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Id Subject Object Predicate Lexical cue
T1 0-97 Sentence denotes Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic
T2 99-188 Sentence denotes During the COVID-19 global pandemic, the cancer community faces many difficult questions.
T3 189-306 Sentence denotes We will first discuss safety considerations for patients with cancer requiring treatment in SARS-CoV-2 endemic areas.
T4 307-437 Sentence denotes We will then discuss a general framework for prioritizing cancer care, emphasizing the precautionary principle in decision making.
T5 439-629 Sentence denotes The first infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to coronavirus disease (COVID-19), were reported in Wuhan, China in December 2019 (ref.1).
T6 630-783 Sentence denotes COVID-19 is associated with presentations ranging from asymptomatic infections to severe viral pneumonia, acute respiratory distress syndrome and death1.
T7 784-900 Sentence denotes As of 30 March 2020, a total of 638,146 cases and 30,039 confirmed deaths have been reported across >150 countries2.
T8 901-963 Sentence denotes The cancer community currently faces many difficult questions.
T9 964-1023 Sentence denotes Herein we address the question of treatment prioritization.
T10 1024-1141 Sentence denotes We will first discuss safety considerations for patients with cancer requiring treatment in SARS-CoV-2 endemic areas.
T11 1142-1272 Sentence denotes We will then discuss a general framework for prioritizing cancer care, emphasizing the precautionary principle in decision making.
T12 1273-1515 Sentence denotes While we aim to provide important perspectives from clinical oncology, infectious disease and oncology-value frameworks, this Comment is intended to expand the conversation on a very challenging topic, rather than provide definitive guidance.
T13 1516-1582 Sentence denotes The current pandemic raises two fundamental patient safety issues.
T14 1583-1713 Sentence denotes First, patients with cancer must leave their homes to visit the cancer clinic and thereby possibly expose themselves to infection.
T15 1714-1823 Sentence denotes Second, cancer treatments themselves can predispose patients to the more serious harmful effects of COVID-19.
T16 1824-1909 Sentence denotes Should patients risk exposure to SARS-CoV-2 in order to receive treatment for cancer?
T17 1910-2060 Sentence denotes The available evidence is limited, but suggests that the symptoms of COVID-19 are probably more severe in patients with cancer than for those without.
T18 2061-2268 Sentence denotes Clear evidence exists that older age and higher levels of comorbidity are associated with more severe COVID-19 symptoms and adverse outcomes; this consideration is highly relevant to patients with cancer3,4.
T19 2269-2435 Sentence denotes A report by Liang et al. currently provides the largest series (n = 1,590) describing how COVID-19 outcomes can vary between patients with, and those without cancer4.
T20 2436-2627 Sentence denotes In this model, which included adjustments for age, sex, and comorbidities, cancer is associated with an increased risk of death and/or intensive care unit admission (OR 5.4, 95% CI 1.8–16.2).
T21 2628-2764 Sentence denotes However, interpretation of this finding is limited by the small sample size; the report included data from only 18 patients with cancer.
T22 2765-2944 Sentence denotes In the midst of the COVID-19 pandemic, oncologists will need to weigh the risks of death and morbidity from COVID-19 against the magnitude of benefit of intended cancer therapies.
T23 2945-3091 Sentence denotes Early estimates from China suggest an overall case fatality rate of 2%, increasing to 8% for 70–79 year-olds, and 15% for those ≥80 years of age1.
T24 3092-3171 Sentence denotes Case fatality rates are also markedly higher among patients with comorbidities:
T25 3172-3275 Sentence denotes 11% for cardiovascular disease, 7% for diabetes, 6% for chronic respiratory disease, and 6% for cancer.
T26 3276-3407 Sentence denotes Case fatality rates were far lower outside of Hubei province (0.4% versus 2.9% in Hubei), therefore, these estimates might be high.
T27 3408-3545 Sentence denotes For many patients with cancer, the probable survival benefits of receiving treatment still far outweigh the risks of death from COVID-19.
