tbuckley/cabot-search huggingface dataset:
Reimbursement recommendations for cancer drugs supported by phase II evidence in Canada.
Authors: Regina Li, Helen Mai, Kaitlyn Chiasson, Maureen E. Trudeau, Kelvin K. Chan, Matthew C. Cheung
Journal: Journal of Clinical Oncology (2020)

e14133 Background: Historically, pharmaceutical companies submitted phase III evidence for consideration of public reimbursement; however, phase II data is being more commonly used as primary evidence. Whether submissions with phase II data lead to similar rates of positive reimbursement recommendations as phase III data has not been comprehensively investigated. We compared frequency of reimbursement recommendations between phase II and phase III submissions for oncologic drugs and assessed for factors associated with a positive or conditional recommendation. Methods: We identified all submissions with phase II data from the CADTH pCODR’s expert review committee (pERC) recommendations from July 2011 to July 2019. We identified fourteen binary variables relating to clinical benefit, patient-based values, economic impact, and adoption feasibility. We used Fisher’s exact test to characterize associations between all variables and the final recommendation. We conducted multivariable analysis with logistic regression for three variables: feasibility of phase III study, hematologic indication, and unmet need. Results: We identified 139 submissions with a pERC final recommendation. Twenty-seven (19%) submissions were supported by phase II evidence, with 63% having a positive recommendation in comparison to 82% among submissions with phase III evidence. Clinical benefit (p &lt; 0.001), gap in current treatment standards (p = 0.047), and patient alignment (p = 0.015) were associated with a positive recommendation, whereas the future feasibility of conducting a phase III study was associated with a negative recommendation (p = 0.040). No significant association was found between the recommendation and factors related to cost effectiveness or adoption feasibility. In multivariable analysis, only feasibility of a phase III study was significantly associated with a negative recommendation (p = 0.024, OR = 0.132). Conclusions: Oncologic submissions with phase II data were less likely to be recommended for public reimbursement than phase III studies. Positive or conditional recommendation was more likely if they demonstrated clinical benefit and aligned with patient values. pERC was less likely to recommend a submission with phase II if a phase III trial was either possible or already initiated.
Effects of psychological intervention on perioperative rehabilitation in patients with esophageal carcinoma
Authors: Guan-xuan Chen, Qing-yu Zhao
Journal: BMJ (2010)

Objective To evaluate effects of psychological intervention on perioperative rehabilitation in patients with esophageal carcinoma. Methods Sixty patients with esophageal carcinoma hospitalized at thoracic surgery department of Sun Yat-sen University Cancer Center from January to October 2008 were randomly divided into intervention group (IG, n = 31 ) and control group ( CG, n = 29). The patients' psychological status was assessed with SCL-90 (symptom check list-90) scores. Psychological intervention was implemented by means of health education, psychological support, stress management,coping strategy and behavior training given by qualified medical interns in the University at three phases,i. e. , pre-operation, post-operation I and post-operation II. Effects of intervention were evaluated in IG as compared with those in CG. Results Scores in domains of somatization, obsession, depression, anxiety,paranoia, hostility and phobbia were all higher in both IG and CG before surgical operation than those of national norm (P<0.05) set in 1986 by JIN Hua et al, but without significant difference between IG and CG (P = 0. 31). Scores of psychological factors in patients of IG demonstrated a steady decreasing tendency,which apparently differed from those of CG four and 24 weeks after surgical operation (t_4=4.71,P_4=0.002;t_(24)=3.82,P_(24)=0.005), respectively. Conclusions Appropriate psychological intervention will help improve psychological status in patients with esophageal carcinoma and benefit their perioperativerehabilitation.

Key words: 
Esophageal carcinoma; Psychotherapy; Rehabilitation
Use of electronic patient records for research: views of patientsand staff in general practice
Authors: 陈丽英, 方力争
Journal: BMJ (2013)

背景
电子病历的应用为开展人群为基础的研究提供了独特的机会。健康研究支持服务(HRSS)中心的试点项目主要是从国立健康和社会保健系统数据库中抽取电子病历，并以标识符的形式将其转化为特定的安全性的文件，以便为研究所应用。


