tbuckley/cabot-search huggingface dataset:
Extended linifanib therapy in patients with advanced solid tumors in a phase I trial.
Authors: B. C. Goh, C. Wong, J. Qian, E. McKeegan, J. L. Ricker, D. M. Carlson, R. A. Soo
Journal: Journal of Clinical Oncology (2010)

3053 Background: Linifanib (ABT-869) is an orally bioavailable, potent, selective VEGF and PDGF RTK inhibitor. Activity was observed in a phase I trial of patients (pts) with advanced solid tumors including PR in non-small cell lung cancer and colorectal cancer (CRC) and prolonged SD in many pts (JCO 2009;27:4718-26); an analysis of pts who continued on linifanib for >1 year is presented. Methods: Pts in this trial had solid tumors refractory to standard therapy or for which no standard therapy existed, ≥1 measurable lesion, ECOG 0-2, adequate bone marrow, renal, and hepatic function. Oral linifanib was dosed daily at 10 mg, 0.1, 0.25, and 0.3 mg/kg. Assessments included tumor response and disease progression (RECIST); target lesions: best % change from baseline in SLD; adverse events (AEs) per NCI CTCAE v3.0. Results: Of the 33 pts treated, 4 received linifanib for >12 m: 1 each with alveolar soft tissue sarcoma (47+ m), renal cell carcinoma (RCC; 31.1 m), CRC (19.9 m) and hepatocellular cancer (HCC; 15.6 m; Table). In these pts, common AEs were myalgia and fatigue, and grade 3 linifanib-related AEs included fatigue, abdominal pain, and palmar-plantar erythrodysesthesia. No cumulative toxicities were apparent with chronic dosing. These pts demonstrated changes in indirect vascular measurements (DCE-MRI Ktrans/CEC) or physiological response to VEGF inhibition (VEGF/PIGF/sFLT-1). Conclusions: In this phase I trial, linifanib monotherapy showed strong signals of activity including prolonged SD and confirmed PRs. In these 4 pts, chronic linifanib treatment provided prolonged clinical benefit. Pt cancer Sarcoma HCC CRC RCC Age, y 29 57 56 67 Gender F M M M Race Asian Asian Arab Asian Start dose, mg 10 10 26.9 (0.25 mg/kg) 14 (0.25 mg/kg) End dose, mg 7.5 10 15.5 5 Prior radiation Y N N N Prior systemic therapies •Number 2 2 6 0 •Best response to most recent PD PD SD — Best % change from baseline in SLD −6.9 −28.0 −17.0 −14.9 Biomarkers, day 15 •Ktrans decrease −35% −30% −42% −40% •CEC Remained low Normalized Remained low Normalized •VEGF increase N* Y Y Y •PIGF increase Y Y Y Y •sFLT-1 decrease Y Y Y Y Abbreviations: SLD, sum of longest diameter; CEC, circulating endothelial cells. * Yes at later time points. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
Graft Versus Leukemia Separates From Graft Versus Host Disease By Magnitude and Avidity Of The Allo-Reactive T Cell Response After Allogeneic Stem Cell Transplantation and Donor Lymphocyte Infusion
Authors: Cornelis A.M. van Bergen, Simone A.P. Van Luxemburg-Heijs, Matthijs Eefting, Maria W. Honders, Inge Jedema, Constantijn J.M. Halkes, Marieke Griffioen, J.H. Frederik Falkenburg
Journal: Blood (2013)
Is there an association between season of birth and blood <scp>DNA</scp> methylation in adulthood?
Authors: P‐A. Dugué, Y. M. Geurts, R. L. Milne, G. A. Lockett, H. Zhang, W. Karmaus, J. W. Holloway
Journal: Allergy (2016)

We recently reported the discovery of season of birth-associated DNA methylation, constituting a plausible molecular mechanism for the effect of season of birth on long-lasting outcomes such as allergic disease, for the first time (1).We write in response to the analysis of season of birthassociated DNA methylation by Dugué and colleagues, from which they conclude the set of season of birth-associated CpGs that we identified may include false positives.We value the contribution of Dugué et al. to the investigation of the hypothesis that epigenetic effects mediate
Relationship between neuroendocrine tumor-related symptoms and PROMIS health-related quality-of-life scores.
