tbuckley/cabot-search huggingface dataset:
Baseline and early post-treatment clinical and laboratory factors associated with severe neurotoxicity following 19-28z CAR T cells in adult patients with relapsed B-ALL.
Authors: Jae Hong Park, Bianca Santomasso, Isabelle Riviere, Brigitte Senechal, Xiuyan Wang, Terence Purdon, Yongzeng Wang, Elizabeth Halton, Claudia Diamonte, Daniel Li, Michel Sadelain, Renier J. Brentjens
Journal: Journal of Clinical Oncology (2017)

7024 Background: CD19-specific chimeric antigen receptor (CAR) modified T cells produce high anti-tumor activity in relapsed or refractory (R/R) ALL, but can be associated with cytokine release syndrome (CRS) and neurotoxicity (NTX). Herein, we report baseline and post-treatment clinical and laboratory factors associated with severe NTX (≥Grade 3) in our phase I clinical trial of CD19-specific 19-28z CAR T cells for adult patients (pts) with R/R B-ALL (NCT01044069). Methods: 51 adult pts with R/R B-ALL were treated with 19-28z CAR T cells following conditioning chemotherapy at MSKCC. In order to identify clinical and serum biomarkers associated with severe NTX (sNTX), we examined demographic, treatment, and clinical blood parameters as well as in vivo CAR T expansion and serum cytokines, and performed univariate and multivariate analysis. Results: In this cohort of ALL pts, 20, 8, 2, 18 and 3 pts experienced Gr 0, 1, 2, 3, and 4 NTX, respectively. No pt developed grade 5 NTX. Disease burden (≥50% blasts) at the time of T cell infusion (p = 0.0045) and post-treatment ≥Gr3 CRS (p = 0.0010) were significantly associated with sNTX, but we found no association with age, weight, T cell dose, choice of conditioning chemotherapy (Flu/Cy s. Cy), and prior lines of treatment. Among the clinical and blood parameters, fever, low PLT, high ferritin and MCHC as well as elevated GM-CSF, IFNγ, IL-15, IL-5, IL-10, IL-2 at day 3 of T cell infusion at day 3 of T cell infusion were significantly associated with sNTX (all p &lt; 0.01). While some of these cytokines were also elevated in severe CRS cases, IL-5 and IL-2 at day 3 were unique to sNTX. Furthermore, in vivo peak CAR T expansion at day 7 (p = 0.0001) significantly correlated with sNTX (p &lt; 0.01). Lastly, multivariate analysis revealed baseline PLT &lt; 60 or MCHC &gt; 33.2% and morphologic disease ( &gt; 5% blasts) has 95% sensitivity and 70% specificity of identifying sNTX pts. Conclusions: These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX. Clinical trial information: NCT01044069.
Understanding Pediatric Patients Who Discontinue Gender-Affirming Hormonal Interventions
Authors: Jack L. Turban, Jeremi Carswell, Alex S. Keuroghlian
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
An open-label, non-randomized, multi-arm, phase II trial evaluating pembrolizumab combined with cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Results of the interim safety analysis.
Authors: Assuntina Gesualda Sacco, Karen Messer, Amanda Natsuhara, Ruifeng Chen, Deborah J.L. Wong, Francis P. Worden, Douglas Adkins, Emily Pittman, Jing Zhang, Gregory A. Daniels, Kathryn A. Gold, Maechelle Espiritu, Brian Sutton, Ezra E.W. Cohen
Journal: Journal of Clinical Oncology (2018)

6037 Background: Pembrolizumab (a humanized monoclonal antibody blocking programmed death receptor-1), and cetuximab (a chimeric monoclonal antibody inhibiting epidermal growth factor receptor) are both FDA-approved as single agents for second-line R/M HNSCC treatment. This is the first trial to combine pembrolizumab with cetuximab to evaluate anti-tumor synergy. As this specific drug combination has not been previously tested, an interim safety analysis was completed per protocol. Methods: Patients (pts) with R/M HNSCC were treated with pembrolizumab at a fixed dose of 200mg IV on day 1 with cetuximab 400mg/m2 loading dose followed by 250mg/m2 weekly (21-day cycle). The first 10 pts who enrolled and completed at least 1 cycle of therapy were included in the safety analysis. A mandatory study hold and Data Safety Monitoring Committee (DSMC) review were required if at least 4 of the 10 pts developed any grade (G) 3-4 non-hematologic toxicity. Results: Of the 10 patients included in the analysis, median age 58y (range 47-79y), M: F 5:5. 8 pts had mucosal (6 oral cavity, 1 oropharynx, 1 nasopharynx) and 2 had cutaneous HNSCC primaries. 65 adverse events (AEs) were reported in 9 pts; G1: 39, G2: 15, ≥G3: 11. Of the 11 ≥G3 AEs, only 1 was treatment-related (see Table). There were no treatment-related deaths or dose-limiting toxicities (DLTs). 3 pts discontinued treatment, none of which were due to toxicity (2 had disease progression, 1 withdrew from study). DSMC reviewed the safety data and permitted resumption of trial accrual. Of 7 evaluable pts, 4 partial responses were noted at first radiographic assessment. Clinical trial information: NCT03082534. Conclusions: Pembrolizumab combined with cetuximab has a very tolerable safety profile, with no DLTs. Efficacy analysis of this combination will be performed. Grade AE Frequency Description Related? Serious? 3 1 Acneiform rash Definite N 3 1 Hypotension Unlikely Y 3 1 Febrile neutropenia Unlikely Y 3 1 Fatigue Unlikely N 3 1 Dysphagia N Y 3 1 Aspiration N Y 3 1 Skin ulceration N Y 3 1 Lung infection N Y 4 1 Sepsis N Y 5 1 Death N Y 5 1 Death N Y
Comprehensive genomic analysis of solid tumors by next-generation sequencing.
Authors: Waled Bahaj, Lara Ann Kujtan, Omer M Toor, Scott Morris, Ashiq Masood, Janakiraman Subramanian
Journal: Journal of Clinical Oncology (2018)

e24291 Background: Tumor profiling by next-generation sequencing (NGS) to identify actionable somatic alterations is the cornerstone of precision oncology. Using this information oncologists can match the actionable targets with therapies. Methods: We retrospectively analyzed the results of patients with solid tumors who underwent NGS testing in 2016 using Paradigm PCDxTM. We excluded samples with quality failures, incomplete information, and targets with no available data. We used the OncoKB precision oncology knowledge base (http://oncokb.org) to identify actionable mutations and copy number alterations (CNA). Results: We identified 2908 unique cancer tissue samples obtained from 2781 patients with cancer. We categorized them into 25 main cancer types, the most common cancer types were breast (31.4%), colorectal (11%), genitourinary (9.9%), non-small cell lung cancer (9.4%), and sarcomas (5.2%). We identified 1942 DNA alterations including single nucleotide variations, CNA and fusion genes in 1370 (49.3%) patients. We identified 1249 (44.9%) actionable alterations in 1103 (39.6%) patients. The most frequently detected alterations were: KRAS (481, 24.7%), PIK3CA (190, 9.7%), EGFR (156, 8.0%), and ERBB2 (118, 6.0%). Conclusions: To our knowledge, this is the largest study from a predominantly community setting on the impact of hot-spot based NGS testing platform in solid tumors. Our study clearly shows that NGS testing was successful in identifying targeted treatment options in a variety of solid tumors.
Feasibility of withholding dexamethasone premedication in patients not experiencing two previous cycles of weekly paclitaxel related infusion hypersensitivity reaction.
Authors: Walailuk Tanpipattanakul, Napa Parinyanitikul
Journal: Journal of Clinical Oncology (2016)

