tbuckley/cabot-search huggingface dataset:
Implementing a clinical risk prediction tool for patients undergoing active cancer treatment.
Authors: Nathan Handley, Adam Binder, Michael Li, Aliya Rogers, Valerie Pracilio Csik
Journal: Journal of Clinical Oncology (2020)

TPS2086 Background: Acute care utilization (ACU), encompassing both emergency department visits and hospitalizations, is common in patients with cancer, with nearly three quarters of patients with advanced disease hospitalized at least once in the year after their diagnosis. Efforts to prospectively identify these patients prior to ACU have led to the development of a variety of scoring systems for specific cancer patient populations, including the elderly and those initiating palliative infusional chemotherapy. Prospectively identifying patients may enable early interventions to reduce ACU. However, few studies have demonstrated effective implementation of such prediction tools in clinical practice. We developed an oncology risk score (ORS) for active oncology patients (defined as patients with an active cancer diagnosis in the last 12 months who had a Medical Oncology encounter in a 180-day period ) to prospectively determine risk of ACU. Patients are defined as high risk (18% of patients, accounting for 57% of historical ACU), intermediate risk (25% of patients, accounting for 25% of ACU), or low risk (56% of patients, accounting for 18% of ACU) by the ORS. We are currently deploying a pragmatic implementation initiative to evaluate the impact of targeted nurse navigator (NN) outreach to patients defined as high risk for ACU by the ORS. Methods: The ORS is embedded within the health system electronic medical record. The ORS will be queried on a weekly basis. NNs will contact identified patients, prioritizing patients not yet identified by the navigation team by other means. Following chart review, NNs will either meet patients in person (if a visit is already planned within 24 hours) or complete standard navigation outreach and documentation (consisting of phone call and barrier assessment, as well as appropriate nursing intervention) if no visit is planned. NNs will determine follow up cadence based on clinical judgement. Efficacy will be determined using a case-control method. Case patients will be OCM patients defined as high risk by the ORS (historical n = 289); control patients will be non-OCM high risk patients (historical n = 388). The total number of patients in the case and control groups, as well as the proportion of patients in the group utilizing acute care, will be monitored over time. Proportion of high risk patients known to navigation will be tracked. ACU in medium and low risk groups will also be monitored. Targeted outreach to high risk patients using the ORS began on 2/5/2019.
Injection mixed drug intratumoral to produce ROS and creating a coagulum as cancer therapeutics drug depot.
Authors: Jian Zhang, Qiang Fu, Bian Li, Yan Han, Dong Chen, Guoqin Zheng, Ming Zhao, Baofa Yu
Journal: Journal of Clinical Oncology (2020)

e15635 Background: To explore the nature of hydrogen peroxide at higher dosage for denature-aggregation of tumor with drugs through aggregation in denatured tumor as a coagulum for drug depot and prolong function of drug. Methods: (1). Preparation for two 5 ml of BLM-I 131 , one diluted with 0.12 ml NS and 0.2 ml (0.2mCi = 49.67µg BLM) for tumor injection in control group; one diluted with 0.12 ml of H2O2 (0.833 mg/ml) and 0.2 ml (0.2mCi = 49.67µg BLM) for tumor injection in experimental group. (2).Tumor imaging with BLM-I 131 analyzed at different time points. (3). Radioactivity in tumor of mice analyzed under SPECT scanning imaging instrument at the 0, 5 h, 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 96 h, 120 h, 144 h and 168 h, activity of isotope I 131 is representing the BLM retaining time in tumor. (4). Also, tumor sectioned and observed cellular and extracellular matrix changes of histological structure. Results: It was observed that BLM-I 131 with ROS in tumors sustained for 168 hours while BLM-I 131 with NS in tumors sustained for 8 hours only. Radioactivity of BLM-I 131 in tumors with ROS reach at peak 1.5 hours and second peak at 20 hours by average to extend to 168 hours, while radioactivity of BLM-I 131 in tumors with NS reached at peak in 0.5 hour, decreased to 30% in 1.5 hour quickly to background in 8 hours; We observed the extracellular matrix changes in experimental tumor while no changes in control tumor. Conclusions: A water soluble oxidant mixed with free drug can play a biological scissors role to chop tumor matrix, then it resulted in a denature tumor matrix into a coagulation for a drug depot, it showed drug of BLM-I 131 sustained in tumor for a long time; while oxidant plays an important role to punch holes on cell membrane and resulted a high permeability for high concentration drug in each cancer cells.
Clinical, radiological, and genomic features of BRAF V600E-mutated adult glioblastoma.
Authors: Mary Jane Lim-Fat, Kun Wei Song, Patrick Y. Wen, David A. Reardon, Elizabeth Robins Gerstner, Isabel Arrillaga-Romany
Journal: Journal of Clinical Oncology (2020)

2554 Background: Although uncommon, detection of a BRAF V600E mutation in adult patients with glioblastoma has become relevant given the increased availability of NGS and encouraging therapeutic activity of BRAF/MEK inhibitors. The clinical course, radiological characteristics and genetic mutations in this patient population has, however, not been well described. Methods: Adult patients treated at Dana-Farber Cancer Institute or Massachusetts General Hospital with glioblastoma diagnosed from 2013-2019 and an identified BRAF V600E mutation on immunohistochemistry staining or institutional NGS platform were included. Patient demographics, treatments and outcomes were collected retrospectively. Molecular diagnostics (Oncopanel or SNaPSHOT) and cytogenetics (array CGH) were reviewed for relevant mutations or copy number variants (CNV). Qualitative MRI data was analyzed using Visually Accessible Rembrandt Images (VASARI) feature set. Response assessment was performed using the RANO criteria. Results: Nineteen glioblastoma patients had a BRAF V600E mutation (16 on NGS and 19 on IHC). The median age at diagnosis was 41 (22-69) years; 13/19 were female, 12/19 were Caucasian. Only 1/19 had an IDH mutation; 10 of the 17 with known methylation status had MGMT unmethylated tumors. The most frequent mutations on NGS or CNV on array-CGH were TERT (12/16), CDKN2A (10/16), EGFR (7/16), PIK3R1 (6/16) and CKDN2B (6/16). Most tumors were well circumscribed (12/19) and all were contrast-enhancing on MRI. While no patient had clear leptomeningeal involvement at diagnosis, 11/19 eventually developed subependymal or leptomeningeal dissemination. Six patients were treated with BRAF/MEK inhibition following progression after standard of care therapy, with 3/6 patients showing partial response and 2 showing stable disease as their best response. PFS after BRAF/MEK inhibition ranged from 1.9 to 19 months. Grade 1 skin rash was present in 1 patient, but no other adverse events were reported. Median OS for the patients with confirmed deaths (15/19) was 22.6 (14.5 – 39.0) months. Conclusions: Compared to the general glioblastoma population, adult patients with BRAF V600E mutations are younger, more frequently female, and have a higher median OS despite a much higher incidence of leptomeningeal dissemination. Outcome following BRAF/MEK targeted therapy was encouraging. Understanding the natural history and features of these tumors may help better screen patients for BRAF/MEK inhibition and identify novel therapeutic strategies.
一例面部蜂窝织炎患者
Authors: 金世红
Journal: BMJ (2006)

有一次,我的一个患者来找我.我对他的情况比较了解.他62岁,是一个退休工程师,平素身体很健康,喜欢运动,经常和退休的老伴出门旅游.他的后背上有几个花生粒大小的脂肪瘤,质软,境界清楚,无痛,已经有将近20年了;在左耳垂上也有一个性质相同、黄豆粒大小的脂肪瘤.我曾经建议他手术切除,但他认为没什么要紧,不想做这个小手术。
慢性乙型肝炎患者拉米夫定治疗后病毒变异及与基因型的关系
Authors: 吴秀娟, 张大军, 吾尔叶提, 东传玲
Journal: BMJ (2007)

