tbuckley/cabot-search huggingface dataset:
ACTR-66. A PHASE 1, OPEN-LABEL, PERIOPERATIVE STUDY OF IVOSIDENIB (AG-120) AND VORASIDENIB (AG-881) IN RECURRENT IDH1 MUTANT, LOW-GRADE GLIOMA: UPDATED RESULTS
Authors: Ingo Mellinghoff, Timothy Cloughesy, Patrick Wen, Jennie Taylor, Elizabeth Maher, Isabel Arrillaga-Romany, Katherine Peters, Changho Choi, Benjamin Ellingson, Alexander Lin, Sunitha Thakur, Brandon Nicolay, Min Lu, Kha Le, Feng Yin, Feng Tai, Steven Schoenfeld, Shuchi S Pandya, Islam Hassan, Lori Steelman, Jennifer Clarke
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Ivosidenib (AG-120, IVO) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), and vorasidenib (AG-881, VOR) is an oral, potent, brain-penetrant inhibitor of mIDH1/2. Both have been evaluated in glioma patients in ongoing phase 1 studies. In orthotopic glioma models, IVO and VOR reduced 2-hydroxyglutarate (2-HG) levels by 85% and 98%, respectively, despite different brain-to-plasma ratios (&lt; 0.04 vs 1.33). METHODS Patients with recurrent, nonenhancing, WHO-2016 grade 2/3, mIDH1-R132H oligodendroglioma or astrocytoma undergoing craniotomy were randomized 2:2:1 to IVO 500mg QD, VOR 50mg QD, or no treatment (cohort 1), or 1:1 to IVO 250mg BID or VOR 10mg QD (cohort 2), for 4 weeks preoperatively. Postoperatively, patients continued receiving IVO or VOR (control patients were randomized 1:1 to IVO or VOR). Tumors were assessed for mIDH1 status, cellularity, and 2-HG and drug concentrations. Treated subjects were compared with controls and mIDH1/wild-type banked reference samples. Primary endpoint: tumor 2-HG concentration following IVO or VOR. RESULTS As of March 1, 2019, 27 patients (18 men; 25/2 grade 2/3) were randomized preoperatively in cohort 1 (IVO 10, VOR 12, untreated 5): 27 received drug (IVO 13, VOR 14); 1 discontinued VOR postoperatively due to disease progression. Of 26 tumors analyzed, 22 were evaluable. Mean brain-to-plasma ratios: 0.13 IVO, 1.59 VOR. Relative to untreated samples, IVO and VOR reduced tumor 2-HG by 92.0% (95% CI 73.2, 97.4) and 92.5% (95% CI 78.1, 97.7), respectively. Common (≥ 4 patients) TEAEs (all cohort 1 patients, all grades): diarrhea (37.0%), constipation, hypocalcemia, and nausea (each 18.5%), anemia, hyperglycemia, pruritus, headache, and fatigue (each 14.8%). Cohort 2 has completed accrual, with analyses ongoing. CONCLUSIONS In cohort 1 of this phase 1 perioperative study, IVO and VOR demonstrated brain penetrance and lowered 2-HG compared with controls. Updated data from both cohorts will be presented.
Long-Term Clearance of Senescent Cells Prevents the Hematopoietic Stem Cell Aging in Naturally Aged Mice
Authors: Yonghan He, Jianhui Chang, Dongwen Lv, Ha-neui Kim, Maria Almeida, Xin Zhang, Xinjian Mao, Xinghui Zhao, Linheng Li, Judith Campisi, Ying Liang, Daohong Zhou
Journal: Blood (2019)
RTHP-21. TREATMENTS FOR RECURRENT MALIGNANT GLIOMAS AND THEIR PROGNOSIS
Authors: Kanji Mori, Tetsuya Kumagai, Maki Kobayashi, Takamitsu Iwata, Kanji Nakagawa, Akira Kudo, Shingo Toyota, Yonehiro Kanemura, Takuyu Taki
Journal: Neuro-Oncology (2019)

Abstract For improvement of glioma therapy, advances in treatment after recurrence are essential, but no standard second line therapy has been estimated. Lately, bevacizumab (Bev) and BCNU wafer became available in Japan, we have more therapeutic choices. Since we took part in Kansai molecular diagnosis network for CNS tumors in 2013, we have referred molecular information. We retrospectively examined and report our experiment about recurrent malignant gliomas in Kansai Rossi Hospital. Twenty-two histopathologically proved grade 3 and grade 4 patients who were diagnosed as recurrence between January 2013 and December 2018 were included. We examined treatment and analyzed factors that influenced overall survival (OS) after recurrence. Glioblastoma were 14 cases (IDH wild 12 cases, IDH mutant one case, unknown one case) Median age and KPS at recurrence were 70 years old and 60%, respectively. Ten patients received any anti-cancer treatment and 2 received best supportive care (BSC). Radiation therapy (RT) with Bev were used in 9 patients (5 with gamma knife). Their median OS after first recurrence was 324 days and significantly longer than that of BSC patients (p=0.00174). Grade 3 gliomas were 8 cases (IDH-mutant 3 cases, IDHwild 5 cases, H2F3A mutant 1 case). Median age and KPS at recurrence were 45 years old and 70%, respectively. Five patients were treated with temozolomide (TMZ) and others were observed. In addition to TMZ, Bev were used for 4 patients and RT for 3. Median OS of these patients was significantly longer (p=0.0198). In both grade, patients with better KPS (&gt;60%) statistically lived longer than poor KPS, but methylation status of MGMT promoter and IDH mutation did not influent their OS. Radiation with Bev for good KPS patients might improve prognosis. Further multicenter prospective study must be needed.
