tbuckley/cabot-search huggingface dataset:
Clinicopathological features and prognosis of colorectal cancer with extranodal tumor deposits.
Authors: Yun Lu, Xianxiang Zhang, Jilin Hu, Dongsheng Wang, Yuan Gao, Maoshen Zhang, Shisong Liu, Guangwei Liu, Peng Zhao, Jinhui Wu, Zhenkai Li, Jiagang Han, Guiying Wang, Yong Feng, Jiansheng Wang
Journal: Journal of Clinical Oncology (2017)

e15005 Background: The study discusses clinicopathological features of colorectal cancer with extranodal tumor deposits(ENTDs) and investigates whether ENTDs is a poor prognostic factor. Methods: 1. Clinicopathological data and follow-up of colorectal cancer with ENTDs who underwent surgery between June 2007 and June 2010 in seven hospitals in North China were collected retrospectively. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis of prognostic factors. 2. The literatures on ENTDs and postoperative survival rate in colorectal cancer published from 1990 to 2016 were retrieved in English literature databases such as MEDLINE/PubMed, Web of Science and Chinese literature databases such as CNKI. Meta-analysis was conducted by Review Manager 5.3 software. Results: 1. A total of 253 cases of colorectal cancer with ENTDs were collected. The 5-year survival with only one ENTD was 49.2% (87/177), with median survival time 60 months. The 5-year survival with more than one ENTD was 17.1% (13/76), with median survival time 44 months. Cox regression analysis revealed that age, tumor size, number of ENTDs, N, m stage, surgical approach and adjuvant treatment were independent risk factors of prognosis of colorectal cancer with ENTDs. 2. The total sample size of the studies was 4731 cases with ENTDs (+) 917 cases. Meta analysis showed that: 5-year overall survival and 5-year relapse-free survival rate were significantly lower in ENTDs (+) group than ENTDs (-) group for colorectal cancer (OR:respectively 0.25,0.30; 95% CI:respectively 0.17-0.37,0.22-0.41; both P &lt; 0.00001); 5-year overall survival rates were both significantly lower in ENTDs (+) group than ENTDs (-) group for patients with N0 and N+ colorectal cancer (N0 group: P = 0.003; N+ group: P = 0.0008; both P &lt; 0.05). Conclusions: 1.Age, tumor size, number of ENTDs, N, m stage, surgical approach and adjuvant treatment were independent risk factors of prognosis of colorectal cancer with ENTDs. 2. ENTDs was a poor prognostic factor in colorectal cancer. The effect of ENTDs on postoperative survival rate might resemble that of between lymph node metastasis and distant metastasis.
Periodontal complications of hyperglycemia/diabetes mellitus: Epidemiologic complexity and clinical challenge
Authors: Thomas Kocher, Jörgen König, Wenche Sylling Borgnakke, Christiane Pink, Peter Meisel
Journal: Periodontology 2000 (2018)

Abstract This report provides a comprehensive overview of the adverse effects of hyperglycemia on the periodontium. It combines data from literature reviews of original data from two large, population‐based epidemiologic studies with comprehensive periodontal health assessment. Emphasis is placed on the exploration of hitherto sparsely reported effects of prediabetes and poorly controlled (uncontrolled) diabetes, in contrast to the umbrella term “diabetes.” This stems from the realization that it is not simply having a diagnosis of diabetes that may adversely affect periodontal health. Rather, it is the level (severity) of hyperglycemia that is the determining factor, not the case definition of the diagnosis of diabetes or the type of diabetes in question. Importantly, based on existing evidence this paper also attempts to estimate the improvements in periodontal probing depth and clinical attachment level that can be expected upon successful nonsurgical periodontal treatment in people with chronic periodontitis, with and without diabetes, respectively. This exploration includes the implentation of new systematic reviews and meta‐analyses that allow comparison of such intervention outcomes between hyperglycemic and normoglycemic subjects. Based on both existing literature and original analyses of population‐based studies, we try to answer questions such as: Is there a glycated hemoglobin concentration threshold for periodontitis risk? Does short‐term periodontal probing depth reduction and clinical attachment level gain after scaling and root planing depend on glycemic control in type 2 diabetes? Are short‐term scaling and root planing outcomes in people with hyperglycemia/diabetes inferior to those in people without diabetes? Do periodontitis patients with diabetes benefit more from the use of adjuvant antibiotics with nonsurgical periodontal treatment than people without diabetes? Does hyperglycemia lead to greater tooth loss in patients in long‐term post‐periodontal treatment maintenance programs? Throughout this review, we compare our new findings with previous data and report whether the results of these new analyses corroborate, or are in discord with, similar scientific reports in the literature. We also explore the potential role of dental health‐care professionals in helping patients control the risk factors that are identical for periodontitis and diabetes. Finally, we suggest various topics that still need exploration in future research.
When participants state that a phase I trial is intended to benefit them, is this therapeutic misconception?
Authors: Rebecca D. Pentz, Ana M Pinheiro, Minisha Lohani, Taylor White, Margie Dixon
Journal: Journal of Clinical Oncology (2016)

e14042 Background: Therapeutic misconception (TM) refers to a patient misconstruing clinical research as personal medical care. TM represents a serious ethical concern because it signals a basic misunderstanding of the purpose of clinical research and thus threatens true informed consent to participate in clinical trials. TM has traditionally been determined by questioning the patient about the research study's purpose, as we have done in prior research. Some recent research has questioned whether TM is as prevalent as reported due to discrepancies between patient and researcher interpretation of TM questions. We aimed to test this question with oncology phase I patients. Methods: Patients participating in oncology phase I clinical trials were interviewed to determine TM. Patients were questioned about the purpose of the trial, as we had done previously: 1.Is the trial mostly intending to help research and gain knowledge?; 2. Is it mostly intending to help you as a person?; 3. You don't know. Participants were then asked what they thought this question was asking: A. What my own intentions are; B. What the official purpose of the research study is; C. Not sure. Results: Of the 54 patients approached, 50 (93%) participated. 33 (66%) were male, 36 (72%) white, and the median age was 60 years. 20 (40%) had a college degree, and 28 (56%) had an income greater than or equal to $60,000. 21/50 (42%) participants, interpreted the question as intended (answering B). Of this 21, 16/50 (32%) were true negative for TM (answering 1-B above) and 5/50 (10%) were true positive for TM (answering 2-B). 19/50 (38%) did not interpret the question as intended (answering A) and therefore cannot be considered to have conventional TM. 10/50 (20%) were unclear about what the question was asking (answering C). Conclusions: Previously, a patient was thought to have TM if they responded to a question about the purpose of the clinical trial as benefitting them as individuals. However, the use of an additional question to clarify their thoughts revealed that most patients interpreted the question differently than intended by the researcher or did not understand the question and therefore cannot be determined to have TM. Only 10% could be categorized as having TM.
Phase 1 dose-escalation study of ACT001 in patients with recurrent glioblastoma and other advanced solid tumors.
Authors: Jason D. Lickliter, Ross Jennens, Charlotte Rose Lemech, Ganessan Kichenadasse, Dongpo Cai, Steven Yung-Chang Su
Journal: Journal of Clinical Oncology (2021)

2037 Background: ACT001, an orally-available parthenolide derivative targeting NF-κB and STAT3 signaling pathways, has immunomodulatory effects and showed promising activity in preclinical models of glioblastoma (GBM). The updated data in this report summarizes clinical findings from this first-in-human clinical trial of ACT001 in patients with advanced solid tumors, including GBM. Methods: Eligible patients were adults with ECOG PS 0-1 and satisfactory hematologic, renal and hepatic function. Additionally, GBM patients had progressive disease despite initial radiation and temozolomide, measurable tumor and no radiation treatment within 3 months prior to enrollment. ACT001 was given orally BID until intolerance or disease progression. Dose escalation followed a standard 3+3 design. Gliomas were imaged with MRI every 8 weeks and responses assessed using RANO criteria. Results: A total of 24 patients were enrolled as of this report: 14 with primary GBM, 2 with secondary GBM, 2 with anaplastic astrocytoma, 2 with colorectal cancer and 1 with each of anaplastic oligioastrocytoma, diffuse intrinsic pontine glioma, non-small cell lung cancer and pleural epithelioid mesothelioma. Median age was 49 years old (range 32-72). ACT001 dose levels were 100 mg BID, 200 mg BID, 400 mg BID, 600 mg BID, 900 mg BID and 1200 mg BID. Study drug treatment was well tolerated with no dose-limiting toxicity or ACT001-related SAE observed. The originally-planned maximum dose of 600 mg BID and the 1200 mg BID dose were expanded to 7 and 5 patients, respectively. The plasma half life of ACT001 was approximately 3-4 hours and no accumulation was observed after multiple dosing. Cmax and AUC 0-last were approximately dose linear across the evaluated dose range. Of the 19 patients with recurrent malignant gliomas, a complete remission was observed in 1 patient with GBM (ongoing 27 months from starting ACT001) and stable disease lasting ≥ 6 months was seen in 3 patients. Preliminary biomarker analysis of PBMC samples revealed a post-treatment reduction in CD4+ Treg cells at some dose levels. Conclusions: In this first-in-human phase 1 study, ACT001 was well tolerated and showed satisfactory bioavailability and preliminary evidence of anti-tumor activity in malignant glioma patients dosed at 400 mg BID or lower. A phase 1b trial in recurrent GBM patients of ACT001 at 200-400 mg BID in combination with anti-PD-1 therapy is planned. Clinical trial information: ACTRN12616000228482.
Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion: A Japanese nationwide survey.
Authors: Takashi Kokudo, Kiyoshi Hasegawa, Yutaka Matsuyama, Tadatoshi Takayama, Namiki Izumi, Masumi Kadoya, Masatoshi Kudo, Yonson Ku, Michiie Sakamoto, Osamu Nakashima, Shuichi Kaneko, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2016)

4067 Background: The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. Methods: We analyzed data for 6,474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2,093 patients who underwent LR and 4,381 patients who received other treatments were compared. The propensity scores were calculated for 1,786 patients in the LR group and 3,758 patients in the non-LR group and we successfully matched 1,229 patients (68.8% of the LR group). Results: The median survival time (MST) in the LR group was 1.93 years longer than that in the non-LR group (2.74 years vs 0.81 years; P < 0.001) and 1.03 years longer than that in the non-LR group (2.41 years vs 1.38 years; P < 0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of the Child-Pugh grade, etiology of HCC, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative mortality rate was 1.4% (29 patients) and the multivariate analysis identified liver cirrhosis (hazard ratio [HR] 1.31), Child-Pugh class B (HR 1.69), and R2 resection (HR 1.60) as significant risk factors for the overall survival other than tumor related factors. Conclusions: As long as the PVTT is limited to the first-order branch, LR leads to a longer survival outcome than non-surgical treatment, especially in the presence of good liver function.
Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population-based surveys with 1·9 million participants
Authors: Regina Guthold, Gretchen A Stevens, Leanne M Riley, Fiona C Bull
Journal: The Lancet Global Health (2018)

