Emergency oncology admissions during COVID-19 pandemic: a major institution experience from Saudi Arabia

Elemam O.*1, Tashkandi E.2, Abdelkhalek S.3, Shalaby I.4, Baraka R.5

Summary. Background: The WHO has declared the coronavirus disease 2019 (COVID-19) pandemic in March 2020. Cancer patients are considered a highly susceptible group. The effect of this pandemic on cancer mortality is still unknown. Aim: Our aim is to know whether or not we need to postpone cancer treatment during viral pandemics in the future. Materials and Methods: A retrospective observational study from March 1, 2020 to June 1, 2020, included cancer patients on active treatment, who have been admitted to our oncology center through the emergency unit, and patients who received oncology treatment in the outpatient treatment unit. COVID-19 positive cases were identified based on polymerase chain reaction testing of nasopharyngeal swab. Results: A total of 1300 patients was included in the study, 1096 patients attended the outpatient clinics, 204 patients were admitted to our oncology floor for emergency care. The cancer diagnosis was mainly breast cancer, followed by colon cancer. The main cause of emergency room visit was mainly fever followed by pain. Admission diagnosis was mainly disease progression followed by symptom control, COVID-19 infection, and febrile neutropenia. 1288 cycles of anticancer therapy were provided to 513 patients in the outpatient treatment unit. Three out of the nineteen patients who had a confirmed COVID-19 infection (16%) died not only due to infection, but also disease progression. Conclusion: Cancer treatment is not a risk factor for COVID-19 infection or its complications. Cancer treatment should not be interrupted during viral pandemics and every effort should be made to give cancer patients the standard of care.

DOI: 10.32471/exp-oncology.2312-8852.vol-43-no-1.15964

Submitted: November 9, 2020.
*Correspondence: E-mail: omymaelemam@gmail.com
Abbreviations used: COVID-19 — coronavirus disease 2019; ER — emergency room; PCR — polymerase chain reaction; SARS-CoV-2 — severe acute respiratory syndrome-related coronavirus 2.

Сoronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly discovered coronavirus — severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in Wuhan, China, in December 2019, and then two months later in Europe. The WHO has declared it a pandemic in March of 2020. Initially, all mortality reports were mainly in elderly people and people with co-morbidities. Cancer patients are considered a highly susceptible group in the current COVID-19 pandemic mainly due to cancer treatment that causes neutropenia in most cases. According to an analysis of Italian patients, 20% of those who died from COVID-19 in the country had active cancer in the last five years [1, 2]. The clinical characteristics of cancer patients who got infected with COVID-19 are unknown [3]. In our cancer center, the treatments of patients with chemotherapy or immunotherapy were not stopped since we assumed that the risks of infection were disparately lower than the risks of the sequela caused by treatment delaying of aggressive forms of cancer. We shifted some patients who are on a routine follow-up to limit exposure and avoid overcrowding in the waiting rooms. One of the theories about the causes of death from COVID-19 is the cytokine storm theory, on other hand, one of the lethal side effects of immunotherapy drugs is pneumonitis [4].

We need to know how the virus will affect the cancer mortality and if we need to hold these drugs during viral pandemics in the future.

MATERIALS AND METHODS

This was a retrospective observational study carried out from March 1, 2020 to June 1, 2020 at King Abdullah Medical City, Oncology Center in Makkah. The study included a total of 1300 patients including 1096 who attended the outpatient clinic and treatment unit in addition to 204 patients who admitted to the oncology floor through the emergency unit during the study period. Patients were identified through a retrospective review of medical records excluding patients on palliative care and those with no detailed clinical information.

The data collected were the characteristics of the patients who received anticancer therapy in the outpatient treatment unit and clinical data of the patients admitted to the oncology floor including date, cause, and outcome of admission. The data also included patients’ age, gender, diagnosis, and treatment data. The treatment data including type of anticancer treatment, date of last chemotherapy cycle and date of the latest radiotherapy.

We identified the COVID-19 positive cases based on polymerase chain reaction (PCR) testing of nasopharyngeal swab and reviewed their clinical data in detail.

