tbuckley/cabot-search huggingface dataset:
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events
Authors: Marcela V Maus, Sara Alexander, Michael R Bishop, Jennifer N Brudno, Colleen Callahan, Marco L Davila, Claudia Diamonte, Jorg Dietrich, Julie C Fitzgerald, Matthew J Frigault, Terry J Fry, Jennifer L Holter-Chakrabarty, Krishna V Komanduri, Daniel W Lee, Frederick L Locke, Shannon L Maude, Philip L McCarthy, Elena Mead, Sattva S Neelapu, Tomas G Neilan, Bianca D Santomasso, Elizabeth J Shpall, David T Teachey, Cameron J Turtle, Tom Whitehead, Stephan A Grupp
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as 'living drugs,' their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.
HSCT is effective in patients with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
Authors: Alexandra Laberko, Vasiliy Burlakov, Sarah Maier, Mario Abinun, Roderick Skinner, Anna Kozlova, Deepti Suri, Kai Lehmberg, Ingo Müller, Dmitry Balashov, Galina Novichkova, Dirk Holzinger, Andrew R. Gennery, Anna Shcherbina
Journal: Journal of Allergy and Clinical Immunology (2020)
Allergic Reactions After the Implantation of Drug-Eluting Stents: Is it the Pill or the Polymer?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Babak Azarbal, Jesse W. Currier
Journal: Journal of the American College of Cardiology (2006)
Myelodysplastic syndrome and acute myeloid leukaemia in patients treated with PARP inhibitors: a safety meta-analysis of randomised controlled trials and a retrospective study of the WHO pharmacovigilance database
Authors: Pierre-Marie Morice, Alexandra Leary, Charles Dolladille, Basile Chrétien, Laurent Poulain, Antonio González-Martín, Kathleen Moore, Eileen Mary O'Reilly, Isabelle Ray-Coquard, Joachim Alexandre
Journal: The Lancet Haematology (2020)
IMMU-02. THE SURVIVAL OUTCOMES ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITORS FOR NON-SMALL CELL LUNG CARCINOMA PATIENTS WITH BRAIN METASTASES IN THE UNITED STATES
Authors: Nayan Lamba, Timothy Smith, Bryan Iorgulescu
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Management of advanced NSCLC has been transformed by PD-1/PD-L1 immune checkpoint inhibitors (ICI), with FDA approvals in 2015 (second-line) and 2016 (first-line). Because patients with brain metastases (BMs) were disproportionately excluded from the pioneering trials, herein we evaluated the overall survival (OS) associated with ICI in NSCLC BMs nationally. METHODS Patients newly-diagnosed with stage 4 NSCLC, including BMs, from 2010–2016 were identified from the National Cancer Database (comprising &amp;gt;70% of all newly-diagnosed cancers in the U.S.) Post-approval, median time from diagnosis to ICI was 58days, and this timepoint was selected for all landmark survival analyses (logrank test and multivariable Cox regression) and for multivariable logistic regression to identify predictors of ICI utilization. RESULTS 50,858 patients presented with advanced NSCLC that involved the brain: representing 27.6% of all newly-diagnosed stage 4 cases. Following initial FDA approvals in 2015, ICI rates for BM patients rose from 7.2% in 2015 to 12.7% in 2016. OS for NSCLC BMs for patients diagnosed post-approval (median 6.3 months, 95%CI: 6.0–6.6) was substantially better than those diagnosed pre-approval (median 5.5 months, 95%CI: 5.4–5.7, p&amp;lt; 0.001) and, in fact, than those diagnosed in 2014 (median 5.9 months, 95%CI: 5.6–6.1, p=0.002). Among patients diagnosed post-approval, ICI receipt demonstrated substantially improved OS in landmark survival analyses (median 13.8 months, 95%CI: 12.2–15.1; vs. 8.5 months, 95%CI: 8.3–8.9, p&amp;lt; 0.001); benefits which persisted in multivariable landmark survival analyses (HR 0.83, 95%CI: 0.71–0.96, p=0.02), independent of patient characteristics, other therapies, and extracranial disease. For patients diagnosed post-approval, who reached the landmark timepoint, ICI receipt was independent of patient demographics, socioeconomic status, and hospital type—with the exception of Medicaid-insured patients, who were less likely than privately-insured patients to receive ICI (OR 0.77, 95%CI: 0.60–0.97, p=0.03). CONCLUSIONS Nationally, the dramatic OS benefits of ICIs for advanced NSCLC were also demonstrated for patients with BMs.
Targeting Mitochondrial Oxidative Stress in Heart Failure: Throttling the Afterburner⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Christoph Maack, Michael Böhm
Journal: Journal of the American College of Cardiology (2011)
Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma
Authors: Franck Morschhauser, Martin J. S. Dyer, Harriet S. Walter, Alexey V. Danilov, Loic Ysebaert, Daniel James Hodson, Christopher Fegan, Simon A. Rule, John Radford, Guillaume Cartron, Krimo Bouabdallah, Andrew John Davies, Stephen Spurgeon, Nishanthan Rajakumaraswamy, Biao Li, Rita Humeniuk, Xi Huang, Pankaj Bhargava, Juliane M. Jürgensmeier, Gilles Salles
Journal: Leukemia (2020)
RADT-31. PATTERNS OF CARE IN THE USE OF ADJUVANT RADIOTHERAPY AND CHEMOTHERAPY IN LOW GRADE GLIOMA PATIENTS IN THE UNITED STATES FROM 2010-2016
Authors: Warren Rehrer, Yazmin Odia, Muni Rubens, Noah Kalman, Michael Chuong, Rupesh Kotecha, Minesh Mehta, Matthew Hall
Journal: Neuro-Oncology (2020)

Abstract PURPOSE In 2016, RTOG 9802 reported an overall survival advantage with the addition of chemotherapy to adjuvant radiotherapy (CRT) in patients with high-risk low grade glioma (LGG). We used the National Cancer Database (NCDB) to measure trends in CRT use in LGG patients from 2010-2016, a period when no Level 1 evidence existed. METHODS The NCDB was queried for WHO Grade II glioma patients treated from 2010-2016 who met the inclusion criteria for RTOG 9802. Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received adjuvant CRT. Relative percent change and average annual percentage change (AAPC) were compared to determine if a change (defined a priori as &amp;lt; 0.01) occurred in the use of adjuvant CRT in LGG patients during this period. RESULTS The analytic cohort consisted of 5,039 patients; 64.3% of patients were 40 years or older and 35.7% were under 40 with subtotal resection. Use of adjuvant CRT increased from 18.9% to 49.7% (p&amp;lt; 0.001) during 2013-2016, with no change observed before 2013. The AAPC in the use of CRT was +39.6% per year (p&amp;lt; 0.001). Corresponding declines in patients treated with surgery alone (p&amp;lt; 0.001) and surgery plus radiotherapy (p&amp;lt; 0.001) were observed during 2013-2016. Logistic regression demonstrated patients who were under 40 years old were significantly less likely to receive adjuvant CRT than patients 40 years or older (Odds Ratio 0.561, 95% CI 0.475-0.663, p&amp;lt; 0.001). Use of adjuvant CRT increased from 12.5% to 45.1% in patients with oligodendroglioma during 2013-2016 (p&amp;lt; 0.001). CONCLUSIONS During 2013-2016, an increasing number of patients with LGG were treated with surgery followed by adjuvant CRT. Future studies may characterize the use of single agent vs. multiagent chemotherapy in this population and the adoption of trimodality therapy by mutation status.
Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy
Authors: Claudio Rapezzi, Perry Elliott, Thibaud Damy, Jose Nativi-Nicolau, John L. Berk, Eric J. Velazquez, Kurt Boman, Balarama Gundapaneni, Terrell A. Patterson, Jeffrey H. Schwartz, Marla B. Sultan, Mathew S. Maurer
Journal: JACC Heart Failure (2020)

Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt). ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt. In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv. There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019). Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889)
NCOG-11. POST-RADIOSURGICAL OUTCOMES OF CYSTIC VESTIBULAR SCHWANNOMAS, A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nima Hamidi, Elie Massaad, Jacalynn Goetz, Alireza Mansouri
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Vestibular schwannomas (VS) are benign neoplasms that present as cystic or solid variants. Cystic VS are associated with fast and unpredictable growth patterns, and their adherence to nearby structures can lead to poor surgical outcomes. While radiosurgery (RS) has gained popularity for VS, the heterogeneity of literature necessitates a systematic review. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), PubMed, EMBASE, Web of Science, and Cochrane were searched for observational studies reporting cystic and solid VS radiosurgical outcomes. Pooled estimates were calculated using random-effect models with generic inverse variance to compare tumor control rates between cystic and solid VS. Quality assessment was done using the Newcastle Ottawa Criteria (NOS). RESULTS The search yielded 2,989 studies from which 680 were selected for full-text screening and 6 were included in this review and meta-analysis. The quality of studies ranged between good (3 studies, NOS 7/9), fair (2 studies, NOS 6/9), and poor (1 study, NOS 4/9). The patient pool included 1,070 solid and 347 cystic VS, all treated by gamma knife RS. No difference in tumor control was observed (RR: 1.02, 95%CI 0.91-1.16, p=0.7). 3 studies reported post-RS complications. Haseguawa reported hydrocephalus in 7 of 74 cystic cases. Ryu reported 1 case of hydrocephalus and 1 case of trigeminal pain in their 14 cystic cases. Shirato reported 5 transient trigeminal Neuralgia, 1 transient vertigo and 1 shunt operation in their 20 cystic cases. CONCLUSION Evidence presented in this meta-analysis supports the safety and efficacy of radiosurgery in treating cystic VS.
NFB-05. AN UNUSUAL PRESENTATION OF RECURRENT LANGERHANS CELL HISTIOCYTOSIS OF THE CRANIOFACIAL BONES IN A PATIENT WITH NEUROFIBROMATOSIS TYPE I
Authors: Blake Chaffee, Alexis Judd, Sarah Rush, Erin Wright
Journal: Neuro-Oncology (2020)

Abstract Neurofibromatosis type 1 (NF1), predisposes patients to benign and malignant tumors due to lack of suppression of the mitogen activated protein kinase (MAPK) signaling pathway. Langerhans cell histiocytosis (LCH) manifests in numerous ways, from localized lesions to multisystem organ involvement secondary to a constitutively active MAPK signaling cascade often driven by BRAF mutations. While both LCH and NF1 are characterized by overactive MAPK signaling, there are few reports of the two diseases occurring simultaneously. We report a novel case of a patient with underlying NF1 and recurrent LCH without a BRAFV600E mutation. She initially presented at 2 years of age with an aggressive appearing mass of the left temporal bone found on surveillance imaging. Pathology was consistent with Langerhans histiocytosis and she was treated with the LCH-III protocol for patients with high-risk LCH due to the location of her lesion. Five years after completion of therapy, MRI demonstrated development of a calvarial mass consistent with relapsed LCH in a new risk site. Lesional curettage was performed and pathology confirmed recurrence of LCH with juvenile xanthogranulomatous features. BRAF testing of blood and the lesion were negative for any BRAF alterations. Further genomic evaluation of the tumor is in progress at this time to evaluate for other known mutations associated with LCH. The patient is currently receiving monthly cytarabine treatment which she has tolerated to date. Our patient represents a unique presentation of recurrent LCH in a patient with NF1 and further molecular evaluation may help identify other drivers of LCH activation.
QOL-04. INFLUENCE OF FAMILY, SCHOOL, AND HOSPITAL SYSTEMS IN SUPPORTING SURVIVORS OF PEDIATRIC BRAIN TUMORS WITH NEUROCOGNITIVE LATE EFFECTS
Authors: Emily Moscato, Lisa Gies, Aimee Miley, Ralph Salloum, Shari Wade
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Pediatric brain tumor survivors (PBTS) are at risk for developing neurocognitive late effects that may interfere with academic and adaptive functioning. To mitigate the potential impact, some PBTS may implement strategies independently, while others may rely on system-level support from family, school, or hospital systems. Given the limited knowledge on survivor and family perspectives of these supports, we conducted a mixed-methods study involving PBTS and their caregivers to examine the influence of family, educational, and hospital supports, and identify areas of unmet need. PARTICIPANTS AND METHODS PBTS (N=56,Mage=18.12,range=10–25) completed questionnaires on academic accommodations. Medical chart reviews provided diagnosis and treatment information. A subset of families, who did not significantly differ from the larger sample on demographics, completed qualitative interviews (N=25). Three coders identified themes separately for parents and survivors and reached consensus (kappa’s &amp;gt; .78) using thematic content analysis. RESULTS Families emphasized the role of family support, including providing individualized help, setting up a structured learning environment, and suggesting metacognitive strategies. Parents also emphasized how they have adjusted their expectations. At school, 53% reported an individualized education plan. Formal accommodations (e.g., modified coursework, small group instruction, extra time) were helpful, yet some noted barriers, including embarrassment and lack of follow-through. Survivors emphasized the value of informal accommodations. Families described unmet needs related to connecting with other survivors, navigating community and educational resources, and transitioning to adulthood. CONCLUSIONS PBTS seem to rely on systems-level supports to mitigate neurocognitive effects. Future work should strengthen communication between systems and adult transition services.
