tbuckley/cabot-search huggingface dataset:
Development of an artificial intelligence model to dynamically predict metastatic recurrence of early-stage breast cancer patients.
Authors: Vivek Prabhakar Vaidya, Smita Agrawal, Sai Vinod M, Sandeep Nagdewani, Prajwal Chandrashekaraiah, Tapasya Bhardwaj, Babu Narayanan
Journal: Journal of Clinical Oncology (2020)

e13078 Background: Models that can dynamically predict risk of metastatic breast cancer (MBC) recurrence based on cumulative historical clinical data could help guide patient care &amp; surveillance decisions. The objectives of this study were to predict risk of MBC recurrence dynamically from any point after 1 year of initial diagnosis in a BC patient’s journey. We show representative results for predicting 4 year risk post 1 year of date of diagnosis. There are established models to predict risk of distant recurrence at the time of diagnosis but we have not found much work on dynamic risk scores. Methods: We used a set of 3807 patients from the Concerto HealthAI database of oncology EMR data that includes clinical data from CancerLinQ Discovery to build this model that were further enriched by expert nurse curators. The average age at diagnosis was 58 &amp; the average follow up period for this cohort of patients was 6.6 years. The cohort included patients of all breast cancer subtypes. 628 patients had metastatic recurrence within 4 years post 1 year of date of diagnosis. We used 60% of the data for training, 20% for hyper-parameter tuning &amp; 20% for testing &amp; tried out various machine learning (ML) algorithms including Linear Regression, Lasso, Random Forest, Extremely Random Forests, &amp; XGBoost. Extremely Random Forest built using 330 features had the best performance. Results: The performance of various ML algorithms for predicting metastatic BC recurrence within 4 years post 1 year from date of diagnosis is provided in the table below with sensitivity held constant at 0.7. Key variables influencing the results in each model are also indicated. The Extremely Random Forest model for predicting risk of metastatic recurrence within 1 year from 1 year post diagnosis yielded an AUC of 0.814 &amp; a balanced accuracy of 0.719. Conclusions: An AI model to predict risk of metastatic recurrence in breast cancer patients built using a real world dataset yielded promising results. Furthermore, analysis of input variables provided insights not only into the key features driving metastatic recurrence risk such as previous surgery, tumor subtype, stage &amp; age at diagnosis etc. Such a model could be a useful for assessing patient risk &amp; treatment options at various points in a breast cancer patients journey as well as stratify patients for different levels of surveillance. [Table: see text]
Impact of systemic corticosteroids on survival outcomes in patients with immune-checkpoint inhibitor enterocolitis.
Authors: Leah L. Thompson, Ethan Katznelson, Donna E. Leet, Sienna Durbin, Jaewon Yoon, Jin K. Park, Michael L. Dougan, Steven T. Chen
Journal: Journal of Clinical Oncology (2020)

e15065 Background: Current guidelines for immune-checkpoint inhibitor enterocolitis (ICI-EC) recommend systemic corticosteroids (SCS) for moderate to severe cases, but whether these therapies have an impact on survival outcomes remains unclear. Prior work has been limited, considering only select cancer types, ICI regimens, and indications for immunosuppression. We therefore sought to examine the relationship between SCS for ICI-EC and survival outcomes, accounting for all other steroid exposures. Methods: We retrospectively reviewed the medical records of patients with biopsy-confirmed ICI-EC seen at our institution between August 2011 and April 2019, collecting patient demographics, cancer features, anti-neoplastic therapies, other immune-related adverse events (irAEs), SCS exposures, progression-free survival (PFS), and overall survival (OS). We further categorized SCS exposures by indication (ICI-EC, other irAE, other medical reason) and previously established dose thresholds (“high” ≥1mg/kg for ≥1 week; “moderate” ≥7.5mg for ≥2 months, or “none”). We assessed the relationship between SCS use for ICI-EC and PFS/OS using Cox proportional hazards models adjusted for age, sex, cancer type and stage, baseline brain metastases, functional status (Eastern Cooperative Oncology Group score), anti-neoplastic therapies, and other SCS exposures. Results: 90 patients (mean age 62.5 years, 37.8% female) had biopsy-confirmed ICI-EC, most commonly precipitated by CTLA-4 monotherapy (43.3%). Nearly all (80.0%) required SCS for their first episode of ICI-EC, with half (46.7%) requiring doses exceeding the highest threshold. Patients who received high-dose SCS for first ICI-EC episode had reduced PFS (HR = 2.50, p = 0.028) compared to those who did not receive SCS for this indication. OS was not affected by SCS therapy for ICI-EC at any dose. Conclusions: In cancer patients with biopsy-proven ICI-EC, receipt of high-dose SCS for first ICI-EC episode was associated with decreased PFS, but not OS. These findings suggest a nuanced and potentially dose-dependent relationship between SCS and survival outcomes meriting further investigation for a larger array of immunotoxicities.
食管癌的X线及CT影像诊断
Authors: 王海屹, 张啸波, 叶慧义
Journal: BMJ (2011)

