tbuckley/cabot-search huggingface dataset:
Risk factors in the HR-NBL-1/SIOPEN study in patients receiving dinutuximab beta (DB) based immunotherapy.
Authors: Ruth Lydia Ladenstein, Ulrike Poetschger, Dominique Valteau-Couanet, Juliet Gray, Roberto Luksch, Walentyna Balwierz, Victoria Castel, Shifra Ash, Maja Beck Popovic, Genevieve Laureys, Godfrey Chi-Fung Chan, Ellen Ruud, Kim Vettenranta, Cormac Owens, Henrik Schroeder, Peter F Ambros, Sabine Sarnacki, Tom Boterberg, Holger N. Lode
Journal: Journal of Clinical Oncology (2020)

10536 Background: We previously developed a risk factor model in HR-NBL1/SIOPEN patients treated without DB including age, LDH and metastatic site index (MSI). We tested if this score (Morgenstern, PBC 2018) would provide meaningful information in DB treated HR-NBL1/SIOPEN patients. Methods: High-risk patients (stage 4 ≥1yr.; stage 4 &lt; 1yr. with MYCN amplification (MNA); stage 2, 3, 0-21y with MNA) received intensive induction, surgery, high dose therapy (HDT) and local radiotherapy (21Gy). Patients with a ≤9 months intervall till HDT/SCT, ≥ partial response prior and no progression received up to 5 cycles of 100mg/m 2 DB: as short-term (STI: 5 days) or long-term infusion (LTI: 10 days ) ± 6 (STI) or 3 (LTI) x 10 6 IU/m 2 subcutaneous interleukin 2 (scIL2 over 2 x 5 days) followed by 2 weeks of 160mg/m 2 oral isotretinoin. Results: DB was used in 1018 patients [512 males; 89% Stage, 1% Stage 4s, 10% loc. MNA; 2.8 yrs median age at diagnosis] in 18 countries. STI was used in 61% patients, LTI in 39% and DB without scIL2 in 62% patients. 2-yrs. event-free (EFS)/overall survival (OS) was 0.65±0.02/0.78±0.01 and 5-yrs. EFS/OS of 0.56±0.02/0.63±0.02. 891/1018 patients were evaluable for risk factor analysis. EFS multivariate analysis included age, MSI, LDH ≥1250U/L, HDT typ, response prior DB, DB schedule and use of scIL2: only age &gt; 1.5yrs.(p = 0.002) and MSI &gt; 1 (p = 0.002) had independent prognostic prediction. If restricted to stage 4 only, LDH ≥1250U/L was also an independent factor (p = 0.049). Points were allocated in proportion to the log-cumulative hazard ratio (cHR): cHR for LDH &gt; 1250U/L was 1.33 (score of 1), cHR for age &gt; 5 years and metastatic site involvement (MSI) &gt; 1 were 1.79 and 1.86 (scores of 2). Using the score (0 to 5) relevant risk groups can be identified: 5-yrs. EFS/OS for scores 0&amp;1 are 0.80±0.06&amp;0.77±0.04, score 2/3 are 0.58±0.03&amp;0.57±0.04 and for scores 4/5 are 0.50±0.06&amp;0.43±0.08. Conclusions: The score adds value in DB treatment groups as it differentiates prognostic subgroups facilitating decision making for future DB add on treatments. Clinical trial information: NCT01704716.
Mediation of black/white disparities in triple negative breast cancer by socioeconomic position, reproductive factors and diabetes in the Nurses’ Health Study Cohorts I &amp; II.
Authors: Lydia Marcus, Keith A. Dookeran
Journal: Journal of Clinical Oncology (2020)

