Stress and Symptom Burden in Oncology Patients During the COVID-19 Pandemic.

CONTEXT: No information is available on oncology patients' level of stress and symptom burden during the coronavirus disease 2019 (COVID-19) pandemic.
OBJECTIVES: To evaluate for differences in demographic and clinical characteristics, levels of social isolation and loneliness, and the occurrence and severity of common symptoms between oncology patients with low vs. high levels of COVID-19 and cancer-related stress. In addition, to determine which of these characteristics were associated with membership in the high-stressed group.
METHODS: Patients were 18 years and older; had a diagnosis of cancer; and were able to complete an online survey.
RESULTS: Of the 187 patients in this study, 31.6% were categorized in the stressed group (Impact of Event Scale-Revised [score of ≥24]). Stressed group's Impact of Event Scale-Revised score exceeds previous benchmarks in oncology patients and equates with probable post-traumatic stress disorder. In this stressed group, patients reported occurrence rates for depression (71.2%), anxiety (78.0%), sleep disturbance (78.0%), evening fatigue (55.9%), cognitive impairment (91.5%), and pain (75.9%). Symptom severity scores equate with clinically meaningful levels for each symptom.
CONCLUSION: We identified alarmingly high rates of stress and an extraordinarily high symptom burden among patients with cancer, exceeding those previously benchmarked in this population and on par with noncancer patients with post-traumatic stress disorder. Given that the COVID-19 pandemic will likely impact cancer care for an indefinite period, clinicians must exhibit increased vigilance in their assessments of patients' level of stress and symptom burden. Moreover, an increase in referrals to appropriate supportive care resources must be prioritized for high-risk patients.

Introduction

A cancer diagnosis and its treatments are stressful experiences for most patients. , The coronavirus disease 2019 (COVID-19) pandemic and associated mitigation procedures have imposed additional stress. Emerging evidence suggests that fear of infection, concerns regarding the efficacy of COVID-19 treatments, the negative impact of various mitigation procedures (e.g., social isolation), and economic uncertainty are associated with higher levels of perceived stress in the general population.3, 4, 5, 6, 7, 8 In addition, oncology patients may experience higher levels of stress if they perceive themselves to be at increased risk for contracting the disease , and for serious adverse events if they become infected with COVID-19.10, 11, 12 Furthermore, the social distancing procedures and restrictions in access to care may increase patients' fears and concerns about receiving cancer treatments and disease recurrence.13, 14, 15

Although the types and duration of stressors can vary, a significant amount of variability exists in individuals' cognitive, emotional, and neurobiological responses to stress. A growing body of evidence from the general population suggests that these interindividual differences in responses to stress contribute to higher rates and severity of both psychological and physical symptoms. Surprisingly, research on the association between stress and symptom burden in oncology patients is limited.

In terms of psychological symptoms, in a meta-analysis of studies that focused on the prevalence of COVID-19-related stress and anxiety in the general population, 29.6% of individuals surveyed reported high levels of stress, 31.9% reported anxiety, and 33.7% reported depression. Although often studied together as psychological distress, , depression occurs in 15%–30% of oncology patients and anxiety in 30%–50%. , In three recent studies that evaluated psychological symptoms in oncology patients during the COVID-19 pandemic,21, 22, 23 occurrence rates for depression and anxiety ranged from 9.3% to 31.0% and from 8.9% to 36.0%, respectively. The wide range in occurrence rates may be related to the instruments and clinically meaningful cutoff scores that were used to dichotomize the samples.

