tbuckley/cabot-search huggingface dataset:
Phase II trial of repeated carcinoembryonic antigen (CEA) radioimmunotherapy (RAIT) with 131I-Labetuzumab post salvage resection of colorectal metastases in the liver
Authors: T. Liersch, J. Meller, T. Lorf, C. Sahlmann, C. Langer, B. Ghadimi, W. Wegener, H. Becker, D. Goldenberg
Journal: Journal of Clinical Oncology (2006)

13572 Background: Complete resection of liver metastases (LM) remains the treatment of choice for colorectal cancer (CRC). As shown recently (Liersch et al., JCO 2005; 23:6763–70), RAIT with a single application of the humanized monoclonal anti-CEA antibody, 131 I-labetuzumab, improved both the median overall survival (OS) and 5-yr survival rates significantly in patients post salvage resection of LM. The major adverse side effects (≤ grade 3 CTC) were transient myelosuppression and/or thrombocytopenia in patients receiving 40 to 60 mCi/m 2 of 131 I-labetuzumab. These encouraging results stimulated the current ongoing Phase-II trial to evaluate the safety of repeated RAIT at doses of 2 × 50 mCi/m 2 (3 mos apart), post salvage resection of LM. Methods: At present, 13 patients (primary CRC: 8x UICC stage IV, 1× UICC stage III and 4× UICC stage II) who underwent surgery for LM of CRC (postsalvage mTMN stages: 4× mT4, 2× mT3, 6× mT2, 1× mT1) have received the first dose of 50 mCi/m 2 131 I-labetuzumab within 2 mos of LM surgery. Three months later, a second infusion of 50 mCi/m 2 has already been given to 5 pts. In two, a dose reduction to 40 mCi/m 2 was performed. At re-staging CT and PET scans) for the 2 nd RAIT, in one patient pulmonary metastases were diagnosed and in another patient a re-resection of hepatic relapse was performed. Results: In the previous trial, at a median follow-up of 67 mos, the median OS from the first liver resection for 19 pts treated with single-dose RAIT was 68.0 mos and median DFS was 18.0 mos. Also, 5-year survival was achieved by 51.3% of RAIT pts independently of bilobar involvement, size and number of LM, or resection margins. In the current study with repeated RAIT, transient grade-4 myelosuppression (2 cases in combination with a myelotoxic thiamazol medication) occurred in 4/13 pts after the first dose (1× grade 4 thrombocytopenia). No cumulative toxicity was seen in 6 of 7 RAIT-re-treated patients. Complete bone marrow recovery was observed in all 6 cases within 5–12 weeks; in one pt severe neutropenia persisted to about week 16 post 2 nd RAIT. As of January, 2006, patient compliance was 100%. Conclusion: RAIT re-treatment to-date appears to be safe, feasible, and well accepted. Extended follow-up data are being collected. [Table: see text]
O-005 Comparative molecular analyses of esophageal adenocarcinoma, esophageal squamous cell carcinoma, and gastric adenocarcinoma, and impact of molecular profile on outcome
Authors: M. Salem, J. Xiu, W. El-Deiry, S. Reddy, P. Philip, Z. Gatalica, S. Khan, C. Denlinger, S. Mikhail, B. Smaglo, M. Pishvaian, J. Hwang, A. Shields, J. Marshall
Journal: Annals of Oncology (2016)
developmental therapeutics Phase I study of the pan-fibroblast growth factor receptor (FGFR) inhibitor BAY 1163877 with expansion cohorts for subjects based on tumor FGFR mRNA expression levels
Authors: M. Joerger, R. Soo, B.C. Cho, A. Navarro Mendivil, C. Sayehli, H. Richly, D. Tai, D.-W. Kim, J. Wolf, P. Cassier, P. Ellinghaus, S. Hildebrandt, S. Behre, C. Helmbrecht, S. Kerpen, D. Zielinski, S. Ince, P. Rajagopalan, M. Ocker, M. Schuler
Journal: Annals of Oncology (2016)
The efficacy of a simple surveillance and ordering system for hepatitis virus B reactivation
Authors: Rika Sakai, Manabu Sakurai, Makoto Ueno, Haruhiro Saito, Kaori Tsuboi, Kikuko Matsuba, Yasufumi Ishiyama, Ayumi Numata, Yukako Hattori, Hirotaka Takasaki
Journal: Annals of Oncology (2016)
QLIF-13. DESCRIBING SYMPTOM BURDEN AND FUNCTIONAL STATUS AT DIAGNOSIS OF LEPTOMENINGEAL METASTASIS
Authors: Julie Walker, Barbara O’Brien, Elizabeth Vera, Terri Armstrong
Journal: Neuro-Oncology (2016)

Patients with leptomeningeal metastases (LM) have disease burden involving the membranes surrounding the brain, spinal cord or both, and a short disease trajectory. Limited studies have explored presenting symptoms and clinical factors and their relationship to functional status and symptom burden. This study aims to investigate associations of primary cancer, tumor characteristics and cancer treatment history with number and type of symptoms, and functional status. Records of 52 patients with LM were reviewed. Endorsed symptoms were recorded using the MDASI-BT and MDASI-SP. Demographic and clinical data were collected. Descriptive statistics were employed to describe the sample, independent sample T tests, and one-way Analysis of the Variance (ANOVA) were performed to explore the mean differences in type of symptoms, number of symptoms and functional status as measured by Karnofsky Performance Score (KPS). Pearson correlations were performed to assess correlation between age and number of symptoms with type of symptoms. Pain was the most frequently reported presenting symptom, followed by numbness/tingling. Fifty-eight percent of patients had poor KPS (KPS<90). Poor KPS was significantly associated with CSF leukocytosis (X2(1)4.46, p=.04). Memory problems (t(50)-4.52, p=.000) and vomiting (t(50)-2.79, p=.007) were significantly associated with a higher number of symptoms overall. Fatigue was significantly associated with spinal radiation (X2(1)19.55, p=.000) and CSF lymphocytosis (X2(2)14.19, p=.001). While the retrospective nature of this study is a limitation, it sheds light on symptom burden and functional status of LM patients at diagnosis, exposing the need for prospective studies interested in symptom burden and quality of life in this population.
MPTH-42. NEUROPATHOLOGICAL AND MOLECULAR CHARACTERIZATION OF LONG-TERM SURVIVAL GLIOBLASTOMAS (LS-GBM): A STUDY ON 52 CASES
Authors: Bianca Pollo, Chiara Calatozzolo
Journal: Neuro-Oncology (2016)

GBM is associated with a very poor prognosis. However a small group of patients had more than 5 years of survival after diagnosis. The clinical and molecular data reported for LS-GBM patients do not explain this favourable outcome. The aim of our study is to evaluate histopathological features, immunohistochemical and molecular genetic profile useful to identify a subset of GBMs with long survival. We reviewed 52 patients with a minimum survival of 5-year among 1126 patients with newly diagnosed GBM, recorded in our Tumor Registry from 2000 through 2010. In these group of LS-GBMs we achieved clinical data and follow-up. Tumor location was supratentorial in all the patients. We analysed the histopathological parameters and the presence of lymphocytic infiltrates, microglia and macrophages. All these cases were evaluated for p53, IDH1(R132H), MGMT methylation status and LOH on 1p, 19q, 9p, 17p and 10q. We also evaluated immunoistochemical expression of: PDGF, PDGFR-α, PDGFR-β, VEGF, EGFR, EGFRvIII, PTEN, FGFR3, c-Met, YKL-40, ATRX and TERT. As a new insight, we assess the immunological status of this group of tumors, investigating the expression of Interferon inducible protein 16 (IFI16), having a role in the immunomodulation of innate and adaptive immunity. Tumor infiltrates were characterized by CD2, CD3, CD4, CD8, CD68 and IBA1. We didn’t found particular molecular profiles in LS-GBM respect short-term ones: no differences on methylation status, only one case with EGFRvIII and 2 cases with IDH1(R132H) mutations. All but one cases were positive for ATRX, while TERT expression was lower than in other GBM. The major part of GBM had p53 positivity, and we observed a correlation with nucleolar expression of IFI16. We detected a major expression of CD3+/CD8+ cells in glioblastomas with prevalent IFI16 nucleolar expression and strong activation of both microglia and macrophages, suggesting an active role of IFI16 in immuno-surveillance.
NIMG-53. PREDICTIVE CYTOLOGICAL TOPOGRAPHY MAPS REGIONS OF PATHOLOGICALLY CONFIRMED NON-ENHANCING HYPERCELLULAR TUMOR IN GLIOBLASTOMA PATIENTS
Authors: Sarah Hurrell, Sean McGarry, Elizabeth Cochran, Jennifer M. Connelly, Scott Rand, Joseph Bovi, Peter S. LaViolette, Kathleen M. Schmainda, Amy Kaczmarowski
Journal: Neuro-Oncology (2016)

Clinical imaging is important in the detection and treatment of glioblastoma (GBM), where different magnetic resonance imaging (MRI) contrasts to classify tumor and plan treatment. Despite advances in modern MRI technology, differentiation of treatment effects from infiltrative tumor remains a difficult and clinically relevant problem. This study uses a new technique, predictive cytological topography (PiCT), which combines imaging and histology to address this issue. Thirteen patients with GBM were assessed at autopsy. Brains were sliced axially to match pre-mortem MR images and samples were collected from various locations (e.g., center of tumor, surrounding rim, normal white and gray matter). The samples were then digitized and cell nuclei were segmented. Samples were then co-registered to matching MRI slices and cell count was assessed voxel-wise. The MRI values and corresponding cell counts were used to train a machine learning algorithm which was then applied to generate PiCT maps of cell density. To validate these maps, tissue samples were taken from new regions predicted to contain hypercellularity and evaluated. Hypercellularity was defined by our board certified pathologist. Predictive maps correctly identified regions of non-enhancing hypercellularity in all 13 patients. We present a new method for predictively mapping brain tumor cellularity beyond contrast enhancement. This technique could improve treatment planning and disease monitoring.
KRAS status and HER2 targeted treatment in advanced gastric cancer
Authors: E. Shinozaki, H. Osumi, K. Chin, M. Ogura, D. Takahari, T. Ichimura, T. Matsushima, T. Wakatsuki, I. Nakayama, Y. Imamura, M. Watanabe, K. Yamaguchi
Journal: Annals of Oncology (2017)
EXTH-58. DEVELOPING POLYMERIC SCAFFOLDS TO ENHANCE NEURAL STEM CELL THERAPY FOR POST-OPERATIVE GLIOBLASTOMA
Authors: Kevin Sheets, Onyinyechukwu Okolie, Simon Khagi, Matthew Ewend, Mahsa Mohiti-Asli, Stephen Tuin, Elizabeth Loboa, Karen Aboody, Shawn Hingtgen
Journal: Neuro-Oncology (2016)

