Music Therapy Combined with Virtual Reality Reduces Prevalent Symptoms in Adult Patients with Advanced Cancer: Randomized Clinical Trial

Abstract

Background:

Music therapy (MT) and virtual reality (VR) are increasingly being used in palliative care for symptom management, though evidence quality remains low.

Objectives:

The aim of our study was to assess the effect of combined MT + VR on the main symptom in palliative cancer patients.

Design:

This study employed an explanatory sequential mixed methods design based on a randomized controlled clinical trial, integrating quantitative outcomes with qualitative patient experiences.

Measurements:

The main symptom was the symptom rated as most severe by the patient on the Edmonton Symptom Assessment System Revised (ESAS-r) scale. Secondary outcomes included the global ESAS-r score, anxiety (additionally measured with State-Trait Anxiety Inventory—State [STAI-S]), emotional distress (DME scale), and heart rate. All variables were assessed at three time points: baseline (T1), post-intervention (T2), and 24 hours post-intervention (T3).

Patients and Settings:

Adult patients attended by palliative care with advanced cancer at a university hospital in Argentina.

Results:

Sixty patients completed the protocol. Significant differences between baseline (T1) and immediate post-intervention (T2) were observed when comparing the MT + VR condition to the control group for the main symptom (1.5 vs. 0, p < 0.001); global symptom score (9 vs. 0.5, p < 0.001); and anxiety (0.2 vs. 0.1, p < 0.001). No significant differences were found between groups at 24 hours post-intervention (T3) compared with baseline. Several categories of interest emerged: (a) affective states, (b) projections, and (c) transcendental experiences.

Conclusion:

The combination of MT + VR improved the main symptom, as compared with the control group. Patient perceptions add valuable information about the factors that influenced this difference.

Keywords

anxiety music therapy palliative care psychological distress virtual reality

Key Message

This study represents the first randomized controlled trial designed to examine the impact of MT + VR combination in patients undergoing palliative care. Our findings reveal a significant decrease in symptoms after patients receive intervention. The qualitative analysis reveals that immersion, projection, and musical entrainment mechanisms likely contribute to these therapeutic effects.

Introduction

People with cancer in the end stages of life present physical, emotional, social, and spiritual needs. These are addressed through pharmacological and nonpharmacological strategies.^1,2 Therefore, one of the fundamental objectives of palliative care is the adequate control of symptoms,^3,4 which can only be implemented in the context of “total palliative care,” which is defined by those interdisciplinary interventions that have scientific evidence demonstrating significant modifications in the quantity or quality of life of patients.⁵

Music therapy (MT) seeks to optimize quality of life based on controlling physical, psychological and emotional symptoms, improving individual and social well-being, and coping with end of life. Virtual reality (VR) is a combination of technological devices that allow users to interact with three-dimensional environments through headsets that create 360-degree sounds and images, producing a sensation of physical presence and immersion.^6,7

The combination of MT and VR has shown effectiveness in different clinical contexts in reducing anxiety,^8–10 pain,¹¹ and mood regulation.⁸ Chirico et al.⁸ compared VR and MT as separate interventions in chemotherapy patients, finding both approaches significantly decreased anxiety and improved mood with no differences between groups, though measurements were limited to immediate post-intervention. However, the combined use of MT and VR has been minimally explored in palliative care. Brungardt et al.¹² conducted the only study to date examining MT + VR combination in 23 hospitalized palliative care patients through a feasibility assessment, reporting positive patient experiences but emphasizing the need for rigorous clinical trials to evaluate efficacy. In palliative care specifically, the quality of evidence for both individual and combined interventions remains low.

A Cochrane systematic review¹³ highlighted that MT studies in palliative care are difficult to compare due to wide intervention variability, insufficient methodological reporting, and small sample sizes (average n = 35). Individual studies of MT in this population have shown promise—including significant anxiety reduction in a 25-patient randomized trial¹⁴ and pain reduction in 14 patients¹⁵—but the evidence base lacks adequately powered randomized controlled trials with standardized methodologies.^16–18 No controlled trials have yet evaluated the combined MT + VR intervention in palliative care patients.

The objective of our study was to evaluate the effect of combining music therapy (MT) and virtual reality (VR) on the main symptom reported by adult patients with advanced cancer under the care of a palliative care team. This main symptom was defined as the one the patient rated as most severe on the Visual Analogue Scale.

Methods

Interventions

We designed a randomized controlled trial using an explanatory sequential mixed methods approach to evaluate the impact of combined MT + VR interventions.

Patients, settings, and procedures

The study was carried out in the Palliative Care Unit of the Austral University Hospital. Patients over 18 years of age with advanced cancer admitted to the Unit were included. Additionally, they needed to have met the following criteria: (1) at least one symptom of the Edmonton Symptom Assessment System Revised (ESAS-r) scale had to be rated by the patient with 7 or more,⁴ (2) the ability to adopt a posture of at least 45 degrees in bed and a state of alertness and adequate response,¹⁹ (3) the absence of cognitive impairment (measured by the Pfeiffer scale > 2 errors),²⁰ and (4) functional hearing (with or without hearing aids or other devices).¹⁶ Patients were excluded if they: Had cognitive impairment (as measured by the Pfeiffer scale > 2 errors) and/or had hearing or visual impairment. Patients who met the inclusion criteria and signed the informed consent form were randomly assigned to one of the following groups: MT + VR or control group. Control group received standard palliative care from the palliative care team without music therapy intervention. The music therapy session combined with virtual reality involved four stages: (a) Background settings; (b) VR video and music selection; (c) Listening experience and VR; and (d) Return to alert status (Fig. 1).

FIG. 1.

MT + VR intervention protocol.

The full protocol has been previously published²¹ and is available in the supplementary material (Supplementary Data S1). In brief, the intervention consisted of a 30-minute session integrating MT with VR, delivered in four sequential phases: (1) background setting, (2) musical audition and video selection, (3) VR video playback with live music, and (4) return to alert status. Patients selected one of four immersive 360° virtual environments—mountain, beach at sunrise, beach at sunset, or lake with stones, viewed through an Oculus Quest 2 headset. Simultaneously, a music therapist facilitated live, personalized music using guitar or violin (instrumental or vocal), tailored to the patient’s preferences to enhance relaxation. The intervention was grounded in musical entrainment principles, with the therapist dynamically adjusting tempo and volume in response to the patient’s vital signs to optimize relaxation. For example, if a patient presented with an elevated respiratory rate (e.g., 24–26 breaths per minute), the music therapist initially matched the musical tempo to the patient’s breathing pattern and then gradually decreased the tempo to facilitate slower breathing. The therapist could directly observe the reduction in respiratory rate as the musical tempo decreased. When vital sign monitors were available, changes in heart rate could also be observed, although respiratory rate remained the primary parameter used to guide entrainment adjustments. This entrainment approach was applied consistently across all participants.

Measurements

The main symptom was defined as the one perceived by the patient as most severe, based on the ESAS-r.⁴ Symptom intensity was evaluated at three time points: baseline, prior to the intervention or control condition (T1); immediately after the condition (T2); and 24 hours post-condition (T3). The ESAS-r was used to assess both the intensity of the main symptom and the overall symptom burden via its total score. We also employed validated ESAS subscales, including:

the Global Distress Score (GDS), the sum of the first nine physical and psychosocial symptoms (range: 0–90),

the Physical Distress Subscale (PHS) (range: 0–60), and

the Psychological Distress Subscale (PSS) (range: 0–20).

A minimum clinically significant difference was defined as a reduction of ≥ 1 point for individual symptom scores and a reduction of ≥ 3 points on the global ESAS score.¹⁹ Clinically significant improvements were also defined as reductions of ≥ 3 in GDS, ≥ 2 in PHS, and ≥ 2 in PSS.²²

Anxiety was measured using the State-Trait Anxiety Inventory—State (STAI-S) scale at the same three time points as the ESAS-r. Emotional distress was assessed using the Detección del Malestar Emocional (Detection of Emotional Distress) (DME) scale, measured only at baseline (T1) and 24 hours post-intervention (T3).

In addition, the following variables were included: demographic information (age, gender, time of measurements); type of cancer; physiological measurements (heart rate); and musical information (importance of music for the patient measured on a Likert scale from 0 to 10, formal musical education measured in years, previous experience using music for relaxation measured as YES/NO, previous experience using virtual reality measured as YES/NO).

