tbuckley/cabot-search huggingface dataset:
Independent adjudicator assessments of platelet refractoriness and rFVIIa efficacy in bleeding episodes and surgeries from the multinational Glanzmann's thrombasthenia registry
Authors: Michael Recht, Madhvi Rajpurkar, Meera Chitlur, Roseline d'Oiron, Rainer Zotz, Giovanni Di Minno, David L. Cooper, Man‐Chiu Poon
Journal: American Journal of Hematology (2017)

Abstract Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder associated with decreased platelet aggregation due to qualitative/quantitative deficiencies of the fibrinogen receptor. Severe bleeding episodes and perioperative bleeding are typically managed with platelet transfusions, although patients can develop anti‐platelet antibodies or experience clinical refractoriness. The GT Registry (GTR) was established to collect efficacy/safety data on hemostatic treatments for GT, including recombinant factor VIIa (rFVIIa). At the request of the United States Food and Drug Administration, three hematology experts evaluated platelet refractoriness, antibody status, and rFVIIa efficacy data on a case‐by‐case basis to support a potential indication for rFVIIa in GT. Adjudication included 195 patients with 810 events (619 severe bleeding episodes, 192 surgeries), and a consensus algorithm was developed to describe adjudicators' coding of refractoriness and antibody status based on treatment patterns over time. Most rFVIIa‐treated events were in patients without refractoriness or antibodies. Adjudicators rated most rFVIIa‐treated bleeding episodes as successful (251/266, 94.4%; rFVIIa only, 101/109, 92.7%; rFVIIa ± platelets ± other agents, 150/157, 95.5%); efficacy was consistent in patients with platelet refractoriness ± antibodies (75/79, 94.9%), antibodies only (10/10, 100.0%), and neither/unknown (166/177, 93.8%). Adjudicators also rated most rFVIIa‐treated surgeries as successful (159/160, 99.4%; rFVIIa only, 65/66, 98.5%; rFVIIa ± platelets ± other agents, 94/94, 100.0%); efficacy was consistent in patients with platelet refractoriness ± antibodies (69/70, 98.6%), antibodies only (24/24, 100.0%), and neither/unknown (66/66, 100.0%). Unblinding the adjudicators to investigator efficacy ratings changed few assessments. Doses of rFVIIa were narrowly distributed, regardless of other hemostatic agents used.
Are oncologists involved in cancer biomarker decisions at their institutions?
Authors: Christine B. Weldon, Julia R. Trosman, Al Bowen Benson, Gregory J. Tsongalis, Kalliopi P. Siziopikou, William John Gradishar, Julian C. Schink
Journal: Journal of Clinical Oncology (2013)

6617 Background: Biomarkers play a critical role in oncology, but differences in accuracy and quality exist between different testing methods for specific markers. ASCO/CAP guidelines call for oncologists, on behalf of patients, to seek information on testing quality and to obtain assurance that testing laboratories are appropriately accredited (Wolff et al, JCO, 2007). We surveyed oncologists and pathologists from the NCI designated cancer centers to collect individual perception of their institution’s decision making on biomarkers, and awareness of lab quality accreditation. Methods: We conducted an IRB approved web survey of pathologists and oncologists at the 58 NCI designated cancer centers providing adult breast, gastric, esophageal and non small cell lung cancer care. The survey included 12 questions on institutional decision processes and lab quality accreditation. We analyzed results using simple frequencies and the Fisher's exact test. Results: The study achieved a response rate of 98% (57/58 sites), with survey responses from 115 pathologists and 156 oncologists. The perception that their institution uses a formal organizational review and decision process on new biomarker tests was reported by 47% (54/115) of pathologists and 31% (48/156) of oncologists (p= .0078). 22% (33/153) of oncologists report they are always involved in institutional decision making on biomarker method selection for their specialty. Awareness of CAP certification status for their institutional laboratory was reported by 88% (99/112) of pathologists and 46% (65/142) of oncologists (p &lt;0.0001). Awareness of whether their institutional laboratory underwent CAP HER2 IHC and/or FISH proficiency testing was reported by 70% (53/76) of pathologists and by 21% (13/63) of oncologists who treat breast cancer (p&lt;.0001). Conclusions: Oncologists are typically not actively involved in their institution’s decision making process to select biomarker testing methods, nor are many of them aware of their institutional lab’s quality accreditation. With the ever increasing role of biomarkers in cancer care, oncologists’ awareness of biomarker testing performance and their participation in decision making related to biomarkers will become critical.
An update on clinical outcome data for a phase II randomized study comparing androgen deprivation therapy plus docetaxel versus androgen deprivation therapy alone in men with locally advanced/metastatic hormone sensitive prostate cancer.
Authors: Adam Hassani, John A. Frew, Rhona Margaret McMenemin, Ashraf S. Azzabi, Ian D. Pedley
Journal: Journal of Clinical Oncology (2017)

259 Background: Androgen deprivation therapy has been the standard of care for advanced prostate cancer for many years. However recent studies have reported a survival benefit for upfront docetaxel chemotherapy in men with hormone sensitive prostate cancer. The GenTax trial was a single institution phase II study investigating clinical outcome and gene profiling for patients with treatment naïve prostate cancer treated with either docetaxel chemotherapy plus androgen deprivation therapy (D+ADT) or androgen deprivation therapy alone (ADT). We report on updated clinical outcome data for this trial. Methods: Patients with newly diagnosed T3/T4, PSA ≥ 50ng/ml or Gleason score ≥ 8, or metastatic disease were enrolled. Patients were randomised to ADT or D+ADT (docetaxel 75mg/m 2 q21 days for 6 cycles). Data were analysed for overall survival, toxicities, time to second line treatment and number of subsequent treatments. Results: 30 patients were randomly assigned to ADT (n = 15) or D+ADT (n = 15) between 10/13/2005 and 12/02/2009. 7 patients in each arm had metastatic disease. Grade 3-4 toxicities were infrequent in D+ADT arm and were not noted in the ADT arm. There were no significant differences between treatment arms for overall survival (log rank p = 0.977) or time to second line treatment (log rank p = 0.954). Median overall survival was 98 months (95% CI 72.3 - 123.7) for ADT and 87 months (95% CI 71.5 - 102.5) for D+ADT. Median time to second line treatment was 45 months (95% CI 13.4 - 76.6) for ADT and 46 months (95% CI 13.2 – 78.8) for D+ADT. Number of subsequent treatments ranged from 0-6 (mean 2.40) for ADT-only and 0-5 (mean 2.13) for D+ADT. Conclusions: The combination of docetaxel and ADT in the hormone sensitive setting is well tolerated, as previously reported. This study was not sufficiently powered to detect statistically significant differences in survival. Patients proceeded to receive a number of subsequent lines of therapy although the order in which these were given was variable. There is a need to establish optimal sequencing of treatments in the upfront docetaxel era. Clinical trial information: 2004-004874-96.
CA184-104: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) with paclitaxel/carboplatin (PC) versus placebo with PC in patients (pts) with stage IV/recurrent non-small cell lung cancer (NSCLC) of squamous histology.
Authors: Martin Reck, Haolan Lu, Greta Gribkoff, Sabine Maier, Rachel McGovern, Jean-Marie Cuillerot, Thomas James Lynch
Journal: Journal of Clinical Oncology (2012)

TPS7611 Background: Years of research in advanced NSCLC have not improved outcomes for the squamous subtype beyond those of standard platinum doublets. Evidence of responses to immune therapies in NSCLC of squamous cell histology supports investigation in this subtype. Ipi, a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi improved overall survival (OS) in advanced melanoma, with side effects managed using product-specific treatment guidelines; immune-related response criteria (irRC) were derived from WHO criteria to better capture response patterns observed with Ipi. A randomized Phase 2 study of Ipi/PC in Stage IV NSCLC pts showed significant improvement in progression-free survival (PFS), as measured by mWHO or irRC, with a trend toward improved OS, over chemotherapy alone in pts receiving phased Ipi/PC (Ipi started after 2 cycles of PC). Phased Ipi/PC appeared to show efficacy in tumors of squamous histology. Addition of Ipi did not exacerbate PC toxicity, and immune-related adverse events were managed using protocol-specific guidelines. A Phase 3 trial (ClinicalTrials.gov identifier NCT01285609) is examining whether phased Ipi/PC will prolong OS in chemotherapy-naïve pts with squamous NSCLC. Methods: Stage IV/recurrent squamous NSCLC with ECOG 0-1 will be included; pts with CNS metastases or history of autoimmune disease will be excluded. Pts are randomized to receive 2 cycles of PC (175 mg/m 2 and AUC=6, respectively; IV), followed by 4 cycles of study drug (Ipi in Arm A, placebo in Arm B; IV) with 4 additional cycles of PC (total 6 cycles). Pts without progressive disease (PD) after induction receive maintenance therapy with blinded study drug Q12W until PD per mWHO. The study will randomize 920 pts 1:1 between arms. The primary endpoint of this study is OS; secondary endpoints include OS among pts who receive blinded therapy, PFS and best overall response rate.
The Principal Eosinophil Peroxidase Oxidant, HOSCN, Potently Induces Endothelial Cell Tissue Factor Activity through Transcriptional Activation Dependent upon NF-kB and ERK1/2: Potential Mechanism for a Prothrombotic and Proinflammatory Endothelial Phenotype in the Hypereosinophilic Syndrome.
Authors: Jianguo Wang, Shawn A. Mahmud, Jake A. Thompson, Jianguo Geng, Nigel S. Key, Arne Slungaard
Journal: Blood (2004)
Confirmation of non-small cell lung cancer (NSCLC) diagnosis using ALK testing and genetic profiling in patients presenting with carcinoma of unknown primary site (CUP).
Authors: William Charles Penley, David R. Spigel, F Anthony Greco, John D. Hainsworth
Journal: Journal of Clinical Oncology (2013)

e19062 Background: Emerging data suggest real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tumor profiling can predict the primary site in CUP. We report on CUP patients (pts) predicted to have NSCLC by RT-PCR, in whom detection of ALK rearrangements provided further diagnostic support. Methods: 4 pts were diagnosed with CUP based on standard clinical, radiographic, pathologic evaluation with immunohistochemistry (IHC), and bronchoscopy/endoscopy where indicated. All pts had a RT-PCR assay (CancerTYPE ID, bioTheranostics, Inc.) performed on tumor specimens for the purpose of predicting a primary site. Tissue was also tested for ALK by FISH using a break-apart probe. Results: Pt characteristics are shown (Table). RT-PCR results prompted ALK testing in Pts 2 and 3. ALK testing and RT-PCR testing were performed concurrently in Pts 1 and 4. Each specimen was diagnosed as lung adenocarcinoma (AC) by RT-PCR gene profiling, and also tested positive for an EML4-ALKrearrangement. All pts are being followed for clinical outcome. Conclusions: Gene expression profiling in CUP diagnosed lung AC in 4 pts who also had ALK rearrangements supporting the diagnosis. Identifying ALK-positive NSCLC among pts who present with CUP improves the site-specific treatment options. [Table: see text]
Characteristics and survival of patients with advanced cancer and <i>TP53</i> mutations in phase I clinical trials.
Authors: Rabih Said, Yang Ye, David S. Hong, Filip Janku, Siqing Fu, Aung Naing, Jennifer J. Wheler, Razelle Kurzrock, Christoforos Thomas, Gary A. Palmer, Kenneth R. Hess, Robert A. Wolff, Apostolia Maria Tsimberidou
Journal: Journal of Clinical Oncology (2013)

2545 Background: The classical hot spot mutations within the central sequence-specific DNA-binding region of p53 protein (R175H in exon 5 and G245S, R248Q, R249S, R273H and R282W in exon 8) disrupt its ability to bind to DNA. These inactivating point mutations of p53 may result in loss of its function and/or acquisition of a gain of function, which has been associated with the development of invasive and metastatic tumors in mouse models. We assessed the frequency and survival of p53 mutations in patients with advanced cancer. Methods: P53 mutation in patients’ tumor was identified in a CLIA-certified laboratory using PCR, sequenom analysis or next generation sequencing. Results: P53 mutations were identified in 212 patients. Median survival by tumor type and distribution of p53 mutations by exon are shown in the Table. The median survival (from time of referral to Phase I clinic) by mutations in “hot spot” amino acids was as follows: R175H, 9.1 months (n=18); R248Q, not reached/5 deaths (n=22); R273H, 12.6 months (n=11); other mutations, 11.9 months (n=160). The median survival of patients with a tumor mutation in exons 5 or 8 appeared to be shorter than that of patients with mutations in other exons (9.4 vs. 14.6 months) although the difference was not statistically significant (p=.12) owing to the small number of patients. Conclusions: Our results demonstrate that the distribution and clinical significance of various p53 mutations differs by tumor type and suggest that mutations in R248Q may be associated with longer survival. [Table: see text]
Differences in attitudes and beliefs toward end-of-life treatments between hematologic (Heme) and solid tumor (ST) oncology specialists.
Authors: David Hui, Swati Bansal, Minjeong Park, Akhila Sunkepally Reddy, Jorge E. Cortes, Frank V. Fossella, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

9524 Background: Patients with Heme malignancies often receive intensive care at the end-of-life. To better understand the end of life decision making process among oncology specialists, we compared the cancer treatment recommendations, and attitudes and beliefs toward palliative care between Heme and ST specialists. Methods: We randomly surveyed 120 Heme and 120 ST oncology specialists at our institution. Respondents completed a survey examining two aspects of end of life care: palliative systemic therapy using standardized case vignettes and palliative care proficiency. We compared the two groups using the Wilcoxon rank sum tests and Chi-square tests, and conducted multivariate logistic regression to identify predictors of treatment preferences. Results: 182/240 (76%) clinicians responded. Compared to ST specialists, Heme specialists were significantly more likely to favor prescribing systemic therapy with moderate toxicity and no survival benefit for patients with ECOG performance status (PS) 4 and an expected survival of 1 month (P<0.0001, Table). This decision was highly polarized. Heme specialists felt less comfortable discussing death and dying (72% vs. 88%, P=0.007) and hospice referrals (81% vs. 93%, P=0.02), and were more likely to feel a sense of failure with disease progression (46% vs. 31%, P=0.04). They were also less likely to refer patients with newly diagnosed cancer (21% vs. 43%, P=0.002) to palliative care. On multivariate analysis, Heme specialty (odds ratio 2.77, P=0.002) and comfort level with prescribing treatment to ECOG 4 patients (odds ratio 3.79, P=0.02) were associated with the decision to treat in the last month of life. Conclusions: We found significant differences in the attitudes and beliefs toward end-of-life care between Heme and ST specialists, and identified opportunities to standardize end-of-life care. Treatment recommendations for case vignettes. Patients Heme* ST* P Expected survival 1 month, PS 4 4 (2, 6) 1 (1, 3) <0.0001 Expected survival 3 months, PS 3 4 (3, 6) 3 (2, 5) 0.0002 Expected survival 6 months, PS 2 5 (4, 6) 5 (4, 6) 0.18 *Median (IQR), where 1=strongly against treatment, 7=strongly favors treatment.
The Use of Plasmapheresis in Patients with Bronchiectasis with <i>Pseudomonas aeruginosa</i> Infection and Inhibitory Antibodies
Authors: Timothy J. Wells, John Davison, Emma Sheehan, Suren Kanagasundaram, Gavin Spickett, Calman A. MacLennan, Robert A. Stockley, Adam F. Cunningham, Ian R. Henderson, Anthony De Soyza
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Whole-body PET/MR in soft tissue sarcoma (STS) patients.
Authors: Stephan Richter, Ivan Platzek, Bettina Beuthien-Baumann, Joerg van den Hoff, Michael Laniado, Joerg Kotzerke, Frank Kroschinsky, Gerhard Ehninger, Markus Kajo Schuler
Journal: Journal of Clinical Oncology (2012)

10068 Background: PET/MR (positron emission tomography/magnetic resonance imaging) is a new whole-body hybrid imaging technique that combines metabolic and cross-sectional diagnostic imaging. To date the only available clinical data are drawn from feasibility studies in small series of head and neck cancers and intracranial tumors. Imaging by combined PET and computed tomography (PET/CT) has been investigated in STS for biopsy guidance, response assessment and grading. Methods: This exploratory analysis evaluated the outcomes of PET/MRI in 21 patients with STS in different treatment settings: (a) neoadjuvant setting, (b) metabolic-driven local therapy in metastatic sarcoma, and (c) palliative treatment. For examination we used an Ingenuity PET/MR system (Philips Healthcare). It combines a 3-Tesla MRI and a PET scanner with time-of-flight technology. Results: PET/MR shows a high contrast imaging without significant artifacts or distortions. (a) Four patients with high-risk sarcoma (3 rhabdo, 1 pleomorphic) completed the planned neoadjuvant therapy. Change in tumor size did not correlat with pathologic response, whereas surgical outcome was well predicted by metabolic changes. Due to this finding the preplanned course of chemotherapy for one patient was changed. (b) To prolong disease stabilization of 3 patients with a remnant metabolic activity in a single spot they underwent a surgical resection of a single metastatic lesion or had a local radiotherapeutic approach. (c) In 3 patients with stable disease after first-line treatment with combination of anthracyline and ifosfamide persisting metabolic activity indicated a switch to another alternative 2nd line regime. Trabectedin as 2nd line therapy decreased metabolic activity that finally resulted in a tumor regression. Conclusions: To our knowledge this is the first report on patients with STS examined with whole-body-PET/MR. PET/MR is feasible in STS and may provide valuable information in treatment, monitoring and prognosis of patients with STS. This technique may help to choose accurate and on-time treatment option without unnecessary time delay. Further prospective studies to evaluate PET/MR in STS are warranted.
Longitudinal changes in physical activity of head and neck squamous cell carcinoma patients.
Authors: Shruti Jolly, Lisa A Peterson, Laura S Rozek, Douglas Brian Chepeha, Mark E Prince, Scott A McLean, Brent Ward, Carol Rossier Bradford, Joseph Helman, Jeffrey Stanley, Francis Worden, Avraham Eisbruch, Gregory T. Wolf
Journal: Journal of Clinical Oncology (2013)