Genetically engineered tumoricidal neural stem cells (tNSCs) are a promising therapy for the highly aggressive brain cancer Glioblastoma (GBM). tNSC therapy recently entered human patent testing based on the strength of pre-clinical studies. Yet, retention of tNSCs within the surgical resection cavity is emerging as a major limitation to this promising therapy. We recently discovered that polymeric scaffolds significantly increase the persistence of therapeutic stem cells in the GBM resection cavity, remain permissive to stem cell tumoritropic homing, and markedly prolong the survival of mice with post-operative GBM. Limitations to previous scaffold designs were likely to prevent the effective application of scaffold/tNSC therapy in a clinical setting. In this study, we combined human tNSCs currently in human patient testing with a panel of bio-degradable polymeric scaffolds to 1) explore the scaffold parameters required to maximize scaffold/tNSC treatment of post-surgical GBM and 2) achieve a scaffold design compatible with eventual patient testing. Using mouse models of GBM resection/recurrence, we tested polymeric poly(L-lactic acid (PLA) scaffolds and found that varying fiber diameter, three-dimensionality, and coating all increased tNSC delivery compared to the clinical standard of direct injection. Delivery was maximal when tNSC were delivered on gelatin-based matrices (GeM). GeM increased tNSC levels 8-fold three days post-delivery compared to direct injection, while prolonging persistence in the surgical cavity 9-fold. GeM remained permissive to tNSC migration as tNSCs populated minimal ­residual tumor foci boarding the resection cavity. Mirroring human patient testing, GeM/tNSC intra-cavity pro-drug enzyme therapy reduced the volumes of surgically resected patient-derived GBMs 11-fold at 35 days post-surgery and extended median survival of tumor-bearing mice from 31 to 46 days. Together, these data begin to define design parameters necessary to engineer effective scaffold/tNSC therapies and suggest a new approach to maximizing the efficacy of tNSC therapy in human patient trials.
RARE-45. PROGRESSIVE LEPTOMENINGEAL DISSEMINATION OF A DNT AFTER WEST NILE VIRUS MENINGOENCEPHALITIS
Authors: Mark Anderson, Parminder Vig, Angel Leis
Journal: Neuro-Oncology (2016)

Dysembryoplastic neuroepithelial tumors(DNT) are low grade glial neuronal tumors typically occuring in the cortex and are removed as a part of epilepsy surgery. Many times when found on imaging and asymptomatic, observation is recommended. Spinal cord and leptomeningeal involvement has rarely been recorded. A 35 yo man presented with hydrocephalus in the setting of a newly diagnosed spinal cord mass. 8 months prior, he had been treated for viral meningoencephalitis due to West Nile virus. MRI of the brain revealed a multifocal cystic lesion in the cerebellum, consistent with a low grade glioneuronal tumor. Spinal MRI revealed a T2 cord lesion with meningeal enhancement, and a nodular lumbar spine lesion with meningeal enhancement. Lumbar spine biospy revealed chronic inflammation and myxoid-like foci. Since no evidence of neoplasm was found, effect of West Nile meningoencephalitis was assumed, as he still had IgM antibodies present in CSF. There was some improvement in the spinal cord imaging, with decreased size of the T2 mass, with chronic steroids, but continued lumbar enhancement. Then the patient developed progressive leptomeningeal enhancement, encasing the brain and spine, growth of the spinal cord mass and new enhancement in the cerebellar lesion over the course of the year, becoming quadriparetic. Biopsy of the cerebellar lesion and meninges again only showed a thickened dura with chronic inflammation and normal cerebellar tissue. Patient elected hospice care. Autopsy revealed a disseminated DNT. A disseminated DNT has rarely been reported. The development of this aggressive course following West Nile virus infection was noted. It has been established that West Nile virus causes S100B pathway activation in astrocytes, which is one of the oncogenic pathways that is activated in dysembryoplastic neuroepithelial tumors. We propose this additive effect may have led to an unusually aggressive behavior in a low grade tumor. Additional studies are needed.
Sublingual Immunotherapy for Allergic Rhinitis
Authors: Linda S. Cox
Journal: JAMA (2017)

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International study of lenalidomide in relapsed/refractory aggressive non-Hodgkin’s lymphoma
Authors: M. S. Czuczman, C. B. Reeder, J. Polikoff, N. M. Chowhan, I. Esseessee, R. Greenberg, A. Ervin-Haynes, D. Pietronigro, J. B. Zeldis, T. E. Witzig
Journal: Journal of Clinical Oncology (2008)

