Prevalence of Anxiety and Depression Among Cancer Patients During the COVID-19 Pandemic: a Systematic Review and Meta-analysis

Background: The COVID-19 pandemic has signicantly affected patients’ access to healthcare. Patients with malignant tumors have experienced treatment interruptions and diculties in seeking medical attention, and these have affected their mental health. The objective of this review is to evaluate the current evidence on the prevalence of depression and anxiety in cancer patients during the COVID-19 pandemic. Methods: We searched the EMBASE, PubMed, WHO COVID-19 database, Cochrane Library, Web of Science, CBM, CNKI, Wanfangdata, CQVIP, and CBM electronic databases for relevant studies published from the rst available day to June 30, 2020. Two researchers independently screened the literature based on predetermined criteria and assessed the risk of bias in each study. Random-effects meta-analyses was used to estimate the pooled prevalence of anxiety and depression among patients with malignant tumors. The review protocol has been registered in PROSPERO (CRD42020196421). Results: Nine eligible studies on 2,335 patients with malignant tumors were included, all of which were cross-sectional studies. The pooled prevalence of anxiety was 52.94% (95% CI: 36.98%-68.91%, I 2 =98.6%) in 9 studies, and the pooled prevalence of depression was 43.25% (95% CI: 25.85%-60.85%, I 2 =98.8%) in 6 studies. Conclusions: Evidence shows that a considerable proportion of patients with malignant tumors suffered from emotional distress during the COVID-19 pandemic. It is important to solve the problem of interruption or delay of treatment and strengthen psychological interventions for patients with malignant tumors during the pandemic.


Introduction
In December 2019, cases of pneumonia of unknown etiology were detected in Wuhan City, Hubei Province of China and attracted intense worldwide attention 1 . On March 11 2020, the World Health Organization (WHO) declared the COVID-19 a global pandemic 2 . During the COVID-19 pandemic, delivery of cancer treatment 3,4 , cancer care 5,6 , and cancer screening 7,8 has become challenging. Many cancer patients suffer from interruption or delay of cancer treatment due to the pandemic crisis, and while this may reduce the risk of COVID-19 infection and death, it may also increase cancer-speci c mortality 9 .
Anxiety and depression are the common types of emotional distress in cancer patients. Among cancer survivors, the prevalence of anxiety and depression is higher than that in the general population [10][11][12] . In two major provincial cancer centers of Canada, 19.0% of cancer patients showed clinical anxiety and another 22.6% showed subclinical symptoms, 12.9% of cancer patients reported clinical depression symptoms and an additional 16.5% displayed subclinical symptoms 10 . Negative emotions such as anxiety and depression can bring negative effects to cancer patients, such as increased side effects of treatment, slow physical recovery, reduced quality of life and survival rates [13][14][15] .
The risk of COVID-19 infection and the interruption of cancer treatment are likely to aggravate the anxiety and depression symptoms of cancer patients and further affect their clinical cancer prognosis. To our knowledge, there has not been a systematic review done on the prevalence of anxiety and depression in cancer patients during the COVID-19 epidemic. The prevalence gures reported thus far also varied widely. Therefore, the purpose of this systematic review and meta-analysis is to understand the impact of the COVID-19 outbreak on the prevalence of anxiety and depression in patients with malignant tumors, and to provide a basis for the need for psychological intervention for this group.

Protocol and guidance
This systematic review was based on the PRISMA statement 16 following the recommendations of the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group 17 . The review protocol has been registered at PROSPERO (CRD42020196421) and can be obtained online (https://www.crd.york.ac.uk/prospero/).

Research strategy and selection criteria
Two researchers (Zewen Zhou, Qiuyan Mo) independently searched electronic databases such as the EMBASE, PubMed, WHO COVID-19 database, Cochrane Library, Web of Science, CBM, CNKI, Wanfangdata and CQVIP for relevant studies from the rst available day to June 30, 2020. These studies have reported the prevalence of depression and anxiety during the COVID-19 pandemic. The following search terms were used: ("cancer" OR "neoplasms" OR "malignancy" OR "tumor" OR "carcinoma") and ("2019 novel coronavirus" OR "COVID-19" OR "SARS-CoV-2" OR "2019-nCov" OR "novel coronavirus pneumonia") and ("depression" OR "anxiety" OR "mental health" OR "psychological"). "Snowball sampling" was performed on each retrieved article by searching reference lists and citation tracking. The research language of the search was limited to English and Chinese. The two researchers independently evaluated the full text according to predetermined criteria.
The subjects were set as those aged 18 years and above, currently or previously diagnosed with malignant tumors, and are living in countries or regions affected by COVID-19. Only studies that used validated assessment methods to assess the prevalence of anxiety and depression were eligible for inclusion.
Studies that use broad terms such as "psychological distress" or "emotional distress" were excluded.
Data extraction and quality assessment The following data were independently extracted from each article using a standardized format: author's name, country or region, sample size, number of males or females, disease characteristics, percentage of anxiety or depression, assessment methods used and their cut-offs. If such information were not reported, the necessary calculations were made where possible (for example, the number and percentage of patients with malignant tumors). When encountered with inconsistent data, we checked the accuracy of the data against the original literature. Disagreement was resolved through discussion. Uncertainties or missing data in the literature were veri ed or supplemented by contacting the author.
According to the Agency for Healthcare Research and Quality (AHRQ) recommendations, an 11-item checklist for cross-sectional studies were used to assess the methodological quality of studies by two authors independently 18 . If it was answered 'YES', the item was scored '1'; if it was answered 'UNCLEAR' or 'NO', the item was scored '0'. The third author (Xianguo Zhou) resolved disagreements. Methodological quality of study was assessed as follows: low quality = 0-3; moderate quality = 4-7; high quality = 8-11.

Data synthesis and statistical analysis
For the purpose of the current study, STATA 15/SE (Stata Corp LP, College Station, TX, USA) was used for statistical analysis. As it is impossible to assume a true effect size due to the different study populations, regions, and assessment methods across studies, a random-effects model (DerSimonian & Laird, 1986) 19 was used to extract the pooled prevalence. Tests of heterogeneity were conducted using I 2 statistics and the Cochran's Q test. Sensitivity analysis was performed by subtracting each study and calculating the pooled prevalence of the remaining studies to identify studies that may severely affect the pooled prevalence 20 . High heterogeneity was de ned as I 2 > 75% and P < 0.05 was regarded to be statistically signi cant.

Results
Eligible studies and study characteristics A PRISMA diagram was used to illustrate the study selection in Fig. 1. After searching electronic databases, 161 relevant studies were found. Among these studies, 70 duplicate studies were removed, and 74 studies were excluded after reviewing their titles and abstracts. 17 studies were identi ed and searched for full-text screening, of which 8 studies did not meet the inclusion criteria. Among the 8 studies, 1 was not conducted on patients with malignant tumors, and 7 did not assess the prevalence of anxiety and depression. Eventually, 9 studies 21-29 with 2,335 participants were included in the analysis. All studies were cross-sectional studies and reported the prevalence of anxiety and depression in patients with malignant tumors during the COVID-19 pandemic (Fig. 1). Table 1 summarizes the characteristics of each study, including the author's name, sample size, country or region, number of males, assessment methods used and their cut-offs, and the percentage of anxiety or depression cases. Of these 9 studies, 7 were conducted in Mainland China, 2 of which were conducted in Wuhan 22,23 , 1 study was conducted in Hong Kong, China 21 , and the other was conducted in New York, USA 24 . All selected studies were evaluated for methodological quality. One study was of high quality, one study was of low quality, and the other studies were of medium quality (Table 1). Note: SAS = Zung Self-Rating Anxiety Scale; HADS = Hospital Anxiety and Depression Scale; PHQ-9 = Patient Health Questionnaire-9; GAD-7 = Generalized Anxiety Disorder Assessment; SDS = Zung Self-Rating Depression Scale.

Anxiety Prevalence
The prevalence of anxiety was estimated in 9 studies [21][22][23][24][25][26][27][28][29] . As shown in Fig. 2 Questionnaire-9 (PHQ-9) scale. In the sensitivity analysis, after removing each study in turn, the merger rates of the remaining studies were evenly distributed on both sides of the total merger rate. Therefore, excluding the differences between the studies had little effect on the overall merger rate (Fig. 3).

Depression Prevalence
As shown in Fig. 4, 7 27 used the Generalized Anxiety Disorder Assessment (GAD-7) scale. In the sensitivity analysis, after removing each study in turn, the merger rates of the remaining studies were evenly distributed on both sides of the total merger rate. Therefore, excluding the differences between the studies had little effect on the overall merger rate (Fig. 5).

