tbuckley/cabot-search huggingface dataset:
Abstract 18425: Total Aortic Volume as a Predictor of Aortic Complications in Marfan Syndrome
Authors: Alexander den Hartog, Romy Franken, Aeilco Zwinderman, Henk Marquering, Barbara Mulder, Maarten Groenink
Journal: Circulation (2012)

Background: Mortality and morbidity in Marfan syndrome, an autosomal dominant systemic connective tissue disorder, is mainly determined by aortic complications (development of aortic aneurysm and subsequent dissection). Dissection of the descending aorta usually occurs at relatively normal aortic diameters and is therefore difficult to predict. The aim of this study was to assess total aortic volume as a predictor for aortic complications in Marfan syndrome. Methods: In 96 adult MFS patients a Gadolinium enhanced 3D MRI of the aorta was performed. Total aortic volume (aortic valve - aortic bifurcation) measurement was performed with 3D vessel analysis software (3mensio vascular, 3mensio medical imaging BV, Bilthoven, the Netherlands). Aortic complications (aortic dissection and aortic surgery) during 3 years follow-up were collected from patients’ medical charts. Results: In the Marfan patients (68 % male), 22% with a history of prophylactic aortic root repair, mean age 36 ± 12 years , mean body surface area (BSA) 2.06 ± 0.24 m2) a mean aortic volume of 114 ± 25ml/m2 was calculated. Aortic complications during 3 year follow-up occurred in 17 Patients. Prophylactic aortic root replacement was performed in 13 patients (14%). Descending aortic dissection occurred in 4 patients, all after previous aortic root replacement and without aortic dilatation in the dissected parts. Mean aortic volume in patients who underwent aortic surgery during the follow-up was significantly higher as compared to the uncomplicated patients (127 ± 22 ml/m2 vs 107 ± 23 ml/m2 p = 0.006). Mean aortic volume in patients with descending aortic dissection was significantly higher as compared to the uncomplicated patients (138 ± 32 ml/m2 vs 107 ± 23 ml/m2 p = 0.012). Regression analysis revealed that total aortic volume corrected for BSA may serve as a predictor for aortic root replacement and as a predictor for descending aortic dissection (OR 1.034 95 % CI 1.008 - 1.061 p = 0,011 and OR 1.042 95 % CI 1.004 - 1. 081 p= 0.028 respectively). Conclusion: Aortic volumes may predict aortic events in Marfan syndrome.
A Novel High Dose Chemotherapy Strategy with Bendamustine In Adjunct to Etoposide, Cytarabine and Melphalan (BeEAM) Followed by Autologous Stem Cell Rescue Is Safe and Highly Effective for the Treatment of Resistant/Relapsed Lymphoma Patients: a Phase I-II Study on 44 Patients
Authors: Giuseppe Visani, Lara Malerba, Pietro Maria Stefani, Saveria Capria, Piero Galieni, Francesco Gaudio, Giorgina Specchia, Giovanna Meloni, Filippo Gherlinzoni, Claudio Giardini, Sadia Falcioni, Federica Loscocco, Francesca Cuberli, Marco Gobbi, Armando Santoro, Barbara Sarina, Marco Rocchi, Alessandro Isidori
Journal: Blood (2010)
A Large-Scale Mutagenesis and Strain Characterization Project To Identify Genetic Variability in Mice: Resources Available from the Jackson Laboratory Program for Genomic Applications (JAX PGA).