Acute Coronary Syndromes: Don't Bypass the Clopidogrel⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Colin M. Barker, H. Vernon Anderson
Journal: Journal of the American College of Cardiology (2009)
Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study
Authors: Ibiyemi Ilesanmi, George Tharakan, Kleopatra Alexiadou, Preeshila Behary, Haya Alessimii, Candace Bovill-Taylor, Julia Kenkre, Sirazum Choudhury, Chedie Doyle, Sanjay Purkayastha, Alex Miras, Christos Tsironis, Harvinder Chahal, Stephen R. Bloom, Nick S. Oliver, Ahmed R. Ahmed, Bernard Khoo, Tricia M.-M. Tan
Journal: Diabetes Care (2020)

Roux-en-Y gastric bypass (RYGB) is an established treatment for type 2 diabetes and obesity. The study objective was to establish RYGB's effects on glycemic variability (GV) and hypoglycemia.This was a prospective observational study of 10 participants with obesity and prediabetes or type 2 diabetes who underwent RYGB. Patients were studied before RYGB (Pre) and 1 month, 1 year, and 2 years postsurgery with continuous glucose measurement (CGM). A mixed-meal test (MMT) was conducted at Pre, 1 month, and 1 year.After RYGB, mean CGM decreased (at 1 month, 1 year, and 2 years), and GV increased (at 1 year and 2 years). Five of the 10 participants had a percent time in range (%TIR) <3.0 mmol/L (54 mg/dL) greater than the international consensus target of 1% at 1 or 2 years. Peak glucagon-like peptide-1 (GLP-1) and glucagon area under the curve during MMT were positively and negatively associated, respectively, with contemporaneous %TIR <3.0 mmol/L.Patients undergoing RYGB are at risk for development of postbariatric hypoglycemia due to a combination of reduced mean glucose, increased GV, and increased GLP-1 response.
CTNI-58. A PROSPECTIVE TRIAL OF RESECTION AND SURGICALLY TARGETED RADIATION THERAPY FOR INITIAL OR SALVAGE TREATMENT OF AGGRESSIVE MENINGIOMA
Authors: Leland Rogers, Peter Nakaji, Emad Youssef, Kris Smith, Terry Thomas, Joseph Zabramski, Christopher Dardis, Dilini Pinnaduwage, Heyoung McBride, David Brachman
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Achieving durable local control (LC) for aggressive or recurrent meningiomas remains problematic. Resection (R) alone is insufficient and even with the addition of radiation therapy (RT), outcomes are suboptimal in many series. OBJECTIVE Hypothesizing R plus Surgically Targeted Radiation Therapy (STaRT) may improve LC, we evaluated a permanently implanted brachytherapy device consisting of Cs-131 seeds positioned within modular resorbable collagen carrier/spacer tiles (GammaTile, GT Medical Technologies, Tempe AZ). METHODS From 2/2013-2/2018 recurrent and newly diagnosed aggressive meningiomas were treated on a prospective single-arm study (NCT#03088579). At completion of maximum safe resection the tumor bed was lined with collagen tiles imbedded with Cs-131, delivering 60–80 Gy at 5 mm depth. No additional local therapy was given absent progression. RESULTS 35 meningiomas in 28 patients were treated; 29 recurrent (22 prior R+RT, 6 R only, and 1 RT only) and 6 without prior therapy. WHO grade was I in 2 patients, II in 28, and III in 5. Median age was 66 years (range 37–82), KPS 80 (70–100), female: male ratio 15:13. Mean time for implantation was 5 minutes. At a median radiographic follow-up of 25.5 months (range 0.1–71) LC was 80% (28/35) and median time to progression had not been reached (95% CI &amp;gt; 35.6 months). LC at 12/24/36/48 months was 100/89/72/72% for all tumors, 100/93/79/79% for Grade II, and 100/50/0/0% for Grade III, respectively. No patient receiving STaRT as their initial RT failed. Median overall survival was 50 months. Four symptomatic adverse events occurred, 2 wound breakdowns requiring surgery and 2 radiation-related brain changes, medically treated. CONCLUSION R+STaRT demonstrates favorable safety and LC outcomes in this single-arm prospective trial that includes heavily pre-treated patients. A commercial version of the device recently received FDA clearance for use in newly diagnosed malignant or recurrent intracranial neoplasms including meningiomas.