tbuckley/cabot-search huggingface dataset:
Associations between psoas muscle area (PMA) and density (PMD) with phase I oncology clinical trial outcomes.
Authors: Pritish Iyer, Peter Whooley, Elizabeth A. Handorf, Matthew Blau, Yana Chertock, Laura Levin, Michael J. Hall, Rishi Jain
Journal: Journal of Clinical Oncology (2020)

7007 Background: Malnutrition and cancer cachexia can lead to loss of muscle mass (sarcopenia) and are associated with poor outcomes. Muscle status can be evaluated by computed tomography (CT)-based radiographic measures, specifically at the L3 vertebrae where the psoas and other core muscles reside. We previously found that baseline malnutrition was associated with worse phase 1 clinical trial outcomes including increased toxicity and reduced survival (Jain et al. Oncologist, 2019). We sought to evaluate the relationship between muscle status and phase 1 trial outcomes. Methods: CT-based psoas muscle area (PMA) and psoas muscle density (PMD) were evaluated in 83 patients who enrolled in a phase 1 trial. We localized the L3 vertebral body on axial imaging and manually outlined the psoas muscle to calculate PMA (standardized to height) and PMD. Two reviewers independently conducted the analyses. We stratified patients by having a PMA or PMD above or below the group’s median. We evaluated for associations between PMA/PMD and the following clinical trial outcomes: rates of grade ≥ 3 toxicity, frequency of dose reductions/interruptions, hospitalizations, tumor response, duration on study (DOS), and overall survival (OS). We also evaluated for correlations between PMA/PMD and a validated measure of nutritional status, the PG-SGA. Chi-square analysis was used to determine statistical significance between groups. Kaplan-Meier curves were used to compare DOS and OS. Results: 83 patients were included (38 male, 45 female), with a median age of 60 (range 28-85). The most common cancer type was gastrointestinal (33%). Mean PMA was 2.89 cm 2 /m 2 (range 1.41-5.72) and mean PMD 37.77 Hounsfield units (range 13.27-56.18). PMA above the median was associated with a reduced risk of grade ≥ 3 toxicity (32.5% vs 67.4%, p = 0.001). There was no association between PMD and grade ≥ 3 toxicity, or between PMA/PMD and other phase 1 trial outcomes. There was a significant correlation between nutritional status and PMA (r = -0.278, p = 0.01) but not PMD. Conclusions: PMA and PMD are readily available CT-based measures of muscle status. In oncology phase 1 clinical trial participants, lower baseline PMA was associated with a two-fold increased risk of grade ≥ 3 toxicity. Baseline PMA was moderately correlated with nutritional status which was previously shown to be associated with poor trial outcomes. More research is necessary to further understand the specific mechanisms by which nutritional status and muscle mass may influence toxicity risk in this population.
慢性心力衰竭的社区干预模式
Authors: 吴彦
Journal: BMJ (2004)

慢性心力衰竭(以下简称心衰)是各种心脏疾病发展到终末阶段表现出的一种临床综合征,是当前惟一一个患病率仍在增加的心血管病,40岁人群平均患病率为1%,年龄每增加10岁患病率增加1倍,大于70岁老年人的患病率达到10%[1].其住院率和死亡率居高不下,医疗费用巨大。
Outcomes among women with brain metastases from gynecologic (gyn) malignancies.
Authors: Kristen Cagino, Ryan Kahn, Susie Chan, Charlene Thomas, Paul J. Christos, Susan Pannullo, Hani Ashmalla, Kevin Holcomb, Melissa Kristen Frey, Eloise Chapman-Davis
Journal: Journal of Clinical Oncology (2020)

e18034 Background: Brain metastasis secondary to gyn malignancy is rare and associated with poor prognosis, with limited available data and no definitive management guidelines. We aimed to identify factors and treatments associated with improved overall survival (OS). Methods: Patients were identified retrospectively with brain metastases from gyn malignancies between 2004-2019. Descriptive statistics were used to describe the cohort of patients using N (%) and median [IQR] for categorical and continuous variables, respectively. Univariate cox proportional hazards regression was performed to evaluate the effect of different prognostic factors on OS. Results: 32 patients presented with brain metastasis from gyn primaries (ovarian/primary peritoneal n = 14, cervical n = 7, uterine n = 11). Median age of initial cancer diagnosis was 62 (54-59). At initial diagnosis 83% of patients were Stage III/IV and underwent surgical management (56%), chemotherapy (100%), or pelvic radiation (31%). The median time from cancer diagnosis to brain metastasis was 18mos. 66% presented with multiple; 34% with isolated brain metastases. The most common presenting symptoms were extremity weakness/numbness (78%), seizures (34%), and headaches (28%). Surgical resection was most often combined with stereotactic radiosurgery (SRS) and/or whole brain radiation therapy (WBRT) (Table 1). Median survival from date of brain metastases was longer in patients treated by SRS alone compared to WBRT alone (95 vs 11 mos). Treatment with SRS + Surgery compared to SRS or WBRT alone revealed a trend toward improved OS (p = .06; p = .07). Increased time from initial cancer diagnosis to brain metastasis was associated with improved OS, with one-month increase in time associated with a 7% reduction in risk of death (p = 0.01). Initial cancer treatment, Stage, histology, and number of brain lesions did not affect OS. Conclusions: Patients with brain metastasis secondary to gyn malignancies with the longest OS had the greatest lag time between initial cancer diagnosis and brain metastasis diagnosis. Treatment with multimodal therapy with radiation and surgical resection was associated with the longest OS. [Table: see text]
Clinical and imaging features of reversible splenial lesion syndrome
Authors: Lang He, Hongyuan Shao, Qiutang Xiong, Luqing Zhao
Journal: BMJ (2017)

The clinical data and imaging findings of 10 patients with reversible splenial lesion syndrome (RESLES) admitted in Shanxi people′s Hospital from August 2014 to August 2016 were retrospectively analyzed. All 10 patients were acute or subacute onset, the etiology included viral meningitis (n=5), purulent meningitis (n=2), tuberculous meningitis (n=1); and one schizophrenic patient receiving antipsychotic drug and one epileptic patient treated with phenytoin. There were 8 patients under 30 years. The clinical manifestations included headache, fever, disorder of consciousness and mental symptoms. Seven patients had prodromic infections before the onset of the disease and focal neurological defects were present in the early stage. The initial MRI showed isolated splenium of corpus callosum (SCC) lesions with homogeneous hyperintense on T2WI, hypointense on T1WI, and patchy, round, ovoid, schistose diffusion with hyperintense on DWI in all 10 cases; and there was no significant strengthening on enhanced MRI in 4 cases. The follow-up MRI showed that SCC abnormalities disappeared after treatment in 9 cases and the neurological symptoms disappeared after one-month follow up in 6 cases. The results indicate that RESLES is frequently secondary to infections, and presents the symptoms of mild encephalitis or encephalopathy.


Key words: 
Splenial lesion syndrome; Pathological comditions, signs and symptoms; Maginetic resonance imaging
血清心肌酶异常的临床解读
Authors: 王国兴
Journal: BMJ (2008)

血清心肌酶是指一组特异性反应心肌损伤的酶学指标,包括心肌酶、肌红蛋白(myoglobin,Mb)及心脏特异性肌钙蛋白(cTn).在急性冠状动脉综合征(acute coronary syndromes,ACS)时心肌细胞缺血坏死,大量血清酶被释放到血液循环中,通过检测上述指标可判定急性心肌梗死的发生并评估治疗效果。
Factors affecting 48-hour methotrexate levels following high-dose methotrexate (HDMTX) in lymphoma.
Authors: Darragh O'Donoghue, Huong Truong, Heidi Diann Finnes, Jennifer McDonald, Stephen M. Ansell, Nelson Leung
Journal: Journal of Clinical Oncology (2020)

e20033 Background: HDMTX is an important component of lymphoma therapy due to its central nervous system penetration. Although HDMTX can be safely administered to most patients, it can cause significant toxicity with those who have prolonged exposure to high plasma concentrations of MTX due to delayed elimination. Therefore, serum MTX concentration monitoring is still a standard approach for identifying patients at high risk of developing MTX toxicity. A majority of MTX is excreted within the first 48 hours of infusion. Higher MTX plasma concentrations at 48 hrs increase the likelihood of delayed MTX elimination. This study will assess baseline characteristics associated with high 48-hour MTX levels (≥ 1µM) which has been associated with increased risk of complications. Methods: A retrospective review of the electronic medical record was conducted to identify lymphoma patients who received HDMTX from 1/1/2002 to 12/31/18. Baseline demographics including age, gender, comorbidities, body surface area, BMI, weight and baseline chronic kidney disease (CKD) were recorded. Demographics, HDMTX dosing per protocol (3.5g/m 2 vs 8g/m 2 ), HDMTX adjusted by renal function (CrCl &lt; 100), and ratio of MTX dose to BSA (MTX/BSA) were compared to 48 hour MTX levels. Analysis was performed in JMP 15. Results: 2553 cycles were of HDMTX were identified. There was a significant association of increasing age, (p = 0.039), male patients (p &lt; 0.001), 8g/m 2 dosing (p &lt; 0.001), higher MTX dose (p &lt; 0.001), MTX/BSA (p &lt; 0.001), GFR by CKD-EPI (p &lt; 0.001) and lower number of comorbidities (p &lt; 0.001) with 48-hour MTX levels ≥1. There was no significant association of 48-hour MTX levels ≥1 and GFR by Cockcroft-Gault (p = 0.73), baseline CKD (p = 0.78), and renal adjusted HDMTX (p = 0.52). Multivariate analysis revealed significance for MTX/BSA, gender, BSA, GFR by CKDEPI (p &lt; 0.001), and age (P = 0.0002). Conclusions: Hematologists should be aware that age, gender, GFR by CKD-EPI, and ratio of MTX dose to BSA are associated with elevated 48-hour MTX levels ≥1.
Systemic mastocytosis: a report of 3 cases and literature review
Authors: Vedamurthy, Adhiyaman, Sonja
Journal: BMJ (2009)

Objective
To review the clinical features, diagnostic work-up, classification, prognosis and treatment of systemic mastocytosis (SM).


Methods
The clinical data of 3 SM patients admitted to Peking Union Medical College Hospital (PUMCH) were retrospectively analyzed and the review of recent literatures was performed.


Results
All the 3 cases were pathologically diagnosed. According to WHO 2008 classification criteria, 2 cases were diagnosed as aggressive SM (ASM) and the other one was diagnosed as indolent SM (ISM). Case 1 was a 60-year-old female patient who had overt mediator release syndrome manifesting as episodes of flushing, fever, vomiting, palpitation, hypotension and syncope. She was diagnosed as aggressive SM based on significantly increased number of abnormal mast cells (accounting for 6% of all nucleated cells) in the bone marrow aspiration sample and biopsy specimen which accompanied with decreased other myeloid and erythroid elements. Her disease was refractory to the treatment of H2 antihistamines and led to a fatal outcome eventually. Case 2 was a 72-year-old male patient who underwent extended proximal gastrectomy with esophagogastric anastomosis due to endoscopically detected diffuse thickening of the gastric fundic mucosa. The diagnosis as indolent SM was established according to the dense infiltrate of abnormal mast cells in the surgically resected part of stomach and regional lymph nodes. He had been in complete remission for more than 6 years ever since then. Case 3 was a 41-year-old female patient who presented with fever, urticaria pigmentosa and diffuse bone lesions. A bone biopsy specimen demonstrated a dense infiltrate of mast cells while the assays for KIT-D816V mutation and FIP1L1-PDGFRα fusion gene yielded negative results. She was diagnosed as aggressive SM and a progression-free survival of more than 1 year had been achieved with the treatment of prednisone, interferon-α and pamidronate.


Conclusions
SM is a rare disease. Diagnosis is primarily dependent on histopathology. There is currently no curative therapy for systemic mastocytosis. Treatment is intended to reduce symptoms and improve quality of life. The prognosis of ISM is much better than that of ASM.


Key words: 
Mastocytosis, systemic; Diagnosis; Therapy
Role of real-world evidence for oncology product registration in the United States: A review of approvals by the U.S. Food and Drug Administration from 2015 to 2019.
Authors: Bhakti Arondekar, Rachel Bhak, Maral DerSarkissian, Lynn Huynh, Kelsey Wang, Eric Davis, Bryon Wornson, Mei Sheng Duh
Journal: Journal of Clinical Oncology (2020)