Authors: Luanne L. Peters, Orah S. Platt, Karen L. Svenson, Beverly J. Paigen, Gary A. Churchill, Carl J. Bult, Phyllis A. Magnani, Heather R. Ellis, Molly A. Bogue
Journal: Blood (2004)
Antileukemic Efficacy of Continuous Vs Discontinuous Dexamethasone in Murine Xenografts of Acute Lymphoblastic Leukemia
Authors: Laura B. Ramsey, Laura Janke, Monique A. Payton, Xiangjun Cai, Sima Jeha, Ching-Hon Pui, William E. Evans, Mary V. Relling
Journal: Blood (2014)
Novel Assay for Ex Vivo Evaluation of Antiproliferative Effect of Hypomethylating Agents 5-Azacytidine and Decitabine in AML Patient Samples
Authors: Pilar Hernandez, Pau Montesinos, Josefina Serrano, Pilar Herrera, Juan Pedro Bergua, Mercedes Colorado, Bernando J Gonzalez, Cristina Gomez, Alicia Robles, Julian Gorrochategui, Jesus Sanchez, Joan Ballesteros, Federico Moscardo, David Martinez, Miguel Angel Sanz, Jaime Pérez de Oteyza, Joaquin Martinez
Journal: Blood (2014)
Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis
Authors: Aoife Kerrin, Paul Fitch, Claire Errington, Dennis Kerr, Liz Waxman, Kay Riding, Jon McCormack, Felicity Mehendele, Henry McSorley, Karen MacKenzie, Sabine Wronski, Armin Braun, Richard Levin, Ulf Theilen, Jürgen Schwarze
Journal: Thorax (2016)

The pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in infants remains poorly understood. Mouse models implicate pulmonary T cells in the development of RSV disease. T cell responses are initiated by dendritic cells (DCs), which accumulate in lungs of RSV-infected mice. In infants with RSV bronchiolitis, previous reports have shown that DCs are mobilised to the nasal mucosa, but data on lower airway DC responses are lacking.To determine the presence and phenotype of DCs and associated immune cells in bronchoalveolar lavage (BAL) and peripheral blood samples from infants with RSV bronchiolitis.Infants intubated and ventilated due to severe RSV bronchiolitis or for planned surgery (controls with healthy lungs) underwent non-bronchoscopic BAL. Immune cells in BAL and blood samples were characterised by flow cytometry and cytokines measured by Human V-Plex Pro-inflammatory Panel 1 MSD kit.In RSV cases, BAL conventional DCs (cDCs), NK T cells, NK cells and pro-inflammatory cytokines accumulated, plasmacytoid DCs (pDCs) and T cells were present, and blood cDCs increased activation marker expression. When stratifying RSV cases by risk group, preterm and older (≥4 months) infants had fewer BAL pDCs than term born and younger (<4 months) infants, respectively.cDCs accumulate in the lower airways during RSV bronchiolitis, are activated systemically and may, through activation of T cells, NK T cells and NK cells, contribute to RSV-induced inflammation and disease. In addition, the small population of airway pDCs in preterm and older infants may reveal a distinct endotype of RSV bronchiolitis with weak antiviral pDC responses.
A phase II, multicenter, open-label, single-arm trial of famitinib in patients with advanced recurrent and/or metastatic nasopharyngeal carcinoma (NPC) after two previous treatment regimens.
Authors: Yan Huang, Li Zhang, Jian-ji Pan, Guoqing Hu, Wu Gang, Jian ping Xiong, Chaosu Hu, Lizhu Lin, Hao Yu, Haoyuan Jiang
Journal: Journal of Clinical Oncology (2013)

6026 Background: Famitinib is an oral, small molecular multiple tyrosine-kinase inhibitor (TKI), targeting stem cell growth factor receptor (c-Kit), platelet derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR). So far, few target therapies show acceptable efficiency in advanced recurrent and/or metastatic nasopharyngeal carcinoma (RM-NPC) patients. The primary object of this study is to determine the safety and efficacy of famitinib in patients with RM-NPC. Methods: This study recruited histologically diagnosed RM-NPC patients who failed more than two lines of systemic chemotherapy. Other eligible criteria included ECOG PS≤2, adequate organ function and no prior exposure to other c-Kit, PDGFR or VEGFR TKIs. The patients received famitinib orally at a dose of 25 mg once daily until the disease progression or intolerable toxicity. Results: From May 2011 to Sep 2012, 58 patients (Simon’s two-stage design, 28+30) were recruited at 8 sites in China. The clinical benefit rate (partial response or stable disease maintained≥12 weeks, tumor response was evaluated every 4 weeks) is 32.8%, including 5 PR and 16 SD patients. Median PFS was 3.2 months. The most frequently observed hematologic toxicities included thrombocytopenia, leucopenia and neutropenia; non-hematologic AEs were hypertension, proteinuria, and hand-foot syndrome. All adverse events were generally mild-to-moderate (grade 1/2) and manageable with supportive treatment; grade 3/4 incidence was relatively low. Conclusions: This phase II study shows that famitinib demonstrates substantial clinical benefits in patients with advanced RM-NPC and the drug-related adverse reactions were most predictable and tolerable, no special toxicity was reported. Biomarker analysis for responder and non-responder is still ongoing and will be present at the meeting. Clinical trial information: NCT01392235.
Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Relapsing after Autologous Stem Cell Transplantation (ASCT): An Analysis of Patients Included in the Coral Study
Authors: Eric Van Den Neste, Norbert Schmitz, Nicolas Mounier, Devinder Gill, Marek Trneny, Noel Milpied, John A. Radford, Nicolas Ketterer, Ofer Shpilberg, Ulrich Dührsen, David Ma, Josette Briere, Catherine Thieblemont, Gilles A. Salles, Craig Moskowitz, Bertran Glass, Christian Gisselbrecht
Journal: Blood (2015)
Sublobar resection with I-125 brachytherapy for early-stage non-small cell lung cancer (NSCLC) using prefabricated mesh
Authors: M. A. Manning, M. Mohamed, D. P. Burney
Journal: Journal of Clinical Oncology (2009)

7586 Background: Lobectomy is standard of care for stage I NSCLC, but it reduces pulmonary reserve. Patients with pulmonary dysfunction may tolerate curative wedge resection with a permanent I-125 mesh implant. We report results using this technique with and without a novel prefabricated mesh device. Methods: Between 7/06 and 5/08, 56 patients with clinical stage I NSCLC had wedge resection and brachytherapy. All had PET-CT staging and were ineligible for lobectomy. Median age was 72 (48–87) and median FEV-1 was 1.3 liters (0.6–3.4 liters). At surgery, a significant proportion were upstaged. Pathologic staging confirmed 60.7% to be stage IA and 23.2% stage IB. Others were IIA (3.6%), IIB (5.4%), IIIA (1.8%), IIIB (1.8%), and IV (3.6%). All implants consisted of absorbable polyglactin mesh containing a median of 40 (30–50) I-125 seeds with a median seed activity of 0.536 mCi (0.47 - 0.63 mCi). Half of the patients received mesh prepared intraoperatively, while the second half received patient-specific prefabricated mesh (BrachyMESH - Oncura). Results: The median hospital stay was 5 days. All were immediately extubated. Common toxicities included air leak delaying chest tube removal, leukocytosis, paroxysmal atrial fibrillation, and increased secretions. Two required repeat chest tube placement for subsequent pneumothorax. Two patients with severe pre-op pulmonary dysfunction (pre-op FEV-1 of 0.6 and 0.68 liters) experienced respiratory failure and expired following prolonged hospital stays. With a median follow-up of 7 months (0–23 months), overall survival is 87.5% and disease free survival is 89%. The local control was 96.4% with the intraoperative mesh and 100% with the prefabricated mesh. Conclusions: Wedge resection with permanent I-125 mesh implant is a generally well-tolerated procedure leading to acceptable early local control in patients ineligible for lobectomy. This technique may not be suitable for patients with pre-op FEV-1 &lt; 0.7 liters; but, it provides accurate surgical staging conferring a diagnostic advantage over non-invasive treatment modalities. The prefabricated device offers similar results to manually prepared devices. No significant financial relationships to disclose.
Randomized phase II trial of preoperative lapatinib versus placebo in HER2-positive breast cancer.
