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Background: Advances in precision oncology led to approval of tumour-agnostic molecularly guided treatment options (MGTOs). The minimum requirements for claiming tumour-agnostic potential remain elusive., Methods: The European Society for Medical Oncology (ESMO) Precision Medicine Working Group (PMWG) coordinated a project to optimise tumour-agnostic drug development. International experts examined and summarised the publicly available data used for regulatory assessment of the tumour-agnostic indications approved by the US Food and Drug Administration and/or the European Medicines Agency as of December 2023. Different scenarios of minimum objective response rate (ORR), number of tumour types investigated, and number of evaluable patients per tumour type were assessed for developing a screening tool for tumour-agnostic potential. This tool was tested using the tumour-agnostic indications approved during the first half of 2024. A taxonomy for MGTOs and a framework for tumour-agnostic drug development were conceptualised., Results: Each tumour-agnostic indication had data establishing objective response in at least one out of five patients (ORR ≥ 20%) in two-thirds (≥4) of the investigated tumour types, with at least five evaluable patients in each tumour type. These minimum requirements were met by tested indications and may serve as a screening tool for tumour-agnostic potential, requiring further validation. We propose a conceptual taxonomy classifying MGTOs based on the therapeutic effect obtained by targeting a driver molecular aberration across tumours and its modulation by tumour-specific biology: tumour-agnostic, tumour-modulated, or tumour-restricted. The presence of biology-informed mechanistic rationale, early regulatory advice, and adequate trial design demonstrating signs of biology-driven tumour-agnostic activity, followed by confirmatory evidence, should be the principles for tumour-agnostic drug development., Conclusion: The ESMO Tumour-Agnostic Classifier (ETAC) focuses on the interplay of targeted driver molecular aberration and tumour-specific biology modulating the therapeutic effect of MGTOs. We propose minimum requirements to screen for tumour-agnostic potential (ETAC-S) as part of tumour-agnostic drug development. Definition of ETAC cut-offs is warranted., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals with cancer have specific and unique health issues and needs. Reports persist of inequalities in the care provided for these patients, making it important to assess the attitudes and knowledge of LGBTQ needs among those who provide care., Materials and Methods: The European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOP Europe) Adolescents and Young Adults Working Group designed this survey comprising 67 questions covering demographics, knowledge, and education of LGBTQ health needs, and attitudes regarding LGBTQ patients with cancer., Results: Among the 672 respondents, a majority do not ask about sexual orientation and gender identity during first visit (64% and 58%, respectively). Only a minority of the respondents considered themselves well informed regarding gay/lesbian and transgender patients' health (44% and 25%, respectively) and psychosocial needs (34%). There was high interest in receiving education regarding the unique health needs of LGBTQ patients (73%)., Conclusions: Survey respondents indicated a willingness to provide care to LGBTQ patients, but a lack of confidence in the knowledge of the health issues and needs of LGBTQ individuals. Lack of training provided in medical schools and postgraduate training programmes and strong interest for additional education on these issues were reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised., Results: A total of 57 experts from 15 countries responded to the survey. The WGs were attended by (i) 11, (ii) 10, (iii) 12, and (iv) 12 experts, respectively, representing a variety of national backgrounds and stakeholder profiles. The most relevant action points identified were as follows: (i) incorporation of clinical context into population, intervention, comparator, outcomes (PICO) schemes, (ii) timely provision of up-to-date therapeutic guidelines, (iii) ensuring the inclusion of MCBS insights into the EU HTA process, and (iv) considering randomized controlled trials (RCTs) as the gold standard and leveraging regulatory insights if development programs only include single-arm trials., Conclusions: The involvement of medical societies is a critical success factor for the EU HTA. The identified key action points foster the involvement of patient associations and medical societies., Competing Interests: Conflicts of InterestJR and EJ received an unrestricted grant from Abbvie, AstraZeneca, Bayer, Novartis, Roche, Sanofi, and Seagen that partially funded this research. The authors have no further financial or non-financial interests to disclose. BPV has received personal honoraria for advisory boards from Pfizer, Astellas Pharma, Bristol Myers Squibb, Ipsen, EUSA Pharma, MSD, EUSA Pharma, Novartis, AAA, Bayer, and Merck; has been an invited speaker for Astellas Pharma, Janssen, Roche, Pfizer, Bristol Myers Squibb, Roche, Bayer, EUSA Pharma, MSD, AstraZeneca, and Merck; and has received travel support from Merck/Pfizer and Bristol Myers Squibb., (© 2024 by the authors.)