拉米夫定是治疗慢性乙型肝炎疗效确切的抗病毒药物之一,在临床上得到了广泛的应用[1].然而,长期应用会诱导乙型肝炎病毒发生YMDD变异.因此,研究病毒变异发生的影响因素,对临床有重要的价值。
The mutation profiles of HBV or HCV infected hepatocellular carcinoma patients underlie the varied responses to second-line immunotherapy.
Authors: Jingxian Duan, Tianhao Mu, Shifu Chen
Journal: Journal of Clinical Oncology (2020)

e16629 Background: HBV and HCV infections facilitate the development of hepatocellular carcinoma (HCC) via different mechanisms, given that the DNA sequence of HBV but not HCV can integrate into the host genome. However, it remains unclear that whether the altered genomic landscape of HCC patients caused by HBV or HCV infection may result in different responses to treatments. Methods: The MSK panel sequencing results and treatment data of 127 HCC patients were downloaded from the TCGA database (MSK, Clin Cancer Res 2018). Profiles of HBV positive and HCV positive patients were extracted. Based on the treatment received, those patients were classified to sorafenib treated groups and sorafenib + immunotherapy (IT) groups. The progression-free survival (PFS, months) and overall survival (OS, months) were compared, and the mutational profiles of patients were analyzed. Results: Among patients who received sorafenib treatment alone, the mean PFS of HBV positive patients (n = 12, 4.9 ±1.1) is similar to that of the HCV positive patients (n = 21, 5.1±1.8). However, the mean OS of HBV positive patients (n = 12, 18.3 ±6.6) was longer than the mean OS of HCV positive patients (n = 21, 10.0 ±1.9). Among the patients who received immunotherapy following sorafenib treatment, the mean IT PFS of HBV positive patients was (n = 5, 4.4 ±1.8), which was longer than the mean IT PFS of HCV positive patients (n = 5, 2.5 ±0.5). Consistently, the mean IT OS of HBV positive patients (n = 5, 10.9 ±4.4) was longer than the mean IO PFS of HCV positive patients (n = 5, 4.6 ±1.0). Overall it seems that the HBV positive patients responded better to second-line immunotherapy, despite the fact that these comparisons did not reach statistical difference due to the limited sample size. By comparing the MSK panel sequencing results, mutations exclusive to the HBV or HCV infected groups were identified. Enrichment analysis showed that 7/35 mutations exclusively found in the HBV positive group are responsible for lymphocyte activation (p &lt; 0.00001), which may underlie the better IT treatment outcome. Among the mutations restricted to the HCV infected group, 9/50 were involved in histone modification, 7/50 were involved in Hepatitis B pathways (p &lt; 0.0001), suggesting that HCV infection may interfere with diverse molecular processes. Conclusions: HBV and HCV infected HCC patients may respond differently to second-line immunotherapy. This difference is perhaps related to the altered genetic landscape of the patients resulted from virus infections by HBV or HCV.
Long-term outcomes of patients with HER2+ breast cancer with small-size residual disease (≤ypT1) in the absence of pathological response after trastuzumab-based neoadjuvant chemotherapy and without adjuvant T-DM1: A monocentric retrospective study.
Authors: Ludovic Doucet, Camille Moreau-Bachelard, Carole Gourmelon, Marie Robert, Dominique Berton, Emmanuelle Bourbouloux, Catherine Guerin, Cyriac Blonz, Nicole Andrieux, Mario Campone, Jean-Sebastien Frenel
Journal: Journal of Clinical Oncology (2020)