e21634 Background: Premedication with dexamethasone is an essential part in prevention of hypersensitivity reaction associated with taxane administration. However, the possibility of stopping dexamethasone premedication has been investigated in previous studies with the intention of reducing steroid’s adverse events, either result and particular protocol was limited. So, our study aims to evaluate the incidence of infusion HSR after discontinuing dexamethasone premedication in patients who did not have experiencing two previous cycles of weekly paclitaxel associated infusion HSR Methods: Early breast cancer patients who received adjuvant weekly paclitaxel in a retro prospective cohort from January 2012 through January 2016 at the King Chulalongkorn Memorial Hospital were reviewed. All patients received a standard premedication protocol prior to the first and second cycle. Dexamethasone was omitted in later cycles in all patients who did not have experiencing infusion HSR. Patients who developed HSR during one or two cycles of paclitaxel infusion were excluded. The incidence of HSR during later cycle of paclitaxel administration and factors associated with this adverse reaction were collected. Results: 74 out of 78 patients who did not experience infusion HSR after two cycles were identified.6 out of 74 patients reported grade II HSR (8.1%), which occurred mostly during the first six cycles (66.7%). Only one patient had continuously developed HSR even adding dexamethasone premedication in later cycle. Temporary discontinued paclitaxel infusion was observed in all HSR patients. No differences regarding age, BMI, menopausal status and underlying disease between HSR and non-HSR group were found. About safety profile, peripheral neuropathy (grade II, 21%), edema (5.7%) and skin rash (4.2%) were commonly reported whereas insomnia and dyspepsia were rarely described in withholding patients. Conclusions: Withholding dexamethasone premedication in non-experiencing HSR patients after two previous cycles of weekly paclitaxel administration was safe and did not impact on higher incidence of HSR.
An observational descriptive study of a newly implemented service of genetic counselling in Pasto (Colombia) between 2015 and 2016 in a low-middle income country.
Authors: Jorge Mauricio Melo, Diana Buitrago, Nathalia maria Muñoz
Journal: Journal of Clinical Oncology (2018)

e13626 Background: in 2015 there were 71.000 new cancer cases diagnostic in Colombia. 10% of cancer cases can be hereditary. Genetic counseling offers to individuals with a family history of cancer the possibility to know their risk. In Colombia a little proportion of eligible patients for genetic counseling have access to it, thus, there is slight evidence about genetic cancer characteristics. We present the features of patients who attended to a genetic counseling in Pasto, where a service of genetic counseling was implemented. Methods: An observational descriptive study of patients older 18 years who had family history of cancer, who attended to a genetic counseling during the years 2015-2016 in the city of Pasto was performed. All patients received genetic counseling, pedigree and on-line test for risk, then patients with risk were included into the study. Results: 101 patients were examined and 23 patients who meet the inclusion criteria were included. Mean age was 44 ±22 years, 74% were female, and 70% came from rural areas. In 65% of consultations the patient paid for their genetic counseling and test. 61% (14/23) of genetic tests were positive, 9% (2/23) VUS and 30% (7/23) negative. In the positive cases, four were associated to familiar colon polyposis; two had a mutation related to medullary thyroid cancer, two cases for cdh1 mutation for gastric cancer and four for hereditary breast ovarian cancer syndrome, two cases were categorized as VUS for breast cancer. As a result of the counseling in 8 patient’s treatments was adjusted. changes in the surgical course and type of surgery was performed. Conclusions: Genetic counseling is a useful tool which can benefit patients; can achieve an early diagnosis and change in treatments. Although practice is uncommon in Colombia, due to in most of the cases health system does not have coverage for that. More efforts on inclusion and public politics are necessary in order to let community have access to this kind of health study. In the future only with a great number of tests can be obtained evidence about the genetic cancer profile in Colombia.
Peritoneal liquid biopsy used to predict cancer recurrence after gastrointestinal cancer surgery.
Authors: Satoshi Murata, Katsushi Takebayashi, Tsuyoshi Yamaguchi, Sachiko Kaida, Hirokazu Kodama, Hiroya Akabori, Hiroya Iida, Naomi Kitamura, Hiromitsu Maehira, Haruki Mori, Toru Miyake, Yuki Kawai, Tsuyoshi Mori, Tomoyuki Ueki, Hiromichi Sonoda, Soichiro Tani, Yoshitaka Terada, Tomoharu Shimizu, Yataro Daigo, Masaji Tani
Journal: Journal of Clinical Oncology (2018)

e16191 Background: To elucidate recurrence pathophysiology after gastrointestinal cancer surgery, the prognostic effect of peritoneal cancer cell spillage during surgery was evaluated in patients (pts) who underwent potentially curative (R0) gastric cancer (GC) or pancreatic cancer (PC) surgery. Methods: Pts with advanced GC (≥pT2 MP) or PC who underwent R0 surgery between 2010 and 2017 were enrolled. Peritoneal washing (PW) fluid before (PW-Pre) and after surgery (PW-Post) was collected and cultured to detect viable cancer cells. The association between cancer cell culture (CCC) and recurrence was evaluated. Results: In 100 consecutive pts with advanced GC negative for PW-Pre-cytology (CY0) and PW-Pre CCC (-), 53 pts showed PW-Post CCC (+) and 47 had PW-Post CCC (-). No clinicopathological difference was observed between the two cohorts. Recurrences (peritoneum: 7, liver: 3, distant lymph node: 9, local: 1) occurred in 20 (37.7%) pts with PW-Post CCC (+). No recurrence was observed in pts with PW-Post CCC (-). Multivariate logistic analysis showed that PW-Post CCC (+) was an independent risk factor for recurrence (Odds 60.3, P = 0.005). The 5-year relapse-free survival rate was 45.4% in pts with PW-Post CCC (+), and 100% in pts with PW-Post CCC (-) (P < 0.0001). In 53 consecutive pts with PC with CY0, 19 (36.5%) showed PW-Pre CCC (+). In 33 pts with PW-Pre CCC (-), 25 (75.7%) developed PW-Post CCC (+), and 8 (24.3%) remained at PW-Post CCC (-). No clinicopathological difference was observed between pts with PW-CCC (+) and PW-CCC (-). Recurrences (peritoneum: 8, liver: 16, lung: 4, distant lymph node: 2, local: 9) occurred in 32/44 (72.7%) pts with PW-CCC (+). One (12.5%) of 8 pts with PW-CCC (-) developed local recurrence. Multivariate logistic analysis showed PW-CCC (+) as an independent risk factor for recurrence after PC surgery (Odds 38.7, P = 0.003). Multivariate Cox analysis demonstrated that PW-CCC (+) was an independent poor prognosis factor (hazards ratio 10.4, P = 0.022). Conclusions: PW-CCC as peritoneal liquid biopsy is a promising predictive biomarker for recurrence after R0 GC or R0 PC surgery. This may rationalize intra-operative intra-peritoneal therapy, and help determine adjuvant chemotherapy intensity.
Clinical Trials—We Get What We Pay For
Authors: Joseph S. Ross
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 17290: Metabolomic Signatures of Birth Weight in 18288 Adolescents and Adults
Authors: Peter Wurtz, Qin Wang, Marjo Niironen, Jaakko Kaprio, Johan Eriksson, Olli Raitakari, Debbie A Lawlor, George Davey Smith, Marjo-Riitta Jarvelin, Mika Ala-Korpela, Kirsi Auro
Journal: Circulation (2016)

Introduction: Lower birth weight is associated with increased susceptibility to cardiovascular disease and diabetes in adulthood, but the underlying molecular pathways are incompletely understood. Aims: We examined associations of birth weight with a comprehensive metabolic profile measured in adolescents and adults. Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts comprising altogether 18,288 individuals (mean age 26, range 15-75). Metabolic biomarker associations with birth weight were adjusted for sex, gestational age, and age at blood sampling. The metabolic associations with birth weight were compared to the corresponding associations with adult BMI. Results: Lower birth weight was adversely associated with numerous cardiometabolic biomarkers, including amino acids, fatty acids, lipoprotein subclasses, and markers of inflammation and impaired liver function (P<0.001 for 46 measures). Associ...
Development of an allogeneic product by CAR-T cells TCR knock-down.
Authors: Susanna Raitano, Simon Bornschein, Jennifer Bolsée, Jérôme Marijsse, Céline Marchand, Fanny Huberty, Benjamin Violle, Thuy N'Guyen, Céline Jacques-Hespel, Nancy Ramelot, Julien Houssa, Sophie Agaugue, David Edward Gilham
Journal: Journal of Clinical Oncology (2018)

e15040 Background: The majority of CAR-T cell therapy studies use the patients’ own autologous cells which carry many potential restrictions related to manufacturing such as quantity and quality of cells. Sourcing cells from an allogeneic healthy donor avoids many of these manufacturing issues. However, the recognition of recipient HLA by the T Cell Receptor of the donor T cells drives a graft versus host (GvH) response leading to normal tissue damage thereby limiting the potential of allogenic T cell therapy. Blunting this response is critical for the successful development of a safe allogeneic CAR-T cell therapy. Hypothesis: Inhibition of TCR activity using shRNAs targeting the CD3 complex can reduce or eliminate TCR driven GvH activity. Objective: To identify candidate shRNA that can knockdown CD3 and achieve inhibition of TCR signaling in primary human T cells. Methods: Peripheral blood derived T cells from healthy donors were transduced with the appropriate vector then subjected to puromycin selection for further 48 hours after transduction. On day 8, cells were finally harvested and characterized. Results: There was a systematic decrease of CD3e or CD3z expression at the RNA level in cells transduced respectively with shRNA against CD3e or CD3z chains of the TCR complex in the Jurkat T cell line as well as in human primary T cells This also correlated with a systematic decrease of CD3e and TCRa/b expression at the protein level in cells transduced with either shRNA against CD3e or CD3z Most interestingly shRNA targeting of the CD3 complex drove reduced TCR signaling as determined by reduced levels of cytokine release upon mitogenic stimulation Conclusions: Targeting of the CD3 complex with shRNA reduced the level of CD3 expression in a Jurkat T cell line as well as in primary human T cells. This resulted in decreased in vitro responses of the engineered T cells during mitogenic stimulation, most likely due to impaired TCR assembly and cell surface expression. These studies support the concept of exploiting shRNA technology for allogenic CAR-T cell therapy that using a single vector, non-gene editing approach.
Abstract P037: Community Lifestyle Intervention Decreases Risk of Suicide and Improves Overall Lifestyle
Authors: Francisco E Ramirez, Neil Nedley
Journal: Circulation (2018)

Background: Morbid thoughts are a dangerous cognitive problem that can lead to suicide. It has been documented that educational lifestyle programs can improve metabolic markers, we study the effect in the psychological realm. This study documents the response of an 8-week lifestyle program on depression levels and morbid thoughts. Methods: Participants from 5 continents who finished a depression program were studied. Those who chose to participate met once a week for 8 weeks for a 2 hour program. It consisted of a 45 minute DVD presentation followed by a small group discussion, work assignments were given at every session. This program focused on educating participants on healthy behaviors such as exercise, plant-based diets, sleep hygiene, thought control and others. Cooking classes and practical exercises helped teach the principles. Each participant answered at the beginning of the program and at the end of the program the Depression and Anxiety Assessment Test. It assessed depression level based on DSM-5 [The Diagnostic and Statistical Manual of Mental Disorders Volume 5]. No questions were asked about individuals' treatment of depression. The depression was classified according to DSM-5 into 4 categories as none (0-6), mild (7-10), moderate (11-19) or severe (20 or more). The test also inquired the frequency of morbid thoughts, which were defined as thinking about death often, considering harming yourself or others. The degree of morbid thoughts were ranked from A-D ([A] having none or rare; [B] having them 1/4 of the days; [C] being 1/2 of the days; [D] being almost every day in a period of 2 weeks). Results: From 5997 participants that finished the 8 week program the mean age was 52.3, SD 15.1, and n= 4209 (70.1%) were female. From this group, n=1924 (32%) participants reported some level of morbid thoughts. Of the morbid thought group, the depression average before the program was 17.7, SD 6.2, median 19, mode 22. At the end of the 8 week program, the depression average of the same group was 9.6, SD 6.5, median 9, mode 5. The pair t-test of depression scores was significant with a t=50.26, p&lt;.001. The levels of morbid thoughts at the beginning was A n=4073, B n=919, C n=587, D=418, and by the end A n=5180, B n=478, C n=236 and D n=103. Conclusion: The educational intervention effectively improves this worrisome symptom decreasing even the everyday morbid thoughts therefore decreasing the risk of suicide. The emphasis of the program is to make the lifestyle changes permanent. A long term study is being planned to investigate how the changes continue on the long term.