Authors: A. De Censi, M. Puntoni, G. Pruneri, A. Guerrieri-Gonzaga, M. Cazzaniga, H. A. Johansson, O. Pala, G. Pagani, M. Marrè Brunenghi, B. Bonanni
Journal: Journal of Clinical Oncology (2010)

576 Background: Ki67 labeling index (LI) after short-term neoadjuvant treatment of breast cancer has prognostic significance (e.g., 5% increased risk of relapse per unit increase of Ki67) and is used to test therapeutic and preventive activity of candidate drugs. Methods: We conducted a randomized, monoinstitutional, phase II, window-of opportunity trial of lapatinib (L), administered for 3 weeks prior to surgery at 1,500 mg/day or matching placebo (P) in women with treatment-naïve T1-2, N0-1, HER2+ve breast cancer (IHC 3+ and/or FISH+). With 60 subjects, the study had 80% power to detect a 35% reduction of tumor Ki67 LI (primary endpoint) on L vs P, assuming a 50% SD of the change. Results: From November 3, 2006 to May 13, 2009, we randomly assigned 29 subjects to L and 31 subjects to P for 20.9 ± 0.7 days. Main characteristics (L vs. P): median age (range), 52 (35-77) vs. 53 (23-73); premenopause, 55% vs. 52%; US tumor diameter (mm), 18.5 (1-26) vs. 19 (9-42); N0, 59% vs 68%; ER+ tumor, 31% vs. 42%; PgR+, 55% vs. 42%; median pTEN score (I*% immunoreactivity), 90 (10-180) vs. 60 (5-180). The mean ± SD % change of Ki67 after 3 weeks was -9.3% ± 34.2 on L and +15.1% ± 30.9 on P (p = 0.007), with a mean % reduction of 20.9% (95% CI, 5.6-36.1) in the L arm relative to P, adjusting for baseline Ki67. The Ki67 reduction was greater in ER/PgR– vs. ER/PgR+ tumors:-33% vs. -9%, and in high (> 60) vs. low pTEN tumors: -22% vs. -7.8%. In the surgical specimens, median Ki67 in ductal intraepithelial neoplasia (DIN) was 15% (5-35) on L vs. 20% (5-60) on P (p = 0.06), and 1% (1-7) on L vs. 3% (1-5) on P in ductal hyperplasia (p = 0.006). Tumor downstaging was significant, the median surgical tumor diameter being 18 mm (11-57) on L vs. 24 mm (10-37) on P (p = 0.009). Median circulating HER2 levels (ng/mL) increased significantly on L vs. P: 11.4 (6.6-20.5) vs. 9.0 (6.3-26.8) (p = 0.001). Grade 1-2 diarrhea (59% vs. 13%) and skin alterations (62% vs. 10%) were more frequent on L vs. P. Conclusions: Lapatinib given for 3 weeks prior to surgery can decrease malignant, dysplastic and hyperplastic cell proliferation and favourably affect tumor size in HER2+ve breast cancer, providing the rationale for its testing as an adjuvant treatment for a variety of HER2+ve neoplasms, including DIN, T1a and focally amplified/overexpressed tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Early safety findings from a phase III trial of capecitabine plus oxaliplatin (XELOX) vs. bolus 5-FU/LV as adjuvant therapy for patients (pts) with stage III colon cancer
Authors: H. J. Schmoll, J. Tabernero, M. Nowacki, J. Maroun, A. Figer, T. Price, R. Lim, E. van Cutsem, D. Haller, F. Braud
Journal: Journal of Clinical Oncology (2005)

3523 Background: In a large phase III study (X-ACT) in stage III colon cancer, adjuvant capecitabine was at least equivalent to bolus 5-FU/LV for disease-free survival (DFS). In the MOSAIC trial, oxaliplatin + 5-FU/LV (FOLFOX4) resulted in superior DFS compared to 5-FU/LV, and has recently been approved for adjuvant therapy. As in metastatic colorectal cancer, capecitabine should be considered as an alternative to i.v. 5-FU in combination with oxaliplatin in the adjuvant setting. Therefore, we compared the safety and efficacy of XELOX to bolus 5-FU/LV (the standard regimen at the start of the study) as adjuvant therapy for stage III colon cancer. Methods: Pts with resected stage III colon cancer received XELOX (capecitabine 1000mg/m2 bid d1–14 + oxaliplatin 130mg/m2 d1, q3w x8) or i.v. bolus 5-FU/LV (Mayo Clinic, LV 20mg/m2 + 5-FU 425mg/m2 d1–5, q4w x6; or Roswell Park [RP], LV 500mg/m2 + 5-FU 500mg/m2 d1, w1–6 in 8w cycles x4). Results: 1719 of the 1886 pts randomized between Apr03 and