tbuckley/cabot-search huggingface dataset:
RTHP-36. CONTRIBUTION OF DWI AND RADIATION THERAPY DOSE DISTRIBUTION TO RESPONSE ASSESSMENT IN PATIENTS WITH RECURRENT GLIOMA TREATED WITH REIRRADIATION
Authors: Andra Krauze, Jason Cheng
Journal: Neuro-Oncology (2016)

Despite increasing use of reirradiation (reRT) in recurrent glioma, there are no standardized criteria to evaluate response to therapy. We aimed to identify imaging and dosimetry features to help define criteria for treatment failure. 25 glioma patients reirradiated at NCI NIH between 2010 and 2016 with available diffusion weighted MRI (DWI) were included. reRT plans were coregistered with DWI at 1 and 2 to 3 months. Enhancing and nonenhancing abnormalities were contoured and analysed in conjunction with dose distribution using ECLIPSETM. Mean recurrence GTV and PTV were 24.8cc and 111.5cc respectively. Median initial dose and reRT dose were 60Gy and 30Gy respectively, median cumulative dose was 96Gy. Median follow-up was 5 months with median overall survival (OS) of 5 months (1.9-95). At 1month, enhancement was increased in 11 (44%) (4 outside the 50% isodose, 7 within the 100% isodose), stable or decreased 13(52%). 13 (52%) maintained increased perfusion. All patients with enhancement outside of the 50% isodose line displayed increased perfusion and all had immediate radiographic and clinical progression and a median OS of 1 month. Increased FLAIR volume at 1 month irrespective of relationship to isodose line did not predict for progression. At 2-3 months, 1 had complete response, 7 (28%) stable/improved enhancement, 6 (24%) progressed clinically, 7 (28%) had increased enhancement and/or FLAIR volume. No statistically significant correlation was identified between pre or post reRT steroid use/dose increase, bevacizumab use, enhancing and T2 FLAIR volume, restricted diffusion and clinical progression or OS. Documenting progression following reRT remains challenging. In our series, perfused enhancement outside of the reRT field was associated with rapid progression, while increased enhancement or T2 FLAIR volume did not necessarily result in progression. Progression post reRT will need to be based on close examination of DWI and reRT isodose lines in conjunction with clinical decline.
Allogeneic Transplant Following Brentuximab Vedotin Treatment in Patients with Relapsed or Refractory CD30+ Lymphomas
Authors: Tim Illidge, Reda Bouabdallah, Robert W. Chen, Ajay K. Gopal, Craig H. Moskowitz, Radhakrishnan Ramchandren, Joseph D. Rosenblatt, Andrei R. Shustov, Herve Tilly, Tanya Trippett, Laurie E. Grove, Ranjana H. Advani
Journal: Blood (2011)
DRES-07. SIGNIFICANT SEX DIFFERENCES IN TEMOZOLOMIDE EFFICACY IN GLIOBLASTOMA (GBM) ARE DETECTABLE IN CELL AND PATIENT BASED EVALUATIONS
Authors: Sara Taylor, Corbin Rayfield, Albert Kim, Melinda Broward, Anu Roy, Scott Weir, Kristin Swanson, Joshua Rubin
Journal: Neuro-Oncology (2016)

A considerable amount of research is currently focused on the biology of sex differences under normal and pathological conditions. The work has highlighted the multiple mechanisms by which sexual differentiation affects disease phenotype. An important aspect of this for brain tumor patients is potential sex differences in therapeutic responses. While a focus on sex differences in immune function, drug metabolism, and blood-brain barrier function are important considerations, the potential for tumor cell-intrinsic mechanisms is often overlooked. We undertook a staged evaluation of cell intrinsic differences in the response of male and female glioblastoma cells to standard and experimental therapeutics. In the first stage, we screened the 5,500 FDA Bioactives Library with male and female murine GBM cells. This screen identified approximately 30 compounds with significant sex differences in activity, including temozolomide and other alkylators, PI3 kinase-AKT-mTOR pathway inhibitors, as well as EGFR antagonists. Next, we determined that temozolomide had significantly greater cytotoxic effects in a panel of female compared to a panel of male primary human GBM specimens. Finally, we assessed the therapeutic response, by way of radial tumor growth rate, on clinical T1 Gadolinium MRIs for 22 female and 38 male patients treated with radiation and temozolomide and found that adjuvant temozolomide exhibited significant sex differences in therapeutic effects in patients. Specifically, female patients exhibited better tumor control as the number of cycles of temozolomide increased. Together, these data indicate that temozolomide treatment may be further optimized by tailoring it to its sex-specific activity and that sex differences for all therapeutics should be further evaluated in lab and clinic based studies. Finally, our murine cell based sex-specific drug screening is a valuable platform for detecting sex differences in therapeutic effects.
Erratum: CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer (Nature Medicine (200) 10 (7-381))
Authors: Zhongmin Guo, Jürgen F. Linn, Guojun Wu, Sarah L. Anzick, Claus F. Eisenberger, Sarel Halachmi, Yoram Cohen, Alexey Fomenkov, Mohammad O. Hoque, Kenji Okami, Gabriel Steiner, James M. Engles, Motonabu Osada, Chulso Moon, Edward Ratovitski, Jeffrey M. Trent, Paul S. Meltzer, William H. Westra, Lambertus A. Kiemeney, Mark P. Schoenberg, David Sidransky, Barry Trink
Journal: Nature Medicine (2004)
Platelet Glycoprotein VI: An Adenine Insertion in Exon 6 Generates a Truncated Form of the Protein Associated with Bleeding Disorder in 4 Chilean Unrelated Patients
Authors: Valeria Matus, José Guillermo Valenzuela, Claudia G Sáez, Patricia Hidalgo, Olga Panes, Jaime Pereira, Diego Mezzano
Journal: Blood (2012)
Case 5-2017
Authors: Michael L. Blute, Jeremy S. Abramson, Kevin C. Cronin, Valentina Nardi
Journal: New England Journal of Medicine (2017)

A 19-year-old man presented with a 2-day history of hematuria, without pain, after hiking. Imaging revealed a well-circumscribed 4.6-cm retroperitoneal mass. A procedure was performed.
PDCT-03. CLINICALLY INTEGRATED SEQUENCING IN THE MANAGEMENT OF CHILDREN WITH HIGH-RISK BRAIN TUMORS
Authors: Carl Koschmann, Bernard Marini, Lydia Benitez Colon, Yi-Mi Wu, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Dan Zamler, Sandra Camelo-Piragua, Sriram Vennneti, Paul Mc Keever, Kathryn McFadden, Andrew Lieberman, Lina Shao, Amanda Fisher-Hubbard, Avneesh Gupta, Lilly Pritula, Jessica Everett, Michelle Jacobs, Rhonda Mcdougall, Marcia Leonard, Cormac Maher, Hugh Garton, Karin Muraszko, Pedro R. Lowenstein, Maria G. Castro, Dan Robinson, Arul Chinnaiyan, Rajen Mody
Journal: Neuro-Oncology (2016)

In contrast to adult tumors, recent studies of pediatric tumors have shown that most harbor relatively few mutational events, many of which may be targetable with clinically available agents. We set out to evaluate the use of integrative clinical sequencing and genetic counseling in the management of pediatric patients with high-risk brain tumors. We performed an observational consecutive case-series involving 31 pediatric patients with brain tumors designated by treating neuro-oncologist to be high risk (>25% chance for treatment failure) (mean age 7.1 years, range age 0-17). Participants underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing and genetic counseling. Results were discussed in a CNS precision medicine tumor board teleconferenced with clinicians at multiple children’s hospitals, which made recommendations. Targeted agents were recommended based on a system involving seven criteria, including pre-clinical/clinical data, CNS penetration data, and availability of the agent either through clinical trial or off-label use. Of the 31 enrolled patients, 25 (80.6%) had adequate tumor specimen for DNA/RNA sequencing [including 7 GBM/DIPGs, 8 medulloblastomas, 4 (16%) relapsed and 8 (32%) metastatic tumors]. Sequencing revealed actionable germline or somatic alterations in 12 (48%) tumors, of which 9 (36%) resulted in an impact on treatment, and 3 (12%) resulted in genetic counseling for germline finding. Seven of 11 patients (63.6%) with glial tumors were found to have an actionable result. Most targeted therapeutic interventions included use of tyrosine kinase inhibitors, HDAC inhibitors, or mTOR inhibitors. Two of 25 patients (8%) with therapeutic intervention achieved partial remission (8 months and 3 months/ongoing) and 6 (24%) had ongoing stable disease (1 to 10 months). In summary, clinically integrated sequencing resulted in alteration of management in 48% of high-risk pediatric brain tumor patients and was of particular relevance to those with glial tumors.
IMST-52. OMX, AN IND-STAGE BROAD-ACTING OXYGEN CARRIER, IMMUNOSENSITIZES THE TUMOR MICROENVIRONMENT AND PROMOTES EFFECTOR T CELL RESPONSES IN THE GL261 INTRACRANIAL SYNGENEIC GLIOBLASTOMA MODEL
Authors: Natacha Le Moan, Philberta Leung, Catherine Bedard, Sarah Ng, Tina Davis, Carol Liang, Kevin Leong, Kevin Tanaka, Tim Keating, Nicholas Butowski, Jonathan Winger, Stephen Cary, Ana Krtolica
Journal: Neuro-Oncology (2016)

Hypoxia, or lack of oxygen, is a hallmark of glioblastoma and is correlated with tumor progression and decreased overall survival. As a key modulator of the tumor microenvironment, hypoxia promotes immunosuppression through activation of multiple signaling pathways such as hypoxia-inducible factor/HIF signaling. OMX is an oxygen carrier biotherapeutic previously shown to: a) be well tolerated in small and large animals, b) efficiently accumulate in spontaneous canine brain tumors and rodent orthotopic glioblastoma (GL261 and F98), and c) significantly reduce hypoxia and improve radiotherapy efficacy in multiple tumor models. We immunohistochemically evaluated in GL261 model CD8+ (CTL) and CD4+ T lymphocyte infiltration into tumor areas that were hypoxic prior to treatment. We then characterized tumor infiltrating populations of NK cells, activated CTL (granzyme B+), and Treg (CD8+ FoxP3+) by flow cytometry in early and late stage GL261 tumors. Similar to previously published findings, we demonstrated CTLs are mostly excluded from hypoxic tumor areas in the GL261 model. Furthermore, a single OMX treatment in GL261 tumor-bearing mice reduces tumor hypoxia, enhances T cell localization in previously hypoxic tumor areas, and increases total CTL accumulation by ~4-fold. OMX treatment increased the activated CTL fraction by ~2 fold, while the immunosuppressive Treg fraction was reduced 2-fold. This resulted in a 3-fold increase of Teffector/Treg ratio, indicating a switch from an immunosupressive to an immunopermissive microenvironment. These data were confirmed in other subcutaneous tumor models. Results from ongoing OMX-checkpoint inhibitor combination survival studies are pending. By delivering oxygen specifically to the hypoxic tumor microenvironment, OMX may restore anti-cancer immune responses in glioblastoma patients. Given its good tolerability, dual mechanism of action as a radiation and immuno sensitizer, and broad multipathway activity, OMX may synergize with both radiotherapy and immuntherapy to enhance tumor control and improve patient outcomes.
Minimal Risidual Disease monitoring in Childhood Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Preliminary Results of JPLSG Ph+ALL04.
Authors: Hirohide Kawasaki, Souichi Adachi, Akira Ohara, Atsushi Kikuta, Atsushi Sato, Hiroyuki Takahashi, Motoaki Chin, Masahiro Tsuchida, Kazuko Hamamoto, Kouichi Matsumoto, Keiko Yagi, Hiromasa Yabe, Makoto Yoshida, Tsutomu Watanabe, Atsushi Manabe
Journal: Blood (2009)
Pimasertib (PIM) versus dacarbazine (DTIC) in patients (pts) with cutaneous NRAS melanoma: a controlled, open-label phase II trial with crossover
Authors: C. Lebbe, C. Dutriaux, T. Lesimple, W. Kruit, J. Kerger, L. Thomas, B. Guillot, F. de Braud, C. Garbe, J.J. Grob, C. Loquai, V. Ferraresi, C. Robert, P. Vasey, R. Conry, R. Isaacs, E. Espinosa, A. Schueler, A. Markivskyy, B. Dreno
Journal: Annals of Oncology (2016)
Differential morphological and functional features of fibroblasts explanted from solar lentigo
Authors: R. Goorochurn, C. Viennet, M. Tissot, F. Locatelli, C. Granger, N. Varin-Blank, P. Humbert, C. Le Roy
Journal: British Journal of Dermatology (2017)

Upon ageing, chronic exposure to ultraviolet radiations and pollution induces benign hyper-pigmented lesions, such as Solar Lentigo maculae (SL) 1. Well-defined histologically, SL is distinguishable from other hyper-pigmented diseases and can be classified relative to its evolution 2-4. Differential gene-profiling analyses comparing SL and normal skin biopsies revealed that SL tissues are mainly composed of epidermal activated melanocytes as well as hypo-proliferating and hypo-differentiated keratinocytes with a background of chronic inflammation. In absence of fibroblast markers, immuno-staining analyses for several growth factors and secreted proteins in the upper dermis of SL biopsies strongly suggest that dermal fibroblasts contribute functionally to dysregulation of epidermal cells 5. These observations are strengthened by recent studies using a pigmented reconstructed skin model that demonstrates the influence of dermal fibroblasts on skin pigmentation 6. However, data on the morphological and functional features of the SL primary fibroblasts that could explain their role in SL disease are not available.

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ACTR-28. USE OF TUMOR TREATING FIELDS IN THE FIRST LINE TREATMENT OF GLIOBLASTOMA
Authors: Manjari Pandey, Lindsey Lands, Madison Michael, Jeffrey Sorenson, Alva Weir, Brandon Baughman, Matthew Ballo
Journal: Neuro-Oncology (2016)

Tumor Treating Fields (TTF) are low-intensity, intermediate frequency, alternating electric fields delivered via a portable medical device (Optune). In October 2015 U.S. Food and Drug Administration (FDA) approved Optune for use with temozolomide in adult patients with newly diagnosed glioblastoma following surgery and concurrent chemoradiation. We identified all patients with glioblastoma at the West Cancer Center treated with Optune TTFs in first line therapy. Retrospective chart review was performed to evaluate patient characteristics, tumor and treatment related variables. From November 2015 - June 2016, 13 patients were started on therapy with TTFs after surgery and chemoradiation. Median age was 59 years (range 26–70); 10 men, 3 women; median ECOG performance score 1. Five patients underwent gross total resection, 5 subtotal resection and 3 had biopsy. MGMT was methylated in 7 patients and unknown in 3. All patients received radiation, 57–60 Gy in 30 fractions with temozolomide. 1 patient switched from temozolomide to bevacizumab/irinotecan during radiation and another patient did not get adjuvant temozolomide. Optune was started 17.6 weeks (median; range 34.7-12.8) after surgery and 38 days (range 5–174) from completion of chemoradiation. Commonly reported adverse effects were skin toxicity (7 pts); fatigue (2 pts) and headaches (2 pts). Compliance ranged from 7.4 to 94.93%, median 69.73%, six pts had compliance <75% (data not available for 2 pts). 7 patients have been on TTFs for over 3 months; 3 progressed and 4 are stable or responding. Experience with the use of TTFs in first line treatment of glioblastoma outside of a clinical trial is limited. Our center is one of the highest volume centers using TTFs, we share our single center experience with the use of this device in our patient population.
Factor VIII and Factor IX Mutation Analysis in 600 U.S. Hemophilia Patients: Correlation of Mutation Type with History of Inhibitor
Authors: Connie H. Miller, Craig Hooper, Thomas C. Abshire, Paula L. Bockenstedt, Doreen B. Brettler, Jorge Di Paola, Gita Massey, Anne T. Neff, Amy D. Shapiro, Michael Tarantino, Brian M. Wicklund, Marilyn J. Manco-Johnson, Amy L. Dunn, Christine Knoll, Melissa Creary, Jane Benson, Dorothy Ellingsen, Jennifer Driggers, J. Michael Soucie
Journal: Blood (2008)
NIMG-35. EFFECT OF BEVACIZUMAB ON TUMOR GLUCOSE UPTAKE IN PATIENTS WITH HIGH GRADE GLIOMAS
Authors: Surabhi Ranjan, Jing Wu
Journal: Neuro-Oncology (2016)

