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      Cancer patients and research during COVID-19 pandemic: A systematic review of current evidence

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          Abstract

          The novel coronavirus, also known as SARS-Cov-2 or COVID-19 has become a worldwide threat and the major healthcare concern of the year 2020. Cancer research was directly affected by the emerging of this disease. According to some Chinese studies, cancer patients are more vulnerable to COVID-19 complications. This observation led many oncologists to change their daily practice in cancer care, without solid evidence and recommendations. Moreover, the COVID-19 manifestations as well as its diagnosis are particular in this special population. In this review paper we expose the challenges of cancer management in the era of SARS-CoV-2, the epidemiological, clinical, pathological and radiological characteristics of the disease in cancer patients and its outcomes on this population. Finally, we focus on strategies that are followed in cancer management with review of national and international guidelines.

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          Most cited references 48

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          COVID-19: global consequences for oncology

          As the coronavirus disease 2019 (COVID-19) pandemic escalates and countries struggle to contain the virus, health-care systems are under increasing pressure. Emergency departments and intensive care units are nearing breaking point, and medical resources are being diverted to tackle the crisis. Moreover, conferences are being cancelled, and research trials are grinding to a halt. So what does COVID-19 mean for patients with cancer, their physicians, and the wider oncology discipline? Patients with cancer are a high-risk group in the COVID-19 pandemic. They are already vulnerable to infection because of their underlying illness and often immunosuppressed status, and are at increased risk of developing severe complications from the virus, including intensive care unit admission or even death. Moreover, for those who develop COVID-19, treatment of the disease will be prioritised, and further cancer therapy could be delayed, although such decisions must be made on a patient-by-patient basis and not based only on the early small reports published in the first few weeks of the pandemic. Media reports have described patients with cancer in quarantined cities being unable to travel to appointments or struggling to obtain essential medicines; the risk of interruptions in drug supply chains and consequent shortages will exacerbate this issue. Scheduled operations, some types of cancer treatment, and appointments are being cancelled or postponed to prioritise hospital beds and care for those who are seriously ill with COVID-19. In England, UK, despite the 2020 budget promising several billion pounds of extra NHS funding to help tackle the outbreak, when cases of COVID-19 peak in the coming weeks the NHS will undoubtedly be forced to delay non-urgent treatments and surgeries as resources and personnel are repurposed. Unfortunately, the effects of COVID-19 are not solely limited to the treatment of patients with cancer, but will also hit the wider oncology community, with inevitable consequences for research, education, and collaboration. University campuses in the worst hit countries have shut down, with many others expected to follow. Some of those affected, including the University of Bologna, Italy, have responded by digitising their teaching programmes, moving classes and exams online to alleviate the educational impact. However, such solutions cannot be used for practical laboratory work or field studies, and ongoing research projects are being jeopardised. Limited resources and capacity will force institutions to decide which clinical trials to prioritise and which to suspend. Many institutions, including the Dana Farber Cancer Institute (Boston, MA, USA) are restricting employees’ work-related travel, and others such as the Fred Hutchinson Cancer Research Center (Seattle, WA, USA—one of the worst-affected US cities) are implementing mandatory work from home policies. However, not all centres in affected regions have similar policies, and such heterogeneity might create imbalances in patient cohorts in multicentre trials, potentially biasing eventual results. With some governments advising against or banning non-essential travel and large-scale events, at least eight major cancer meetings and conferences have been cancelled or postponed, with many more expected to follow. As a result, innumerable opportunities for discussion and collaboration will be lost, the latest research will not be presented, and patients will subsequently be affected by the delay in dissemination of information on the latest treatment to their doctors. Although some congresses are being reorganised to take place online, face-to-face meetings are a crucial aspect of team science and cannot be eliminated completely. Furthermore, societies and organisations postponing or cancelling meetings will probably face financial consequences that could have long-term effects on their ability to fund key activities in the future. The American Society of Clinical Oncology—which at the time of writing had not yet decided about their 2020 annual meeting—relied on a huge US$43 million in revenue from education and meeting registration fees in 2018. For smaller societies that rely on their annual meetings financially, cancellations could threaten their existence. With the situation constantly changing, all we can do for now is watch, wait, and adapt as best we can until the immediate and long-term effects of this pandemic fully materialise. Ultimately, the situation might lead to substantial changes in how research and medicine are practiced in the future, such as reduced international travel and increased remote networking and telemedicine. Until the COVID-19 pandemic is over, we can only hope that the consequences are not too devastating for patients and that the oncology community and beyond are able to weather this unprecedented storm. © 2020 CDC/Science Photo Library 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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            The official French guidelines to protect patients with cancer against SARS-CoV-2 infection

            On request of the French Health Ministry, the French High Council for Public health (Haut Conseil de Santé Publique [HCSP]) entrusted a representative group of French medical oncologists and radiation oncologists, working across academic and private practice, with the task of preparing guidelines to protect patients with cancer against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while maintaining the possibility of cancer treatment. After finalisation of the guidelines on March 10, 2020, the coordinator of the group (BY) was interviewed by HCSP on March 11, 2020. The guidelines were adopted and published by HCSP on March 14, 2020. The preparation of these guidelines is justified by data 1 suggesting patients with cancer are at high risk of respiratory complications related to SARS-CoV-2 infection. The susceptibility of patients with cancer to influenza was described 2 before the emergence of SARS-CoV-2. For patients with cancer infected with influenza, the risk of hospital admission for respiratory distress is four times higher, and the risk of death ten times higher than patients without cancer. This exacerbation seems to be particularly marked in those with neutropenia or lymphopenia, a feature commonly seen in patients with cancer treated with multiple therapies. 2 A Comment 1 from Wenhua Liang and colleagues, published in The Lancet Oncology, on the situation in China suggests that patients with cancer are at higher risk of infection with SARS-CoV-2 than the general population (1% of patients with COVID-19 in the study had cancer, whereas the incidence of cancer in the Chinese population is 0·29%), which could be related to the closer medical follow-up of these patients. More concerning is the increased risk of severe respiratory complications requiring time in the intensive care unit in patients with cancer, as compared with patients without cancer (39% vs 8%, respectively; p=0·0003). A covariate significantly associated with this risk was a history of chemotherapy or surgery in the month preceding infection (odds ratio 5·34, 95% CI 1·80–16·18; p=0·0026), a factor that includes the majority of patients with cancer. Finally, patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days vs 43 days; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69). The following guidelines apply to adult patients with solid tumours only, and should be considered complementary to the standard rules adopted by the French health authorities for the general population. First, some prevention measures can be implemented in oncology departments. The basic principle is for patients with cancer and oncology or radiotherapy departments to avoid—as much as possible—any contact with people with coronavirus disease 2019 (COVID-19). Oncology and radiotherapy departments should ideally remain COVID-19-free sanctuaries. The admission of patients with COVID-19 in oncology or radiotherapy departments should be avoided. If, despite this principle, such patients were admitted to hospital in oncology or radiotherapy departments, they should be isolated from other patients with cancer and referred to departments specialised in the fight against COVID-19 as quickly as possible. Given the susceptibility of patients with cancer to SARS-CoV-2 infection, their presence at hospitals should be minimised. Any measures that would enable management of patients with cancer at home should be encouraged. This includes telemedicine and phone calls to replace safety visits, as well as replacement of intravenous drugs with oral drugs (eg, chemotherapy and hormone therapies) where possible, along with infrastructure and logistics to allow home administration of intravenous and subcutaneous anticancer agents. Adjustment of dosing schedules of chemotherapy or radiotherapy treatments can be considered to reduce the frequency of hospital admissions (eg, every 3 weeks, rather than weekly administration, of the same regimens or hypofractionated radiotherapy). Moreover, some patients with slowly evolving metastatic cancers could be given temporary breaks in their treatment at the discretion of the referring oncologist, with disease assessment extended to every 2–3 months, to avoid hospital admissions. Despite these measures, some patients with cancer will have to be admitted to hospital for systemic treatment or radiotherapy. The caregivers are advised to organise daily phone calls to patients with cancer planned to be admitted the following day, to ensure these patients do not present any symptoms compatible with COVID-19 before being admitted to oncology or radiotherapy wards. Patients with cancer who have symptoms of COVID-19 should be referred to departments specialised in the fight against COVID-19. To protect patients with cancer, open-space chemotherapy outpatient centres should integrate separation measures (eg, minimum space between seats, mobile walls, wearing of masks by patients and staff). Patients with cancer who do not have COVID-19, or who have recovered, can continue treatment, with the aforementioned adjustments to limit their presence at the hospital. If access to hospital cancer care is reduced because of requisition of facilities for management of patients with COVID-19, or if the likelihood of viral infection and life-threatening complications were deemed too high, a selection of patients to be admitted to hospital for cancer treatment, prioritised by type of care or treatment, might be required. The prioritisation in the management of patients will integrate the essence of curative or non-curative intent therapeutic strategy, age of patients, life expectancy, time since diagnosis (eg, early setting recently diagnosed or first-line treatment, or late setting in patients who have been treated with multiple lines of chemotherapy), and symptoms. The following priority order is proposed (but remains at the discretion of the patient's clinician and team): (1) patients with cancers managed with curative intent treatments (favouring those patients aged ≤60 years or life expectancy ≥5 years, or both); (2) patients with cancers managed with non-curative intent treatments, and aged 60 years or younger, or life expectancy of 5 years or more, or both, and in first-line of the therapeutic strategy (early setting); and (3) other patients with cancers managed with non-curative intent treatments, favouring those whose cancerous lesions extend or whose symptoms might jeopardise their lives quickly in the case of treatment discontinuation. Patients with cancer who need to be hospitalised for supportive care (eg, pain management, bacterial infection, or palliative care before death) could be referred to non-specialised cancer departments, or home care. In summary, patients with cancer are at high risk of severe and urgent clinical complications and patients with cancer with COVID-19 should discontinue their systemic anticancer treatments until complete resolution of symptoms (at clinician discretion). If hospital admission is deemed necessary, the patient should be admitted to departments involved in the fight against COVID-19 so that oncology and radiotherapy departments remain COVID-19-free sanctuaries. For patients with cancer without COVID-19, hospital admission for in-patient cancer care should be minimised, and management at home favoured. In a situation where available care facilities are scarce, prioritisation should involve the patients managed with curative-intent therapeutic strategies, and those with a life expectancy of 5 years or more, acknowledging that final decisions lie with the referring clinicians. Patients with cancer should be closely monitored owing to their susceptibility to SARS-CoV-2 infection. © 2020 Gustoimages/Science Photo Library 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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              Letter from Italy: First practical indications for radiation therapy departments during COVID-19 outbreak

              Introduction The number of people infected by SARS-CoV-2 is dramatically increasing worldwide. 1 The first person-to-person transmission in Italy was reported on February 21, 2020, and led to an infection chain that represents the largest outbreak outside Asia to date. 2 As of March 12, 2020, in Italy, there are 10,590 positive patients, 827 deaths, and 1045 healed, with numbers varying from hour to hour. The COrona VIrus Disease 19 (COVID-19) incubation interval varies from 5 to 14 days. 3 On January 30, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern, and the Italian government declared a public health emergency the next day. In the first phase, the government defined areas at different risk of infection: (1) high risk (“red zone or level 1 risk zone”); (2) mean risk (level 2 risk zone); and (3) the rest of the national territory, to be on alert but considered at low risk (level 3 risk zone). In the subsequent phases of the crisis, following the indications of a scientific and technical committee and in agreement with the WHO, the government finally decided to extend the “red zone” to the whole nation (March 8, 2020). All public hospitals faced an unprecedented emergency, with drastic changes in all organizational processes. All patients with cancer were consequently involved at different levels. We here report the experience of a group of Northern Italy radiation therapy departments that are located inside or very close to the first red zone and thus were the first to face the emergency. The main problem was how to continue activity while protecting patients, families, and health professionals from COVID-19. The authors met virtually with other radiation oncologists (see Acknowledgments) to share experiences and possible solutions, which were defined according to the local and national health authorities' indications. The indications we propose are structured as (1) definition of priorities, (2) problem analysis, and (3) suggested solutions. Priority 1: To Ensure Radiation Therapy Delivery To Patients with Cancer Problem analysis Radiation therapy is a life-saving treatment and should be guaranteed to all patients with cancer for whom it is indicated. 4 Suggested solutions Regional and hospital management must ensure the full functioning of Italian radiation therapy facilities, even in emergency conditions. Priority 2: To Ensure Safety of Health Professionals, Patients, and Caregivers Problem analysis A widespread infection among the staff working in a radiation therapy facility would effectively result in the closure of part of the activities. Failure to identify suspected or infected patients would increase the risk of spread to operators and patients undergoing treatment. Suggested solutions 1. If a triage point at the entrance to the hospital has not been activated, the indication is to carry out triage at access to the radiation therapy department to verify possible contact with COVID-19–positive patients and evaluate suspected symptoms in all others (patients, caregivers) accessing radiation therapy areas. 2. Provide a hydroalcoholic solution for hand disinfection at the entrance of the radiation therapy center. 3. Wear surgical masks, as recommended for all health professionals and patients according to WHO indications 5 and in particular if (1) the operator has respiratory symptoms, to protect others; and (2) if the operator is in close contact with a person who has respiratory symptoms, to protect herself or himself. 4. Use sterile disposable overalls (tunic and trousers), sterile disposable gown, FFP2 masks, clogs, and overshoes when treating patients with highly suspected or verified COVID-19, if they need to continue radiation therapy according to medical indications. Priority 3: Management of COVID-19 Suspected or Positive Patients Problem analysis We need practical guidelines on the appropriate behavior in the case of symptomatic, suspected, or verified COVID-19 patients accessing radiation therapy facilities. The triage evaluation should immediately report to the appropriate internal structures all patients who have symptoms possibly related to COVID-19, according to the existing regional regulations. Suggested solutions 1. If the patient has a cough, fever, or dyspnea owing to pre-existing morbidity, the patient should wear a protective mask, and radiation therapy should be continued. 2. If a new patient has confirmed COVID-19, do not start treatment. 3. If a patient on treatment is suspected to have onset of typical COVID-19 symptoms (cough and/or fever and/or dyspnea) and is waiting for diagnosis, stop treatment.