1565 Background: The higher rates of triple negative (TN) breast cancer (BC) observed among black compared to white women may be attributable to social and reproductive factors, as well as biological conditions like diabetes mellitus type 2. We examine the extent to which the black/white race disparity in TNBC is transmitted through these factors. Methods: Data are from the Nurses’ Health Study I and II prospective cohorts and include non-Hispanic (nH) black (n = 97) and nH white (n = 8,876) women aged 25-55 years at enrollment with invasive BC diagnoses. Participant characteristics are self-reported or drawn from medical records. We estimated average controlled direct associations (ACDA) using logistic regression with model-based standardization to evaluate the age/body mass index (BMI)-adjusted prevalence difference for TN versus luminal A/B type BC by race, and performed a series of ACDA (with comparison of rescaled coefficients (RC)) controlling for diabetes, mean family income before diagnosis (cont.), husband’s education ( &lt; college, college, graduate school), parental ownership of participant’s childhood home (yes/no), age at menarche (cont.), age at first birth (cont.), parity (integer), and breastfeeding (BF) (parous/never BF, parous/ever BF). Results: Compared to nH whites, nh black women had higher prevalence of TNBC (24.5% v. 45.4%; p &lt; 0.01), higher prevalence of diabetes (5.5% v. 11.3%; p = 0.01), lower prevalence of BF (59.2% v. 46.6%; p = 0.02), higher mean BMI (26.1 v. 29.9; p &lt; 0.01), and lower mean family income ($17,304 v. 15,750; p &lt; 0.01). BMI, age, and menopause were positively associated with prevalence of diabetes. In the age/BMI adjusted model, nH black women were 20%-points more likely than nH whites to have TNBC (95% Confidence Interval (CI): 0.11, 0.29). This disparity was reduced to 18.1% after also adjusting for BF (95% CI: 0.09, 0.28), to 13.7% after additionally adjusting for socioeconomic indicators (95% CI: 0.02, 0.25), and to 13.3% after adjusting for all potential mediators (95% CI: 0.01, 0.26). Based on the method of RC, socioeconomic indicators accounted for the largest fraction of mediated effects and BF accounted for most of main effect attenuation associated with reproductive factors; diabetes accounted for negligible effect. Conclusions: Our findings support the hypothesis that observed racial differences in TNBC diagnoses may be at least partially mediated by differences in socioeconomic position and reproductive patterns, namely breastfeeding.
Comorbidities and patient-reported outcomes among individuals with cancer enrolled in a digital health coaching program.
Authors: Kelly Jean Brassil, Jonathan Patterson, Matthew Allison, Stephen Burton, Thupten Norbu, Mazi Rasulnia, Dhiren Patel
Journal: Journal of Clinical Oncology (2020)

e19278 Background: Many individuals with cancer, as high as 90% in some studies, experience co-morbidities, which are associated with survival, quality of life and health care costs. Patient reported outcomes (PRO) have demonstrated efficacy in tracking outcomes for individuals with cancer and other chronic conditions. We present real world evidence of co-morbidities and PRO data from a cohort of individuals with cancer engaged in a digital health coaching program. Methods: A retrospective analysis was conducted of self-reported co-morbidity data and PROs collected from individuals with cancer upon enrollment in a digital health coaching program. Descriptive statistics define frequency of co-morbidities and means of PRO, including the Patient Reported Outcome Measures Information System-Global Health (PROMIS-GH)10, for individuals with cancer only compared with those who also had a co-morbid condition. Results: Of 570 individuals, 127 reported a co-morbid condition on enrollment into the coaching program (22%). Of these, 49.6% (n = 63) reported 1, and 50.4% (n = 64) reported 2 or more conditions, of which the most commonly reported were cardiovascular (45.6%), metabolic (39.3%), and immune-related (22.8%). Mean PRO scores at baseline are presented for each measure for individuals who reported either no or 1 or more co-morbid conditions at baseline (Table). Interestingly individuals with at least 1 comorbidity reported higher PRO scores for physical and mental health at baseline than those with cancer alone. Conclusions: Co-morbid conditions, while known to influence clinical outcomes among individuals with cancer, may also influence trends in PRO. Higher scores in this cohort may suggest that experience with a pre-existing condition may support the individual’s ability to cope with a cancer diagnosis and its physical and emotional sequelae. Digital health coaching may offer a unique non-clinical approach to gather this data and to support individuals to optimize self-efficacy, improving health outcomes beyond the clinical setting. [Table: see text]
A first in-human study of A166 in patients with locally advanced/metastatic solid tumors which are HER2-positive or HER2-amplified who did not respond or stopped responding to approved therapies.
Authors: Yongheng Liu, Wei Lian, Xi Zhao, Wei Qi, Jian Xu, Liang Xiao, Yan Qing, Tongtong Xue, Jingyi Wang
Journal: Journal of Clinical Oncology (2020)

1049 Background: HER2 is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker. Methods: This was a single arm, open-label, multicenter, dose escalating Phase 1 first-in-human study of A166 as monotherapy in solid tumor patients. Dose escalation and MTD identification was directed using a Bayesian logistic regression model with overdose control. The following dose levels were evaluated in this study: 0.3, 1.2, 3.6, 4.8 mg/kg. (ClinicalTrials.gov NCT03602079) Results: As of November 1, 2019 35 pts have completed the DLT evaluation period across 4 dose levels. Overall, A166 had an acceptable toxicity profile with no unexpected toxicities related to the study drug. No adverse events recorded met the protocol specified definition of a dose limiting toxicity at any studied dose level. Most frequently (≥10%) occurring TEAEs include were Keratitis, Decreased appetite, Dry eye, Vision blurred etc. Overall incidence of ophthalmic toxicities in the 3.6 mg/kg cohort was 80% and in the 4.8 mg/kg cohort it was 83%. Among the 27 patients evaluable for efficacy, best response was progression of disease in 11 patients (41%), stable disease in 9 patients (33%) and partial response in 7 patients (26%), for the total disease control rate of 59%.Responses were seen only at the dose levels of 3.6 mg/kg and 4.8 mg/kg. Conclusions: A166 demonstrated clinically meaningful efficacy in heavily pretreated patients with relapsed or refractory advanced solid cancers. The achievement of an ORR of 36% at efficacious dose levels and up to 100% in HER2 positive patients regardless of histology (2 CRC, 1 BC and 1 NSCLC) at the highest studied dose level exceed Clinical trial information: NCT03602079 .
Effect of local therapies on survival in patients with metastatic adrenocortical carcinoma.
Authors: Impana Shetty, David J. Venzon, Michal Mauda-Havakuk, Bj Thomas, Donna Bernstein, Crystal Flowers, Victoria Anderson, Margarita Raygada, Elliot B Levy, Bradford J. Wood, Brigitte C. Widemann, Karlyne Reilly, Jaydira Del Rivero
Journal: Journal of Clinical Oncology (2020)

e17114 Background: Adrenocortical carcinoma (ACC) is a rare cancer with an incidence of 0.7 – 2 cases per million persons per year, and generally has a poor prognosis with a 5-year survival rate of 20-25%. In a previous review of 330 patients with ACC, the median overall survival time of patients with Stage IV ACC was 0.9 years. Currently, complete surgical resection is the only curative treatment for ACC. Cases of recurrent or metastatic ACC are infrequently curable by surgery alone and systemic therapies have limited benefit. A previous study has suggested that local interventions to resect liver metastases improve survival. We hypothesize that local therapies increase survival of patients with metastatic ACC and here we describe the characteristics of various types of regional therapies. Methods: We conducted a retrospective chart review of 26 patients with ACC who were seen at the National Institutes of Health (NIH) between 2002 and 2019 and who are currently alive. These patients had multiple interventions that were performed including surgeries, radiofrequency ablations/embolizations/cryoablations and systemic therapies. Results: The group of patients we studied were 92% female and 8% male. The ages ranged from 23 to 77, with an average age of 57. Out of the 26 patients, 11 (42%) patients had liver metastases, 17 (65%) patients had lung metastases, 4 (15%) patients had retroperitoneal recurrence, and 5 (19%) patients had lymph node involvement. All patients with lung, retroperitoneum, liver, and lymph node metastases underwent surgical intervention. In patients with liver metastases, 73% underwent liver-directed therapies and 91% received systemic therapy. In patients with lung metastases, 59% underwent radiofrequency ablation or cryoablation and 94% had systemic therapy. Among the systemic therapies, 15% of patients received zero lines of treatment, 50% of patients received one line, 12% of patients received two lines, 19% of patients received three lines, and 4% of patients received more than three lines of treatment. Conclusions: The analysis of this cohort indicates that multiple local therapies could increase patient survival. ACC metastases are most common in the liver, followed by the lungs. Patients with recurrent/metastatic ACC should be considered for regional therapies such as metastasectomy/ablation in experienced hands which can increase long-term survival in selected patients.
MSI/MMR test usage and checkpoint inhibitor practices in Europe.
Authors: Bradley Smith, Jeffrey Hodge, Caroline Anger, Fil Manuguid, Kriti Jindal
Journal: Journal of Clinical Oncology (2020)

e19327 Background: Micro-Satellite Instability (MSI) or DNA Mismatch Repair (MMR) is an established prognostic test associated with response to chemotherapies in Lynch Syndrome, colorectal cancer and other indications. Recently, MSI/MMR status has been shown to predict response to immune checkpoint inhibitors (CPI). Pembrolizumab has been approved in the USA for MSI-high or mismatch repair deficient patients for all indications. A similar approval has not been obtained in the EU. This data research project examined MSI/MMR testing in Europe and its possible association with use of CPI therapies. Methods: This study was conducted using Oncology Dynamics, an IQVIA oncology cross-sectional survey, collecting anonymized real-world patient-level data. 97,807 and 96,111 drug treated patients for solid tumors in 2018 &amp; 2019, respectively, were collected across 5 European countries (France, Germany, Great Britain, Italy and Spain). Data included number of patients tested for MSI/MMR, results of the test, site and funding type, and the drug(s) prescribed. Results: European MSI/MMR test rates ranged from 3% in Italy in 2018 to 12% in France in 2019. Testing rates increased modestly in all countries over the period. Testing rates were determined in 25 specific indications plus all other indications. As expected, rates were highest in colorectal and stomach cancer. Testing was observed in other indications including Esophageal, Brain and Melanoma all with rates of 10% or higher. The percentage of MSI-High patients ranged from a low of 13% in Italy in 2019 to 26% in France in 2019. Finally, 17% of MSI-High patients are treated with CPIs compared to 5% of MSI-Low patients across all countries in 2019. Conclusions: The results over two years and almost 200,000 patients present insights into the use of MSI testing in 5 European countries. MSI testing is performed in many indications in addition to those typically associated with the biomarker. The increase in CPI use in MSI-High patients suggest that test results may impact use of checkpoint inhibitors although causation may not be inferred from the current analysis. However, the correlation suggests that further analysis is warranted.
近年雌激素补充治疗概念与方法的变迁
Authors: 廖丰
Journal: BMJ (2005)

20世纪30年代末期,人工合成的雌激素补充治疗(ERT)被开始用来减轻与绝经相关的症状.70年代中期,孕激素被用于仍有子宫的妇女以预防子宫内膜癌发病的增加.这种雌、孕激素的联合补充称为HRT.以后相当长的时间中,ERT/HRT曾一度被推崇为防治心血管病的有效手段.20世纪70到90年代进行的很多临床研究提示,服用ERT/HRT的妇女与不服用激素的人群相比,冠心病发生率减少20%～50%.然而,这些观察性的结果并不能排除选择服用激素的妇女是由于其他相伴随的生活或健康方面的原因而出现心血管疾病发病率下降的.只有通过随机取样、双盲对照的临床研究,才可能获得明确的结论.的确,以后此类工作的完成修正了人们的认识。
促红细胞生成素防治极低出生体重儿贫血16例
Authors: 王广方, 杨爱琳, 黄凤玲, 李玉华
Journal: BMJ (2005)

34例极低出生体重儿随机分为治疗组(16例)和对照组(18例),均于出生第4天起口服葡萄糖酸亚铁糖浆(按元素铁9 mg·kg-1·d-1计算)、维生素C 0.2 g/d、维生素E 15 mg/d.治疗组在上述治疗的基础上加用重组人类促红细胞生成素(rh-EPO),每周600 IU/kg, 分3次皮下注射,疗程6周.结果示治疗组治疗后网织红细胞计数较对照组明显升高(P＜0.01);两组血红蛋白及红细胞压积均于出生后逐渐下降,但治疗组下降缓慢,在治疗后第1、3、5、7周相比差异均有统计学意义(P＜0.01);治疗组疗程结束后存在贫血者4例(25.0%),明显低于对照组13例(72.2%),P＜0.01;治疗组输血2例,而对照组输血11例.提示rh-EPO加铁剂能有效防治极低出生体重儿贫血。
Nasal high flow oxygen therapy for chronic obstructive pulmonary disease with hypercapnia
Authors: Wenying Xu, Guochao Shi
Journal: BMJ (2019)

Nasal high flow oxygen therapy (HFNC), an open nasal catheter system conveying heated and humidified air or oxygen, has been used to treat hypoxemic respiratory failure. At present, some researches indicated that HFNC can be applied for chronic obstructive pulmonary disease (COPD) with hypercapnia, which attenuates the retention of carbon dioxide by positive end-expiratory pressure effect, washing out anatomical dead space and reducing work of breath. HFNC is proved to decrease respiratory frequency, increase alveolar ventilation and end-expiratory lung volume, and its therapeutic effect is similar to non-invasive ventilation. Application of HFNC managed to be optimized in a way of increasing the flow rate in a single prong and mouth-closed breathing. This article summarizes the application of HFNC in COPD with hypercapnia.

Key words: 
Chronic obstructive pulmonary disease; Hypercapnia; High flow nasal cannula
Patterns of cancer screening, incidence and treatment disparities in China: protocol for a population-based study
Authors: 姚能亮, 王家林, 蔡远楚, 袁璟, 王海鹏, 龚继勇, Anderson Roger, 孙晓杰, 张楠
Journal: BMJ (2017)

引言
癌症已成为中国居民的主要死因。有关中国癌症治疗模式和人群差异都存在诸多研究空白。中国的卫生服务研究者尚无法获得高质量的癌症研究数据。在中国，只有一些关于癌症发病率和病死率的研究，尚没有对癌症筛查、治疗模式及其差异进行严谨的研究。以前的文献没有分析社会经济地位在如何影响癌症治疗方面潜在的差异,尚没有研究用人群数据来计算中国癌症治疗成本。本项目旨在分析山东省癌症筛查、发病和治疗的模式，分析控癌当中人群差异的成因。


方法与分析
我们将在中国建立第一个链接肿瘤登记数据与医疗保险报销数据的数据库。我们从6个市/县（1 063万人口）获得了2011—2014年的乳腺癌、胃癌、肠癌和肺癌发病的肿瘤登记数据，以及他们的医疗保险报销数据，并利用医院病历数据对链接数据进行验证。我们将问卷调查1 600名癌症患者，以收集患者社会经济地位、职业和癌症治疗费用信息。将使用频率分析、空间数据分析、纳入工具变量的多元logistic回归、广义线性回归和亚组分析来分析以下内容：接受癌症筛查率、诊断期(早/晚)、是否按诊疗指南施治以及癌症治疗成本。患者特征、肿瘤特性、医院特征、患者并发症和县域特征等将被用作多元分析中的协变量。


伦理和传播
山东大学公共卫生学院伦理审查委员会批准了本项研究（20140201）。本研究相关数据将会对所有中国卫生服务研究人员开放，研究结果将会在同行评议的学术期刊和国内外学术会议上发表。
Real-world burden of chemotherapy-induced myelosuppression: Results of a U.S. online survey of patients with cancer.
Authors: Robert S. Epstein, Matti S. Aapro, Upal K. Basu Roy, Tehseen Salimi, JoAnn Krenitsky, Megan L. Leone-Perkins, Jeffrey Crawford
Journal: Journal of Clinical Oncology (2020)

e19299 Background: Research into the real-world impact of chemotherapy (CT)-induced myelosuppression on patients’ lives is limited. This study aimed to investigate the impact of CT-induced myelosuppression on patients with lung, breast, or colorectal cancer (CRC). Methods: Following Institutional Review Board approval to proceed with exception, a survey of participants identified from an online U.S. patient panel was conducted in Nov/Dec 2019. Participants who had been treated with CT in the past year and experienced ≥1 episode of myelosuppression (‘a decrease in bone marrow activity resulting in the reduced production of blood cells’) were eligible for participation. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Descriptive statistics were used to summarize key findings. P values were calculated using the Chi-square test. Results: 301 participants completed the online survey (breast cancer, n = 153 [51%]; lung cancer, n = 100 [33%]; CRC, n = 48 [16%]). Most participants were aged &gt; 40 years, 60% were female, 60% were currently employed, and 75% had been diagnosed with cancer within the last 3 years. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Fatigue was the most commonly noted side-effect of CT (reported by 72% of participants), with 55% of participants rating it as highly bothersome (9 or 10 on a 1–10 scale of ‘bothersomeness’). Most participants (89%) considered myelosuppression to have a moderate or major impact on life (major life impact, 40%; moderate life impact, 49%; minor life impact, 12%). Patient-reported impact of myelosuppression was significantly higher among participants aged &lt; 50 years vs those aged ≥50 years (p = 0.01); however, no significant differences were observed when participants were stratified by sex, employment status, comorbidities (depression, diabetes, hypertension), or type of cancer. Significantly more participants with fatigue, considering themselves to have a weakened immune system, or noticing easy bruising/bleeding reported a major life impact vs those without these side effects (44% vs 27%, 52% vs 26%, and 50% vs 34%, respectively; all p &lt; 0.01). Conclusions: These data provide further insights into the substantial real-world patient burden of symptoms arising from CT and associated with myelosuppression. Preventing or proactively managing CT-induced myelosuppression could have a major impact on patients’ quality of life.
Accuracy of clinical staging in stage I and IIa/b testicular nonseminomatous germ cell tumors (NSGCT) and implications on survival.
Authors: Arnav Srivastava, Hiren V. Patel, Sinae Kim, Isaac Kim, Eric A. Singer, Thomas L Jang
Journal: Journal of Clinical Oncology (2020)

e17058 Background: Clinical stage (CS) dictates treatment in men with testicular cancer and its inaccuracy may affect clinical outcome. We evaluate the accuracy of clinical staging in men with CS I and CS IIA/B NSGCT and explore the implications of inaccurate staging on overall survival. Methods: Using the National Cancer Database (NCDB), we abstracted all patients with clinical Stage I-IIB NSGCT who received a primary retroperitoneal lymph node dissection (RPLND) from 2004 to 2014. Primary RPLND was defined as RPLND performed for CS I-IIB patients without prior chemotherapy. CS was cross-tabulated with pathologic nodal staging data. Survival for patients who were accurately staged (CS I patients with pN 0 disease, CS IIA patients with pN 1 disease) and for CS I patients found to have pN+ disease was determined using the Kaplan Meier method. Results: 1,639 CS I-IIB patients underwent primary RPLND. Among CS I patients, 23% had upstaging of disease (pN 1-3 ), of which 13.9%, 8%, and 1.1% were pN 1 , pN 2 , and pN 3, respectively (Table). Pathologic N 1-3 disease was higher in CS IB vs. CS IA patients (35.1% vs 14.2%, respectively). Of CS IIA patients, 23.1% had pN 0 disease, while 44.8%, 13.4%, and 1.3% had pN 1 , pN 2 , and pN 3 disease, respectively. At a median follow-up of 56.3 months, mortality rates for CS I patients who had pN 1 , pN 2 , and pN 3 disease were 2.8%, 4%, and 9.1%, respectively, and &lt; 1% for men with pN 0 disease. 10-year overall survival for CS1 patients was significantly less favorable if upstaged to pN2 or pN3 disease after RPLND vs. pN0 or pN1. Conclusions: Nearly a quarter of patients with CS I NSGCT are under-staged and are found to have pN 1-3 after RPLND. Nodal disease burden is associated with survival. Novel imaging techniques and biomarkers are needed to improve the sensitivity of detecting NSGCT. [Table: see text]