Discussion
The COVID-19 pandemic has made a profound impact on all aspects of society. For humans, these include not only physical but also psychological effects. Collecting high-quality data to assess the mental health impact of the COVID-19 pandemic on the entire population, especially vulnerable groups (such as cancer patients) is an urgent area for research 24 . This aid understanding of the mental health status of vulnerable groups and can provide a basis for psychological intervention during a pandemic.
This systematic review and meta-analysis of 9 cross-sectional studies with 2,335 participants provided evidence. Our results showed that the prevalence of anxiety and depression in patients with malignant tumors was 53.17% and 46.08% respectively. It revealed that factors such as fear, worry, and treatment interruptions during the COVID-19 pandemic resulted in a considerable proportion of patients with malignant tumors experiencing anxiety and depression. This result is not only higher than that during the non-epidemic period 10,11 , but also higher than the prevalence of anxiety and depression in the general population and healthcare workers during the COVID-19 pandemic [30][31][32] . Studies have shown that anxiety and depression not only reduce the compliance of cancer patients with drug treatment 33,34 , but also affect the body's immune system to recognize and kill tumor cells, leading to immunosuppression and increasing their risk of death 35,36 . In recent years, due to the high prevalence of anxiety in cancer patients, it has been designated as the sixth vital sign of cancer patients 37,38 and many countries have adopted anxiety as a routine screening item for cancer patients 39 and its reduction as an index of e cacy evaluation 40,41 . Therefore, in response to the rising prevalence of anxiety and depression in cancer patients caused by the sudden international public health emergency, the COVID-19 pandemic, early targeted intervention measures should be considered 41 .
Early, effective, and timely intervention can not only reduce the incidence of unhealthy emotions and their psychological pressure in cancer patients, but also help patients receive anti-tumor and symptomatic supportive treatment with a better attitude and improve their treatment e cacy and prognosis. In recent years, Mindfulness-based Therapy (MBT) has become an increasingly popular psychological intervention method for cancer patients. The current research results show that the anxiety, depression, and stress of different types of cancer patients were signi cantly reduced after receiving MBT, with improved quality of life, post-traumatic growth, and mindfulness attitudes [42][43][44] . In addition, previous studies have also proposed the use of psychological education 45 , group therapy 46 , structured counseling 47 , self-esteem training 48 , and cognitive behavioral therapy 49 to provide psychological interventions for cancer patients.
These measures have a positive effect on alleviating the anxiety and depression of cancer patients.
However, there is an urgent need for more rigorous research before recommending speci c psychological interventions for cancer patients 50 .
It is worth noting that the results of our study show a high level of heterogeneity, which means that the prevalence of anxiety and depression is quite different in the included studies. Due to limited conditions, we only performed a subgroup analysis of the assessment methods. Although we still observed large heterogeneity, the sensitivity analysis suggests that when a certain study is removed, we can still obtain robust results. Heterogeneity between studies may be due to differences in many factors such as the severity of cancer, cancer treatment status, the prevalence of COVID-19 in different countries or regions, or how cancer patients are treated in different regions.
To our knowledge, the present study is the rst systematic review and meta-analysis of the comprehensive prevalence of anxiety and depression in cancer patients during the COVID-19 outbreak. However, our review still has some limitations. Since various studies are cross-sectional, the prevalence of anxiety and depression will also change with the passage of the epidemic. Therefore, the results of anxiety and depression obtained in a certain study may only represent the level during that certain period of the epidemic. Different assessment methods were also used in the studies, and some of them were convenience sampling, snowball sampling, or online survey. It was thus di cult to re ect the diversity of research representatives, and the research results obtained may have bias. In addition, although we conducted extensive searches in different databases, most of the included studies were conducted in Mainland China and Hong Kong, China. Only one study was conducted in New York, USA. The generalization of our research results is also subject to certain restrictions. Given that the COVID-19 epidemic in countries around the world has led to delayed surgeries and treatment interruption for cancer patients [51][52][53][54] , it is reasonable to believe that the prevalence of anxiety and depression among cancer patients in other countries or regions also increased signi cantly, and psychological interventions targeting this group is necessary.

Conclusion
Our systematic review and meta-analysis combined available evidence in a timely and comprehensive manner to highlight the high prevalence of depression and anxiety in cancer patients during the COVID-19 pandemic. The results help to quantify the incidence of negative emotions in cancer patients during the COVID-19 epidemic, thus providing information for effective targeted psychological interventions targeting this population.

Declarations
Ethics approval and consent to participate Not applicable.

Consent for publication
Not applicable.

Availability of data and materials
Datasets are available through the corresponding author upon reasonable request.

Competing interests
There are no con icts of interest. Sensitivity analysis of pooled depression prevalence