The Combination of the BCL-2 Antagonist Venetoclax with the CD70-Targeting Antibody Cusatuzumab Synergistically Eliminates Primary Human Leukemia Stem Cells
Authors: Carsten Riether, Tanja Chiorazzo, Amy J. Johnson, Christina Diane Drenberg, Khaja Waheeduddin Syed, Mahan Moshir, Anna Hultberg, Nicolas Leupin, Hans De Haard, Adrian F Ochsenbein
Journal: Blood (2019)
Key Histopathology Features of Cutaneous Acute Graft-Versus-Host Disease Can be Detected Noninvasively
Authors: Inga Saknite, Melissa Gill, Alessi-Fox Christi, Jeffrey P Zwerner, Julia S Lehman, Michi M Shinohara, Roberto A Novoa, Michael T Byrne, Madan Jagasia, Salvador Gonzalez, Marco Ardigo, Eric R. Tkaczyk
Journal: Blood (2019)
Periodontal disease and risk of benign prostate hyperplasia: a cross-sectional study
Authors: Lan Wu, Bing-Hui Li, Yun-Yun Wang, Chao-Yang Wang, Hao Zi, Hong Weng, Qiao Huang, You-Jia Zhu, Xian-Tao Zeng
Journal: Military Medical Research (2019)

Abstract Background Both periodontal disease and benign prostatic hyperplasia are age-related diseases that affect millions of people worldwide. Hence, this study aimed to investigate the association between periodontal disease and the risk of benign prostatic hyperplasia. Methods A total of 4930 participants were selected from an available health examination that was carried out in 2017, only males were considered for further analysis. All eligible males were divided into benign prostatic hyperplasia and normal groups, the benign prostatic hyperplasia group was then divided into prostate volume ≤ 60 g and &gt; 60 g subgroups; all their periodontal status was extracted and then into normal (CPI score of 0), periodontal disease (CPI score between 1 and 4), and periodontitis (CPI score between 3 and 4) groups. The correlation between periodontal disease and benign prostatic hyperplasia was investigated using logistic regression analyses and greedy matching case-control analysis. Subgroup analysis based on prostate volume was also performed. All analyses were conducted with SAS 9.4 software. Results A total of 2171 males were selected for this analysis. The presence of periodontal disease significantly increased the risk of benign prostatic hyperplasia by 1.68 times ( OR = 1.68, 95% CI: 1.26–2.24), and individuals with periodontitis showed a higher risk ( OR = 4.18, 95% CI: 2.75–6.35). In addition, among matched cases and controls, this association remained robust (periodontal disease: OR = 1.85, 95% CI: 1.30–2.64; periodontitis: OR = 4.83, 95% CI: 2.57–9.07). Subgroup analysis revealed that periodontal disease significantly increased benign prostate hyperplasia risk as well (for prostate volume ≤ 60 g: OR = 1.64, 95% CI: 1.22–2.20; for volume &gt; 60 g: OR = 2.17, 95% CI: 1.04–4.53), and there was a higher risk in the group with a prostate volume greater than 60 g. Conclusion Periodontal disease is significantly and positively associated with an increased risk of benign prostatic hyperplasia. Further validation studies should be performed to explore the relationship between periodontal treatment and benign prostate hyperplasia.
