tbuckley/cabot-search huggingface dataset:
P14.19 Regorafenib in recurrent glioblastoma patients: a large real-life experience
Authors: M Caccese, G Cerretti, M Padovan, V Zagonel, G Lombardi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Regorafenib (REG), an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases showed encouraging benefit in recurrent GBM patients enrolled in the randomized, phase 2 REGOMA trial. We investigated the clinical outcome and safety of REG in a real-life population of recurrent glioblastoma patients treated at Veneto Institute of Oncology as off-label use. MATERIAL AND METHODS Patients receiving REG at Veneto Institute of Oncology (Padua, Italy) were entered prospectively on a clinical database. Data were retrospectively analyzed. The primary endpoints of the study were overall survival (OS) and safety. The major inclusion criteria were: histologically confirmed diagnosis of GBM, disease progression as defined by RANO criteria after surgery followed by radiochemotherapy with temozolomide, ECOG PS ≤ 2; PTS with ≥ 2 prior lines of therapy were excluded. According to original schedule, patients received REG 160 mg once daily for the first 3 weeks of each 4-week cycle until disease progression, death, unacceptable toxicity, or consent withdrawal. Kaplan-Meier method was used to estimate the survival curves, RANO criteria for radiological assessment, CTCAE v5.0 for drug related adverse events. RESULTS From February 2018 to September 2020, 54 consecutive patients were treated with REG and enrolled in this study: median age was 56, ECOG PS 0–1 in 91% of patients, MGMTmet in 53%, second surgery at the time of relapse were performed in 30% of enrolled patient, 41% of patients underwent steroids at baseline. At the time of analysis, median follow-up was 11.1 ms, 30 PTS (56%) had died and 50 PTS (93%) had progressed. Median OS was 10.2 ms (95%CI, 6.4–13.9), 12m-OS was 43%; median PFS was 2.3ms (95%CI, 1.3–3.3) and 6m-PFS was 18%. All patients were evaluable for response: disease control rate (DCR) was 46.3%; stable disease was reported in 38.8% and partial response in 7.4%. Age, MGMT status and corticosteroid use at baseline were not statistically significant on multivariate analysis for OS. Grade 3 drug-related adverse events (AEs) occurred in 10 patients (18%) and the most frequent were hand-foot skin reaction, asthenia and increased lipase and transaminases; 1 PT (2%) reported a grade 4 AE (rash maculo-papular). AEs led to REG dose reductions in 37% of patients and, it was permanently discontinued in 5%. No death was considered to be drug-related. CONCLUSION We reported a large, mono-institutional “real world” experience of REG in recurrent glioblastoma patients. Overall, results are close to those reported in REGOMA trial although, we showed a longer OS. Toxicity was moderate and manageable. Encouraging clinical benefits of REG in recurrent GBM population were confirmed.
Feasibility of a child life specialist program for oncology patients with minor children at home: Demand and implementation.
Authors: David Lysecki, Daryl Bainbridge, Tracy Akitt, Georgia Georgiou, Ralph M. Meyer, Jonathan Sussman
Journal: Journal of Clinical Oncology (2021)

28 Background: Up to 24% of adult oncology patients have minor children at home. Children may experience emotional problems, somatic complaints, social isolation, depression, and post-traumatic stress as a result. Typical support networks often fail to meet the needs of these families. To address this gap, an innovative Child Life Specialist (CLS) program for patients with minor children at home was offered at a tertiary oncology center. Methods: To understand the feasibility of this program, we examined the demand for and implementation of the CLS program over its initial 10 months. Demand was characterized using administrative data (referred patient/family demographics, referral details, and disease/treatment characteristics). Implementation was described through encounter data (audience, type of visit, interventions provided, time for preparation, and time of direct interaction for each encounter). Results: The program received 100 referrals, 93 of whom accessed the program. Patients were most often female (66%) with a median age of 45 years (range: 19 to 72). 81% were parents of minor children, 10% grandparents, and 9% other. Families predominantly had multiple children (98%), most commonly school-aged (ages 5-9, 39%; 10-14, 37%). 53% of families had two birth parents co-parenting in the same household; the remainder had alternate parent/living scenarios. Most referrals came from social work (57%). Median time from diagnosis to referral was 79 days (range: 9d-6.5y). Breast cancer (26%) was the most common diagnosis, followed by gastrointestinal (19%) and hematologic (16%). Cancer phase at referral was defined as at new diagnosis (within 30d, 18%), undergoing treatment with curative intent (20%), undergoing treatment with palliative intent (39%), at end of life (within 30d, 16%) and after death/bereavement (5%). 1 patient (1%) did not have cancer. The CLS recorded 257 unique encounters. 55% of encounters included patients, 40% non-patient parents, 21% children, and 21% others. 75% were individual encounters, while 25% were group encounters. 95% of encounters that included children also included an adult. Phone calls were the most frequent encounter type (43%), but hospital visits consumed the largest proportion of recorded CLS time (38%). Mean encounter time (all visit types) included 20min for preparation and 51min of direct interaction. CLS interventions included: guidance on talking with children (67% of encounters), providing resources (37%), diagnostic teaching (21%), end-of-life support (18%), discussing change in status (10%), grief (8%), and emotional expression (4%). Conclusions: This study characterized the demand for this program and described its implementation over the pilot period. This period occurred during the Covid-19 pandemic, which dramatically altered healthcare and family visitation, likely influencing the results of this study.
U.S. health utility in advanced non-small cell lung cancer (NSCLC) patients harboring MET exon 14 (METex14) skipping mutations treated with tepotinib.
Authors: Paul K. Paik, Mo Yang, Emma Knowles, Anthony Hatswell, Helene Vioix, Frank Xiaoqing Liu
Journal: Journal of Clinical Oncology (2021)

319 Background: To complement the clinical findings, utilities were analyzed based on patient-reported outcomes (PROs) from VISION trial (Cohort A; data cut: July 1, 2020), a Phase II trial showed durable clinical activity of tepotinib in advanced NSCLC METex14+. Methods: The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaires were completed at Day 1, every 6 weeks for 9 months, then every 12 weeks, for up to 30 days after the last tepotinib dose. The Quality of Life Utility Measure-Core 10 dimensions (QLE-C10D) and EQ-5D-5L utilities were derived using the utility algorithm from published literature and the US crosswalk, respectively. Utilities are preference-based, health-related quality of life (HRQoL) metrics expressed on a scale including 0 (dead) and 1 (full health). Linear mixed regression models were used to analyze utilities at baseline, pre-progression, and post-progression, and to understand the relationship between EQ-5D and QLE-C10D. Utilities were assessed by both independent review committee (IRC) and investigators. Results: Utilities were estimated for 150 of 152 pts, with 983 observations for EORTC and 907 for EQ-5D. Mean EORTC utilities increased after tepotinib initiation, from 0.691 at baseline to 0.722 in the IRC-assessed progression-free period, and decreased after progression (0.671). Consistent trends were identified when progression was based on investigator's assessment. Analyses of EQ-5D utilities yielded similar findings and utilities. The two questionnaires were generally highly correlated (Table). Prior treatment (yes/no; p=0.554), adenocarcinoma (p=0.881), or squamous histology (p=0.841) were not statistically significant predictors of EQ-5D utility, while progression status significantly predicted utility in all progression-based models (p≤0.002). Conclusions: VISION is the first trial of a MET inhibitor to provide data on PROs and utilities in NSCLC harboring METex14 skipping mutation. EORTC and EQ-5D (minimally important difference: 0.08) utilities show an increase in HRQoL from baseline during tepotinib treatment until progression. Utility with tepotinib did not vary by prior treatment status or histology. Clinical trial information: NCT02864992. [Table: see text]
Michael Peckham: professor of oncology and artist
Authors: Penny Warren
Journal: BMJ (2021)

peckham210921.f1 



Art was at Michael Peckham’s core. He painted and exhibited all his life, and his vibrant artworks cheered each office he inhabited. He said being an artist gave him balance as a doctor and health researcher. “If you’re an artist you have to take the holistic view. I think it’s prevented me from retreating into overspecialised activities.”

Inspired by working in 1960 with Gwen Hilton in the radiotherapy department at University College Hospital in London, Peckham specialised in oncology. He spent two years in Paris, working with Maurice Tubiana on the cell biology of lymphoma at the Institut Gustave Roussy. Returning to London, he took a job as a lecturer at the Institute of Cancer Research, Royal Marsden Hospital, and in 1973 was appointed professor of radiotherapy. He went on to become dean in 1984.

Peckham instigated several clinical and laboratory programmes and furthered the research he had seen in Paris into lymphoma …
The thermogenic activity of adjacent adipocytes fuels the progression of ccRCC and compromises anti-tumor therapeutic efficacy
Authors: Gang Wei, Honglin Sun, Kai Dong, Libing Hu, Qi Wang, Qian Zhuang, Yan Zhu, Xianjing Zhang, Yaodi Shao, Huiru Tang, Zhenfei Li, Suzhen Chen, Junxi Lu, Yibing Wang, Xinxin Gan, Tao P. Zhong, Dingkun Gui, Xiaoyong Hu, Linhui Wang, Junli Liu
Journal: Cell Metabolism (2021)
Tattoo Inks for Optical Biosensing in Interstitial Fluid
Authors: Martalu D. Pazos, Yubing Hu, Yuval Elani, Kathryn L. Browning, Nan Jiang, Ali K. Yetisen
Journal: Advanced Healthcare Materials (2021)

Abstract The persistence of traditional tattoo inks presents an advantage for continuous and long‐term health monitoring in point of care devices. The replacement of tattoo pigments with optical biosensors aims a promising alternative for monitoring blood biomarkers. Tattoo inks functionalization enables the control of interstitial biomarkers with correlated concentrations in plasma, to diagnose diseases, evaluate progression, and prevent complications associated with physio pathological disorders or medication mismatches. The specific biomarkers in interstitial fluid provide a new source of information, especially for skin diseases. The study of tattoo inks displays insufficient regulation in their composition, a lack of reports of the related complications, and a need for further studies on their degradation kinetics. This review focuses on tattoo optical biosensors for monitoring dermal interstitial biomarkers and discusses the clinical advantages and main challenges for in vivo implantation. Tattoo functionalization provides a minimally invasive, reversible, biocompatible, real‐time sensing with long‐term permanence and multiplexing capabilities for the control, diagnosis, and prevention of illness; it enables self‐controlling management by the patient, but also the possibility of sending the records to the doctor.
PL03.2.A Radiotherapy is associated with a deletion signature that contributes to poor outcomes in glioma patients
Authors: E Kocakavuk, K J Anderson, F S Varn, K C Johnson, S B Amin, E P Sulman, M P Lolkema, F P Barthel, R G W Verhaak
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Diffuse gliomas are highly aggressive brain tumors that invariably relapse despite treatment with chemo- and radiotherapy. Treatment with alkylating chemotherapy can drive tumors to develop a hypermutator phenotype. In contrast, the genomic effects of radiation therapy (RT) remain largely unknown. MATERIAL AND METHODS We analyzed the mutational spectra following treatment with RT in whole genome or exome sequencing data from 190 paired primary-recurrent gliomas from the Glioma Longitudinal Analysis (GLASS) dataset and 3693 post-treatment metastatic tumors from the Hartwig Medical Foundation (HMF). RESULTS We identified a significant increase in the burden of small deletions following radiation therapy that was independent of other factors (P = 3e-03, multivariable log-linear regression). These novel deletions demonstrated distinct characteristics when compared to pre-existing deletions present prior to RT-treatment and deletions in RT-untreated tumors. Radiation therapy-acquired deletions were characterized by a larger deletion size (GLASS and HMF, P = 1.5e-04 and P = 6e-16, respectively; Mann-Whitney U test), an increased distance to repetitive DNA elements (P &amp;lt; 2.2e-16, Kolmogorov-Smirnov test) and a lack of microhomology at breakpoints (P = 6.6e-05, paired Wilcoxon signed-rank test). Furthermore, mutational signature analysis confirmed the distinct genomic characteristics of RT-associated deletions when compared to deletions arising via homologous recombination deficiency or microsatellite instability. These observations suggested that canonical non-homologous end joining (c-NHEJ) was the preferred pathway for DNA double strand break repair of RT-induced DNA damage. Furthermore, RT resulted in frequent chromosomal deletions and significantly increased frequencies of CDKN2A homozygous deletions in IDHmut glioma (P= 1.9e-05, Fisher’s exact test). Finally, a high burden of RT-associated deletions was associated with worse clinical outcomes (GLASS and HMF, P = 3.4e-02 and P &amp;lt; 1e-04, respectively; log-rank test). CONCLUSION Our results collectively suggest that effective repair of RT-induced DNA damage is detrimental to patient survival and that inhibiting c-NHEJ may be a viable strategy for improving the cancer-killing effect of radiotherapy. Furthermore, CDKN2A homozygous deletion at recurrence may be leveraged as a promising clinical biomarker of RT-resistance in IDHmut glioma. Taken together, the identified genomic scars as a result of RT reflect a more aggressive tumor with increased levels of resistance to follow up treatments.
When adopting Global Lung Function Initiative reference values, can we also adapt them to a local context as needed?
Authors: Sylvia Verbanck, Eef Vanderhelst, Shane Hanon
Journal: European Respiratory Journal (2021)