Bevacizumab, is a monoclonal antibody directed against the vascular endothelial growth factor receptor. It alters tumor vasculature and likely underlying tumor cell metabolism. Studies using metabolic positron emission tomography (PET) methods like [18F]-fluoro-3-deoxy-3-L-fluorothymidine and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine have shown that changes in PET uptake after bevacizumab infusion are predictive of progression-free and overall survival. The effect of bevacizumab on glioma glucose uptake as evaluated by 18F-fluorodeoxyglucose (FDG) PET is unknown. Establishing an imaging biomarker capable of identifying tumor response during treatment with anti-angiogenic therapy may be worthwhile. Under an institutional review board approved retrospective protocol, uptake values of FDG-PET scans performed before and after bevacizumab infusion were analyzed in 47 cases of recurrent high grade gliomas (30 glioblastomas, 12 anaplastic astrocytomas, 3 anaplastic oligodendrogliomas and 2 anaplastic oligoastrocytomas). Baseline FDG-PET scans prior to bevacizumab infusion revealed that 41 patients (87.2%) showed a high FDG uptake, 4 patients (8.5%) showed an intermediate FDG uptake signal between white and gray matter, and 2 patients (4.3%) showed no increased FDG uptake. After bevacizumab infusion, 20 patients (42.5%) showed a decreased FDG uptake. Twenty-five patients (53.2%) had no change in FDG uptake after bevacizumab infusion. Two patients (4.3%) showed an increase in FDG uptake as compared to baseline FDG-PET scan. Tumor metabolism as assessed by FDG uptake was decreased in nearly half of the recurrent high grade gliomas after bevacizumab infusion. Further studies are needed to determine if this decrease in FDG-PET signal after bevacizumab is an early predictive signal of therapeutic response to anti-angiogenic agents.
Clinical outcome of patients with advanced biliary tract cancer in a dedicated phase 1 unit
Authors: R. Sundar, A. Custodio, J. Lim, M. Chenard-Poirier, D. Collins, S. Kaye, T.A. Yap, U. Banerji, J. Lopez, J.S. de Bono
Journal: Annals of Oncology (2016)
Alemtuzumab as a Single Agent or Combined with Methylprednisolone (MPD) or Fludarabine (FDR) for the Treatment of CLL Patients with p53 and ATM Deletions.
Authors: A. Sebrango, A. De la Iglesia, J.A. Garcia-Vela, S. Ferrer, E. Ruiz, B. Navarro, R. Fores, F. Carbonell, P. Sanchez-Godoy, M.N. Fernandez, Jose A. Garcia-Marco
Journal: Blood (2007)
STMC-13. TUMORSPHERE ISOLATION FROM WHO GRADE IV GLIOMAS ACCORDING TO THE WEIGHT OF FRESH SPECIMENS
Authors: Kyoung-Su Sung, Jin-Kyong Shim, Ji-Hyun Lee, Se Hoon Kim, Sohee Park, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Jong Hee Chang, Seok-Gu Kang
Journal: Neuro-Oncology (2016)

A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma (GBM) patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.
EXTH-29. DEVELOPMENT OF TERT-TARGETING THERAPY AGAINST GLIOBLASTOMA
Authors: Masamichi Takahashi, Yuko Matsushita, Shunichiro Miki, Kohei Fukuoka, Yoshiko Maida, Mami Yasukawa, Mitsuhiro Hayashi, Akitake Mukasa, Ryo Nishikawa, Kenji Tamura, Akinobu Hamada, Kenkichi Masutomi, Yoshitaka Narita, Koichi Ichimura
Journal: Neuro-Oncology (2016)

Despite the intense genome analysis, an effective molecular targeting therapy is yet to be developed for glioblastoma (GBM). The mutation in the promoter region of telomerase reverse transcriptase (TERT) is observed in approximately 60-80% of GBM, causing upregulation of TERT protein, which helps maintain telomeres. It has been reported recently that TERT has an RNA-dependent RNA polymerase (RdRP) activity (Maida, Nature2009) and TERT-RdRP activity controls cell cycle and maintains stem cell phenotype, suggesting that TERT can be directly targeted to suppress tumor cell proliferation. We have previously identified eribulin as a specific inhibitor of RdRP activity of TERT through a drug screening. Here we investigated the anti-tumor efficacy of eribulin using human GBM cell lines. The TERT promoter status was examined in 20 glioma cell lines. Seven cell lines were subjected to in vitro cytotoxicity assay. U87MG was either subcutaneously or intracranially transplanted in nude mice. Tissue or plasma concentration of eribulin was measured by LC-MS/MS. All GBM cell lines tested that harboured TERT promoter mutations were highly sensitive to eribulin. Intraperitoneal administration of eribulin completely suppressed the growth of U87MG subcutaneous tumor in nude mice. In brain tumor mouse model, a high concentration of eribulin was detected in the brain tumour tissues as early as 15 minutes after intravenous injection of eribulin, which remained stable even 24 hours later when the plasma concentration of eribulin became undetectable. Finally, intraperitoneal administration of eribulin significantly prolonged the survival of mice with intracranial U87MG xenograft (p<0.001). The RdRP activity in tumor tissue was diminished after eribulin administration. Our results showed that eribulin has a strong anti-tumour effect against GBM cells possibly through inhibition of RdRP activity. Eribulin thus appears to be a promising novel TERT-targeting therapeutic agent against GBM. A clinical trial is being scheduled.