tbuckley/cabot-search huggingface dataset:
Prognostic impact of hexokinase and glucose transporter expressions and clinicopathologic features related to F-18-FDG uptake in esophageal cancer.
Authors: Liesbeth M Schreurs, Bareld B Pultrum, Kirill Pavlov, Jan Pruim, Henk Groen, Harry Hollema, John Theodorus Plukker
Journal: Journal of Clinical Oncology (2012)

39 Background: Elucidation of prognostic predictors based on biological viability may be useful for a better detection of patients with a high risk of relapse or death from esophageal cancer. Methods: Maximum standardized uptake values (SUV max ) were measured in the preoperative 18F-FDG positron emission tomography (PET) scans of 47 patients who had a radical esophageal resection without previous treatment. Expression levels of hexokinase-II (HK-II), glucose transporter I (GLUT-I), hypoxia inducible factor-1α (HIF-Iα), vascular endothelial growth factor (VEGF), p53 and the proliferative activity (MIB-I score) were determined immunohistochemically on paraffin-embedded tumor tissue. Correlations and survival functions were calculated to identify independent correlations between FDG-uptake and prognostic expression levels. Results: High HK-II expression was significantly correlated with reduced SUV max values (p= 0.002) and HK-II expression was significant higher among adenocarcinomas than squamous cell carcinomas (36/37 vs. 5/9, p= 0.004). The five years survival was significant better for patients with SUV max ≤ 3 in their primary tumors (75% vs. 25%) and a lymph node (LN) ratio ≤0.20 (40% vs. 6%). There were also significant disease free survival benefits for different expression rates of GLUT-I, p53 and MIB (log rank p= 0.03, p= 0.03 and p= 0.04 respectively) in patients with a lymph node ratio &gt;0.20. Conclusions: FDG-uptake and LN ratio are strong prognostic predictors in patients with esophageal cancer. The level of GLUT-I and p53 expression and the MIB score may be useful prognostic markers that provide information about tumor aggressiviness in esophageal cancer.
Comparing long-term toxicity between external beam radiotherapy modalities: A SEER/Medicare database study.
Authors: Chandana A. Reddy, Jay P. Ciezki, May Abdel-Wahab, Kenneth Angermeier, James Ulchaker, Kevin L. Stephans, Rahul D. Tendulkar, Andrew Altman, Nabil Chehade, Eric A. Klein
Journal: Journal of Clinical Oncology (2012)

118 Background: The use of intensity modulated radiotherapy (IMRT) for the treatment of prostate cancer (CaP) has been widely promoted due to the hypothesized benefit of low late toxicity. Methods: The SEER-Medicare database was queried for CaP patients treated with external beam radiotherapy (EBRT), 1991-2007. CPT billing codes were used to identify patients treated with IMRT or standard EBRT (sEBRT), which was comprised of conformal radiotherapy or a four-field technique. Patients without a treatment billing code were excluded from the analysis. Information on dose is unavailable. CPT codes were also used to identify procedures associated with gastrointestinal (GI) or genitourinary (GU) toxicity related treatments. Cumulative incidence rates for GI and GU toxicity were calculated with death treated as a competing event. Results: A total of 137,427 patients who were 65 years or older at the time of CaP diagnosis and who had CaP as their only cancer diagnosis were retrieved from the SEER-Medicare database: 60,806 were treated with EBRT and a treatment billing code was identified for 35,388 patients. No patient received combined therapy. Seventeen percent of patients received IMRT. The median follow-up for patients receiving IMRT is 40 months (mo) (range 2-157) vs 77 mo (range 0-203) for patients receiving sEBRT. Overall, 3,699 (10%) patients experienced a toxicity requiring an intervention. The five year rate of GI The gastrointestinal (GI) and genitourinary (GU) toxicity comparisons are listed in the table. For both endpoints, rate of toxicity at five years was higher for the IMRT group. The most common GU toxicity for both groups was dilation of a urethral stricture (3.8% of all sEBRT patients vs 3.4 of all IMRT patients). Cauterization of rectal bleeding was the most common GI toxicity (2.4% of all sEBRT patients vs 1.6 of all IMRT patients). Conclusions: While the rates of GI toxicity between IMRT and sEBRT are comparable, of concern is the higher rate of GU toxicity for the IMRT patients despite this group having a shorter follow up than the sEBRT group. [Table: see text]
Tyrosine kinase inhibitors and development of brain metastasis in metastatic renal cell carcinoma: A retrospective review.
Authors: J. Verma, E. Jonasch, P. Allen, N. M. Tannir, A. Mahajan
Journal: Journal of Clinical Oncology (2011)

340 Background: Tyrosine kinase inhibitors (TKIs) have been shown to improve overall survival (OS) in metastatic renal cell carcinoma (mRCC) but their effect on brain metastasis (BM) development is unclear. The purpose of our study is to evaluate the impact of TKIs on incidence of BM and OS in patients with mRCC. Methods: Searched the M. D. Anderson Cancer Center (MDACC) tumor registry for patients who presented with mRCC in 2002-2003 and 2006-2007 with no BM at initial staging. The following items were retrospectively collected: age, sex, Fuhrman grade, sites of disease, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), MSKCC risk category, BM treatment, and vital status. Interaction between OS and incidence of BM and these variables was estimated using the Cox proportional hazards model. OS and incidence of BM were estimated using the Kaplan-Meier (K-M) method. Results: 338 patients were identified; 154 (46%) were treated with a TKI prior to BM, and 184 (54%) were not. There were no significant differences in age, histology, involved sites of disease other than lung, nephrectomy, or MSKCC risk category between the groups. A higher proportion of the nonTKI group received other systemic agents and had lung metastasis at initial staging (p=0.03). Median OS was longer in the TKI-treated group (25 months versus 12.1 months, p&lt;0.0001). In Cox multivariate analysis, TKI treatment (HR=0.53, 95% CI 0.38-0.74, p&lt;0.001) was associated with improved OS and lung/mediastinal involvement and ECOG performance status &gt; 2 (HR 1.87, 95% CI 1.28-2.71, p=0.001) were associated with poor OS. Median OS after BM was not significantly different between TKI treated and untreated groups. 44 patients (13%) developed a BM, including 29 (15.8%) of the nonTKI group and 15 (9.7%) of the TKI group. In K-M analysis, the 5-year incidence of BM was 40% versus 17% respectively (logrank p&lt;0.001). In Cox multivariate analysis, TKI treatment was associated with lower incidence of BM (HR=0.39, 95% CI 0.21-0.73, p=0.003). Lung metastasis increased the risk of BM (HR=9.61, 95% CI 2.97-31.1, p&lt;0.001). Conclusions: Treatment with TKI agents reduces the incidence of BM in mRCC. Lung metastasis is a risk factor for BM development. No significant financial relationships to disclose.
Body Image Disorders and Abuse of Anabolic-Androgenic Steroids Among Men
Authors: Harrison G. Pope, Jag H. Khalsa, Shalender Bhasin
Journal: JAMA (2016)

This Viewpoint discusses the health risks of the use of anabolic-androgenic steroids by men with muscle dysmorphia, a form of body image disorder characterized by obsessive preoccupation with a muscular appearance.
MicroRNA profile in gastrointestinal stromal tumors (GISTs) and correlation with KIT/PDGFRA kinase genotype.