<b>When applying GLI reference values to a local patient population, discrepancies may arise due to population or equipment characteristics. This is illustrated with a specific example and request to GLI for guidance.</b>https://bit.ly/3jmATb9
Evaluating the Cost-effectiveness of Prehospital Plasma Transfusion in Unstable Trauma Patients
Authors: Katherine A. Hrebinko, Jason L. Sperry, Francis X. Guyette, Joshua B. Brown, Brian J. Daley, Richard S. Miller, Brian G. Harbrecht, Jeffrey A. Claridge, Herb A. Phelan, Matthew D. Neal, Brian S. Zuckerbraun, Mark H. Yazer, Kristina J. Nicholson
Journal: JAMA Surgery (2021)

Prehospital plasma transfusion is lifesaving for trauma patients in hemorrhagic shock but is not commonly used owing to cost and feasibility concerns.To evaluate the cost-effectiveness of prehospital thawed plasma transfusion in trauma patients with hemorrhagic shock during air medical transport.A decision tree and Markov model were created to compare standard care and prehospital thawed plasma transfusion using published and unpublished patient-level data from the Prehospital Plasma in Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial conducted from May 2014 to October 2017, health care and trauma-specific databases, and the published literature. Prehospital transfusion, short-term inpatient care, and lifetime health care costs and quality of life outcomes were included. One-way, 2-way, and Monte Carlo probabilistic sensitivity analyses were performed across clinically plausible ranges. Data were analyzed in December 2019.Relative costs and health-related quality of life were evaluated by an incremental cost-effectiveness ratio at a standard willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY).The trial included 501 patients in the modified intention-to-treat cohort. Median (interquartile range) age for patients in the thawed plasma and standard care cohorts were 44 (31-59) and 46 (28-60) years, respectively. Overall, 364 patients (72.7%) were male. Thawed plasma transfusion was cost-effective with an incremental cost-effectiveness ratio of $50 467.44 per QALY compared with standard care. The preference for thawed plasma was robust across all 1- and 2-way sensitivity analyses. When considering only patients injured by a blunt mechanism, the incremental cost-effectiveness ratio decreased to $37 735.19 per QALY. Thawed plasma was preferred in 8140 of 10 000 iterations (81.4%) on probabilistic sensitivity analysis. A detailed analysis of incremental costs between strategies revealed most were attributable to the in-hospital and postdischarge lifetime care of critically ill patients surviving severe trauma.In this study, prehospital thawed plasma transfusion during air medical transport for trauma patients in hemorrhagic shock was lifesaving and cost-effective compared with standard care and should become commonplace.
Oncology rapid assessment clinic and effect on ED visits.
Authors: Marie S. Dreyer, Marcus Paschall, Theodore Karrison, Blase N. Polite
Journal: Journal of Clinical Oncology (2021)