食管癌是我国最常见的恶性肿瘤之一,也是食管最常见的疾病.其发病率具有明显的地域性,北方高于南方,山西、河南为高发区,男性多于女性.发病年龄多在40岁以上,发病高峰为50 ～ 70岁.食管癌病理类型以鳞癌最多见,腺癌或未分化癌少见,偶见鳞癌与腺癌并存的腺鳞癌.食管癌的转移途径多为淋巴组织与血行.如果癌组织仅浸润至黏膜、黏膜下层,并且无淋巴结转移称为早期食管癌,如果癌组织已经累及肌层或达外膜或外膜以外,有局部或远处淋巴结转移,则定义为中晚期食管癌.食管癌早期临床症状不明显,偶有间歇性的食物滞留感或异物感.癌组织逐渐增大则可出现持续性或进行性的吞咽困难,这也是食管癌最常见的临床症状。
Real-world incidence, duration, and severity of treatment-emergent (TE) neutropenia among patients (pts) with metastatic breast cancer (MBC) treated with ribociclib (RIB) or palbociclib (PAL).
Authors: Lee S. Schwartzberg, Juan Pablo Zarate, David Chandiwana, Chu-Ling Yu, Sanjeev Balu, Hemanth Kanakamedala, Stuart J Turner
Journal: Journal of Clinical Oncology (2020)

e13048 Background: Neutropenia is the most common adverse event following administration of CDK4/6 inhibitors RIB and PAL for hormone receptor–positive (HR+) MBC. There are limited comparative real-world data on TE neutropenia in pts receiving these agents. Here we report incidence, duration, and severity data on TE neutropenia in such pts from an electronic health record dataset and administrative claims. Methods: This retrospective study comprised 2 mutually exclusive cohorts of pts with MBC receiving RIB or PAL. Pts were matched 1:1 based on age and year of treatment start. Prior baseline activity of ≥6 mo was required. The MarketScan claims databases was used to evaluate incidence rates of TE neutropenia from Jan 1, 2015, to Dec 31, 2018, in pts receiving RIB or PAL. Rate ratio was calculated using a Poisson model. Data on neutropenia severity and duration were obtained from Optum de-identified Electronic Health Record dataset. Neutropenia severity was defined by neutrophil counts from lab tests (grade 1/2, 1000- &lt; 1500/μL; grade 3, 500- &lt; 1000/μL; grade 4 &lt; 500/μL) within the first 180 days of treatment. Neutropenia duration was estimated using Kaplan-Meier analysis and defined as the time between first abnormal neutrophil result and a lab result demonstrating neutropenia resolution. Results: After 1:1 matching, 152 pts from the MarketScan database were included in both the PAL and RIB cohorts; 168 matched pts were included from the Optum dataset. Neutropenia was reported in 38 pts (25%) in the PAL group and 25 pts (17%) in the RIB group. The rate of neutropenia per person–treatment year was 0.5 (95% CI, 0.4-0.7) in PAL pts vs 0.4 (95% CI, 0.3-0.6) in RIB pts. The rate ratio of neutropenia between treatments (PAL vs RIB) was 1.4 (95% CI, 0.8-2.3), which was not statistically significant, likely due to small sample size. Rates of neutropenia by severity with PAL vs RIB were 32% vs 32% for grade 1/2, 35% vs 26% for grade 3, and 4% vs 4% for grade 4, respectively. The rate ratio for grade 3 or grade 4 neutropenia (PAL vs RIB) was 1.3 (95% CI, 0.9-1.8). Median neutropenia duration was 29 vs 20 days ( P&lt; .01) with PAL vs RIB. Conclusions: Treatment of HR+ MBC with RIB and PAL requires optimal management of TE neutropenia. Real-world data showed that pts with MBC receiving PAL had a numerically higher rate of neutropenia than pts receiving RIB. Rates of grade 3 neutropenia were higher with PAL vs RIB, and duration of neutropenia was longer with PAL vs RIB. Economic burden analyses of neutropenia will be presented.
Pain progression at initiation of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of PROSELICA.
Authors: Nicolas Delanoy, Johann S. De Bono, Florence Mercier, Christine Geffriaud-Ricouard, Mario A. Eisenberger, Stephane Oudard
Journal: Journal of Clinical Oncology (2020)

