tbuckley/cabot-search huggingface dataset:
Optimal Exercise Programs for Patients With Peripheral Artery Disease: A Scientific Statement From the American Heart Association
Authors: Diane Treat-Jacobson, Mary M. McDermott, Ulf G. Bronas, Umberto Campia, Tracie C. Collins, Michael H. Criqui, Andrew W. Gardner, William R. Hiatt, Judith G. Regensteiner, Kathleen Rich
Journal: Circulation (2019)
A Critical Role of Growth Arrest-Specific Gene 6-Mer Axis in the Pathogenesis of Endothelial Damage Contributing to Thrombotic Microangiopathy Associated with Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Miki Furukawa, Wang Xintao, Hiroshi Ohkawara, Masahiko Fukatsu, Lobna Alkebsi, Hideyoshi Noji, Kazuei Ogawa, Takayuki Ikezoe
Journal: Blood (2018)
Lymph nodes metastases and appropriate lymph node dissection modes in patients with clinical stage IA non-small cell lung cancer.
Authors: Zhang Zhirong, Mao Yousheng
Journal: Journal of Clinical Oncology (2014)

e18517 Background: It is still controversial whether or not complete lymph node dissection is necessary for stage IA primary non-small cell lung cancer patients. This study was designed to investigate the pattern of lymph node metastases and the appropriate modes of mediastinal lymph node dissection in those patients. Methods: Data of 270 eligible clinical stage IA NSCLC patients who underwent surgical treatment in our hospital between March 2012 and August 2013 were retrospectively analyzed to investigate the relationship between the clinicopathological features and metastatic patterns of lymph nodes. Patients with multiple primary carcinomas and those who received any chemotherapy or radiotherapy or did not undergo systematic nodal dissection were excluded. The criteria for systematic nodal dissection included removal of at least six lymph nodes from at least three mediastinal stations, one of which must be subcarinal. Results: The postoperative morbidity rates were 14.8% and no death occurred. Of those, 34 had pure ground glass opacity lesions and 47 part-solid nodules, and 189 solid nodules. Among the 236 nodule cases, ≤1cm lesion were in 22 cases, 1~2cm lesion in 138 cases, 2~3 cm lesion in 76 cases based on CT findings.The overall lymph node metastasis rate was 18.9% (51/270). The incidence of lymph nodes involvement was 0.0% , 2.1% (1/47) and 26.5% (50/189) in p-GGO, part-solid nodules and solid nodules, which was 18.2% (4/22), 14.5% (20/138) and 35.5% (27/76) in the lesions with ≤1cm,1~2cm,2~3cm in diameter, respectively. The rates of lymph node metastases in the non-specific tumor-draining regions detected in the positive lobe-specific lymph node involvement group and negative group were 20.0%-50.0% and 0.0%-2.9%(P<.001). Conclusions: Because stage I p-GGO usually has no lymph node metastasis, systematic nodal dissection may not be necessary. Intraoperative frozen-section examination for the lobe-specific lymph nodes should be performed routinely in patients with stage IA NSCLC. If negative, systematic nodal dissection may not be recommended and selective mediastinal lymphadenectomy may be sufficient. But if positive, systematic nodal dissection should be performed.
Successful Treatment of MYC rearrangement Positive Large B Cell Lymphoma Patients with R-CHOP21 Plus Lenalidomide: Results of a Multicenter Phase II HOVON Trial
Authors: Martine E.D. Chamuleau, Marcel Nijland, Josée M Zijlstra, Rogier Mous, P.J. Lugtenburg, Daan Dierickx, Gustaaf van Imhoff, Joost Vermaat, Katerina Bakunina, Erik W.A. Marijt, Otto Visser, Caroline Mandigers, Yavuz Bilgin, Coreline Burggraaff, Otto Hoekstra, Daphne de Jong, Marie José Kersten
Journal: Blood (2018)
Validation of two biologically distinct HPV-associated head and neck cancer subtypes and correlation with E5 expression.
Authors: Zhixiang Zuo, Arun Khattri, Michaela K. Keck, Ezra E.W. Cohen, Mark W. Lingen, Everett E. Vokes, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2014)

6031 Background: Human Papilloma Virus (HPV) is involved in the etiology of 60-80% of oropharyngeal head and neck cancers (HNC) in the US. HPV16 is the dominant HPV type present in 90% of HPV-positive HNC. We previously discovered the presence of two distinct HPV(+) HNC groups, based on gene expression profiling and consensus clustering. In this study we apply our classifier to TCGA data, and analyze viral gene expression. Methods: Using consensus clusteringbased on literature derived microarray gene expression profiles of 371 HNC samples we built a gene expression based classifier for HNC. We then applied the gene signature to RNA-Seq data of 424 TCGA samples and 134 Agilent array samples of the Chicago HNC Genomics Cohort (CHGC) using nearest centroid method.HPV status was determined by E6/E7 expression and confirmed with an HPV signature. We determined HPV type and the E5, E6 and E7 mRNA level for the TCGA samples using RNA-Seq data. Results: Three stable groups were obtained for the 371 cross-platform HNC samples. The signature for the three groups similarly classified 415 out of 424 TCGA samples, and all 134 samples in the CHGC cohort. Groups were named Mesenchymal (MS), Basal (BA), and Classical (CL), with HPV samples falling into two groups in both CHGC and TCGA cohorts supporting the presence of two distinct HPV subgroups: MS-HPV and CL-HPV. Out of 54 HPV16 positive CHGC samples, 26 were in MS group and 28 were in CL group; similarly, out of 47 HPV16 positive TCGA samples, 24 were in MS group and 23 were in CL group. MS-HPV was characterized by EMT, and high expression of immune related genes, CL-HPV by high expression of cell cycle genes. Furthermore, in the TCGA dataset, all 23 samples in MS-HPV group showed high expression level of E5, alongside E6 and E7, while all samples with low E5 fell into the CL-HPV. E5 expression differed significantly between the two groups (P=7.763e-05, Fisher exact test). Conclusions: In conclusion, we confirm the presence of two biologically distinct HPV subgroups – MS-HPV, and CL-HPV in two large, independent cohorts, with distinct biologic characteristics. Subtypes are characterized by differential E5 expression. Further study into the underlying mechanisms is indicated.
Analysis of KRT14 and SFTPB expression by immunohistochemistry method in squamous cell carcinoma of lung and head-neck cancer tissue.
Authors: Nattaya Poovorawan, Poonchavist Chantranuwat, Somboon Keelawat, Piyada Sitthideatphaiboon, Napa Parinyanitikul, Chanida Vinayanuwattikun, Suebpong Tanasanvimon, Virote Sriuranpong
Journal: Journal of Clinical Oncology (2014)

e22127 Background: Concomitant lung squamous cell carcinoma (LSCC) and head-neck squamous cell carcinoma (HNSCC) may occur in smokers as a result of field cancerization. To distinguish between the two primary organs may require a technically demanding multigene assay. Our aim was to investigate the utility of determining expression of SFTPB and KRT14 by immunohistochemistry (IHC) in distinguishing LSCC and HNSCC tissue. Methods: We selected eighty-three tumor samples of known LSCC or HNSCC (42 LSCC, 41 HNSCC) during 2008-2012. Demographic, clinical and pathological data were reviewed. IHC testing for SFTPB and KRT14 were done in all recruited samples. Results: KRT14 expressions were not statistically different in LSCC and HNSCC samples [36/42(85.7%) vs. 40/41(97.6%), p=0.68]. Similarly, the detection rate of SFTPB expression by IHC in LSCC and HNSCC samples were not statistically different [3/42(7.1%) vs. 2/41(4.9%), p = 0.68]. However, with a semi-quantitative scoring system, HNSCC samples had a significantly higher mean percentage of KRT14 expression than LSCC samples [70.2 ± 37.3% vs. 41.3 ± 38.0%, p< 0.01]. We used ROC curves to determine the highest performance of the KRT14 staining score. At the cut-off value of 85%, KRT14 expression had the sensitivity and specificity of 61.0 % and 78.6 % respectively in differentiating HNSCC from LSCC. Conclusions: Our analyses indicate that HNSCC has significantly higher KRT14 expression score than LSCC. A quantitative KRT14 expression by IHC may serve as a potential biomarker to distinguish the primary LSCC versus lung metastatic from HNSCC.