Authors: S. Formica, A. Astolfi, M. Nannini, M. A. Pantaleo, M. Ferracin, B. Zagatti, M. Negrini, D. Santini, P. Paterini, M. di Battista, A. Maleddu, M. Saponara, M. C. Pallotti, A. Mandrioli, C. Lolli, F. Catena, A. P. Dei Tos, G. Biasco
Journal: Journal of Clinical Oncology (2011)

10056 Background: Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic mutations of KIT and PDGFRA receptors. However about 10%-15% of adult GISTs do not harbor any KIT or PDGFRA gene mutation and are defined as wild-type (WT). Studies reported that gene expression profile and genome are strongly different between WT and mutated cases. On the contrary, up to now, really few data are available on microRNAs. We studied the miRNA profiles in GISTs correlated with kinase genotype. Methods: We analyzed the miRNA profile of 13 GIST tumor samples, of which 9 carry either KIT or PDGFRA mutations, and 4 do not carry any KIT and PDGFRA mutations. Total RNA was labeled, hybridized to Agilent microRNA microarrays; differential microRNAs were selected by a two-fold change cutoff and Benjamini and Hochberg-corrected unpaired t test. Gene targets of differentially expressed miRNAs were selected if supported by at least five Prediction Algorithms out of six (miRDb, PicTar, Elmmo, MiRanda, PITA, TargetScan). Results: The miRNA profile is different in WT and mutated GIST samples, with 56 microRNAs differentially expressed (0.05 cutoff p-value). By correlation with gene expression profiling data, we identified the miRNA target genes differentially express between WT and mutated tumors. hsa-let-7b and hsa-let-7c microRNAs are the most significantly differentially expressed miRNAs, resulting less expressed in WT samples and able to target IGF1R receptor. We reported that WT-GISTs overexpress IGF-1R, in spite of Copy-Number-Analysis by high-resolution mapping arrays demonstrated no IGF-1R amplification. These data suggest that overexpression of IGF1R in WT-GISTs could be associated to the downregulation of microRNAs targeting these gene. Validation studies on the significance of the identified miRNAs are ongoing. Conclusions: WT-GISTs have a different miRNA profile compared with mutated patients. hsa-let-7b and hsa-let-7c, targeting IGF1R, are the most significantly differentially expressed. microRNA expression difference between WT and mutated GISTs needs to be more investigated in order to understand the biological role on the pathogenesis, clinical behavior and treatment responsiveness.
Disparity in Perceptions of Disease, Treatment Effectiveness and Treatment Adherence Between Physicians and Patients with Myelodysplastic Syndromes (MDS)
Authors: David P Steensma, Rami S. Komrokji, Richard M. Stone, Alan F. List, Guillermo Garcia-Manero, John Huber, Betsy Dennison, Mikkael A. Sekeres
Journal: Blood (2012)
High-dose radiotherapy with or without androgen-deprivation therapy for intermediate-risk prostate cancer: Cancer control and toxicity.
Authors: S. Edelman, P. J. Rossi, S. Cooper, A. B. Jani
Journal: Journal of Clinical Oncology (2011)

67 Background: Randomized studies show an improvement in biochemical failure-free survival (BFFS) and overall survival (OS) with the addition of androgen therapy (ADT) to external-beam radiotherapy (EBRT) for high-risk prostate cancer (PC). However, the role of ADT in intermediate risk PC in the current dose-escalation era remains poorly defined, as studies evaluating ADT in this group have included high-risk patients or did not use dose-escalation. Our goal was to evaluate the impact of ADT on cancer control and toxicity in intermediate-risk PC. Methods: From a multi-institutional IRB-approved database of 850 pts, we identified 251 intermediate risk PC patients (defined as ≥ T2b or PSA &gt; 10 or Gleason score [GS] of 7, with none of the following: ≥ T3, PSA &gt; 20, GS ≥ 8, positive nodes, distant metastases) treated with EBRT to a dose of ≥70 Gy (no brachytherapy or prostatectomy). Eighty-seven men received ADT; 164 did not. BFFS (Phoenix definition) and OS survival curves for ADT vs no-ADT arms were compared with the log rank test. Univariate and multivariate analyses of major demographic, disease and treatment factors were performed, as were chi-square analyses of genitourinary (GU) and gastrointestinal (GI) toxicity. Results: Median follow up was 47 mo. Mean dose [ADT vs no-ADT] was 76.8 Gy vs 76.2 Gy (p=0.41; range: 70.0-81.0 Gy). The ADT group had a higher mean PSA (12.0 vs 8.9, p&lt;0.001), proportion of ≥ T2b (22 vs 11%, p&lt;0.01) and proportion of pelvic XRT use (49 vs 22%, p&lt;0.001) than the no-ADT group, but the groups were well-balanced by age, race, GS, EBRT dose and intensity-modulated radiotherapy (IMRT) use. For ADT vs no-ADT, 5-yr BFFS was 80% vs 76% (p=0.17) and 5-yr OS was 84% vs 76% (p=0.82). On multivariate analysis, only ADT (p=0.006) and GS (p=0.006) were significantly associated with BFFS, and only PSA (p=0.028) and IMRT use (p=0.011) reached significance for OS. There were no significant differences in acute or late GU or GI toxicity. Conclusions: While RTOG 0815 is exploring this study question in a randomized setting, our study suggests that the addition of ADT to dose-escalated EBRT may improve BFFS, but without a demonstrated OS benefit, and is not associated with additional EBRT-related GI or GU toxicity. No significant financial relationships to disclose.
Phenotypic and Functional Characterization of Mesenchymal Stromal Cells Derived from CD271+- Bone Marrow Mononuclear Cells and Mesenchymal Stromal Cells Derived through Plastic Adherence.
Authors: Selim Kuci, Kathrin Puetsch, Zyrafete Kuci, Sabine Huenecke, Hermann Kreyenberg, Chandra Sekhar Amara, Christoph Piechaczek, Ulrike Koehl, Thomas Klingebiel, Peter Bader
Journal: Blood (2007)
Human newborn B cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus
Authors: Jop Jans, Matthew Pettengill, Dhohyung Kim, Cas van der Made, Ronald de Groot, Stefanie Henriet, Marien I. de Jonge, Gerben Ferwerda, Ofer Levy
Journal: Journal of Allergy and Clinical Immunology (2016)
Adenovirus-Interferon-g (TG1042) Demonstates Clinical Activity in Relapsing Primary Cutaneous Lymphoma (PCL): A Phase I/II Multicentric Trial.
Authors: Mirjana Urosevic, Thomas E. Luger, Wolfram Sterry, Brigitte Dreno, Olivier Dereure, Marion Baudard, Martine Bagot, Pascal Bleuzen, Jean-Francois Rossi, Rheinard Dummer
Journal: Blood (2005)
Monitoring Immune Function in the Allogeneic Transplant Recipient: Predicting Graft vs Host Disease (GvHD) and Infection.
Authors: Elias J. Anaissie, Jose A. Diaz, Monica L. Grazziutti, Marisa H. Miceli, Michele Fox-Cottler, Bart Barlogie, Frits van Rhee
Journal: Blood (2007)
Graft-Versus-Host Disease (Gvhd) Prophylaxis with Tacrolimus and Mycophenolate Mofetil (MMF) in 131 Matched Sibling Nonmyeloablative (NMA) Transplant Recipients: Long-Term Follow-up Confirms Extremely Low Incidence of Acute (a) Gvhd, High Incidence of Extensive Chronic (c) Gvhd and Favorable Disease Outcome.
Authors: Waleed Sabry, Annie-Claude Labbé, Richard Le Blanc, Guy Sauvageau, Denis-Claude Roy, Lambert Busque, Sandra Cohen, Thomas Kiss, Silvy Lachance, Jean Roy
Journal: Blood (2008)
Efficacy of allergen immunotherapy in reducing the likelihood of developing new allergen sensitizations: a systematic review
Authors: D. Di Bona, A. Plaia, M. S. Leto‐Barone, S. La Piana, L. Macchia, G. Di Lorenzo
Journal: Allergy (2016)

Guidelines and position papers indicate that allergen immunotherapy (AIT) is the only disease-modifying treatment, including prevention of the onset of new allergen sensitizations. However, this preventive effect was shown by only a few observational studies. Our aim was to systematically review the efficacy of AIT in preventing the onset of new allergen sensitizations.Computerized bibliographic searches of Medline, EMBASE, and the Cochrane Library (through June 2015) were supplemented with manual searches of reference lists. Observational studies or randomized controlled trials with a long-term observation period were included. Paired reviewers extracted data about study characteristics and assessed biases. The end point was the risk difference in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy. The strength of the evidence was graded based on the risk of bias, consistency, and magnitude of effect, according to the GRADE Working Group's guide.Eighteen studies (1049 children, 10 057 adults) met the inclusion criteria. The risk of bias was high in all but one study. Low evidence supports the position that AIT prevents the onset of new allergen sensitizations, with 10 of 18 studies reporting a reduction in the onset of new sensitizations in patients treated with AIT vs placebo. Small studies and studies with a shorter follow-up showed the highest benefit of AIT.The overall evidence provides a low-grade level of the evidence supporting the efficacy of AIT in preventing the onset of new allergen sensitizations, but high-quality studies could change this estimate.
Time Interval from Last Chemotherapy to Stem Cell Collection Correlates with Peripheral Blood Absolute Lymphocyte Count at Apheresis and Survival Post-Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma.
Authors: Shernan G. Holtan, Luis F. Porrata, David J. Inwards, Stephen A. Ansell, Ivana N.M. Micallef, Mark R. Litzow, Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Dennis A. Gastineau, Ayalew Tefferi, Michelle Elliott, William J. Hogan, Suzanne Hayman, Svetomir N. Markovic
Journal: Blood (2004)
The urinary metabolomic signature of Barrett's esophagus.
Authors: Vanessa Wylie Davis, Dan E. Schiller, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2012)

36 Background: Current screening and surveillance strategies for Barrett’s esophagus are inadequate. More reliable tools are needed. A unique urinary metabolomic signature could fill this niche. We applied metabolomic techniques to identify urinary metabolites capable of facilitating in the diagnosis of Barrett’s esophagus. Methods: Urine samples from patients with histologically confirmed Barrett’s esophagus (n=32) and normal, healthy volunteers (n=25) were collected and examined using 1 H-NMR spectroscopy. Targeted profiling of spectra using Chenomx NMR Suite 7.0 software permitted the detection and quantification of 66 distinct metabolites. Unsupervised (principal component analysis, PCA) and supervised (partial-least squares discriminant analysis, PLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra of patients with Barrett’s esophagus and healthy volunteers using SIMCA-P (version 11, Umetrics, Umeå, Sweden). Results: Significant differences were found when comparing the concentrations of 59 metabolites in the urine of healthy volunteers and patients with Barrett’s esophagus. Those metabolites contributing the most class discriminating information included 3-hydoxybutyrate, adipate and choline. Clear distinction between patients with Barrett’s esophagus and healthy controls was noted when PLS-DA was applied to the data set. Model parameters for both the goodness of fit R 2 , and the predictive capability Q 2 , were high (R 2 = 0.96; Q 2 = 0.90). Model validity was tested using response permutation and results were suggestive of excellent predictive power. Conclusions: Urinary metabolomics identified a discrete signature associated with Barrett’s esophagus compared to healthy controls. This profile has the potential to aid in diagnosis and the development of new therapeutic targets.
A phase II study of pomegranate extract for men with rising prostate-specific antigen following primary therapy.
Authors: M. A. Carducci, C. J. Paller, P. Wozniak, P. Sieber, R. Greengold, B. Stockton, B. Hertzman, R. Roper, H. Liker, X. Ye
Journal: Journal of Clinical Oncology (2011)

11 Background: Pomegranate extract (POMx) demonstrates promising antitumor effects in prostate cancer (PCA). Prior published work reveals an increase in PSA doubling time (PSADT) in a single arm study of pomegranate juice (POM) in PCA patients (pts) with a rising PSA after local therapy. We sought to determine the effects of low (1 gram) or high (3 grams) daily POMx on PSADT in a similar but broader population of men seeking to defer androgen deprivation therapy. Methods: Our multi-center, double bind phase II trial randomized men with rising PSA and without metastases to receive high or low dose POMx, stratified by baseline PSADT and Gleason score, and with no restrictions for PSADT and no upper limit PSA value. Men were treated until progression or for 18 months. PSA levels were obtained every 3 months. This study was designed to detect a 6 month increase in PSADT from baseline. Results: 104 patients were enrolled and treated for up to 6 (92%), 12 (70%) and 18 months (36%). Median PSADT lengthened in the Intent to treat population (96% white, median age 74.5 years, median Gleason score 7) from baseline 11.9 (range 1.6-54.6) compared to 18.5 (2-1523) months after treatment (p&lt;.001).There was no significant treatment difference on PSADT between the dose groups (p=.920). Declining PSA levels were observed in 13 pts (13%) during the study. No significant changes occurred in testosterone in either group. Although no clinically significant toxicities were seen, mild to moderate diarrhea was seen in 8 pts (7.7%). Conclusions: POMx treatment significantly increased the PSADT by over 6 months in both treatment arms, with no effect on testosterone. This IND-conducted study confirms slowing of PSADT after treatment with POMx as was found with POM, yet in a PCA patient population with greater high risk progression features. [Table: see text]
Denosumab safety and efficacy in giant cell tumor of bone (GCTB): Interim results from a phase II study.
Authors: J. Blay, S. P. Chawla, J. Martin Broto, E. Choy, M. Dominkus, J. Engellau, R. Grimer, R. M. Henshaw, E. Palmerini, P. Reichardt, P. Rutkowski, K. M. Skubitz, D. M. Thomas, Y. Zhao, Y. Qian, I. A. Jacobs
Journal: Journal of Clinical Oncology (2011)

10034 Background: GCTB, an osteolytic tumor causing skeletal morbidity, contains osteoclast-like giant cells and mononuclear cells expressing RANKL, a mediator of osteoclast activation. Denosumab binds RANKL, inhibiting osteoclast activity. In an initial phase 2 study, 86% of subjects with GCTB responded to denosumab. We report data from a prespecified 12‐month interim analysis in a second open-label phase 2 study of denosumab in GCTB. Methods: Subjects with surgically unsalvageable GCTB (cohort 1) or salvageable GCTB with planned surgery (cohort 2) received subcutaneous denosumab 120 mg every 4 weeks, with a 120 mg loading dose on days 8 and 15. The primary objective was to evaluate the safety of denosumab. The analysis also included subjective assessments of disease progression and the proportion of cohort-2 subjects for whom surgery was delayed, reduced in scope, or not required. Safety analyses included all subjects who received denosumab; efficacy analyses included subjects who received denosumab for ≥6 months. Results: Enrolled subjects were 62% women, mean (SD) age 35 (13) years. Most (87%) had a Karnofsky status ≥80%; 52% had recurrent unresectable disease. AEs were reported in 126/158 subjects (80%) who received denosumab; most frequent were fatigue (15%) and headache, back pain, and extremity pain (13% each). Osteonecrosis of the jaw was reported in 3 of 158 subjects (1.9%). No other serious AEs were attributed to denosumab. Two subjects died on study: 1 from bone sarcoma and 1 from respiratory failure, neither attributed to denosumab. Hypocalcemia was reported in 7 subjects (4%); no cases were serious. Based on subjective assessment of disease status at study month 12, there was no disease progression in 72 of the 73 evaluable subjects (99%) in cohort 1. Among 23 cohort-2 subjects who had planned surgery at baseline, 15 (65%) had no surgery in the first 12 months of the study; 5 of 8 subjects (62%) undergoing surgery had less morbid procedures than originally planned. Conclusions: Denosumab appeared to be well tolerated in subjects with GCTB and was associated with inhibited disease progression and reduced requirements for surgery. Denosumab continues to be studied as a potential treatment alternative for GCTB.