5558 Background: PROSELICA phase III trial (NCT01308580) showed that cabazitaxel 20 mg/m2 (C20) is non-inferior to C25 in mCRPC patients (pts) post-docetaxel (DOC) (Eisenberger JCO 2017). Pts enrolled were symptomatic or not. This post-hoc analysis evaluates the influence of progression type at randomization on outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (Radio-p), no pain), Radio-p (± PSA-p, no pain) or pain progression (pain-p, ±PSA-p, ±Radio-p). The relationship between progression type and overall survival (OS), radiological progression-free survival (rPFS) and PSA response (confirmed PSA decrease ≥ 50%) was analyzed. Results: All patients randomized (n = 1200) had received prior DOC and 25.7% had received prior abiraterone or enzalutamide. Progression type was evaluable in 1065 pts (PSA-p = 24.5%, radio-p = 20.9%, pain-p = 54.6%). Pain progression was associated with clinical and biological features of aggressive disease and worse outcomes (decreased PSA response, rPFS and OS) vs PSA-p or radio-p (Table). The survival (rPFS and OS) on C25 was numerically higher than on C20 in pts with radio-p and pain-p. Conversely, C20 and C25 equally benefited pts with PSA-p only. In multivariate analysis (all arms combined), pain progression was an independent predictor of poor OS. Conclusions: This post-hoc analysis of PROSELICA shows that pain progression at initiation of cabazitaxel in mCRPC pts previously treated with DOC is prognostic. The activity of C25 was numerically higher than C20 in patients with radiological or pain progression. Clinical trial information: NCT01308580 . [Table: see text]
Models to predict injury, physical fitness failure and attrition in recruit training: a retrospective cohort study
Authors: Robin M. Orr, Bruce S. Cohen, Stephen C. Allison, Lakmini Bulathsinhala, Edward J. Zambraski, Mark Jaffrey
Journal: Military Medical Research (2020)