Moreover, this research protocol was approved by the Institutional Review Board Committee. Since the study performed is retrospective, we obtained a waiver of informed consent from IRB.

RESULTS AND DISCUSSION

From March 1st to June 1st, we treated 1096 patients in outpatient clinics, 845 females and 251 males with age range from 14 to 95 years. The most common diag­nosis was breast cancer 58% followed by colorectal 11% then lymphoma 6%. Chemotherapy was the active oncology treatment in 44% followed by hormonal therapy in 39% then targeted therapy in 13% and immunotherapy in 3%. Comorbidities, mainly diabetes and hypertension were reported in 62% of cases. Most of the patients in the outpatient setting were in good performance status I followed by II and nearly half of them were in stage IV of their disease (Table 1). Out of those patients, 513 received intravenous anti-cancer treatment either chemotherapy, immunotherapy, target therapy, or anti-angiogenesis. A total of 1288 cycles were administered; names of protocols are presented in Figure.

Table 1. Characteristics of patients attending oncology clinics for active cancer treatment

Number of patients 1096 % Cancer
Age Breast 635 58%
range 14–95 Colorectal 120 11%
median 54 Lymphoma 62 6%
Gender Lung 29 3%
female 845 77 Head and neck 31 3%
male 251 23 Liver 1 0.1%
BMI Pancreatic-biliary 22 2%
range 13–58.9 Gastro-esophageal 9 1%
median 27.9 Kidney 13 1%
Comorbidity Prostate 23 2%
no 675 62 Testis 0 0%
yes 421 38 Gynecological 74 7%
Most common comorbidities Sarcoma 14 1%
asthma 7 1 CNS 6 1%
CKD 7 1 Neuroendocrine 5 0.5%
DM 135 12 Thyroid 1 0.1%
DVT 11 1 Other 25 2%
HTN 141 13 Class
IHD 24 2 Chemotherapy 481 44%
other 72 7 Hormonal 431 39%
PE 14 1 Targeted 139 13%
ECOG Immunotherapy 30 3%
1 606 55 Number of Cycles
2 286 26 IV Chemotherapy/immunotherapy 1288
3 65 6 Immunotherapy 77
4 10 1
Stage
Stage I 79 7
Stage II 209 19
Stage III 325 30
Stage IV 482 44
Notes: PE — pulmonary embolism, DM — diabetes, DVT — deep venous thrombosis, HTN — hypertension, IHD — ischemic heart disease, CKD — chronic kidney disease.
 Emergency oncology admissions during COVID 19 pandemic: a major institution experience from Saudi Arabia
Figure. Outpatient anticancer protocols used to treat our patients during the pandemic. Only protocols with 10 or more counts are placed in the graph

In the same study period, we admitted 204 patients to our oncology floor. Out of them 88 were males, 116 females. 38% have additional comorbidities. The cancer diagnosis was mainly breast cancer followed by colon cancer. Ninety-nine patients have comorbidities in addition to the cancer diagnosis. Causes of emergency room (ER) visits were mainly fever followed by pain. Admission diagnosis was mainly disease progression followed by symptom control, followed by COVID-19 infection, followed by febrile neutropenia, and bacteremia. Admission was related to therapy in 19 cases mostly due to febrile neutropenia, two cases with drug-induced pancytopenia one case of drug-induced diarrhea, one case of erlotinib toxicity, and one case of pneumonitis related to immunotherapy. COVID-19 infection was suspected in 80 cases and COVID-19 swab was done for all of them. Neutropenia was observed in 20 cases. At admission, 10 patients were admitted to the ICU, 28 patients died. The cause of death was COVID-19 infection in three cases (Table 2).

