Joharatnam-Hogan, N

Khan, K

English

UCL Discovery

COMMENTARY Open AccessCOVID-19 cancer conundrum—evidencedriving decisions or the lack of it?Nalinie Joharatnam-Hogan1,4 and Khurum Khan1,2,3*Keywords: COVID-19, Oncology research, Chemotherapy, Public health, Cancer care, Cancer screeningBackgroundThe novel coronavirus SARS-CoV-2, the causativepathogen of the COVID-19 pandemic, is characterisedpathologically by inflammation, a feature considered tobe a hallmark of another uncontrolled pandemic, “can-cer”. Whilst these two diseases are separate entities withdisparate aetiologies, they share some overlapping fea-tures—including multi-organ involvement, widespreadinflammation, and a paucity of definitive treatmentoptions. The pandemics are also comparable in theirscale. The World Health Organisation (WHO) reported18.1 million new global cancer cases and 9.6 millioncancer-related deaths in 2018, with COVID-19 having4.7 million cases and 316,289 fatalities as of 19 May2020 [1]. There has been a decades-long drive to im-prove cancer outcomes, utilising the expertise of cancerresearchers, epidemiologists, translational and clinicalscientists, immunologists, statistical modellers, andhealth economists. The urgent, round-the-clock race todevelop a vaccine or feasible treatment for COVID-19 isinvolving a similar multi-discipline effort.Examining the evidenceThere is a notion that cancer patients, due to theirhigher average age, prevalence of co-morbidities, andimmunosuppression, may be at higher risk of increasedmorbidity and mortality associated with COVID-19. Thereis particular concern for those receiving chemotherapy.Current evidence supporting this concern remains incon-clusive and is an active focus of ongoing research. Due tothe high prevalence of cancer patients in the UK, many ofwhom are receiving chemotherapy, we recognise anurgency in defining any excess risk of COVID-19 andcancer.A prospective nationwide analysis of 1590 patientswith COVID-19 in China, of whom 1% had a history ofcancer, has shown an increased likelihood of having a se-vere event (a composite of invasive ventilation or death)in those patients with cancer (39% versus 8% in patientswithout cancer, p = 0.0003) [2]. These data must beinterpreted with caution due to the small sample size ofcancer patients (n = 18) and significant heterogeneity be-tween these tumour types. A subsequent study fromWuhan comparing 105 patients with cancer to 536 age-matched patients without cancer demonstrated a higherfrequency of severe events related to COVID-19 particu-larly in patients with haematological malignancies, lungcancer, or metastatic disease [3]. Our group formed aNorth London collaboration of five hospitals and foundno significant differences in mortality of two consecutivecohorts comprising of COVID-19 positive cancer andnon-cancer patients [4]. It is possible there may be aconfounding factor of chemotherapy-associated im-munosuppression having a protective effect against someof the inflammatory processes of COVID-19 by virtue ofdampening the cytokine storm. All of these studies hadsignificant limitations due to the retrospective nature ofthe data, heterogeneity amongst the patient population,and lack of pre-determined study parameters, whichmay offer logical explanation for the conflicting results.© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data.* Correspondence: khurum.khan1@nhs.net1Gastrointestinal Oncology Service & Cancer of Unknown Primary Service,University College London Hospital NHS Foundation Trust, London, UK2UCL Cancer Institute, London, UKFull list of author information is available at the end of the articleJoharatnam-Hogan and Khan BMC Medicine          (2020) 18:182 https://doi.org/10.1186/s12916-020-01649-zCancer care compromisedThe surge of COVID-19 cases threatened to overwhelmacute health services in almost every country in theworld. To create the necessary critical care capacity,countries such as the UK, Italy, and the USA were re-quired to re-structure non-acute services. Patients withcancer worldwide have faced disruption of their care,including delaying of urgent procedures, deferral of sur-gery, discontinuation of systemic therapy, and modifica-tion of standard radiotherapy procedures [5]. Cancerscreening programmes have been paused and cancerdiagnoses heavily impacted. In the UK, a 25% reductionin urgent cancer referrals has been recorded, estimatedto equate to 2300 undiagnosed cases every week [6].Mirroring the pandemic caseload, there has been a surgeof novel clinical trials assessing both vaccine and treat-ment candidates for COVID-19. However, there hasbeen a precipitous reduction in cancer trial recruitmentand development.The rationale for modifying cancer services is under-pinned by the balance of clinical need and significantpossible risks to patients from the COVID-19 infection,as well