tbuckley/cabot-search huggingface dataset:
A phase I open-label study using lenalidomide and docetaxel in castration- resistant prostate cancer
Authors: D. P. Petrylak, K. Resto-Garces, M. Tibyan, S. G. Mohile
Journal: Journal of Clinical Oncology (2009)

5156 Background: Based on efficacy of docetaxel (D) and possible synergism with antiangiogenic agents in AIPC demonstrated by results from a NCI trial of D ± thalidomide, a phase I trial evaluating escalating doses of D and lenalidomide (Ln), a derivative of thalidomide with immunomodulatory and antiangiogenic properties, was designed. Methods: Eligibility requirements include progressive measurable disease or rising PSA levels after antiandrogen withdrawal and &lt; 2 prior chemotherapy regimens. All patients were required to have a castratete testosterone &lt;50 ng/dl and to continue medical castration. Dose of D was 60 mg/m2 on Day 1 of 21-day cycle for dose level (L)1 and 75 mg/m2 for L 2–6. Ln dose levels were: 10 mg (L1–2), 15 mg (L3), 20 mg (L4), 25 mg (L5) and 30 mg (L6) for days #1–14. Pts were given prednisone 5 mg po |[BI]D continuously and 8 mg of decadron 12, 8 and 1 hour prior to D without prophylactic anticoagulation. 6 patients (pts) were entered at each level, escalation to the next level occurred if no more that 1 dose limiting toxicity|[(D]LT) was observed during cycle 1. Results: Thirty four pts were enrolled in L1–6; all pts are evaluable for toxicity. Pt characteristics include median age of 70 yrs (range 47–85), median baseline PSA of 101.9 ng/ml (range 5.9–7480), 14 pts (41%) had received prior chemotherapy (7 with 2 prior regimens). All had overt metastatic disease to viscera or bone; 21 pts had measurable disease. Median number of cycles for L1-L5 was 8 (range 2–19). DLT's observed: L2: Grade 4 Neutropenia (1 pt); L3–5 None. Of the 3 patients treated at L6, 2 developed DLTs (febrile neutropeina, grade 4 neutropenia) precluding further dose escalation. Other Grade 3/4 toxicities observed after cycle 1 included deep venous thrombosis (2 pts), grade 3 neutropenia (2 pts), grade 3 facial edema (1 pt) Of 31 pts evaluable for post treatment PSA declines; 8/17 (47%) untreated pts 7/14 (50%) previoustly treated pts had a &gt;50% decline in PSA. Five pateints achieved a partial response in measurable disease, one had a near complete resolution of a biopsy proven metastatic pulmonary nodule. Conclusions: The recommended dose for is 75 mg/m2 D Q 3 weeks day 1 and Ln 25 mg PO D1–14. An expanded cohort of 10 patients will be treated at this level to further define toxicities. No significant financial relationships to disclose.
Hexokinase-2 Regulates Hypoxia-Inducible Autophagy, Leading to Enhance Anti-Apoptotic Capability of Refractory Multiple Myeloma
Authors: Sho Ikeda, Fumito Abe, Matsuda Yuka, Akihiro Kitadate, Takahiro Kobayashi, Naoto Takahashi, Hiroyuki Tagawa
Journal: Blood (2019)
The 17-Gene Leukemic Stemess Score Can Predict Treatment Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia
Authors: Dennis Dong Hwan Kim, Taehyung Kim, Tracy Murphy, Steven M Chan, Mark D. Minden, Zeyad Al-Shaibani, Wilson Lam, Arjun Law, Fotios V. Michelis, Auro Viswabandya, Jeffrey H. Lipton, Rajat Kumar, Jonas Mattsson, Jean C.Y. Wang
Journal: Blood (2019)
Sustained Therapeutic Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: Gang Heng, Jiankun Jia, Shiqi Li, Gang Fu, Meiling Wang, Dabing Qin, Yunyan Li, Li Pei, Xiaobo Tian, Jiasi Zhang, Yi Wu, Shali Xiang, Jia Wan, Wei Zhu, Pei Zhang, Qianzhen Zhang, Xi Peng, Linling Wang, Ping Wang, Zhihao Wei, Yingzi Zhang, Guiqin Wang, Xue Chen, Chengcheng Zhang, Yanni Sun, Wenxu Zhao, Yahan Fan, Zhi Yang, Jieping Chen, Cheng Qian
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Immunogenicity derived from the murine scFv, a major molecular compomemt of chimeric antigen receptors (CARs), may limit the persistence of CAR T cells, resulting in tumor relapse of patients in complete remission (CR). In this study, we developed a humanized anti-CD19 scFv CAR-T (hCAR-T) to treat patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). Patients and Methods: In this one-arm, open-labeled study, we infused the T cells modified with hCAR to patients with r/r ALL. Patients were evaluated with long-term follow-up for response and safety of the treatment. The study was registered at Clinicaltrials.gov (NCT02349698). Results: Ten patients with r/r ALL were recruited for this study. All were response evaluable and all achieved CR; eight patients remained CR, and six were in CR for over 18 months without further treatment. A long-term persistence of hCAR T cells was observed in most of the patients. Among these patients, four of them with high tumor burden and rapidly progressive disease (median, 58%) experienced grade 3–4 cytokine release syndrome (CRS) and neurotoxicity. These severe CRSs were successfully controlled by tocilizumab, glucocorticoid, and plasma exchange. Conclusions: T cells expressing the humanized anti-CD19 scFv CARs exhibited sustained therapeutic efficacy in the treatment of r/r ALL. Low replase rate was associated with the long-term persistence of CAR T cells.
SCIDOT-50. A RAT MODEL FOR LASER INTERSTITIAL THERMAL THERAPY FOR GLIOBLASTOMA: EFFECTS ON PERI-ABLATION BLOOD-BRAIN BARRIER AND IMPLICATIONS FOR POST-ABLATION CHEMOTHERAPY
Authors: Tavarekere Nagaraja, James Ewing, Katelynn Farmer, Grahm Valadie, Stephen Brown, Robert Knight, Glauber Cabral, Swayamprava Panda, Ian Lee
Journal: Neuro-Oncology (2019)

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas, brain tumors in eloquent regions or otherwise inaccessible to traditional open surgery. LITT offers quicker recovery and shorter hospital stays as additional advantages. A laser fiberoptic catheter is positioned in the body of the tumor under magnetic resonance imaging (MRI) guidance via a twist drill hole in the skull. Using MR thermometry, the tumor is ablated by laser heating to lethal temperatures. The peri-ablation zones get heated to sub-lethal temperatures and subsequently recover. It has been reported in humans that opening of the blood-brain barrier (BBB) occurs, lasting several weeks after ablation. We have adapted Visualase®, a clinically available LITT system, for use in a rat glioblastoma model. Athymic female rats (n=7) were implanted with U251 tumor cells in one brain hemisphere. Tumor growth was monitored using MRI. When tumors reached about 4 mm in diameter, they were ablated under supervision of MR diffusion-weighted MRI, sparing the surrounding normal brain tissue. Contrast-enhanced MRI data were obtained before LITT, immediately after and at post-LITT 24 h. The brains were processed for histopathology and stained with hematoxylin and eosin (H&amp;E) for visualizing the extent of the tumor and for major histocompatibility complex (MHC) to identify the human-derived U251 cells. All rats survived the LITT procedure. A ring of contrast enhancement around ablation perimeter was observed immediately after, and also at 24 h. H&amp;E data showed near-complete ablation of the tumors. However, MHC staining showed U251 cells still remaining in the ablation vicinity. These data suggest this model is useful for examining the temporal and spatial development of peri-ablation BBB opening following LITT. Concurrent timing of post-ablation chemotherapy to the development and presence of post-LITT BBB opening may aid in efficient targeting of remaining tumor cells.
Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker <i>Post Hoc</i> Analysis of the VELOUR Trial
Authors: Eric Van Cutsem, Caroline Paccard, Marielle Chiron, Josep Tabernero
Journal: Clinical Cancer Research (2019)

Aflibercept is a targeted anti-VEGF therapy used to treat patients with metastatic colorectal cancer (mCRC) following progression on oxaliplatin-based regimens. This post hoc study evaluated the effect of prior bevacizumab treatment and growth factor levels on patient outcomes associated with aflibercept in the VELOUR phase III trial.Baseline biomarker plasma concentrations were measured using a bead-based multiplex assay. Patients were grouped according to prior bevacizumab treatment, second-line treatment, and serum biomarker concentrations, and analyzed for overall survival (OS) and progression-free survival (PFS).Plasma samples were available for 553 patients (placebo n = 265; aflibercept n = 288), of which 169 had received prior bevacizumab. Nine biomarkers implicated in angiogenesis or bevacizumab resistance correlated with prior bevacizumab therapy. VEGF-A and placental growth factor (PlGF) were the most significantly increased in patients who had received prior bevacizumab compared with those who had not received prior bevacizumab. In the placebo group, patients with high VEGF-A (>144 pg/mL) levels at baseline had worse OS and PFS compared with patients with lower levels at baseline (9.6 vs. 12.9 months). This was also seen in patients who received placebo and had high baseline PlGF (>8 pg/mL; 9.7 vs. 11.7 months). In the aflibercept group, prolonged OS and PFS were observed regardless of baseline VEGF-A or PlGF levels.High VEGF-A and PlGF serum levels may underlie development of resistance to bevacizumab in patients with mCRC. Aflibercept retains its activity regardless of baseline VEGF-A and PlGF levels and may be an effective second-line treatment for patients with bevacizumab-induced resistance.
"Real-World" Peripheral T-Cell Lymphomas Experience in Portugal: Is There Reason for Optimism?
Authors: Ivan Dlouhy, Rita Gavancha, Inês Coelho, Catalina Gomez, Inês Barbosa, Susana Carvalho, Maria Ceu Trindade, Ana Filipa Moita, Gonçalo Esteves, Paula Gameiro, Jose Cabecadas, Maria Silva
Journal: Blood (2019)
NCMP-02. MYASTHENIA GRAVIS INDUCED BY AVELUMAB
Authors: Carlen Yuen, Gini Fleming, Betty Soliven, Michael Myers, Kourosh Rezania
Journal: Neuro-Oncology (2019)

Abstract Monoclonal antibodies targeting PD- 1 (nivolumab and pembrolizumab) and PD-L1 (avelumab, atezolizumab, and durvalumab) are FDA approved for the treatment of metastatic cancers. Immune-related adverse events (irAEs) are autoimmune diseases which occur following treatment with PD-1 and PD-L1 inhibitors. Neurological irAEs following PD-L1 blockade are rarely reported, and mainly consist of Myasthenia Gravis (MG) and myositis. MG induced by avelumab has not been previously reported. We present a 74-year-old female with stage IV ovarian adenocarcinoma who entered a clinical trial involving avelumab and entinostat after disease progression following extensive resection, chemotherapy with doxorubicin, then docetaxol and cisplatin. She developed progressive generalized weakness and fatigue two months after entering the trial, leading to respiratory weakness and hypoventilation, and resulting in intubation and mechanical ventilation. Exam showed head-drop, diplopia, and proximal &gt; distal upper and lower limb weakness. Antibodies to acetylcholine receptors, muscle specific tyrosine kinase, and voltage-gated calcium channels (P/Q and N type) were negative, and serum creatine kinase was normal. Repetitive nerve stimulation showed significant decrement in the left spinal accessory nerve motor response with recording at trapezius. She was diagnosed with seronegative MG and was treated with IVIG, 2 grams/kg divided over 4 days, prednisone 60 mg daily, and pyridostigmine, which resulted in successful extubation, followed by gradual resolution of MG symptoms over a period of 3 months. At approximately 2 year follow-up, she remains on maintenance IVIG at 0.5 grams/kg every 3 weeks, as she develops proximal lower limb and neck extension weakness at the end of each IVIG cycle. We conclude that MG is a potentially life threatening but treatable irAE associated with avelumab. Our case also adds to the accumulating literature of the role of PD-1 signaling in the pathogenesis of autoimmune diseases of the muscles and neuromuscular junctions.