Less is known about the impact of the COVID-19 pandemic on physical symptoms. Although fatigue occurs in 60%–90% of oncology patients, recent evidence suggests that higher levels of stress correlated with increased fatigue in oncology patients undergoing chemotherapy. Sleep disturbance is reported by 30%–88% of oncology patients. , Although findings from preclinical and clinical studies suggest that stress has a negative impact on the sleep-wake cycle, , no data are available on the relationship between stress and sleep disturbance in oncology patients. Similarly although increased stress can exacerbate chronic pain, , less is known about this relationship in patients with cancer. Our study was the first to report significant levels of stress in patients with chemotherapy-induced peripheral neuropathy. In another study that assessed both combat and cancer-related post-traumatic stress disorder (PTSD) in veterans with oral-digestive cancers, patients with both types of stress had an 8.49 times higher odds of experiencing chronic pain. Finally, cancer-related cognitive impairment occurs in 75% of oncology patients and has been associated with increased levels of stress. , In terms of the relationships between physical symptoms and COVID-19, in one study of patients with breast cancer, 12.9% of women reported moderate and 4.0% reported severe insomnia. In another study of patients with heterogeneous cancer diagnoses, higher levels of fatigue and pain were associated with higher risk for mental disorders.

The loneliness and social isolation imposed by COVID-19 stay-at-home orders are additional sources of stress. , Although not extensively studied in oncology patients, loneliness and social isolation are associated with a higher symptom burden, poorer health, and higher all-cause mortality in older adults.

Given the paucity of research on the associations between COVID-19 and cancer-related stress and the severity of common symptoms in oncology patients, we evaluated for differences in demographic and clinical characteristics, levels of social isolation and loneliness, and the occurrence and severity of common symptoms between oncology patients with low vs. high levels of COVID-19 and cancer-related stress. In addition, we determined which demographic, clinical, symptom, and stress characteristics were associated with membership in the high-stressed group. We hypothesized that patients in the high-stressed group would have a higher symptom burden and higher levels of social isolation and loneliness.

Methods

Sample and Settings

Patients were recruited from a registry of individuals who participated in our previous National Cancer Institute-funded studies (CA187160, CA212064, and CA151692). Potential participants received an electronic mail (e-mail) with a brief explanation of the study and a link that directed them to the study's enrollment page. This study was exempt from requiring written informed consent by the Institutional Review Board at the University of California, San Francisco. Patients were included if they were 18 years and older; were able to read, write, and understand English; had a diagnosis of cancer; and were able to complete the survey online.

Survey Administration

E-mails were sent to potential participants beginning May 27, 2020. Patients who received the survey link were asked to complete the survey within two weeks. One e-mail reminder was sent 14 days after the initial request. Patients were asked to answer all the survey questions in relationship to their experiences in the past 14 days. The entire survey took approximately 60 minutes to complete. All the instruments were completed online using the Research Electronic Data Capture system. , Responses as of July 10, 2020 are presented in this article.

Instruments

Demographic and Clinical Characteristics

Patients completed demographic and clinical questionnaires, Karnofsky Performance Status scale, and Self-Administered Comorbidity Questionnaire (SCQ).

Stress Measure

The 22-item Impact of Event Scale—Revised (IES-R) was used to measure COVID-19 and cancer-related stress. Patients rated each item based on how distressing each potential difficulty was for them during the past 14 days with respect to their cancer and its treatment and the COVID-19 pandemic. Each item was rated on a 0–4 Likert scale. Three mean subscale scores were created that evaluated levels of perceived intrusion, avoidance, and hyperarousal. A total IES-R score was created by summing the responses to the 22 items and can range from 0 to 88. A total IES-R score of ≥24 indicates clinically meaningful post-traumatic symptomatology, and scores of ≥33 indicate probable PTSD. , The IES-R has been used to assess COVID-19-specific stress in the general population in China, the Chinese workforce, health care workers, psychiatric patients, and oncology patients.21, 22, 23

Additional measures of stress included the Perceived Stress Scale (PSS, general stress), , Connor Davidson Resilience Scale (resilience), and Comprehensive Score for Financial Toxicity (financial stress).

Loneliness and Social Isolation

The University of California, Los Angeles Loneliness Scale assesses an individual's subjective feelings of loneliness and social isolation.58, 59, 60 A score of 36.0 represents a normative value for the general population. Social Isolation Scale evaluates an individual's perceptions of connectedness and belongingness. A score of between 10 and 15 suggests that an individual is at risk for social isolation, and a score of ≤9 indicates social isolation.

Symptom Measures

To assess the occurrence and severity of the most common symptoms associated with cancer and its treatment, patients completed Center for Epidemiological Studies-Depression scale (CES-D), Spielberger State-Trait Anxiety Inventories, General Sleep Disturbance Scale (GSDS), Lee Fatigue Scale (which assessed levels of morning and evening fatigue and morning and evening energy), Attentional Function Index, and Brief Pain Inventory.

Data Analysis

Data were downloaded from Research Electronic Data Capture system , into the Statistical Package for the Social Sciences, Version 27 (IBM Corporation, Armonk, NY). Descriptive statistics were generated for sample characteristics and study measures. Using the IES-R total score, patients were dichotomized into the stressed (i.e., ≥24) and nonstressed (i.e., <24) groups. , To determine symptom occurrence rates, symptoms were dichotomized based on clinically meaningful cutoff scores for each of the symptom measures. Between-group differences were evaluated using independent-sample t-tests, Chi-squared analyses, and Mann-Whitney U tests. Multiple logistic regression analysis was used to evaluate for predictors of stress group membership. A P-value of <0.05 was considered statistically significant.

Results

A total of 627 e-mails were sent, 250 patients began the survey (39.9% response rate), and 187 provided complete information (29.8% completion rate). The characteristics of the total sample and the two stress groups are presented in Table 1 .

Table 1

Differences in Demographic, Clinical, and Behavioral Characteristics Between the Stress Groups

Characteristic	Total Sample	Nonstressed Group	Stressed Group	Statistics
	(n = 187)	68.4% (n = 128)	31.6% (n = 59)
	Mean (SD)	Mean (SD)	Mean (SD)
Demographic and clinical characteristics
Age (yrs)	63.3 (10.9)	63.0 (12.4)	62.8 (10.5)	t = 0.41; P = 0.680
Number of people in your household including yourself	1.9 (0.9)	2.0 (0.9)	1.9 (0.9)	t = 0.49; P = 0.624
Body mass index (kg/m2)	26.3 (5.4)	26.5 (5.8)	25.9 (4.4)	t = 0.71; P = 0.476
KPS score	92.8 (9.1)	93.7 (9.1)	90.7 (8.9)	t = 2.14; P = 0.033
Number of comorbidities	1.6 (1.4)	1.4 (1.4)	2.0 (1.4)	t = −2.53; P = 0.012
SCQ score	3.2 (3.0)	2.7 (2.8)	4.1 (3.1)	t = −3.06: P = 0.003
Time since cancer diagnosis (yrs)	9.7 (6.9)	10.9 (7.4)	7.2 (4.6)	U = 0.001
Time since cancer diagnosis—median	8.1	8.7	6.4
Number of previous cancer treatments	3.0 (1.0)	3.1 (1.0)	2.9 (0.9)	t = 1.64; P = 0.103
Number of current cancer treatments	0.3 (0.5)	0.3 (0.5)	0.3 (0.5)	t = −0.19; P = 0.851
	n (%)	n (%)	n (%)
Female (% yes)	183 (97.9)	125 (97.7)	58 (98.3)	FE, P = 1.000
Living arrangements
Private home or apartment	186 (99.5)	127 (99.2)	59 (100.0)	χ2 = 0.46; P = 0.496
Assisted living facility	0 (0.0)	0 (0.0)	0 (0.0)
Other	1 (0.5)	1 (0.8)	0 (0.0)
Lives alone (% yes)	56 (29.9)	39 (30.5)	17 (28.8)	FE, P = 0.865
Married/partnered (% yes)	115 (61.5)	77 (60.2)	38 (64.4)	FE, P = 0.630
Race/ethnicity				FE, P = 0.838
White	154 (82.4)	106 (82.8)	48 (81.4)
Nonwhite	33 (17.6)	22 (17.2)	11 (18.6)
Highest level of education
High school	5 (2.7)	4 (3.1)	1 (1.7)	U, P = 0.107
Some college	37 (19.9)	28 (22.0)	9 (15.3)
College graduate	48 (25.8)	35 (27.6)	13 (22.0)
Some graduate school	28 (15.1)	17 (13.4)	11 (18.6)
Advanced degree	68 (36.5)	43 (33.9)	25 (42.4)
Currently employed (% yes)	75 (40.3)	53 (41.7)	22 (37.3)	FE, P = 0.631
Annual household income
<$20,000	8 (5.0)	5 (4.7)	3 (5.8)	U, P = 0.957
$20,000–$59,000	39 (24.5)	26 (24.3)	13 (25.0)
$60,000–$100,000	35 (22.0)	25 (23.4)	10 (19.2)
>$100,000	77 (48.5)	51 (47.6)	26 (50.0)
Chronic conditions (% yes)
Heart disease	15 (8.2)	9 (7.1)	6 (10.5)	FE, P = 0.561
High blood pressure	52 (28.1)	31 (24.2)	21 (36.8)	FE, P = 0.110
Lung disease	10 (5.5)	6 (4.8)	4 (7.0)	FE, P = 0.505
Diabetes	8 (4.3)	7 (5.5)	1 (1.8)	FE, P = 0.438
Ulcer or stomach disease	6 (3.3)	5 (4.0)	1 (1.7)	FE, P = 0.667
Kidney disease	3 (1.6)	2 (1.6)	1 (1.8)	FE, P = 1.000
Liver disease	3 (1.7)	3 (2.4)	0 (0.0)	—
Anemia or blood disease	4 (2.2)	3 (2.4)	1 (1.8)	FE, P = 1.000
Depression	47 (25.7)	19 (15.0)	28 (50.0)	FE, P < 0.001
Osteoarthritis, degenerative arthritis	53 (28.8)	35 (27.8)	18 (31.0)	FE, P = 0.727
Back pain	59 (32.6)	37 (29.8)	22 (38.6)	FE, P = 0.306
Rheumatoid arthritis	7 (4.0)	6 (5.0)	1 (1.8)	FE, P = 0.437
Cancer diagnosis
Breast cancer	149 (80.6)	102 (80.3)	47 (81.0)	χ2 = 6.60; P = 0.360
Gastrointestinal	6 (3.2)	3 (2.4)	3 (5.2)
Lung	1 (0.5)	1 (0.8)	0 (0.0)
Malignant melanoma	1 (0.5)	1 (0.8)	0 (0.0)
Gynecological	9 (4.9)	4 (3.1)	5 (8.6)
Prostate	1 (0.5)	1 (0.8)	0 (0.0)
Multiple cancer types or other	18 (9.8)	15 (11.8)	3 (5.2)
The presence of metastatic disease (% yes)	45 (24.7)	29 (23.2)	16 (28.1)	FE, P = 0.579
Currently receiving cancer treatment (% yes)	49 (26.2)	33 (25.8)	16 (27.1)	FE, P = 0.859

KPS = Karnofsky Performance Status; SCQ = Self-Administered Comorbidity Questionnaire; FE = Fischer's exact test; U = Mann-Whitney U test.

Demographic and Clinical Characteristics

Of these 187 patients, 31.6% (n = 59) were categorized in the stressed group. Compared with the nonstressed group, the stressed group had a higher number of comorbidities, a higher comorbidity burden, were fewer years from their cancer diagnosis, were more likely to report a diagnosis of depression, and had a lower functional status score (all P < 0.05; Table 1).

Stress, Social Isolation, and Loneliness Scores

Compared with the nonstressed group, the stressed group had significantly higher scores for general stress, intrusion, avoidance, hyperarousal, and loneliness. In addition, they had lower scores (indicating worse outcomes) for resilience, social isolation, and financial toxicity (Table 2 ).