目的
确定在初级保健中HRSS试点项目的可行性和合理性。


方法
与患者和医疗工作者进行访谈及小组讨论。


结果
HRSS得到了来自患者和医疗工作者双方的普遍支持。但对于HRSS选择退出的方案制定，患者和医疗人员反应不一，一方面认为参与者自动退出研究是合理性的，但另一方面又担忧真正同意退出后，对所提取资料数据的安全性和保密性方面提出忧虑。将患者信息打包的作法受到患者及医生的严厉批评。对全科医师、全科医疗实践活动及国家健康服务中心(NHS)信任与否是患者决定是否参与HRSS项目的决定性因素。


结论
尽管患者及医疗工作者广泛地支持HRSS，他们仍要求了解以医学研究为目的的医疗记录被合理使用的详细信息。选择退出相对于选择加入有更多争议，如果利用常规医疗记录进行科学研究是NHS的核心内容，那么还需要更完善和长远的考虑。
Impact of malnutrition and anemia at diagnosis in both: Pathological response and tumor-infiltrating-lymphocytes post neoadjuvant chemotherapy.
Authors: Katia MERCEDES Roque, Marco Galvez Nino, Carlos Arturo Castaneda Altamirano, Miluska Castillo Garcia, Joselyn Sanchez, Luis A. Bernabe, Hugo Alejandro Fuentes, Gustavo Sandival, José M. Cotrina, Jorge Antonio Dunstan, Julio Abugattas, Raúl Mantilla, Miguel De La Cruz, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2020)

e12654 Background: The response after neoadjuvant chemotherapy (NAC) is the main prognostic factor in breast cancer (BC), likewise, malnutrition, anemia and systemic inflammation have also been associated to prognosis in breast cancer. We evaluated the association between pathological response (PR) and tumor infiltrating lymphocytes (TILs) post NAC with nutritional predictors as body mass index (BMI), prognostic nutritional index (PNI), anemia and neutrophil/lymphocyte index (N/L). Methods: This is a retrospective analysis of women diagnosed with BC between 2006 to 2017 at Instituto Nacional de Enfermedades (INEN) who received NAC. Pathological response was classified through residual cancer burden (RCB) and TILs post NAC which were prospectively evaluated by a pathologist. Clinical and pathological features as well as survival status were obtained from patient files. Results: We identified 439 women with BC who received NAC. Median age was 49 years, histological grade 3 was found in 245 patients (55.8%) and stage IIIB was the most frequent at diagnosis with 257 patients (58.5%). Luminal B subtype was the most frequent (43.7%). Rate of pCR was 10.5% and median TILs post NAC was 20%. About nutritional predictors, we use the median as a cutoff to discriminate between high and low values, for BMI was 27.5, for PNI was 56, for hemoglobin was 13.2 and for NLR was 1.84. There was no association for TILs post NAC with BMI (p = 0.38), PNI (p = 0.057) and hemoglobin (p = 0.43). We found a positive association between ILN and TILs post NAC (p = 0.001). On the other hand, we don’t found association for RCB with BMI (p = 0.45), PNI (p = 0.641), ILN (p = 0.2) and hemoglobin (p = 0.15). In the multivariate analysis, only RCB was an independent predictor for DFS (95 % CI, 87-100.5; p = 0.00001) and OS (95 % CI, 101.8-114.1; p = 0.00001). There was no association between BMI, PNI, ILN and anemia with OS and DFS. For the TILs post NAC there was a tendency to association with DFS (p = 0.07) and OS (p = 0.07). Conclusions: There are association between neutrophil/lymphocyte index with TILs after NAC. There was no association between nutritional and systemic predictors with long-term outcomes. The pathologic response is a biomarker for predicting the long-term outcomes of breast cancer patients.
Relevant factors in predicting the relapse of Graves disease after treatment with antithyroid drugs
Authors: Lin Liu, Hong-wen Lu, Chang-shan Liu, Yang Liu
Journal: BMJ (2012)