9607 Background: Head and neck cancer (HNCa) treatment results in unfavorable changes in physical function, body composition and quality of life. The ability of these patients to perform physical activity after cancer treatment has not been previously evaluated. To develop clinical models that will guide the care of HNCa survivors, it is important to characterize these physical activity changes. Methods: From 2008 to 2011, as part of an institutional Head and Neck SPORE longitudinal epidemiology project, health survey data including the Physical Activity Scale in the Elderly (PASE) was collected at baseline, 6 months and annually thereafter. The PASE score assesses the hours doing leisure time physical activity, walking, occupational, and household chores over a typical 7-day period. During follow up, subjects deceased, were lost to follow-up, or refused survey completion. Paired t-test was used to compare the mean PASE score at various endpoints from baseline. Results: 294 HNCa patients completed the survey at baseline. Following a mean follow-up of 25.7 (+/-11.9) months, 66%(n=193), 73%(n=215) and 42%(n=124) of patients completed the assessment at 6-months, 1-year and 2-years respectively. Majority (97%) of the HNCa patients had oropharynx, oral cavity or larynx cancer, which were treated by chemoradiation (36%), surgery followed by chemoradiation (23%) or surgery alone (20%). Results of the PASE score revealed the lowest levels of physical activity at baseline with steady statistically significant improvement at each subsequent timepoint (p&lt;0.05). Stratifying by treatment modality, the difference between baseline and 1-year PASE score was significant only for chemoradiation patients (p&lt;0.05). Conclusions: Baseline cancer burden appeared to have the most impact on physical activity levels in HNCa patients. In patients who completed the survey, the levels of physical activity improved longitudinally over time and are most notable for patients treated by chemoradiotherapy. Therefore, the most benefit of a physical activity intervention would be either during or immediately following treatment.
Melphalan and Prednisone (MP) Versus Melphalan, Prednisone and Thalidomide (MPT) as Initial Therapy for Previously Untreated Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials.
Authors: Prashant Kapoor, S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, David Dingli, Robert Kyle, Morie A. Gertz, Philip . R Greipp, Shaji Kumar, Sumithra J. Mandrekar
Journal: Blood (2009)
Phase II randomized study comparing concurrent chemoradiation versus neoadjuvant chemotherapy followed by chemoradiation in locally advanced unresectable squamous cell carcinoma of esophagus.
Authors: Pritee Baburao Chaudhari, Subhash Chander, B. K. Mohanti, Atul Sharma, Jaspreet Kaur, Sushmita Pathy, S. V. S. Deo
Journal: Journal of Clinical Oncology (2013)

e15138 Background: A significant number of patients diagnosed with esophageal cancer (EC) presents with locally advanced disease. Nonsurgical curative therapy for unresectable EC has limited outcome. Methods: Phase II randomized control trial to assess early locoregional response (LRR) to neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiation (CRT) versus definitive CRT in surgically unresectable squamous cell carcinoma of esophagus (ESCC). A total of 30 patients were randomly assigned to two arms. Arm 1: 2 cycles NACT regimen of 5-fluorouracil (750mg/m2 D1-4) and cisplatin (80mg D1-2) followed by CRT, radiation of 56Gy/ 28 Fr concurrent with weekly paclitaxel 50mg/m2 and carboplatin AUC2. Arm2: CRT; consisting of radiation 56Gy/28Fr and weekly paclitaxel 50mg/m2 and carboplatin AUC2. All the patients were followed till 6 months post treatment. LRR assessment was done at 1, 3 and 6 months post treatment. Wilcoxon multivariate analysis was carried out and difference of the factors were assessed by chi square test (x 2 p&lt;0.05). Results: Mean age in two arms were 52 and 54 years respectively. The study had median follow up of 6.6 months. Conclusions: In unresectable EC, CRT showed higher LRR, treatment completion and lesser toxicity compared to NACT combined with CRT. In this pilot cohort of locally advanced unresectable EC paclitaxel and carboplatin combined with radiotherapy has good tolerance and compliance. [Table: see text]