Insufficient physical activity is a leading risk factor for non-communicable diseases, and has a negative effect on mental health and quality of life. We describe levels of insufficient physical activity across countries, and estimate global and regional trends.We pooled data from population-based surveys reporting the prevalence of insufficient physical activity, which included physical activity at work, at home, for transport, and during leisure time (ie, not doing at least 150 min of moderate-intensity, or 75 min of vigorous-intensity physical activity per week, or any equivalent combination of the two). We used regression models to adjust survey data to a standard definition and age groups. We estimated time trends using multilevel mixed-effects modelling.We included data from 358 surveys across 168 countries, including 1·9 million participants. Global age-standardised prevalence of insufficient physical activity was 27·5% (95% uncertainty interval 25·0-32·2) in 2016, with a difference between sexes of more than 8 percentage points (23·4%, 21·1-30·7, in men vs 31·7%, 28·6-39·0, in women). Between 2001, and 2016, levels of insufficient activity were stable (28·5%, 23·9-33·9, in 2001; change not significant). The highest levels in 2016, were in women in Latin America and the Caribbean (43·7%, 42·9-46·5), south Asia (43·0%, 29·6-74·9), and high-income Western countries (42·3%, 39·1-45·4), whereas the lowest levels were in men from Oceania (12·3%, 11·2-17·7), east and southeast Asia (17·6%, 15·7-23·9), and sub-Saharan Africa (17·9%, 15·1-20·5). Prevalence in 2016 was more than twice as high in high-income countries (36·8%, 35·0-38·0) as in low-income countries (16·2%, 14·2-17·9), and insufficient activity has increased in high-income countries over time (31·6%, 27·1-37·2, in 2001).If current trends continue, the 2025 global physical activity target (a 10% relative reduction in insufficient physical activity) will not be met. Policies to increase population levels of physical activity need to be prioritised and scaled up urgently.None.
Sidedness and prognostic factors of peritoneal metastatic colorectal cancer: A single center experience.
Authors: Aysegul Ilhan, Umut Demirci, Bulent Aksel, Ferit Aslan, Lutfi Dogan, Berna Oksuzoglu
Journal: Journal of Clinical Oncology (2017)

e15050 Background: Peritoneal metastasis in colorectal cancer (pCRC) is associated with poor prognosis. This study aimed to present a single centre experience for patients with pCRC. Methods: Between 2012 and 2016, 60 patients diagnosed with pCRC included in this study. Demographic and clinico-pathologic characterictics of patients were retrospectively analysed using patient medical records. Results: A total of 60 patients (31 female) were included and the median age was 61. Fifty-five patients (91%) had peritoneal metastases at the initial diagnosis, 37 patients (61%) had the left-sided colon cancer and 33 patients (55%) had the visceral metastases. Peritoneal metastasis was detected in 7 patients during the primary surgery. 30 patients (50%) received biologic therapy; 25 patients (41.6%) received anti-VEGF (bev) and 5 patients (8.3%) received anti-EGFR (cet/ pan) as the first line therapy. Seven (11%) patients underwent cytoreductive surgery and HIPEC. Median PFS of the analyzed patients was 10 months (SE: 2; 95% CI 6-13.9) and mOS was 20 months (SE: 4.2; 95% CI 11.7-28.7). The mPFS and mOS were 16.6 months (SE: 4.9; 95% CI 6.9-26.4) and 28 months (SE:7.1; 95% CI 13.8-42.1) in the group received surgery and HIPEC, respectively. No statistically significant survival difference was detected in terms of primary tumor localization, the presence of visceral metastasis (Table 1). Conclusions: In our study, the prognosis of pCRC patients was observed to be worse regardless of localization and the presence of accompanying visceral disease. A statistically significant difference was observed in the survival of the patients that received biologics. [Table: see text]
Assessing the uncertainty around the survival estimates used in multi-criteria decision anlaysis (MCDA). the alectinib case in Argentina using the Latin America federation of pharmaceutical industry (FIFARMA) framework.
Authors: Panos Orfanos, Claudio Martin, María De San Martín, Juan Pablo Denamiel, Francisco Tellechea, Lucas Najun Dubos, Joice Valentim
Journal: Journal of Clinical Oncology (2018)

e21123 Background: PFS & OS are key endpoints in the assessment of cancer medicines. Existing MCDA frameworks focus on criteria selection, weighting and scoring techniques but limited attention is paid on how actual survival is estimated, extrapolated and synthesized or the impact of the uncertainty around those estimates. Objective of this analysis is to assess the impact of these elements in MCDA. Methods: The FIFARMA MCDA framework was applied in Argentina, comparing alectinib versus ceritinib and chemotherapy, on ALK+ NSCLC, previously treated with crizotinib. Criterias were: Efficacy (OS & PFS, % of response on brain metastasis), Safety (Grade 3-5 Adverse Ev), Economic (Treatment cost and cost savings), Disease burden (severity, # of population affected, unmet need) and Quality of Evidence. Sensitivity analysis was performed on the survival estimates in order to define the magnitude of this uncertainty over the final results but also vs the uncertainty on the other MCDA elements such as weighting, scoring and criteria selection. Survival sensitivity scenarios covered median survival, extrapolated mean estimates with different parametric models, H2H and indirect comparisons with competitive treatments. To address both clinical and preference uncertainty, a probabilistic sensitivity analysis (PSA) of 5,000 iterations was performed, where both clinical and preference estimates varied simultaneously within defined confidence intervals. Results: The MCDA baseline scores demonstrated alectinib’s superiority with an incremental score of 0.19 and 0.34 versus ceritinib and chemotherapy respectively. Limited deviation (+/- 7%) was observed between participants’ preferences. Survival estimates were the key driver, varying the incremental scores to a range of +/- 25% among scenarios tested. Conclusions: Most frameworks assess survival and its durability using either limited data or calculation methods that are subjective and cognitively complicated. Emphasis is required on the survival estimation and the uncertainty around it, for a more robust assessment of the technologies.
Clinicopathological and genetic features of patients with colorectal cancer containing mucinous component.
Authors: Liu Yang, Yanhong Deng, Yue Cai, Jianwei Zhang, Huabin Hu, Zehua Wu, Ru Deng, Jianxia Li
Journal: Journal of Clinical Oncology (2018)

e15661 Background: Patients with mucinous adenocarcinoma(MC), has inferior outcomes compared to patients with adenocarcinomas (AC), but little is known for patients with mucinous component (MAC), whose adenocarcinoma compriseless than 50% proportion of mucinousrs ,This study is to investigate the features in patients with MAC colorectal cancer . Methods: Patients diagnosed with all CRC pathological type in Sixth Affiliated Hospital of Sun Yat - sen University between 12/2013 and 1 /2017 were respectively collected. Clinicopathological and genetic features(include KRAS,NRAS,BRAF,PIK3CA) were compared among MAC, MC and AC. Overall survival(OS) was compared. Results: Totally 2154 patients were recruited in analysis. The clinclinicopathological and genetic feature difference among the three type of patients were shown in table 1. 1847 cases were available for OS analysis ,the median survival time of MAC was 45.0 months(range,8-81 months). in multivariate analysis ,Age, pathological type , stage were found associated with OS (p < 0.05) . In detail, pathological types had significant influence on OS (p = 0.002),compare with AC, MC patients has inferiority OS HR 2.525 95% CI 1.444-4.414(P = 0.001) ,However, MAC patients has no significant difference in OS compare with AC,HR 0.881 95% CI 0.481-1.617(P = 0.683). Conclusions: This study demonstrated that MC is associated with higher mortality in CRC patients, MAC patients have some similar clinical and genetic characteristic with compared to MC patients, While OS survival behavior is similar to AC patients. Table 1. All MAC MC AC Characteristic (case) 2154 243 345 1565 Age Mean(y) 58 55 54 59 < 60 1098 135 212 750 ≥60 1056 108 133 815 Sex Male 1307 142 216 948 Female 847 101 129 617 Tumor location Right colon 429 62 110 257 Left colon 709 69 93 546 Rectal 1016 112 142 762 Disease stage I 203 20 25 158 II 793 104 127 560 III 878 78 93 707 IV 280 41 99 140 Microsatellite state 1996 223 253 1520 MSI 153 37 53 63 MSS 1843 186 200 1457 Genetic state 1898 195 137 1566 Wild type 885 53 34 798 Single Mutation 844 107 81 656 KRAS 695 90 67 583 NRAS 50 1 1 48 BRAF 45 14 8 23 PIK3CA 54 2 5 47 Double Mutation 169 35 22 112 KRAS+PIK3CA 154 29 19 107 NRAS+PIK3CA 3 1 0 2 BRAF+PIK3CA 9 4 3 2 KRAS+NRAS 3 1 0 1