key: cord-323148-rsjocuh3
authors: Assaad, Souad; Fuhrmann, Christine; Avrillon, Virginie; Ray-Coquard, Isabelle; Blay, Jean-Yves
title: Risk of death of cancer patients presenting with severe symptoms of infection, with or without documented COVID-19
date: 2020-09-06
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2020.08.018
sha: 
doc_id: 323148
cord_uid: rsjocuh3

nan

We would like to thank Dr van Dam and colleagues (1) for their letter and the careful attention they dedicated to our work (2) .

We want first to express our full agreement to their conclusion stating that cancer patients must « have maximal access to (adapted) treatment and if necessary maximal supportive care in times of SARS-CoV-2 pandemic ».

Indeed, the COVID-19 epidemic is affecting deeply the care of patients with cancer for at least three reasons.

The first one is the delay to treatment that had to be given at the spike of the COVID-19 outbreak (in our case in the period of March to April 2020). These delays were requested 1) to cope with the concentration of healthcare resources on the epidemic, and 2) also often at patient request who feared to come to the health care services.

Reports of delayed treatments were issued in many countries from known cancer patients already followed by multidisciplinary services (3) . In the period reported in our work, this effect was of limited magnitude in the center from which the patients were recruited. An increase in the number of patients receving cancer treatment at home (+452%, n=181 vs n=40 as compared to the 8 previous weeks of 2020), with an increase of teleconsultations (+ 24550%, n=5886 vs n=24 in the previous 8 weeks of 2020). The access to ICU for cancer patients was never limited in our region, in contrast with other region in our country our in Europe. Although a longer follow-up will be needed to investigate the long term outcome of cancer patients in this time period, such delays are unlikely to have affected the survival of the patients in our series.

The second one, delays to the access to initial diagnosis and initial treatment, reported also in several countries, are associated with a maximal risk of increased deaths for curable patients. While the magnitude of increased risk of deaths varies considerably across cancer types, an 6 to 15% increase risk of death related delay to diagnosis and treatment suggested by recent studies (3, 4) . In 9 centres of the French Unicancer Federation (Ms in preparation), a mean reduction of 36% of new incident cancer diagnosis was observed in this period of 8 weeks leading to estimates similar to those in the work of Maringe et al (3) . Here again, the impact on the long term outcome of cancer patients will require additional years of follow-up.

The third impact of COVID-19 on cancer patients is of course the high of death in the weeks following infection for cancer patients in active phase of the disease. As rightly pointed out by van Dam et al, prognostic factors are here crucial to distinguish different patient populations. Age, gender, metastasis and usual prognostic critera such as PS and lymphopenia were all correlated with an increased risk of death in our series, and others. Prognostic factors are however not consistent across reported series of cancer patients (2, 5, 6) . Of note the immune response of cancer patients to COVID, as evaluated by seroconversion assays, may be less efficient in treated cancer patients as compared to previously healthy individuals (6) , in line with the observation that lymphopenia is a negative prognostic factor.

The striking observation of our series is the high risk of death (actuarial survival close to 20% at day 28) of cancer patients who did not demonstrate detectable SARS-COV-2 using the standard Cobas test. Most often multiple testing were performed and no other possible other aetiology was identified. It is here important to remember that the 30 days death rates of cancer patients hospitalized with seasonal flu and H1N1, is close to 9% to 15% in large series close from that reported in our series of patients with no proven COVID-19 (8, 9) , and larger than that of historical series of cancer patients treated with cytotoxics (10) . The high death rates of RT-PCR negative cancer patients observed in our series may result from a sensitivity of SARS-COV-2 diagnostic assays (false negativity), and also other undocumented infections in the context of patients with a progressive cancer.

From these different series and works, it can be concluded that cancer patients under active treatment are at high risk of lethal complications when presenting with symptoms resembling those of COVID -19 and requiring hospitalisation even in the absence of documented SARS-COV-2 infection. These patients must be managed with the greatest attention, similar to that of COVID-19 documented patients, even if negative for SARS-COV-2 on RT-PCR testing.

High Mortality Rate in Cancer Patients With Symptoms of COVID-19 With or Without Detectable SARS-COV-2 on RT-PCR

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study

Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic

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

SARS-Cov-2 infection in cancer patients undergoing active treatment: analysis of clinical features and death

Lower detection rates of SARS-COV2 antibodies in cancer patients vs healthcare workers after symptomatic COVID-19

Epidemiology and outcomes of serious influenza-related infections in the cancer population

Influenza in patients with cancer after 2009 pandemic AH1N1: An 8-year followup study in Mexico. Influenza Other Respir Viruses

Bachelot et al; ELYPSE Study Group. Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas

J o u r n a l P r e -p r o o f

In reply to van Dam et al. Souad Assaad, Christine Fuhrmann, Virginie Avrillon, Isabelle Ray-Coquard, Jean-Yves Blay

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: