tbuckley/cabot-search huggingface dataset:
ACTR-60. A PHASE 2, HISTORICALLY CONTROLLED STUDY TESTING THE EFFICACY OF TTFIELDS WITH ADJUVANT TEMOZOLOMIDE IN HIGH-RISK WHO GRADE II AND III ASTROCYTOMAS (FORWARD)
Authors: David Tran, Ashley Ghiaseddin, Anne Allen
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A long-standing observation in neuro-oncology concerns a group of patients with WHO Grade II and III gliomas expressing isolated hTERT promoter mutations, which exhibit indolent histological features but are highly aggressive and resistant to standard chemoradiation therapy. These patients show an overall survival rate similar to glioblastoma WHO Grade IV, necessitating new treatment options. This represents the first study of its kind testing novel treatment for this rare subgroup of lower grade gliomas with high-risk cytogenetics. METHODS This Phase 2, single arm, multicenter open label study [NCT03906448] will enroll 100 adult patients with newly diagnosed WHO grade II and III astrocytoma without IDH mutations and 1p/19q codeletions and with isolated hTERT promoter mutations who have completed standard radiotherapy with concurrent temozolomide, followed by adjuvant temozolomide for 12 cycles in combination with 24 months of TTFields therapy. The primary endpoint is overall survival compared to historical controls. Secondary endpoints are safety, quality of life, and progression free survival. Correlative studies will examine the effect of TTFields on intratumoral immune microenvironment and the role of electric field distribution on disease control and outcomes. Sample size was based on improvement in median OS versus historical controls (N=59; median survival 22 months). Improvements in median overall survival was based on a one-sided Wald test of the Weibull regression coefficient (H0: beta=0, alpha=0.05). A consortium of 15 institutions across the US will participate, with the first enrollment May 2019. Total accrual of 100 is planned over 36 months. The survival results and the correlative studies are designed to provide new insights for future therapeutic development for these patients.
Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx) in Refractory/Relapsed (R/R) DLBCL. a Real Life Study in Patients Ineligible for Autologous Transplantation
Authors: Clarisse Cazelles, Karim Belhadj, Helene Vellemans, Vincent Camus, Christiane Copie, Liana Veresezan, Emmanuel Itti, Stephanie Becker, Muriel verlinde Carvalho, Jehan Dupuis, Fabien Le Bras, Francois Lemonnier, Louise Roulin, Taoufik El Gnaoui, Fabrice Jardin, Nicolas Mounier, Herve Tilly, Corinne Haioun
Journal: Blood (2019)
IGLL5-BCL2L1 Rearrangement with Loss of BCL2 Dependency As Mechanism of Venetoclax Resistance in Multiple Myeloma (MM)
Authors: Jean-Baptiste Alberge, Sarthak Sinha, Ranjan Maity, Arzina Jaffer, Justin Donovan, Madison Kong, Stephane Minvielle, Paola Neri, Nizar Bahlis
Journal: Blood (2019)
The Factor VIII Variant X5 Enhances Hemophilia a Gene Therapy Efficiency By Its Improved Secretion
Authors: Franziska Horling, Johannes Lengler, Wenjing Cao, Biao Dong, Bagirath Gangadharan, Maurus De La Rosa, Werner Hoellriegl, Birgit M Reipert, Friedrich Scheiflinger, Weidong Xiao, Hanspeter Rottensteiner
Journal: Blood (2019)
RTHP-10. PREDICTORS OF LINEAR ACCELERATOR VERSUS GAMMA KNIFE STEREOTACTIC RADIOSURGERY USE FOR BRAIN METASTASES IN THE UNITED STATES
Authors: Shearwood McClelland III, Catherine Degnin, Yiyi Chen, Gordon Watson, Jerry Jaboin
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) for brain metastases is predominantly delivered via single-fraction Gamma Knife SRS (GKRS) or linear accelerator (LINAC) in 1–5 fractions. Predictors of SRS modality have been sparsely examined on a nationwide level. METHODS The 2010–2016 National Cancer Database identified brain metastases patients from non-small cell lung cancer throughout the United States (US) having undergone SRS. A multivariable logistic regression model characterized SRS receipt, adjusting for patient age, dose, geographic location of treatment, facility type, and distance from treatment facility. RESULTS A total of 1,760 patients received GKRS, while 1,064 patients received LINAC SRS. Treatment at non-academic facilities was associated with increased LINAC SRS receipt, most prominently in the Midwestern (OR= 6.23; p&lt; 0.001), Northeastern (OR= 4.42; p&lt; 0.001), and Southern US (OR= 1.96;p&lt; 0.001). Administered doses of 18–19 Gy (OR= 1.42;p= 0.025), 20–21 Gy (OR= 1.82;p&lt; 0.001), and 22–24 Gy (OR= 3.11;p&lt; 0.001) were associated with increased LINAC SRS receipt, as was patient location within 20 miles of a radiation treatment facility (OR= 1.27;p= 0.007). CONCLUSIONS Despite Gamma Knife being more prominently used over LINAC for SRS, patients treated at non-academic facilities outside of the Western US were substantially more likely to receive LINAC over Gamma Knife. Patients located in the Midwest were 523% more likely, Northeast 342% more likely, and South 96% more likely to receive LINAC when treated at a non-academic facility. Increasing dose independently predicted LINAC over GKRS, indicating that smaller tumors – particularly those less than two centimeters (consistent with RTOG 90-05 recommendations) – are being treated with LINAC. Finally, patients residing in close proximity to a treatment center were 27% more likely to receive LINAC, likely indicative of the increased geographic accessibility of LINAC compared with GKRS. These findings should result in hypothesis-generating questions to further explore predictors of LINAC versus GKRS.
