key: cord-0975251-1x000b4c
authors: Indini, Alice; Rijavec, Erika; Ghidini, Michele; Cattaneo, Monica; Grossi, Francesco
title: Developing a risk assessment score for cancer patients during COVID-19 pandemic
date: 2020-05-31
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2020.05.017
sha: a51ab8e1bbc2dbcd1c5f85fe4080e7194e0e16c7
doc_id: 975251
cord_uid: 1x000b4c

The novel coronavirus (CoV) pandemic is a serious threat for cancer patients, who have an immunocompromised status, and are considered at high risk for infections. Data on the novel CoV respiratory disease (COVID-19) in cancer patients are still limited. Unlike other common viruses, CoV have not shown to cause a more severe disease in immunocompromised subjects. Along with direct viral pathogenicity, in some individuals CoV infection triggers an uncontrolled aberrant inflammatory response, leading to lung tissue damage. In cancer patients treated with immunotherapy (e.g. immune-checkpoint inhibitors), COVID-19 may therefore represent a serious threat. After a thorough review of the literature on CoV pathogenesis and cancer, we selected several shared features to define which patients can be considered at higher risk for COVID-19. We combined these clinical and laboratory variables, with the aim of developing a score to weight the risk of COVID-19 in cancer patients.

The novel coronavirus (CoV) pandemic is a serious threat for cancer patients, who have an immunocompromised status, and are considered at high risk for infections. Data on the novel CoV respiratory disease in cancer patients are still limited. Unlike other common viruses, CoV have not shown to cause a more severe disease in immunocompromised subjects. Along with direct viral pathogenicity, in some individuals CoV infection triggers an uncontrolled aberrant inflammatory response, leading to lung tissue damage. In cancer patients treated with immunotherapy (e.g. immune-checkpoint inhibitors), COVID-19 may therefore represent a serious threat. After a thorough review of the literature on CoV pathogenesis and cancer, we selected several shared features to define which patients can be considered at higher risk for COVID-19. We combined these clinical and laboratory variables, with the aim of developing a score to weight the risk of COVID-19 in cancer patients.

Worldwide health services are facing the challenge of the novel coronavirus (CoV) disease (COVID-19) pandemic [1] , which is wide spreading rapidly and severely. Some categories of patients, including patients with cancer, are considered more at risk than others. Cancer itself develops in an immunocompromised field, supporting the evidence that oncologic patients are more at risk of infections, and this risk is further increased by certain oncologic treatments (e.g. chemotherapy, radiotherapy). Medical oncologists have arranged their daily clinical practice in view of the current emergency, through the implementation of protective measures [2] . To date, no evidence-based recommendations have been provided due to limited data of COVID-19 in oncologic patients. Evidence from small case series suggest that COVID-19 diffusion in cancer patients is not prominent as expected [3] [4] [5] [6] . Rather, other comorbidities (e.g. cardiovascular disease, diabetes, chronic obstructive pulmonary disease) correlate with a higher risk of infection and severe events [7] .

Due to the peculiar pathogenesis of CoV in humans, and to the mechanisms of action of novel oncologic treatments, the link between CoV and cancer patients might not be straightforward.

Unlike other common viruses, CoV have not shown to cause a more severe disease in immunocompromised subjects [7] . Along with a direct viral pathogenicity, the host immune response plays a crucial role in COVID-19. In some individuals, CoV infection triggers an uncontrolled aberrant inflammatory response to external factors leads to lung tissue damage [8] .

Since the introduction of anti-cancer immunotherapy (e.g. immune-checkpoint inhibitors [ICIs]), most oncologic patients have changed their features of immunocompromised subjects. Rather, their immune system is somehow "boosted" by the cancer treatment they receive. This might translate into a distinct susceptibility of these subjects towards CoV infections. The cross-interference of CoV and ICI may worsen the clinical course of COVID-19 which, in turn, may intensify ICI-related side effects [9] . Altogether, these evidences suggest that in patients treated with immunotherapy COVID-19 (e.g. immune-checkpoint inhibitors), may represent a serious threat [8] .

The present article focuses on developing a score to weight the risk of COVID-19 in cancer patients. The main issue raised by the pandemic is whether the risk of COVID-19 outweighs that of cancer treatment delay. In the present situation, oncologists need to decide which kind of patient should start (or continue) which kind of treatment, and how much will this increase the risk of complications in case of COVID-19 [10] . After a thorough review of the literature on CoV pathogenesis and cancer, several shared features have been selected to define which patients can be considered at higher risk of complications in case of COVID-19.

The score includes clinical and laboratory variables, as indicated in Table 1 . Regarding patient's characteristics, all recognized risk factors for COVID-19 were included: older age, presence of comorbidities, obesity, and male sex [7] . Two more variables were included: performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG) scale, and corticosteroid treatment. ECOG PS is a recognized risk factor for outcome, and the presence of poor ECOG PS (i.e. ≥ 2) has been confirmed to be detrimental in cancer patients with COVID-19 [6] . Long-lasting treatment with high-dose corticosteroids, commonly used as supportive therapy for patients with cancer and potentially associated with an increased risk of opportunistic infections, seems to have a negative impact on COVID-19 outcome [5] .

Regarding the underlying tumor characteristics, limited available data suggest that lung cancer diagnosis and ongoing thoracic radiotherapy (RT) at the time of COVID-19 onset, were common features of patients with severe disease [3] [4] [5] [6] . In our score, these two items are meant to be included only once for patients with lung tumors. In fact, thoracic RT is commonly used as treatment of patients with lung tumors; however, this does not seem to further increase the risk according to available data. Nonetheless, patients with extra-thoracic tumors receiving thoracic RT (e.g. for palliative treatment of metastases) should be considered at risk, due to the potential radiation damage to the lung tissue.

Considering all the above-mentioned issues, the type and intent of oncologic treatment might impact on the risk of COVID-19 complications. The therapeutic setting (i.e. adjuvant versus treatment for metastatic disease) has an impact due to differences in tumor burden and patients' general conditions. Immunotherapy, or the combination of immuno-and chemotherapy are considered high-risk treatments, followed by chemotherapy, and other anti-cancer drugs (e.g. hormonal therapy, targeted agents). Among patients receiving immunotherapy, those with a history of immune-related adverse events (irAEs) and/or disease response to treatment, might be even more at risk. There is plenty of evidence that irAEs correlate with a higher efficacy of immunotherapy, suggesting that an adequate immune response harms both the tumor and the host [11] .

Common laboratory findings of patients with severe COVID-19 are lymphopenia, high neutrophilto-lymphocyte ratio (NLR), high levels of inflammatory markers (e.g. C-reactive protein [CRP]) and lactate dehydrogenase (LDH) [1] . Polarization of the immune response towards a proinflammatory profile also correlates with lower efficacy of immunotherapy and tumor progression, and baseline NLR correlates with survival outcomes and response to immunotherapy.

Altogether, these variables can be used to group oncologic patients in distinct classes of risk in the actual COVID-19 emergency. The purpose of risk assessment is to help clinicians in treatment decisions. Given the lack of data in this field and the absence of a validation in the clinical setting, the assumption of a precise role of these variables is only conceptual. Prospective data collection is needed to translate these observations in clinical practice, with the aim of guiding risk-to-benefit considerations and treatment decision in specific subgroups of patients. Customization of cancer treatment should be pursued, in order to provide patients with the best care in this critical situation. 

Clinical Characteristics of Coronavirus Disease 2019 in China

Reorganisation of medical oncology departments during the novel coronavirus disease-19 pandemic: a nationwide Italian survey

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Risk of COVID-19 for patients with cancer

Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China

SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China

Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis

Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic

SARS-COV-2 infection in cancer patients undergoing checkpoint blockade: clinical course and outcome

Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic

Funding: The present work was partially financed by the Italian fiscal contribution "5x1000" 2016 devolved to the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Pfizer. Research Funding: Bristol-Myers Squibb. Travel, Accomodations, Expenses: Bristol-Myers Squibb