Background: Financial toxicity, defined as both the objective financial burden and subjective financial distress from a cancer diagnosis and its treatment, is a topic of interest in the assessment of the quality of life of patients with cancer and their families. Current evidence implicates financial toxicity in psychosocial, economic and other harms, leading to suboptimal cancer outcomes along the entire trajectory of diagnosis, treatment, supportive care, survivorship and palliation. This paper presents the results of a virtual consensus, based on the evidence base to date, on the screening and management of financial toxicity in patients with and beyond cancer organized by the European Society for Medical Oncology (ESMO) in 2022., Methods: A Delphi panel of 19 experts from 11 countries was convened taking into account multidisciplinarity, diversity in health system contexts and research relevance. The international panel of experts was divided into four working groups (WGs) to address questions relating to distinct thematic areas: patients with cancer at risk of financial toxicity; management of financial toxicity during the initial phase of treatment at the hospital/ambulatory settings; financial toxicity during the continuing phase and at end of life; and financial risk protection for survivors of cancer, and in cancer recurrence. After comprehensively reviewing the literature, statements were developed by the WGs and then presented to the entire panel for further discussion and amendment, and voting., Results and Discussion: A total of 25 evidence-informed consensus statements were developed, which answer 13 questions on financial toxicity. They cover evidence summaries, practice recommendations/guiding statements and policy recommendations relevant across health systems. These consensus statements aim to provide a more comprehensive understanding of financial toxicity and guide clinicians globally in mitigating its impact, emphasizing the importance of further research, best practices and guidelines., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology., Materials and Methods: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data., Results: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data., Conclusion: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice., Competing Interests: Disclosure AP declares training of personnel role for AstraZeneca and Italfarma; advisory board role for BMS, travel grant from Janssen; and speaker’s engagement for Roche. FT declares full or part-time employment with Politecnico di Milano as researcher and lecturer for high-level education; and as cofounder of MLcube. CG declares advisory board role for Amgen, Roche, Sanofi, Takeda; speaker’s engagement from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck-Sharp-Dohme, and Novartis; institutional funding from AstraZeneca and Bristol Myers Squibb; institutional research grant from Italian Ministry of Health; clinical trials PI for AstraZeneca and Roche; and non-remunerated activities as member or AIOM, AIOT, ASCO, FONICAP, IASLC, and ISLB. SER declares speaker’s engagement from Amgen, BMS, Astellas, and GSK; writer’s engagement from BMS and Amgen; and travel and accommodation from Janssen and MSD. LC-B declares full time employment with ESMO as Scientific and Medical division Fellow. JD declares consultant role for MJH Life Sciences at ASCO Clinical Congress Consultants at ASCO 2022. ATP declares advisory board role for Abbvie, Elevar, Prelude Therapeutics, and Privo; institutional research grant from Abbvie and Kura; and non-renumerated activity as PI for Adenoid Cystic Carcinoma Research Foundation and Cancer Research Foundation. GLR declares advisory board role for AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, and Sanofi; speaker’s engagement from Italfarnaco; institutional funding as local PI for Amgen, AstraZeneca, BMS, Celgene, GSK, MSD, Novartis, Roche and Sanofi. CP declares personal fees from Italfarmaco, AstraZeneca, BMS, Merck Sharp and Dohme, and Janssen; and institutional funding from Novartis. ST declares speaker’s engagement from IDEA Pharma, Merck, MSD, Roche, and Ventana; institutional funding from Andy Quick Charitable fund, Complete genomics, CRUK, CRUK training and career development board, CRUK Welcome Trust, Harry J Lloyd Charitable Trust Career Development Award, NIHR, RMH/ICR/BRC/Imperial AHSC/Faculty of Medicine, Rosetrees Trust, The Francis Crick Institute, The Robert McAlpine Foundation, and Ventana. MK declares advisory board role for Bayer, MSD, Pierre Fabre, Servier; speaker’s engagement for BMS, Merck; institutional funding from Amgen, BMS, Merck, Nordic Farma, Novartis, Pierre Fabre, Servier; institutional research grant from Bayer, Bristol Myers Squibb, Personal Genomics Diagnostics, Pierre Fabre, Roche, Servier, Sirtex; trial chair for Servier; non-remunerated activities for Leadership Role for Dutch Colorectal Cancer Group and ESMO; advisory role for KWF, Patient representative organization (Kanker.nl), ZiNNL; and non-remunerated activity as ESMO faculty member. SD declares advisory board role for AstraZeneca, Besins Healthcare, Cellectis, Elsan, Isis/Servier, Novartis, Orion, Pierre Fabre, Rappta, Sanofi; speaker’s engagement for AstraZeneca, Exact Sciences, Gilead, Lilly, MSD, Pfizer, Seagen; institutional funding as steering committee member for AstraZeneca, BMS, Pfizer, Puma, Sanofi, Roche Genentech; institutional funding as local PI for Orion; institutional funding as coordinating PI for Taiho; institutional funding from GE; non-remunerated activity as PI for European Commission; and non-remunerated activity as Board of Directors member for SFSPM. JNK declares advisory board role for DoMore Diagnostics, Owkin, and Panakeia; and speaker’s engagement from Eisai, Fresenius, and MSD. FGMDeB declares speaker’s engagement from Ambrosetti, Amgen, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, Merck Group, MSD, Nadirex, Pfizer, Roche, Sanofi, Seagen, and Servier; consultation/advisory role from Mattioli 1885, AstraZeneca, BMS, EMD Serono, Incyte, Menarini, MSD, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi, and Taiho; funding as coordinating PI from Basilea Pharmaceutica International AG, BMS, DAICHI SANKIO Dev. Limited, Exelixis Inc, F. Hoffman-LaRoche Ltd, Ignyta Operating INC, IQVIA, Janssen-Cilag International NV, Kymab, LOXO Oncology Incorporated, MedImmune LCC, Merck KGaA, Merck Sharp & Dohme Spa, MSD, Novartis, Pfizer, and Tesaro; and think tank funding from MCCann Health. MCG declares speaker’s engagement from AstraZeneca, ecancer, GrupoPacifico-Secretaria Tecnica ICAPEM/AstraZeneca, Medscape, MSD, MSD Italia, S.O.S S.r.l, WebMD, WebMD Oncology/Takeda; consultation/advisory role from AstraZeneca/MedImmune, Daiichi Sankyo, AstraZeneca Poland, AstraZeneca UK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Mirati Therapeutics, MSD, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi/Prex, Sanofi Genzyme corporation, Seagen International GmbH, and Takeda; institutional funding as local PI for Phase III studies from Amgen, AstraZeneca, Bluprint, BMS, GlaxoSmithkline, Incyte Corporation, IPSEN Bioscience, MedImmune LCC, Novartis, Roche, and Sanofi; institutional funding as local PI for Phase II studies from AstraZeneca, Celgene Corporation, Daiichi Sankyo Development, MedImmune LCC, Merck KGaA, Merck Serono, Spectrum Pharmaceuticals, and Turning Point Therapeutics; institutional funding as local PI for Phase I studies from Exelixis Inc., Janssen; institutional funding as local PI from Bayer, Janssen, Merck, Pfizer, Otsuka Pharmaceutical Italy; institutional funding as Coordinating PI from AstraZeneca, MSD; steering committee member of the MK-3475 KN671 Steering Committee (KEYNOTE-671) from MSD, MK-3475 KN671 Steering Committee from MSD, Steering Committee ML41118 from Roche, and steering committee of Pfizer Global Lung Cancer Educational Programme; personal financial interests as PACIFIC-R Scientific Committee from AstraZeneca, PACIFIC-R Global Scientific Committee from AstraZeneca, Pacific 6 International Coordinating Investigator from AstraZeneca, steering Committee member and Co-chair at the AstraZeneca Lung Cancer Summit 2019, GSK-Garassino-ZEAL Steering Committee 2020-23, GSK Lung Cancer Global Council, Jannesen Scientific Advisory Board and Therapeutic Area Steering Committee Meeting on Lung Cancer, Seattle Genetics Lung Cancer Platform Study; travel, accommodations and expenses from AstraZeneca, Pfizer, and Roche; non-remunerated activities as principal investigator of AO Spedali Civili Brescia, Eli Lilly Studio TYME trial, European Thoracic Oncology Platform (ETOP) phase III trial, GOIRC Studio CHANCE trial, GOIRC RAME trial, GUSTAVE-ROUSSY PARIGI LIPI TRIAL, Istituto dei Tumori Pascale MILES 5 trial, Istituto dei Tumori Pascale IND227 trial, Istituto dei Tumori Pascale Beverly trial, Istituto Nazionale dei Tumori Progetto Timoma trial, Istituto Nazionale dei Tumori APOLLO trial, Istituto Nazionale dei Tumori Bando finalizzata Mesotelioma trial, Istituto Nazionale dei Tumori POST-ALK trial, Istituto Nazionale dei Tumori TERAVOLT trial, Istituto Nazionale dei Tumori FAME trial, MSD People, Pfizer STYLE trial, and Sant’Orsola Malpighi Creta trial; non-remunerated activities as member of AIOM, AIOT, ASCO, EMA Scientific Advisory Group, ESMO, IPOP, TUTOR, WCLC, Women for Oncology Italy; and non-remunerated activities as Scientific Programme Committee of AACR. GP declares full time employment from ESMO. ALGP declares personal financial interests for stocks/shares as cofounder of Agade s.r.l. and AllyArm s.r.l; institutional financial interests for co-funding of the Professorship Chair by Associazione Univerlecco and Congregazione Suore Infermiere dell’Addolorata; institutional financial interests for licensing/royalties as co-inventor of Patent No. 10201900000848 (Load compensation device, registered with Politecnico di Milano, surrendered in January 2023 with a royalty return plan), Patent No. 102018000006950 (System for detection and kinematic monitoring of body movements in water, and relative method, registered with Politecnico di Milano and Fondazione per la Ricerca Scientifica Termale; PCT/EP2019/067618) and Patent No. 102017000027918 (Device for controlled assistance of the grip; PCT/IB2018/051652); and non-financial interests as a member of the International Conference of Rehabilitation Robotics, member of the Institute of Electrical and Electronics Engineers (IEEE), IEEE Robotics and Automation Society, IEEE Engineering in Medicine and Biology Society and IEEE Women in Engineering. All other authors have declared no conflicts of interest., (Copyright © 2023 European Society for Medical Oncology. All rights reserved.)

Background: Cancer is a global public health problem, requiring efficient health system investments to deliver sustainable impact on population health. Access to medicines is a critical component of health systems, having a crucial role in delivering therapeutic benefits. Since 1977, the World Health Organization (WHO) has published a Model List of Essential Medicines (EML) that includes key health interventions for the prevention and control of conditions of public health relevance. Essential medicines are selected for inclusion in the EML based on the evidence of efficacy, safety, therapeutic value, and the potential to impact population health. With the rapid changes in the therapeutic landscape of cancer treatment with new medicine approvals, there is a critical need to select and prioritise specific cancer interventions based on their intrinsic value., Materials and Methods: The European Society for Medical Oncology (ESMO) has developed a decisional methodology based on a threshold with a minimum set of technical specifications and a consensus-based procedure for decisions to select candidate cancer medicines to be submitted to the WHO for consideration for the WHO EML., Results: ESMO recognises the WHO EML as an important reference guide for medicines that all countries should include in their national EMLs. Cancer medicines on the WHO EML are used in the treatment of the majority of cancers, and are recommended in the evidence-based ESMO Clinical Practice Guidelines that medical oncologists use to treat patients. ESMO's submissions to the WHO EML in 2019 and 2021 and their respective outcomes are presented in the manuscript., Conclusion: Due to the rising costs associated with newly available therapies, structured, reproducible, and field-tested tools to evaluate the added clinical benefit from these therapies need to be implemented in pre-selecting potential candidate medicines to be included in the WHO EML. ESMO is proud to collaborate closely with WHO on this important global public health initiative., Competing Interests: Disclosure TA reports personal fees from CeCaVa, institutional grants and personal fees from Novartis, institutional grants from NeraCare, personal fees and travel grants from BMS, personal fees and travel grants from Pierre Fabre, institutional grants from Sanofi, institutional grants from SkylineDx and institutional grants from iFIT, outside the submitted work. GC has received personal fees from AstraZeneca and Daiichi Sankyo; has received grants or contracts from Merck and AstraZeneca; has received personal fees as advisory board member for AstraZeneca, BMS; Ellipsis, Merck; Lilly, Pfizer, Roche, Veracyte; has received institutional research grant from Merck; has received institutional funding for phase I studies from Astellas, AstraZeneca, BMS, Blueprint Medicine, Daiichi Sankyo, Kymab, Novartis, Philogen, Roche, Sanofi; has received consulting fees from Roche, BMS, Novartis, Lilly, Pfizer, Seagen, AstraZeneca, Ellipsis, Gilead, Merck, Celcuity, Sanofi, Exact Sciences, and Daiichi Sankyo; has received payment or honoraria for presentations, lectures, speaker bureaus, manuscript writing, or educational events from AstraZeneca, Novartis, Lilly, Pfizer, Seagen, Roche and Daiichi Sankyo; has received support for attending meetings or travel from AstraZeneca and Daiichi Sankyo; has participated on a data safety monitoring board or advisory board for Roche, BMS, Novartis, Lilly, Pfizer, Seagen, Ellipsis, Gilead, Merck, Celcuity, AstraZeneca, and Daiichi Sankyo; has an advisory role and is Member of the Scientific Council of Europa Donna, is an Officer of the Consiglio Superiore di Sanità, Italian National Health Council as Advisor for Ministry of Health, and has an advisory role in Fondazione Beretta Cancer Research Foundation. RG reports being an invited speaker from Apogen, Lilly, Mylan, Novartis, Roche, Pfizer, Medicines for Europe, Mabxience and the European Access Academy (all with no fee received); she received personal fees from AstraZeneca and travel grants form Roche; she reports an advisory role for UICC ATOM Medicines (January 2023); she reports being a full member of the Cancer Drug Development Forum (CDDF); she is co-chair and member of the European Medicines Agency (EMA) Healthcare Professional Working Party (HCPWP) and a member of the EMA Cancer Medicines Forum; she serves as expert for the evaluation of proposals submitted to Horizon Europe Health Cluster-for the Health and Digital Executive Agency (HaDEA). DT reports being a member of the EMA Healthcare Professional Working Party (HCPWP), a member of the WHO SAGE IVD and a member of the WHO EML Cancer Medicines Working Group. GB, MG, NJL and GP are full-time employees of ESMO. All the other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Access to biomolecular technologies has become an essential requirement to ensure optimal and timely treatment of patients with cancer. This study sought to provide a comprehensive overview of the availability and accessibility of biomolecular technologies to patients, the status of their use and prescription, barriers to access, and potential economic issues related to cost and reimbursement., Materials and Methods: A total of 201 field reporters from 48 European countries submitted data through an electronic survey tool between July and December 2021. The survey methodology mirrored that from previous ESMO studies addressing the availability and accessibility of antineoplastic medicines, in Europe and worldwide. The preliminary data were posted on the ESMO website for open peer-review, and amendments were incorporated into the final report., Results: Overall, basic single-gene techniques are widely available, whereas access to advanced biomolecular technologies, including large next-generation sequencing panels and complete genomic profiles, is highly heterogeneous. In most countries, advanced biomolecular technologies remain largely inaccessible in clinical practice, are limited to clinical trials or basic research, and associated with progressively increasing cost as the technique becomes more advanced. Differences also exist regarding national sequencing initiatives or molecular tumour boards. The most important barriers to multiple versus single-gene sequencing techniques are the reimbursement of the test (59% versus 24%), and the availability of a suitable medicine, either through reimbursement of treatment (48% versus 30%), off-label treatment (52% versus 35%), or clinical trial enrolment (53% versus 39%)., Conclusions: Cost and availability of both treatment and test are the two main factors limiting patients' access to advanced biomolecular technologies and as a consequence to innovative anticancer strategies. In the era of precision medicine, tackling the accessibility to biomolecular technologies is a key step to reduce inequalities to transformative cancer care., (Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers., Methods: We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and 'on-tumour' status (established tumour-gene association)., Results: Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%., Conclusion: Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven 'most actionable' cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type., Competing Interests: Disclosure AGe reports receipt of honoraria for participation in advisory board from AstraZeneca, receipt of honoraria as invited speaker from GSK and receipt of honoraria for performing editorial and research review from Roche. HH reports receipt of honoraria for participation in advisory board from AstraZeneca and nonfinancial interest for leadership role as Chair of the UK Cancer Genetics Group. KS reports receipt of honoraria for providing expert testimony from Axa-PPP and receipt of honoraria as invited speaker from Everything Genetic, Merck, Pfizer. AK reports receipt of honoraria as invited speaker from AstraZeneca, receipt of honoraria for professional service agreement with HCA Healthcare and owning stocks/shares in Perci Health. CBW reports receipt of honoraria for participation in advisory board from BMS, Celgene, Rafael, RedHill, Roche, Shire/Baxalta; receipt of honoraria for providing expert testimony from Janssen; receipt of honoraria as invited speaker from Amgen, Bayer, BMS, Celgene, Chugai, Falk, GSK, Janssen, Merck, MSD, Roche, Servier, Sirtex and Taiho; receipt of travel support from Bayer, Celgene, RedHill, Roche, Servier and Taiho; receipt of personal and institutional research grant with no financial interest from Roche and nonfinancial interest as officer in the AIO – Arbeitsgemeinschaft Internistische Onkologie. EC reports receipt of honoraria for participation in advisory board from Astellas, AstraZeneca, Bayer, Janssen, MSD and Pfizer; receipt of honoraria as invited speaker from Astellas, AstraZeneca, Clovis, Janssen and Pfizer; receipt of honoraria for writing engagement from Pfizer; institutional funding from AstraZeneca and Pfizer; research grants to institution from Bayer and Janssen and institutional financial interest as local principal investigator from Janssen and Pfizer. JR reports receipt of honoraria for participation in advisory board from Ellipses Pharma, iOnctura SA, Kelun Pharmaceuticals/KLUS Pharma, Molecular Partners and Peptomyc; receipt of institutional research grant with no financial interest for clinical research from Aadi Bioscience, Amgen, Bicycle Therapeutics, BioMed Valley Discoveries, Cellestia, Curis, Deciphera, ForeBio, Hutchison MediPharma, Ideaya, Linnaeus Therapeutics, Loxo Oncology, Merus, Mirati, Nuvation, Roche Pharmaceuticals, Taiho and Tango Therapeutics; receipt of institutional research grant with no financial interest for research funding/clinical research from Hummingbird and Yingli; receipt of institutional research grant with no financial interest for research funding from Vall d’Hebron Institute of Oncology/Cancer Core Europe; receipt of institutional nonfinancial interest for clinical research from Bayer, BioAtla, CytomX, Genmab, GlaxoSmithKline, Kelun-Biotech, Novartis, Pfizer, Spectrum Pharmaceuticals, Symphogen and Takeda-Millennium; receipt of institutional financial interest for research funding from Black Diamond, Blueprint Medicines, Merck Sharp & Dohme; receipt of consultancy fees from Boxer Capital, LLC and Tang Advisors, LLC; receipt of travel reimbursement from the European Society for Medical Oncology and reports academic collaborations with Chinese University of Hong Kong, VHIO/Ministerio De Empleo Y Seguridad Social. JM reports receipt of honoraria for participation in advisory board from Amgen, AstraZeneca, Clovis Oncology, Janssen and Roche; receipt of honoraria as invited speaker from AstraZeneca, Guardant Health and MSD; no financial interest for serving as a steering committee member from AstraZeneca and Pfizer Oncology; receipt of research grant to institution from AstraZeneca and Pfizer Oncology and nonfinancial interest for receipt of product samples, access to drugs in early development for preclinical testing from AstraZeneca. GJB reports receipt of honoraria as invited speaker from AstraZeneca. MFB reports receipt of honoraria for participation in advisory board from Eli Lilly and PetDx. CT reports receipt of honoraria for participation in advisory board from Roche and receipt of honoraria as invited speaker from AstraZeneca. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure AK reports personal fees as an invited speaker from Roche; fees paid to his institution for advisory board membership from Roche; institutional funding from Bristol Myers Squibb (BMS); non-remunerated role as a principal investigator for Roche. TB reports fees paid to his institution as a study oncologist, for expert testimony and study-related travel expenses from Roche. CP reports fees paid to her institution as an invited speaker from Roche; institutional funding as a coordinating principal investigator from Roche. GB reports personal fees for advisory board membership from Gensenta; institutional funding as a Steering Committee member from Bayer; non-remunerated roles as a principal investigator for Eli Lilly, Merck Sharp & Dohme (MSD) and Roche; member of the American Society of Clinical Oncology (ASCO). SD reports personal fees as an invited speaker from Bracco Germany; non-remunerated leadership role as President (2010-2012) and Vice-President (2012-2014) of DEGUM (German Ultrasound Society); non-remunerated role as member and chairman of the ‘Radiation Protection in Medicine’ (2017-2020) working group for the Radiation Protection Commission (SSK) at the German Federal Ministry of Environmental Protection. KH has reported no potential conflicts of interest. LM reports a non-remunerated role as co-chair of the Steering Committee for the CUPISCO trial from Roche. HM reports personal fees as an invited speaker from Amgen and Roche; personal fees for advisory board membership from AstraZeneca, Janssen and Merck; institutional funding from Roche. KO reports institutional funding from BioClavis, BioTheranostics and Leica; non-remunerated advisory role as member of Steering Group for Early Detection and Diagnosis of Cancer Roadmap for Cancer Research UK and as member of Innovation Expert Advisory Group (EAG) for NHS England Cancer Innovation Programme; co-author of the RCPath dataset on CUP and malignancy of unknown origin for the Royal College of Pathologists; Cancer Research UK affiliate at the Beatson Institute; member of the National Cancer Research Institute (UK). AP reports personal fees for a congress subscription from Amgen; personal fees for advisory board membership in urothelial cancer from Basilea; personal fees for congress expenses from Janssen. HW reports personal fees as an invited speaker and for advisory board membership from Array BioPharma, Bayer, BMS, Celgene, Erytech, Incyte, Merck KGaA, Pierre Fabre, Servier Sirtex Medical and Roche/Genentech; personal fees for consultancy from OnoSil; personal fees for an advisory role and as a Trial Steering Committee member from Zymeworks; personal fees and institutional funding for an advisory role, as a coordinating principal investigator and member of Trial Steering Committee from Sirtex Medical; non-remunerated advisory roles with Bayer, Pfizer and Pierre Fabre. GZ reports personal fees as an invited speaker from Amgen, Ipsen, Leo Pharma and Merck. GP is the Chief Medical Officer for ESMO and member of ASCO and the Hellenic Cooperative Oncology Group and the Hellenic Society of Medical Oncology (HeCOG). KF reports personal fees for advisory board membership from Curevac and Orion; fees paid to his institution as an invited speaker from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, Pfizer and Sanofi; fees paid to his institution for advisory board membership from AAA, Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis/AAA and Pfizer; institutional funding as trial chair from AstraZeneca, Bayer, BMS, Janssen, MSD, Orion and Pfizer; non-remunerated role as principal investigator and trial chair for Bayer, BMS, Merck, Novartis/AAA and Orion. TO has declared no conflicts of interest.

Background: Cancer epidemiology is unique in adolescents and young adults (AYAs; aged 15-39 years). The European Society for Medical Oncology/European Society for Paediatric Oncology (ESMO/SIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries., Patients and Methods: We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population., Results: Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment., Conclusions: Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden., Competing Interests: Disclosure DS reports receipt of honoraria for providing academic peer review for research programme from French INCa, non-financial interest for advisory role in the clinical reference group advising NHS England about cancer policy in children and young people and non-remunerated membership of the Association of Cancer Physicians of the UK, SIOP Europe Adolescent Cancer Committee; IBS reports receipt of honoraria for participation in Advisory Board from Roche, receipt of honoraria as invited speaker from AstraZeneca, Novartis, Pfizer, Roche, receipt of personal and institutional financial interest as local PI from Novartis, Roche, non-financial interest for serving as local PI in EORTC Breast Group, OncoDistinct studies and non-remunerated advisory role in the Ethical Committee Serbia, National Agency for Drug Registration Serbia, the Working Group for Oncology of the Ministry of Health Serbia; NG reports receipt of honoraria to institution for participation in Advisory Board from Y-mAbs Therapeutics, receipt of financial support to institution from Eisai for covering travel expenses and registration fees as invited speaker at international meeting for the presentation of the results from the studies as international PI, receipt of consultancy fee to institution from Ipsen, non-remunerated Co-chair of the Fostering Age inclusive Research (FAIR) trial group of ACCELERATE; non-remunerated member of the Executive Committee of EEC (Euro-Wing Consortium), non-financial interest for leadership role as Chair of the FOSTER Consortium (Fight Osteosarcoma Through European Research) and non-remunerated member of GO-AJA, SFCE, SIOP Europe; FP reports receipt of honoraria for participation in Advisory Board from Roche Diagnostics, receipt of honoraria for providing expert testimony from Ipsen, Merck and non-financial interest for leadership role as Scientific Director of the European School of Oncology; ATo reports receipt of honoraria for participation in Advisory Board from MSD, AstraZeneca, Pfizer, Eli Lilly, receipt of honoraria as invited speaker from Eli Lilly, Novartis and non-remunerated member of AIOM; KS reports receipt of honoraria for participation in Advisory Board from Bayer, Novartis, Novo Nordisk, Roche, non-financial interest for leadership role in PanCare, SPOG, SSPHO and non-remunerated member of Board of Directors of SIOP Europe; GM reports receipt of honoraria for participation in Advisory Board from BMS, Janssen, Roche, Takeda, and receipt of honoraria as invited speaker from Amgen, AstraZeneca, MSD, Novartis, Pfizer; SB reports receipt of honoraria for participation in Advisory Board from Bayer Healthcare, Boehringer Ingelheim, Eli Lilly, Hofmann La Roche, MAP-Biopharma; non-financial interest as principal investigator of the Bayer’s larotrectinib study; and non-remunerated member of the European Musculoskeletal Oncology Society (EMSOS), German Pediatric Oncology Society (GPOH); ES reports receipt of honoraria for participation in Advisory Board from AstraZeneca A.E., AstraZeneca UK Ltd., Gilead Sciences Hellas, Merck, Sharp & Dohme, Pfizer Hellas, receipt of honoraria as invited speaker from Amgen Hellas, Pfizer Hellas, receipt of honoraria for providing expert testimony from Ipsen and non-remunerated member of Board of Directors of Hellenic Oncology Research Group, Hellenic Society of Medical Oncology. All other authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research., Methods: A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care., Results: The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP., Conclusions: This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients., Competing Interests: Disclosure JLPG has taken part in advisory boards for Bristol Myers Squibb (BMS), Merck, Merck Sharp & Dohme (MSD), Seattle Genetics, Gilead; reports speaker honorarium from BMS, MSD, Roche; reports funding from Ipsen, Roche; reports role as principal investigator (PI) for Amgen, BMS, Roche, Seattle Genetics. NP reports a research grant from Bayer. EC has taken part in advisory boards for Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Chugai, Elevation Oncology, Janssen, Monta, MSD, Nanobiotix, Nouscom, Novartis, Servier, T-knife, TargImmune; reports speaker/lecturer honorarium from OncoDNA, PharmaMar, Roche/Genentech; reports full or part-time employment by HM Hospitales Group, START Madrid; reports member of board of directors of PharmaMar; reports ownership interest in Oncoart Associated, START; reports steering committee member of BeiGene, Sanofi. AA has taken part in advisory boards from Amgen, AstraZeneca, Bayer, Daiichi, Eisai, Genomic Health, Hengrui, Innate, Ipsen, Leo Pharma, Lilly, Merck, MSD, Novartis, Pfizer, Seattle Genetics. Speaker fees from Amgen, AstraZeneca, Bayer, Daiichi, Eisai, Genomic Health, Ipsen, Leo Pharma, Lilly, Merck, MSD, Novartis, Pfizer, Seattle Genetics. Research grants from BMS, Roche. HTA has taken part in advisory boards for Beigene, iOnctura; reports speaker honorarium from Guardant, Servier; reports role as PI for multiple small and large Pharma/Biotechs. TA reports speaker honorarium from BMS, Novartis, Pierre Fabre; reports writers honorarium from CeCaVa; reports research grants from iFIT, Novartis; reports funding from NeraCare, Novartis, Sanofi, SkylineDx; reports non-financial interests in ASCO, Portuguese Society of Medical Oncology; reports other from INFARMED. VG has taken part in advisory boards for APOGEPHA, BMS, Debiopharm, Eisai, EUSA Pharma, Merck Serono, MSD, Nanobiotix, Oncorena, PCI Biotech, Pfizer, Roche; reports speaker honorarium from Astellas, AstraZeneca, BMS, Eisai, Ipsen, Janssen-Cilag, Merck Serono, MSD, Novartis, Pfizer, Roche; reports stocks/shares in AstraZeneca, BMS, MSD, Seattle Genetics; reports research grants from BMS, Ipsen, MSD, Pfizer; reports steering committee member for BMS, Eisai, Ipsen, Novartis; reports trial chair for PharmaMar; reports non-financial interests in ASCO, German Cancer Society, German medical Oncology and Hematology Society, Working Group medical oncology. MFS has taken part in an advisory board for Numab; reports speaker honorarium from MSD; reports a research grant from Roche; reports non-financial interests in BMS. GB has taken part in advisory boards for Janssen, Merck, Novartis, Roche, Servier. MPL has taken part in advisory boards for Amgen, Astellas, AstraZeneca, Bayer, INCa, Janssen-Cilag BV, MSD, Novartis, Pfizer, Roche, Sanofi, Servier; reports consulting role for Julius Clinical; reports research grants from Astellas, Janssen, MSD, Sanofi. MDN reports PI roles in studies sponsored by Amgen, BMS, Mundipharma, Novartis, Roche, Sanofi, Merck, Nektar Therapeutics, Incyte, Genentech, Beigene, Hookipa. PGC reports institutional research/educational funds from: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar. RG reports being a past core member of the European Medicines Agency (EMA) Scientific Advisory Group-Oncology (SAG-O, 2012-2021), member of the EMA Healthcare Professional Working Party and of the EMA Cancer Medicines Forum; an expert evaluator of proposal submitted to EU Commission on prevention (2020) and on artificial intelligence (2022); member of the Health Technology Assessment stakeholders group, former HTAN, and of the EUnetHTA stakeholder group; member of the steering committee of the World Health Organization (WHO) Decide Health Decision Hub; member of the Cancer Drug Development forum. She also provided consultation/lectures (no remuneration) for Novartis, Mylan, Roche, Lilly, Apogen, Pfizer and medicines for Europe and institutional financial support (clinical trials, Italy—2018) for MDS and Novartis. GP has taken part in advisory boards for Amgen, AstraZeneca, BMS, Lilly, Merck, MSD, Roche; reports role as PI for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Debiopharm, Ipsen, Lilly, Merck, MSD, Roche, Servier; reports grants from Amgen, AstraZeneca, Roche; reports funding from Boehringer Ingelheim, BMS, Enorasis, Genekor, Ipsen, Janssen, Merck, MSD, Pfizer, Sanofi, Servier. LCB has declared no conflicts of interest., (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

In 2021, the Food and Drug Administration Oncology Center of Excellence announced Project Optimus focusing on dose optimization for oncology drugs. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Taskforce met to review and discuss the optimization of dosage for oncology trials and to develop a practical guide for oncology phase I trials. Defining a single recommended phase II dose based on toxicity may define doses that are neither the most effective nor the best tolerated. MDICT recommendations address the need for robust non-clinical data which are needed to inform trial design, as well as an expert team including statisticians and pharmacologists. The protocol must be flexible and adaptive, with clear definition of all endpoints. Health authorities should be consulted early and regularly. Strategies such as randomization, intrapatient dose escalation, and real-world eligibility criteria are encouraged whereas serial tumor sampling is discouraged in the absence of a strong rationale and appropriately validated assay. Endpoints should include consideration of all longitudinal toxicity. The phase I dose escalation trial should define the recommended dose range for later testing in randomized phase II trials, rather than a single recommended phase II dose, and consider scenarios where different populations may require different dosages. The adoption of these recommendations will improve dosage selection in early clinical trials of new anticancer treatments and ultimately, outcomes for patients., (Copyright © 2022 European Society for Medical Oncology. All rights reserved.)

Background: The European Society for Medical Oncology (ESMO) Designated Centres (DCs) of Integrated Oncology and Palliative Care is an incentive programme established in 2003 aiming to improve the integration of oncology and palliative care services provided by oncologists and oncology centres worldwide. Currently, the ESMO DCs programme has over 250 centres accredited from 54 countries worldwide, in all six world regions., Materials and Methods: To evaluate how ESMO can support centres to improve programme development, education and research and vice versa what each single centre can do to improve in these areas, we developed a survey which was shared with all active centres. Two hundred and seven ESMO DCs representing 44 countries were invited to participate. We used content analysis to identify response categories using a stepwise approach. After reviewing and coding all responses to each question separately, they were placed into categories, counted and labelled., Results: Of the 207 centres that were invited to participate, 146 centres started the survey, representing 43 countries. Five overarching topics were identified. They included (i) joint events and educational activities; (ii) sharing of materials and defining common standards; (iii) sharing of experiences, scientific knowledge and expertise; (iv) research collaboration; and (v) ESMO support. Respondents were willing to support the ESMO DC community group in all topics and were also asking ESMO to support their centres in these issues in the future., Conclusion: The study showed that the ESMO DCs are willing to provide support to improve education, research and programme development. They are also eager to contribute and collaborate amongst each other, but also request ESMO to offer advice and help to improve these issues in the DCs. In the future, facilitation of joint research projects and development of arenas to share experiences, educational and programme developments, and other resources are to be explored and could be offered to the DCs worldwide., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship., Design and Methods: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research., Results: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care., Conclusions: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking., (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer., Methods: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19., Findings: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR 30 ) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR 30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR 30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10 9  cells/L, p=0.0098)., Conclusion: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2., Competing Interests: Competing interests: KJH declares research funding from AstraZeneca, Boehringer-Ingelheim, MSD, Replimune and advisory board fees/honoraria from Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak Biosciences, Inzen Therapeutics, Merck-Serono, MSD, Pfizer, Replimune. DA reports consultation/advisory role for AstraZeneca, Bristol Myers Squibb, Merck Sharp reports speaker’s engagement from AstraZeneca, Bristol Myers Squibb, Merck Sharp reports serving as local PI for Bristol Myers Squibb, Pierre Fabre Pharma and coordinating PI for OncoLytics; reports grant funding from AbbVie; reports being/been DSMB chair of Sanofi (Genzyme); reports being/been a steering committee member of Roche. Olivier Michielin reports personal fees from Bristol-Myers Squibb, MSD, Novartis, Roche, Amgen, NeraCare, outside the submitted work. JR received speaker or advisory fees from Roche, Astra Zeneca, Merck, Ferrer, Persan Farma, Teva Pharma, Leo Pharma, Fresenius kabi, MSD, BMS. Travel expenses support from BMS, MSD, RocheUrania Dafni reports honorarium as Member of the Tumor Agnostic Evidence Generation Working Group of Roche, outside the submitted work. GP reports grants from Amgen, Lilly; grants, personal fees and nonfinancial support from Merck; grants and non-financial support from AstraZeneca; grants and personal fees from Roche, Bristol Myers Squibb, MSD, Novartis, outside the submitted work. Solange Peters reports consultation/advisory role for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol- Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody; talk in a company’s organized public event for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda; receipt of grants/research supports from being a (sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. Emanuela Rromano reports investigator-initiated trial (funds paid to the institution) supported by Astra-Zeneca, BMS; serves on the consultancy/advisory board for Astra-Zeneca, Merck, Roche, Pierre Fabre. ML acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work.Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis and Roche. Joan Brunet has declared consulting/advisory role for MSD and Astra Zeneca. Aleix Prat has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. Mark Bower received speakers’ fee from EISAI pharma, Gilead Sciences, Merck and ViiV. JT reports consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; speaker’s fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource; and institutional research support from Amgen, Array Biopharma, AstraZeneca Pharmaceuticals, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Health, Merck Sharp and has had leadership roles in the European AIDS Clinical Society, UNAIDS, WHO, and The European Hematology Association/ European Society of Medical Oncology. DJP received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, DaVolterra and Astra Zeneca; research funding (to institution) from MSD and BMS. AC received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers’ fee from AstraZeneca, MSD, Novartis and Eisai. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made., Competing Interests: Disclosure GA reports receipt of honoraria for participation in Advisory Board from Astellas, AstraZeneca, Bayer, Janssen, Novartis, Orion, Pfizer, Sanofi, Sapience, receipt of honoraria as invited speaker from Astellas, AstraZeneca, Janssen, receipt of royalties for licensing fees from Janssen, receipt of institutional research grants from Astellas and Janssen, non-remunerated activities as a PI in Astellas, Janssen, and non-remunerated advisory role in AstraZeneca and Janssen; FCB reports receipt of honoraria for participation in Advisory Board from Archer, BioNTech, Lilly, Novartis, Pfizer, receipt of honoraria to institution for participation in Advisory Board from AstraZeneca, receipt of honoraria as invited speaker from AstraZeneca, Novartis, Pfizer, Roche, Seagen, receipt of honoraria to institution as invited speaker from Pfizer, Sanofi, receipt of honoraria for expert testimony from Hikma, institutional non-financial interest for research as a coordinating PI from AstraZeneca, Pfizer, ProLynx, Saga and Seagen; GC reports receipt of honoraria for participation in Advisory Board from AstraZeneca, Bristol Myers Squibb (BMS), Daiichi Sankyo, Ellipsis, Exact Sciences, Lilly, Merck, Pfizer, Roche, Veracyte, receipt of honoraria as invited speaker from AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Roche, receipt of honoraria for writing engagement from Pfizer, institutional research grant for investigator initiated clinical trial from Merck, institutional funding for conduct of phase I studies from Astellas, AstraZeneca, Blueprint Medicine, BMS, Daiichi Sankyo, Kymab, Novartis, Philogen, Roche, Sanofi, non-remunerated activities as an officer of the Italian National Health Council—Advisor for Ministry of Health, non-remunerated advisory role as a member of the Scientific Council of Europa Donna, non-remunerated advisory role in Fondazione Beretta, and non-remunerated member of Board of Directors of the Lega Italiana Lotta ai Tumori; LDMA reports receipt of honoraria as invited speaker, participation in speaker bureau from Roche, institutional research collaboration grant from NanoString and receipt of education grant from BMS; MD reports receipt of honoraria for participation in Advisory Board from AstraZeneca, Boehringer Ingelheim, Genentech, Gritstone Oncology, Illumina, receipt of honoraria for consultancy from BioNTech, Novartis, RefleXion, Roche, has ownership interest with CiberMed, Foresight Diagnostics, receipt of royalties for licensing fees from Foresight Diagnostics, Roche Diagnostics, receipt of institutional financial interest as a coordinating PI from AstraZeneca, Varian, receipt of funding from Genentech, non-financial interest for receipt of reagents from Illumina, non-remunerated activities as a member of Board of Directors of Foresight Diagnostics; AI reports receipt of honoraria for participation in Advisory Board from Bayer, Chugai Pharmaceutical Co, GlaxoSmithKline, Philips, Roche, institutional non-financial interest as a coordinating PI from AstraZeneca, Bayer, Ipsen, Merck, Merck Sharp & Dohme (MSD) and Roche; JL reports receipt of honoraria to institution as invited speaker from Roche; JDM reports receipt of honoraria for participation in Advisory Board from Illumina, BMS, receipt of honoraria for consultancy from PierianDx, receipt of royalties for licensing fees administered by Stanford University from the United States Patent Office, non-remunerated activities as a member of Board of Directors of the Association for Molecular Pathology, non-remunerated leadership role as a Chair of the Informatics Subdivision of the Association for Molecular Pathology, non-remunerated leadership role as a Vice Chair of the CLSI MM23—Molecular Diagnostic Methods for Solid Tumors Committee of the Clinical and Laboratory Standards Institute (CLSI), non-remunerated activities in the US NIH/NCI as a PI for the NIH 1-UG1-CA233333-01, UNITS: The UNC/UT National Clinical Trials Network Group Integrated Translational Science Production and Consultation Center; CM reports receipt of honoraria for participation in Advisory Board from Biocartis, Merck Serono, receipt of honoraria as invited speaker from Amgen, Guardant Health, Merck Serono, and Pierre Fabre, Roche, receipt of royalties for licensing fees administered by Institut Investigació Hospital del Mar; NN reports receipt of honoraria for participation in Advisory Board from AstraZeneca, Bayer, Biocartis, Incyte, Novartis, Qiagen, Roche, receipt of honoraria as invited speaker from BMS, Eli Lilly, Illumina, Merck, MSD, Sanofi, Thermo Fisher, receipt of institutional research grants from AstraZeneca, Biocartis, Blueprint, Illumina, Incyte, Merck, Qiagen, Roche, Thermo Fisher, leadership non-remunerated role as a President of the International Quality Network for Pathology (IQN Path) and President of the Italian Cancer Society (SIC); KP reports receipt of honoraria for participation in Advisory Board from MSD, Menarini, Hello Healthcare, Sanofi, receipt of honoraria as invited speaker from Abcam, Ipsen Pharma, Medac, Agena, institutional financial interest from Angle plc, European Liquid Biopsy Society, Böhringer Ingelheim and for participation in IMI JT ID Cancer from EU/IMI Cancer-ID consortium; SP reports receipt of honoraria for participation in Advisory Board from Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Guardant Health, Janssen, Eli Lilly, Merck KGaA, Novartis, Roche, Takeda, institutional financial interest for research as a coordinating PI from Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, as a local PI from AstraZeneca, GlaxoSmithKline, Roche, Trizell, as a sub-investigator from Amgen, MSD, non-remunerated advisory role in ALK Positive UK, International Association for the Study of Lung Cancer, Lung Cancer Europe, Ruth Strauss Foundation, non-remunerated leadership role in the British Thoracic Oncology Group as a Chair of Steering Committee, European Thoracic Oncology Platform as a Foundation Council Member, non-remunerated member of Thoracic malignancy Faculty in the European Society for Medical Oncology, non-remunerated member of Board of Directors in the Mesothelioma Applied Research Foundation; JSRF reports consultancy fees from Goldman Sachs, Repare Therapeutics, Paige.AI and Eli-Lilly, membership of the Board of Directors Group Oncoclinicas, stock ownership of Repare Therapeutics, and honoraria for ad hoc participation in the Scientific Advisory Board of Repare Therapeutics, Paige.AI, Roche Tissue Diagnostics, Novartis, Roche/Genentech, Invicro and Personalis; JT reports consultancy fee from Haystack Oncology, receipt of honoraria for participation in Advisory Board from AstraZeneca, BMS, MSD, Inivata, Pierre Fabre, receipt of honoraria as invited speaker from Merck Serono, Amgen and Servier; JS reports ownership interest as a co-founder of Mosaic Biomedicals SL, member of Board of Directors of Northern Biologics Inc., receipt of institutional research grants from Roche Glycart AG, Mosaic Biomedicals SL, Hoffmann-La Roche Ltd, Northern Biologics Inc., Ridgeline Therapeutics, non-remunerated activities as a member of Board of Directors of Asociación Española Contra el Cáncer and a member of Board of Directors, Secretary General of the European Association for Cancer Research (AACR); TY reports receipt of honoraria as invited speaker from Bayer, Chugai, Eli Lilly, Merck Biopharma, Ono, Taiho, receipt of institutional research grants from Amgen, MSD, Ono, Taiho, receipt of institutional financial interest as a local PI from Chugai, Daiichi Sankyo, MSD, Ono, Parexel International, Sanofi and Sumitomo Dainippon; NT reports receipt of honoraria for participation in Advisory Board from Arvinas, AstraZeneca, BMS, GlaxoSmithKline, Lilly, MSD, Novartis, Pfizer, Repare Therapeutics, Roche/Genentech, Zentalis Pharmaceuticals, institutional funding for research from AstraZeneca, MSD, Pfizer, Roche/Genentech, institutional non-financial interest for provision of material for research from BioRad and for provision of assays from Guardant Health. JS is co-founder of Mosaic Biomedicals and has ownership interests from Mosaic Biomedicals and Northern Biologics and reports receipt of grant/research support from Mosaic Biomedicals, Northern Biologics, Roche/Glycart and Hoffmann la Roche. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)