),and IL-32 in serum and induced sputum were measured by enzyme-linked immunosorbent assay (ELISA).The correlations among IL-32,IL-8,TNF-α,and lung functions were investigated. The data were analyzed using a statistical software package (SPSS 13.0).Variables were compared with one-way ANOVA,and correlations among variables were analyzed using Pearson's correlation coefficient or Spearman's correlation coefficient.Results The serum IL-32 level was significantly higher in AECOPD patients [(175 ± 88) ng/L] than in healthy subjects [ (59 ± 21 ) ng/L] and in stable COPD patients [ (89 ± 34) ng/L] (P ＜ 0.05) ; the serum IL-32 level was also significantly higher in stable COPD patients than in healthy subjects (P ＜ 0.05).The sputum IL-32 level was significantly higher in AECOPD patients [ ( 163 ± 117) ng/L] than in healthy subjects [ ( 75 ± 38 ) ng/L] and stable COPD patients [ ( 108 ± 63 )ng/L] (P ＜0.05); the sputum IL-32 level was also significantly higher in stable COPD patients than in healthy subjects ( P ＜ 0.05 ).The sputum IL-32 level in AECOPD patients was positively correlated with the sputum IL-8 and TNF-α levels (r =0.49 and 0.53,respectively) (P ＜0.01 ).The sputum IL-32 level in AECOPD patients was negatively correlated with FEV1 predicted values,FEV1/FVC,and PaO2 (r =-0.44to -0.33) (P ＜ 0.01 ).The serum IL-32 level in AECOPD patients was positively correlated with the serum IL-8 and TNF-o levels (r =0.45 and 0.61,respectively) (P ＜ 0.01 ).The serum IL-32 level in AECOPD patients was negatively correlated with FEV1 predicted values,FEV1/FVC,and PaO2 (r =-0.46to - 0.29) ( P ＜ 0.01 ).Conclusions IL-32 may be involved in the pathogenesis of airway inflammation in COPD.IL-32 may be a useful marker of acute exacerbation of COPD.

Key words: 
Pulmonary disease, chronic obstructive ;  Interleukins-32 ;  Interleukins-8 ;  Tumor necrosis factor-alpha
Predictive value of circulating B cells and T cell subsets in melanoma patients treated with neoadjuvant ipilimumab and interferon.
Authors: Arjun Khunger, Ghanashyam Sarikonda, Jenn Tsau, Zeni Alfonso, Jane Gao, Anil Pahuja, Christian Laing, Ju Young Kim, Jennifer Bordeaux, Christine Vaupel, Naveen Dakappagari, Shabnam Tangri, Ahmad A. Tarhini
Journal: Journal of Clinical Oncology (2020)

e15036 Background: Patients with locally/regionally advanced melanoma were treated on a clinical trial with a neoadjuvant combination of ipilimumab (ipi) and high dose IFNα2b (HDI) (Tarhini et al, JITC 2018). In this study, immune cell composition in peripheral blood samples collected at various time points was measured to determine any correlation with clinical outcomes and investigate the immune modulating effect of the combination therapy. Methods: Patients were randomized to neoadjuvant ipi at 3 mg/kg or 10 mg/kg, both given in combination with HDI. Tumor radiologic responses were designated as complete (CR), partial (PR), stable disease (SD) or disease progression (PD). Pathologic complete response (pCR) was defined as absence of viable tumor on histologic assessment. Peripheral blood mononuclear cells (PBMC) from treated patients (N = 28) were tested at baseline (before initiating ipi-HDI), then at 6-weeks, 3-months and 12-months (following neoadjuvant ipi-HDI). High complexity (14-color) flow cytometry analysis was performed to detect key immunological biomarkers including myeloid derived suppressor cells (MDSCs), B cells, regulatory T cells (Tregs), PD-1 and TIM3 expression on T-cells, and differentiation of T-cells into Th1, Th2 or Th17 phenotype at different time points during systemic immunotherapy. Statistical significance was determined using R-package employing Kruskal’s test. Results: Lower levels of peripheral Tregs (p = 0.02), MDSCs (p = 0.05), and CD4 effector memory cells (p = 0.04) at 3-months post treatment correlated with radiologic response. In addition, lower change from baseline at 3 months in CD4/CD8 ratio (p = 0.04), levels of Tregs (p = 0.01) and CD4 effector memory cells (p = 0.02) was associated with radiologic response. Patients exhibiting pCR had significantly lower Tregs (p = 0.04) at 6-months post treatment and significantly higher CD8 central memory cells at both 3 months (p = 0.04) and 12 month time-points (p = 0.01) as compared to patients without pCR. Finally, patients without pCR had significantly lower change from baseline in CD19 B cells at 6 months (p = 0.01) and 12 months (p = 0.04) as compared to patients with pCR. Conclusions: Our data demonstrates that the levels of immunosuppressive cells including Tregs and MDSCs in periphery are negatively associated with response. Higher levels of CD8 memory cells and B cells on-treatment are associated with clinical benefit.
An analysis of trends in prostate cancer treatment from a CMS database.
Authors: Andre A. Konski, Elizabeth Lin Jewell, Laura J Havrilesky, Jason A. Efstathiou, Peter A. Johnstone
Journal: Journal of Clinical Oncology (2020)

e19288 Background: The Centers for Medicare and Medicaid services (CMS) has announced a new payment model for radiotherapy services, a Radiation Oncology Alternative Payment Model (ROAPM), for 17 malignancies. The data used to calculate the base payments were released with the program announcement. The purpose of this study was to analyze trends in treatment as well as payments for each treatment modality in an attempt to provide a baseline for future comparison once the ROAPM has been completed. Methods: The database, CY2015-2017, contains payment, site of service, anatomic site and limited patient data for 517,988 patients, 91,551 having a diagnosis of prostate cancer. Only CPT codes for radiotherapy were included in the calculation of payment and only codes registered 90 days after a treatment planning charge were included. Stata 15m College Station, Texas, was used to perform all statistical analysis. Chi squared test was used to determine associations between variables. The Kruskal-Wallis H test was used to determine the relationship of total payment to clinical variables. Results: Treatment included IMRT (66,663 patients[pts], conventional therapy[ceb] (8,942 pts), brachy therapy (7,156 pts), stereotactic radiotherapy (srs) (5,120 pts) and proton beam therapy [pbt] (3,661). A slight majority of patients, 51%, were treated in the outpatient setting. Patients treated in a freestanding center were significantly more likely to have more than 41 fractions (54%) as compared to patients treated in an outpatient setting (32%), P &lt; 0.001. Patients receiving pbt were significantly younger when compared to patients receiving other therapies, p &lt; 0.001. Pbt was significantly costlier, mean $45,606.85 when compared to IMRT, $26,33.14, ceb, $10,242.27, srs, $16,514.98, or brachytherapy, $15,615.44, p &lt; 0.001. In addition, patients treated at an outpatient center with IMRT experienced higher cost compared to patients treated at a freestanding setting, $25,448.48 vs $22,934.69 p = 0.001. Conclusions: These data gives baseline treatment practice information prior to the implementation of a ROAPM. These data, however, are limited and do not give any indication as to the outcome, both disease specific metrics, and quality of life metrics. Post ROAPM analysis will be needed to determine the effect of a new payment paradigm on treatment practices of this malignancy.
Exclusion rates of patients living with HIV from cancer immunotherapy clinical trials.
Authors: Kruti Bhagirath Vora, Mark M. Awad
Journal: Journal of Clinical Oncology (2020)

e19035 Background: Although patients living with HIV are at increased risk for developing several cancers, they have often been excluded from practice-changing immunotherapy clinical trials across many tumor types. Emerging retrospective and prospective studies indicate that immunotherapies can be safe and effective in patients with HIV. ASCO and Friends of Cancer Research have supported the inclusion of patients with HIV in cancer clinical trials. We determined the rate of HIV exclusion from recent cancer immunotherapy clinical trials according to tumor type, immunotherapy treatment, and phase of trial. Methods: We compiled trials on the ClinicalTrials.gov database with study start dates from January 1, 2019 to October 10, 2020, using the search term “cancer” for disease, and the following intervention terms: “immunotherapy, PD-1, PD-L1, CTLA-4, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, cemiplimab, ipilimumab, tremelimumab, sintilimab, spartalizumab.” Observational studies and trials not offering immune checkpoint inhibitors (ICIs) or cellular immunotherapy were excluded. Eligibility criteria for each trial were reviewed to determine rate of exclusion for HIV, human immunodeficiency virus, acquired immunodeficiency, or immune deficiency. Cellular immunotherapies were defined as modified T cell, dendritic cell, NK cell, or other peripheral blood leukocyte treatments. Results: Of 1090 analyzed trials, 795 (72.9%) specifically excluded patients with HIV, and another 80 (7.3%) trials included patients with HIV only if certain criteria were met (e.g. undetectable viral load, minimum CD4+ T cell count). By tumor type, the rate of HIV exclusion ranged from 60.9% (renal cancer) to 85.7% (cervical cancer), with hematologic malignancies having a significantly higher rate of HIV exclusion than solid tumor trials (85.2% vs. 73.3%, p = 0.015). Trials combining ICIs with cellular immunotherapies were more likely to exclude HIV (N = 22, 90.9% exclusion) than trials with ICIs alone (N = 1003, 71.4% exclusion, p = 0.044). Phase I (N = 271, 73.1% exclusion, p = 0.0012), I/II (N = 165, 70.9% exclusion, p = 0.010), and II trials (N = 519, 77.5% exclusion, p &lt; 0.0001) had higher rates of exclusion than phase III trials (N = 101, 55.4% exclusion). Conclusions: Despite ASCO and Friends of Cancer Research recommendations to include patients with HIV in cancer clinical trials, the vast majority of immunotherapy clinical trials in 2019 exclude patients with cancer and HIV.