tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma.
Authors: Shiao-Pei S. Weathers, Stan Xiaosi Han, Diane D Liu, Charles A. Conrad, Mark R. Gilbert, Monica Elena Loghin, Barbara Jane O'Brien, Marta Penas-Prado, Vinay K. Puduvalli, Ivo Tremont-Lukats, W. K. Alfred Yung, John Frederick De Groot
Journal: Journal of Clinical Oncology (2015)

2005 Background: Antiangiogenic therapy can rapidly reduce vascular permeability, but high doses of bevacizumab (BEV) may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose BEV in combination with lomustine (CCNU) compared to standard dose BEV in patients with recurrent glioblastoma. Methods: Eligibility criteria included age > 18 yrs with recurrent glioblastoma after temozolomide chemoradiotherapy. Patients were stratified by age, KPS, 1st/2nd/3rd recurrence, and scheduled surgery and randomized to BEV 5 mg/kg every 3 weeks plus CCNU 90 mg/m2 every 6 weeks or BEV 10 mg/kg every 2 weeks. The primary objective was progression free survival (PFS) with secondary objectives of radiographic response (RR), 6 month progression-free survival (PFS-6), overall survival (OS), time to progression (TTP), and safety. Results: 70 of 82 patients accrued were randomized and 68 were treated from 2010-2014. Median follow-up was 30.5 months. At the time of this analysis, 62 patients had progressed or died. For 68 evaluable patients, median PFS was not significantly longer in the BEV + CCNU arm (4.34 months, CI: 2.96-8.34) compared to the BEV alone arm (4.11 months, CI: 2.69-5.55, p = 0.19). In patients with one recurrence (n = 24 and 23, respectively), there was a trend towards statistical significance in longer median PFS time in the BEV + CCNU arm (4.96 months, CI: 4.17-13.44) compared to the BEV alone arm (3.22 months CI: 2.5-6.01, p = 0.08). Median OS in patients with 1 recurrence on BEV + CCNU was longer (13.05 months, CI: 8-19.17) than those treated with BEV alone (8.79 months, CI: 6.42-20.22, p = 0.77) but this did not reach statistical significance. No unexpected grade 3 or 4 toxicities were observed. The trial was closed early due to futility. Conclusions: The combination of low dose BEV + CCNU is a safe and effective regimen. The study was not designed to test only at first recurrence, but in that subgroup there was a strong trend towards the combination supporting the findings of the recently published BELOB trial.With a larger sample size, a statistically significant difference in median PFS between treatments arms would likely have been observed. Clinical trial information: NCT01067469.
NCOG-11. COMPARISON OF NEUROCOGNITIVE FUNCTIONING IN PEDIATRIC BRAIN TUMOR SURVIVORS AND CHILDREN WITH NEURODEVELOPMENTAL ADHD
Authors: Christina Sharkey, Anthony Gioia, Victoria Willard, Karin Walsh, Kristina Hardy
Journal: Neuro-Oncology (2016)