Abstract Background Attrition rate in new army recruits is higher than in incumbent troops. In the current study, we identified the risk factors for attrition due to injuries and physical fitness failure in recruit training. A variety of predictive models were attempted. Methods This retrospective cohort included 19,769 Army soldiers of the Australian Defence Force receiving recruit training during a period from 2006 to 2011. Among them, 7692 reserve soldiers received a 28-day training course, and the remaining 12,077 full-time soldiers received an 80-day training course. Retrieved data included anthropometric measures, course-specific variables, injury, and physical fitness failure. Multivariate regression was used to develop a variety of models to predict the rate of attrition due to injuries and physical fitness failure. The area under the receiver operating characteristic curve was used to compare the performance of the models. Results In the overall analysis that included both the 28-day and 80-day courses, the incidence of injury of any type was 27.8%. The 80-day course had a higher rate of injury if calculated per course (34.3% vs. 17.6% in the 28-day course), but lower number of injuries per person-year (1.56 vs. 2.29). Fitness test failure rate was significantly higher in the 28-day course (30.0% vs. 12.1%). The overall attrition rate was 5.2 and 5.0% in the 28-day and 80-day courses, respectively. Stress fracture was common in the 80-day course ( n = 44) and rare in the 28-day course ( n = 1). The areas under the receiver operating characteristic curves for the course-specific predictive models were relatively low (ranging from 0.51 to 0.69), consistent with “failed” to “poor” predictive accuracy. The course-combined models performed somewhat better than the course-specific models, with two models having AUC of 0.70 and 0.78, which are considered “fair” predictive accuracy. Conclusion Attrition rate was similar between 28-day and 80-day courses. In comparison to the 80-day full course, the 28-day course had a lower rate of injury but a higher number of injuries per person-year and of fitness test failure. These findings suggest fitness level at the commencement of training is a critically important factor to consider when designing the course curriculum, particularly short courses.
Molecular imaging in lymphoma beyond 18F-FDG-PET: understanding the biology and its implications for diagnostics and therapy
Authors: Xaver U Kahle, Filipe M Montes de Jesus, Andor W J M Glaudemans, Marjolijn N Lub-de Hooge, Annelies Jorritsma-Smit, Wouter J Plattel, Tom van Meerten, Arjan Diepstra, Anke van den Berg, Thomas C Kwee, Walter Noordzij, Elisabeth G E de Vries, Marcel Nijland
Journal: The Lancet Haematology (2020)
A case of jejunum stromal tumor with perforation as the first manifestation
Authors: Huyun Gao, Yaowen Yan, Huafeng Shen
Journal: BMJ (2017)

胃肠间质瘤来源于胃肠道间叶组织，可发生在食管至直肠的消化道任何部位，大部分发生于胃，小肠间质瘤可表现为非特异性的消化道出血、腹部不适、腹痛、腹部包块等。本文报道1例以穿孔为首发表现的空肠间质瘤病例的临床资料。
Phase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Authors: Lillian L. Siu, Barbara Burtness, Ezra E.W. Cohen, Kevin Joseph Harrington, Lisa F. Licitra, Danny Rischin, Ying Zhu, Chooi Peng Lee, Cecilia Pinheiro, Ramona F. Swaby, Jean-Pascal H. Machiels, Makoto Tahara
Journal: Journal of Clinical Oncology (2020)

TPS6589 Background: The PD-1 inhibitor pembrolizumab is currently approved as first-line monotherapy for patients with R/M HNSCC whose tumors express PD-L1 combined positive score (CPS) ≥1. In a phase 1b/2 trial (NCT02501096) of pembrolizumab plus lenvatinib (multikinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRa, RET, and KIT) in solid tumors, the combination demonstrated promising antitumor activity and a manageable safety profile in patients with HNSCC. LEAP-010 (NCT04199104) is a randomized, double-blind, placebo-controlled, phase 3 study that will evaluate the efficacy and safety of first-line pembrolizumab with or without lenvatinib in patients with PD-L1–positive R/M HNSCC. Methods: Key eligibility criteria include histologically confirmed R/M HNSCC incurable by local therapies, PD-L1–positive tumor (CPS ≥1) as determined by central laboratory, measurable disease as assessed by blinded independent central review (BICR) per RECIST v1.1, and ECOG performance status (PS) 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab plus lenvatinib or pembrolizumab plus placebo. Randomization will be stratified by PD-L1 status defined by tumor proportion score ( &lt; 50% vs ≥50%), human papillomavirus status for oropharynx cancer (positive vs negative), and ECOG PS (0 or 1). Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles (~2 years) and oral lenvatinib 20 mg or placebo once daily; patients may continue to receive lenvatinib or placebo after pembrolizumab treatment is complete. Treatment will continue until BICR-verified disease progression or unacceptable toxicity. Pembrolizumab retreatment (second course) for 17 additional cycles will be allowed for eligible patients who stop pembrolizumab and subsequently experience BICR-verified disease progression. These patients could have stopped treatment with stable disease, partial response, or complete response or after 35 cycles of pembrolizumab for reasons other than disease progression or toxicity. Tumor imaging assessment will be performed at week 6, then every 6 weeks until 1 year, and thereafter every 9 weeks. Primary end points are objective response rate and progression-free survival, assessed by BICR per RECIST v1.1, and overall survival. Secondary end points are duration of response and safety and tolerability. Recruitment is ongoing; planned enrollment is ~500 patients. Clinical trial information: NCT04199104 .
Relationship between cerebral artery stenosis and obstructive sleep apnea
Authors: Dongping Zhang
Journal: BMJ (2016)