589 Background: The Katherine trial has shown that adjuvant T-DM1 improved invasive disease free survival (iDFS) of patients with HER2+ breast cancer who did not achieve a pathological complete response (pCR) with trastuzumab-based neoadjuvant chemotherapy (NAC). However, some subgroups may benefit less from this treatment escalation. Methods: All HER2+ breast cancer patients treated with trastuzumab-based NAC between 2006 and 2016 were retrieved from our institution’s database. Neo- or adjuvant T-DM1 was an exclusion criterion. We then selected the patients who did not achieve a pCR and analyzed the outcome (iDFS and overall survival (OS)) according to ypT, ypN and several factors analyzed in the Katherine trial. Results: Out of the 182 patients, 117 patients reached the inclusion criteria. Patient’s characteristics were similar to the trastuzumab arm of the Katherine trial. With a median follow-up of 75.4 months (29.3–149.7), 28 events (24%) occurred, among which 22 distant relapses. In univariate analysis, ≤ypT1 vs &gt; ypT1, ypN0 vs ypN+, no capsular rupture, signs of histological response (Sataloff not D in T or N) were associated with a better iDFS. In multivariate analysis, only ypT status remained significant. Of note, patients with ≤ypT1 (ypTis, ypT0, ypTmic, ypT1) (n = 81; 69%) had an excellent outcome: 3 years (y) and 5y iDFS rates of 90% (83.6-96.8) and 88.6% (81.9-95.9) respectively. The remaining patients (n = 36; 31%) had a significantly lower 3y and 5y iDFS: 69.2% (55.6-86.2) and 59.5% (45-78.6) respectively (p = 0.0017). OS in a multivariate analysis was also improved in pts with the smaller residual and/or node negative disease (3y OS rates of 100% (100-100) vs 92.1% (85.7-99); 5y OS rates of 96% (90.7-100) vs 81.1% (71.6-91.9); p = 0.02). Conclusions: In the absence of pCR after trastuzumab-based NAC, patients with pathological response scored as ≤ypT1 (ypTis,ypT0, ypTmic, ypT1) have an excellent outcome. These patients may derive less benefit from adjuvant T-DM1.
A new model to prognosticate man breast cancer in China.
Authors: Yunjiang Liu, Shuo Zhang, Yueping Liu, Chao Song, Ning Wang, Jiyu Tang, Meng-Li Zhou, Ming-Shuo Chen, Skye Hung-Chun Cheng
Journal: Journal of Clinical Oncology (2020)

e15579 Background: Male breast cancer is rare, and much of our understandings in this disease is still extrapolated from data in women with breast cancer. However, it has been suggested that male breast cancer may exist different etiology and biology from female by comparing the results of 21-gene Breast Recurrence Score (RS). However, the patient cohorts of these studies involved mainly patients being identified as Caucasian. Racial and ethnic disparities exist in genetic and biological factors that could influence the disease. A new model RecurIndex, based on a genomic database from RNA expression of Asian patients predominantly, is mainly developed for predicting the distant metastasis (DM) in female Breast cancer patients. We aim to validate whether this model can prognosticate male breast cancer in China. Methods: A total of 23 male patients with breast cancer were enrolled in a retrospective study in the single medical center. Kaplan-Meier survival curves was used to calculate the survival rate. The primary endpoint was relapse free survival (RFS)。Differences between male and female patients in terms of individual mRNA expression level were also determined. Results: Among the 23 patients enrolled in this study, Recurindex classified 11 patients as low risk 12 patients as high risk in distant metastasis respectively. When the low- and high-risk groups according to the Recurindex results were compared, there were only significant different in lymph node stage among individual clinical factors. 16 Patients with follow-up information which were stratified in DM low risk group have higher survival probability than high risk group. Mean quantitative gene expression of Recurindex signatures comparison between 16 men and 267 women patients reveals gene expression differences in numbers of gene. Conclusions: Based on genetic profiling assay specific designed for Asian population, the current study exhibits some different genetic features of male breast cancer. Our multigene signatures may also be utilized by male patient.
Impact of body mass index on survival rates in patients receiving immune checkpoint inhibitors.
Authors: Diana Maslov, Karine Tawagi, Victoria Simenson, Helen Yuan, Cameron Parent, Adi Bamnolker, Richa Goel, Zoe Blake, Madhav KC, Marc Ryan Matrana, Daniel H. Johnson
Journal: Journal of Clinical Oncology (2020)