A novel method of developing a high-affinity monoclonal antibody to detect native or pegylated human granulocyte colony-stimulating factor (G-CSF)
Authors: Yuan Zhou, Xin Wang, Hongzhi Liu
Journal: Cancer Research (2008)

3507  G-CSF (granulocyte-colony stimulating factor) is a haematopoietic growth factor which uis sually used as a drug with chemotherapy to boost white blood cell regeneration. In current studis, an association of the augmented expression of G-CSF has been revealed in many advanced tumors and/or poor prognosis in some clinical cases. Using immunohistochemical analysis and immunoassay to determine the protein expression level of G-CSF in advanced-stage or poorly differentiated adenocarcinoma become essential to monitor patients who are receiving or are to receive medication. Thus, the detection of human G-CSF level becomes one of the important tools in carcinoma-bearing patients.  In this study, by using our proprietary techniques, we’ve developed a panel of high-affinity monoclonal antibodies which were selected by native G-CSF and Pegylated G-CSF in vitro. The Kd of the monoclonal G-CSF antibodies is ranged from 50 picomolar to 1 micromolar. Higher affinity antibodies to pegylated human G-CSF and relatively low affinity antibodies to native human G-CSF were observed when animals were challenged by the same dosage of two different format of proteins. We’ve selected the highest affinity antibody as a capture reagent, and detected the lowest levels of native human G-CSF at 2.1 pg/ml and pegylated G-CSF at 4.8 pg/ml by recovery assays. The linear range of G-CSF detection is 5 pg/ml-15 ng/ml in both proteins.  In conclusion, we have developed a novel technique to produce a panel of high affinity antibodies. Additionally, we discovered the different performance of the native G-CSF and pegylated G-CSF in vivo. Our observation provided contradictory concerns in protein drug discovery: half-life enhancement or minimum immunogenicity.
Rituximab and Obinutuzumab Induce Direct B-Cell Death Via B-Cell Receptor (BCR) Signaling, but Rituximab Elicits Stronger BCR-Derived Pro-Survival Signals Diminishing Apoptosis
Authors: Jennifer Edelmann, Arran Dokal, Karlheinz Holzmann, David James Britton, Emma Vilventhraraja, Ryan Jack Smith, Mark S Cragg, Andrejs Braun, Hartmut Döhner, Pedro Cutillas, John G. Gribben
Journal: Blood (2019)
NIMG-53. 3D BRAIN TUMOR MODELING FACILITATES NEURO-ONCOLOGY CLINIC VISIT AND IMPROVES PATIENT HEALTH LITERACY AND VISIT SATISFACTION
Authors: Zoe Landau, Sarah Flora, Na Tosha Gatson
Journal: Neuro-Oncology (2019)

Abstract Explanation of brain tumor imaging (BTI) complexities to patients is a challenge in neuro-oncology. With limited tools, neuro-oncologist attempt to demonstrate tumor volumes and anatomy, estimate surgical risks, and treatment responses. Arming clinicians with alternative BTI might help alleviate the stress of initial patient consults and follow-up surveillance visits. These interactions are critical to the physician-patient relationship, patient compliance, and satisfaction. Currently, 2D-MRI review is standard, often leaving the patient with a less-than-complete understanding of their tumor. Historically, 3D-Brain-Tumor-Modeling (3DBTM) has been used for neurosurgical simulation and planning. Here, we evaluated the use 3DBTM alongside routine MRI impact on patient health literacy and satisfaction. Our institution introduced 3DBTM as a best practice approach. Images were presented as 3D video or tangible 3D color renditions, or 2D MRI. We collected patient pre-visit and post-visit surveys to assess patient’s understanding of tumor features, opportunity to review images, and patient level of satisfaction. Data from 277 pre-visit and 159 post-visit surveys was collected from the Geisinger Neuro-Oncology Clinic over a six-month period. Post-visit survey categories included reviews of: 3DBTM (n=54), 2D-MRI (n=51), and no imaging (n=55). Patients without CNS tumors were excluded (n=101). Pre-visit surveys showed 30% (n=82) of patients had little-to-no prior understanding of their tumor location and size, and 53% (n=147) of patients believed that a 3DBTM would improve their understanding. Post-visit analysis demonstrated that only 21% (n= 29) of patients reported not seeing any imaging during the visit. Nearly 85% (n=46) of patients who had reviewed a 3DBTM noted improved tumor understanding. Of the patients who solely viewed 2D-MRI, 68% (n=35) reported improved understanding of their tumor but would like more advanced imaging teaching. In total, 84% of patients noted overall satisfaction with the clinic visit. These results support the use of 3DBTM in patient education and facilitating clinical interviews.