Table 2

Differences in Stress and Symptom Scores Between the Stress Groups

Characteristica	Total Sample	Nonstressed Group	Stressed Group	Statistics
	n = 187	68.4% (n = 128)	31.6% (n = 59)
	Mean (SD)	Mean (SD)	Mean (SD)
Stress scores
IES-R—total score (≥24)	18.6 (14.8)	10.2 (6.9)	36.9 (10.1)	t = −18.43; P < 0.001
IES-R—intrusion subscale	0.9 (0.8)	0.4 (0.4)	1.8 (0.6)	t = −15.56; P < 0.001
IES-R—avoidance subscale	0.8 (0.7)	0.5 (0.5)	1.5 (0.5)	t = −13.22; P < 0.001
IES-R—hyperarousal subscale	0.8 (0.8)	0.4 (0.4)	1.7 (0.7)	t = −13.92; P < 0.001
Perceived Stress Scale (≥14.0)	14.6 (7.3)	12.0 (6.1)	20.2 (6.7)	t = −8.20; P < 0.001
CDRS	29.9 (6.4)	31.4 (5.8)	26.6 (6.5)	t = 5.07; P < 0.001
SIS (≤9 is social isolation; 10–15 at risk for social isolation)	23.3 (4.1)	24.0 (3.7)	21.8 (4.7)	t = 3.15; P = 0.002
UCLA Loneliness Scale (≥36)	37.5 (10.8)	35.0 (9.3)	42.8 (11.9)	t = −4.82; P < 0.001
COST	31.3 (10.1)	32.4 (9.8)	29.1 (10.7)	t = 2.04; P = 0.043
Symptom scores
CES-D (≥16)	14.5 (10.0)	10.8 (7.7)	22.4 (9.8)	t = −8.02; P < 0.001
Trait anxiety (≥31.8)	36.0 (10.7)	32.5 (8.5)	43.4 (11.3)	t = −6.60; P < 0.001
State anxiety (≥32.2)	34.5 (12.6)	30.6 (10.3)	42.7 (13.2)	t = −6.22; P < 0.001
GSDS (≥43.0)	50.2 (21.4)	45.6 (19.7)	60.1 (21.8)	t = −4.54; P < 0.001
Morning fatigue (≥3.2)	3.4 (2.5)	2.8 (2.3)	4.8 (2.4)	t = −5.5; P < 0.001
Evening fatigue (≥5.6)	5.0 (2.2)	4.6 (2.1)	5.7 (2.2)	t = −3.09; P = 0.002
Morning energy (≤6.2)	5.0 (2.4)	5.4 (2.4)	4.1 (2.2)	t = 3.65; P < 0.001
Evening energy (≤3.5)	2.8 (2.1)	2.9 (2.2)	2.6 (1.9)	t = 0.77; P = 0.441
Attentional Function Index (<5 = low cognitive function; 5–7.5 = moderate cognitive function; and >7.5 = high cognitive function)	6.7 (1.7)	7.2 (1.6)	5.6 (1.6)	t = 6.29; P < 0.001
Types of pain				χ2 = 10.61; P = 0.0140 > 1
None	38.8 (71)	45.6 (57)	24.1 (14)
Only noncancer pain	14.8 (27)	10.4 (13)	24.1 (14)
Only cancer pain	25.1 (46)	24.8 (31)	25.9 (15)
Both noncancer and cancer pain	21.3 (39)	19.2 (24)	25.9 (15)
Worst pain intensity score	6.6 (2.2)	6.8 (2.0)	6.3 (2.5)	t = 1.17; P = 0.245
Mean pain interference score	3.2 (2.2)	2.9 (2.1)	3.6 (2.2)	t = −1.63; P = 0.105

IES-R = Impact of Event Scale—Revised; CDRS = Connor Davidson Resilience Scale; SIS = Social Isolation Scale; UCLA = The University of California, Los Angeles; COST = Comprehensive Score for Financial Toxicity; CES-D = Center for Epidemiological Studies-Depression scale; GSDS = General Sleep Disturbance Scale.

Clinically meaningful cutoff scores are provided in parentheses.

Symptom Scores

As shown in Table 3 , compared with the nonstressed group, the stressed group had significantly higher occurrence rates for all the symptoms except decrements in evening energy. In addition, compared with the nonstressed group, the stressed group had significantly higher scores for depressive symptoms, trait and state anxiety, sleep disturbance, and morning and evening fatigue. In addition, they had lower scores (indicating a higher level of symptom severity) for morning and evening energy and attentional function (Table 2).

Table 3

Differences in Symptom Occurrence Rates Between the Stress Groups

Symptom Occurrence	Total Sample	Nonstressed Group	Stressed Group	Statistics
	(n = 187)	68.4% (n = 128)	31.6% (n = 59)
Depression	39.8	25.4	71.2	FE, P < 0.001
Trait anxiety	59.1	48.8	81.4	FE, P < 0.001
State anxiety	48.4	34.6	78.0	FE, P < 0.001
Sleep disturbance	59.7	51.2	78.0	FE, P < 0.001
Morning fatigue	45.9	38.6	72.9	FE, P < 0.001
Evening fatigue	40.5	33.3	55.9	FE, P = 0.004
Decrements in morning energy	69.2	62.7	83.1	FE, P = 0.006
Decrements in evening energy	67.7	66.9	69.5	FE, P = 0.866
Decrements in cognitive function	68.3	57.5	91.5	FE, P < 0.001
Pain	61.2	54.4	75.9	FE, P = 0.006

FE = Fischer's exact test.

Factors Associated With Stressed Group Membership

In the logistic regression analysis, clinical characteristics (i.e., time since cancer diagnosis, SCQ score, Karnofsky Performance Status score), stress scores (i.e., PSS, University of California, Los Angeles Loneliness Scale, Social Isolation Scale, the Connor Davidson Resilience Scale, Comprehensive Score for Financial Toxicity), and symptom severity scores (i.e., CES-D, Spielberger Trait Anxiety Inventory, Spielberger State Anxiety Inventory, GSDS, morning and evening fatigue, morning energy, Attentional Function Index, the presence of pain) that were significantly different between the two stress groups in the bivariate analyses were included in the model. Although the number of comorbidities and proportion of patients with a diagnosis of depression were significantly different between the two stress groups, they were not included in the analysis because the total SCQ and CES-D scores were used in the logistic regression.

As shown in Table 4 , the overall model was significant (χ2 = 85.20; P < 0.001). Three variables were significant in the final model (i.e., length of time since cancer diagnosis, PSS score, and occurrence of pain). Patients who were a shorter time from their cancer diagnosis; had a higher level of general stress; and who reported the occurrence of pain were more likely to be in the stressed group.

Table 4

Multiple Logistic Regression Analysis Predicting Stress Group Membership (n = 169)

Predictor	Odds Ratio (95% CI)	P
KPS score	1.06 (1.00–1.13)	0.072
SCQ score	1.15 (0.97–1.35)	0.102
Time since cancer diagnosis in years	0.92 (0.85–0.99)	0.028
Perceived Stress Scale score	1.13 (1.01–1.27)	0.033
CDRS score	0.97 (0.87–1.09)	0.646
SIS score	0.95 (0.80–1.12)	0.518
UCLA Loneliness Scale score	0.96 (0.90–1.04)	0.329
COST	1.04 (0.98–1.10)	0.171
CES Scale score	1.11 (1.00–1.25)	0.062
Trait anxiety score	1.00 (0.90–1.11)	0.995
State anxiety score	0.99 (0.92–1.06)	0.737
GSDS score	0.98 (0.95–1.02)	0.294
LFS—morning fatigue score	1.34 (0.94–1.89)	0.102
LFS—evening fatigue score	0.94 (0.71–1.25)	0.686
LFS—morning energy score	1.22 (0.92–1.61)	0.172
Attentional Function Index score	0.72 (0.47–1.11)	0.140
Occurrence of pain	5.02 (1.64–15.4)	0.005
Overall model fit: degrees of freedom = 17; χ2 = 85.2; P < 0.001

KPS = Karnofsky Performance Status; SCQ = Self-Administered Comorbidity Questionnaire; CDRS = Connor Davidson Resilience Scale; SIS = Social Isolation Scale; UCLA = The University of California, Los Angeles; COST = Comprehensive Score for Financial Toxicity; CES = Center for Epidemiological Studies; GSDS = General Sleep Disturbance Scale; LFS = Lee Fatigue Scale.

Discussion

Consistent with a prevalence rate of 29.6% for high levels of COVID-19-related stress in the general population, 31.6% of our patients were categorized into the stressed group. Although the IES-R score of 18.6 for the total sample was below the clinically meaningful cut point, patients in our stressed group had a mean score of 36.9 (±10.1; range 24–60), which is alarmingly high and consistent with probable PTSD. It should be noted that, although most patients in the present study were females, white, well educated, had an annual income of ≥$60,000, had completed their cancer treatment, and had a high functional status, the IES-R cutoff score used in this study was established with war veterans, earthquake survivors, and survivors of the Tokyo Metro sarin gas attack. By way of comparison, in our study of patients receiving chemotherapy before COVID-19, IES-R scores ranged from 15.4 (±12.1) to 27.9 (±13.8). In addition, in two recent studies of oncology patients during the COVID-19 pandemic, IES-R total scores ranged from 19.7 to 28.2. Taken together, these findings indicate that during this COVID-19 pandemic, oncology patients are experiencing a clinically meaningful level of stress that exceeds previously reported benchmarks and equates with probable PTSD.

In addition to the COVID-19 and cancer-related stress measure, patients completed a measure of general stress (i.e., PSS). For the total sample, their PSS score slightly exceeded the clinically meaningful cut-point score of ≥14.0 (i.e., 14.6 [±7.3]) and was significantly higher in the stressed group (i.e., 20.2 [±6.7]). In the study mentioned previously of patients receiving chemotherapy, PSS scores ranged from 8.5 (±4.5) to 25.4 (±6.7). During these particularly stressful times, which include the stressors associated with the pandemic as well as societal and political challenges, the use of a general measure of stress captures additional information on patients' experiences.

Consistent with the known associations between COVID-19 mitigation procedures and heightened levels of loneliness in the general population, it is not surprising that patients in our stressed group reported higher levels of social isolation and loneliness. Although our sample did not meet the clinically meaningful cut point for social isolation, the loneliness score for the total sample was above the clinically meaningful cut point. Finally, given the economic consequences of the COVID-19 pandemic and the financial toxicity associated with cancer and its treatment, it is not surprising that the stressed group reported more financial concerns. Given that most patients in this study had a relatively high annual income, additional research is needed on the added stress of the COVID-19 pandemic on patients with fewer economic and health care resources.

The population-based studies that evaluated for associations between COVID-19-related stress and symptoms assessed anxiety and depression. As noted in a recent systematic review of these studies, the prevalence rates for COVID-19-related anxiety and depression were 31.9% and 33.7%, respectively. In addition, in studies of oncology patients during COVID-19, occurrence rates for depression and anxiety ranged from 9.3% to 31.0% and from 8.9% to 36.0%, respectively. Although for our total sample, the rate of depression was comparable (i.e., 39.8%), our rates for trait (59.1%) and state (48.4%) were considerably higher. Reasons for these differences may include the measures used to evaluate the symptoms; differences in sample characteristics; and/or various additional stressors not evaluated in the questionnaires (e.g., access to care, sociopolitical stress). However, it is notable that in studies of oncology patients before the COVID-19 pandemic, rates of depression and anxiety ranged from 15% to 30% and from 30% to 50%, respectively. , In addition, in the current sample, between-group differences in the severity of both anxiety and depression represent not only statistically significant but also clinically meaningful differences (d = 1.07 for state anxiety to d = 1.38 for depression). In addition, the CES-D scores of the patients in the stressed group (i.e., 22.4 [±9.8]) suggest the need for a clinical evaluation of depression.