e15108 Background: Obesity is associated with 13 different cancer types, accounting for 40% of all cancers 1 . A few studies have linked a higher Body Mass Index (BMI) with longer Progression Free Survival (PFS) and Overall Survival (OS) from immune checkpoint inhibitors (CPI)s in patients with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma 2,3,4 . Our study evaluates CPI efficacy in patients with multiple tumor types in relation to Body Mass Index (BMI). Methods: We retrospectively collected data from patients treated with CPIs alone who also received steroids during their treatment from a single institution. This data included demographics such as age, sex, and BMI. Response and progression were defined per RECIST v1.1. The association of BMI and PFS was assessed by exact chi-square test. Kaplan Meier and Cox proportional hazard regression methods were used to estimate the survival probability and hazard ratios. Results: We identified a total of 129 overweight or obese patients (49%) with stage IV cancer who received CPI therapy. CDC guidelines define overweight as BMI &gt; 25 and obese as BMI &gt; 30. There was a significant relationship between PFS and BMI. Median PFS for those overweight was 287 days and 479 days for obese. Those with BMI 18.5-25 (normal), median PFS was 128 days and 103 days for those underweight (BMI &lt; 18.5), (p = .0024). There was also a significant relationship between OS and BMI. Median OS for those obese was 751 days, for those overweight was 462 days. Median OS for those normal weight was 281 days and those underweight was 273 days (p = .0005). Obese patients had a 48% reduced risk of progression of disease/death as compared to those who had normal BMI (Hazard Ratio 0.52, p = .019). Overweight had a 31.5% relative risk reduction (HR 0.685, p = .05). Overall Response Rate was not significant between the two groups but there was a strong trend (p = .087). Conclusions: Higher BMI was associated with improved PFS and OS in patients with metastatic cancer across 20 different tumor types. Further investigation into the immune mechanisms behind this may lead to improvement in CPI efficacy for all patients.
Correlation of free fatty acids with carotid artery intima-media thickness in patients with type 2 diabetes
Authors: Xiu-jing Wang, Jing Wang, Yong Ruan, Qing-ying Tan
Journal: BMJ (2013)

Seventy patients with type 2 diabetes (T2DM), 23 subjects with impaired glucose tolerance (IGT) and 35 individuals with normal glucose tolerance (NGT) were recruited in the study. Fasting free fatty acids (fFFA) and postprandial free fatty acids (2 hFFA) after oral glucose tolerance test (OGTT) were measured; homeostasis model assessment of insulin resistance (HOMA-IR), area under the curve of free fatty acids (AUCFFA) were calculated. The carotid artery intima-media thickness (IMT) was assessed by color ultrasonography. HOMA-IR, fFFA, 2 hFFA, AUCFFA and IMT in T2DM group were 3.3±3.2, (0.55±0.20)mmol/L, (0.28±0.18)mmol/L, (0.83±0.34)mmol·L-1·h-1 and (0.12±0.05)cm, which were significantly higher than those in NGT group, respectively [1.9±1.3, (0.41±0.15)mmol/L, (0.12±0.10) mmol/L, (0.53±0.20)mmol·L-1·h-1 and (0.09±0.03)cm, all P<0.05]. Both HOMA-IR and IMT were positively correlated with fFFA, 2 hFFA and AUCFFA (all P<0.05). The results indicate that the levels of fasting and postprantial free fatty acid were related with insulin resistance and atherosclerosis of carotid artery.


Key words: 
Carotid artery intima-media thickness; Insulin resistance; Free fatty acids
Effect of beta blocker use in soft tissue sarcomas.
Authors: Edward De Leo, Wissam Hanayneh, Chintan Shah, Yu Wang, Ji-Hyun Lee, Julia Lee Close, Nam H. Dang
Journal: Journal of Clinical Oncology (2020)

e23571 Background: Soft tissue sarcomas (STS) are a rare, heterogenous group of cancers that tend to have a poor prognosis and few effective treatment strategies. Beta blockers (BB), in particular non-selective BB such as propranolol, have been shown to have an antitumor effect in different malignancies, including breast, colon, and angiosarcomas. The underlying mechanism is unclear but it is thought to be related to the inhibition of beta receptors on malignant cells, which leads to decrease in tumor vascularity and hematogenous spread. In this retrospective analysis, we examined the effect of BB on the outcomes of STS at a tertiary referral center. Methods: Adult patients from 2000 through 2019 with a diagnosis of STS with adequate follow up were included, and were divided into 2 groups: patients on BB at any point during treatment and/or up to 6 months prior to diagnosis, and patients without BB. The patient and tumor data were extracted and analyzed. The primary outcome was overall survival (OS). Statistical methods included descriptive analysis, univariable and multivariable Cox proportional hazard regression analyses and Kaplan-Meier survival plots. Results: 448 patient charts were analyzed. Median age at diagnosis was 55 (range 18-89). 54% were male. 4.9% of patients were diagnosed with stage 4 disease. Histologies included: undifferentiated pleomorphic sarcoma 26.1%, leiomyosarcoma 10%, synovial sarcoma 9.2%, liposarcoma 7.8%, osteosarcoma 2.7%, Ewing sarcoma 2% and others 42.2%. 18.1% of patients were on BB during treatment, with metoprolol the most commonly used (59%). 96% of patients on BB had HTN and 44% had coronary artery disease. Patients on BB were less likely to receive adjuvant therapy (18% vs 26%). Patients on BB were more likely to have stage 4 disease at presentation (9.9% vs 3.8%). Multivariate analysis showed there was no significant difference in overall survival between patients on BB and those not on BB, HR 1.3 (CI 0.8-2.1, p = 0.24). Conclusions: There is no difference in overall survival in patients on beta blockers during treatment for STS after controlling for stage, comorbidities, smoking, and age. Further studies are needed to evaluate the effect of specific beta blocker drugs on soft tissue sarcoma outcomes.
Profiling antigen specificity concurrently with protein and mRNA quantification using high throughput single-cell multiomics reveal surprising similarities between bystander and tumor specific CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) in renal cell carcinoma (RCC).
Authors: Aaron Tyznik, Yannick Simoni, Shamin Li, Summer Zhuang, Evan Newell
Journal: Journal of Clinical Oncology (2020)

e15014 Background: Recently, using human colorectal and lung cancer, we showed that CD8 + T cells infiltrating tumor tissue (TILs) are not only specific for tumor antigens, but are also composed of CD8 + TILs specific for cancer unrelated epitopes – called bystander – such as HCMV, EBV or flu epitopes. We also showed that the surface marker CD39 can be useful for discriminating bystander (CD39 − ) from tumor-specific (CD39 + ) CD8 + TILs (Simoni et al, Nature, 2018). Methods: Here, our aim was to test these findings in human Renal cell Carcinoma (RCC) and to better understand the biology of these bystander CD8 + TILs. Results: Surprisingly, our primary CYTOF analyses showed heterogeneity within bystander CD8 TILs that possess various phenotypes including effector (CD45RO+), memory (CD45RO+ CCR7+), Trm (CD69+ CD103+/–), and senescent (CD57+ KLRG1+) cell features. Using targeted mRNA single-cell sequencing combined with BD AbSeq assay, we analyzed sorted CD8 + TILs from RCC patients and identified bystander CD8 + TILs using oligo-tagged tetramers. Gene signature analysis of these different subsets revealed transcriptomic similarities with the tumor-specific CD8 + TILs. Conclusions: Our data provide a comprehensive perspective of cancer unrelated CD8 + TILs in RCC and suggest functional roles for these cells in tumor immune responses, which could lead to new diagnostic and therapeutic strategies.