tbuckley/cabot-search huggingface dataset:
EPID-15. SURVIVAL TRENDS SUGGEST OLIGOASTROCYTOMA, OLIGODENDROGLIOMA, AND ASTROCYTOMA ARE THREE DISTINCT DISEASE ENTITIES: A SEER-BASED SURVIVAL ANALYSIS
Authors: Tyler Lanman, Jason Compton, Brian Hirshman, Kate Carroll, Mir Ali, Clark Chen
Journal: Neuro-Oncology (2016)

Certain pathologic diagnoses are proposed to overcome challenges associated with cases of histologic ambiguity. A case-in-point involves oligoastrocytoma – a diagnosis invoked in rare tumor specimens that contain features of oligodendroglioma and astrocytoma. Whether oligoastrocytoma represents a distinct disease entity or rather, a misdiagnosed astrocytoma or oligodendroglioma remains an open question We reasoned that if oligoastrocytoma represents a distinct disease entity, the survival pattern of afflicted patients would be distinct from those with oligodendroglioma and astrocytoma. We utilized the Surveillance, Epidemiology, and End Results Program (SEER, 1999-2012) to test this hypothesis. We identified patients diagnosed with WHO grade II astrocytoma (A2, n= 4,113), grade III astrocytoma (A3, n=2,755), oligodendroglioma (grade II (O2), n=2,378; grade III (O3), n=11,028), and oligoastrocytoma (OA, n=1,505) The survival pattern of OA patients appeared distinct from those of A2, A3, O2, and O3. For patients without radiation therapy (RT) or surgery, OA exhibited overall survival comparable to A2 (median survival time (MST) of 68 and 52 months, respectively). However, for patients who underwent RT, overall survival of OA was superior to A2 (MST of 31 and 18 months, respectively). Irrespective of radiation, A3 patient exhibited the worst survival (MST with RT: 11 months, without RT: 4 months) and O2 patients exhibited the longest survival (MST with RT: 92 months, without RT: >150 months). Unlike A2 patients, OA patients do not show significant survival benefit after gross total resection, a finding also observed in O2. Monte Carlo simulations showed that the survival pattern observed in OA cannot be reconstituted using different combinations of SEER A2 or O2 cohorts The survival pattern of oligoastrocytoma patients appears distinct from those of grade II and III astrocytoma and oligodendroglioma, suggesting that oligoastrocytoma represents a distinct pathologic entity rather than misdiagnosed astrocytoma or oligodendroglioma.
OS7.2 A Phase II Study of ANG1005, a novel BBB/BCB Penetratant Taxane in Patients with Recurrent Brain Metastases and Leptomeningeal Carcinomatosis from Breast Cancer
Authors: P. Kumthekar, S. Tang, A. J. Brenner, S. Kesari, C. K. Anders, J. A. Carrillo, P. Chalasani, P. Kabos, M. S. Ahluwalia, N. K. Ibrahim
Journal: Neuro-Oncology (2016)