Table 2. Characteristics of emergency oncology admissions

Total number of admissions 204 COVID infected patients Cause of ER visit Neutropenia at presentation COVID infected patients
Age Range 17–90 43-84 Fever 66 (32%) Yes 20 (10%) 1 (5%)
Median 55 55 Pain 56 (27%) No 184 (90%) 18 (95%)
Male 88 (43%) 7 (37%) SOB 36 (18%) COVID-19 suspected COVID infected patients
Female 116 (57%) 12 (63%) Cough 27 (13%) Yes 80 (39%) 19 (100%)
Diagnosis: COVID infected patients Diarrhoea 7 (3%) No 124 (61%) 0
Breast cancer 45 (22%) 8 (4%) Poor oral intake 6 (3%) Active oncology treatment within 4 weeks COVID infected patients
Colon/rectum 34 (17%) 4 (2%) Dehydration 3 (1%) Chemotherapy 54 (26%) 8(42%)
Lymphoma 21 (10%) 1 (0.5%) Decreased level of consciousness 3 (1%) Hormonal 26 (13%) 5(26%)
Lung cancer 18 (9%) 2 (1%) Poor general condition 3 (1%) Immunothe­rapy 11 (5%) 1 (5%)
Pancreatic cancer 13 (6%) 1 (0.5%) Bleeding 1 (1%) CD4/6 inhi­bitor 9 (4%) -
Ovarian cancer 8 (4%) - Admission diagnosis: TKI 2(1%) -
Uterine cancer 7 (3%) - Disease progression 56 (27%) ICU admission COVID infected patients
Urinary bladder 6 (3%) - Pain and symptom control 21 (10% Yes 10 (5%) 2 (11%)
Comorbidities: COVID infected patients COVID-19 infection 19 (9%) No 194 (95%) 17 (89%)
Yes 99 (49%) 12 (63%) Febrile neutropenia 14 (7%) Death COVID infected patients
No 105 (51%) 7 (37%) Bacteraemia 11 (5%) Yes 28 (14%) 3 (16%)
Metastatic disease COVID infected patients Pleural effusion 9 (4%) No 176 (86%) 16 (84%)
Yes 140 (69%) 12 (63%) Brain metastasis 6 (3%) Cause of death
No 64 (31%) 7 (37%) Other 68 (33%) COVID related 3 (1%) 3 (16%)
Treatment related admission Non COVID related 25 (12%)
Yes 19 (9%)
No 185 (90%)

Nineteen patients had confirmed COVID-19 infection with PCR testing. Most of them presented with fever, cough, shortness of breath (SOB), and two with diarrhea, 12 have comorbidities in addition to cancer. Out of them 3 died not only with infection but also with disease progression (see Table 2). Five of the COVID-19 infected patients received oncology treatment within 4 weeks. Four out of the five recovered from infection and one patient died due to disease progression in addition to COVID-19 infection, their clinical data are summarized in Table 3.

Table 3. Characteristics of COVID-19 infected patients who received chemotherapy within 4 weeks from infection

Patient Age Sex Diagnosis Metastasis Comorbidities Symptoms at presentation Last oncology treatment Interval from last cycle ICU admission Outcome and cause of death Disease res­ponse
1 59 F Breast cancer No Chronic cardiomyopathy, DM HTN Cough, fever Weekly paclitaxel One week No Recovered CR
2 59 M Pancreatic cancer Yes DM HTN Fever Gemcitabine One week No Death PD
3 55 F Mycosis fungoides Yes None Diarrhea, nausea, generalized body aches Gemcitabine /vinblastine 20 days No Recovered PD
4 62 F Breast cancer No None Fever, cough EC Three weeks No Recovered CR
5 54 M Colorectal cancer Yes None Fever, dry cough Cetuximab/irinotecan/capecitabine 1 month No Recovered PD
Notes: F — female; M — male; DM — diabetes; HTN — hypertension; CR — complete response; PD –progressive disease; EC — Epirubicin/cyclophosphamide.

Makkah is the holy capital of Saudi Arabia, a place where people in millions from all over the world visit all over the year. On March 2, the first case of COVID-19 virus infection was reported in Saudi Arabia, then the number of cases progressively increased, despite the early and strictly enforced curfew. The number of cases was highest in Makkah [5, 6]. We assumed that patients with cancer are at increased risk of infection with COVID-19 and will most likely have adverse outcomes with this infection due to increased age, tendency to have more comorbidities, immunosuppression due to cancer treatment, including steroids in addition to their lower performance status. Despite the current pandemic, we continued the standard cancer care as delaying cancer treatment can have an adverse outcome. Nevertheless, we managed to give more than one thousand chemotherapy cycles during this time without any major or unexpected complications.

