ABSTRACT
Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.
ABSTRACT
The impact of COVID-19 pandemic on paediatric asthma, the most common chronic condition of childhood, in Australia remains unknown. In a multicentre study, we examined the impact of COVID-19 on paediatric asthma in New South Wales Australia. Method(s): Time series analysis was performed to determine trends in asthma hospital presentations in children aged 2-17 years in pre-pandemic (Jan 2015-Dec 2019) and COVID-19 pandemic years (Jan 2020-August 2021) using emergency department and hospital admission datasets from two large tertiary paediatric hospitals. Result(s): In the pre-pandemic years there were in total 492,863 hospital presentations in children aged 2-17 years, of these 13,160 (2.67%) were due to asthma and in pandemic years there were 163,521 hospital presentations of which 3,364 (2.05%) were due to asthma. We observed a significant decrease in asthma hospital presentations during lockdown periods of COVID-19 pandemic including April (68.85%), May (69.46%) and December (49.00%) of 2020 and August 2021 (66.59%) compared to pre-pandemic predictions. The reduction in asthma hospital presentation in April-May of 2020 and August 2021 was observed across all the age-groups excluding children aged 2-5 years. Conclusion(s): While this decline may be associated with reduced exposure to outdoor environmental factors from restricted movement due to lockdowns, such an approach is not feasible or sustainable in the absence of an infectious disease outbreak. Therefore further research to determine the positive factors associated with this observed pattern will help develop strategies to build a resilient health system.
ABSTRACT
The arrival of COVID-19 has led to the emergence of a large amount of information, and inaccurate information will lead to group polarization and cognitive dissonance, so the management of public opinion information has become urgent. In this paper, the COVID-19 public opinion information analysis system selects the data sources on weibos as reference, and weibo hot topics, as the platform that users mainly focus on, are more authoritative and more credible compared to emerging media As the main platform for users' attention, Weibo hot topics are more authoritative and credible than emerging media. The selection of such a large platform can also ensure the openness and transparency of information. This paper focuses on a series of development processes such as acquisition and analysis of COVID-19 data and database design of COVID-19 public opinion information analysis system. The system not only realizes the basic functions of COVID-19 public opinion information analysis system, but also runs smoothly and interactively. © 2022 SPIE. All rights reserved.
ABSTRACT
This paper proposes a joint model based on the generalized LASSO to smooth a time-varying graph. The model generalizes the gLASSO from a purely spatial setting to a spatial-temporal one. In the proposed model, the first term measures the fitting error, while the second term incorporates the structural information of graphs and total variations of time sequence, and hence the model can extract both temporal and spatial information. To illustrate the performance of the proposed model, we analyzed the simulated datasets for epidemic diseases and the real datasets for COVID-19 and mortality rate in mainland China. The results show that the proposed model can capture the trends/regions simultaneously in both temporal and spatial domains, being an effective model to analyze the problems that can be modelled as time-varying graphs. Author
ABSTRACT
Study Objective: Many studies to date have looked at reasons for patient hesitancy or refusal to vaccinate. Demographic and socioeconomic factors, safety concerns, and beliefs about vaccines impact a patient or parent’s willingness to vaccinate. The speed of vaccine development and approval, divisive political climate surrounding COVID-19, underlying suspicion or lack of education about the virus, and effects of social media are factors that may make a COVID-19 vaccine uniquely contentious compared to other vaccines. Several studies have recently looked at vaccine hesitancy specifically related to COVID-19, exploring factors such as personal experience with COVID-19, personal knowledge about the virus, perception of virus severity, general confidence in vaccines, and trust in biomedical science and health care professionals. Recently, citywide studies have shown the disparities of vaccine uptake among various demographic groups;only 33% of Black adults have taken a vaccine dose while the rate for Hispanic adults is 4%;50% for white adults, and 70% for Asian adults. We believe the emergency department provides the opportunity to investigate and close these gaps by addressing hesitancy and offering the vaccine in the emergency department. Methods: We developed a questionnaire to evaluate patients’ and caregivers’ attitudes and knowledge of COVID-19 vaccine and investigate the reasons for the vaccine hesitancy amongst patients in the emergency department. Adult patients and caregivers of children 0-17 years were asked to complete this survey voluntarily using a QR code and a link to the questionnaire. Results: To date, 66 respondents accessed and completed the survey (34 adults and 32 caregivers). Though 64% of adult patients and 81% of caregivers thought that the COVID vaccine would be beneficial to their community, many were unsure or reported they would not take the vaccine. 56% of adult patients and 59% of caregivers were hesitant to receive the vaccine for themselves and 48% of caregivers were hesitant to give the COVID-19 vaccine to their children. The most commonly cited reasons being concern about safety of the vaccine and its side effects and poor understanding of the vaccine. 90% of the adult patients and 83% of caregivers stated they would take the vaccine for themselves in the emergency department if offered, and 85% of caregivers would consider giving it to their children. Many respondents belonged to communities of color (Black 16-36%, Hispanic 73-82%), where vaccine uptake was the least. Conclusion: The emergency department can address patients’ vaccine hesitancy and alleviate the disparities by making vaccines available in the emergency department.