Brain metastases (BM) are an increasing challenge.Insight in the pathology of the brain metastatic cascade, and in particular in the characteristics of the BM initiating cells can help to identify new treatment targets.PHK26 membrane dye was used in stably GFP expressing human breast cancer to differentiate slow from fast cycling cells by membrane signal intensity changes using multiphoton laser scanning microscopy, both in vitro and in vivo.The heterogeneous population of fast and slow cycling cells as well as resting cells was injected intracardially and followed with in vivo repetitive multiphoton laser microcopy via a chronic intracranial window.Here, slow cycling cells, representing only 16% of the entire cell population, were the only ones that mastered all steps of the brain metastatic cascade (0% marcometastasis formation after intravascular arrest of fast cycling cells vs. 6.15% marcometastasis formation after intravascular arrest of slow cycling cells; p<0.001), namely intravascular arrest, extravasation, perivascular survival, and marcometastasis outgrowth.These slow cycling cells showed a high overlap with established markers for tumor stem-like cells, like Oct4/Sox2, Notch and WNT, and also (but less) with low 26S proteasome activity.Illumina gene expression profiling of slow versus fast cycling JIMT1 breast cancer cells revealed up-regulation of N-Myc down regulated gene (NDGR1).Knock down of NDRG1 resulted in complete inhibition of BM formation by preventing successful colonization of the perivascular niche.In conclusion, slow cycling cells resemble the population of BM initiating cells.Increased NDRG1 expression is a characteristic of slow cycling cells, and is a pivotal molecular precondition for successful BM formation that might serve as a potential target for BM prevention or treatment. OS7
A Selective PIM Kinase Inhibitor Is Highly Active In Multiple Myeloma: The Biology of Single Agent and PI3K/AKT/mTOR Combination Activity
Authors: Allen J. Ebens, Leanne Berry, Yung-Hsiang Chen, Gauri Deshmukh, Jake Drummond, Changchun Du, Michael Eby, Karen Fitzgerald, Lori S. Friedman, Stephen E. Gould, Jane R. Kenny, Heather Maecker, John Moffat, Marina Moskalenko, Patricia Pacheco, Alham Saadat, Dion Slaga, Laura Sun, Gina Wang, Yagai Yang, Veerendra Munugalavadla
Journal: Blood (2010)
Cog-Pro: Impact of new generation hormono-therapy on cognitive functions in elderly patients treated for a metastatic prostate cancer
Authors: F. Joly, M. Lange, N. Heutte, A. Leconte, I. Léger, K. Fizazi, F. Di Fiore, B. Giffard, A. Capel, H. Laviec, M. Dubois, B. Clarisse, C. Hélène
Journal: Annals of Oncology (2016)
Retrospective study of weekly paclitaxel-cetuximab (WPC) in unselected patients (p) with recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN)
Authors: I. Pajares Bernad, J. Mártinez Trufero, L. Calera Urquizu, A. Cebolleo de Miguel, R. Pazo Cid, M. Lanzuela Valero, M.J. Agsustín, E. Millastre, C. Santander Lobera, M. Alvarez Alejandro, N. Gimeno, M. Malo Yague, Y. Llorente, A. Antón Torres
Journal: Annals of Oncology (2016)
Alternative measures predicting clinical benefit in advanced non-small cell lung cancer (NSCLC) from Southwest Oncology Group (SWOG) randomized trials: Implications for clinical trial design
Authors: P. N. Lara, M. W. Redman, K. Kelly, M. J. Edelman, S. K. Williamson, J. J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2006)

7006 Background: Although objective response (CR/PR) &amp; overall survival (OS) are typical efficacy measures for new treatments in advanced stage NSCLC, each has its limitations; e.g., some patients (pts) have no measurable disease or achieve only disease stabilization (SD) while OS is influenced by effective salvage therapies. Alternative methods of determining “clinical benefit” are needed. Methods: Pooled data from 984 pts entered onto 3 randomized SWOG trials of platinum-based chemotherapy (S9509: carbo/paclitaxel (CP) vs. cisplatin/vinorelbine; S9806: carbo/gemcitabine -&gt;P or cisplatin/vinorelbine -&gt; docetaxel; &amp; S0003: CP ± tirapazamine) were analyzed for survival using the Landmark method. Results: Pt characteristics: median age = 62 years; male sex = 647 pts (66%); stage IV = 826 pts (84%); weight loss ≥ 5% = 404 pts (42%); performance status (PS) 0/≥1 = 340 (36%)/606 (64%). Tumor response was seen in 260 pts (26%). Median time to response (TTR), time to progression (TTP) &amp; OS were 1.9, 4.3 and 8.9 months. PS &gt; 0 &amp; weight loss were associated with worse survival (hazard ratio [HR] 1.38 and 1.28; p 0 (HR 0.75, p=0.03) and weight loss (HR 0.74, p = 0.03). Shorter TTP was associated with PS&gt;0, stage IV, &amp; weight loss (HR 1.34, 1.08, 1.34 and p = 0.0001, 0.01, &lt; 0.00001). Of 886 pts alive at month 2 (time of initial response assessment following 2 treatment cycles), 62% had SD while19% had CR/PR for a disease control rate (CR+PR+SD, aka DCR) of 81%; 18% had progressive disease (PD). Although CR/PR at month 2 was associated with longer survival (HR 0.62, p&lt;0.001), DCR had a much stronger association (HR 0.38, p&lt;0.0001). Inclusion of DCR in the regression model improved its fit (p&lt;0.00001), reducing the significance of CR/PR as an independent variable. Median survival among pts with CR/PR, SD, &amp; PD were 13.5, 8.4, &amp; 3.1 months. Conclusions: 1)DCR at month 2 is a more powerful predictor of subsequent survival than the CR/PR rate. 2) If validated, this “early look” statistical measure could enhance efficacy assessment. 3) These findings may have broad implications for the design of future trials in advanced NSCLC &amp; will be prospectively tested in SWOG. No significant financial relationships to disclose.
nab-paclitaxel (nab-P) + carboplatin (C) induction therapy in patients (Pts) with squamous (SCC) NSCLC: Interim safety results from the phase 3 ABOUND.sqm study
Authors: O.J. Vidal, D. Daniel, M. Johnson, J. Knoble, T. Chen, M. McCleod, T.J. Ong, N. Trunova, E. Kim
Journal: Annals of Oncology (2016)
The Kinetics of Reduction of Minimal Residual Disease Impacts on Duration of Survival and Response of Adult Patients with Acute Myeloid Leukemia.
Authors: Adriano Venditti, Luca Maurillo, Francesco Buccisano, Giovanni Del Poeta, Carla Mazzone, Benedetta Neri, Francesco Lo Coco, Sergio Amadori
Journal: Blood (2005)
RTHP-21. CLINICAL OUTCOMES AND PATTERN OF FAILURE IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME TREATED WITH DOSE ESCALATION INTENSITY MODULATED RADIOTHERAPY (IMRT)
Authors: Thirada Ruetairuengnont, Chakkapong Chakkabat
Journal: Neuro-Oncology (2016)