Many cancer centers held their services in response to early reports from China. When a retrospective cohort study was reported, the study included cancer patients with confirmed COVID-19 infection. Twenty-eight patients were included. Fifteen (53.6%) patients had severe events and the mortality rate was 28.6%. If the last cancer treatment was within 14 days, the risk of developing severe events was significantly increased (HR = 4.079, 95% CI 1.086–15.322, p = 0.037). The authors recommended the avoidance of immunosuppressive medications [7]. Researchers also found that microvascular COVID-19 lung vessels­ obstructive thromboembolic syndrome causing micro clots is one of the main theories of the cause of death in COVID infection and it is well known that cancer patient is more prone to thrombosis not only by disease but also by medication like chemotherapy and antiangiogenic agents [8].

We collected all the oncology admissions during this pandemic aiming to identify major complications to our cancer management. Two hundred and four cases were admitted over three months. 19 admissions were treatment-related 56 admissions were related to disease progression. We are reporting here only 19 cases of COVID-19 infection occurred in three months period after the pandemic has been declared. All our COVID positive cases were hospitalized as per our policy and not due to the severity of their conditions.

The mortality rate among our COVID cases was 16%. Five of COVID infected cases received chemotherapy within the last 4 weeks before catching COVID-19 infection. Only one of them died and the others recovered. This is in agreement with a retrospective study from a Pakistan reported the outcome of cancer patients diagnosed with COVID-19 infection within 4 weeks of receiving anticancer treatment. This study concluded that mortality in cancer patients with COVID-19 is mainly driven by the advanced stage of disease and chemotherapy is not significant risk factor [ 9].

Multiple oncology centers reported high mortality from COVID-19 infection among cancer patients on active treatment. A large cancer center in Saudi Arabia published their data of 19 COVID-infected cancer patients and reported a very high mortality of 39% [10]. In the CCC-19 (COVID-19 and Cancer Consortium) one of the largest world datasets investigating the risk of death in cancer patients with COVID-19 infection was reported in the ASCO meeting 2020. The study reported 928 patients with cancer and confirmed COVID-19 infection by RT-PCR including 21% breast cancer, 16% prostate cancer, 12% gastrointestinal cancer, 11% lymphoma, and 10% thoracic malignancies. The CCC-19 study reported a 13% mortality rate and 14% ICU admission. Independent factors for mortality in CCC-19 were older age, poor performance, active chemotherapy and the presence of comorbidities. In China, the mortality rate was higher in cancer patients compared to a non-cancer patient and in New York mortality rate were significantly higher in cancer patients 25% to 14% in non-cancer patients [11–13].

The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) study reported 400 thoracic cancer patients with confirmed COVID-19 RT-PCR, clinically suspected infection, and radiologically suspected cases. The authors concluded that patients on steroids and anticoagulation, prior to the diagnosis, were at increased risk of mortality from COVID-19, and prior administration of chemotherapy as a unique modality or in combination with immune checkpoint inhibitors was associated with increased risk of death while immunotherapy and tyrosine kinase inhibitors were not [14].

On the other hand, a recent study reported from the UK strongly supports our finding, they explored the effect of anticancer treatment during the ­COVID-19 pandemic and with multivariate analysis, they concluded that the administration of chemotherapy within 4 weeks before confirmed COVID-19 infection is not a signi­ficant factor to more severe disease or a predictor of death from COVID-19 infection. They observed the same for other therapies like immunotherapy and target therapy [15].

A little is known about the effect of immune checkpoint inhibitors on COVID-19 infection in patients with cancer. In our study a total of 1288 anti-cancer treatment cycles were successfully administered, including 77 cycles of immunotherapy without unexpected complications. Among thirty patients treated with immunotherapy, only one diagnosed with COVID infection and recovered without complications. This is in contrast to a study from New York found that ­COVID-19 infected cancer patients who received immune checkpoint inhibitors had a statistically significant increase in risk of hospitalization and this was based on the treatment of 31 patients [16].