Sep04 are evaluable for safety. Treatment arms were well balanced: median age (years, range), XELOX (59.7, 22–83), 5-FU/LV (60.6, 24–82); gender (% M/F), XELOX (55/45), 5-FU/LV (52/48); nodal status (% N1/N2), XELOX (65/35), 5-FU/LV (64/36). Grade 3/4 adverse events (AEs) were 39.3%/5.9% (XELOX) and 33.2%/8.9% (5-FU/LV). The table shows the most common treatment-related grade 3/4 AEs. 60-day all cause/treatment-related mortality within 28 days from last dose were 0.9%/0.6% for XELOX and 1.1%/0.6% for 5-FU/LV. Conclusions: Early safety data from the largest population of pts treated with XELOX indicate that XELOX causes less myelosuppression and stomatitis, but more skin and neurosensory toxicity than 5-FU/LV, and compares favorably with FOLFOX4. XELOX has now been incorporated in the 3-arm AVANT adjuvant trial (FOLFOX4 vs. FOLFOX4 + bevacizumab vs. XELOX + bevacizumab). Gr 3/4 AEs (%) 5FU/LV total (n=838) Mayo (n=591) RP (n=237) XELOX(n=881) FOLFOX*(n=1108) Diarrhea 17.1 13.5 26.2 15.6 11.8 Stomatitis 7.9 11.2 0 0.6 2.7 Nausea 3.9 2.2 8.4 4.1 5.1 Vomiting 2.5 1.7 4.6 5.0 5.8 Neurosensory 0 0 0 8.1 12.4 HFS 0.2 0.2 0.4 3.6 2.0 Neutropenia 10.9 14.0 3.0 5.3 41.1 Febrile neutropenia 3.8 4.7 1.7 0.2 1.8 * MOSAIC trial (André T, et al. N Engl J Med 2004;350:2343–51). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis AstraZeneca, Roche, Sanofi, sanofi-aventis Roche AstraZeneca, Aventis, Lilly Oncology, Novartis, Roche, sanofi-aventis AstraZeneca, Roche
Patient activation measures, distress levels, and causes of distress in chronic lymphocytic leukemia.
Authors: Karina I. Halilova, Emily Van Laar, Uma Borate, Bradford E. Jackson, Maria Pisu, Pamela M. Peters, Thomas Wayne Butler, Randall S. Davis, Amitkumar Mehta, Aras Acemgil, Sara J. Knight, Monika M. Safford, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2016)

201 Background: Patients with chronic lymphocytic leukemia (CLL) reporting high levels of distress due to knowledge gaps and emotional concerns can have negative outcomes and suffer from lower quality of life. Understanding patients’ activation levels, causes of distress, knowledge gaps, and psychosocial needs are crucial in high quality care. Optimally activated, educated and empowered patients are better positioned to communicate effectively with providers regarding selection of, and adherence to, CLL treatment protocols and long-term care plans, and potentially improving quality of life. Methods: We recruited 44 adults with CLL from the University of Alabama at Birmingham Health System Cancer Community Network from April to July of 2015 as part of an educational and quality improvement initiative. Patient-reported distress assessments were collected to evaluate distress levels and causes of distress. The Patient Activation Measure (PAM 13) was used to evaluate patient activation (1-4 scale with 4 maximally activated). Results: The median participant age was 69 years old (range 50-89 years). Thirty percent had completed ≤ 12 years of education, 20% had some college education. Thirty-nine percent were on active treatment, 59% were in observation; 2% were uncertain of treatment. Fifty seven percent of participants were maximally activated (level 4); 11% had an activation level of 3; 20% had a level of 2; and 11% had the lowest level of activation (level 1). Twenty-five percent reported moderate distress (≥ 4) and 5% reported severe distress (≥ 8); 34% reported distress due to psychosocial concerns and 25% due to knowledge gaps. Conclusions: This project demonstrates a need to improve patient activation levels and minimize patient distress related to knowledge gaps and psychosocial concerns related to CLL. Well-designed, easily accessible educational interventions and multi-level quality improvement programs may be helpful in improving patient engagement by providing necessary knowledge to improve patient-provider communication and optimize patient outcomes.
Capecitabine plus temozolomide (CAP-TEM) in patients with advanced neuroendocrine neoplasms (NEN): An Italian multicenter retrospective analysis.
Authors: Francesca Spada, Caterina Fumagalli, Lorenzo Antonuzzo, Luca Messerini, Davide Radice, Roberta Di Rocco, Salvatore Galdy, Viola Barucca, Eleonora PISA, Massimo Barberis, Francesco Di Costanzo, Nicola Fazio
Journal: Journal of Clinical Oncology (2014)

281 Background: A combination of capecitabine (CAP) and temozolomide (TEM) has been successfully used as first-line treatment in low-grade pancreatic neuroendocrine neoplasms (PNEN). We reviewed activity and toxicity of the same regimen in patients with advanced NEN with different primary and grading. Methods: Clinical data of patients who had received oral CAP 1500 mg/m2/day over 14 days bid plus oral TEM 150-200 mg/m2/day on days 10-14 of each 28-day cycle, were retrospectively reviewed. The methylenguanilmetiltransferase (MGMT) methylation-status (MGMT-gene &gt;5% = responders) and TS-polymorphisms (2R/2R, 2R/3R = responders, 3R/3R = non-responders) in tumor-tissue/peripheral-blood were evaluated by pyrosequencing. Results: Since March 2012, 29 patients were selected. The primary tumor was: pancreas in 14 patients (48%), gastrointestinal (GI) in 5 (17%), unknown in 2 (7%), lung in 8 (28%). According to 2010 WHO classification, Ki67 was &lt;2% (G1) in 3%, 3-20% (G2) in 45% patients, &gt;20% (G3) in 21% with two "low G3" (Ki67 21-30%), and unknown in 3%. Among lung: 7% typical and 21% atypical (Travis’ classification). 72% patients (21/29) were progressive on different therapies: peptide-receptor-radiotherapy (38%), chemotherapy (38%), everolimus (14%). Partial-response (PR) occurred in 14% (4/29) of patients (95% CI: 4-32), stable-disease (SD) in 59% (17/29) (95% CI: 39-77) mainly PNET. The two "low G3" responded. Disease control rate (PR+SD): 72% (95% CI: 53-87). Median TTP: 9 months (95% CI: 5.6-N.E.). Thrombocytopenia was the most frequent grade 3 toxicity, always temporary. All 4 PR patients had genotype 2R/3R-2R/2R investigated for the 28 base-pair (bp) variable number of tandem repeats (VNTR) in the 5'UTR of the TS-gene, and MGMT-gene inactivation by epigenetic silencing. Conclusions: This analysis suggests that CAP-TEM chemotherapy could be active and well tolerated in pretreated patients with advanced NEN of different origins and grading. This warrants a prospective investigation in a more homogeneous population (G2 and “low-G3” GEP NEN or lung carcinoids), in order to validate the predictive value of MGMT methylation-status and TS-polymorphisms.
Discovery Of Genome Wide Epigenetic Programming In t(4;14) Multiple Myeloma and In The Progression From Myeloma To Plasma Cell Leukemia Via Methyl Binding Domain Protein Capture and Sequencing
Authors: Martin F Kaiser, Alexander Murison, Christopher P Wardell, David C Johnson, Charlotte Pawlyn, Fabio Mirabella, Lorenzo Melchor, Kerry Fenwick, Iwanka Kozarewa, Faith E Davies, Brian A Walker, Gareth J Morgan
Journal: Blood (2013)
Outcomes and Correlative Studies Of a Phase I Trial With The Oral PARP1-2 Inhibitor Veliparib In Combination With Bortezomib In Patients With Relapsed Or Refractory Multiple Myeloma
Authors: Paola Neri, Peter Duggan, Kathy Gratton, Li Ren, Douglas A. Stewart, Jonathan J Keats, Nizar J. Bahlis
Journal: Blood (2013)