Attention and working memory symptoms are among the most common late effects in survivors of pediatric brain tumors (BT). These difficulties lead to declines in academic and social functioning, as well as quality of life. In order to facilitate identification of these deficits and development of treatments, an ADHD framework has frequently been applied to the pediatric BT population, but it is unclear the extent to which the cognitive phenotypes overlap between these groups. The present study is the first to directly compare neurocognition in BT survivors and children with neurodevelopmental ADHD. Neuropsychological data from clinically-referred samples of BT survivors (n=109, Mage=11.89, 51.4% male) and children with ADHD (n=184, Mage=11.08, 64.1% male) were abstracted. Data consists of a battery of parent-report questionnaires and performance-based measures of attention and executive functioning. Survivors averaged 5.98 years (SD=3.91) at diagnosis, and were evaluated 5.63 (SD=3.29) years later. Tumor types varied, with the most common being medulloblastoma (18.5%), ependymoma (16.7%), and low-grade glioma (13.9%); 63.1% received radiation therapy and 77.6% underwent surgical resection. Twenty-six survivors (23.9%) met symptom criteria for ADHD. Participants with neurodevelopmental ADHD and survivors who met ADHD criteria had significantly greater parent- (p<0.001) and teacher-reported (p<0.001) working memory and behavior regulation difficulties than survivors who did not meet criteria. Children with ADHD and survivors with ADHD symptoms also performed worse on measures of sustained attention than survivors without ADHD symptoms (p<0.001). Additionally, survivors with ADHD symptoms had greater performance-based working memory difficulties than survivors without attention problems and children with neurodevelopmental ADHD (p=0.002). While some neurocognitive deficits are pervasive among survivors, a subset have attention and working memory problems that are similar to those observed in children with ADHD. Screening for ADHD symptoms could potentially help providers and investigators better identify and intervene with this at-risk group.
Outcomes of Unrelated Cord Blood Transplantation in Patients with Multiple Myeloma a Eurocord, CBC-Cellular Therapy & Immunobiology Working Party and Chronic Malignancies Working Party-EBMT Study
Authors: Annalisa Paviglianiti, Erick Xavier, Patrice Ceballos, Annalisa Ruggeri, Eric Deconinck, Jan Cornelissen, Stephanie Nguyen-Quoc, Natacha Maillard, Guillermo Sanz, Pierre-Simon Rohrlich, Laurent Garderet, Eliane Gluckman, Nicolaus Kroeger, Vanderson Rocha, Nathalie Fegueux, Mohamad Mohty
Journal: Blood (2015)
Activity and School Impairment By EPR-3 Asthma Control Guidelines in Children with Severe or Difficult-to-Treat Asthma
Authors: Leonard B. Bacharier, Ronina A. Covar, Tmirah Haselkorn, Ahmar Iqbal, David R. Mink, Hubert Chen, Robert S. Zeiger
Journal: Journal of Allergy and Clinical Immunology (2017)
A Phase III Study Comparing Thalidomide/Cyclophosphamide/ Dexa Vs Thalidomide/Dexa Vs Thalidomide/Melphalan/Prednisone In De Novo Multiple Myeloma Patients Not Eligible for ASCT
Authors: Edvan Crusoe, Angelo Maiolino, Rosane Bittencourt, Dorotea Beatriz Fantl, James Maciel, Manuella Sampaio, Adriana Quero, Ana Lucia Peres, Eliana C M Miranda, Daniel Mercante, Flavia Parra, Carlos S Chiattone, Vania Hungria
Journal: Blood (2011)
Imatinib as Front-Line Treatment in Chronic Myelogenous Leukemia: How Important is the Achievement of Complete Cytogenetic Response after 3 Months?
Authors: Roberto Latagliata, Massimo Breccia, Ida Carmosino, Federico Vozella, Paola Volpicelli, Caterina Stefanizzi, Michelina Santopietro, Rosa De Cuia, Mauro Nanni, Marco Mancini, Giuliana Alimena
Journal: Blood (2009)
Evaluating <i>RASSF1</i> promoter methylation and the 16-gene signature as a prognostic marker in hepatoblastoma.
Authors: Melanie Eichenmuller, Michaela Kreuder, Ivonne Regel, Beate Haberle, Josef Muller-Hocker, Dietrich von Schweinitz, Roland Kappler
Journal: Journal of Clinical Oncology (2012)

63 Background: Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although combination of neoadjuvant chemotherapy and surgery has improved the outcome of standard-risk HB-patients up to 94% the outcome of high-risk HB-patients with metastatic tumors or invasion of large hepatic veins is still dismal and only 60% of these patients survive. Therefore, the identification of biomarkers that could help early detection of high-risk HB-patients and lead to risk-adapted therapies is of utmost importance. Methods: Genomic DNA of tumor and normal liver samples from 21 HB patients was extracted with standard procedures and bisulfite-treated using EpiTect Bisulfite Kit (Qiagen). Methylation status of the Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) gene was analyzed by methylation-specific-PCR. cDNA of tumor and normal liver samples was used to determine the 16-gene expression signature according to Cairo et al. (2008, Cancer Cell) using real-time PCR. Association studies of molecular and clinical data were performed with GraphPad Prism Version 3.0 using two-tailed Chi square test. Results: We identified 9/21 HB cases hypermethylated in the RASSF1 promoter region. Interestingly, RASSF1 promoter methylation was significantly associated with metastases (p=0.0166) and occurrence of this epigenetic marker was associated with a reduced overall survival of patients (p=0.0008). Moreover, we discriminated HB tumors in C1 and C2 subclasses by using the 16-gene signature and correlation of these subtypes with the methylation status of RASSF1 showed a significant association (p=0.0037) for aggressive C2 tumors (8/11), but not C1 tumors (1/10). Conclusions: RASSF1 promoter hypermethylation is a strong prognostic marker for metastasis and worse outcome and correlates with an aggressive C2 HB-tumor profile. Since the detection of tumor-derived methylated DNA in the blood stream of cancer patients is nowadays practical, our data advise RASSF1 methylation assays to be used for risk assessment in HB-patients in the future.
Good General Health In Survivors of Childhood AML Treated with Chemotherapy Only: A NOPHO-AML Study.
Authors: Henrik Hasle, Heidi Glosli, Kirsi Jahnukainen, Marianne Jarfelt, Guđmundur Jónmundsson, Johan Malmros-Svennilson, Karsten Nysom, Lene Molgaard-Hansen
Journal: Blood (2010)
Cardiovascular risk factors in young adult survivors of childhood malignancies.
Authors: Joanna Sulicka-Grodzicka, Andrzej Surdacki, Jaroslaw Krolczyk, Tomasz Grodzicki
Journal: Journal of Clinical Oncology (2016)

138 Background: Survivors of childhood cancer are at increased risk of early cardiovascular (CV) diseases related to previous cancer therapy, chronic stress and unhealthy behaviors, as well as traditional cardiovascular risk factors. The aim of the study was to assess the prevalence of cardiovascular risk factors in young adult survivors of childhood malignancies. Methods: Medical records of 155 adult childhood cancer survivors were analyzed to extract data on cancer treatment, demographical characteristics, family history, smoking, blood pressure (BP), lipids, fasting glucose, creatinine measured during a routine visit in our follow-up clinic for adult childhood cancer survivors. Results: The prevalence of traditional CV risk factors was high, with 55% of patients presenting with prehypertension (office systolic BP 120-139 mmHg or diastolic 80-89 mmHg) and 15,4% with hypertension (BP ≥ 140 mmHg and/or ≥ 90 mmHg or being on antihypertensive drugs). The prevalence of overweight and obesity was 23,5% and 3,7%, respectively. A classic “atherogenic lipid profile” (28% patients with elevated total cholesterol and 27% with elevated LDL cholesterol) was more common than a dyslipidemic pattern (elevated triglycerides 11% and reduced HDL cholesterol 7,8%). Two or more CV risk factors were found in 50% of patients and only 16% did not have any of traditional risk factors. Conclusions: Major CV risk factors are common in very young adults with cancer history in the childhood and may substantially increase risk for future CV events in this population. These finding support the need for screening of adult survivors of childhood malignancy for early detection and treatment of modifiable risk factors. [Table: see text]
Survival outcome of early versus delayed bevacizumab treatment in patients with recurrent glioblastoma.
Authors: Mohamed Ali Hamza, Jacob Mandel, Charles A. Conrad, Mark R. Gilbert, W. K. Alfred Yung, Vinay K. Puduvalli, John Frederick De Groot
Journal: Journal of Clinical Oncology (2013)

2042 Background: Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma (GB). Differences in outcome between early versus delayed BEV treatment of recurrent GB are not well defined. We examined the relationship between the time of start of BEV treatment and outcomes in patients with recurrent GB. Methods: In this retrospective chart review derived from our longitudinal database, we identified patients with recurrent GB between 2001 and 2011, who were treated with BEV alone or BEV-containing regimens. Data was analyzed to determine overall survival (OS) from time of diagnosis and progression free survival (PFS) from time of BEV start. Early BEV was defined as start of BEV treatment at first recurrence, while delayed BEV was defined as start of treatment at second recurrence or later. Results: A total of 298 patients with recurrent GB who received BEV were identified, of whom 149 patients received early BEV, 134 patients received delayed BEV, and 15 patients who were excluded because they received BEV upfront. There were no significant differences in the age, sex, performance status and extent of resection between patients treated with early BEV and those treated with delayed BEV. The median time from diagnosis to first recurrence was more than 6 months (mos.) for both groups (6.5 mos. for early BEV and 7.6 mos. for delayed BEV, p = 0.01). The median time from diagnosis to start of BEV was 7.9 mos. for patients with early BEV and 15.6 mos. for patients with delayed BEV (p&lt;0.001). There was no significant difference in PFS between patients that received early BEV and those that received delayed BEV (5.73 mos. vs. 4.33 mos., p = 0.07). Patients who were treated with delayed BEV had longer OS when compared to those treated with early BEV (25.9 mos. vs. 19.7 mos., p = 0.0002). Conclusions: In patients with recurrent GB, there was no significant difference in PFS between early and delayed BEV; however, patients treated with delayed BEV have longer OS when compared to those treated with early BEV. These results indicate that delaying treatment with BEV is not detrimental and may be associated with a favorable survival outcome.
Capecitabine/oxaliplatin (XELOX) versus XELOX plus bevacizumab (XELOX + bev) cost-effectiveness for metastatic colorectal cancer (mCRC) in first line treatment: a Brazilian public hospital analysis
Authors: F.M. Peria, A.Q. Ungari, F.N. Dos Santos, T. Lins-Almeida, A.A. Nunes
Journal: Annals of Oncology (2016)
Four-Dimensional Microvascular Analysis Reveals That Regenerative Angiogenesis in Ischemic Muscle Produces a Flawed Microcirculation
Authors: John-Michael Arpino, Zengxuan Nong, Fuyan Li, Hao Yin, Nour Ghonaim, Stephanie Milkovich, Brittany Balint, Caroline O’Neil, Graham M. Fraser, Daniel Goldman, Christopher G. Ellis, J. Geoffrey Pickering
Journal: Circulation Research (2017)

Angiogenesis occurs after ischemic injury to skeletal muscle, and enhancing this response has been a therapeutic goal. However, to appropriately deliver oxygen, a precisely organized and exquisitely responsive microcirculation must form. Whether these network attributes exist in a regenerated microcirculation is unknown, and methodologies for answering this have been lacking.To develop 4-dimensional methodologies for elucidating microarchitecture and function of the reconstructed microcirculation in skeletal muscle.We established a model of complete microcirculatory regeneration after ischemia-induced obliteration in the mouse extensor digitorum longus muscle. Dynamic imaging of red blood cells revealed the regeneration of an extensive network of flowing neo-microvessels, which after 14 days structurally resembled that of uninjured muscle. However, the skeletal muscle remained hypoxic. Red blood cell transit analysis revealed slow and stalled flow in the regenerated capillaries and extensive arteriolar-venular shunting. Furthermore, spatial heterogeneity in capillary red cell transit was highly constrained, and red blood cell oxygen saturation was low and inappropriately variable. These abnormalities persisted to 120 days after injury. To determine whether the regenerated microcirculation could regulate flow, the muscle was subjected to local hypoxia using an oxygen-permeable membrane. Hypoxia promptly increased red cell velocity and flux in control capillaries, but in neocapillaries, the response was blunted. Three-dimensional confocal imaging revealed that neoarterioles were aberrantly covered by smooth muscle cells, with increased interprocess spacing and haphazard actin microfilament bundles.Despite robust neovascularization, the microcirculation formed by regenerative angiogenesis in skeletal muscle is profoundly flawed in both structure and function, with no evidence for normalizing over time. This network-level dysfunction must be recognized and overcome to advance regenerative approaches for ischemic disease.
Cytomegalovirus (CMV) gB3 Genotype Is Associated with Acute Gvhd and CMV Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients (HSCT)
Authors: Débora de Campos Dieamant, Sandra Helena Alves Bonon, Francisco J P Aranha, Gislaine O. Duarte, Virginio C.O. Fernandes, Carmino Antonio De Souza, Sandra Cecília Botelho Costa, Afonso Celso Vigorito
Journal: Blood (2011)
The elderly breast cancer patient: Association of age, tumor size, and grade with sentinel lymph node status.
Authors: Meaghan Working O'Malley, Kent A. Griffith, Michael S. Sabel, Lisa A. Newman, Tara M. Breslin, Alfred E. Chang, Vincent M. Cimmino, Celina G. Kleer, Kathleen M. Diehl
Journal: Journal of Clinical Oncology (2012)

