tbuckley/cabot-search huggingface dataset:
Molecular alterations with hyperprogression in lung cancer patients treated with immune checkpoint inhibitors in a large health system.
Authors: Eyob ale Tadesse, Kayla Heslin, Mohamed Hendawi, Jonathan Hirsch, Christopher Idyro, Michael A. Thompson
Journal: Journal of Clinical Oncology (2020)

e15082 Background: Immune checkpoint inhibitor (ICI) therapy has become a mainstay of lung cancer treatment. However, not all NSCLC patients (pts) benefit, a subset paradoxically experience accelerated tumor growth while on immunotherapy. Hyperprogression (HP) refers to accelerated tumor growth on ICI with worsening clinical status. Various molecular alterations may be associated with HP including MDM2/MDM4 amplifications, EGFR aberrations, and STK11/LKB1 mutations. Kato et al. ( http://ow.ly/2n8a30nQpZv ) showed HP in 6/6 pts with MDM2/MDM4 amplification and in 2/10 pts with EGFR alterations. Methods: Lung cancer pts treated with ICI from Jan 2017 to Jan 2019 at Aurora Health Care were reviewed after IRB approved. Pts with NSCLC histology (ICD diagnosis codes and / or manual chart review), ICI treatment, and molecular testing were identified via the real world data (RWD) integrated in the Syapse platform. Additional chart review to ascertain HP was performed, and molecular results obtained via Syapse molecular lab integrations were analyzed. Pts had various forms of real world biomarker testing including oligo NGS panels. HP is defined as: 1) time-to-treatment failure (TTF) &lt; 2 months (time from the start of treatment with ICI to ICI discontinuation for any reason, including progression, patient preference, toxicity, or death), 2) &gt; 50% increase in tumor burden by RECIST, 3) spread of the disease to a new organ between baseline and first radiologic evaluation or clinical deterioration, and 4) ECOG PS ≥2 during the first 2 months of treatment. HP &gt; = 3, Progression 1-2, non-progressor 0 criteria fulfilled.Pts with and without HP were compared using Chi-squared and Fisher Exact tests. T-tests were performed for continuous variables. Results: Out of 1536 lung cancer patients 350 (22.8%) were treated with ICI including: atezolizumab (35), durvalumab (6), nivolumab (177), pembrolizumab (145). Some pts were treated with more than one ICI. 64/350 (18.2%) pts had HP. 79/350 (22.5%) pts had progressive disease without meeting the definition of HP. Biomarker associations with HP are shown in the table. Conclusions: Only the STK11/LKB1 mutation was associated with HP (P = &lt; 0.0001) with 5 of 6 STK11 pts treated with ICI showing HP. Other potential HP biomarkers will be assessed prospectively as larger panels are utilized. [Table: see text]
Survey on awareness of hyperuricemia among patients and medical personnel in Yuetan community in Beijing
Authors: Jie Chen
Journal: BMJ (2016)

Objective
To survey the awareness of hyperuricemia in patients and medical personnel in Yuetan community.


Methods
By using random sampling method, 492 patients with hyperuricemia and 84 medical personnel in Yuetan community were selected for questionnaire survey.


Results
The rate of awareness of hyperuricemia in patients was 33.2%(1 472/4 428), and 95.5% (470/492)of them had the requirement of health education on hyperuricemia. The awareness rate of hyperuricemia in medical personnel was 73.0%(736/1 008), and 46.4%(39/84) of them thought health education on hyperuricemia as important or very important.


Conclusion
The awareness of hyperuricemia is insufficient in patients and medical personnel. Health education should be reinforced for community management on hyperuricemia.


Key words: 
Hyperuricemia; Questionnaires; Cognition
Association between Medicaid expansion status and metastatic disease at diagnosis in patients with melanoma.
Authors: Jesus C. Fabregas, Jeannine M. Brant
Journal: Journal of Clinical Oncology (2020)

7030 Background: The Affordable Care Act (ACA) expanded Medicaid coverage in 2010. It is unknown what impact the ACA expansion has had on a timely diagnosis for patients with melanoma. We hypothesize Medicaid ACA expansion has decreased the odds of being diagnosed with Stage IV melanoma. Methods: The National Cancer Database was queried. Analysis was restricted to patients diagnosed (dx’d) in or after 2010. Stage IV dx was the outcome variable. Predictors were dx’d at an already expanded ACA state (ES) or not (NES). Covariates were age, race, sex, education status, income, rural setting, and Charlson co-morbidity index. Univariate and Multivariate analyses were performed using logistic regression (table). The outcome model was adjusted using a generated Propensity Score as a continuous variable. An interaction term was used to evaluate for effect modification of ES on the association between race and Stage IV. Results: 219,475 patients diagnosed in 2010 or later were included. Median age was 62 years. By Univariate analysis, NES, age &gt; = 65, black race, male sex, lower educational and income level, rural area, and a higher Charlson score were significantly associated with increased odds of being dx’d with Stage IV melanoma (all p &lt; 0.001). By Multivariate Analysis, these associations persisted except for rural area and age. After adjusting for propensity score, ES patients were 9% less likely to be diagnosed with Stage IV melanoma as compared with NES patients (OR = 0.91 p &lt; 0.001; 95% CI 0.867 – 0.959). ACA expansion status was an effect modifier on the association between race and late diagnosis (p = 0.004 for interaction term). For NES patients, black race had 3.26 odds (p &lt; 0.001 95% CI 2.56 – 4.18) of being diagnosed with Stage IV as compared with white patients. The odds dropped to 1.76 (p 0.004; 95% CI 1.20 – 2.57) for ES patients. Conclusions: ES patients were less likely to be diagnosed with Stage IV melanoma as compared to NES patients. Medicaid expansion decreased the likelihood for black patients to be diagnosed with Stage IV as compared with whites. This suggests Medicaid expansion improves access to care and earlier diagnosis of melanoma and decreases racial gaps. [Table: see text]
Frequency of brain metastases in patients with locally advanced triple negative breast cancer after neoadjuvant platinum-based chemotherapy: Impact of <i>BRCA1/2</i> mutations.
Authors: Elena Glazkova, Marina Stenina, Mona A. Frolova, Ekaterina Ignatova, Alexey Rumyantsev, Alexander Petrovsky, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2020)

1079 Background: patients with triple negative breast cancer has poor survival outcomes. Achievement of pathological complete response (pCR) after neoadjuvant chemotherapy can significantly improve survival of these patients, however some patients will relapse even after pCR. Methods: we reviewed prospectively-maintained outcomes database of N.N. Blokhin NMRCO. We extracted information about patients with locally advanced non-metastatic (stage IIIA-IIIC) triple negative breast cancer who were treated with neoadjuvant platinum based chemotherapy in 2014-2018 years. All included patients were tested for the presence of BRCA1/2 mutation with whole-exome next-generation sequencing or for “founder” hot-spot mutations. Results: we identified 80 patients who received neoadjuvant treatment with various platinum-based regimens. Pathological complete response rate was 62.5%. BRCA-mutations was found at 22 (27.5%) patients. Median follow-up time was 35.6 months (17.0 – 61.3). 2-year DFS was 77.3%, and 3-year DFS was 70.0%, there was significant differences in DFS in patients, who achieved and patients with residual tumor – 85,2% vs 64,3% (p=0,028). 2-year OS was 91%, 3-year OS was 78,5%. 18 patient had disease progression, the most common sites of disease progression were brain (9 [50.0%]), lungs (5 [27.8%]), 3 (16.7%) patients had locoregional relapses and 1 (5,6%) liver metastases. We separately analysed characteristics of patients with brain metastases (table). There were no significant differences in tumour pathologic response and patient age. All patients, who relapced after pCR, had brain metastases. We also found, that 7 of 9 patients with brain metastases had different BRCA mutations. Brain metastases developed in 40,9% (9/22) of patients with BRCA1 mutations and 3,4% (2/58) of patients with wild type BRCA1 (p&lt;0,00001). Conclusions: BRCA1 mutation is significant prognostic factor for brain metastases development in locally advanced triple negative breast cancer. [Table: see text]
Efficacy of sequential or single balloon angioplasty in treatment of lower extremity arterial occlusive diseases
Authors: Hui Zhuang, Pingfan Guo, Tenghui Zhan, Hongyu Chen
Journal: BMJ (2016)

Objective
To compare the therapeutic effect of sequential balloon angioplasty with conventional single balloon angioplasty in treatment of chronic total occlusion (CTO) of femoropopliteal artery.


Method
Thirty patients with femoropopliteal CTO treated with sequential balloon angioplasty from July 2015 to January 2016 (sequential group), and 82 patients were treated with conventional single angioplasty from January 2014 to June 2015 (control group). There were no differences in age [(70±8) vs. (74±8)years, χ2=0.046, P=0.876], Rutherford classification (3.9±0.9 vs. 4.0±0.8, χ2=0.315, P=0.749), ankle-brachial pressure index (ABI)(0.49±0.17 vs. 0.46±0.18, χ2=-0.871, P=0.388), comorbidity(χ2=2.024, P=0.567)and outflow vessels(χ2=4.678, P=0.914)between two groups. The Residual stenosis rate, dissection rate, stent length, stent number, Rutherford classification, ankle-brachial pressure index (ABI), hospitalization expenses, surgery expenses and 6-months follow-up were documented and compared between two groups.


Results
Compared with conventional single angioplasty group, the residual stenosis rate [13%(4/30) vs. 37%(30/82), χ2=5.617, P=0.018] was lower and stent lengths [(23.3±47.2)mm vs. (58.7±75.4) mm, t=-2.929, P=0.004] was shorter in sequential group without increase of hospitalization expenses and surgery expenses. There were no differences in Rutherford classification and ABI after operation, ABI at 6-month follow-up, reoperation rate and cost of second operation between two groups.


Conclusions
Sequential balloon angioplasty technique can be use as an effective balloon expansion procedure in treatment of femoropopliteal artery occlusive disease.


Key words: 
Peripheral arterial disease; Arterial occlusive diseases; Angioplasty, balloon, sequential
Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with pembrolizumab in patients with advanced/metastatic breast or non-small cell lung cancer (NSCLC): A phase Ib, multicenter, study.
Authors: Hossein Borghaei, Benjamin Besse, Aditya Bardia, Julien Mazieres, Sanjay Popat, Bincy Augustine, Anthony Michael D'amelio, Daniel Barrios, Hope S. Rugo
Journal: Journal of Clinical Oncology (2020)