Making Progress in Graft-Versus-Host Disease Prophylaxis and Microbiome Analysis in the Blood and Marrow Transplant Clinical Trials Network: Progress III (1703)/MI-Immune (1801)
Authors: Shernan Holtan, Ami S. Bhatt, Raphael Fraser, Miguel-Angel Perales, Leslie Kean, Wael Saber, Mehdi Hamadani, Brent R. Logan, Javier Bolaños-Meade
Journal: Blood (2019)
Clinical Relevance of Somatic Mutations in Chronic Myelomonocytic Leukemia Undergoing Allogeneic Stem Cell Transplantation
Authors: Nico Gagelmann, Anita Badbaran, Rashit Bogdanov, Olivier Nibourel, Friedrich Stoelzel, Christina Rautenberg, Heiko Becker, Aleksandar Radujkovic, Michael Koldehoff, Maximilian Christopeit, Peter Dreger, Jürgen Finke, Guido Kobbe, Uwe Platzbecker, Marie Robin, Dietrich W. Beelen, Nicolaus Kroeger
Journal: Blood (2019)
Carbuncle of the Kidney
Authors: R. A. K. Wiener
Journal: BMJ (1949)

CORRESPONDENCEB my cases decrease of the E.S.R. was parallel to the decrease of symptoms.Finally, I should like to add that co-operation between the radiotherapist and the orthopaedic surgeon is of prime impor- tance.By synchronizing the treatnments at their disposal, a crippled patient is usually converted to an able citizen.-Iam, etc., Coventry. K. SICHER.SIR,-In the Journal of Feb. 5 (P. 214)there appeared an article on ankylosing spondylitis by Drs.N. R. W. Simpson and C. J. Stevenson.Under the heading of " Initial Diagnosis" they make the following statement: "Only 102 (51%) of the cases were admitted . . .with a correct dilagnosis already made.This lends further weight to the suggestion of Gilbert Scott (1942) that x-ray examination of the sacro-iliac joints should be a routine investigation in all cases of persistent low back pain."
Maintenance Rituximab in Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in the First Line Setting or at Relapse
Authors: Dahlia Sano, Paolo Strati, Pedro Alcedo, V Ahalya Rao, Prachee Singh, Roberto N. Miranda, Jillian R Gunther, Chelsea Camille Pinnix, Bouthaina S. Dabaja, Feng Lei, Hun Ju Lee, Raphael E Steiner
Journal: Blood (2019)
Impact of Capacity Development Program on Outcomes for Pediatric Hematologic Malignancies in Tanzania
Authors: Kristin Schroeder, Tyler Rizzieri, Joanna Robles, Hillary Sued, Patricia Scanlan, Judith Mafwimbo, Mastidia Maxmilian, Jacqueline Kamanga, Nestory Masalu, Nelson J. Chao
Journal: Blood (2019)
New Technique to Reduce the Risk for Hypocalcemia in Thyroid Surgery
Authors: Martin Almquist, Anders Bergenfelz
Journal: JAMA Surgery (2019)

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Comprehensive Investigation of White Blood Cell and Gene Expression Profiles As Risk Factors for Multiple Myeloma in African Americans
Authors: Linda Kachuri, Zhaohui Du, Niels Weinhold, Gregory Song, Kristin Alyse Rand, David Van Den Berg, Amie Hwang, Xin Sheng, Victor Hom, Sikander Ailawadhi, Ajay K Nooka, Seema Singhal, Edward S. Peters, Cathryn Bock, Ann Mohrbacher, Alexander Stram, Sonja I Berndt, William J. Blot, Esther M. John, Leslie Bernstein, Antoinette Stroup, Maurizio Zangari, Frits van Rhee, Andrew Olshan, Wei Zheng, Sue Ann Ingles, Michael Press, John David Carpten, Stephen J Chanock, Jayesh Mehta, Graham A Colditz, Jeffrey Wolf, Thomas G. Martin, Mark A. Fiala, Howard R. Terebelo, Nalini Janakiraman, Laurence Kolonel, Kenneth C. Anderson, Loic Le Marchand, Daniel Auclair, Brian C.-H. Chiu, Daniel Stram, Ravi Vij, Leon Bernal-Mizrachi, Gareth Morgan, Jeffrey A. Zonder, Carol Ann Huff, Sagar Lonial, Robert Z. Orlowski, David Conti, Christopher A. Haiman, Elad Ziv, John S Witte, Wendy Cozen
Journal: Blood (2019)
RTHP-28. TTFIELDS TREATMENT AFFECTS TUMOR GROWTH RATES: A POST-HOC ANALYSIS OF THE PIVOTAL PHASE 3 EF-14 TRIAL
Authors: Noa Urman, Gitit Lavy-Shahaf, Shay levi, Ze’ev Bomzon
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The pivotal EF-14 trial showed that Tumor Treating Fields (TTFields) extend Progression Free Survival (PFS) in newly Diagnosed Glioblastoma (ndGBM) patients. This leads to the hypothesis that TTFields therapy leads to local control of tumors, yielding a significant decrease in tumor growth rates. Here we present an analysis testing this hypothesis in biopsy-only patients who participated in the EF-14 trial. METHODS Biopsy patients of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=37/60, control: N=12/29). Volumes of enhancing tumor were segmented on T1c MRIs at baseline and at progression. Tumor growth rate was calculated as: growth_rate=(ln(v0)-ln(v1))/dt. (v0- tumor volume at baseline), v1- Tumor volume at progression, dt- days to progression), which models tumor volume as increasing exponentially over time. Median growth rates in the treatment and control arms were compared. RESULTS The median growth rate was lower in the treatment arm than in the control. (control: 0.14±0.12 mL/month, TTFields -0.011±0.11 mL/month, p&lt; 0.008 Wilcoxon rank-sum) DISCUSSION AND CONCLUSIONS This study shows that tumor growth rates are slower in patients treated with TTFileds+Temozolomide (TMZ) than in patients treated with TMZ alone. This analysis was restricted to biopsy-only patients since the definition of tumor volume is ambiguous in patients that underwent resection since a large portion of the tumor has been removed. The negative median growth rate for patients in the treatment arm may indicate that a significant number of TTFields-treated patients a decrease in tumor volume was observed, suggesting that TTFields enhances local tumor control. References: [1] Stupp, Roger, et al. Jama 318.23 (2017): 2306–2316.[[2 Stensjøen, Anne Line, et al. Neuro-oncology 17.10 (2015): 1402–1411.
ACTR-03. FINAL RESULTS OF A PHASE II STUDY OF HYPOFRACTIONATED RADIOTHERAPY WITH CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN PATIENTS OVER 70 YEARS OLD WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Mehran Yusuf, Jeremy Gaskins, Shiao Woo, Eric Burton
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND We sought to determine the efficacy and tolerability of hypofractionated radiotherapy (HFRT), 34Gy given over two weeks with concurrent and adjuvant temozolomide, in patients over 70 years old with newly diagnosed GBM. METHODS Patients ≥ 70 years of age with newly diagnosed GBM received HFRT to a dose of 34 Gy in 10 fractions over 2 weeks, delivered with concurrent and adjuvant TMZ. Quality of life (QOL) data using the validated functional assessment of cancer therapy-brain (FACT-BR) questionnaire was collected. Kaplan-Meier methods and log-rank tests were used for survival analyses. A random intercepts growth model with baseline and linear effect in time terms was used to assess QOL with relation to protocol treatment. RESULTS Eleven patients were enrolled from 12/1/2015 to 2/5/2018. Median age and KPS of the cohort was 74 years (range 70 -81) and 80 (range 60–100). Eight patients have died. Median follow-up of the cohort was 13.8 months (range 3 – 26 months). The median progression free survival (PFS) was 6.0 months (CI 4.7 months -not achieved (NA) and the median overall survival (OS) was 24.5 months (CI 10.2 months –NA). MGMT methylation status was significantly associated with both PFS (p =0.02) and OS (p =0.02). All patients completed HFRT with no patients developing ≥ grade 3 adverse treatment events. QOL did not significantly worsen over time with therapy (p =0.75). CONCLUSIONS This completed phase II trial suggest a HFRT schedule of 34Gy delivered over 2 weeks with concomitant and adjuvant TMZ is well tolerated in elderly GBM patients without compromising clinical outcomes. This result compares favorably to the longer HFRT regimen of 40Gy over 3 weeks. ClinicalTrials.gov identifier: NCT01985087
Center Effects on Outcomes in the Treatment of Acute Myelogenous Leukemia (AML): A Multilevel, Community-Based, Case-Controlled Study
Authors: Charles F. Lemaistre, Ju-Hsien Chao, Tonya Cox, Jose Carlos Cruz, William B. Donnellan, Alireza Eghtedar, Jared Holder, Suman Kambhampati, Shahbaz Malik, Michael B. Maris, Marcello Rotta, Frank Thomas Slovick, Minoo Battiwalla
Journal: Blood (2019)
IMMU-36. THE ROLE OF PD-L1 IN GLIOBLASTOMA-DERIVED EXTRACELLULAR VESICLES IN THE INDUCTION OF IMMUNOSUPPRESSIVE MONOCYTES
Authors: Benjamin Himes, Timothy Peterson, Jasmine Tyson, Helen Lee, Tristan deMooij, Luz Cumba-Garcia, Mi-Yeon Jung, Michael Gustafson, Allan Dietz, Aaron Johnson, Haidong Dong, Rachel Maus, Markovic Svetomir, Fabrice Lucien-Matteoni, David Yan, Sarah Uhm, Mina Abukhadra, Daniel Parney, Ian Parney
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common and lethal primary brain tumor, and novel therapeutic strategies that make a substantial impact on outcomes are sorely needed. Immunotherapies have shown great promise in the treatment of a number of cancers in recent year, and a concerted effort is being made to apply these treatment paradigms to GBM. However, many GBM patients exhibit profound immunosuppression, likely limiting the efficacy of such approaches. The mechanisms of this immunosuppression are poorly understood, but tumor-derived extracellular vesicles (EVs), may play a role. We demonstrate that GBM-derived EVs induce the development of myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs). We further demonstrate that these EV-induced monocytic cells are immunosuppressive, resulting in impaired T cell proliferation upon co-culture. We found that the immunosuppressive effects of tumor-derived EVs appear to be driven by the induction of these immunosuppressive monocytes, as EV treatment of T cells did not significantly impact T cell proliferation. Further, we sought to characterize the important of programmed death ligand 1 (PD-L1) in the induction of these immunosuppressive monocyte populations. We found PD-L1 to be expressed in the EVs from GBM cell lines, and that modulation in PD-L1 expression via either constitutive overexpression or shRNA-mediated knockdown resulted in concordant changes in expression in tumor-derived EVs. We demonstrate that PD-L1 is important for the induction of NCM but not for MDSCs. Taken together, these findings point to a significant role for tumor-derived EVs in the induction of immunosuppressive monocytes in GBM, and that these cells may be a driving force of systemic immunosuppression. PD-L1 is one factor expressed in EVs that has immunomodulatory properties, but additional EV cargo likely plays a major role in the induction of immunosuppressive cells.
Altered Expression of Hoxa1 Perturbs Haematopoiesis in a Dose-Dependent Manner and Induces Myelodysplasia in Mice
Authors: Shuhying Tan, Alistair Chalk, Ana C Maluenda, Lenny Straszkowski, Jack O'Halloran, Meaghan Wall, Louise E Purton
Journal: Blood (2016)
A Randomized Controlled Clinical Study of Peg-Rhg-CSF for Preventing Chemotherapy-Induced Neutropenia in Patients with B-Cell Non-Hodgkin Lymphoma
Authors: Changqing Zhen, Mei Ding, Kang Lu, Xueling Ge, Na Chen, Xiaosheng Fang, Xiaohui Sui, Jiang Yujie, Xin Liu, Ying Li, Xianghua Wang, Ying Li, Lingyan Zhang, Hongzhi Xu, Juan Fan, Xin Wang
Journal: Blood (2019)
QOLP-18. A TIME-BASED MODEL OF EARLY PALLIATIVE CARE INTERVENTION IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA, A SINGLE INSTITUTION FEASIBILITY STUDY
Authors: Margaret Johnson, Luis Ramirez, James Herndon, Woody Massey, Eric Lipp, Mary Affronti, Jung-Young Kim, Henry Friedman, Annick Desjardins, Dina Randazzo, David Ashley, David Casarett, Katherine Peters
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE There is no validated model for delivering palliative care (PC) in the glioblastoma (GBM) population. The primary objectives were to assess the feasibility and determine the acceptability of a time-based model of integrated specialty PC to patients and providers. Secondary objectives were to estimate the impact on healthcare utilization and quality of life (QoL) compared to historical controls. METHODS We consented and referred patients to PC at their initial Neuro-Oncology consultation between 4/2018 and 5/2019. We conducted QoL assessments (NCCN Distress Tool; Functional Assessment of Cancer Therapy-Brain (FACT-BR); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); Epworth Sleepiness Scale (ESS)) at (1) baseline (2) immediately after chemoradiation, and (3) 6 months following chemoradiation. Ongoing PC follow-up was at the discretion of the PC provider. We administered the Edmonton Symptom Assessment System (ESAS) before and after PC visits. We measured patient and referring provider satisfaction using FAMCARE-16 and a PC departmental survey, respectively. RESULTS We did not meet our goal enrollment of 50 patients. 32 were offered participation, 12 consented and 8 attended at least one PC visit. The mean number of PC visits was 1.6. Mean age was 62 (42–79). 75% had a KPS ≥80. Of those that did not complete the study, 2 died and 5 either withdrew consent or declined further visits. At baseline, 91.7 % had a NCCN distress score ≥4. Patients were overall satisfied with the intervention. CONCLUSION Introduction of specialty PC at the time of GBM diagnosis is challenging. Participants reported their experience as overall positive. Results from referring providers are pending. Due to low-enrollment we did not pursue further statistical comparisons regarding healthcare utilization compared to historical controls.