The impact of COVID 19 pandemic on pattern of cancer mortality in Najran, Saudi Arabia: a single-cancer center experience

Background: The aim of this paper is to compare the patterns and determinants of cancer mortality in Najran region before and after the COVID-19 epidemics. The association between cancer mortality and each of age, sex, site of cancer, stage, and the 30-days survival rate after the last dose of chemotherapy were assessed. Materials: & Methods: Adult cancer patients who died of cancer in King Khalid Hospital in Najran Saudi Arabia, were included in this retrospective observational study. We compared mortality patterns in a period of 6 months in 2020 (March to August) with the corresponding period of 2019. Results: : 50 dead adult cancer patients were included, 24 in 2019 and 26 in 2020. Among them, 21% vs 42% were younger than 65 years of age;61% vs 62% were males, for the years 2019 & 2020 respectively. The top three killers in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas. About 16.7% of patients died within 30 days of receiving anti-cancer treatment in 2019 in comparison with 7.7% in 2020. The difference in the 30-days mortality after receiving anti-cancer treatment was not statistically significant between 2019 and 2020 (p = 0.329). Conclusion: The Year 2020, the time of the COVID-19pandemic, was not associated with a significant increase in short-term mortality among patients with malignancy in Najran, Saudi Arabia. Our results generally reflect the crucial role of strict preventive national measures in saving lives and warrants further exploration.


Introduction
Cancer is the main barrier for improving life expectancy. Factor like aging and changes in lifestyle are the main risk factors associated with increasing incidence and mortality of cancer 1 . Due to serious outcomes associated with COVID-19, it is expected to nd higher levels of mortality in cancer patients than those in normal population. Patients with cancer are usually susceptible to infectious diseases, and it is known that infections are a leading cause of death among this patient population 2 . Cancer may result in a weakened immune system due to the negative effect on immune cells, affecting their quantity or quality, as is the case in leukemia or lymphoma. Cancer therapy itself, whether it is surgery, radiotherapy, or chemotherapy, disturbs the immune system in various ways and results in an increased risk of infection 3 .
Globally, cancer is the second leading cause of death with over 10 million death in 2018 4,5 .
Patients with cancer are likely to have other comorbidities, whether due to age or exposure to cancer risk factors, such as smoking, obesity, and other lifestyle choices. Chronic diseases and comorbidities were identi ed previously as risk factors for COVID-19mortality. All these factors lead to the predisposition of patients with cancer to a high risk of acquiring infectious diseases with a worse outcome than patients without cancer 6 .
The rst COVID-19 case was con rmed in Saudi Arabia on 2 March 2020. The total number of reported cases of COVID-19 has reached 357,872 cases, recovered 347,513, with 5,919 deaths (last updated on 2 December 2020). Whilst there are still no data available on COVID-19 cases by their age group and other demographic factors in Saudi Arabia, the lower mortality rate might be a re ection of the young population in the kingdom and the strict preventive national measures 78 .
There is accumulating evidence that suggests that patients with cancer have an increased risk for COVID-19 infection and subsequent morbidity and mortality 5 .
The aim of this paper is to describe the pattern of cancer mortality in Najran region during the COVID-19 epidemics and to explore the association with age, sex, site of cancer, stage, and the interval between the last dose of chemotherapy given within the last 30 days before death.

Materials And Methods
Adult cancer patients who died of cancer in King Khalid Hospital in Najran Saudi Arabia, irrespective of the cancer stage and treatment type, were included in this retrospective observational study. The target population included adults aged ≥ 18 years who were histologically diagnosed with cancer, irrespective of the cancer stage, and class of anti-cancer treatment received, aiming to explore the association with age, sex, site of cancer, stage, and the interval between the last doses of chemotherapy given within the last 30 days before death. Cases with non-histologically con rmed diagnosis with cancer, or have incomplete record were excluded.
We selected the start date of March 2020 in concordance with the announcement of the rst con rmed COVID-19 case in Saudi Arabia, while the end date was August 31 2020 in concordance with the drop of the cases & resumption of the near-normal life. We compared these 6 months in 2020 (March to August) with the corresponding period of 2019. Data were extracted from the electronic medical records based on the monthly mortality report for the medical department. Patient data con dentiality was maintained, and the declaration of Helsinki was followed.
Results 50 dead adult cancer patients were included, 24 in 2019 and 26 in 2020 (Fig. 1). Among them, 21% vs 42% were younger than 65 years of age (Fig. 2); 61% vs 62% were males, for the years 2019 & 2020 respectively (Fig. 3). Regarding the metastatic stage, 91% vs. 85% for the years 2019 & 2020 respectively (Fig. 4). The top three killers in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas (Fig. 5). About 16.7% of patients died within 30 days of receiving anti-cancer treatment in 2019 in comparison with 7.7% in 2020 (Fig. 6). The difference in the 30-days mortality after receiving anti-cancer treatment was not statistically signi cant between 2019 and 2020 (p = 0.329).The main direct cause of death in the two years was cancer progression (Fig. 7), while COVID-19was the direct cause in only 3% of the cases (Fig. 8).

Discussion
To the best of our knowledge, this study is the rst trial evaluating the effect of the COVID-19pandemic on cancer patients in Najran-Saudi Arabia 9 . Our study revealed a comparable mortality for patients with cancer patients before and during COVID-19 pandemic. There is a doubling of the death risk in the year 2020 among patients younger than 65 (42% vs 21%), this can be explained by the death of two young lymphoma cases with chest infection of unknown etiology 5 .
Korean study revealed a death rate of 64% in patients with chronic comorbidities during the pandemic, including those with cancer. The low mortality among our patients can be explained by the implementation of extra precautionary measures to ensure that these vulnerable patients are not exposed to the virus 10 .
The limitation of our study is the small number of patients and the retrospective nature of the study design. Covid 19 testing was done only for the suspected cases as per the regulation of the ministry of health.
It is prudent to ensure that all possible precautionary measures be implemented to protect oncology patients from being exposed to Covid 19; developing additional protective measures, such as a vaccine, is important to prevent infection in this vulnerable population. Developing effective antiviral treatment will help in saving the lives of affected patients 11 .

Conclusions
The Year 2020, the time of the COVID-19pandemic, was not associated with a signi cant increase in the short-term mortality among patients with malignancy in Najran, Saudi Arabia. Our results generally re ect the crucial role of strict preventive national measures in saving lives and warrants further exploration.

Declarations
Ethics approval and consent to participate This study was conducted after approval of the Cancer Research Committee in the oncology Department at King Khalid Hospital in Najran.
All authors have approved the manuscript for submission.
The content of the manuscript has not been published, or submitted for publication elsewhere. 21% vs 42% were younger than 65 years of age The top three killers in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas