tbuckley/cabot-search huggingface dataset:
A new complementary approach to endoscopy for esophageal cancer diagnosis.
Authors: Gengxi Jiang, Hongmei Tao, Xing Tang, Da Lou, Yue Lin, Yutao Li, Junjie Wu, Baoxia Wang, Ning Ding, Pengkun Xu, Xing He, Hao Hu, Chris Chang Yu, Hezhong Chen, Xuedong Du
Journal: Journal of Clinical Oncology (2017)

42 Background: For esophageal cancer, no viable non-invasive detection technologies are available today. In earlier investigations, Cancer Differentiation Analysis (CDA) Technology which measures information relating to both protein fragments and cellular signals in blood samples in a single test has showed a significant advantage in esophageal cancer diagnosis. Methods: Blood samples from 105 individuals in EDTA tubes were collected from Shanghai Changhai Hospital, China, between July and December 2014, CDA and endoscopy tests were carried out on all samples before clinically diagnosed. A performance predication model of CDA and endoscopy test results was built using pROC package in R Language for the data of Area Under the Curve (AUC) and CDA threshold values. Further analysis was carried out based on the CDA threshold values. Results: Out of the 105 individuals, samples from 6 individuals diagnosed as esophageal benign diseases were selected as control group. 99 samples from individuals diagnosed as esophageal cancer, of which 3 and 82 cases were adenocarcinoma and squamous carcinoma, 2, 26, 33, 31 and 7 cases were classified as stage 0,I,II, III, IV, respectively. Details of AUC results of endoscopy, and CDA plus endoscopy for each group were given in Table 1 below. Conclusions: Even though the sensitivity of the endoscopy is usually high due to its pathological examination, this investigation showed that CDA technology could further enhance the diagnosis sensitivity of endoscope, especially for early stage of esophageal cancer, and it (CDA) can be an effective complementary tool to clinical diagnosis and operation determination while obtaining the pathological information via endoscopy. In conclusion, CDA technology is of great value in esophageal diagnosis and therapeutic decision-making. [Table: see text]
Association between levels of hormones implied in steroid biosynthesis pathway and activity of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): An exploratory analysis.
Authors: Marcello Tucci, Francesca Vignani, Valentina Bertaglia, Consuelo Buttigliero, Alfredo Berruti, Giorgio V. Scagliotti, Massimo Di Maio
Journal: Journal of Clinical Oncology (2015)

e16066 Background: AA inhibits 17α-hydroxylase and C17,20-lyase, blocking androgen biosynthesis. It is approved for treatment in patients with mCRPC. Aim of this analysis was to describe changes in hormonal levels determined by AA, and to explore the association between levels (both baseline and changes) of hormones implied in steroid biosynthesis pathway and drug activity. Methods: Pts receiving AA 1000 mg daily + prednisone 5 mg twice daily for mCRPC, after failure of docetaxel, were included in this mono-institutional study. Serum levels of progesterone, 17OH-progesterone, cortisol, DHEA sulfate, androstenedione, testosterone, sex hormone binding globulin, aldosterone, plasma renin activity, ACTH and cholesterol, were determined at baseline and every 12 wks, until progression. Hormonal levels at baseline vs subsequent samples were compared by Wilcoxon matched-pairs test. Association between hormones and treatment activity ( ≥ 50% PSA reduction) was tested (1) comparing baseline levels of responders vs non-responders; (2) comparing progression-free survival (PFS) of pts with baseline low vs high values of each hormone; (3) comparing levels after 12 wks of responders vs non-responders, adjusted by baseline levels. Results: 49 pts were included in the analysis (median age 70, ECOG PS 0/1/2 61%/33%/6%, median baseline PSA 116.95). 82% were metastatic to bone. PSA reduction was obtained in 26 pts (53.1%). Median PFS was 10.2 months. Baseline levels of all hormones were not statistically different between responders and non-responders. For all hormones, difference in PFS of pts with low baseline values vs pts with high baseline values was not statistically significant. Several hormones showed significant and sustained changes vs baseline, but all significant changes were similar between responders and non-responders. Conclusions: Although limited by low statistical power, our exploratory analysis does not suggest a significant association between baseline levels of hormones implied in steroid biosynthesis, or changes induced by AA, and treatment activity.
A retrospective comparison of the characteristics and recurrence outcome of triple-negative and triple-positive breast cancer.
Authors: Jaskirat Singh Randhawa, Vyshak Alva Venur, Hameem Kawsar, Timothy Peter Spiro, Abdo S. Haddad, Rajesh Kumar Bagai, Hamed Daw
Journal: Journal of Clinical Oncology (2013)