The results of this study extend the findings of previous studies of COVID-19 stress, by evaluating the impact of this added stress on the occurrence and severity of physical symptoms in oncology patients. In the previous study of patients with breast cancer who were evaluated during COVID-19, only 12.9% of women reported moderate and 4.0% reported severe insomnia. In contrast, nearly 60% of the total sample and 78% of the stressed group reported clinically meaningful levels of sleep disturbance. The severity of sleep disturbance reported by the stressed group (i.e., GSDS score of 60.1) is comparable to that of permanent shift workers or parents of newborn infants. Consistent with the very high level of sleep disturbance in these patients, the occurrence rates for and severity of morning fatigue as well as decrements in morning and evening energy represent clinically meaningful levels of all three symptoms. Previous work from our research team demonstrated that although morning and evening fatigue as well as morning and evening energy are associated with depression, they are distinct symptoms.74, 75, 76 Although cancer-related cognitive impairment occurs in 75% of oncology patients, 91.5% of the patients in the stressed class reported clinically meaningful decrements in cognitive function. Finally, although fewer patients in the nonstressed group (54.4%) compared with the stressed group (75.9%) reported pain, both groups reported pain severity scores in the moderate-to-severe range that had a moderate impact on their functional activities. Taken together, these findings demonstrate an extremely strong relationship between COVID-19 and cancer-related stress and a significant symptom burden. Although this relationship was stronger in the stressed group, the occurrence rates and severity of symptoms in the nonstressed group are clinically meaningful, higher than normative data, and warrant immediate assessment and management.

In terms of the regression analysis, shorter time since the cancer diagnosis, higher levels of general stress (i.e., higher PSS scores), and the occurrence of pain were significant predictors of membership in the stressed group. Although in a recent systematic review, no association was found between time since cancer diagnosis and PTSD, this nonmodifiable characteristic may be used to identify high-risk patients. It is interesting to note that patients with higher scores on our measure of general stress were more likely to be in the stressed group. This finding suggests that stressors other than those related to COVID-19 and cancer (e.g., social unrest, family stress) can contribute to the overwhelming stress reported by the patients in our sample.

Of note, pain was the only symptom associated with membership in the stressed group. Consistent with previous reports, , patients with pain were 5.02 times more likely to be in the stressed group. Sixty-one percent of the total sample and 75.9% of the stressed group reported this symptom. The most common causes of noncancer pain were low back pain (20.7%) and arthritis (24.5%). In terms of cancer pain, 16.0% reported chronic postsurgical pain and 19.7% reported chemotherapy-induced peripheral neuropathy. Given that the severity of and level of interference from pain were relatively high in both groups, effective management of this symptom (e.g., cognitive behavioral therapy) is warranted.

Although this study provides new information on the significant impact of COVID-19 and cancer-related stress on oncology patients, several limitations warrant consideration. Given that most patients were well-educated women with breast cancer, the generalizability of our findings to men or patients with other cancer diagnoses warrant confirmation in future studies. Given that most of our patients were white, had health insurance (97.7%), and reported annual incomes of >$60,000, we may be significantly underestimating the impact of the stress associated with this pandemic, particularly among individuals who are socioeconomically disadvantaged. Expansion of this research to underserved populations is needed to inform planning and implementation of appropriate interventions to decrease stress and symptom burden. Longitudinal studies are needed to assess the relationships among changes over time in stress and symptom burden as the COVID-19 pandemic evolves.

In conclusion, we identified alarmingly high rates of stress and an extraordinarily high symptom burden among patients with cancer in the COVID-19 pandemic, exceeding those previously benchmarked in this patient population and on par with noncancer patients with PTSD. Given that the COVID-19 pandemic and the ensuing economic downturn will likely impact cancer care for an indefinite period, clinicians must exhibit increased vigilance in their assessments of oncology patients' level of stress and symptom burden. In addition, clinicians need to educate patients on the benefits of using simple strategies (e.g., relaxation exercises, stress reduction techniques) to manage stress and decrease symptoms. Equally important, an increase in referrals to appropriate supportive care resources (e.g., online peer support groups, exercise therapy, psycho-oncology, symptom management services) must be prioritized for high-risk patients. At the institutional level, we recommend that supportive care services increase; patients have increased access to these services using telehealth approaches; and concerted efforts be made to provide these services to our most vulnerable and underserved patients. Future research should identify additional factors that contribute to heightened stress levels and increased symptom burden among patients with cancer and how these factors may vary with race, socioeconomic status, and other important social determinants of health.