Objective To evaluate the prognostic factors of predicting the outcome of Graves disease (GD) after treatment with antithyroid drugs.Methods A retrospective audit was performed for 306 consecutive patients with newly diagnosed GD.They were divided into successful and failure groups (including recurrent and non-stop subgroups )according to the treatment outcomes.Different prognostic factors after treatment with antithyroid drugs were compared and the state of thyrotropin suppression was observed as the euthyroid state at Months 3,6 and 12 respectively.Results Among them,141patients (46.1％ ) were cured and 165 patients (53.9％) had treatment failures.Age at the time of diagnosis was (46 ±10) years in the successful group and (36 ±9) years in the failure group(t =3.152,P =0.002).Free T3 ( FT3 ) was (25.2 ±8.9) and ( 18.7 ±9.4) pmol/L in the failure and successful groups respectively (t =3.326,P =0.001).The FT3 to FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were higher in the failure group ( t =3.331,3.389,P =0.001).Logistic regression analysis showed that thyroid size,FT3 to FT4 ratio and TRAb at the time of diagnosis were associated with failure outcomes.The ratio of continuing thyrotropin suppression in the recurrent subgroup was more than that in the successful group ( X2 =77.515,114.441,136.232,all P ＜ 0.01).Conclusions The GD patients with a large thyroid size and high pre-mediation levels of TRAb and FT3 to FT4 ratio are more prone to respond unfavorably to antithyroid drug treatment.And those with a large thyroid size and post-medication ophthalmopathy and continuing thyrotropin suppression have a high rate of recurrence.

Key words: 
Graves disease; Recurrence; Antithyroid agents; Prognostic factors
The use of patient health information outside the circle of care: Consent preferences of patients from a large academic cancer centre.
Authors: Fei Fei Liu, Sarah Tosoni, Indu S Voruganti, Rebecca Wong, Carl Virtanen, Donald Willison, Ann Heesters
Journal: Journal of Clinical Oncology (2020)

e14122 Background: Massive volumes of patient health information (PHI) are required to realize the anticipated benefits of artificial intelligence in future clinical medicine. To maintain public trust in medical research however, consent policies must evolve to reflect contemporary patient preferences. Methods: From January-December 2019, patients attending clinics at a large academic cancer centre were invited to complete a 27-item iPad survey on consent preferences. Survey items focused on: (a) broad vs. specific consent; (b) opt-in vs. opt-out approaches for research contact; (c) comfort sharing with different recipients; (d) perceptions on commercialization; and (e) options to track information use and study results. Demographic questions addressed cancer type, treatment stage, age, gender, ethnicity, education level, and household income. Results: A total of 222 participants were included in the analysis (112 males, 108 females; 2 rather not say); 83% were comfortable sharing PHI with researchers at their own hospital. While 56% of patients preferred broad consent, 38% preferred to be contacted with study details and asked to consent every time (specific consent); 6% prefer not to share at all. Younger patients ( &lt; 49 years) most often chose specific consent (50%); significantly more than those 75+ years (24%; p &lt; .05). Younger patients ( &lt; 49 years) were also significantly more uncomfortable than older patients (50+ years) sharing even within their own hospital (13% uncomfortable vs. 1% uncomfortable; p &lt; .05). A significant majority of patients (63%, p = .0001) preferred to be asked for permission before being entered into a contact pool vs. automatic entry with opportunity to opt-out. The majority of patients were uncomfortable sharing PHI with commercial enterprises (51% uncomfortable, 27% comfortable, 22% neutral). A significant majority expressed the desire to track who is using their PHI (61%, p &lt; .0001), and be notified regarding study results (70%, p &lt; .0001). Conclusions: While most patients were willing to share their PHI with researchers at their own hospital, many preferred a transparent and reciprocal consent process. These data also suggest a generational shift, wherein younger patients preferred more informed consent options. Modernizing consent policies to reflect increased patient interest in the exercise of their autonomy is crucial in fostering sustained public engagement in medical research.
Impact of timing of antibiotic use on clinical outcomes in patients with urothelial cancer treated with immune checkpoint inhibitors (ICIs).
Authors: Chana Weinstock, Pradeep Bandaru, Laura L Fernandes, Elaine Chang, Andrew Girvin, Shenghui Tang, Sundeep Agrawal, Daniel L. Suzman, Harpreet Singh, Michael Holman Brave, James Xu, Kirsten B. Goldberg, Amna Ibrahim, Marc Robert Theoret, Richard Pazdur, Julia A. Beaver
Journal: Journal of Clinical Oncology (2020)

5045 Background: Although recent evidence has suggested that patients who receive antibiotics (ABX) during the course of ICI treatment might decrease overall survival (OS) (1), our previous analysis did not support a difference in OS in urothelial cancer patients who did and did not use ABX during the course of ICI treatment without regard to timing (2). This updated analysis aims to addresses the question of timing; specifically, use of ABX in the 30-day window pre- or post- initiation of ICI treatment. Methods: We pooled data from 7 trials that led to drug approval and which included 1747 patients with advanced urothelial cancer treated with an ICI. Five trials enrolled patients who received prior platinum and 2 enrolled cisplatin-ineligible patients. Concomitant medication datasets were searched for systemic ABX use. The association between ABX use and survival was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression models stratified by study. Results: Overall, 56% of patients were exposed to antibiotics (ABX+) and 43% were not exposed (ABX-). In an exploratory analysis, median OS was similar between arms: 9.7 vs. 9.3 months in ABX+ vs. ABX- patients, respectively (HR 0.96). However, OS results differed in the 27% of patients who were exposed to antibiotics in the 30-day window pre- or post- initiation of ICI treatment, for whom median OS was 4.7 months vs. 11.5 months in the ABX+ vs. ABX- patients, respectively (HR 1.8). This remained true after controlling for baseline risk prognostic factors (Bajorin and Bellmunt scores). Similar trends were observed for progression-free survival (PFS). Conclusions: Patients treated with ABX while on therapy with an ICI for urothelial cancer had similar OS outcomes to those not treated with ABX. However, in an exploratory analysis looking at ABX use in the 30-day window pre- or post-initiation of ICI treatment, OS appeared decreased in ABX+ vs ABX- patients. Our exploratory analyses appear to show an association of OS/PFS with timing of antibiotics. References: 1) Routy B, Science (2017) 2) Weinstock C, ASCO 2019, abstract. [Table: see text]
Understanding and predicting fatigue, cardiovascular (CV) decline &amp; events after breast cancer treatment (UPBEAT): A prospective multi-center wake forest NCORP research-base study.
Authors: Susan Faye Dent, Kerryn Reding, Glenn Jay Lesser, Heidi D. Klepin, Lynne I. Wagner, Dalane Kitzman, Peter H. Brubaker, Shannon Mihalko, Nancy E. Avis, Karen Marie Winkfield, Bonnie Ky, Teresa Crotts, Robin Kikuchi, Tonya Calhoun, W. Gregory Hundley
Journal: Journal of Clinical Oncology (2020)

TPS602 Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients, treated with modern anticancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and the future development of CV events. The comprehensive assessment includes: ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, expanded short physical performance battery), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2 peak via cardiopulmonary exercise test), and fatigue (via FACT-F). Eligibility criteria: age &gt; 18 years; ECOG 0-2, able to walk without symptoms; receiving chemotherapy +/- HER2 targeted agent(s). To date, 244 participants are enrolled through 12 NCORP or ECOG-ACRIN sites. An additional 7 sites are onboarding and will be enrolling later in the year. Participants will be followed for 9 years with active surveillance of CV events (i.e., heart failure, myocardial infarction, stroke, all-cause and CV death). EA NCORP Grant: 2 UG1 CA189828 06; Research Base Grant: 2UG1 CA189824; R01: 1R01CA199167. Clinical trial information: NCT02791581 .
Circulating tumor DNA (ctDNA) to evaluate stage III and stage IV metastatic breast cancer (MBC), describe tumor heterogeneity, and outcome.
Authors: Qiang Zhang, Zheng Cai, Lorenzo Gerratana, Andrew A. Davis, Saya Jacob, Paolo D’Amico, Elena Vagia, Youbin Zhang, Wenan Qiang, Firas Wehbe, Katy Lucretia Kerby, Lisa E. Flaum, Ami N. Shah, Amir Behdad, William John Gradishar, Leonidas C. Platanias, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2020)

1028 Background: MBC is a challenging clinical condition treated with palliative intent due to tumor heterogeneity. We reported in 2019 ASCO that the correlation of HER2 and ESR1 mutations of ctDNA with CTCs results in worse prognosis in MBC. Here we reported that ctDNA mutations is a key point which is different between Stage III and Stage IV, and it would be helpful to evaluate the MBC metastasis and outcome. Methods: This study included 33 Stage III and 204 Stage IV MBC patients who received systemic treatments at NMH (2016-2019). Plasma ctDNA before treatment was isolated from patients and then was analyzed by Guardant 360 Health NGS-based assay for a 73 genes panel for genomic alterations including single nucleotide variants, insertions/deletions, gene fusions/rearrangements and copy number variations. Causal Inference with Ensembel Learning was used for statistical analyses. Results: Among stage III patients, 40% are luminal, 44% are HER2 + and 16% are TNBC, while in stage IV 50% patients are luminal, 20% are HER2 + and 30% are TNBC. The major differences in ctDNA between two stages lie in several genes including PIK3CA, ERBB2 and KRAS. On the top of the list is PIK3CA, which is detected in 2 out of 33 stage III patients (1 luminal, 1 HER2 + ) (6.06%) in baseline, each of them carries 1 mutation on PIK3CA (E542K, E545G). In 43 out of 204 stage IV patients (21.57%) who carry this gene, 15 show 1 amplification, 34 have 1 mutation (mainly H1047R, E542K, E545K and H1047L), 11 have 2 mutations (E542K/E726K, D454N/D1029N, E545K/D1017H, E545K/L287L, H1047R/E453K, H1047R/N426S and P539R/H1047R), and 1 has 3 mutations (E542Q/D454N/D1029N and E545K/E726K/R93Q). On treatment effects, PIK3CA is found to be very detrimental on prognosis and on its effects on the treatment outcome. Patients without any mutation in PIK3CA live 2.65 times longer than those with more than one mutations on PIK3CA ( p-value = 4.47e-06, CI = [1.731, 3.926]). PIK3CA, ESR1, TP53 and ARID1A are found to significantly affect liver metastasis when RET, FBXW7, ERBB2, CCND2, BRAF and MET are found to be associated with lung metastasis for both stages. EGFR, KIT and ARID1A are associated with CNS metastasis. Conclusions: We elucidated that ctDNA mutations on PIK3CA and other genes dramatically increased in Stage IV patients compared to Stage III patients which provides a new insight on the Stage III and Stage IV MBC determination. New set of genes especially PIK3CA are identified to correlate with metastasis and affect the outcome which may also be reliably used to monitor the response to therapy.
The economic impact of cancer-related premature mortality in Brazil: A human capital approach analysis.
Authors: Marianna De Camargo Cancela, Leonardo Borges Lopes de Souza, Luis Felipe Leite Martins, Dyego Souza, Anton Barchuk, Arthur Correa Schilithz, Paul Hanly, Linda Sharp, Alison Pearce, Isabelle Soerjomataram
Journal: Journal of Clinical Oncology (2020)

7068 Background: One method of calculating indirect costs of cancer is the analysis of productivity loss. Using the human capital approach, we estimate how much cancer-related premature mortality indirectly impacts the economy. Given the diverse causes of cancer death and sociodemographic profiles in Brazil, we estimated lost productivity due to cancer by regions, providing evidence for local decision-makers. Methods: Data of all cancers deaths among working-age people (15-64 years for men and 15-60 for women) occurring in 2016 were extracted from the National Mortality System, by region, sex and age-group. Data on life expectancy, workforce participation, unemployment and wages were extracted from the Brazilian National Institute of Geographics and Statistics. Loss of productivity was calculated as the value of time between death and potential retirement age. Results: In total 536,827 (men) and 407,737 (women) years of potential productive life (YPPLL) were lost in 2016, corresponding to US$ 6,196,682,092 (PPP) for Brazil. The profile of YPPLL by cancer type varied by region. In the affluent South and Southeast regions, the cancers with higher impact in men were lung (12.4% and 9.9% of total YPPLL) and colorectal (9.6% and 10.4% of total YPPLL) while in the less affluent North and Northeast, stomach cancer was responsible for 17% and 12% of YPPLL, respectively. Among women, breast cancer had the highest impact in all regions (21.7%-26.2%), excepting the North, where cervical cancer was responsible for 31.3% of the YPPLL. Nationally, individual YPPLL was higher for testicular cancer in males (31.3 years) and Hodgkin’s disease in females (20.2). In the North and the Northeast, despite lower mortality rates, the economic impact of productivity loss was higher, representing 0.23 and 0.29% of the regional GDP. Conclusions: Our results show the indirect economic impact of premature cancer mortality in Brazil, at a total cost of US$ 6,196,682,092 in 2016, representing 0.2% of the entire country’s GDP. The regional patterns highlight the need for adaption of public policies, typical from a country in transition, with the impact of lifestyle and infection-related cancers simultaneously and differently affecting economically the regions.