8509 Background: Lenalidomide is active with manageable side effects in non-Hodgkin’s lymphoma (NHL). This study aims to confirm the activity, safety, and predictors of response previously reported for lenalidomide in patients with relapsed/refractory (r/r) aggressive NHL in an international setting. Methods: Patients with r/r aggressive NHL with measurable disease (≥2 cm) after ≥1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1- 21 every 28 days and continued therapy as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Predictors of response were investigated by univariate analyses using Fisher’s exact test. Results: As of August 25, 2007, 46 patients were eligible for response assessment and 79 for safety evaluation. Median age was 65 (21–84) years, 74% were male, and 96% had received prior rituximab. Median time from diagnosis was 2 (0.2–12) years and median number of prior treatment regimens was 3.5 (1–13). An objective response was observed in 13 patients (28%); 10 patients had stable disease. Lenalidomide response was associated with low tumor burden (33% for <50 cm2 v 17% for ≥50 cm2) and time from last rituximab dose to lenalidomide treatment (44% for ≥230 days v 5% for <230 days). The response rate in patients with favorable values for these predictive factors (n=20) was 50% versus 12% in patients with unfavorable values (n=26; P=0.007). Most common grade 3/4 adverse events were neutropenia (24%), thrombocytopenia (16%), leukopenia (9%), anemia (6%), dehydration (5%), and fatigue (5%). Conclusions: Lenalidomide has activity in r/r aggressive NHL with a favorable safety profile. Early data appear to confirm that patients with low tumor burden and longer duration from prior rituximab are more likely to respond. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Corporation Celgene Corporation Celgene Corporation
DLEU1 siRNA Gene Knockdown IN BURKITT LYMPHOMA (bl) IS ASSOCIATED with A SIGNIFICANT Decrease IN Cyclophosphamide (CY) and/or Rituximab Induced Apoptosis: Mechanism of Drug Resistance in BL.
Authors: Nancy Day, Janet Ayello, Carmella van de Ven, Megan S Lim, Sherrie L. Perkins, Warren Sanger, Lauren Harrison, Stanton Goldman, Mitchell S. Cairo
Journal: Blood (2009)
Ictal PET in Ohtahara Syndrome With Hemimegalencephaly
Authors: Shambo Guha Roy, Madhavi Tripathi, Manjari Tripathi, Bhargavi Ramanujam, Abhinav Singhal, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2017)

Ohtahara syndrome is one of the causes of infantile epilepsies, which presents with refractory seizures and characteristic EEG changes. It is often associated with structural anomalies in the brain. We report a case of 5-month-old girl with Ohtahara syndrome with hemimegalencephaly who presented with refractory seizures and ictal FDG PET/CT helped in localizing the seizure focus.
Abstract 14780: How Representative of the General Population Are the Cohorts Included in the Clinical Trials That Drive Our Guidelines?
Authors: M. Rizwan Sardar, Marwan Badri, Catherine Prince, Wajeeha saeed, Jonathan Seltzer, Mark Williams, Peter R Kowey
Journal: Circulation (2013)

Background:  Guidelines from professional organizations represent the basis for evidence-based cardiovascular care and have become a standard to measure the performance of health care providers. It is therefore critical that these guidelines are applicable to the general patient population. We examined the demographics of the populations in the studies that have driven the ACC/AHA guidelines for atrial fibrillation (AF), heart failure (HF) and acute coronary syndromes (ACS).   Methods:  All of the references contained in the AF/HF/ACS guidelines were screened; only randomized controlled trials (RCT) were included, and relevant demographic data were collected from each. The majority of these trials were multicenter (69.2% of AF, 66.9% of HF and 82.1% of ACS trials)   Results:  Out of 900 AF, 810 HF and 957 ACS references in the guidelines, 227, 230 and 191 were RCTs respectively. Enrollment in ACS trials (772429) was greater than for AF and HF trials (p=75% of the cohorts [p=   Conclusions:  Despite temporal improvement study size and in minority representation, women and minority races remain heavily under-represented in most of the RCTs used to formulate the ACC/AHA guidelines. This limitation raises questions about the applicability of guideline recommendations to a more diverse population.
Cancer-related fatigue in breast cancer survivors: more evidence for a physiological substrate
Authors: J. Ramos, B. Cantos, C. Maximiano, H. Cebolla, C. Fiuza-Luces, L. Gutierrez, P. Osorio, J. Cerrato, J.L. Sanchez, B. Nuñez, A. Garate, I. Pagola, L.B. Alejo, A. Lucia, A. Ruiz-Casado
Journal: Annals of Oncology (2016)
Evaluation of an interactive electronic patient reported outcome (e-PRO) system in outpatient with oral chemotherapy
Authors: M. Rasschaert, K. Papadimitriou, S. Altintas, M. Huizing, J. Van den Brande, T. Van den Mooter, P.M.C. Specenier, C.D. Rolfo, S. De Keersmaecker, I. Van Brussel, J. Ravelingien, M. Peeters
Journal: Annals of Oncology (2016)
STMC-36. CD109 REGULATES TUMOR PROPAGATION OF RADIO-RESISTANT GLIOMA STEM CELLS
Authors: Alessandra Audia, Mutsuko Minata, Xing Guo, Farah Mukheef, Hetshree Patel, Ravesanker Ezhilarasan, Erik Sulman, Ichiro Nakano, Krishna Bhat
Journal: Neuro-Oncology (2016)

GBM patients are uniformly treated with chemo-radiation, but the tumor invariably recurs and the exact molecular mechanisms driving treatment resistance in GBMs are unknown. Newer molecular targeted therapies including VEGF inhibitors, have failed to extend the dismal (approximately 14.6 month median) survival in GBM. Of the molecular subtypes of GBM, the mesenchymal (MES) subtype is considered most aggressive and we have recently shown that these cells exhibit radio-resistance in a NF-κB dependent manner. Prospectively identifying the MES subset of radio-resistant, cancer stem cells has been challenging due to a lack of cell surface markers to identify these populations. In this study we discovered CD109 as a novel tumor initiation marker for the MES subtype of glioma stem cells. Here we report that exposure of glioma stem-like cells (GSCs) to ionizing radiation (IR) promotes a persistent transcriptomic and phenotypic shift toward a MES subtype in a CD109-dependent manner. We observed that in both de novo and IR-induced MES GSCs, CD109+, but not CD109- populations are highly clonogenic in vitro and radio-resistant and tumorigenic in vivo. In addition, inhibition of CD109 through shRNAs attenuates clonogenicity, tumor propagation and radio-resistance and dramatically inhibits YAP/TAZ signaling in MES GSCs. In support of these results, CD109 is significantly associated with the MES subtype of GBMs, correlates with YAP/TAZ expression, and poorer prognosis of GBM patients.
Evaluation of exposure of regorafenib and its metabolites in cancer patients with renal impairment by modelling, simulation, and clinical study
Authors: M. Block, B. Ploeger, J. Grevel, K. Schnizler, M. Gerisch, F.-T. Hafner, S. Reschke, F. Huang, Z.J. Trnkova, I. Sturm, A. Cleton
Journal: Annals of Oncology (2016)
Inhibition of PTEN Tumor Suppressor Promotes the Generation of Induced Pluripotent Stem Cells
Authors: Jiyuan Liao, Tomotoshi Marumoto, Shinji Okano, Saori Yamaguchi, Takenobu Nii, Hirotaka Kawano, Yoko Nagai, Chika Sakamoto, Michiyo Okada, Yoshie Miura, Hiroyuki Inoue, Masato Tanaka, Kaori Nagatoshi, Kohichi Kawahara, Akira Suzuki, Kenzaburo Tani
Journal: Blood (2011)
The location of colorectal cancer (right- vs. left-sided colon and rectum) affects the prevalence of BRAF V600E, non-V600E and PIK3CA mutations: a prospective registration study in the Aichi Cancer Network
Authors: H. Taniguchi, K. Uehara, H. Nakayama, G. Nakayama, T. Takahashi, Y. Nakano, H. Matsuoka, S. Utsunomiya, E. Sakamoto, Y. Mori, K. Komori, M. Tajika, K. Muro, Y. Yatabe
Journal: Annals of Oncology (2016)