www.nature.com/bjc REVIEW ARTICLE COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic Alvin J. X. Lee 1 and Karin Purshouse 2 The SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT— chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care. British Journal of Cancer https://doi.org/10.1038/s41416-021-01324-x BACKGROUND from SARS-Cov-2.7,9,10 Further, the backlog of patients for whom Since the SARS-Cov-2 pandemic began at the start of 2020, cancer diagnosis and treatment were delayed during the first wave will teams around the world have adapted their practice in the aim of see an increasing need for all forms of cancer treatment, and likely protecting patients. After a period where restrictions were eased, at a more advanced cancer stage. Understanding which treatment many countries have returned to national lockdowns as case modalities confer the highest risk is vital in order to discuss the numbers rise. The challenge of protecting patients with cancer in a relative risks with patients and facilitate collaborative decision- world where SARS-Cov-2 is endemic has become all the more making. apparent. During the first international phase of the SARS-Cov-2 Cancer registries of patients infected with SARS-Cov-2 emerged pandemic, cancer services were paused as it was feared that during the first wave to address these uncertainties, and to date patients with cancer were at particular risk of severe infection. The they likely offer the most comprehensive clinical data to guide immunomodulatory effect of both cancer and many systemic anti- cancer teams. These have ranged from local or regional databases cancer treatments (SACT) was identified as a risk factor for this to national and international registries. In this review, we aim to group, particularly given the evidence from previous infection collate the evidence from large national and international outbreaks.1–3 This was supported by early evidence from Wuhan registries and highlight trends and challenges these data present. province, China, that cancer patients, and particularly those who Fig. 1 illustrates the timeline of establishment of major COVID-19 had recently received chemotherapy or surgery, were at increased and cancer registries, and significant COVID-19 and cancer risk.4,5 Cancer treatment (including SACT and radiotherapy) and events. Overall, these studies suggest that patients with cancer care inherently requires physical contact and can result in side who develop SARS-Cov-2 have a higher probability of death effects, thereby further increasing the risk to patients. Many compared with patients without cancer. Common risk factors for countries adopted ‘shielding’ policies, advising patients to stay at mortality following SARS-Cov-2 infection identified in patients home.6 Remote consultations and rationalisation of treatment with cancer include age, male sex, smoking history, the number of modalities were introduced to minimise the risks for patients comorbidities and poor performance status (PS). Oncological requiring active treatment. Cancer services were also reorganised features that may predict for worse outcomes include tumour to allow clinical services to prioritise the high clinical acuity of stage and progressive disease, and possibly lung cancer. COVID-19 patients, including redeploying staff to other clinical Evidence for the safety of SACT is more conflicting with most areas. Overall, cancer teams and their patients made huge studies identifying no association with adverse outcomes, while adaptations in the face of significant uncertainty.3,7,8 others report that in some groups, chemotherapy or immunother- As further waves of SARS-Cov-2 take hold, cancer teams around apy may confer an increased risk. Recent data have suggested the world must make decisions about how to move forward. There that timing of receipt of SACT in relation to SARS-Cov-2 is significant concern that delays to both cancer diagnosis and diagnosis may affect outcomes following SARS-Cov-2 infection.11 treatment will lead to the mortality from cancer exceeding that A key challenge underlying any comparisons lie in the diversity 1UCL Cancer Institute, University College London, London, UK and 2CRUK Edinburgh Cancer Research Centre, The University of Edinburgh, Edinburgh, UK Correspondence: Alvin J. X. Lee ([email protected]) Received: 30 October 2020 Revised: 8 February 2021 Accepted: 19 February 2021 © The Author(s) 2021 Published