Glioblastoma multiforme (GBM) is the most common malignant brain tumor. The major pattern of treatment failure is locally in-field recurrence. Optimal radiation dose and fractionation is currently under investigation to improve local control and survival. This study aimed to evaluated pattern of recurrence, tumor control and survival of dose-escalated radiotherapy (>60 Gy), using intensity modulated radiation therapy (IMRT) with simultaneous integrated boost technique (SIB), in GBM patients. Newly diagnosed GBM patients received Intensity Modulated Radiation Therapy (IMRT) with convention dose (60Gy in 30 fractions) (CD-IMRT) and escalated dose (66-75Gy in 30 fractions) (ED-IMRT) were retrospectively reviewed. All patients were evaluated for tumour response using RANO criteria. Pattern of failure were classified as central/in field, marginal and distant failure based on MRI and radiation treatment planning. Survival analysis were evaluated using Kaplan Meier analysis. 102 newly diagnosed GBM between June 2010 and January 2016 were retrospectively reviewed, 63 and 39 patients were treated with conventional dose (CD-IMRT) and escalated dose (ED-IMRT), respectively. With median follow-up time of 16 months, the median progression free survival of CD-IMRT and ED-IMRT were 9 and 13 months (p= 0.154). The median overall survival was 14 months in CD-IMRT but was not reached in ED-IMRT (p=0.017). One-year overall survival (OS) and progression-free survival (PFS) were 60.4% and 35.4% in CD-IMRT and 78.6% and 53.1% in ED-IMRT. For the pattern of failure evaluation, 79% and 100% were recurrence central/in field in CD-IMRT and ED-IMRT. Initial outcome of escalated radiation dose IMRT showed improvement of overall survival and progression free survival. The radiation dose escalation did not change pattern of recurrence, which was still locally in field failure.
P21.04 Clinical pathway in glioma management; from NOSC (Neuro-Oncology Scientific Club) meetings to bedside practice
Authors: K. Anvari, M. Fazl Ersi, H. Etemad-Rezaie, S. Nekooie, F. Arbabi, B. Ganjeifar, F. Bidouei, K. Nikkhah, M. Afarid, M. Torabi-Nami
Journal: Neuro-Oncology (2016)
Total Therapy 2 (TT2) for Multiple Myeloma (MM): Thalidomide (T) Effects Superior Complete Response (CR) and Event-Free Survival (EFS); Similar Overall Survival (OS) Linked to Shorter Post-Relapse Survival.
Authors: Guido Tricot, Erik Rasmussen, Elias Anaissie, Frits van Rhee, Maurizio Zangari, Klaus Hollmig, Lisa Jackson, Joshua Epstein, John Shaughnessy, John Crowley, Bart Barlogie
Journal: Blood (2005)
Adiponectin in Youth
Authors: Fida Bacha, Rola Saad, Neslihan Gungor, Silva A. Arslanian
Journal: Diabetes Care (2004)

We appreciate the comments of Stefan et al. (1) in this issue of Diabetes Care regarding adiponectin in youth. We are excited to have received the opinion of investigators in internal medicine, since traditionally pediatric investigations seldom cross the boundaries to adult medicine. The changing face of childhood diabetes might be playing a role (2). We offer the following responses.

1 ) Our study demonstrated associations and correlations between adiponectin and proinsulin and the proinsulin-to-insulin ratio. We never implied that a direct effect of adiponectin on insulin secretory function exists. However, as recommended by Stefan et al., we …
Inotuzumab Ozogamicin Versus Standard of Care for Relapsed/Refractory Acute Lymphoblastic Leukemia in the Phase 3 Randomized INO-Vate Trial: Outcomes By Salvage Treatment Phase
Authors: Anjali S. Advani, Elias J. Jabbour, Matthias Stelljes, Daniel J. DeAngelo, Michaela Liedtke, Wendy Stock, Nicola Gökbuget, Susan O'Brien, Kongming Wang, Tao Wang, M. Luisa Paccagnella, Barbara Sleight, Erik Vandendries, Hagop M. Kantarjian
Journal: Blood (2016)
Pharmacodynamic Activity and Preclinical Safety of CSL362, a Novel Humanised, Affinity Matured Monoclonal Antibody Against Human Interleukin 3 Receptor
Authors: Eva Herzog, Samantha Busfield, Mark Biondo, Gino Vairo, Mark DeWitte, Ingo Pragst, Gerhard Dickneite, Andrew Nash, Sabine Zollner
Journal: Blood (2012)
STMC-20. MIGRATING GLIOMA CELLS EXPRESS STEM CELL MARKERS AND GIVE RISE TO NEW TUMORS UPON XENOGRAFTING
Authors: Sune Munthe, Mia Sørensen, Mads Thomassen, Mark Burton, Torben Kruse, Justin Lathia, Frantz Poulsen, Bjarne Kristensen
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is the most frequent and malignant brain tumor with an overall survival of only 14.6 months. Although these tumors are treated with surgery, radiation and chemotherapy recurrence is inevitable. A critical population of tumor cells in terms of therapy, the so-called cancer stem cells (CSCs), has been identified in gliomas and many other cancers. These tumor cells have a stem cell-like phenotype and are suggested to be responsible for tumor growth, chemo- and radio-resistance as well as recurrence. However, functional evidence for migrating glioma cells having a stem cell-like phenotype is currently lacking. In the present study, the aim was to characterize the phenotype of migrating tumor cells using a novel migration assay based on serum-free stem cell medium and patient-derived spheroid cultures. The results showed pronounced migration of five different GBM spheroid cultures, but not of the commercial cell line U87MG. An in vitro limiting dilution assay showed preserved but reduced spheroid formation capacity of migrating cells. Orthotopic xenografting in mice showed preserved but reduced tumorigenic capacity. Profiling of mRNAs revealed no significant deregulation of 16 predefined CSC-related genes and the HOX-gene list in migrating cells compared to spheroids. Determination of GBM molecular subtypes revealed that subtypes of spheroids and migrating cells were identical. In conclusion, migrating tumor cells preserve expression of stem cell markers and functional CSC characteristics. Since CSCs are reported to be highly resistant to therapy, these results emphasize that the CSC phenotype should be taken into consideration in future treatment of GBMs.
Phase 1/2 study of the safety and clinical activity of durvalumab in patients with non-small cell lung cancer (NSCLC)
Authors: S.J. Antonia, J.R. Brahmer, S. Khleif, A.S. Balmanoukian, S.-H.I. Ou, M. Gutierrez, D.-W. Kim, S.-W. Kim, M.-J. Ahn, J. Leach, R. Jamal, D. Jaeger, G. Jerusalem, X. Jin, A. Gupta, J. Antal, N.H. Segal
Journal: Annals of Oncology (2016)
PEG Intron Treatment in 90 Patients with Essential Thrombocythemia (ET) Final Report of a Phase II Study.
Authors: Luigi Gugliotta, S. Bulgarelli, N. Vianelli, D. Russo, A. Candoni, S. Rupoli, R. Latagliata, S. Sacchi, V. Martinelli, E. De Biasi, A. Bucalossi, S. Mazzotta, A. Tabilio, F. Passamonti, A. Grossi, E. Cacciola, R. Cacciola, E. Pogliani, F. Bonifazi, R. Fanin, P. Leoni, F. Mandelli, A. Zaccaria, F. Lauria, M. Lazzarino, M. Gobbi, A. Bosi, P. Mazza, G. Fincato, P. Favini, M. Baccarani
Journal: Blood (2005)
Pre-Clinical Studies of Anti-CD123 CAR-T Cells for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Tianyu Cai, Roman Galetto, Agnès Gouble, Julianne Smith, Antonio Cavazos, Sergej Konoplev, Andrew A. Lane, Monica L. Guzman, Hagop M. Kantarjian, Naveen Pemmaraju, Marina Konopleva
Journal: Blood (2016)
Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes
Journal: Diabetes Care (2016)