as the need to optimise already stretched re-sources and capacity [7]; however, concerns remainabout the likely impact on individual cancer care andcancer mortality. Warnings have been made about a sec-ond wave of COVID-19 infections [8], which theoretic-ally could coincide with a wave of delayed presentationsof advanced cancer or early progression of disease.What the future holdsRe-establishing gold-standard cancer care and researchin the post-COVID-19 era is likely to be challenging. Re-search is currently being undertaken to determine whatchanges to care delivery and clinical research, imple-mented in response to COVID-19, could be retained,and how delivery of care can be amended [9]. Data is re-quired on the likely impact COVID-19 will have on mor-bidity and mortality. It has been estimated that therewill be a 20% increase in deaths occurring over a year inEngland in patients with new cancer diagnoses as resultof the COVID-19 pandemic, equivalent to an additional6270 deaths [10]. Prospectively collected precise data onthe alterations made to cancer services and true mortal-ity of these patients is required to better understand thepotentially severe unintended consequences of the re-sponse to the COVID-19 pandemic, to inform the ap-propriate management and prioritisation of healthcareservices.ConclusionWe are entering a recovery phase of the COVID-19 pan-demic; however, it is inevitable that cancer services willnot resume in the manner they did in the pre-COVIDera. Healthcare services need to adapt to the presence ofboth global burdens, cancer and COVID, to minimisecomplications from either. The generation of timely evi-dence on the impact of COVID-19 on cancer care andpatient outcomes is required to guide future cancer caredelivery and cancer research. We need to ensure on-going sustainability and safety of future managementpathways and enable a coordinated response of all over-lapping specialities in the fight against this and any fu-ture pandemics.AbbreviationsWHO: World Health OrganisationAcknowledgementsNot applicableAuthors’ contributionsAll authors read and approved the final manuscript.FundingNone to declareAvailability of data and materialsNot applicableEthics approval and consent to participateNot applicableConsent for publicationNot applicableCompeting interestsNone to declareAuthor details1Gastrointestinal Oncology Service & Cancer of Unknown Primary Service,University College London Hospital NHS Foundation Trust, London, UK. 2UCLCancer Institute, London, UK. 3North Middlesex University Hospital, London,UK. 4MRC CTU UCL, London, UK.Received: 20 May 2020 Accepted: 20 May 2020References1. World Health Organisation (WHO). Coronavirus disease (COVID-19)pandemic. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed 19 May 2020.2. Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients inSARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21(3):335–7.3. Dai M, Liu D, Liu M, Zhou F, Li G, Chen Z, et al. Patients with cancer appearmore vulnerable to SARS-COV-2: a multi-center study during the COVID-19outbreak. Cancer Discov. 2020:CD-20-0422.4. Joharatnam-Hogan N, Hochhauser D, Shiu K-K, Rush H, Crolley V, Butcher E,et al. Outcomes of the 2019 Novel Coronavirus in patients with or withouta history of cancer - a multi-centre North London experience. medRxiv.2020:2020.04.16.20061127. Online ahead of print.5. The LO. Safeguarding cancer care in a post-COVID-19 world. Lancet Oncol.2020;21(5):603.6. Cancer Research UK. How coronavirus is impacting cancer services in theUK. Available at: https://wwwcancerresearchukorg/. Accessed 19 May 2020.7. National Institute for Health and Care Excellence (NICE). COVID-19 rapidguideline: delivery of systemic anticancer treatments Available at: https://wwwniceorguk/guidance/ng161/chapter/6-Prioritising-systemic-anticancer-treatments. Accessed 7 May 2020.8. Xu S, Li Y. Beware of the second wave of COVID-19. Lancet. 2020;395(10233):1321–2.Joharatnam-Hogan and Khan BMC Medicine          (2020) 18:182 Page 2 of 39. American Society of Clinical Oncology (ASCO). THe Road to Recovery:Cancer Care and Research in a Post-COVID World. Available at:https://wwwascoorg/sites/new-wwwascoorg/files/content-files/blog-release/pdf/2020-the-road-to-recovery-covid19-april2020pdf?cid=DM4954&bid=42598701. Accessed 19 May 2020.10. Lai A, Pasea L, Banerjee A, Denaxas S, Katsoulis M, Chang WH, et al.Estimating excess mortality in people with cancer and multimorbidity in theCOVID-19 emergency 2020.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Joharatnam-Hogan and Khan BMC Medicine          (2020) 18:182 Page 3 of 3

COVID-19 cancer conundrum-evidence driving decisions or the lack of it?

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COVID-19 cancer conundrum-evidence driving decisions or the lack of it?

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