Randomized phase II study of axitinib versus standard of care in patients with recurrent glioblastoma.
Authors: Bart Neyns, Johnny Duerinck, Stephanie Du Four, Frank Bouttens, Vincent Verschaeve, Hendrik Everaert, An Van Binst
Journal: Journal of Clinical Oncology (2014)

2018 Background: Vascular endothelial growth factor receptor (VEGFR) signal transduction mediates glioblastoma (GB) associated neo-angiogenesis. Axitinib is an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the VEGF-receptors, approved for the treatment of metastatic renal cell carcinoma. Methods: Axitinib (5 mg BID starting dose) vs. best alternative choice of therapy was studied in an open label, randomized, phase II clinical trial in patients (pts) with recurrent GB. Six-month progression-free survival (6mPFS) was the primary endpoint. Results: Between Sep 2011 and Oct 2013, 44 pts who failed surgery, RT and temozolomide were randomized 1:1 at 3 sites. Median age 54y (range 20-79), 33M/11F, WHO-PS 0/1/2/3: 6, 26, 11, and 1 pt. In the control arm 20 pts received bevacizumab and 2 pts received lomustine at standard doses. Axitinib (n=22) was generally well tolerated. Most common axitinib related AEs consisted of dysphonia (3x G2), fatigue (6x G2, 2x G3), hypertension (5x G2), oral hyperesthesia (7x G2, 1x G3), diarrhea (2x G2, 2x G3), and hypothyroidism (3x G2). In 4 pts axitinib dosing was interrupted and subsequently dose reduced because of toxicity; in 4 other pts axitinib was dose escalated to 7 or 10 mg BID (2 pts each). Tumor response by RANO criteria was 28% in the axitinib arm vs. 23% in the control arm (Table). All pts had an increased uptake on 18F-FET PET at baseline. A decrease (-26 to -100%) of SUVmax/background was documented in 6/7 pts on axitinib at the time of response on MRI. Corticosteroids could be stopped in 4/12 and tapered in an additional 5/12 pts in the axitinib arm. After a median follow-up of 10.5 mths, the 6mPFS for axitinib was 22% (95% CI 5-40) vs. 19% (95% CI 2-36) for the control arm. Median PFS and OS were respectively 2.9 vs. 2.6 mths, and 10.3 vs. 7.4 mths for pts treated in the axitinib vs. control arm. Conclusions: Axitinib has single-agent activity and manageable toxicity in pts with recurrent GB. The survival on the axitinib arm was comparable to that on the contemporary control arm. Further evaluation of axitinib for recurrent GB is warranted. Clinical trial information: NCT01562197. Axitinib Control BOR Confirmed BOR BOR Confirmed BOR CR 5 2 1 1 PR 6 4 5 4 SD 5 7 PD 5 8 NE 1 1 Abbreviations: BOR, best overall tumor response; NE: not evaluable.
APC combination with savary bougienage via endoscopy for the anastomotic-stenosis after esophageal cancer surgery.
Authors: Ruinuo Jia, Xiaoshan Feng, Gang Liu, Kaili Ding, Na Li, Shuoguo Li, Shegan Gao
Journal: Journal of Clinical Oncology (2014)

e15060 Background: Esophageal cancer (EC) is one of the most common cancers worldwide and Surgery remains the primary treatment. Anastomotic-stenosis is a common complication following surgery and often refractory to treatment. Although several endoscopic dilation techniques have been reported, none of these methods have been shown to be superior. Methods: 90 patients with anastomotic-stenosis following esophageal cancer surgery and showed dysphagia Atkinson grades III to IV were randomized into 3 study groups: (1) Combination group (Comb.) (APC performed in combination with SB), (2) APC group (APC alone) or (3) SB group (SB alone). Primary endpoints after 6 months were the mean time of need re-treatment from the first dilation (days), the secondary endpoints were the effective rates (ER) of Complete Response (CR) and Partial Response (PR) after 1week, 2 and 3 months (CR: anastomotic stoma diameter enlargement ≥ 200% and common food intake, PR: the anastomotic stoma diameter enlargement > 100% and semifluid food intake). Results: No severe complications occurred within 3 groups. Primary endpoints: 6 months after treatment, the mean days of need re-treatment from the first dilation of Comb. group significantly longer than the others (Comb. (122.82; 95% CI, 121.82-123.82) vs. APC (41.97; 95% CI, 41.39-42.55), P = 0.000; Comb. vs. SB (18.56; 95% CI, 18.13-19.00), P = 0.000). Secondary endpoints: after treatment 1 week: there was no significant difference in ER between the Comb. and the other groups (Comb. (100%) vs. APC (93.3%), P = 0.472, SB (100%) = Comb.). 1 month: ER of the Comb. group was no significant difference from APC group, but significantly higher than SB group, (Comb. (93.3%) vs. APC (80%), P = 0.255, Comb. vs. SB (20%), P = 0.000); 3 months: ER of the Comb. group was significantly higher than the others, (Comb. (80%) vs. APC (20%), P = 0.000, Comb. vs. SB (3.3%), P = 0.000). Conclusions: In esophageal cancer patients with dysphagia caused by anastomotic-stenosis after esophagogastrostomy, dilation treatment by APC combined with SB was significantly more effective than APC or SB alone and was safe and well tolerated. Clinical trial information: ChiCTR-TRC-13003757.
Phase 2 clinical trial of ixabepilone in metastatic cervical carcinoma.
Authors: Mauricio Emmanuel Burotto Pichun, Sanjeeve Bala, Maureen Edgerly, Julia Wilkerson, Margarita Velarde, Herbert L. Kotz, Susan Elaine Bates, Antonio Tito Fojo
Journal: Journal of Clinical Oncology (2014)

5593 Background: Ixabepilone is a microtubule-stabilizing agent approved for metastatic breast cancer. Preclinical data indicates activity in taxane-sensitive and resistant cells. Metastatic cervical carcinoma (mCC) has a poor prognosis and no accepted second line therapies. This study assessed the efficacy and safety of Ixabepilone in previously treated mCC. Methods: Patients with histologically confirmed mCC and at least one prior regimen received ixabepilone [6mg/m2/d X 5d] every 21 days. Primary endpoint was PFS by RECIST. Secondary endpoints were response rate, overall survival, and safety. We calculated the rate of tumor growth (g) as an additional efficacy measure. Results: Forty-one patients were enrolled; thirty four tumors were squamous. The median number of prior therapies was 2 (range1-6). Four patients (9.7%) had partial responses. Median time to progression in months was 2.3 for all, 3.84 for taxane-naive and 2.03 for taxane pre-treated patients (p=0.13). Consistent with this we found the rate of growth (g) in taxane-naive patients (0.0035/day) to be two-thirds the rate in taxane pre-treated patients (0.0053/day). Median overall survival (OS) was 5.84 months. Thirty-two patients discontinued treatment due to progression, two because of death, two for toxicity, and five for other reasons. The most frequent toxicities included vomiting (43%), sensory neuropathy (21%), and fatigue (60%). G3/4 toxicities were noted in 53% patients; all resolved without interventions Conclusions: Ixabepilone was well tolerated but showed very modest activity in second or higher line mCC. A trend to worse outcomes and a faster rate of growth was observed in taxane-pre-treated patients compared to taxane-naive patients. New strategies are needed for refractory mCC. Clinical trial information: NCT00924066.
Accuracy and content-enhanced exome and transcriptome sequencing to guide therapeutic decision making in cancer treatment.