OBJECTIVE In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ∼4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed. RESEARCH DESIGN AND METHODS All surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider’s judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated. RESULTS A total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P &amp;lt; 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02). CONCLUSIONS In high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.
Expression of mRNA as a prognostic factor of colon-rectal cancer.
Authors: Takafumi Watanabe, Kazuhiko Tamura, Masanobu Enomoto, Hitoshi Saitho, Yoshiaki Ohsaka, Yuu Takagi, Akihiko Tsuchida
Journal: Journal of Clinical Oncology (2013)

585 Background: Several cancer-associated genes are known as prognostic factors of colon-rectal cancer. We measured and compared mRNA expression levels for each gene in colon-rectal cancer tissues obtained from biopsied and excised specimens. Methods: 53 cases of colon-rectal cancer surgery were examined. By the DNP method, mRNA expression levels of cancer-associated genes were measured. Measurements and examinations were performed for 10 genes: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR and VEGF. Results: Among 53 patients who underwent operations for colon-rectal cancer, a comparison was conducted between 43 recurrence-free patients and 10 metastatic recurrent patients. Conclusions: The results thereof showed a tendency in metastatic recurrent cases toward decreased activity of Topo-I. Topo-I’s decrease in activity is said to be related to CPT-11 tolerance, and its low degree of activity in metastatic recurrent cases is predicted to be a factor in poor prognoses. At the same time, ERCC1 showed a tendency toward high activity in metastatic recurrent cases. ERCC1 is said to reduce sensitivity to platinum-based medications. Based on these results, further observation of the progress of treatment in each case is intended.
Validation and genomic interrogation of the <i>MET</i> variant rs11762213 as a predictor of adverse outcomes in clear cell renal cell carcinoma.
Authors: A. Ari Hakimi, Irina Ostrovnaya, Anders Jacobsen, Jonathan A. Coleman, Paul Russo, Roy Mano, Alexander Sankin, Robert John Motzer, Mark Purdue, Mark Pomerantz, Matthew L Freedman, Toni K. Choueiri, James Hsieh, Robert J. Klein
Journal: Journal of Clinical Oncology (2014)

395 Background: The exonic single nucleotide variant rs11762213 located in the METoncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC) (Schutz et al, Lancet Oncol 2013). We sought to validate this finding and explore the biologic implications using The Cancer Genome Atlas (TCGA) cohort. Methods: The variant call file (VCF) and expression data was available for 272 patients. We then extracted the data for rs11762213 as follows for the "normal" sample: allelic fraction for variant allele &gt; 80% is homozygous variant while allelic fraction for variant allele 30% to 70% is heterozygous. Paired tumor-normal materials, genomic data (whole exome, RNAseq, and DNA methylation) and clinical information were acquired from publically available TCGA datasets. Kaplan-Meier method was used to estimate the survival probabilities. Cancer specific survival (CSS) was analyzed using the competing risk method and Cox proportional hazard regression was used for analysis of time to recurrence. Multivariate competing risk models were also fitted in the TCGA cohort in order to adjust for the Mayo Clinic SSIGN score. Results: Overall, the variant allele of rs11762213 was detected in 10.3% of the cohort and was associated with higher nuclear grade (p=0.03) and trended toward higher clinical stage (p=0.07). After adjusting for the prognostic SSIGN score, the risk allele remained a significant predictor for adverse cancer specific survival (CSS; p&lt;0.0001; Odds Ratio [OR] 3.88, 95% confidence interval [CI] 1.99-7.56) and time to recurrence (TTR; p=0.003; OR 2.97; 95% CI 1.44-6.2). RNA sequencing data for MET did not reveal differences in tumor mRNA expression when stratified by risk allele, but did show differences in the normal kidney expression (p=0.02) in a smaller cohort (n=61). Conclusions: The exonic MET variant rs11762213 is an independent predictor of adverse CSS and TTR in ccRCC and could be integrated into clinical practice for prognostic stratification. Gene expression analysis suggests that inherited variation at MET influences expression of the gene in normal kidney tissue. Further external validation and biological interrogation is necessary.