TPS1100 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and potent topoisomerase I inhibitor. In a phase II trial in patients (pts) with heavily pretreated, metastatic HER2+ breast cancer (BC), T-DXd had a confirmed objective response rate (cORR) of 60.9% (112/184) and median progression-free survival (PFS) of 16.4 mo (Modi N Engl J Med 2019); these results led to the recent FDA approval for HER2+ unresectable or metastatic BC after ≥ 2 prior anti-HER2 based regimens. For HER2-low BC and HER2-expressing/mutated NSCLC, no HER2-directed therapies have been approved. In a phase I trial of T-DXd in pts with HER2-low BC or HER2-expressing/mutated NSCLC, cORR was 44.2% (19/43) (Modi SABCS 2018), and 55.6% (10/18) (Tsurutani Thorac Oncol 2018), respectively. In preclinical models, T-DXd combined with an anti–PD-1 antibody was more effective than monotherapy with either agent (Iwata Mol Cancer Ther 2018). Here we describe a phase Ib study of T-DXd in combination with pembrolizumab in pts with locally advanced/metastatic HER2-expressing BC or HER2-expressing/mutated NSCLC (DS8201-A-U106; NCT04042701). Methods: This is an open-label, multicenter, nonrandomized, multidose, 2-part study in adult (aged ≥18 y) pts in the United States and Europe. In part 1 (dose escalation), pts received T-DXd 3.2 or 5.4 mg/kg IV q3w and pembrolizumab 200 mg IV q3w to determine the recommended dose for expansion (RDE). The RDE will be given to 4 cohorts (part 2): 2 cohorts with BC (HER2+ [IHC 3+ or IHC 2+/ISH+] with progression on prior T-DM1; and HER2-low [IHC 1+ or IHC2+/ISH-] with progression on prior standard treatments) and 2 cohorts with NSCLC (anti–PD-1, –PD-L1, and -HER2 treatment naive either HER2-expressing [IHC ≥ 1+] or HER2-mutated). Enrollment began in February 2020 with approximately 115 to 133 pts planned to be enrolled at 5 sites for part 1 and expanding to 25 sites for part 2. The primary endpoint in part 1 is dose-limiting toxicities. The part 2 primary efficacy endpoint is cORR by independent central review (ICR) per RECIST 1.1. Additional endpoints include duration of response, disease control rate, and progression-free survival by ICR, overall survival, safety, and pharmacokinetics. Clinical trial information: NCT04042701 .
糖尿病合并肺癌郎伯综合征一例
Authors: 徐爱娜
Journal: BMJ (2009)

患者男,60岁.因乏力、嗜睡2个月于2007年9月27日入院.吸烟30余年,有2型糖尿病史5年,血糖控制较好.其父有2型糖尿病史.2个月前无诱因出现乏力,初以下肢为主,后发展至全身,白天明显,晨起时及夜间症状减轻,当地医院诊断为2型糖尿病神经病变,经维生素B1及甲钴胺治疗无好转,乏力进行性加重,伴嗜睡、口干、毛发脱落、阳痿.无咳嗽、咳痰、咯血及其他症状.自发病以来,精神差,食欲可,二便正常,体重无变化。
Low expression of gamma-glutamyl transpeptidase 1 is an independent poor prognostic factor in ovarian clear cell carcinoma, in relation to up-regulation of immune suppressive genes and EMT-related genes.
Authors: Hiroshi Asano, Ryosuke Matsuoka, Kanako C Hatanaka, Daisuke Endo, Ayako Nozaki, Kei Ihira, Takashi Mitamura, Tatsuya Kato, Yosuke Konno, Yoshihiro Matsuno, Yutaka Hatanaka, Hidemichi Watari
Journal: Journal of Clinical Oncology (2020)

6042 Background: Ovarian clear cell carcinoma (OCCC) is a distinct entity from other epithelial ovarian cancers such as the most prevalent high-grade serous cancer (HGSC), and often exhibit less sensitivity to platinum-based chemotherapy. Several studies using cell lines have reported that glutathione (GSH) metabolism plays an important role in chemo-resistance of OCCC. Here, we aimed to correlate the prognosis of OCCC and the expression of gamma-glutamyltransferase 1 (GGT1), one of the key enzymes in GSH metabolism. Methods: We prepared a FFPE-tissue microarray, and analyzed 56 OCCC patients with the follow-up periods over 3 years. Expression level of GGT1 was evaluated by immunohistochemistry (IHC) using H-score (0-300), and was correlated with clinical outcomes. The prognostic significance was assessed by multivariate analysis using Cox regression model. To investigate the possible related pathways, we performed transcriptome analysis using Ion AmpliSeq Transcriptome Human Gene Expression Kit (Thermo Fisher Scientific) from the frozen tissue specimens collected from 33 ovarian cancer patients including 15 OCCC patients and 18 HGSC patients. Results: The OCCC patients were divided into two populations in the histogram of H-score in IHC staining, and the cut-off value was 90; 44 cases showed GGT1-high, and remaining 12 cases were GGT1-low. Follow-up periods, FIGO stage, and optimal surgery rate were not significantly different between two groups. However, platinum-resistant recurrent rate was significantly higher (42% vs. 14%, p=0.027), and overall survival (OS) was significantly shorter (5-year OS; 42% vs. 72%, p=0.0226) in GGT1-low OCCC. Multivariate analysis revealed that low expression of GGT1 was one of the independent poor prognostic factors as well as platinum-drug resistance. In enrichment analysis, the genes related to GSH metabolism, such as SLC3A1, GGT1, CSE, and GPX3 were up-regulated and positively correlated with HNF1B expression in OCCC. The expression level of GGT1 was inversely correlated with that of immune suppressive genes (TGF-b, IFNG, IL10, FOXP3, PD-L1, CTLA4) and epithelial-mesenchymal transition (EMT)-related genes (CDH2, VIM, TWIST1, ZEB1, ZEB2) in OCCC samples. Conclusions: Low expression of GGT1 is an independent poor prognostic factor probably in part due to suppression of tumor immunity and induction of EMT in OCCC.
Overview of relation between tobacco smoke and sinusitis
Authors: Peng He, Bo Teng, Weifang Tong, Lianji Wen, Qingjie Feng, Yafang Wang, Xuelei Zhang, Lijing Zhao
Journal: BMJ (2016)

Sinusitis is a common and frequent otolaryngological disease. For its high morbidity, sinusitis has become a global public health problem, leading to heavy health burden and social costs. Epidemiological studies suggest that as a main factor of indoor air pollution, tobacco smoke plays an important role in the upper respiratory tract diseases such as sinusitis. Tobacco smoke can damage the integrity of sinonasal mucous epithelia and innate immune functions to induce or aggravate sinusitis. This article reviews the impact and pathogenesis of sinusitis induced by tobacco smoke, to provide a basis for prevention and treatment of this disease.


Key words: 
Sinusitis; Tobacco smoke pollution; Etiology
The landscape of genomic alterations detected in serial circulating tumor DNA (ctDNA) in clinical progressive metastatic breast cancer.
Authors: Saya Jacob, Andrew A. Davis, Lorenzo Gerratana, Ami N. Shah, Neelima Katam, Qiang Zhang, Firas Wehbe, Lisa E. Flaum, Kalliopi P. Siziopikou, Leonidas C. Platanias, William John Gradishar, Amir Behdad, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2020)

1084 Background: Metastatic breast cancer (MBC) is associated with genomic evolution, representing a challenge at clinical progression. While tissue and blood next-generation sequencing (NGS) allows for the baseline detection of alterations, non-invasive longitudinal assessment of ctDNA can provide a tool for monitoring tumor evolution. We characterized genomic changes using serial ctDNA testing in patients with clinical progression. Methods: Patient data was obtained under an IRB-approved protocol and ctDNA was collected at Northwestern University between 2015-2019. All ctDNA samples were analyzed using the Guardant360 NGS assay. Of 255 patients with MBC, 86 had at least two serial ctDNA collections with the second collection drawn at first progression (P1) by imaging and clinical assessment. Participants were followed until second clinical progression (P2). We analyzed type of alterations, mutant allele frequency (MAF), number of alterations (NOA), and sites of disease on imaging in close proximity to ctDNA evaluation. Matched pairs variations in MAF and NOA at P1 and P2 were tested through Wilcoxon test. Results: We identified 44 HR+, 20 HER2+ and 22 TNBC cases. Median lines of therapy were 3 (interquartile range (IQR): 1-6) for HR+, 3 (IQR: 1-5) for HER2+, and 2 (IQR: 1-4) for TNBC. The most likely alterations between baseline to P1 were TP53 (p &lt; 0.0075), PIK3CA (p &lt; 0.0126), AR (p &lt; 0.0126), FGFR1 (p &lt; 0.0455) and ESR1 (p &lt; 0.0143). In the HR+ subset , ESR1 was statistically more likely at P1. ESR1 at P1 was also associated with development of new liver lesions (p &lt; 0.0320). ERBB2 mutation at P1 was associated with new lung (p &lt; 0.0050) or bone lesions (p &lt; 0.0030). Increase in NOA was observed between baseline and P1 (p &lt; 0.0001), P1 and P2 (p &lt; 0.0001), and baseline to P2 (p &lt; 0.0004). MAF was increased between baseline and P2 (p &lt; 0.0480). Conclusions: Serial ctDNA testing identified resistance alterations ( TP53, PIK3CA, AR, ESR1, FGFR1), with some mutations indicating new sites of disease ( ESR1, ERBB2). Heterogeneity of ctDNA was significantly associated with progressive disease. Prospective evaluation of the impact of serial ctDNA testing on treatment decisions is needed to expand the role of precision medicine in MBC. [Table: see text]
中老年反复呼吸道感染患者外周血Th细胞亚群分析
Authors: 焦桐, 叶丽娅, 赵武述
Journal: BMJ (2005)

以20例健康中老年人为对照,采用酶联免疫斑点法检测35例中老年反复呼吸道感染患者外周血Th细胞亚群.结果显示,患病组 Th1细胞数明显低于正常对照组,差异有统计学意义(P 0.05)。
Impact of metastases directed radiation therapy on CDK4/6 inhibitors dose reduction and treatment discontinuation for metastatic HR+/HER2- breast cancer (MBC).
Authors: Icro Meattini, Erika Scoccimarro, Calogero Saieva, Isacco Desideri, Luca Visani, Luca Dominici, Cecilia Cerbai, Michele Aquilano, Lucia Pia Ciccone, Valeria Emma Palmieri, Vieri Scotti, Jacopo Nori, Marco Bernini, Lorenzo Orzalesi, Luis Sanchez, Maria Vittoria Dieci, Simonetta Bianchi, Lorenzo Livi
Journal: Journal of Clinical Oncology (2020)

562 Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) represent the standard I-II line for hormonal receptors positive/human epidermal growth factor receptor 2 negative metastatic breast cancer (MBC) patients. Metastases directed radiotherapy (RT) for these patients is commonly used with palliative or radical schedules during systemic treatment. Although encouraging preliminary results were published, there is still a lack of robust data on the safety concerning RT during CDK4/6i treatment. Methods: we analyzed at Our Institution 85 consecutive patients treated in I (n=47) and II line (n=38) for MBC with CDK4/6i between April 2017 and September 2019 (22 ribociclib, 63 palbociclib). Overall, 25 (29.4%) patients received metastases directed RT during CDK4/6i treatment, including 14 concomitant (16.5%) and 11 sequential (12.9%). Estimated CDK4/6i half-life is 26 and 30 hours for palbociclib and ribociclib, respectively. Five half-lives are required to reduce drug concentration by 95-97%; thus, we also analyzed CDK4/6i treatment as non-concomitant or sequential to RT. Main endpoints of our analysis were impact of RT on CDK4/6i dose reduction and discontinuation, overall adverse events rate (any grade and grade ≥2), and neutropenia grade ≥2 as per CTCAE scale version 5.0. Results: at a median follow up of 12 months (range 3-29), we observed a CDK4/6i dose reduction in 35 patients (41.2%) and 5 patients (5.9%) discontinued treatment due to adverse events; 82 patients (96.5%) experienced any grade of toxicity, 72 (84.7%) a grade ≥2 and 70 patients (82.4%) neutropenia grade ≥2. We did not observe significant difference in terms of CDK4/6i dose reduction or discontinuation, any grade or grade ≥2 toxicity, neutropenia grade ≥2 in the comparison between patients receiving RT versus no RT and between patients receiving concomitant RT versus sequential RT versus no-RT (Table). Conclusions: our results showed that the prescription of a metastases directed RT during treatment with a CDK4/6i as I-II line for MBC did not significantly impact on dose reduction or discontinuation caused by an exceeding in adverse event rate. Although these promising results, caution should be used and cooperative initiatives strongly encouraged. [Table: see text]