The Indian Medical Service
Authors: T. C. Allbutt, H. Marsh, D. J. Cunningham, R. F. C. Leith, R. M. Murray, R. Stockman
Journal: BMJ (1902)

<h3>Abstract</h3> <h3>Objective</h3> The characteristics of discrete intracardiac electrograms in selective left bundle branch (SLBB) pacing (SLBBP) have not been described in detail previously. This study aimed to examine the effect of different high-pass filter (HPF) settings on discrete ventricular components in an intracardiac electrogram (EGM) and to analyze its possible mechanisms. <h3>Methods</h3> This study included 95 patients with indications of permanent cardiac pacing. EGMs were collected at four different HPF settings (30, 60, 100, and 200 Hz) with a low-pass filter at 500 Hz, and their possible mechanisms were analyzed. <h3>Results</h3> LBBP was successfully achieved in 92.6% (88/95) of patients. SLBBP was achieved in 80 patients. The occurrence rates of discrete EGM were 18.9%, 40.0%, 74.7%, and 84.2% for HPF settings of 30 Hz, 60 Hz, 100 Hz, and 200 Hz, respectively. The analysis of discrete ECG detection showed significant differences between the different HPF settings. By using the discrete EGM as the SLBB capture golden standard, the results of EGMs revealed that the 30 Hz HPF has a sensitivity of 23% and specificity of 100%. The 60 Hz HPF had a sensitivity of 48% and a specificity of 100%. The 100 Hz HPF had a sensitivity of 89% and a specificity of 100%. The 200 Hz HPF had a sensitivity of 100% and specificity of 100%. <h3>Conclusions</h3> An optimal HPF setting of 200 Hz is recommended for discrete electrogram detection. A discrete EGM should exhibit an isoelectric interval. A <b>steep</b> deflection and spinous ventricular EGM morphology nearly identify an intrinsic EGM morphology.
Chemotherapy of Cancer
Authors: D. A. Karnofsky
Journal: CA A Cancer Journal for Clinicians (1955)

The chemotherapy of cancer will continue to be a major area of biological and medical research until chemicals are found that control the growth of, or obliterate, all forms of the disease. Thus far, as a result of recent efforts, drugs have been introduced into clinical practice that exert regular therapeutic effects on some forms of neoplastic disease. They are useful in the management of many patients with nonresectable or disseminated cancer. A number of indirect benefits to the cancer patient have accrued from the work in chemotherapy. It has stimulated active concern for patients with advanced cancer, and, as a result, these patients are better cared for, and all the resources of medicine are being brought to bear on their individual problems. It has provided productive opportunities for clinical research, particularly in those patients who demand active therapy during the course of a relentless disease. It has kept patients and their families hopeful and cheered by the fact that something is being done. It has trained physicians to regard disseminated cancer as another form of chronic disease and impressed on them the therapeutic rewards from the skilled management of their patients through a sometimes rocky, progressive, and often protracted clinical course.