PATH-01. MGMT METHYLATION CUTOFF VALUE IN QUANTITATIVE ANALYSIS RELATED TO PROGNOSIS OF NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Jun-ichi Adachi, Mitsuaki Shirahata, Tomonari Suzuki, Kazuhiko Mishima, Ryo Nishikawa
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND MGMT promoter methylation is an important biomarker related to glioblastoma therapeutic response and prognosis. There are qualitative and quantitative methods as assays for MGMT methylation. Although the qualitative method is common, there is a disadvantage that low or high methylation cannot be distinguished. The quantitative method is an excellent method for evaluating methylation of tumors characterized by intratumoral heterogeneity like malignant glioma, but cutoff value of methylation that defines the prognosis of glioblastoma is unknown. Therefore, we examined the cutoff value of quantitative MGMT methylation assay determining the prognosis in glioblastoma. METHODS 180 newly diagnosed glioblastoma which underwent radiotherapy and temozolomide treatment after tumor removal in our department were included. MGMT methylation was quantitatively analyzed by methylation-specific high resolution melting (MS-HRM) analysis. For each level of methylation, progression-free survival (PFS) and overall survival (OS) were calculated and statistically analyzed. RESULTS In the low MGMT methylation cases in which the proportion of methylation was 25% or less in PFS and 30% or less in OS, no difference was observed in PFS and OS as compared with those of unmethylated cases. The cutoff value of MGMT methylation most contributing to survival was calculated to be 35% by the survival classification and regression tree method. CONCLUSION The prognosis for MGMT hypomethylated group is as poor as unmethylated one. In the quantitative MS-HRM method, we found that the value of MGMT methylation of 35% is useful as a cut off determining the prognosis of glioblastoma.
SCIDOT-15. DISRUPTING THE BLOOD-BRAIN BARRIER IN NEURO-ONCOLOGY: INNOVATIONS, ACHIEVEMENTS, AND LESSONS LEARNED FROM CLINICAL TRIALS
Authors: Justine Philtheos, Aram Abbasian, Brij Karmur, Alireza Mansouri
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The blood-brain barrier (BBB) presents a formidable challenge for the development of effective therapeutics in neuro-oncology. Several strategies for the disruption of the BBB have been investigated in humans. An in-depth analysis of the concepts, design, and outcomes from these trials can provide insight into optimizing strategies for safe, selective, and efficacious BBB disruption for drug delivery. METHODS The clinicaltrials.gov database was searched on June 9th, 2019 using the term blood-brain barrier. Results were screened for studies relevant to neuro-oncology. When available, linked publications were also reviewed for supplemental information. The Pubmed database was also searched for BBB disruption strategies, to identify publications not linked to a trial registry. Details regarding patient eligibility, intervention, comparators, outcomes and other design criteria were extracted. RESULTS Among 288 registered studies, 42 were relevant to neuro-oncology. Drug-based methods predominated (33/42) but there has been a surge in device-based methods with all registrations after 2015. Mannitol was the most common drug-based method (16/33, 5 Phase II), followed by RMP-7 (8/33, 3 Phase II), Ang1005 (7/33, 4 Phase II and one pending Phase III), and Regadenoson (2/33, one Phase 0 and one Phase I). MR-guided focused ultrasound was the most common device-based method (5/9), followed by MR-guide laser ablation (2/9), Sonocloud (1/9), and transcranial magnetic stimulation (1/9). All device studies have been early phase. Most early phase studies focusing on safety and tolerability met objectives. Some Phase II studies showed preliminary efficacy but control arms were lacking. Many Phase II studies have been terminated/suspended. CONCLUSIONS Diverse BBB disruption methods have been investigated and most appear to be safe and tolerable. Advanced phase studies focusing on survival differences have been limited by heterogeneous tumors and lack of control arms. Objective establishment of BBB disruption was limited. Concerted and standardized clinical trial efforts are needed.
Characteristics and Trends of Sickle Cell Disease Patients Once Presented to the Emergency Department, Reflecting on a Possible Burden: United States (2010-2015)
Authors: Tarek Haykal, Ragheed Al-Dulaimi, Josiane Kerbage, Varun Samji, Sowmya Goranta, Smit Deliwala, Ghassan Bachuwa
Journal: Blood (2019)
Central Nervous System Prophylaxis Is Required and Associated with a Prolonged Overall Survival in Both Early and Advanced-Stage Primary Adrenal/Renal Diffuse Large B-Cell Lymphoma
Authors: John Xie, Motohide Uemura, Shigeaki Nakazawa, Teresa Calimeri, Andres JM Ferreri, Francisco Socola, Hana Safah, Nakhle S. Saba
Journal: Blood (2019)
Urinary Infection in Childhood
Authors: P. L. Masters, I. C. Lewis
Journal: BMJ (1965)

It was unnecessary for Professor Conn to select cases of primary aldosteronism from our published results,68 since we had reported these conclusions in the same group of cases -in Professor Conn's presence-more than a year before.8Professor Milne's case was not one of these.Our recent paper9 was a pro- gress report on a patient described in some detail earlier.6 We said of this case in 1963 that the association of low plasma-renin concentration and increased aldosterone secretion suggested an aldosterone-producing adrenal tumour, and that we were studying the effects of spironolactone treatment before removing the tumour.'It thus seems obtuse of Professor Conn to misconstrue2 the intention of our paper' as " final proof " of his more recent " thesis."We should further make it clear that neither we nor Professor Conn and his colleagues can rightly claim priority for the prediction of low plasma renin in primary aldosteronism, or for the removal of a tumour from a patient investigated in this way.Any such credit belongs to others.0"-We are, etc.,
TMIC-08. IDENTIFICATION OF TUMOR SPECIFIC LYMPHOCYTES IN A MURINE GLIOMA MODEL
Authors: David Shin, Nikhil Lamba, Catherine Flores, Bayli Divita, Tyler Wildes, Adam Grippin, Brandon Fernandez, Kyle Dyson, Duane Mitchell
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION One major challenge in the use of immunotherapy for glioblastoma is the identification of tumor specific lymphocytes within the tumor microenvironment. Previous studies in non-glioma cancer models have identified CD39 and PD1 as lymphocyte markers of tumor specificity. In this study, we demonstrate the existence of this specific T cell phenotype and show correlation with anti-tumor activity. METHODS We implanted KR158B murine glioma cells into right caudate nucleus into yellow fluorescent protein (YFP) interferon-gamma reporter mice for a total of 104 cells using stereotaxis. At 4 weeks, mice were sacrificed followed by organ harvest. Samples taken included tumor, cervical draining lymph nodes, spleen, and peripheral blood. These were processed into single cell suspensions and then stained for CD3, CD8, CD39, and PD1. Flow cytometry was performed on a BD FACSCanto II. Gating analysis was performed with FlowJo while data analysis was performed with GraphPad Prism. RESULTS Gating for CD3+ CD8+ on tumor lymphocytes reveals a significant population of CD39 and PD1 double positive (DP) cells (61.4%) not found in the peripheral organs (&lt; 1.0%). Evaluation of these cells for YFP expression demonstrated significantly greater median fluorescence intensity (MFI) in the DP group as opposed to either of the single positive (SP) or double negative (DN) groups (DP = 225.4, SP-CD39 = 40.54, SP-PD1 = 82.7, DN = 29.5, p &lt; 0.0001). CONCLUSION Here we demonstrate the existence of a unique phenotype of CD39+ and PD1+ expression on lymphocytes within the tumor microenvironment. These DP cells also had high levels of interferon gamma production compared SP and DN groups. This phenotype is not observed in peripheral circulating lymphocytes. Enrichment for this subpopulation will allow for delivery of purified lymphocyte-based immunotherapy in this murine glioma model.
Single typical trichoscopic feature predictive of tinea capitis
Authors: F. Dhaille, A.‐S. Dillies, F. Dessirier, P. Reygagne, M. Diouf, T. Balthazard, F. Lombart, V. Hébert, M. Chopinnaud, L. Verneuil, C. Becquart, E. Delaporte, C. Lok, G. Chaby
Journal: British Journal of Dermatology (2019)

This study which was carried out in four university hospitals in France was designed to assess the usefulness of the technique, trichoscopy, in the diagnosis of tinea capitis, also known as scalp ringworm.
Expectant Management of Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue (BALT)
Authors: Yan Leyfman, Erel Joffe, Esther Drill, Sridevi Rajeeve, Andrew D. Zelenetz, Maria Lia Lia Palomba, Craig H. Moskowitz, Carol S. Portlock, Ariela Noy, Steven M. Horwitz, Alison J. Moskowitz, Paul A. Hamlin, Matthew J Matasar, Anita Kumar, Gottfried R. von Keudell, Connie Lee Batlevi, Anas Younes, David J. Straus
Journal: Blood (2019)
Quantitative Monitoring of T315I BCR-ABL Mutation by the Invader Assay.
Authors: Kazuhiko Kakihana, Kazuteru Ohashi, Yuho Najima, Taku Kikuchi, Yasunobu Nagata, Toshimitsu Ueki, Takeshi Kobayashi, Takuya Yamashita, Hideki Akiyama, Toshikazu Yamaguchi, Hisashi Sakamaki
Journal: Blood (2007)
Retrospective Comparison between MEC and FLAG-Ida Regimens for Refractory or Relapsed Acute Myeloid Leukemia in Adults
Authors: Wellington F Silva, Lidiane Inês Da Rosa, Fernanda S Seguro, Douglas R. A. Silveira, Luciana Nardinelli, Valeria Buccheri, Elvira DRP Velloso, Vanderson Rocha, Eduardo M Rego
Journal: Blood (2019)
Effect of sunscreen on vitamin D
Authors: R.E. Neale, S.R. Khan, R.M. Lucas, M. Waterhouse, D.C. Whiteman, C.M. Olsen
Journal: British Journal of Dermatology (2019)

Vitamin D is essential for bone health and is produced by the skin in response to ultraviolet radiation (UVR) from sunlight. UVR is also the main cause of skin cancer, the UK's most common type of cancer. Therefore, there have been several concerns that sun protection methods such as using sunscreen can affect vitamin D production. Researchers from the QIMR Berghofer Medical Research Institute in Australia, and the Australian National University, systematically reviewed for the first time all published experimental studies, field trials, and observational studies published between 1970 and 2017, totalling 75 studies, in order to understand the effect of sunscreen use on vitamin D levels. The researchers found that while the experimental studies (using artificial light sources in a laboratory setting) support the theoretical risk that sunscreen use may affect vitamin D, the weight of evidence from field trials and observational studies (taking place in real‐life situations involving natural sunlight) suggests that the risk is low. The researchers explain that the conditions in the experimental studies did not reflect those of the real world, so the results cannot be used to inform practical recommendations for the public. The authors of this review concluded that there is little evidence that sunscreen, when used in real‐life settings, decreases vitamin D levels and in some cases sunscreen use was associated with higher vitamin D levels. Therefore, concerns about vitamin D levels should not interfere with skin cancer prevention advice. Future trails should consider high sun protection factor sunscreens which are now widely recommended.