Abstract
The present study assessed the impact of the COVID-19 pandemic on adult oncology patients at an oncology clinic in Atlantic Canada. Patients completed a survey about their cancer diagnosis, treatment, and the impact of the COVID-19 pandemic on their health between September 2021 and April 2022. Seroprotection from the COVID-19 vaccine was assessed in a subset of patients. Of the 178 patients who provided consent, 161 completed the survey and 134 provided blood samples for seropositive analysis. Most reported no perceived delays in their cancer diagnosis (93.2%), treatment (91.8%), or follow-up care (98.1%) because of the pandemic. Although 75.2% of patients reported anxiety about contracting COVID-19, majority (96.3%) did not miss their appointments because of the pandemic. Seroprotection rates after COVID-19 vaccination did not differ significantly by treatment type; however, patients with hematological cancers had a significantly lower response. This study offers a snapshot of how the COVID-19 pandemic affected the diagnosis, treatment, and well-being of patients with cancer. The findings may help to guide clinical decisions and mitigate care delays in the future.
Keywords
Introduction
Patients with cancer (PWC) were disproportionately affected during the peak of the COVID-19 pandemic. 1 They are considered a high-risk group for COVID-19 infection due to their immunocompromised state, advanced age, and multiple comorbidities. 2 During the COVID-19 pandemic, PWC were more likely to experience severe infections (requiring the use of ventilators), ICU admission, and death than patients without cancer.3,4 Before the COVID-19 vaccines were available, PWC who contracted COVID-19 had a 25.6% greater risk of mortality than patients without cancer, especially those with hematological malignancies or lung cancer. 5
COVID-19 caused significant challenges to cancer care. A survey of 312 cancer patients in the United States found that routine cancer care was often delayed by at least 4 weeks, and approximately half the study patients avoided routine or emergency care to decrease their risk of contracting COVID-19. 6 To reduce the risk of infection and facilitate access to care, healthcare providers shifted towards virtual care. 7
There are some reports of PWC experiencing isolation and negative impacts on their mental well-being because of delays in cancer treatment,6,8,9 limited research to date has investigated the experiences of PWC during the COVID-19 pandemic.
Originally, PWC were excluded from COVID-19 vaccine clinical trials because of their immunocompromised state. As a result, little was known about the safety, tolerability, and efficacy of these novel vaccines in this group. Despite the scarcity of information on COVID-19 vaccines, health authorities in Canada encouraged cancer patients to take the vaccine after discussing with their primary healthcare provider the risks and benefits of the vaccine, the risks and consequences of a COVID-19 infection, and the timing of vaccination in relation to their cancer therapy. 10
Research has found that PWC have tolerated COVID-19 vaccines well and have experienced mild reactogenicity, such as a sore arm, tiredness, and headache.11–13 However, patients with hematological malignancies exhibited a weaker serologic response against the virus post-vaccination. A systematic review and meta-analysis of the immunogenicity of COVID-19 vaccines showed that patients with hematological malignancies had seropositive rates of 30% and 62.3% after their first and second vaccine doses, respectively. Patients with solid tumors and healthy participants had higher seropositive rates, suggesting increased protection against COVID-19. 14 This is supported by a study conducted in Israel, where 423 participants vaccinated twice against COVID-19 showed patients with hematologic malignancies had a lower seropositive response (74.6%) with a median antibody titer of 85 AU/ml, which was significantly lower when compared with participants with no hematologic malignancies, in whom 99.1% developed a seropositive response, with median antibody titer of 157 AU/ml. 15 Another systematic review also found that patients with hematological malignancies had significantly lower seroconversion rates than patients with solid tumors or those in remission. 16 Serological tests detect the level of antibodies after vaccination, with lack of detectable antibodies equating to lack of protection. 17 However, with unstandardized thresholds and poor correlation data between the anti-Spike protein and protective role of vaccination, serological tests may not show the complexity of immune protection against COVID-19.17,18
The goal of the current study was to gather real-world evidence of the impact of the COVID-19 pandemic on the management and treatment of PWC at an oncology clinic in a mid-sized city in New Brunswick, Canada. Data on the patient experience during the COVID-19 pandemic and real-world immunogenicity data can improve our understanding of the effect of vaccines on PWC and guide the decision-making of healthcare providers and patients.