Authors: J. L. Beaumont, Z. Liu, S. Choi, J. C. Yao, A. T. Phan, D. Cella
Journal: Journal of Clinical Oncology (2010)

6109 Background: Neuroendocrine tumors (NETs) can secrete hormones that cause flushing and diarrhea (carcinoid syndrome) and disrupt health-related quality of life (HRQL). The objective of this study was to evaluate the relationship between severity of these symptoms and HRQL. Methods: NET patients were invited via email to participate in an online anonymous survey which consisted of demographics, disease-related questions and two standardized measures of HRQL (RAND-36 and PROMIS-29). PROMIS-29 scores were compared between groups defined by frequency of bowel movements and flushing episodes using analysis of variance. Score differences of 2.5-5.0 points are generally regarded as clinically meaningful. Lower scores on the physical function and social role scales of the PROMIS indicate worse HRQL. Higher scores on other scales indicate worse HRQL. Results: 663 patients participated. 66% were female; 39% were ≥60 years old. Among evaluable cases, 214/637 (34%) reported an average of ≥4 bowel movements per day; 323/608 (53%) had ≥ 1 flushing episode in the past 2 weeks. Patients who reported greater symptom severity had worse PROMIS scores (all p<.05). HRQL was decreased by >3 points in patients who had an average of ≥4 bowel movements per day. Patients reporting ≥ 1 flushing episode also demonstrated a meaningful reduction in HRQL (Table). Conclusions: Patients with more frequent bowel movements and flushing episodes report worse HRQL. Optimal management of carcinoid syndrome is needed to achieve best possible quality of life. Further analysis of treatment effect on HRQL is warranted. Mean (SD) PROMIS scores by symptom frequency* Average # bowel movements per day Total # flushing episodes past 2 weeks 0-3 (n = 423) 4+ (n = 214) 0 (n = 285) 1+ (n = 323) Physical function 46.8 (9.1) 41.7 (8.9) 47.9 (8.8) 42.7 (9.0) Anxiety 53.4 (8.7) 55.9 (8.8) 51.6 (8.1) 56.5 (8.8) Depression 50.6 (8.5) 53.8 (9.5) 48.8 (7.9) 54.1 (9.2) Fatigue 52.5 (10.5) 58.8 (9.2) 51.2 (10.1) 57.4 (10.2) Pain interference 50.4 (9.1) 55.7 (9.5) 49.1 (8.3) 54.9 (9.9) Sleep disturbance 50.9 (9.2) 55.0 (8.8) 49.2 (9.0) 54.9 (8.9) Social role 48.3 (10.7) 42.6 (9.8) 49.2 (10.4) 43.9 (10.3) * Scores for U.S. general population normalized to 50. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
A phase I study of XL228, a multitargeted protein kinase inhibitor, in patients (pts) with solid tumors or multiple myeloma.
