Introduction
Each year in the United Sates, millions of Americans are diagnosed with cancer (Siegel et al. Reference Siegel, Miller and Fuchs2022). This pervasive disease touches countless lives and subjects patients to psychological distress and physical pain. Research indicates that a significant majority of cancer patients who are actively undergoing treatment (e.g., chemotherapy, radiotherapy, surgery, and other painful procedures) face an ongoing battle with anxiety and pain (Evenepoel et al. Reference Evenepoel, Haenen and De Baerdemaecker2022; Wool and Mor Reference Wool and Mor2005; Li et al. Reference Li, Xiao and Yang2017). This phenomenon is not only exacerbated by the very nature of the treatments themselves but also intensifies symptoms and contributes to adverse psychological and physical outcomes (Li et al. Reference Li, Xiao and Yang2017; Zaza and Baine Reference Zaza and Baine2002). Moreover, inadequate management of pain intensifies anxiety and distress, and vice versa, (Zaza and Baine Reference Zaza and Baine2002) and increases risk of continued reliance on prescription opioids for effective pain management. Emerging evidence underscores how continued reliance on prescription opioids might contribute to a patient’s downward spiral of reduced quality of life (Garland et al. Reference Garland, Froeliger and Zeidan2013). These circumstances emphasize the significance of effectively addressing psychological distress and pain management in patients with cancer, particularly while they undergo treatment. The field of oncology is now challenged to ensure delivery of safe and effective supportive care to patients undergoing cancer treatments to alleviate symptoms and enhance overall quality of life.
An emerging body of literature highlights the beneficial effects of complementary and alternative medicine (CAM) strategies as a supportive approach for patients actively undergoing anti-cancer treatment (Balneaves et al. Reference Balneaves, Watling and Hayward2022). Virtual reality (VR) and neurofeedback (NF) are 2 evidence-based CAM approaches used in the management of cancer symptoms (Baños et al. Reference Baños, Espinoza and García-Palacios2013; Rolbiecki et al. Reference Rolbiecki, Craig and Megan2023a). NF is a non-invasive, evidence-based biobehavioral treatment that teaches mindful awareness and real-time modification of one’s own neural state in order to enhance executive function (Viviani and Vallesi Reference Viviani and Vallesi2021) and reduce emotional disturbances (Trambaiolli et al. Reference Trambaiolli, Kohl and Linden2021). Immersive VR is another supportive CAM strategy that has been explored for management of cancer-related symptoms (Baños et al. Reference Baños, Espinoza and García-Palacios2013). When immersive VR techniques are integrated with NF, mindful awareness of brain function corresponds with the virtual environment, creating a synergistic bio-cognitive feedback loop that helps the user maintain focus on the immersive experience. This bio-cognitive feedback loop promotes a state of calm for the user, rather than allowing them to ruminate on their pain, anxiety, or other negative thoughts associated with their cancer experience. However, the evidence for combining VR and NF (VR + NF) specifically for management of anxiety and cancer pain for patients undergoing treatment is limited. To our knowledge, we are the only study team to explore VR + NF as a non-pharmacologic approach to manage cancer symptoms for patients undergoing anti-cancer, systemic treatments (Rolbiecki et al. Reference Rolbiecki, Craig and Megan2023a, Reference Rolbiecki, Govindarajan and Froeliger2023b).
Our preliminary study of VR + NF delivered to cancer patients in an ambulatory infusion clinic revealed that the approach was not only feasible, but that patients found the intervention acceptable in terms of management of cancer symptoms (Rolbiecki et al. Reference Rolbiecki, Craig and Megan2023a). That preliminary pilot served as a foundation for the present study, in which we compared the VR + NF intervention to VR alone, and explored feasibility of delivering VR + NF across multiple treatment sessions. Therefore, the purpose of this brief report is to summarize our study and intervention protocol and share our preliminary results with regard to treatment retention and preliminary impact of VR + NF on patient-reported outcomes such as anxiety and pain.
Methods
Study design
We utilized a parallel arm trial design to compare preliminary impact of VR only and VR + NF on cancer symptoms among patients who are actively receiving cancer treatment. Patients were randomized to either group using a sequentially numbered, opaque, sealed envelope technique.
Sample
This study took place in an ambulatory infusion unit at a large Midwestern academic hospital. Thirty (N = 30) non-terminal cancer patients above the age of 18 years were recruited to participate. Patients had to (1) be receiving cancer treatment within the ambulatory infusion unit, (2) be without visual or hearing deficits or impairments, (3) be willing to participate in the intervention and subsequent data collection, (4) be presently experiencing cancer symptoms (e.g., pain, nausea, fatigue, anxiety, etc.), and (5) speak and understand English to participate. All study activities were approved by the institution’s review board.