19
The aims of this study were to:
Determine the impact that the COVID-19 pandemic had on the management of PWC. Determine the impact that the COVID-19 pandemic had on patients’ anxiety towards their cancer care. Assess the type and frequency of any side effects from the COVID-19 vaccine experienced by cancer patients who underwent treatment. Assess whether the COVID-19 vaccine provides effective seroprotection against the COVID-19 virus to PWC. Compare seroprotection rates among patients undergoing different types of cancer treatments.
Method
Study Design and Data Collection Procedure
Using a cross-sectional design and convenience sampling method, we recruited PWC at an oncology clinic in New Brunswick, Canada between September 2021 and April 2022 to participate in this study. Patients were invited to complete a survey about their experiences in seeking care during the COVID-19 pandemic and their experiences with COVID-19 vaccination. They were also invited to participate in an optional sub-study to test their seroprotection rates after COVID-19 vaccination. All methods and procedures described herein were granted institutional approval by the health authority's Human Research Protection Program/Research Ethics Board (File #101291).
Patients aged ≥ 19 years who were seeking care for their cancer, regardless of type or stage, were eligible for inclusion. Efforts were made to recruit as many patients as possible who were actively undergoing or had recently undergone cancer treatment; however, patients who had completed treatment were also eligible to participate. Patients who had received at least two doses of a COVID-19 vaccine were invited to participate in an optional sub-study to evaluate seroprotection rates after vaccination. The vaccines approved in Canada at the time of the study were the Pfizer and Moderna mRNA-based COVID-19 vaccines and the AstraZeneca viral vector-based COVID-19 vaccine.
Oncologists and hematologists were contacted by the principal investigator to recruit patients for the study. All patients attending a clinic visit during the study duration were approached by the treating physician to briefly describe the study and its objectives. Interested patients were given an informed consent form in clinic, and research staff followed-up with the patient at a subsequent visit or by phone. Phone contact was used whenever possible because of the ongoing COVID-19 pandemic. Surveys took approximately 30 min to complete and could be done either on paper or online via an e-mail provided link.
Measures
We developed a 10-item questionnaire to collect demographic characteristics (ie, age, sex, marital status, employment status, education level, drug coverage, income) and clinical information (ie, type of cancer, date of diagnosis, type of treatment, and date of treatment start).
We also developed a 48-item questionnaire to ascertain information regarding the impact of COVID-19 on cancer patients. Questions spanned many psychosocial domains but generally inquired about patients’ anxiety, stress, and their overall health, as well as the socioeconomic impacts of COVID-19.
An adverse events questionnaire (adapted from the Patient-Reported Outcome–Common Terminology Criteria for Adverse Events; PRO-CTCAE) was administered to collect information regarding 10 vaccine side effects, including pain at injection site, swollen lymph nodes, tiredness, headache, nausea, vomiting, fever, chills, achy/painful muscles, and achy/painful joints. 20 For each symptom, patients rated its frequency (0 = never, 1 = rarely, 2 = occasionally, 3 = frequently, 4 = almost constantly). Additional questions assessed participants’ vaccine experiences including the date(s) of vaccination, side effect commencement and duration, and whether patients visited a healthcare provider or the clinic as a result of the vaccine.
Seroprotection
Patients who consented to participate in the serology sub-study had one tube of blood collected during a routine appointment at the oncology clinic provided that at least 4 weeks had passed since the date of their second dose of a primary vaccine series. After the COVID-19 vaccine boosters were announced, the study was amended to include patients for whom 2 weeks had passed since their booster dose for their immune system to produce antibodies. Samples were centrifuged within 2 h of collection at 1300xg for 10 min. Serum was separated into two aliquots, one primary and one backup, and kept frozen at −80 degrees until the coded primary samples were shipped in batches to a partnering laboratory for analysis. Testing was performed using the Anti-SARS-CoV-2 Total (Anti-Spike) Assay manufactured by QuidelOrtho and analyzed on a Vitros XT 7600.
Several adjustments to the procedure were undertaken that should be mentioned. First, research staff used clinic pharmacy records to crosscheck the type of cancer treatment the patients in the serology sub-study were receiving at the time of their COVID-19 vaccination. This was required because the type of treatment patients were taking at the time of the survey may have changed since the time of their vaccination as there was no fixed timeframe for survey completion. Second, patients were categorized as being on treatment if they were on treatment for the first vaccine but stopped treatment before the second vaccine. Lastly, as a result of the approval and rollout of the booster during the study, some patients had their blood sample taken after their third dose of the vaccine, rather than after the second dose as originally intended. The protocol was amended and approved to ensure inclusion of patients who had already received the recommended booster, and new patients after implementation signed an updated consent form. Previously consented patients were not re-consented with the amended consent form.
Data Analysis
All data were analyzed using the IBM SPSS software (version 27). Prior to analysis, variables were examined for fit with their distributions and test assumptions according to procedures set out by Tabachnick and Fidell. 21 Descriptive statistics were used to summarize all variables of interest. For treatment group comparisons, each treatment group was compared with a combined group consisting of all other patients who received different treatments. Chi-square analysis was used for group comparisons for categorical variables. In the event that any of the 2 × 2 cell values had an expected frequency of less than five, Fisher's exact test was used in place of chi-square given that under these conditions, chi-square produces overly conservative P-values. Welch's t-tests were used for group comparisons for continuous outcomes. Welch's t-test was chosen over Student's t-test because Welch's t-test adjusts for heteroskedasticity concerns, which was anticipated due to small and unequal treatment subgroup sample sizes. Under homoskedastic conditions, Welch's and Student's t-tests are equivalent.
Alpha was set at 0.05. Effect sizes were reported which include Cramér's V for chi-square/Fisher's exact tests (small = 0.10, medium = 0.30, large = 0.50) and Cohen's d for t-tests (small = 0.20, medium = 0.50, large = 0.80).
Results
Demographic and Clinical Characteristics of Patients
A total of 178 patients consented to participate in the study, with 161 completing the survey and 134 participating in the serology sub-study. The mean age of the patients was 65.8 years (SD = 10.80) and there were similar numbers of male and female participants (50.3% and 49.7%, respectively) (Table 1). Hematologic cancers were the most common type of cancer (32.6%), and the most common treatment modalities were chemotherapy (39.8%) and targeted therapy (39.8%) (Table 1).
Demographic and Clinical Characteristics of Patients.
Note: Overall sample is N = 178 but sample sizes varied across variables due to missing data.
Other cancers include bladder, liver, melanoma, mesothelioma, ovarian, pancreatic, prostate, and testicular.
Delivery and Quality of Cancer Care
Most participants perceived no delays in diagnosis (93.2%), treatment (91.8%), or follow-up care (98.1%) due to the pandemic (Table 2). Additionally, majority of the patients (96.3%) did not miss their appointments because of the pandemic (Table 2).
Delivery and Quality of Cancer Care.
Note: Overall sample N = 161 but sample sizes varied across variables due to missing data.
Patient Anxiety due to the COVID-19 Pandemic
COVID-19 impacted patient's anxiety level is shown in Table 3, with majority (75.2%) being either somewhat, moderately, or extremely anxious. Majority of the patients (63.1%) also worried about spreading the virus to someone else and 73.3% had increased anxiety (somewhat, moderately, or a lot) about their health due to the pandemic and it's restrictions.
Patient Anxiety Due to the COVID-19 Pandemic.
Note: Overall sample N = 161 but sample sizes varied across variables due to missing data.
Antibody Production by Cancer and Treatment Type After COVID-19 Vaccination
Patient-Reported side Effects by Treatment Group
Patients receiving immunotherapy (n = 31) compared to other patients (n = 129) experienced significantly less frequent pain (M = 1.65, SD = 1.14 vs M = 2.12, SD = 1.28) at the injection site, t(49.83) = 2.05, P = 0.046, d = 0.381. In addition, patients receiving immunotherapy reported significantly less frequent chills (M = 1.06, SD = 0.25 vs M = 1.26, SD = 0.75) than the other patients, t(142.63) = 2.51, P = 0.013, d = 0.203 (Table 4).
Antibody Production by Cancer and Treatment Type After COVID-19 Vaccination.
Note: Overall sample N = 134 due to serology sub-study.
All P-values based on Fisher's exact test.
Patients receiving targeted therapy (n = 60) compared to other patients (n = 100) experienced significantly less frequent swollen lymph nodes (M = 1.07, SD = 0.41 vs M = 1.28, SD = 0.87), t(150.90) = 2.11, P = 0.037, d = 0.293. In addition, patients receiving targeted therapy reported significantly less frequent nausea (M = 1.03, SD = 0.18 vs M = 1.18, SD = 0.59) than the other patients, t(127.04) = 2.30, P = 0.023, d = 0.304 (Table 4).
No differences (P-values range from 0.115 to 0.931) in the frequency of side effects were observed for chemotherapy (n = 62) and non-chemotherapy (n = 98) patients. No differences (P-values range from 0.111 to 0.710) were observed between hormone therapy (n = 7) and non-hormone therapy (n = 153) patients. Group differences could not be evaluated between patients undergoing radiation therapy (n = 3) and non-radiation therapy patients (n = 157) due to a prohibitively small number of radiation therapy patients as well as no variation in their side effect frequency scores apart from pain at site of injection (P = 0.644) (Table 4).
Seropositivity and Antibody Production
Results from the seroprotection analysis are found in Table 4. Seroprotection rates after receiving the COVID-19 vaccine did not differ by treatment group. Seroprotection rates did not differ among most cancer types with the exception of hematologic cancer. Significantly lower antibody production in patients with hematologic cancers (n = 38) than other cancers (n = 83) (79.2% vs 96.5%, P = 0.002, V = 0.281) after COVID-19 vaccination (Table 4).
Discussion
Our study provides insight into patients’ experiences during the COVID-19 pandemic, which created unprecedented challenges in healthcare. Most patients felt their care was not negatively impacted by the pandemic and associated restrictions. The majority of participants reported no perceived delays in diagnosis (93.2%), treatment (91.8%), or follow-up care (98.1%). The perceived positive experience of the patients could be due to enhanced infection control measures from the hospital/clinic. The clinic adapted their guidelines on the frequency of visits to ensure the visits were minimized, while also ensuring the care was not compromised. For example, patients receiving immunotherapy were seen every 6 weeks instead of every 3 weeks, which was satisfactory to the patients, in conjunction with the virtual visits. A report by New Brunswick Institute for Research, Data and Training, showed that although cancer screenings declined during the initial peak of COVID-19 in 2020, the cancer treatments did not decline, echoing our patient experience of no perceived delays. 22 Consistent with our findings, a survey conducted in Germany revealed that most PWC (87%) did not experience changes in their treatment and care plan during the pandemic. 23 It is important to acknowledge that a small group of our patients did experience disruptions in care, which can have a substantial impact on patient's health. Patients at other institutions reported similar delays and disruptions in cancer care, for instance, in a national survey in the United States, about a third of patients reported that their cancer care was changed, delayed, or canceled; factors such as age, sex, insurance status, and comorbidities were significant predictors of care disruptions.24–26
We found that 75.2% of patients reported some level of anxiety about contracting COVID-19. Similarly, a study conducted in Germany found that 55% of PWC reported feeling anxious. 23 Although most of our patients expressed some level of pandemic-related anxiety, 99.4% of patients were not deterred from visiting a medical professional by the fear of infection. One possible explanation could be attributed to the relatively small size of the clinic compared with those in larger cities where the risk of interactions with other patients or staff is higher, thus increasing the risk of contracting COVID-19.
Although most patients (96.3%) in our study did not miss their appointments because of the pandemic, the modality of appointments was changed to comply with COVID-19 restrictions and to keep patients safe. In total, 32.9% of appointments were conducted remotely (ie, by phone or virtually). Most of the patients whose appointments were conducted this way (65.5%) were satisfied with this change. In another study, virtual care was positively received by most patients with breast cancer, but only 28% preferred a virtual initial consultation over an in-person visit. 27 Similarly, virtual care was positively received by 76% of PWC who considered virtual and in-person visits to be equal, with 13.5% rating virtual care to be better than in-person appointments and 10.5% rating it worse. 28
After COVID-19 vaccination, patients receiving immunotherapy reported pain at the injection site and chills less often than other patients. Patients receiving targeted therapy reported swollen lymph nodes and nausea less frequently than other patients. Although there are limited studies on COVID-19 side effects in PWC, we suspect that low response in side effects could be due to depleted lymphocyte levels after receipt of chemotherapy or targeted therapy.29,30 A study conducted with 621 breast cancer patients reported slightly less injection site soreness, headaches, and chills than the general population, supporting the notion that weaker immune systems yield fewer side effects. 31 In other studies, pain at injection site, sore arms, fatigue, and headache were the most commonly reported side effects in these patient groups.13,32 Further research is needed to explore the effects of different vaccination doses on immunogenicity, for patients with different types of cancers and receiving different types of treatment.
Considering the small sample size, we did not find any significant difference in seroprotection rates among treatment groups. In general, cancer treatments can help patients by inhibiting the growth of cancer and other fast-growing cells through different mechanisms (ie, chemotherapy, targeted therapy, hormone therapy, radiation therapy), or by strengthening the patient's immune system to fight the cancer (ie, immunotherapy). 33 Patients receiving immunotherapy (n = 27) had a 100% positive antibody production, along with patients receiving hormone therapy (n = 6) and radiation therapy (n = 3) (Table 4). Though not clinically significant, positive antibody production was lower in patients receiving chemotherapy and targeted therapy, compared to patients receiving immunotherapy, likely attributable to chemotherapy-induced myelosuppression or cytopenia for patients receiving targeted therapy.34,35 Although patients on chemotherapy and targeted therapy did not show a significantly lower seropositive response (87.7% and 84.9%, respectively), it may still be advisable to frequently monitor the patients to ensure better clinical outcome (Table 4).
Consistent with other studies, PWC responded to the COVID-19 vaccine. The rate of antibody response, however, was significantly lower in patients with hematological cancer (79.2%) relative to patients with other cancers (96.5%) (Table 4), reflecting a moderate difference.14–16,36 Since hematological cancers directly target the immune system, the low seroprotection rates after COVID-19 vaccination could be due to the nature of hematological cancers in addition to the treatment. 37 A study conducted with 12 patients with lymphoid malignancy who received B-cell targeted therapy and did not respond well to COVID-19 vaccination suggests that it could be due to class switching defect and suggested optimal vaccine schedule or regimen to produce a stronger immune response in patients with hematological malignancies. 38 Since patients with hematological malignancies have a lower seropositive response to the vaccine, close monitoring may be suggested for patients either on or off treatment.
Limitations
Several methodological limitations to this study should be noted. The anxiety questionnaire implemented in this study is not validated. Although many measures of anxiety are available, an anxiety measure specific to cancer patients with respect to the COVID-19 pandemic was not available; however, could be improved in future by using validated tools to strengthen findings. Given the nature of convenience sampling and small sample size (ie, radiation therapy (n = 3) and hormone therapy (n = 9)), generalizations should be made with caution. In addition, the decision to capture treatment type based on the patient's status at the time of first vaccine dose may influence seroprotection results.
The most notable events beyond the investigator's control which may have impacted the results were pandemic-related hospital restrictions and a hospital labor strike. Resultingly, there was a significant time delay between study recruitment and blood sample collection because many appointments had to be changed to phone consultations. Hospital-imposed restrictions placed severe limitations on clinic access for research purposes. Many patients had blood samples taken at locations other that the oncology clinic and had phone follow-up visits. These disruptions created discrepancies in the length of time between most recent vaccine dose and date of blood sample, which may have affected seroprotection rates, and may have impacted recruitment given that only 134 of the 178 patients who provided consent were able to provide a blood sample. As a result of the pandemic-related restrictions to clinic access, patients were only approached when in clinic for a routinely scheduled visit which varied greatly. This required flexibility with timing of recruitment and survey completion in relation to vaccine administration, and relied heavily on patient recollection for side effects and psychosocial impacts. In addition, study staff was unable to control when patients completed the survey once online link was provided. Serological tests themselves may not capture the complexity of immune protection against COVID-19, due to lack of correlation between the anti-Spike protein and the protective role vaccination, along with lack of standardized detection threshold.17,18 We should also consider that our significant findings could be spurious because of the number of tests performed for different side effects, cancers, and treatment types.
Conclusion
This study offers a snapshot of how the COVID-19 pandemic affected cancer patient perception of their oncology care at an oncology clinic in Atlantic Canada. Collected patient responses indicate the majority were satisfied with their oncology care and did not feel it was in any large extent adversely affected by pandemic-based restrictions. Enhanced infection control measures and communication strategies put in place to help patients navigate care during the pandemic likely contributed to a better perceived experience during this period. The changes in care necessitated by the pandemic also served as a proof of practice for alternate care models for the clinic. Based on these reported outcomes, the implementation of virtual visits or a hybrid care model in a preparedness plan and their implementation during a future pandemic will reduce patient anxiety about possible negative effects on their oncology care.
Due to the small number and convenience sampling of subjects for the seropositivity sub-study, it is difficult to draw any concrete conclusions regarding the effects of oncology treatments on vaccination efficacy. However, our results suggest that there are some trends consistent with other studies and would be worth exploring in further detail. The immunotherapy group showed the highest positive antibody production (100%), compared to other treatment types, such as chemotherapy or targeted small-molecule inhibitors. Hormone therapy and radiation therapy groups also showed 100% positive antibody production, albeit based on a very small sample size. As expected, given the nature of these diseases, patients with hematological malignancies had a significantly lower antibody production following vaccination when compared to other cancer types.
In summary, these results demonstrate that patients received satisfactory oncology care management in this Atlantic Canadian oncology clinic during the COVID-19 pandemic, based on patient feedback. The seropositivity sub-study results provide additional evidence of reduced vaccination efficacy in hematology patients. A future, risk-based assessment of patients based on vaccine efficacy and their cancer treatment type, may help guide clinical decisions and mitigate delays under similar circumstances in the future.
Footnotes
Acknowledgements
We would like to acknowledge Jennifer Thomas for editing of the manuscript.
Author Contributions
Conceptualization and design were done by MAS and AM; data collection was done by LR, MAS, PO, MS, NAS, MA, and RS; data analysis and interpretation were done by DDC, MAS, LR, ICC, and LB; manuscript writing was done by LB, LR, ICC, DDC, and MAS; manuscript review and editing was done by LB, LR, MAS, DDC, and ICC.
Consent to Participate
Each participant provided written informed consent before engaging in the study.
Consent for Publication
Each participant provided written informed consent to publish the findings of the study.
Data Availability
The datasets generated during and/or analyzed during the current study are not publicly available because participants did not give written consent for their data to be shared publicly but are available from the corresponding author on reasonable request.
Declaration of Conflicting Interest
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical Considerations
The study received institutional approval from Horizon Health Network's Human Research Protection Program/Research Ethics Board (File # 101291).
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The author(s) received financial support from The Friends of the Moncton Hospital.