Authors: D. C. Smith, C. Britten, E. B. Garon, G. Vlahovic, R. Chugh, M. A. Lee, B. Cancilla, D. O. Clary, S. C. Robertson, H. Hurwitz
Journal: Journal of Clinical Oncology (2010)

3105 Background: XL228 is a multitargeted protein kinase inhibitor targeting IGF1R, the AURORA kinases, FGFR1-3, ABL, ALK, and SRC family kinases. The previously established maximum tolerated dose (MTD) level has been expanded to enroll pts with solid tumors, lung cancer, colon cancer, or multiple myeloma. Methods: XL228 is administered as weekly 1-hr IV infusions at the MTD of 6.5 mg/kg. MTD expansion cohorts are being evaluated for safety, preliminary efficacy, pharmacokinetics, and pharmacodynamic effects. Response in pts with solid tumors is assessed by RECIST or the International Myeloma Working Group Uniform Response Criteria for multiple myeloma pts. Results: The dose escalation phase is complete, with 41 pts treated with XL228 at dose levels ranging from 0.45 to 8.0 mg/kg. The dose limiting toxicity was Grade 3 and 4 neutropenia occurring at the 8.0 mg/kg dose level. The rate of stable disease (SD) for ≥ 12 weeks or partial response (1 confirmed: NSCLC) in the escalation phase was 32%. The SD duration ranged from 12.3 - 58.3 weeks. Twenty-two additional pts enrolled in the MTD expansion cohorts are evaluable for response, 41% of whom have experienced SD of ≥ 12 weeks (range 14.0 - 29.1+ weeks), including 5 of 9 (56%) NSCLC pts. Drug-related adverse events (AEs) in ≥ 15% of all pts include hyperglycemia, neutropenia, nausea, dysgeusia, hypotension, and fatigue. The majority of these events were Grade 1 or 2. Grade 3 or 4 drug-related AEs in ≥ 5% of pts include neutropenia and hyperglycemia. Serious events of Grade 2 or 3 hypotension (n=4), Grade 2 bradycardia (n=2), and Grade 4 AV block (n=1) during or post infusion have occurred in 5 pts. Pharmacodynamic assessment of matched pre- and post-dose tumor biopsies has demonstrated decreases in phosphorylation of IGF1R, FGFR, and AKT for up to 24 hours. In a pt with melanoma, enlargement of tumor nuclei (average nuclear area increase of 30%) suggests Aurora B inhibition and endoreduplication. Conclusions: XL228 has a manageable toxicity profile and has demonstrated biological activity through decreases in target pathway phosphorylation and alterations in tumor nuclei. XL228 has shown encouraging preliminary activity in heavily pre-treated pts dosed at the MTD. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Exelixis Exelixis
Association of NaF PET/CT findings with PSA and alkaline phosphatase in untreated castration-sensitive prostate cancer.
Authors: Anna Couvillon, Baris Turkbey, Maria Liza Lindenberg, Peter L. Choyke, Mirna Martinez, Yolanda McKinney, Aradhana Kaushal, Deborah E. Citrin, Andra Krauze, Deborah McNally, Luz Giordano, Guinevere Chun, Cheryl Royce, Hui Han, Fatima Karzai, Howard L. Parnes, Peter A. Pinto, James L. Gulley, William L. Dahut, Ravi Amrit Madan
Journal: Journal of Clinical Oncology (2015)

122 Background: NaF PET/CT is an emerging imaging technique with potentially high sensitivity in detecting bone metastasis (mets), however, its role in castration-‐sensitive prostate cancer (CSPC) is undefined and it remains unclear which CSPC patients should have NaF PET/CT. Methods: We retrospectively reviewed NaF PET/CT scans done on 45 patients with untreated, high risk CSPC with the goal of determining which disease features were associated with positive findings. Two blinded radiologists reviewed each scan and determined by consensus if findings were negative for metastasis (0% liklihood of mets), possible (50%), probable (75%), or consistent with mets (90%). Prostate specific antigen (PSA) and alkaline phosphatase (AP) values were then evaluated at time of NaF scan when available. Results: Of the 45 patients 2 were Gleason 6, 5 were Gleason 7, 36 were Gleason 8 to 10, 2 unknown. When grouped by findings on NaF PET/CT, there were no substantial differences seen between median PSA or AP values. When patients with both PSA and AP values &gt; median were evaluated, there was no clear association with NaF PET/CT findings. Conclusions: Preliminary findings from this small retrospective analysis suggest that there may be limited associations between PSA and/or AP with findings on NaF PET/CT scan in untreated patients with CSPC. Further analysis in larger cohorts of pts is required. [Table: see text]
Abstract P3-01-01: Insulin, Insulin-like Growth Factor-1 and cycling estrogen predict premenopausal mammographic density.
Authors: H Frydenberg, VG Flote, A Iversen, SE Finstad, A-S Furberg, M Fagerland, EA Wist, E Schlichting, PT Ellison, A McTiernan, G Ursin, I Thune
Journal: Cancer Research (2012)

Abstract Background: Mammographic density, a strong biomarker for breast cancer risk, represents epithelial and stromal proliferation. Insulin and insulin-like growth factor (IGF)-1 are suggested to influence cellular proliferation, while estrogen is a key factor in breast cancer development. However, whether the effects of these hormones among premenopausal women are mediated through mammographic density is less known. Material and Methods: Fasting serum insulin, IGF-1, and IGF binding protein (IGFBP)-3 were assessed among 202 healthy premenopausal women (Norwegian Energy Balance and Breast cancer Aspects study-I (EBBA-I). Daily salivary levels of 17β-estradiol throughout an entire menstrual cycle were measured at the reproductive Ecology Laboratory, Harvard University, USA. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms taken at day 7–12 of the menstrual cycle. Uni- and multivariable regression models were used to study the associations between hormones and premenopausal percent mammographic density. Results: Among women with a mean age of 30,7 years, a mean premenopausal percent mammographic density of 29.8 % was observed. Throughout the menstrual cycle when comparing women with a high percent mammographic density (≥28.5%) to women with a low percent mammographic density (&amp;lt;28.5%), we observed insulin, IGF-1 and IGFBP-3 independently and in combination with cycling 17β-estradiol to predict premenopausal percent mammographic density. We observed among women with either serum insulin ≥89 pmol/, IGF-1 ≥24 nmol/l, IGFBP-3 ≥ 100 nmol/l, having a high (≥28.5%) versus a low (&amp;lt;28.5%) percent mammographic density was associated with an increase in overall average 17β-estradiol of 4.0 %, 10.9 % and 14.9%, respectively. Moreover, we observed a higher adjusted Odds Ratio (OR) for having a high percent mammographic density for each standard deviation (SD) increase in overall average 17β -estradiol, insulin, IGF-1 and IGFBP-3: 17β-estradiol, 1.55 (1.06–2.27); insulin, 1.62 (0.76–3.48), IGF-1, 1.90 (1.10–3.27); IGFBP-3, 1.88 (1.05–3.37) (adjusted for age, body mass index-BMI kg/m2)). Conclusion: Our study supports that insulin, IGF-1 and IGFBP-3 independently, and in combination with cycling estrogen, predicts premenopausal mammographic density. These hormones may be important biomarkers in breast cancer control and clinical practice. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-01.
Abstract 15042: The First Clinical Use of Fractional Flow Reserve Derived From Coronary CT Angiography (FFR-CT) in the ‘Real World’ Predicts Standard of Care Guided Revascularization
Authors: Rene R Packard, Rine Nakanishi, Alexandra Lajoie, Matthew J Buddoff, Ronald P Karlsberg
Journal: Circulation (2015)

Introduction: Fractional flow reserve computed tomography (FFR-CT), approved by the FDA in November 2014, provides functional assessment of anatomic severity and blood flow in the coronary arteries without changes in acquisition, medication, contrast or radiation, with an area under the receiver-operating characteristic curve of 0.90 compared to invasive FFR. We obtained FFR-CT in the largest group of patients in the United States post-FDA release and applied this measure to patients who had previously undergone invasive coronary angiography after baseline Coronary CTA. Hypothesis: To determine whether FFR-CT predicts subsequent coronary revascularization in patients who underwent Coronary CTA prior to invasive angiography and were treated with standard of care in a large urban Cardiology practice. Methods: Consecutive patients who underwent Coronary CTA followed by invasive angiography over a 12-month period from 2012-2013 were identified. Studies that did not fit inclusion criteria (e.g. prior revascularization, motion artifact, severe calcification) were excluded. The remaining studies (n=61) were sent for FFR-CT analysis and patients who received stents (n=15) were identified. FFR-CT values were compared in territories that were stented (n=15) with those that were not (n=163). Baseline FFR-CT values were obtained retrospectively, and therefore results did not interfere with clinical decision-making. Results: In territories that were not intervened upon, baseline FFR-CT values had a median of 0.87, with 75% of territories displaying an FFR-CT &gt; 0.80. In territories that underwent PCI, baseline FFR-CT values were all &lt; 0.75, with a median of 0.65 (P&lt;0.0001 PCI vs. no stent). Of 18 patients with an FFR-CT &lt; 0.70; 11 underwent PCI, 2 had chronic total occlusions and the remaining 5 pursued aggressive medical management based on clinical judgment. Conclusions: We established baseline FFR-CT values in patients who underwent PCI in the real world outside of a research protocol. The role of FFR-CT in clinical decision-making and to determine the need for revascularization requires prospective trials; however FFR-CT determined prior to invasive coronary angiography accurately predicts subsequent revascularization in clinical practice.