Objective
To investigate the relationship of obstructive sleep apnea and atherosclerotic cerebral artery stenosis.


Methods
One hundred and twenty patients with acute cerebral infarction were enrolled in the study. Patients underwent polysomnography monitoring; according to the results, the sleep apnea/hypopnea index (AHI) was ≥5/h in 60 patients (OSA group) and AHI was <5/h in another 60 patients (non-OSA group). The degree, quantity and distribution of cerebral artery stenosis were compared between OSA and non-OSA group.


Results
The results showed that there were no significant differences in gender, age, NIHSS score and rates of diabetes, coronary heart disease, hyperlipidemia and smoking between two groups (P> 0.05). The rates of increased BMI [(26.07±2.39)vs.(23.59±2.73) kg/m2] and hypertension [70%(42/60)vs. 43%(26/60)] in OSA group were higher than those in non-OSA group (t=5.304, χ2=7.603, all P 0.05). The severity of cerebral artery stenosis in OSA group was higher than that in non-OSA group (χ2=17.801, P 0.05).


Conclusion
The study indicates that there is a close relationship between OSA and stenosis of atherosclerotic cerebral arteries.


Key words: 
Sleep apnea, obstructive; Cerebral arterial stenosis
Documentation patterns and impact on observed side effects of the CANKADO ehealth application: An exploratory analysis of the PreCycle trial.
Authors: Tom Degenhardt, Nadia Harbeck, Peter A. Fasching, Rachel Wuerstlein, Diana Lüftner, Ronald E. Kates, Johannes Schumacher, Claudia Wenzel, Timo Schinkoethe, Marcus Schmidt
Journal: Journal of Clinical Oncology (2020)

2083 Background: PreCycle (NCT03220178), a multicenter, randomized phase IV Intergroup trial evaluates the impact of ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer patients (pts) treated by palbociclib (P) and an aromatase inhibitor or P+fulvestrant. Pts willing to use the web/APP-eHealth solution CANKADO are eligible. Patients are randomized (2:1, stratified by therapy line) to the active (CANKADO PRO-React) or inactive inform arm. Primary endpoint is time to deterioration (TTD) of QoL. Methods: The trial started in 2017 and is ongoing (81 centers); regular safety reports are routinely provided to the study sponsor. Analysis of distribution of serious adverse events (SAE) was initiated by the trial leadership and performed using the Oct 15, 2019 safety report. Data that could bias primary or secondary endpoints were not analyzed. Bayesian inference (non-informative prior) was used to estimate probabilities; no corrections for potential multiplicities were made. Results: At data cut-off, 261/281 randomized patients had received study medication and provided CANKADO documentation. At time of evaluation, a total of 40298 days were documented. CANKADO was used on 59% (+/-10%) of all days over a 2-year period. SAEs were observed in 26/175 (14.9%) of all active-arm patients vs. 18/86 (20.9%) of inform-arm patients (90% probability of reduction in inform patients). Total SAEs were 36 (active) vs. 27 (inform); corresponding SAE incidence per hundred patients was 20.6 vs. 31.4, a relative reduction of about one-third. Conclusions: CANKADO is well accepted and used regularly by pts in PreCycle, so far over a 2-year period. The present (unplanned) analysis suggests a potentially substantial, clinically relevant reduction in relative SAE incidence among 1 st L pts using PRO-React, with a more modest decrease overall. This analysis is preliminary, representing a snapshot, and cannot provide a definitive explanation for the observed SAE reduction. PreCycle will continue to enroll patients in order to further evaluate the potential benefits of interactive eHealth support. Collaborators: WSG WOMEN´S HEALTHCARE STUDY GROUP, CANKADO, Pfizer, AGO-TraFo, AGO-B, Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V. Sponsor: Palleos Healthcare GmbH Keywords: eHealth, Adverse Events, Palbociclib Clinical trial information: NCT03220178.
Indication of adjuvant chemoradiation post neoadjuvant chemotherapy in very locally advanced borderline resectable head and neck cancer.
Authors: Sudeep Das, Vijay Maruti Patil, Vanita Noronha, Sachin Babanrao Dhumal, Amit Joshi, Nandini Sharrel Menon, Sujay Srinivas, Dilip Harindran Vallathol, Hollis D'souza, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