Our study has limitations being a single center study with few cases of COVID-19 infection, however, the number of cases who received anticancer treatment is large and representing most of the protocols used in cancer treatment.

According to our data, cancer treatment is not a risk factor for COVID-19 infection or its complications. Cancer treatment should not be interrupted during pandemics and every effort should be made to give cancer patients the standard of care. In this study, most of the COVID-19 infected patients recovered completely without complications, and deaths were not only due to COVID-19 infection but also because of disease progression. Particularly during pande­mics cancer treatment prioritization should balance interventions based on the magnitude of benefits. Treatment guidelines should be regularly updated to fulfill this concept. This requires active collaboration between experts.

ACKNOWLEDGMENTS

The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors declare no competing financial interest.

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УРГЕНТНА ГОСПІТАЛІЗАЦІЯ ОНКОЛОГІЧНИХ ХВОРИХ ПІД ЧАС ПАНДЕМІЇ COVID-19: ДОСВІД ВЕЛИКОГО МЕДИЧНОГО ЦЕНТРУ САУДІВСЬКОЇ АРАВІЇ

O. Елемам1, 2, *, E. Ташканді1, 3 С. Абдельхалек1, 4, I. Шалабі5, Р. Барака6

1Онкологічний центр, медичне місто ім. короля Абдалли, Мекка 24246, Саудівська Аравія
2Онкологічний центр, Університет Мансура, Мансура 35516, Єгипет
3Медичний коледж, Університет Умм Аль-Кура, Мекка 24246, Саудівська Аравія
4Відділення променевої терапії, Університет Мансура, Мансура 35516, Єгипет
5Відділення радіології, медичне місто ім. короля Абдалли, Мекка 24246, Саудівська Аравія
6Факультет природничих наук, Університет штату Колорадо, Форт-Колінз 80523, США

Стан питання: ВООЗ оголосила пандемію коронавірусної хвороби 2019 (COVID-19) у березні 2020 р. Вважається, що хворі на рак є дуже вразливими до цієї інфекції. До цього часу невідомо достеменно, чи впливає пандемія на показники смертності внаслідок онкологічних захворювань. Мета: З’ясувати на майбутнє, чи слід відтерміновувати лікування онкологічних хворих під час вірусної пандемії. Матеріали та методи: Ретроспективне обсерваційне дослідження, яке охоплювало період з 1 березня до 1 червня 2020 р., включало хворих на рак у фазі активної терапії, які надходили до нашого онкологічного центру у зв’язку з необхідністю у невідкладній допомозі або ж отримували лікування в амбулаторному відділенні. COVID-19-позитивних хворих виявляли за результатами полімеразної ланцюгової реакції в назофарингеальних мазках. Результати: Усього в дослідження було включено 1300 хворих, з них 1096 лікувались амбулаторно, і 204 хворих було госпіталізовано у зв’язку з необхідністю невідкладної допомоги. Серед діаг­нозів переважав рак молочної залози, на другому місці був рак товстої кишки. Основною причиною звернення за невідкладною допомогою були лихоманка та біль. Основним діагнозом під час надходження до клініки було прогресування онкологічного захворювання. Далі серед причин звернення за допомогою були необхідність усунення симптомів, інфекція COVID-19 та фебрильна нейтропенія. Амбулаторно було проведено загалом 1288 циклів протипухлинної терапії 513 хворим. 3 з 19 хворих із підтвердженим COVID-19 (16%) померли, але не тільки через COVID-19, а також і через прогресування онкологічного захворювання. Висновок: Протипухлинне лікування не є фактором ризику щодо COVID-19 або його ускладнення. Тому терапію онкологічного захворювання не слід переривати під час пандемії. Навпаки, слід робити все можливе, аби надавати онкологічним хворим у цій ситуації лікування згідно зі стандартами.

Ключові слова: госпіталізація онкологічних хворих, COVID-19, протипухлинна терапія.

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