Cutaneous graft-versus-host disease incidence is similar in haploidentical and matched unrelated hematopoietic transplant recipients: A retrospective cohort study
Authors: Meghan M. Heberton, Shivani Tripathi, Michael Slade, Kathryn Trinkaus, Rizwan Romee, Milan Anadkat
Journal: Journal of the American Academy of Dermatology (2019)
PATH-03. DIFFERENCES IN CLINICAL COURSE OF GROUP-A AND GROUP-B POSTERIOR FOSSA EPENDYMOMA (PFA, PFB) AS DEFINED BY H3K27ME3 IMMUNOHISTOCHEMICAL ANALYSIS
Authors: Ushio Yonezawa, Fumiyuki Yamasaki, Motoki takano, Hiroki Taniguchi, Kazuhiko Sugiyama, Kaoru Kurisu
Journal: Neuro-Oncology (2019)

Abstract PURPOSE Posterior fossa ependymoma is classified as PFA and PFB based on underlying genetic/mutational characteristics, and PFA is reported to have poor prognosis compared to PFB. Recently, immunohistochemical findings of negative H3K27me3 have been reported to suggest PFA and attracted the attention as a surrogate marker. We classified our cases into PFA and PFB guided by immunohistochemical staining results of H3K27me3 and examined their clinical course. MATERIALS AND METHODS Between 1999 and 2018, 17 cases of posterior fossa ependymoma were treated at our institute. Negative immunostaining for H3K27me3 was classified as PFA, and positive as PFB. We evaluated age, gender, pathological diagnosis, progression free survival (PFS) and overall survival (OS) in both groups. RESULTS Nine cases were classified as PFA and eight as PFB. The median age of the PFA group was 4 years-old, 4 males, 5 females, pathological diagnosis was ependymoma in 5, and anaplastic ependymoma in 4 cases. The median follow-up period was 50 months, recurrence was confirmed in 5 cases (56%), PFS was 27.6 months. Three of the 5 patients who relapsed died (33%), and the OS was 50 months. The median age of the PFB group was 50 years, 4 males and 4 females, the pathological diagnosis was ependymoma in 6, and the anaplastic ependymoma in 2 cases. The median follow-up period was 111 months, recurrence was observed in 2 cases (25%), PFS was 98 months and all patients were alive during the period of this research. CONCLUSION Immunohistochemical results of H3K27me3 correlated with prognosis, implying the possibility of it being a surrogate marker of posterior fossa ependymoma.
ANGI-04. A NOVEL TROY-JAK1 SIGNALING COMPLEX IN GLIOBLASTOMA INVASION
Authors: Zonghui Ding, Jean Kloss, Serdar Tuncali, Nhan Tran, Joseph Loftus
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common and deadly malignancy of the central nervous system in adults with a median survival of about 15 months after diagnosis. Its aggressive and highly infiltrative nature renders the current standard treatment of maximal surgical resection, radiation, and chemotherapy relatively ineffective. Identifying the molecular events that regulate GBM migration/invasion is required to develop more effective therapeutic regimens to treat GBM. Expression of TROY, an orphan receptor of the TNFR superfamily, increases with increasing glial tumor grade, inversely correlates with patient survival, stimulates GBM cell invasion in vitro and in vivo, and increases resistance to temozolomide and radiation therapy. Conversely, silencing TROY expression inhibits GBM cell invasion, increases sensitivity to temozolomide, and prolongs survival in a preclinical intracranial xenograft model. Thus, the TROY signaling pathway represents an attractive therapeutic target. We previously reported that increased TROY expression strongly activates NF-kB. We have identified for the first time that TROY forms a unique signaling complex with JAK1. Interaction with TROY stimulates phosphorylation of JAK1 and significantly increases the activation of STAT3. TROY specifically associates with JAK1 as it does not associate with other JAK family members. Co-immunoprecipitation analysis demonstrated that TROY interacts with JAK1 through its cytoplasmic domain as a TROY variant without its extracellular domain associates with JAK1 while a TROY variant without a cytoplasmic domain fails to bind JAK1. Luciferase reporter assay confirmed that full length TROY or a variant lacking the extracellular domain are able to induce STAT3 activation, but not a TROY variant lacking the cytoplasmic domain. Pharmacological inhibition of JAK1 by the FDA approved inhibitor ruxolitinib or knockdown of JAK1 by siRNAs significantly inhibited TROY-induced STAT3 activation and GBM cell migration. Together, our data indicate that the TROY-JAK1 complex represents an unappreciated therapeutic target to inhibit glioma invasion and decrease therapeutic resistance.
"Prevalence and Outcome of Avascular Necrosis of the Hip (AVN) Among Young Omani Patients with Sickle Cell Disease"
Authors: Iman Al Fadhali, Farah Al-Kindy, Naema Alshibli, Salam Alkindi, Murtadha Al-Khabori, Abdulhakim Al Rawas, Asma Al Shezawi, Yasser Mahfouz, Surekha Tony Mevada, Yasser Wali
Journal: Blood (2019)
GENE-21. ROLE OF POT1 MUTATION IN GLIOMA PROLIFERATION AND SEXUAL DIVERGENCE OF SURVIVAL
Authors: Ali Jalali, Kwanha Yu, Vivek Beechar, Deepika Mehra, Brittney Lozzi, Melissa Bondy, Benjamin Deneen
Journal: Neuro-Oncology (2019)

Abstract Germline POT1 mutations are associated with risk of several cancers including glioma. In The Cancer Genome Atlas, we found that the level of POT1 gene expression in tumors is associated with overall survival in IDH wild-type glioma independent of age and tumor grade (P=0.036). To assess if POT1 expression in a native mouse model of IDH wild-type glioma (referred to as C3 tumors) affects survival, we targeted both mouse POT1 orthologs (Pot1a/Pot1b) in C3 tumors using CRISPR/Cas9, generating C5 tumors. Interestingly, we noted a sexual divergence of survival, with female C5 mice dying faster than males (P=0.0034), whereas C3 mice show no sexual divergence in survival. To assess the genes and pathways underlying this divergence, we performed RNAseq profiling on C3 and C5 tumors and normalized the sex differences in the C5 profile for baseline sex differences in the C3 profile. Compared to males, female C5 tumors had lower enrichment of numerous gene sets related to immune surveillance. To specifically assess the effects of glioma-associated human POT1 variants, we expressed these variants in a mouse tumor sphere culture. We noted that expression of POT1-G95C variant increased the rate of sphere formation in vitro. In vivo expression of this variant in embryonic mouse brain during the gliogenic period increased the proliferative rate as assessed by BrdU uptake (P=0.008). These findings suggest a potential role for human POT1 variants in growth and proliferation of glial progenitor cells as well as glioma tumor cells. Additionally, the sexual divergence of survival in C5 tumors points to a differential interaction between POT1 loss and sex in regulation of immune response to these tumors.
RARE-54. MEK INHIBITION FOR AGGRESSIVE GLIOMAS IN ADULTS WITH NEUROFIBROMATOSIS TYPE 1
Authors: Carlos Romo, Bronwyn Slobogean, Lindsay Blair, Jaishri O Blakeley
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Neurofibromatosis type 1 (NF1) is caused by mutations of the tumor suppressor gene NF1 resulting in decreased levels of neurofibromin and dysregulation of the RAS pathway, including MEK/ERK upregulation. Central nervous system malignancies have an overall standardized incidence ratio of 37.5 in population studies, with higher rates of aggressive gliomas in adults with NF1. Further, the response to standard glioma therapies in this population is mixed in published series. MEK1/2 inhibitors have shown activity in both NF1 driven plexiform neurofibromas and low grade gliomas, however, data is lacking about their optimal dose or sequencing relative to standard glioma therapies for adults with NF1 associated aggressive gliomas. We present recent experiences with the MEK1/2 inhibitor trametinib in adults with NF1 and newly diagnosed aggressive gliomas. METHODS A retrospective chart review was conducted on all adult patients with NF1 and astrocytoma treated with trametinib at the Johns Hopkins Brain Cancer Program from 2016 to 2018. RESULTS Four patients met selection criteria. Median age at diagnosis was 37 years [25–43]. Histologic diagnoses were: pilocytic astrocytoma (1), diffuse astrocytomas (2), and anaplastic astrocytoma (1). All tumors were IDH1 wild-type. Three received trametinib as frontline therapy (2 mg daily), one as second line treatment. All achieved a partial radiographic response within 2 months from the start of trametinib. Median overall survival was 15 months [4–19]; three patients are alive at publication, with a median of 12 months from diagnosis. Median progression-free survival was 2.5 months [1–11]. CONCLUSIONS Astrocytomas in adults with NF1, including histologically low-grade tumors, often have a more aggressive course than suggested by histology. These cases demonstrate clinical benefit from single agent MEK inhibition as well as possible synergistic effects with conventional therapies for gliomas in people with NF1, however, prospective investigation is needed.
North American Practice Patterns for PET-2 Positive Hodgkin Lymphoma
Authors: Muhammad Saad Hamid, Sarah C. Rutherford, Seongho Kim, Nancy L. Bartlett, Mary-Kate Malecek, Marcus Watkins, Kami J. Maddocks, David A. Bond, Tatyana A. Feldman, Gabriela Magarelli, Ranjana H Advani, Michael A Spinner, Sairah Ahmed, Deborah M. Stephens, Pamela Allen, Krish Patel, Michael T. Tees, Reem Karmali, Bruce D. Cheson, Maryam Sarraf Yazdy, Christopher Strouse, John M. Pagel, Radhakrishnan Ramchandren
Journal: Blood (2019)