by Springer Nature on behalf of Cancer Research UK COVID-19 and cancer registries: learning from the first peak of the. AJX Lee and K Purshouse 2 Timeline of establishment of Timeline of significant COVID-19 and cancer registries COVID-19 and cancer events First novel viral pneumonia Dec 2019 reported in Wuhan, China First COVID-19 case outside China, in Thailand Jan 2020 First COVID-19 case in USA First COVID-19 cases in UK, Italy, Spain TERAVOLT (thoracic cancers) WHO declares COVID-19 outbreak a pandemic CCC-19 (mainly North American) The National Institute for Health and Care Excellence (NICE), UK March 2020 issues guidance on SACT during UKCCMP (UK) pandemic UK cancer patients advised to OnCovid (UK, Italy, Spain) shield to reduce risk of COVID-19 1234567890();,: DOCC (Dutch) UK nation wide stay at home order issued GCO-002 CACOVID-19 (French) ASCO Registry (USA) April 2020 SAKK 80/20 CaSA (Swiss) ESMO-CoCARE (mainly Europe and Asia) NCCAPS (USA) May 2020 Ongoing lifting of UK stay at June 2020 home restrictions Aug 2020 UK shielding advice lifted Fig. 1 Timeline of establishment of COVID-19 and cancer registries, and significant COVID-19 and cancer events. Figure created with BioRender.com. between these registries and the populations they describe, METHODS noting that the population of cancer patients actively treated A search of the PubMed database, and European Society for during the first wave of SARS-Cov-2 may not reflect the overall Medical Oncology (ESMO) and American Society of Clinical cancer population. Oncology (ASCO) meeting abstracts was undertaken for articles COVID-19 and cancer registries: learning from the first peak of the. AJX Lee and K Purshouse 3 up to October 14, 2020. Keywords used were “COVID-19”, rate of 33.6%, comparable with those from other European patient “SARS-Cov-2”, “cancer”, “malignancy”. Registries that were cohorts, and similarly identified age, male gender and more than described as national or multinational were included. We note two comorbidities as risk factors. Interestingly, while they also that other registries have been established and have not yet reported no negative survival impact of SACT overall, they also published their findings, such as the ESMO-CoCARE Registry12 and identified that SACT was associated with better outcomes (HR NCI COVID-19 in Cancer Patients Study (NCCAPS)13 and these 0.71, 95% CI 0.53–0.95; P = 0.019) but noted that this cohort had a studies have been excluded from the review. Table 1 summarises greater proportion of young, female and less comorbid patients. the published output from the registries identified, which are explored in more detail below. TERAVOLT This cohort is composed solely of thoracic cancers, including small and non-small cell lung cancers and rarer subtypes such as COVID-19 AND CANCER REGISTRIES pulmonary neuroendocrine neoplasms. In their preliminary find- CCC-19 ings, they identified that 76% of patients were hospitalised and The Clinical impact of COVID-19 on patients with Cancer (CCC-19) 33% died. Multivariate analysis only identified smoking history as a cohort study included adult patients with active or previous risk factor for death.20 An update presented at the ESMO 2020 cancer with a serological confirmation of SARS-Cov-2 infection in congress of 1012 patients from 20 countries identified age (>65), patients from over 120 institutions across the USA, Canada and cancer stage (stage > III), current smoker status and steroids prior Spain. The first analysis of 928 patients showed 39% were on to SARS-Cov-2 infection confirmation as risk factors for death after active anti-cancer treatment, and only 43% had active (measur- multivariate analysis. Neither chemotherapy nor tyrosine kinase able) cancer. The mortality rate was 13%, and after logistic inhibitors (TKIs) were associated with increased mortality, and this regression analysis, age, male gender, smoking, comorbidities >2, analysis identified a reduced risk for mortality for patients on active cancer and ECOG PS > 2 were associated with increased immunotherapy.21 In the TERAVOLT cohort, the majority of 30-day mortality. Neither cancer type nor recent anti-cancer patients were on active cancer treatment (74% in the first analysis, therapy or surgery were associated with increased mortality.14 This 65% in the second), the highest of all the SARS-Cov-2 cancer is the lowest mortality rate seen in any cancer registry study and registries.