Authors: Anil Jayant Patwardhan, Elena Helman, Michael Clark, Deanna Church, Sean Boyle, Mark Pratt, Shujun Luo, Nan Leng, Christian Haudenschild, Richard Chen, John West
Journal: Journal of Clinical Oncology (2014)

e22107 Background: With the advent of next-generation sequencing techniques, tumor mutations that guide therapeutic decisions can be identified on a large scale. The ability to accurately detect these mutations is crucial but often impaired by obstacles such as sequencing coverage gaps, small sample size, low cellularity, and tumor heterogeneity. Before sequencing can help direct personalized cancer therapies, these obstacles must be overcome. Methods: We developed a unique targeted exome sequencing assay to augment and improve detection of major cancer mutations. We compared our enhanced exome to standard exome using a set of ten cell lines from the NCI-60 panel. To gauge assay performance on cancer-related genes, we curated a comprehensive set of cancer genes that have previously been implicated in a range of tumor types and annotated them with clinically relevant information. Bioinformatics pipelines were developed to accurately call somatic point mutations and indels, amplifications, and deletions. Finally, we performed transcriptome sequencing to determine mRNA expression, allelic expression, alternative splicing, and gene fusion events in these samples. Results: We define a “finished” gene as a gene sequenced at 20x depth or higher across at least 99% of its bases. By this definition, our enhanced exome finishes 828 of 883 cancer genes (94%), compared with standard exome, which finishes just 577 cancer genes (65%) with the same amount of sequencing (12G). Within this set of genes, we report several known clinically-actionable driver mutations. We also annotate current clinical trials and FDA-approved therapies for the mutated genes. Finally, we combine RNA-seq evidence to validate expressed mutations discovered in the exome, as well as quantify transcript isoform expression, and identify known gene fusions in these cell lines. Conclusions: For cancer exome and transcriptome analysis to effectively guide clinical decisions, accuracy across cancer genes is of paramount importance. The enhanced exome plus transcriptome analysis presented here will lead to increased patient-therapy matching and, it is our hope, to improved patient outcomes.
Minimal Residual Disease (MRD) Status after Induction Therapy Is a Strong Prognostic Factor in the Treatment of Adult Ph (-) Acute Lymphoblastic Leukemia (ALL): Results of a Prospective Study (ALL MRD2008 Study)
Authors: Koji Nagafuji, Toshihiro Miyamoto, Tetsuya Eto, Ryosuke Ogawa, Naoyuki Uchida, Ken Takase, Noriaki Kawano, Tomoaki Fujisaki, Tomohiko Kamimura, Atsushi Wake, Hirokazu Okumura, Yasuhiko Miyazaki, Yasushi Takamatsu, Toshiro Kurokawa, Yuju Ohno, Shouhei Yokota, Koichi Akashi
Journal: Blood (2018)
Abstract 18669: A Simple Noninvasive Score for Predicting Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Replacement
Authors: Jared M Routh, Lee Joseph, Brodie R Marthaler, Prashant Bhave
Journal: Circulation (2015)

Introduction: Cardiac conduction abnormalities requiring permanent pacemaker (PPM) are well-recognized complications of TAVR. However, a clinical prediction tool for assessing the risk of post-TAVR PPM placement is not available. Hypothesis: The purpose of this study was to create a novel clinical prediction tool for assessing the risk of PPM following TAVR. Methods: A total of 114 patients who underwent TAVR using the balloon-expandable Edwards SAPIEN valve at the University of Iowa Hospitals and Clinics were identified. We then excluded patients with a pre-existing PPM, who required conversion to an open/salvage procedure, and those without available CT data. Binomial logistic multivariate regression was performed to construct a scoring system. Results: A total of 84 patients were included in the study and PPM was placed in 9 patients (10.7%). From the binomial logistic regression analysis using RBBB, valve size to Sinus of Valsalva diameter ratio, and sex as predictors, pre-existing RBBB (odds ratio [OR]: 6.5, 95% confidence ratio [CI]: 1.1-37.1, p=0.035) and the ratio of valve size to diameter of Sinus of Valsalva (OR: 1.2, 95% CI: 1.03-1.3, p=0.012) were identified as significant predictors of PPM post-TAVR. We created a novel clinical prediction tool for PPM post-TAVR with patients being designated with score 0 if they had no RBBB and valve size to diameter of sinus of Valsalva ratio &lt; 81.4 (optimal cut-off based on ROC curve) and score 1 if they had RBBB, or valve size to diameter of sinus of Valsalva ratio ≥ 81.4, or both (OR: 12.6, 95% CI: 1.5-106.8, p=0.009; sensitivity, 0.90; specificity, 0.59). Conclusions: Our clinical prediction score for PPM following TAVR expands upon the available literature for pre-procedural risk-stratification. The components of the score have biological plausibility, as pre-existing conduction system disease and relative valve prosthesis oversizing would be expected to confer a higher risk of post-procedural AV block. Implantation of PPM prior to TAVR in patients at risk for high-grade AV conduction abnormalities, based on this simple risk score, could have important implications for morbidity/mortality, length of stay, and cost. Moving forward, this prediction score requires validation in multicenter cohorts.