e14130 Background: There are few concrete examples of real world evidence (RWE) used to support clinical development in regulatory filings despite growing interest in this field. This study systematically reviewed FDA oncology approvals to identify use cases of RWE. Methods: FDA’s new drug application (NDA) and biologics license application (BLA) approvals for oncology products from 2015-2019 were systematically reviewed. Among cases with RWE, data characterizing the submission and RWE details (data source, study design, FDA comments) were synthesized. Results: 93 approved NDAs and BLAs were identified; 6 included RWE in support of efficacy (see Table), approved on or after 2017, and were largely retrospective studies that contextualized results to pivotal trial, with primary endpoints overall survival (OS), overall response rate (ORR), and time to treatment discontinuation (TTD). Flatiron data were used in 3 of these as database analyses, 1 was an expanded access program (EAP), 1 was a meta-analysis, and 1 was a retrospective chart review. Conclusions: In the past 5 years, few FDA decisions incorporated RWE in oncology drug approvals. When used, RWE has been a complement rather than a supplement for clinical trial data. Early engagement, a priori protocol development, and robust research design (adjusting for bias, comparability to clinical trial population) remain key determinants for successful use of RWE in FDA decision making. [Table: see text]
Acquired RB1 mutations in estrogen receptor-positive (ER+) clinically advanced and metastatic breast cancer (MBC).
Authors: Kimberly McGregor, Ethan Sokol, Natalie Danziger, Dean Pavlick, Julia Andrea Elvin, Jo-Anne Vergilio, Jonathan Keith Killian, Douglas I. Lin, Erik Abraham Williams, Shakti H. Ramkissoon, Eric Allan Severson, Amanda Hemmerich, Daniel Duncan, Richard Huang, Jon Chung, Venkataprasanth P. Reddy, Jeffrey Venstrom, Alexa Betzig Schrock, Brian Michael Alexander, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2020)

1053 Background: Prior to use of cell cycle inhibitor drugs such as palbociclib, mutations in the retinoblastoma cell cycle inhibitory gene ( RB1) were extremely uncommon. To assess recent descriptions of RB1 mutations in MBC as treatment related, we compared primary untreated ER+ breast cancer samples from patients who developed MBC with ER+ MBC metastasis biopsies in post-primary treatment patients. Methods: Extracted DNA from 15 untreated primary breast tumors (PBx) and 36 treated metastatic MBC tumors (MBx) were sequenced by hybrid capture genomic profiling to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA. PD-L1 expression was determined by IHC (Dako 22C3). Results: The age distribution, GA per tumor, CDH1 and ERBB2 GA frequencies were similar in PBx and MBx. GA in ESR1 (P &lt; 0.0008), classically associated with acquired hormonal therapy resistance, and PIK3CA (p &lt; 0.11) were increased in the MBx vs the PBx samples. RB1 GA were more frequent in the MBx samples (11%) than the pre-treatment PBx samples (0%, P &lt; 0.31). GA not associated with targeted therapy programs were similar in both groups. In addition to low frequencies of ERBB2 amplification in the ER+ tumors, the most frequent potentially targetable GA identified in both PBx and MBx included GA in FGFR1 and NF1. BRCA1 GA were identified in the MBx group only. Biomarkers of potential immunotherapy benefit including MSI status, TMB levels and PD-L1 IHC staining were at similarly low levels in both groups. Additional cases are being identified to expand the cohort sizes for final presentation. Conclusions: In addition to the well-known acquisition of hormonal therapy resistance mutations in ESR1 and PIK3CA in ER+ MBC, this study also supports the acquisition of RB1 mutations when post-treatment metastasis biopsies are sequenced rather than pre-treatment primary tumors. This increase in RB1 mutation identification is associated with exposure of the tumors to anti-cell cycle drugs such as palbociclib in the treated but not the untreated cohort. [Table: see text]
Changes of quality of life after liver transplantation in patients with liver cancer
Authors: Xue-feng Hua, Jin Zhang, Min-qiang Lu, Gui-huo Chen
Journal: BMJ (2009)

Twenty six patients with liver cancer who received liver transplantation were enrolled in the study. The patients were assessed by SF-36 scale and QOL-LC V2.0 scale before and 0 -6, 7 - 12, > 12 months after the liver transplantation. Scores in physical function domain and social function domain decreased significantly in the early stage post LT (0 -6 month post-LT). While in later stage ( >7 months post-LT), the scores showed no significant difference or even higher than that of pre-LT. In psychological function domain, no significant difference was found pre- and post-LT. The scores were improved significantly in later stage post-LT than pre-LT and early stage post-LT.

Key words: 
Liver transplantation; Quality of life
Primary cytoreductive surgery with or without Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: The OVHIPEC-2 trial in progress.
Authors: Ruby M. van Stein, Simone N. Koole, Karolina Sikorska, Desmond P. Barton, Lewis Perrin, Donal Brennan, Oliver Zivanovic, Berit J. Mosgaard, Anna Fagotti, Pierre-Emmanuel Colombo, Valesca P. Retel, Gabe S. Sonke, Willemien J. Van Driel
Journal: Journal of Clinical Oncology (2020)

TPS6100 Background: The addition of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. The effect of HIPEC remains undetermined in patients who are eligible for primary cytoreductive surgery. We hypothesize that the addition of HIPEC to a complete or near-complete (residual disease ≤2.5 mm) primary cytoreductive surgery improves overall survival in patients with FIGO stage III ovarian cancer. Methods: This international, randomized, open-label, phase III trial enrolls patients with newly diagnosed, histological proven FIGO stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with resectable umbilical, spleen or local bowel lesions may be included. Following complete or near-complete primary cytoreduction, patients are intra-operatively randomized (1:1) to receive HIPEC or no HIPEC. Patients in both study arms will receive six courses of adjuvant carboplatin-paclitaxel and maintenance PARP-inhibitor or bevacizumab according to current guidelines. The primary endpoint is overall survival. To detect a Hazard Ratio of 0.67 in favor of HIPEC, 200 overall survival events are required. Assuming that accrual will be completed in 60 months, and 12 months additional follow-up, 538 patients need to be randomized. All randomized patients will be included in the analysis for overall survival according to the intention to treat principle. Pre-specified subgroup analyses will be performed based on stratification factors (peritoneal cancer index at start of surgery, completeness of surgery), histologic subtype (high-grade serous versus other), and BRCA mutation (BRCA1/2 mutation versus wildtype). Secondary endpoints are recurrence-free survival, time to first subsequent anticancer treatment, and treatment related complications and toxicity. Exploratory endpoints are time to second subsequent anticancer treatment, health-related quality of life, and cost-effectiveness. The Institutional Review Board of the Netherlands Cancer Institute approved the trial, which is actively enrolling patients since January 2020. Clinical trial information: NCT03772028.
A novel pretreatment model identifying high-risk of refractoriness after transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma.
Authors: Xin Yin, Ke Shu Hu, Shen Xin Lu, Bei Tang, Zhenggang Ren
Journal: Journal of Clinical Oncology (2020)

e16641 Background: Refractoriness to transcatheter arterial chemoembolization is common during the therapeutic process of hepatocellular carcinoma, which is an intractable issue and may compromise the prognosis. We aim to establish a pre-treatment model to identify patients with high risks of refractoriness. Methods: From 2010 to 2016, 824 patients who had initially underwent at least two sessions of transcatheter arterial chemoembolization in Zhongshan Hospital, Fudan University were retrospectively enrolled. These patients were randomly allocated into a training cohort and a validation cohort. The pre-treatment scoring model was established based on the clinical and radiological variables using logistic regression and nomogram. The discrimination and calibration of the model were also evaluated. Results: Logistic regression identified vascularization pattern, ALBI grade, serum alpha-fetoprotein level, serum γ- glutamyl transpeptidase level and major tumor size as the key parameters related to refractoriness. The p-TACE model was established using these variables (risk score range: 0-19.5). Patients were divided into six risk subgroups based on their scores ( &lt; 4, ≥4, ≥7, ≥10, ≥13, ≥16). The discriminative ability, as determined by the area under receiver operating characteristic curve was 0.784 (95% confidence interval: 0.741-0.827) in the training cohort and 0.743 (95% confidence interval: 0.696-0.789) in the validation cohort. Moreover, satisfactory calibration was confirmed by Hosmer-Lemeshow test with P values of 0.767 and 0.913 in the training cohort and validation cohort. Conclusions: This study presents a pre-treatment model to identify patients with high risks of refractoriness after transcatheter arterial chemoembolization and shed light on clinical decision making.
颈部疼痛
Authors: 孙天胜, 赵广民
Journal: BMJ (2011)

颈部疼痛通常指非特异性颈痛或单纯颈痛(nonspecific or simple neck pain)[1],是骨科临床上最常见的疾病之一.颈痛的发生往往没有外伤史,而是因为姿势原因或机械应力劳损所致,但具体的原因并不明确,更多地认为颈痛的发生是多因素作用的结果.颈痛的发生率仅次于非特异性腰痛(non specific back pain).在西方发达国家,随着现代社会工作方式和生活方式的变化,尤其是电脑的使用和文案工作的普及,颈痛的发生率逐年增加,女性约为17％,男性为14％[2].在我国,虽然缺乏相应的流行病学统计数据,但在城市工作的人群发生率相当高,几乎成为都市白领的职业病,且发生人群有年轻化的趋势。