e18505 Background: Adjuvant chemoradiation (ACRT) is indicated in the presence of margin positivity or extranodal extension. However, indications of ACRT post neoadjuvant chemotherapy (NACT) is not well defined. At our centre, ACRT is administered in the majority of patients who undergo NACT. This analysis was performed to identify indications for the avoidance of ACRT post NACT. Methods: 160 very locally advanced borderline resectable HNSCC who underwent surgery after NACT were selected. The adjuvant treatment administered was either radiation or chemoradiation at the discretion of the joint clinic. The post-surgical tumour and nodal specimen were graded in accordance with modified tumour regression grade (MTRG). Where grade 1 indicated a complete pathological response. The primary endpoint was disease-free survival (DFS). The patients were divided into 3 biological distinct classes. Group-1 had a pathological complete response (CR) in both tumour and nodes, Group-2 had pathological CR in either tumour or nodes and Group 3 had no pathological CR. Kaplan Meier method was used for the estimation of DFS. The stratified (for groups) log-rank test was used for evaluating the impact of adjuvant radiation. Stratified Cox regression analysis was used for the calculation of hazard ratio. A p-value of 0.05 was considered significant. Results: There were 56 patients (35%) in group 3, 75 (46.9%) in group 2 and 29 (18.1%) in group 1. The overall median DFS was 89.067 months (95%CI 15.345-162.788). The 5-year DFS was 22.1% in group 3, 75.4% in group 2 and 92.3% in group 1 ( P-value &lt; 0.0001). Adjuvant radiation was received by all patients and concurrent chemotherapy was received by 134 (83.8%) patients. Use of concurrent chemotherapy decreased the hazard of disease recurrence (HR-0.297 95%CI 0.135-0.656, P-value = 0.003). The stratified log-rank test p-value was 0.002. Conclusions: Adjuvant chemoradiation is needed after neoadjuvant chemotherapy in very locally advanced borderline resectable head and neck cancer
良性前列腺增生症的外科治疗
Authors: 邵强
Journal: BMJ (2010)

症状性良性前列腺增生(BPH)引起的下尿路症状是患者的切身感受,可严重影响老年男性的生存质量~([1]).因此,下尿路症状及其所致生存质量的下降是患者寻求治疗的主要原因.许多研究证实,BPH是缓慢进展性疾病~([2-3]),其症状随患者年龄的增加而进行性加重,下尿路症状加重而导致患者生存质量下降、最大尿流率进行性下降,发生急性尿潴留、血尿、复发性尿路感染、肾功能损害等,故BPH患者接受外科治疗是疾病进展的最终表现形式。
To control risk factors and reinforce the prevention and treatment of ischemic stroke
Authors: 龚涛
Journal: BMJ (2009)

中国卫生部2007年统计信息显示,导致中国公众死亡的疾病中,脑血管病排在第一位.脑卒中是脑血管病最常见类型,其中缺血性脑卒中占所有脑卒中的80%～85%. 缺血性卒中的病因(发病机制)主要有2种,一种为微栓子,如心源性、动脉源性及反常栓子;另一种为血流动力学异常,最常见的原因是动脉粥样硬化导致动脉狭窄(≥70%)甚至梗阻,其远端脑灌注量下降.其他少见病因包括:血管痉挛、机械压迫等。