T28 3546-3643 Sentence denotes The risk of transmitting SARS-CoV-2 can be mitigated through hospital infection control policies.
T29 3644-3917 Sentence denotes We emphasize the importance of meticulous screening of patients and staff (including consideration of symptoms and travel history) before permitting entry into outpatient clinics together with the importance of engineering patient flow to minimize contact between patients.
T30 3918-4042 Sentence denotes These strategies are also important for staff safety, to ensure maximal availability of both clinical and nonclinical staff.
T31 4043-4214 Sentence denotes To reduce the number of clinic visits and the inherent risks, shorter radiotherapy fractionation and conversion of intravenous to oral systemic regimens can be considered.
T32 4215-4339 Sentence denotes The opportunity exists for stopping or reducing frequency of selected maintenance treatments, or those with a long duration.
T33 4340-4680 Sentence denotes For example, at our centre we will be moving from 2-weekly to 4-weekly administration of durvalumab as consolidation therapy for patients with non-small-cell lung cancer (reducing frequency), and recommending the consideration of treatment breaks for those receiving maintenance pemetrexed, or even forgoing maintenance pemetrexed entirely.
T34 4681-4928 Sentence denotes Based on the UNESCO working definition, the precautionary principle dictates that “when human activities may lead to morally unacceptable harm that is scientifically plausible but uncertain, actions shall be taken to avoid or diminish that harm”5.
T35 4929-5093 Sentence denotes This principle should be applied to both our system-level approach to COVID-19 risks, and to treatment recommendations for patients with cancer during the pandemic.
T36 5094-5289 Sentence denotes In balancing these competing priorities, waiting times should be kept as short as reasonably achievable, with careful consideration given to both patient-level and system-level risks of COVID-19.
T37 5290-5387 Sentence denotes We propose a conceptual framework for prioritizing cancer treatment during the pandemic (Fig. 1).
T38 5388-5506 Sentence denotes The examples provided involve radiotherapy and systemic therapy, although the principles are also relevant to surgery.
T39 5507-5662 Sentence denotes Interpretation of this framework will rely heavily on the capacity of locoregional health systems and the position of a given system on the epidemic curve.
T40 5663-5846 Sentence denotes Our discussion will focus on three scenarios: (1) preparedness (with no confirmed cases); (2) moderate health-care resource limitation; and (3) severe health-care resource limitation.
T41 5847-5969 Sentence denotes Fig. 1 Conceptual framework for prioritizing the use of radiotherapy and systemic treatments during the COVID-19 pandemic.
T42 5970-6109 Sentence denotes The lowest and highest priority categories are unevenly spaced to illustrate the concept that prioritization between subgroups is variable.
T43 6110-6191 Sentence denotes The spacing of categories in this diagram is conceptual rather than prescriptive.
T44 6192-6312 Sentence denotes Priority of indications within each category is also variable and subject to the principles discussed in the commentary.
T45 6313-6534 Sentence denotes These include the magnitude of treatment benefit, possible effects of treatment delays or interruptions on outcomes, patient-specific considerations and the availability of staff and resources to safely deliver treatment.
T46 6535-6659 Sentence denotes This overlap implies that some items listed in a lower category could be prioritized over items listed in a higher category.
T47 6660-6782 Sentence denotes Disease indications in each box are meant to serve as illustrative examples and are not intended to be an exhaustive list.
T48 6783-6817 Sentence denotes NSCLC, non-small-cell lung cancer.
T49 6818-7014 Sentence denotes Priority-setting for the delivery of cancer therapies in the context of a pandemic will be strongly influenced by both the magnitude of potential treatment benefit and therapeutic intent (Fig. 1).
T50 7015-7210 Sentence denotes Other considerations include the effects of delays or interruptions on outcomes (if known), patient-specific considerations, and the availability of staff capable of safely delivering treatments.
