COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

BACKGROUND: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. METHODS: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. RESULTS: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. CONCLUSIONS: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

[89Zr]Df-crefmirlimab PET/CT imaging to assess the in vivo distribution of CD8+ T-cells in hospitalized COVID-19 patients

Aim/Introduction: COVID-19 patients may present with lymphopenia. The degree of lymphopenia, in particular reduced CD8+ T-cell numbers, is strongly correlated with clinical deterioration and ICU admission [1,2]. It has been postulated that lymphopenia in COVID-19 is caused by;1) sequestration of CD8+ T-cells in peripheral tissues (e.g. lung) [3], 2) accelerated maturation and exhaustion [4,5] or 3) decreased lymphopoiesis [6]. The lack of data on in vivodistribution of CD8+ T-cells hampers a more thorough understanding of this critical prognostic factor. We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Df-crefmirlimab PET/CT imaging. Material(s) and Method(s): This is a prospective, observational non-randomized pilot study in hospitalized patients with microbiologically proven SARS-CoV-2 infection. The prior use of immune suppressive medication was an exclusion criterion. Whole body [89Zr]Df-crefmirlimab PET/CT scan were acquired at 24 hrs after intravenous injection of 1.5mg protein dose labelled with 37 MBq (1 mCi)89Zr. Peripheral blood samples were collected for multi-colour flowcytometry to phenotype homing receptors and immune senescence markers, and transcriptomics. Result(s): Three patients were enrolled (all male, average 83 yrs (78-89 yrs)), admitted at 5.3 days (2-10 days) after onset of symptoms and scanned at 2.7 days (2-4 days) after admission. Two patients completed vaccination (2x plus booster), one patient was not vaccinated. Two patients had with lymphocyte count <1.0 x10e9/L and one patient had normal lymphocyte counts on admission. One patient required oxygen suppletion 3L/min. PET/CT scans showed remarkable differences in uptake in the upper respiratory tract versus lower respiratory tract, involvement of distant organs and distribution of CD8+ T-cells across secondary lymphoid organs, spleen and hematopoietic system. Quantification of the scans, flow cytometry and transcriptomic analyses are ongoing. Conclusion(s): In vivo imaging of CD8+ T-cells in hospitalized COVID-19 patients reveals distinct patterns of CD8+ T-cell distribution in early stages of localized infection versus systemic involvement at later stages. Translational data on T-cell phenotyping is currently processed and will be presented.

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: A joint analysis of OnCovid and ESMO-CoCARE registries

Background: As management and prevention strategies against Coronavirus Disease-19 (COVID-19) evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients (pts) with cancer. Method(s): In a joint analysis of ICI recipients from OnCovid (NCT04393974) and ESMO CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated pts with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19. Result(s): The study population consisted of 240 pts diagnosed with COVID-19 between Jan 2020 and Feb 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95%CI: 17.8-30.7%). 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.001), hospitalization rate (27.5% vs 63.2%, p<0.001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.003), COVID-19 complication rate (11.9% vs 34.6%, p=0.004), and COVID-19-specific therapy (26.3% vs 57.9%, p=0.001) compared with unvaccinated pts. IPTW-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated pts experienced a decreased risk of death at 30 days (aOR 0.08, 95%CI: 0.01-0.69). 38 pts (15.8%) experienced at least 1 irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumour (p=0.037) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR: 0.47, 95%CI: 0.33-0.67). Pts who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.009). Conclusion(s): Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify pts with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2. Clinical trial identification: NCT04393974 OnCovid. Legal entity responsible for the study: Imperial College London & ESMO. Funding(s): Imperial Biomedical Research Centre ESMO. Disclosure: A. Cortellini: Financial Interests, Personal, Advisory Board: MSD, OncoC4;Financial Interests, Personal, Invited Speaker: Eisai, AstraZeneca;Financial Interests, Personal, Expert Testimony: Iqvia. D.J. Pinato: Financial Interests, Personal, Invited Speaker: ViiV Healthcare, Bayer, BMS, Roche, Eisai, Falk Foundation;Financial Interests, Personal, Advisory Board: Mina Therapuetics, Eisai, Roche, DaVolterra, AstraZeneca. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

Durvalumab (D) +/- tremelimumab (T) + chemotherapy (CT) in 1L metastatic (m) NSCLC: Overall survival (OS) update from POSEIDON after median follow-up (mFU) of approximately 4 years (y)

Background: In the Phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in PFS and OS (OS HR 0.77;95% CI 0.65-0.92;p=0.0030;mFU 34.9 mo in censored pts) vs CT alone in pts with mNSCLC. D+CT showed a statistically significant improvement in PFS and a positive trend for OS improvement vs CT that did not reach significance (OS HR 0.86;95% CI 0.72-1.02;p=0.0758). Here we report an updated exploratory analysis of OS, and histology and mutational status subgroups, after a mFU of ~4 y. Method(s): Pts with EGFR/ALK wild-type mNSCLC were randomised 1:1:1 to 1L D (until progression) +/- limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles);or CT (up to 6 cycles). Alpha-controlled endpoints were PFS and OS for D+CT vs CT and T+D+CT vs CT. Pt tumours were molecularly characterised via sequencing of tissue and/or ctDNA samples. Result(s): At an updated data cutoff (DCO) of 11 Mar 2022 (mFU 46.5 mo in censored pts), T+D+CT continued to show OS benefit vs CT (HR 0.75;95% CI 0.63-0.88) with an estimated 25.0% of pts alive at 3 y vs 13.6% (Table). D+CT continued to numerically improve OS vs CT (HR 0.84;95% CI 0.71-0.99;3 y OS 20.7%). Consistent with results at the earlier DCO, OS benefit appeared more pronounced with T+D+CT vs CT in pts with non-squamous (than squamous;data will be presented) histology. A trend for OS benefit with T+D+CT vs CT continued to be observed in non-squamous subgroups with mutations (m) in STK11 (Table), KEAP1 or KRAS (data will be presented). No new safety signals were identified based on collection of serious AEs during long-term FU. [Formula presented] Conclusion(s): The results of this exploratory analysis from POSEIDON, after mFU of ~4 y, demonstrate the durable long-term OS benefit of adding a limited course of T to D and 4 cycles of CT. These data support the use of this regimen as a 1L treatment option for pts with mNSCLC, including harder-to-treat mutational subgroups such as STK11m, KEAP1m or KRASm. Clinical trial identification: NCT03164616 (release date: 23 May 2017). Editorial acknowledgement: Medical writing support for the development of this , under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca PLC. Funding(s): AstraZeneca. Disclosure: B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc;Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO;Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp, J INTS BIO;Financial Interests, Personal, Royalties: Champions Oncology;Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp;Financial Interests, Personal, Advisory Role, Consulting: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines;Financial Interests, Personal, Other: DAAN Biotherapeutics. J.A. Alatorre Alexander: Financial Interests, Personal, Speaker's Bureau: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen;Financial Interests, Personal, Advisory Board: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen. S. Lucien Geater: Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Novartis, Boehringer Ingelheim;Financial Interests, Personal, Advisory Role: Pfizer. K. Sang-We: Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial I terests, Personal, Research Grant: Yuhan;Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Boehringer Ingelheim, Norvatis, Lilly, Takeda, Therapex, and Yuhan. M. Hussein: Financial Interests, Personal, Advisory Board: AbbVie, Aptitude Health, AstraZeneca, Biopahrama, BMS, Exelixis, Mirati Therapeutics, Cardinal Health, Coherus Biosciences, Athenex, Karyopharm Therapeutics, IntegraConnect, Oncocyte. C.T. Yang: Financial Interests, Personal, Principal Investigator: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Merck, Amgen, Johnson & Johnson, AbbVie, Hanso Pharma, Roche, Ono, BMS, Chugai. L.H. Araujo: Financial Interests, Personal, Invited Speaker: MSD, Roche, Pfizer, AstraZeneca, Takeda, Lillly, Janssen, Amgen, Novartis, BMS, Sanofi;Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, AstraZeneca, Sanofi. H. Saito: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, ONO Pharmaceutical;Financial Interests, Personal, Principal Investigator: AstraZeneca, Chugai Pharmaceutical ONO Pharmaceutical, Bristol Myers Squibb. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Hoffmann-La Roche, Janssen, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Other: Symphogen: Data Safety Monitoring Board. Z. Lai, H. Mann, X. Shi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure;Financial Interests, Institutional, In ited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati;Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier;Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca;Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS;Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS;Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK;Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati;Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar;Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01;chair ALEX;steering committee BFAST;steering committee BEAT-Meso;steering committee ImPower-030, IMforte: Roche/Genentech;Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos;Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO;Non-Financial Interests, Personal, Officer, Council Me ber & Scientific Committee Chair: ETOP/IBCSG Partners;Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities;Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Bejart Lausanne Foundation;Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK;Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR;Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO;Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO;Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. E.B. Garon: Financial Interests, Personal, Advisory Board: ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, Eisai, Eli Lilly, EMD Serono, Gilead, GSK, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio Therapeutics;Financial Interests, Personal, Research Grant: ABL Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, Novartis. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. Limi, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians' Education Resource, Pfizer, PrIME Oncology, Research to Practice, RochePharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., T;Financial Interests, Personal, Advisory Board: AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim Pharmaceuticals Inc., Bristol Myers Squibb Company, C4 Therapeutics, Inc, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lily, Loxo-Oncology Inc., Lunit, Inc., Mer k Serono, Merck Sharp & Dohme, Mirati Therapeutics, Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnolo;Financial Interests, Personal, Member of the Board of Directors: AstraZeneca PLC, HutchMed;Financial Interests, Personal, Full or part-time Employment: The Chinese University of Hong Kong (Full-Time);Financial Interests, Personal, Stocks/Shares: Aurora Tele-Oncology Ltd., HutchMed, Act Genomics-Sanomics Group, Loxo-oncology, Virtus Medical Group and Lunit USA, Inc;Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery;Financial Interests, Personal, Leadership Role: Lunit USA, Inc., ACT Genomics-Sanomics Group, Aurora;Financial Interests, Personal, Other, Independent contractor: AbbVie Inc., ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, Berry Oncology, BI, Blueprint Medicines Corporation, BMS, C4 Therapeutics, Inc, CStone Pharmaceuticals, Curio Science, Daiichi Sa, Loxo-Oncology, Merck Serono, MSD, Mirati Therapeutics Inc., MoreHealth, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Roche Pharmaceuticals, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Takeda Pharmaceuticals HK Ltd., Vert, Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/ WebMD, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHea. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie;Acerta;Adaptimmune;Amgen;Apexigen;Arcus B osciences;Array BioPharma;Artios Pharma;AstraZeneca;Atreca, BeiGene;BerGenBio;BioAtla;Boehringer Ingelheim, Calithera Biosciences;Checkpoint Therapeutics;Corvus Pharmaceuticals;Curis;CytomX, Daiichi Sanyo;Dracen Pharmaceuticals;Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan Kettering, Merck, Merus, Mirati Therapeutics, NeoImmuneTech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Pharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics;Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, IDEAYA Biosciences, iTeos, Janssen, Merck, Mirati Therapeutics, Novartis, Oncorus, Regeneron Pharmaceuticals, Revolution Medicines, Ribon Therapeutics, Sanofi, Turning Point Therapeutics, WindMIL. All other authors have declared no conflicts of interest. Copyright © 2022

Can Practice-Based Research Networks foster integrated care across the healthcare system? A scoping review

Background: Integrated health care, particularly between the broader health care system and primary care can ease the patient journey, improve outcomes and reduce healthcare costs. The rise of both Primary Health Networks and Advanced Health Research and Translation Centres in Australia expands the requirement for Australia's Practice Based Research Networks (PBRNs) to incorporate a focus on integration. However little is known about the ways in which PBRNs can help align and coordinate different parts of the health care system. Aim/Objectives: To conduct a scoping review to examine how PBRNs have been used to foster integrated care across the healthcare system. Method(s): Our scoping review used the PRISMA-ScR framework and was based on Valentijn's conceptual framework for integrated care. Two independent reviewers used CovidenceTM to search titles, s, and full texts in Ovid Medline, EMBASE, CINAHL and Scopus. We sought to identify peer-reviewed empirical studies conducted since 2000 that examined collaboration between PBRNs and the broader healthcare system. We excluded studies that solely used PBRNs for recruitment and those restricted to a single practice. Finding(s): We identified 3022 articles, of which 74 studied primary care PBRNs. Of these, 13 focussed on 'integrated care.' The studies documented collaboration between primary care and a wide range of professions and organisations. Only one explored integration at a clinical, organisational and system level, and few showed how collaborations could be established or maintained. Most prioritised population health rather than clincial care. Implications: While system integration is beginning to be explored as PBRNs evolve, there is a paucity of information on how PBRNs form and foster integration between primary care and the broader healthcare system. An improved understanding of the role of PBRNs in integration is important given the focus on system integration and sustainability within Australia's new 10 Year Plan for primary health care.

An update on the overall epidemiology, clinical characteristics, and outcomes from the COVID-19 and Cancer Consortium (CCC19)

Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate [CFR], mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary [17%], diabetes mellitus [16%], cardiovascular [19%], renal [21%]), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/ progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity;and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials.

DSP Gene Mutation – A Cause of Recurrent Myocarditis: A Case Series

Myocarditis has gained clinical awareness with the current COVID-19 pandemic. A recent ESC Expert Consensus document discussing management of acute myocarditis and chronic inflammatory cardiomyopathy has been published [1]. Although the document alludes to genetic predisposition, by stating that “patients with mutations responsible for arrhythmogenic cardiomyopathy may be at risk for acute myocarditis,” the growing clinical experience in this area suggests that perhaps pursuit of an inflammatory diagnosis has been at the cost of recognising an underlying genetic cause, with important implications for the patient and their family. Desmoplakin (DSP)-related arrhythmogenic cardiomyopathy (AC) is characterised by LV systolic dysfunction, subepicardial late gadolinium enhancement on cardiac magnetic resonance imaging (CMR) and frequent ventricular ectopy [2,3]. In ∼15% of DSP-related AC involving the LV, a clinical event indistinguishable from myocarditis can be the initial manifestation [4]. Myocarditis often precedes fibrosis and LV dysfunction. In this case series, we describe 3 unrelated young individuals (aged 21–28 years) diagnosed by our service with DSP pathogenic variants. In all cases the initial diagnosis was myocarditis and the diagnostic odyssey was characterised by multiple presentations with significant troponin elevations, including one in whom chronic inflammatory myocarditis was the diagnosis over many years. Since the COVID-19 pandemic, presentations for myocarditis have increased considerably [5]. This has increased the importance of the clinician considering genetic arrhythmogenic cardiomyopathy as an alternative diagnosis. Any case of myocarditis should prompt 3-generational family history, and recurrent presenters should have a CMR and be referred for consideration of genetic testing.

The Role of Anaesthesiologists in the COVID-19 Pandemic: Practical lessons from Groote Schuur Experience

Clinicians worldwide have been called to action against COVID-19, requiring development of effective systems to respond to the surge of pandemic cases. Anaesthesiologists are equipped to fulfil many roles in the operating room, critical care and retrieval settings. However, it was anticipated that the case load could overwhelm our existing referral structures, and put staff and patients at increased risk. We describe, using the “4S” components of surge capacity development, how systems, staff, space and stuff were utilised to create a COVID Anaesthesia, Intubation and Retrieval (CAIR) Team at Groote Schuur Hospital, Cape Town, South Africa. The primary aims of the team are to provide safe anaesthesia for patients with known or suspected COVID-19, and perform intubation and transfer in COVID wards or high care areas to intensive care units. Concurrently, promotion of strict infection control practices and risk mitigation through the use of a dedicated group of low-risk, highly trained individuals was achieved. Staff support systems, protocols for streamlined patient management, reallocation of spaces within the hospital, the capital and disposable equipment required for the service, and use of continual audit and iterative improvement are discussed in this article. © World Federation of Societies of Anaesthesiologists 2022.

Oncology: navigating the COVID-19 Pandemic and Steer the Course

Medical oncologists are steering a difficult course during the COVID-19 pandemic between three opposing forces: revisiting optimal standards of cancer care, facing constantly evolving shortages as some resources are being redirected, and acknowledging the paradoxical need to keep patients away from the health care facility. This article compiles recommendations from cancer societies and expert opinions to provide guidance and practical solutions for the oncology clinic. We propose that optimal standards of care be upheld, and short-term safety concerns due to exposure to SARS-CoV-2 be weighed against a long-term compromise in cancer prognosis when deciding on adjustments in cancer care. Proper mitigation strategies in the clinic and use of less resource-heavy but equivalent treatment alternatives often allow optimal cancer care. The magnitude of benefit of cancer treatments needs to be systematically considered.

MetaMap versus BERT models with explainable active learning: Ontology-based experiments with prior knowledge for COVID-19

Emergence of the Coronavirus 2019 Disease has highlighted further the need for timely support for clinicians as they manage severely ill patients. We combine Semantic Web technologies with Deep Learning for Natural Language Processing with the aim of converting human-readable best evidence/ practice for COVID-19 into that which is computer-interpretable. We present the results of experiments with 1212 clinical ideas (medical terms and expressions) from two UK national healthcare services specialty guides for COVID-19 and three versions of two BMJ Best Practice documents for COVID-19. The paper seeks to recognise and categorise clinical ideas, performing a Named Entity Recognition (NER) task, with an ontology providing extra terms as context and describing the intended meaning of categories understandable by clinicians. The paper investigates: 1) the performance of classical NER using MetaMap versus NER with fine-tuned BERT models;2) the integration of both NER approaches using a lightweight ontology developed in close collaboration with senior doctors;and 3) the easy interpretation by junior doctors of the main classes from the ontology once populated with NER results. We report the NER performance and the observed agreement for human audits. Copyright © 2022 for this paper by its authors.

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

Consumer Debt in Germany: Status and Development

This article looks at over-indebtedness in Germany and its current status and trends. COVID-19 created increased attention on private debt and over-indebtedness. Various studies within the last two years show the severe financial impact of the pandemic;the situation has only eased in phases, but remains critical overall. A fundamental undersupply of efficient and effective debt counselling has become apparent. Current developments (especially with regard to energy prices) have increased the need for debt counselling. © 2022, Der/die Autor:in.

Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET): Achievements after 4 years of networking, collaboration and training

Introduction OMEGA-NET (2017-2022) is a COST Action network, funded by EU, involving about 200 occupational health researchers in 40 countries, including non-European partners. The goal is to create a network to optimize the coordination and use of occupational, industrial, and population cohorts in Europe and beyond, to inform evidence-based interventions and policy. Material and Methods A range of networking tools are available for COST Actions, such as meetings, workshops, conferences, training schools, short-term scientific missions (STSMs) and dissemination activities. Results Despite COVID-19 restrictions, the network has made great achievements, including two online searchable inventories: the Inventory of Occupational Cohorts, with more than 140 cohorts registered, and the Inventory of Occupational Exposure Tools, with about 75 tools, of which half are Job-Exposure Matrices. Working groups have discussed and written papers on harmonisation and standardisation of occupational exposure and health outcome information. So far, 15 papers are published, some as editorials or position papers, others are accepted or in progress. A webinar series, available on YouTube, present work of OMEGA-NET. The Action also includes opportunities for networking, leadership and training for early career researchers in occupational epidemiology and exposure assessment, and visits to other research institutions (STSMs), as well as stakeholder engagement. Conclusions OMEGA-NET is the largest coordination activity on occupational health globally and will substantially enhance future European and international research.

The impact of COVID-19 on cancer care and oncology clinical research: an experts' perspective.

The coronavirus disease-19 (COVID-19) pandemic promises to have lasting impacts on cancer clinical trials that could lead to faster patient access to new treatments. In this article, an international panel of oncology experts discusses the lasting impacts of the pandemic on oncology clinical trials and proposes solutions for clinical trial stakeholders, with the support of recent data on worldwide clinical trials collected by IQVIA. These lasting impacts and proposed solutions encompass three topic areas. Firstly, acceleration and implementation of new operational approaches to oncology trials with patient-centric, fully decentralized virtual approaches that include remote assessments via telemedicine and remote devices. Geographical differences in the uptake of remote technology, including telemedicine, are discussed in the article, focusing on the impact of the local adoption of new operational approaches. Secondly, innovative clinical trials. The pandemic has highlighted the need for new trial designs that accelerate research and limit risks and burden for patients while driving optimization of clinical trial objectives and endpoints, while testing is being minimized. Areas of considerations for clinical trial stakeholders are discussed in detail. In addition, the COVID-19 pandemic has exposed the underrepresentation of minority groups in clinical trials; the approach for oncology clinical trials to improve generalizability of efficacy and outcomes data is discussed. Thirdly, a new problem-focused collaborative framework between oncology trial stakeholders, including decision makers, to leverage and further accelerate the innovative approaches in clinical research developed during the COVID-19 pandemic. This could shorten timelines for patient access to new treatments by addressing the cultural and technological barriers to adopting new operational approaches and innovative clinical trials. The role of the different stakeholders is described, with the aim of making COVID-19 a catalyst for positive change in oncology clinical research and eventually in cancer care.

Named Entity Recognition and Relation Extraction for COVID-19: Explainable Active Learning with Word2vec Embeddings and Transformer-Based BERT Models

Deep learning for natural language processing acquires dense vector representations for n-grams from large-scale unstructured corpora. Converting static embeddings of n-grams into a dataset of interlinked concepts with explicit contextual semantic dependencies provides the foundation to acquire reusable knowledge. However, the validation of this knowledge requires cross-checking with ground-truths that may be unavailable in an actionable or computable form. This paper presents a novel approach from the new field of explainable active learning that combines methods for learning static embeddings (word2vec models) with methods for learning dynamic contextual embeddings (transformer-based BERT models). We created a dataset for named entity recognition (NER) and relation extraction (REX) for the Coronavirus Disease 2019 (COVID-19). The COVID-19 dataset has 2,212 associations captured by 11 word2vec models with additional examples of use from the biomedical literature. We propose interpreting the NER and REX tasks for COVID-19 as Question Answering (QA) incorporating general medical knowledge within the question, e.g. “does ‘cough’ (n-gram) belong to ‘clinical presentation/symptoms’ for COVID-19?”. We evaluated biomedical-specific pre-trained language models (BioBERT, SciBERT, ClinicalBERT, BlueBERT, and PubMedBERT) versus general-domain pre-trained language models (BERT, and RoBERTa) for transfer learning with COVID-19 dataset, i.e. task-specific fine-tuning considering NER as a sequence-level task. Using 2,060 QA for training (associations from 10 word2vec models) and 152 QA for validation (associations from 1 word2vec model), BERT obtained an F-measure of 87.38%, with precision = 93.75% and recall = 81.82%. SciBERT achieved the highest F-measure of 94.34%, with precision = 98.04% and recall = 90.91%. © 2021, Springer Nature Switzerland AG.