P2-077: Prediction of distant relapse risk in stage I-II NSCLC by gene expression profiling
Authors: Jacek Jassem, Michal Jarzab, Jacek Niklinski, Malgorzata Kowalska, Malgorzata Oczko, Witold Rzyman, Grazyna Kobierska-Gulida, Lech Chyczewski, Marcin Skrzypski, Barbara Jarzab
Journal: Journal of Thoracic Oncology (2007)
Case 10-1974
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Gordon S. Myers, James B. Caulfield
Journal: New England Journal of Medicine (1974)

Presentation of CaseAn 86-year-old woman was admitted to the hospital because of dyspnea.Twenty-seven years previously a basal blowing systolic murmur was heard. Eleven years before admission a calcified coin lesion in the upper lobe of the right lung was demonstrated on an x-ray film of the chest. Isoniazid was taken sporadically; no change in the lesion was seen. Six years before entry the patient came to the hospital because of weight loss. A Grade 2 systolic murmur was heard and was maximal at the lower left sternal border. An x-ray film of the chest (Fig. 1) showed cardiac . . .
P3-214: Caspase-3 and c-myc expression in completely resected non-small cell lung cancer and its prognostic significance.
Authors: Deog Gon Cho, Kyu Do Cho, Chul Ung Kang, Byoung Yong Shim, Chi Hong Kim, Sung Whan Kim, Meyung Im Ahn, So Hyang Song, Jinyoung Yoo, Hoon-Kyo Kim
Journal: Journal of Thoracic Oncology (2007)
Chromosomal gains and losses in marginal zone B-cell lymphoma detected by comparative genomic hybridization
Authors: J Dierlamm, C Rosenberg, M Stul, S Pittaluga, L Michaux, Iwona Wlodarska, Gregor Verhoef, José Thomas, M Janssen, T Bakker-Schut, W Zeller, Jean-Jacques Cassiman, A Raap, C De Wolf-Peeters, Herman Van den Berghe, Anne Hagemeijer-Hausman
Journal: Blood (1996)
Outcomes of Patients with Acute Coronary Syndromes and Non-obstructive Coronary Artery Disease: Analysis from the Randomized ACUITY Trial
Authors: Eugenia Nikolsky, Alexandra Lansky, Roxana Mehran, Adriano Caixeta, George D Dangas, Iulian Benetato Giuran, Walter Desmet, Gregg W Stone
Journal: Journal of the American College of Cardiology (2009)
Preliminary Comparison of Capsule Endoscopy and Double-Balloon Enteroscopy in Patients with Suspected Small-Bowel Bleeding
Authors: M. Nakamura, Y. Niwa, N. Ohmiya, R. Miyahara, A. Ohashi, A. Itoh, Y. Hirooka, H. Goto
Journal: Endoscopy (2006)

Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have been introduced as modalities for examining the entire small bowel. The aim of the present study was to assess the clinical effects of CE and DBE to consider the roles of CE and DBE and the indications for the procedures in patients with suspected small-bowel bleeding.Between June 2004 and January 2005, 32 patients in whom a site of bleeding in the gastrointestinal tract had not been identified were enrolled in the study. Twenty-eight patients were examined with both methods. Bleeding sources were categorized as either A1 lesions (immediate hemostatic procedures required) or A2 lesions (close observation required). CE and DBE were evaluated with regard to whether or not they were capable of accessing the entire small bowel and provided a diagnosis, and the access and diagnostic rates were calculated.On CE, 13 patients were diagnosed with A1 lesions and six with A2 lesions; on DBE, 11 had A1 lesions and one had an A2 lesion. The access rate for the entire small intestine on CE was 90.6 % (29 of 32), significantly higher than with DBE at 62.5 % (10 of 16; P < 0.05). The diagnostic rate on CE was 59.4 % (19 of 32), higher than with DBE at 42.9 % (12 of 28; P = 0.30), but not significantly different. Among patients with A1 lesions who were diagnosed with DBE, histological diagnoses were obtained in six of the 11, and three patients were treated.In many suspected small-bowel bleeding cases, CE should be selected for the initial diagnosis and DBE for treatment or histopathological diagnosis after detection of the bleeding site on CE.
P3-089: Gefitinib (G) treatment outcome after progression on erlotinib (E) in patients with advanced non-small-cell lung cancer (NSCLC)
Authors: Francesco Grossi, Carlotta Defferrari, Annalisa Brianti, Maura Loprevite, Gianluca Catania, Maria Giovanna Dal Bello, Paolo Pronzato
Journal: Journal of Thoracic Oncology (2007)
Trial Reporting in ClinicalTrials.gov — The Final Rule
Authors: Deborah A. Zarin, Tony Tse, Rebecca J. Williams, Sarah Carr
Journal: New England Journal of Medicine (2016)

B) an amount equal to the modified workload adjustment factor for fiscal year 2007 (as determined under paragraph (3)).''(2) TYPES OF FEES.-Of the total revenue amount determined for a fiscal year under paragraph (1)-''(A) one-third shall be derived from fees under subsection (a)(1) (relating to human drug applications and supplements); ''(B) one-third shall be derived from fees under subsection (a)(2) (relating to prescription drug establishments); and ''(C) one-third shall be derived from fees under subsection (a)(3) (relating to prescription drug products).''(3) MODIFIED WORKLOAD ADJUSTMENT FACTOR FOR FISCAL YEAR 2007.-Forpurposes of paragraph (1)(B), the Secretary shall determine the modified workload adjustment factor by determining the dollar amount that results from applying the methodology that was in effect under subsection (c)(2) for fiscal year 2007 to the amount $354,893,000, except that, with respect to the portion of such determination that is based on the change in the total number of commercial investigational new drug applications, the Secretary shall count the number of such applications that were active during the most recent 12month period for which data on such submissions is available.''( 4) ADDITIONAL FEE REVENUES FOR DRUG SAFETY.-''(A)IN GENERAL.-For each of the fiscal years 2008 through 2012, paragraph (1)(A) shall be applied by substituting the amount determined under subparagraph (B) for '$392,783,000'.''(B) AMOUNT DETERMINED.-For each of the fiscal years 2008 through 2012, the amount determined under this subparagraph is the sum of-''(i) $392,783,000; plus ''(ii)(I) for fiscal year 2008, $25,000,000; ''(II) for fiscal year 2009, $35,000,000; ''(III) for fiscal year 2010, $45,000,000; ''(IV) for fiscal year 2011, $55,000,000; and ''(V) for fiscal year 2012, $65,000,000.''.(c) ADJUSTMENTS TO FEES.-(1)INFLATION ADJUSTMENT.-Section 736(c)(1) (21 U.S.C. 379h(c)(1)) is amended-(A) in the matter preceding subparagraph (A), by striking ''The revenues established in subsection (b)'' and inserting ''For fiscal year 2009 and subsequent fiscal years, the revenues established in subsection (b)''; (B) in subparagraph (A), by striking ''or'' at the end; (C) in subparagraph (B), by striking the period at the end and inserting '', or''; (D) by inserting after subparagraph (B) the following: ''(C) the average annual change in the cost, per fulltime equivalent position of the Food and Drug Administration, of all personnel compensation and benefits paid with respect to such positions for the first 5 years of the preceding 6 fiscal years.'';and (E) in the matter following subparagraph (C) (as added by subparagraph (D)), by striking ''fiscal year 2003'' and inserting ''fiscal year 2008''.Applicability.