T51 7211-7452 Sentence denotes The selection of specific indications for which interventions should be postponed is beyond the scope of this Comment; however, a number of published resources are available that quantify the benefits of radiotherapy and systemic therapy6,7.
T52 7453-7553 Sentence denotes We emphasize that even within one group of this hierarchy, prioritization and exceptions will exist.
T53 7554-7646 Sentence denotes Ongoing prioritization requires regular data-driven reassessments in order to minimize harm.
T54 7647-7860 Sentence denotes Importantly, how long the patient has (already) been waiting will change case priority; what constitutes an acceptable delay will vary by priority level, indication and the contextual factors described previously.
T55 7861-8030 Sentence denotes We note that the availability of resources for systemic therapy, radiotherapy and surgery will fluctuate independently to some degree, requiring separate prioritization.
T56 8031-8258 Sentence denotes In addition to the current system environment, the general framework will need to be considered in light of patient-level factors (such as age and/or comorbidities) and patient preferences regarding risks and benefits (Fig. 1).
T57 8259-8329 Sentence denotes Specific risks of cancer therapy might also influence decision making.
T58 8330-8411 Sentence denotes For example, thoracic radiotherapy and drug toxicities might limit lung function.
T59 8412-8661 Sentence denotes Similarly, patients with treatment-related T cell and B cell-mediated immunosuppression might have more severe viral infections, as will patients who are heavily immunosuppressed, such as those who have received haematopoietic stem cell transplants.
T60 8662-8983 Sentence denotes For health systems anticipating COVID-19 cases, but without confirmed cases, continuation of most treatments while considering postponing treatments without an anticipated adverse effect on cancer outcomes (such as treatments for patients with basal cell carcinomas or low-risk prostate cancers) is a reasonable approach.
T61 8984-9107 Sentence denotes Deferring routine follow-up appointments for several months also seems reasonable for most patients in these circumstances.
T62 9108-9218 Sentence denotes Some clinic visits could be replaced with ‘virtual’ assessments conducted by videoconference and/or telephone.
T63 9219-9406 Sentence denotes This approach seeks to balance patient outcomes with system capacity when the anticipated quarantines, isolations and hospitalizations begin to affect the capacity to deliver cancer care.
T64 9407-9514 Sentence denotes These measures also ensure patient safety by reducing the risks of transmission to a vulnerable population.
T65 9515-9775 Sentence denotes When the number of new COVID-19 cases starts to increase, and moderate limitations in human and other health-care resources begin to emerge (such as supply chain interruption), the prioritization of beneficial treatments will become a higher priority (Fig. 1).
T66 9776-9882 Sentence denotes Clear evidence exists that, for certain indications, treatment postponement can adversely affect outcomes.
T67 9883-10055 Sentence denotes For example, a 16% increased risk of death exists for every month of delay of radiotherapy for patients with head and neck cancer (risk ratio (RR) 1.16, 95% CI 1.02–1.32)8.
T68 10056-10272 Sentence denotes Furthermore, delays in receiving adjuvant chemotherapy for colorectal cancer (HR 1.14, 95% CI 1.10–1.17 per 4 weeks)9 and breast cancer (RR 1.08, 95% CI 1.01–1.15 per 4 weeks)10 are associated with inferior survival.
T69 10273-10417 Sentence denotes Although data are currently insufficient, negative effects on outcomes owing to treatment delays seem very plausible for many other indications.
T70 10418-10489 Sentence denotes Thus, the precautionary principle should be applied in decision making.
T71 10490-10722 Sentence denotes Multidisciplinary case conferences (which might be coordinated ‘virtually’ during a pandemic) will remain important venues to prioritize the care of complex patients and to continuously review policies in a rapidly changing context.
T72 10723-10983 Sentence denotes Under the scenario of severe resource constraints, treatment might only be possible in oncological emergencies, including diseases with an imminent risk of early mortality (such as acute leukaemias) or substantial morbidities (such as spinal cord compression).
T73 10984-11154 Sentence denotes If health-system capacity allows, the next level of cancer therapy priorities would be other treatments with a curative intent and a high probability of success (Fig. 1).
T74 11155-11270 Sentence denotes Arrangements might also need to be made to transfer patients to other regions or jurisdictions during the pandemic.
T75 11271-11321 Sentence denotes Triaging should be dynamic, with daily variations.
T76 11322-11591 Sentence denotes On 12 March 2020, ASCO issued a guidance document that further expands on these issues, and other guidance documents are emerging, including from the UK National Health Service, Cancer Care Ontario, ESMO, ASTRO and ESTRO, in addition to a new online resource from ASCO.
T77 11592-11667 Sentence denotes Guidance from regional bodies is important in ensuring consistency in care.
T78 11668-11720 Sentence denotes Open communication between all groups is imperative.
T79 11721-11805 Sentence denotes The COVID-19 pandemic has the potential to overwhelm current health-system capacity.
T80 11806-12064 Sentence denotes Postponing cancer treatments might be associated with some risk, although these risks will need to be considered in light of the magnitude of potential benefits, the impact of waiting times on outcomes and competing patient-level and system-level priorities.
T81 12065-12237 Sentence denotes Throughout the pandemic, supporting our patients’ emotional wellbeing and ensuring that adequate psychosocial support systems are in place will be more important than ever.
T82 12238-12468 Sentence denotes Treatment decisions during the COVID-19 pandemic will rely on the precautionary principle, transparent and evidence-based prioritization of cases for triage, and fluidity in recognizing that local contexts can change very rapidly.
T83 12470-12489 Sentence denotes Further information
T84 12490-12567 Sentence denotes ASCO coronavirus resources: https://www.asco.org/asco-coronavirus-information
T85 12568-12785 Sentence denotes Clinical guide for the management of cancer patients during the coronavirus pandemic: https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/specialty-guide-acute-treatment-cancer-23-march-2020.pdf
T86 12786-12856 Sentence denotes COVID-19 and cancer: https://www.esmo.org/newsroom/covid-19-and-cancer
T87 12857-13047 Sentence denotes COVID-19 clinical oncology frequently asked questions (FAQs): https://www.asco.org/sites/new-www.asco.org/files/content-files/blog-release/pdf/COVID-19-Clinical%20Oncology-FAQs-3-12-2020.pdf
T88 13048-13183 Sentence denotes COVID-19 recommendations to radiation oncology practices: https://www.astro.org/Daily-Practice/COVID-19-Recommendations-and-Information
T89 13184-13365 Sentence denotes Pandemic planning clinical guideline for patients with cancer: https://www.obgyn.utoronto.ca/sites/default/files/oh-cco_pandemic_planning_clinical_guideline_final_2020-03-10_002.pdf
T90 13366-13505 Sentence denotes “Radiotherapy in a time of crisis”, ESTRO Presidents’ statement: https://www.estro.org/About/Newsroom/News/Radiotherapy-in-a-time-of-crisis
T91 13507-13523 Sentence denotes Acknowledgements
T92 13524-13561 Sentence denotes The authors gratefully acknowledge S.
T93 13562-13574 Sentence denotes Berry and M.
T94 13575-13608 Sentence denotes Brundage (Queen’s University), A.
T95 13609-13647 Sentence denotes Detsky (University of Toronto), and A.
T96 13648-13745 Sentence denotes Purushotham (King’s College London) for comments provided on an earlier draft of this manuscript.
T97 13746-13896 Sentence denotes We are also grateful to leaders and our clinical colleagues in the Department of Oncology at Queen’s University for input into the proposed framework.
T98 13897-14045 Sentence denotes T.P.H. holds a research chair provided by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario (#IA-035).
T99 14046-14174 Sentence denotes C.M.B. is supported as the Canada Research Chair in Population Cancer Care through funding provided by the Government of Canada.
T100 14176-14195 Sentence denotes Competing interests
T101 14196-14239 Sentence denotes The authors declare no competing interests.