Recruitment took place between September 2022 and April 2023. We utilized a convenience sampling technique to recruit study participants. The study’s research specialist worked collaboratively with clinic staff to screen a list of eligible patients for the day before recruiting them to participate. When eligible patients were identified, the research specialist approached them during the initial portion of their clinic visit to explain details of the study and ask whether they would like to participate. If patients demonstrated interest, the research specialist provided them an iPad with the consent form uploaded via REDCap (Research Electronic Data Capture). The research specialist reviewed the consent before requesting they digitally acknowledge consent to participate in the study. Demographics were then collected via the iPad using REDCap. After demographics were collected, patients were then given an envelope with their randomization to either the VR only or VR + NF group. Once randomized, clinic staff set the patient up with their regular treatment protocol and then notified the research specialist to begin either the VR only or VR + NF conditions.
VR + NF procedure
For this study we used Healium™ as the NF intervention condition. Participants randomized to this group received their regular cancer treatment protocol in addition to Healium™ intervention. Healium™ is the world’s first evidence based VR experience powered solely by brainwaves (Tarrant et al. Reference Tarrant, Viczko and Cope2018). In this study, the Healium™ software was delivered using an Oculus VR headset and a Brainlink – a wearable electroencephalography (EEG) device – which detected electrical activity in the patient’s brain. In Healium™, the Brainlink connects with the VR headset using Bluetooth technology and utilizes EEG data to provide patients feedback as the immersive VR experience continues. Patients saw their EEG data displayed with a small orb of light (called a “firefly”) on the lower portion of the screen. If patients remained in a relaxed or focused state while engaging in the immersive VR experience, the firefly moved above the baseline, signifying successful adherence to the Healium™ protocol. If patients became distracted or started to ruminate on pain or other cancer symptoms, the data picked up via the EEG trigger the experience to pause and change the scene’s colors while coaching the patient back to a state of focus and calm.
Patients in the intervention group engaged in a 22-minute immersive nature-based VR experience, called extended meditation. The experience itself consisted of several guided meditations that take place in nature-based scenes (e.g., near a waterfall, by the beach, during a snow day, etc.). The experience also included calming music and soft noises found in nature. The experience ended with a guided meditation that took place in a kaleidoscope of soothing colors. After finishing the Healium™ protocol, patients completed follow-up data collection, which is described below.
VR only procedure
In addition to receiving their regular treatment protocol, patients randomized to the VR only group were asked to watch an 11-minute nature-based video using the VR headset and participate in the same data collection procedures as the intervention group.
Measures
Primary outcomes were cancer symptoms assessed using the Edmonton Symptom Assessment Systems Revised (ESAS-r) form. The ESAS-r is a well-validated assessment of cancer symptom severity in which patients rate the severity of each symptom on a scale from 0 to 10 (10 being the worst possible severity) (Richardson and Jones Reference Richardson and Jones2009). In this study, all patients were asked to report ESAS-r scales at 2 timepoints during their cancer therapy sessions, a “pre” timepoint which was before starting to use VR (VR only or VR + NF) and a “post” timepoint which was after completing the use of VR. VR or VR + NF was administrated to patients in 2 consecutive therapy sessions, which were about 22 days apart. Data of ESAS-r scales were collected in those sessions and timepoints and were stored and managed using REDCap.
Analysis
Each outcome of the ESAS-r item scale was assessed of its association to the fixed effects of timepoint (pre vs post), study group (VR only vs VR + NF), session (session 1 vs. session 2), and their interaction, using a mixed effect model. A random effect was used to account for within person correlation due to repeated measurements in timepoints and sessions. Post hoc means were compared between timepoints in each session and each VR group, and changes of means were compared between VR groups in each session. Due to exploratory nature and relatively small sample size of the study, statistical tests were not adjusted for multiple comparisons. As a backup, medians of each outcome were compared between timepoints using a nonparametric Wilcoxon signed-rank test at each session and for each group. The changes of each outcome were compared between groups at each session using a nonparametric Wilcoxon rank-sum test. Results from both parametric approaches (i.e., mixed effect models) and nonparametric approaches are reported below. Baseline characteristics were summarized using frequency (in %) and assessed of their associations to either group using Fisher’s exact tests. Numerical baseline variables were summarized using mean (±), standard deviation (std), and median (minimum, maximum) and compared between both study groups using parametric 2-sample t-tests and nonparametric Wilcoxon rank-sum tests, respectively.
All statistical analyses were performed using SAS 9.4 software (SAS, Cary, NC). P-values < 0.05 were considered statistically significant.