258 Background: The use of the Emergency Department (ED) by oncology patients for lower acuity issues is common. Oncology Rapid Assessment Clinics (ORAC) may play a key role in reducing ED visits among oncology patients. We analyzed whether the advent of ORAC was associated with lower ED utilization by patients receiving cancer care at University of Chicago Medical Center (UCMC). Methods: UCMC opened its ORAC in March 2019 to provide supportive care and symptom management to cancer patients who needed acute medical issues addressed. To identify active cancer patients, we identified those that had either a forward or reverse 9 month rolling count of greater than or equal to 2 Outpatient Clinic Visits (complete or future). Of all those patients, we identified any ED visit made within the time period considered Pre-ORAC (6/2018-2/2019) and Post-ORAC (6/2019-2/2020). To determine effect of ORAC on ED utilization, we performed t-test comparison of rates. Results: A total of 9,043 unique patients were seen in the Pre-ORAC period and 8,753 in the Post-ORAC period. Predominant cancers seen in both periods were Breast, Lung/Head &amp; Neck, GI, Lymphoma/Leukemia, GU, and Multiple Myeloma. The ED visit rate was 0.252 (2279/9043) in Pre-ORAC period and 0.237 (2075/8753) in the Post-ORAC period (p = 0.02). Conclusions: There was a decrease in ED visit rates for oncology patients cared for by UCMC in the immediate period after the opening of the ORAC clinic. More substantial declines are expected in the future as the capacity and efficiency of the ORAC clinic grows and the concept is socialized among cancer providers.
Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial
Authors: Eugenio Mercuri, Francesco Muntoni, Giovanni Baranello, Riccardo Masson, Odile Boespflug-Tanguy, Claudio Bruno, Stefania Corti, Aurore Daron, Nicolas Deconinck, Laurent Servais, Volker Straub, Haojun Ouyang, Deepa Chand, Sitra Tauscher-Wisniewski, Nuno Mendonca, Arseniy Lavrov, A. Seferian, S. De Lucia, S. Tachibana, A. Jollet, S. Mouffak, M. Pedemonte, N. Brolatti, S. Morando, A. Vanlander, E. De Vos, V. Tahon, A. Govoni, F. Magri, G. Comi, M. Foa, V. Parente, L. Buscemi, F. Dal Farra, O. Schneider, A. Jonas, A.C. Defeldre, E. Pagliano, R. Zanin, M.T. Arnoldi, V. Schembri, M. Del Sole, A. Mandelli, M.C. Pera, L. Antonaci, G. Coratti, R. de Sanctis, M. Pane, M. Scoto, K. Groves, L. Edel, F. Abel, H. Van Ruiten, R.M. Lofra, E. Thompson
Journal: The Lancet Neurology (2021)
Full-length HLA sequencing in adult T cell leukemia–lymphoma uncovers multiple gene alterations
Authors: Keita Tamaki, Satoko Morishima, Shingo Suzuki, Atsuko Shigenari, Ikumi Nomura, Yutaro Yokota, Kazuho Morichika, Yukiko Nishi, Sawako Nakachi, Shiki Okamoto, Takuya Fukushima, Takashi Shiina, Hiroaki Masuzaki
Journal: Leukemia (2021)
Emotional demands at work and risk of long-term sickness absence in 1·5 million employees in Denmark: a prospective cohort study on effect modifiers
Authors: Elisabeth Framke, Jeppe Karl Sørensen, Kristina Alexanderson, Kristin Farrants, Mika Kivimäki, Solja T Nyberg, Jacob Pedersen, Ida E H Madsen, Reiner Rugulies
Journal: The Lancet Public Health (2021)
Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications
Authors: Monika Gawałko, Thomas A Agbaedeng, Arnela Saljic, Dominik N Müller, Nicola Wilck, Renate Schnabel, John Penders, Michiel Rienstra, Isabelle van Gelder, Thomas Jespersen, Ulrich Schotten, Harry J G M Crijns, Jonathan M Kalman, Prashanthan Sanders, Stanley Nattel, Dobromir Dobrev, Dominik Linz
Journal: Cardiovascular Research (2021)

Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk factors, including heart failure, hypertension, obesity, and coronary artery disease. We also discuss the potential anti-arrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.