1038 Background: Triple-negative (estrogen/progesterone-receptors negative and HER2-negative; TNBC) and Triple-positive (estrogen/progesterone-receptors positive and HER2-positive; TPBC) breast cancers are very distinctive in terms of tumor behavior as well as disease management. Due to lack of an effective targeted therapy, the treatment options are limited for TNBC. We conducted a retrospective review to compare various characteristics and recurrence outcome in TNBC and TPBC. Methods: Over 3000 non-consecutive female breast cancer patients (diagnosed between 2000-2012) were reviewed. Of these, 406 patients (206 TNBC, 200 TPBC) were included. The following data at diagnosis were studied: age, tumor size, stage, grade, lymph node involvement, distant metastases and smoking history. Analyses are performed using R statistical software (Version 2.15.2). Numeric data are summarized by median and quartile with comparisons between groups performed by Wilcoxon Rank Sum Tests. Categorical data are summarized by frequency and percentage and comparisons between groups are performed by chi-square tests. Statistical significance is determined by a p-value ≤ 0.05. Results: Both TNBC and TPBC were diagnosed at similar median ages of 56.5 and 55 years respectively (p= 0.059). TNBC were more likely to have poorly differentiated histology (75.63%) whereas TPBC were more often moderately differentiated (54.79%) (p&lt; 0.001). At diagnosis, Triple-Positive (TP) tumors were larger (median 2.4 cm) compared to Triple-Negative (TN) tumors (median 2 cm) (p= 0.013). However, there were no significant differences with respect to lymph node involvement and distant metastases in the two groups. Importantly, recurrences were more common in TNBC 33.85% (65/192) compared to TPBC 4.21% (8/190) (p &lt; 0.001) and there was no association found with smoking history or active smoking status. Conclusions: TN tumors although smaller in size compared to TP were more likely to have poorly differentiated histology, showed higher recurrence rates and therefore were more aggressive in behavior. Both TNBC and TPBC were diagnosed at similar median age and exhibited no recurrence association with smoking history.
Stereotactic ablative body radiotherapy (sabr) outcomes for primary and metastatic non-small cell lung cancer (nsclc) pulmonary tumours.
Authors: Isabelle Thibault, Ian Poon, Darby Erler, Anthony Kim, Brian Keller, Latifa Yeung, Suneil Jain, Hany Soliman, Fiona Lochray, Patrick Cheung
Journal: Journal of Thoracic Oncology (2013)
Authors’ reply to Farrar
Authors: Stefan Schandelmaier, Reed A C Siemieniuk, Thomas Agoritsas, Per O Vandvik, Gordon H Guyatt, Jason W Busse
Journal: BMJ (2017)

Farrar questions the finding of our systematic review—that low intensity pulsed ultrasound (LIPUS) was not effective12—based on two hypotheses. Firstly, that despite being ineffective in fresh fractures, LIPUS may work in non-union fractures and, secondly, that its effectiveness is dose dependent.

Our systematic review included three trials that enrolled patients with non-union of a fracture, all of which were at high risk of bias, and none reported outcomes that are important to patients. We …
Real-Time Genomic Profiling Identifies Novel Mutations and Improved Therapy for Histiocytoses
Authors: Lynn Lee, Anjelika Gasilina, Jayeeta Roychoudhury, Jason Clark, Francis X McCormack, Joseph Gerald Pressey, Robert B. Lorsbach, Siraj M Ali, Mark Bailey, Philip Stevens, Jeffrey S Ross, Vincent A. Miller, Nicolas Nassar, Ashish R Kumar
Journal: Blood (2016)
Effect of cell-free ascites containing mitochondrial DNA (mtDNA) from ovarian cancer (OC) patients on human neutrophils and neutrophil extracellular traps (NETs).
Authors: Kassondra S. Grzankowski, Anm Nazmul H. Khan, Melissa Grimm, Bonnie Hylander, Kelly L. Singel, Kirsten B. Moysich, Nonna Kolomeyevskaya, Kunle Odunsi, Brahm H. Segal
Journal: Journal of Clinical Oncology (2014)

e22087 Background: Mitochondrial damage-associated molecular patterns, made of mtDNA and formylated peptides, are released after cellular injury and recruit/activate neutrophils. NETs made of stretches of extracellular DNA, histones, and granular constituents, trap and kill invading pathogens, but also cause tissue injury. In mice, NETs bind tumor cells and accelerate invasion and metastasis. Mitochondrial extract and mtDNA activate NETs in human neutrophils. In addition, we observed that increased pretreatment mtDNA levels in serum and ascites significantly correlate with shorter PFS and OS in OC patients. Based on these findings, we aimed to evaluate: a) The effects of cell-free ascites from OC patients on normal donor neutrophils; b) Whether tumor-infiltrating neutrophils undergo NETosis. Methods: Purified neutrophils were cultured with media, mtDNA, or cell-free ascites from patients with OC collected at surgery. Arginase 1 (ARG1) expression in neutrophils (CD15+), which in tumor-bearing mice is associated with an immunosuppressive phenotype, was assessed by flow cytometry. NETs were identified by immunofluorescence microscopy showing co-localization of extracellular DNA, histone, and neutrophil elastase. In separate studies, we evaluated NETosis in fixed, paraffin-embedded cytokeratin-7 OC tumor, and NETs were identified by co-localization of the same immunofluorescence markers. Results: Cell-free ascites from different patients had variable effects on ARG1 expression, ranging from no effect to a reduction in ARG1 levels, while purified mtDNA decreased ARG1 expression. In addition, ascites and purified mtDNA induced NET generation in normal neutrophils. Finally, we observed NETs in resected OC tumor (n = 3). Conclusions: Pretreatment serum and ascites mtDNA levels are promising prognostic biomarkers in patients with OC. Our findings support a model in which mtDNA released as products of necrosis during OC, accelerate tumor progression by recruitment/activation of neutrophils and stimulation of NETosis. Further work will delineate the relationship between quantitative markers of NETosis and PFS in patients with OC.
Exploring optimal sequence of abiraterone and enzalutamide in patients with castration-resistant prostate cancer: The Kyoto-Baltimore collaboration.
Authors: Naoki Terada, Benjamin Louis Maughan, Shusuke Akamatsu, Takashi Kobayashi, Toshinari Yamasaki, Takahiro Inoue, Tomomi Kamba, Osamu Ogawa, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2017)

219 Background: Abiraterone (ABI) and enzalutamide (ENZA) are novel hormonal treatments for castration-resistant prostate cancer (CRPC) used before and after docetaxel (DTX) chemotherapy. We aimed to evaluate and compare the efficacy of sequential treatment with ABI followed by ENZA or vice versa in patients with CRPC, using combined data from two institutions. Methods: We retrospectively evaluated data on 352 consecutive patients who had received both ABI and ENZA for CRPC at Kyoto University Hospital and at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Using Kaplan-Meier analysis and log-rank tests, we compared PSA progression-free survival (PSA-PFS) and overall survival (OS) in patients treated with sequential ABI-to-ENZA versus ENZA-to-ABI without intervening therapies. Results: The number of patients receiving ABI-to-ENZA and ENZA-to-ABI were 163 (pre-DTX: 116, post-DTX: 47) and 189 (pre-DTX: 85, post-DTX: 104), respectively. The &gt; 50% PSA response rates to ABI and ENZA were 47% and 52% in the first-line CRPC setting, and were 9% and 29% in the second-line setting. In the pre-DTX population, median PSA-PFS was not significantly different between ABI (median: 194 days) and ENZA (median: 126 days) in the first-line setting (p = 0.411), but there was an advantage favoring ENZA (median: 91 days) compared to ABI (median: 55 days) in the second-line setting (p = 0.008). Furthermore, the combined PSA-PFS was significantly longer in the ABI-to-ENZA sequence (median: 455 days) than in the ENZA-to-ABI sequence (median: 296 days) (p &lt; 0.001). There was no statistical difference in OS between the two sequences (p = 0.598). Conclusions: The ABI-to-ENZA sequence may have more favorable efficacy in terms of combined PSA-PFS than the ENZA-to-ABI sequence, although no differences in OS were observed. This may possibly be attributable to higher PSA response rates and longer PSA-PFS to second-line ENZA compared to ABI (i.e., ENZA retains activity after ABI but not vice versa).
Impact of next-generation sequencing (NGS) on treatment decisions in the community oncology setting.
Authors: Lindsay Carol Overton, Christopher L. Corless, Manish Agrawal, Vasily J. Assikis, Nancy L. Beegle, Sibel Blau, Marc Chernoff, Stephen G. Divers, David H. Henry, Petros Nikolinakos, Colleen Oliver, Eric Scott Schaefer, Frederick M. Schnell, Dennis Slater, Daniel Lewis Spitz, Vicki Tosher, Robert J. Green
Journal: Journal of Clinical Oncology (2014)

11028 Background: Mutational testing has become standard of care in melanoma, lung, and colorectal cancers. The advent of Next Generation Sequencing (NGS) and increasing availability of new targeted therapeutics raise the question of how broader use of testing will impact care in the community setting. Methods: We conducted a retrospective chart review of patients (pts) seen at a network of community oncology practices whose tumors were tested with NGS for actionable mutations in AKT1, ALK, BRAF, DDR2, EGFR, ERBB2, FGFR1/3, GNA11, GNAQ, MAP2K1, HRAS, KDR, KIT, KRAS, MET, NF1, NRAS, NTRK1/2/3, PIK3CA, PIK3R1, PTEN, RET, STK11, TSC1, and TSC2. Under IRB approval, data were collected on diagnosis, date of testing, treatments, mutational results, treatment outcomes, and survival. Results: 632 pts had NGS, of whom 360 harbored actionable mutations (57%). Of these, 301 were included for review: 59 were excluded based on disease stage or insufficient clinical data. There were 26 different cancer types; lung, colorectal and breast cancers represented over half. As of December 2013, 45% of pts had started new therapies after NGS results were available. Mutational testing guided treatment in 34% of these pts, with over half enrolling on clinical trials targeting specific mutations. A minority (6.6%) was treated off label with FDA approved medications targeting the mutations. Conclusions: When performed in a timely manner, NGS had a clinically meaningful impact on treatment planning in one third of pts. The availability of molecularly targeted clinical trials played a significant role in the importance of the testing. Our data provide an initial view of how NGS can impact treatment decision making in the community setting. Total number pts 632 Patients with actionable mutations 57% (n=360) Eligible for analysis based on advanced stage and availability of clinical information 48% (n=301) Were test results available before the latest treatment was started? Yes (45%, n=136) No (55%, n=165) Did results guide subsequent therapy? Treatment status? Yes (34%, n=34) No (66%, n=102) Still on last treatment Not on treatment Hospice/died Other Clinical trial Standard of care Off-label use Patient alive? 52% 22% 26% Yes 76% No 24% 30% 28% 37% 5%
A chemically-modified miR-21 inhibitor (ADM-21) as a novel potential therapy in bladder cancer.
Authors: Alexandra Drakaki, Marina Koutsioumpa, Neil A. O'Brien, Christina Vorvis, Dimitrios Iliopoulos, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2017)

335 Background: MicroRNAs are key regulators of cancer signaling pathways.Targeting their expression has therapeutic potential. MicroRNA-21 (miR-21) acts as an oncogene in several cancers. Here we describe its functional significance in bladder oncogenesis and the therapeutic properties of a novel chemically-modified miR-21 inhibitor (ADM-21). Methods: MiR-21 expression was assessed by RT-PCR in a panel of human bladder cancer tissues and cell lines. Transcriptomic profiling of 28 bladder cancer cell lines performed to identify miR-21-dependent gene signatures. ADM-21 is a chemically-modified (phosphorothioate backbone and locked-nuclei-acid) antisense oligo against miR-21 with high potency and stability.The efficacy of ADM-21 treatment was evaluated in vitro and in vivo. Results: MiR-21 was up-regulated by 5-fold in bladder tumors relatively to normal tissue and by 3-fold in advanced compared to early stage bladder cancers. The 28 cancer cell lines were stratified in 3 groups (high, intermediate, low) according to miR-21 levels. Transcriptomic analysis revealed a 15-gene signature that negatively correlated with miR-21 levels. Protein Phosphatase 2 Regulatory Subunit B Isoform A (PPP2R2A) displayed tumor suppressive properties in bladder cancer. Moreover, PPP2R2A represents a novel miR-21 direct target gene and a negative regulator of the AKT/mTOR pathway. ADM-21 (10uM) treatment suppressed 43.5% the growth and 90% the invasiveness of 5367 bladder cancer cells. Also, intravenous (I.V.) administration of ADM-21 was proven more effective than intraperitoneal (I.P.) administration in mouse xenografts. Specifically, 15mg/kg of ADM-21 (I.V.) every 5 days for 3 cycles reduced 37% and 47% (day 16) the growth rate of tumors originating from injections of 5367 and RT-112 cells, respectively. Conclusions: Integrative analysis of human bladder tumors and cell lines revealed a novel 15-gene signature that correlates with miR-21 levels. PPP2R2A is a miR-21 direct target and regulator of the AKT/mTOR pathway. ADM-21effectively reduces bladder cancer growth in vitro and in vivo. Upon completion of ADM-21 toxicology studies and confirm safety we will design phase I clinical trial for advanced bladder cancer.
First Corticosteroid Approved for Duchenne Muscular Dystrophy
Authors: Rebecca Voelker
Journal: JAMA (2017)

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Clinical outcome of pediatric brainstem glioma treated with concurrent chemoradiotherapy with temozolomide: An institutional experience.
Authors: Subhash Gupta, Haresh Kunhiparambath, Supriya Mallick, Manikandan Annamalai, Dayanand Sharma, Pramod Kumar Julka, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2015)

e13045 Background: Introduction: Brainstem glioma (BSG) is an aggressive tumor of childhood. Treatment outcomes remain dismal and role of concurrent chemoradiotherapy (CTRT) is not established in these patients .We intended to study the clinical characteristics along with outcome of pediatric BSG patients treated with CTRT. Methods: We retrospectively evaluated 57 patients, age less than 18 years, with BSG treated at our department in the period Jan 2007 to December 2012. Demographic and disease characteristics in this patient cohort were recorded, and their progression free survival (PFS) was analyzed with respect to sex, grade, and use of CTRT and adjuvant chemotherapy. Results: Median age at presentation was 9 years (range 3-18 years), with a male: female ratio of 1.8.18 patients presented with gait ataxia and 16 presented with cranial nerve palsies.24 patients were diagnosed radiologically as high grade. None of the patient underwent surgery. Radiotherapy dose was 56-60 Gray over 5.5 -6 weeks at 1.8-2 gray/fraction. All patients completed their radiotherapy except 4 patients.18 patients received concurrent Temozolomide (75 mg/m2) ,11 patients received adjuvant Temozolomide (150-200 mg/m2 D1-5 q4 weeks for 3-6 cycles) and 6 patient received both concurrent and adjuvant Temozolomide. Median follow up duration was 7.97 months (range 1.7-38.3 months).At last follow up, 27 patients had progressive disease. Median PFS for the entire group was 12.49 months. PFS was not significantly altered in the patients who received concurrent Temozolomide than those who did not (p 0.12) on Univariate analysis. Sex, grade, and adjuvant chemotherapy did not statistically alter treatment outcomes. Conclusions: Outcome of Pediatric BSG remains dismal .CTRT with Temozolomide does not affect survival. Radiotherapy alone with standard fractionation remains the treatment of choice in inoperable pediatric BSG.