15 Background: Nodal evaluation of the elderly breast cancer patient remains controversial, and some have suggested that selected older women with breast cancer may not require sentinel lymph node biopsy (SLNB). Methods: An IRB-approved database was queried for patients undergoing SLNB for invasive breast cancer from 2000-2006. We compared 8 cohorts: age &lt;40 years, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, and &gt;70 years. Logistic regression and chi-square test were used. Results: Procedure success rate was above 95% for all groups in a total sample size of 1268 patients. Patients &gt;70 years had lower grade tumors than patients &lt;40 years (Grade 1: 25% vs. 7%; Grade 2: 53% vs. 47%; Grade 3: 17% vs. 40%, p&lt;0.0001) and higher ER expression (ER+: 83% vs. 59%, p&lt;0.0005). Patients &lt;40 years also had a higher proportion of multifocal disease (21% vs. 9%, p&lt;0.002), lymphovascular invasion (20% vs. 10%, p&lt;0.007), and number of positive sentinel lymph nodes (PSLN) removed (mean: 3.7 vs. 2.7, p&lt;0.028). Upon multivariate analysis, the odds of a PSLN decrease 9% for every 5-year increase in age (OR 0.91, p&lt;0.003), but increase significantly with certain tumor characteristics (ER+ vs. ER-: OR 1.7, p=0.002), larger size (0.5 cm increase: OR 1.26, p&lt;0.0001), and higher grade (Grades 2-3: OR 1.99, p&lt;0.0007). The predicted probability of a PSLN for patients age 35, 55, and 70 years is 27%, 22%, and 16%, assuming each had a ER+, low grade, 2 cm tumor. Conclusions: Older breast cancer patients have more favorable pathology, and the chance of a PSLN decreases as age increases. However, the odds of a PSLN are significantly higher in patients with certain tumor characteristics, which are known prior to definitive surgery. Given recent reports that older patients are less likely to receive standard treatment for breast cancer and prognosis may worsen as a result, tumor size and characteristics rather than age should dictate the decision to perform SLNB, and we should continue appropriate, aggressive staging of the older breast cancer patient.
Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines
Authors: Ewout J. Hoorn, Robert Zietse
Journal: Journal of the American Society of Nephrology (2017)

Hyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.
The impact of reproductive factors and oral contraception on breast cancer risk in women with brca mutation or family history of breast cancer
Authors: A. Toss, G. Grandi, S. Pavesi, L. Marcheselli, E. De Matteis, E. Razzaboni, C. Tomasello, A. Cagnacci, L. Cortesi
Journal: Annals of Oncology (2016)
GMP-Grade Large-Scale Expansion of Bone-Marrow- (BM) Derived Human Mesenchymal Stem/Stroma Cells (MSC): Comparison of Efficacy of Different Expansion Systems and Role of Cytokines/Chemokines
Authors: Markus Rojewski, Natalie Fekete, Daniel Fuerst, Philippe Bourin, Ramin Lotfi, Volker Mailaender, Gerlinde Schmidtke-Schrezenmeier, Luc Sensebé, Hubert Schrezenmeier
Journal: Blood (2010)
Value in the Step 2 Clinical Skills Examination—Reply
Authors: Carolyn L. Treasure
Journal: JAMA Internal Medicine (2017)

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Cucurbitacins, a Family of Natural Compounds That Effectively Disrupt Stat3 Signaling in Antigen-Presenting Cells (APCs) Are Promising Agents To Overcome Tumor-Induced CD4+ T-Cell Tolerance.
Authors: Fengdong Cheng, Hongwei Wang, Alfonso Suarez, Pedro Horna, Said Sebti, Eduardo M. Sotomayor
Journal: Blood (2005)