∗ 4. If a patient on treatment is positive and is symptomatic, discontinue treatment.∗ 5. If a patient on treatment is positive but is asymptomatic, discontinue treatment.∗ 6. If a patient had confrimed COVID-19 but is declared healed by the infectious disease team, carefully plan to start or restart treatment according to cancer-related clinical conditions. If possible, COVID-19 patients should be treated at the end of the linear accelerator shift to limit the chances of infection for other patients. For confirmed COVID-19 patients (or patients waiting for diagnostic confirmation), the waiting and bunker areas should be sanitized at the end of the treatment session. Priority 4: Staff Reorganization Problem analysis It is necessary to avoid the usual professional behavior that favors the aggregation of all professional figures (medical doctors, nurses, therapists, physicists, administrative staff) working in the radiation therapy facility. Suggested solutions Medical, technical, nursing, physics and administrative staff must operate in separate areas, avoiding meetings that cannot ensure the safety distances required for prevention. In the event of infection of health professionals and therefore in the case of a severe shortage of staff: 1. report the current situation to the hospital management for help in solving the problem (eg, hiring new staff); 2. connect with other radiation therapy centers for external personnel to avoid interruption of ongoing therapies; 3. call for the service of retired personnel following the procedures already defined by the administrations; 4. redistribute patients to available machines—variation of fractionation, when feasible, is advised. Priority 5: Reduction of Patients' Access to Radiation Therapy Facilities Problem analysis It is advisable to limit the patients' access to the radiation therapy departments while maintaining optimal care conditions. Suggested solutions 1. Adopt hypofractionated regimens when possible. 2. Postpone follow-up visits. 3. Use palliative medical treatments at home instead of radiation therapy, when deemed to be of similar efficacy. 4. Delay nonurgent and deferrable radiation therapy treatments for patients with a better prognosis (eg, adjuvant radiation therapy for patients with breast cancer, radical radiation therapy for patients with low/intermediate-risk prostate disease). 5. Postpone therapies for benign and functional diseases. Discussion The COVID-19 spread in Italy was initially subtle and then unexpectedly rapid in its expansion. Because the first affected regions (especially Lombardia) were characterized by a very high population density, the virus dramatically spread throughout Northern Italy in a few weeks. As a consequence, all cancer therapy flows were altered: surgery, systemic therapies, and radiation therapy. The radiation therapy centers located in the hospitals that were the first to face the emergency gained rapid field experience and started monitoring the situation and collecting data. This report presents a few practical suggestions from the first 2 weeks of collective work under emergency conditions and is the result of a joint effort to ensure continuity of therapies while protecting patients, health professionals, and the general population. The indications were integrated with the WHO recommendations and with the local health authorities’ guidelines. The primary aim was to share information and provide guidance to radiation therapy departments worldwide. The report is mainly focused on how to deal with symptomatic, suspect, or confirmed COVID-19 patients undergoing radiation therapy. We identified five key priorities, here described, together with a brief analysis of the problems and the possible solutions.
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                Author and article information

                Contributors
                Journal
                Crit Rev Oncol Hematol
                Crit. Rev. Oncol. Hematol
                Critical Reviews in Oncology/Hematology
                Elsevier B.V.
                1040-8428
                1879-0461
                22 April 2020
                22 April 2020
                Affiliations
                Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Lebanon
                Author notes
                [* ]Corresponding author. hampig.kourie@ 123456hotmail.com
                Article
                S1040-8428(20)30110-4 102972
                10.1016/j.critrevonc.2020.102972
                7174983
                © 2020 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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