Results
Demographics
A total of 30 cancer patients (N = 30) were recruited to the study and equally randomized to either group (VR only or VR + NF). Participants’ baseline characteristics are summarized in Table 1. No statistical differences were found between the groups. Most participants identified as female (63%), white (90%), were married or partnered (53%), had some level of college of college/trade school (67%), were retired or not employed at the time of the study (60%), and had an income level of over 40k (47%). On average study, participants were 60.2 years of age (SD = 12.9, range = 29–79 years). Additional characteristics of study participants, including infusion treatment type (e.g., chemotherapy vs. immunotherapy), and whether they had received pharmacologic pain intervention at time of study treatment can be found in Table 1.
Table 1. Summary of baseline characteristics
a Cells in these variables are mean ± std/median (min, max). Cells in all other variables are frequency (%).
b P-values were from t-tests/Wilcoxon rank-sum tests. All other P-values were from Fisher’s exact tests.
Treatment retention
Sixty-seven percent (n = 20) of participants returned to participate in a second VR session, and the rates of returning were the same between the groups. Of the 10 (33%) who were lost to follow-up: 2 finished chemo/immunotherapy prior, 2 transitioned to hospice or a different hospital system, 1 passed away, and the remaining 5 ignored staff contact regarding their continued participation.
Outcomes
Changes of ESAE-r scales between pre and post timepoints were summarized in Table 2. Figure 1 demonstrates improvements of scales in both sessions. Patients in the VR + NF group showed improvements in anxiety after both sessions 1 and 2, while patients in the VR only group showed significant improvements in pain and depression after both sessions. In addition, Table 2 shows an improvement of pain in VR + NF patients after the first session and improvements of appetite, nausea, and tiredness in the VR only group in the same session.
Figure 1. Cange in Outcomes after Both Sessions.
Table 2. Changes of ESAS-r levels before (pre) and after (post) VR intervention
a Pt and Pw indicate P-values were obtained from mixed effect models and Wilcoxon signed-rank tests, respectively.
There were no significant differences of improvements between the 2 groups (supplement table) except for appetite after completing session 1 (mean ± std of change: −2.1 ± 2.6 in VR only vs. −0.2 ± 1.5 in VR + NF, P = 0.024, Figure 2).
Figure 2. Change of Appetite for Both Groups.
Discussion
Our research team is the first to explore VR + NF as a supportive intervention for patients receiving cancer treatment, with a specific goal of managing cancer symptoms. While this study did experience a drop in retention because of patient death, patients transitioning to hospice, and patients ending their treatment protocols in the clinic, only 5 (n = 5) patients were truly lost to follow up due to ignoring staff contact or asking to unenroll in the study. These findings suggest that we should refine our inclusion criteria for future studies (e.g., having patients start the study when treatment protocols begin). Despite this limitation, we were able to successfully retain most patients (66%) over multiple treatment sessions.
Our findings suggest that VR and NF remain promising treatment approaches with regard to impact on patient-reported outcomes like anxiety and pain. These findings provide valuable insights into the multifaceted nature of cancer symptom management. First, the reduction of pain by both VR and VR + NF highlights the potential in addressing this challenging physical symptom, which originates from the cancer itself and is exacerbated by the treatments. Second, the greater effectiveness of VR + NF in reducing anxiety suggests a promising approach to tackling the often intertwined relationship between anxiety and pain, particularly among patients who are actively receiving treatment. Finally, the specific relief of appetite, nausea, and tiredness by VR alone underscores its potential for mitigating symptoms more directly associated with the disease and its treatments.
This study further emphasizes the importance of tailored interventions for managing a spectrum of cancer-related symptoms and highlights the potential of VR and VR + NF as valuable tools in improving overall well-being of patients. While this study did not indicate statistically significant reductions in pain and anxiety for the VR + NF group, our results do suggest that immersive VR combined with NF may be particularly helpful for reducing cancer diagnosis- and treatment-related anxiety. This study further emphasizes the importance of tailored interventions for managing a spectrum of cancer-related symptoms and highlights the potential of VR and VR + NF as valuable tools in improving overall well-being of patients. Additional research is required to determine whether VR + NF compared to VR alone would produce significant treatment effects among this population. Future exploratory work with a larger sample with more symptomatic patients (e.g., those who are experiencing higher levels of pain and clinically significant anxiety) and continued follow-up might reveal significant differences across the 2 groups.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S1478951524000385.
Acknowledgments
This research did not receive specific grant funding from federal or public agencies or commercial sectors. This research was supported by the Department of Family and Community Medicine at the University of Missouri School of Medicine.
Competing interests
The authors declare none.