A multicenter phase II toxicity study of lung-sparing intensity modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM).
Authors: Marjorie Glass Zauderer, Andreas Rimner, Kenneth Rosenzweig, Abraham Jing-Ching Wu, Ellen Yorke, Camelia S. Sima, Neha Bhattacharjee, Zarine Patel, Daniel Richard Gomez, Anne S. Tsao, David C. Rice, Reza J. Mehran, Prasad S. Adusumili, Valerie W. Rusch, Lee M. Krug
Journal: Journal of Clinical Oncology (2014)

7581 Background: Given the trend away from extrapleural pneumonectomy (EPP) towards pleurectomy/decortication (P/D), we are developing a technique to deliver radiation to the pleura in patients with two intact lungs. In our initial experience with 36 patients (20 post P/D), 20% had grade ≥ 3 pneumonitis, most treated effectively with steroids, and survival was promising (Rosenzweig 2012). We now report our prospective, multicenter, phase II study of the safety and efficacy of pleural IMRT as part of a multimodality, lung-sparing, treatment approach. Methods: Patients with stage I-IV MPM received <4 cycles of pemetrexed and platinum chemotherapy. If feasible, P/D was performed. IMRT was delivered to the pleura (goal of 50.4 Gy, 28 fractions). The primary endpoint was the incidence of ≥ grade 3 radiation pneumonitis (RP); those who received any IMRT were considered evaluable. A Simon two-stage design was used: among the initial 9 patients, one case of grade 3 reversible RP occurred, so the cohort expanded to 28. Results: 39 patients are enrolled: 23 evaluable, 5 to receive IMRT, and 11 off-study before IMRT (7 due to disease progression, 3 were poor IMRT candidates at the time of simulation, and 1 withdrew consent). Demographics are in Table 1. 21 patients completed IMRT: 4 had grade 2 RP and 1 had grade 3 RP and was weaned from oxygen after a course of steroids. No grade 4 or 5 radiation-related toxicities were observed. Follow-up PFTs demonstrated an average decrease in DLCO of 18% (range 6-34%) from baseline. Conclusions: Pleural IMRT for MPM is safe with an acceptable rate of RP and feasible in a multicenter setting. The incorporation of IMRT with chemotherapy and P/D could form a new treatment paradigm for locally advanced MPM. In order to increase the number of patients able to complete all therapy and to improve local control in areas of bulkier disease, we plan a follow up study with upfront P/D, followed by chemotherapy and then radiation with dose-painting techniques. Clinical trial information: NCT00715611. All N=39 (%) Age, median (range) 68 (38-75) Gender M/F 35 (90)/4 (10) Stage I II III IV 2 (5) 10 (26) 14 (36) 13 (33) Histology Epithelioid Sarcomatoid Biphasic 32 (82) 3 (8) 4 (10) Surgery P/D Unresectable 21 (54) 18 (46)