Data analyses

The descriptive analysis was conducted using the median as the central measure and the range as a measure of dispersion. Additionally, percentages were included. For inferential analysis, significance tests were chosen with a statistical significance threshold of p < 0.05. The analysis was performed using the R Studio program, employing the Wilcoxon test.

Changes in each variable were analyzed within each condition (MT + VR and Control) by comparing paired data across three time points: baseline (T1), immediate post-intervention (T2), and 24 hours post-intervention (T3). To assess between-group differences, change scores were calculated (T1–T2 and T1–T3), and these were compared between the MT + VR and Control groups using unpaired data analyses.

To code the qualitative data, a structured procedure was followed. This involved a thorough reading and analysis of participants’ responses to the ad hoc questionnaire (see Supplementary Data S2), which was administered to those who received the intervention. Relevant data segments were identified and assigned specific labels or codes. These codes were then grouped into broader categories to capture overarching themes. The coding and categorization process was carried out using the web-based version of the Atlas.ti software.

This research has been approved by the Evaluation Committee under the number: ID-P21-069 on September 15, 2022.

This trial was registered with Clinical Trials under the number: NCT05603767. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee (ID-P21-069).

The STAI requires a license for its use. It was purchased and granted under number #52411 to the Civil Association for Higher Studies Asociación Civil de Estudios Superiores, Facultad de Ciencias Biomédicas (ACE FCB).

Results

Between September 2022 and May 2023, a total of 151 patients were admitted to the Palliative Care Unit, of whom 79 were excluded from the study for not meeting the inclusion criteria. Out of the 72 randomized patients, 60 successfully completed the protocol. The Consolidated Standards of Reporting Trials (CONSORT) diagram (Fig. 2) illustrates the reasons for exclusion and the causes of drop-off during the study period.

FIG. 2.

CONSORT flow diagram showing patient enrollment, randomization, and follow-up throughout the clinical trial.

The baseline characteristics of patients in the control group were compared with those in the treatment group (Table 1).

Table 1.

Characteristics of Included Patients

	Total sample n = 60	MT + VR n = 30	Control n = 30	Mean diff (IC 95%)	Odds ratio	p value
Age (years), mean (SD)	55.1 (13.8)	53.6 (12.1)	56.8 (15.5)	3.2 (−13.6,7.3)		0.54
Gender, (*) n (%)					1.22 (0.37,5.29)
Female	20 (67)	11 (69)	9 (64)
Male	10 (33)	5 (31)	5 (36)
Musical education, n (%)					0.58 (0.069,4.38)
Yes	7 (23.3)	3 (18.8)	4 (28.6)
No	23 (76.7)	13 (81.3)	10 (71.4)
Hospitalization place, n (%)					0.0	0.49^a
Central Hospital	28 (93)	14 (87.5)	14 (100)
Palliative Care Unit	2 (7)	2 (12.5)	0 (0)
Underlying Oncological Disease by Systems, (*), n (%)						0.73^b
Digestive Tumors	10 (33.3)	7 (43.7)	3 (21.4)
Lung	4 (13.3)	2 (12.5)	2 (14.2)
Breast	8 (26.6)	4 (25)	4 (28.5)
Genitourinary	5 (16.6)	2 (12.5)	3 (21.4)
Other tumors	3 (10)	1 (6.25)	2 (14.2)
Music importance					Inf	0.48^a
Medium (<8)	2 (6.6)	2 (12.5)	0 (0)
High (≥8)	28 (93.3)	14 (87.5)	14 (100)
Past use of music for relaxation, n (%)					1.91 (0.37,13.5)
Yes	26 (86.6)	14 (87.5)	11 (78.5)
No	4 (13.3)	2 (12.5)	3 (21.5)
Past use of VR, n (%)						0.52 (0.0, 3.7)
Yes	5 (16.6)	2 (12.5)	3 (21.5)
No	25 (83.4)	14 (87.5)	11 (78.5)

*Shapiro test for Normality p value > 0.05.

^aFisher’s exact test.

^bChi-square test.

VR, virtual reality.

Effects on primary outcomes

The distribution of main symptoms varied between groups. In the treatment group, anxiety (30%) and pain (23%) were most frequently reported, followed by lack of appetite (10%), tiredness (10%), drowsiness (10%), nausea (7%), shortness of breath (7%), and depression (3%). The control group showed a similar pattern with pain (47%) being most common, followed by anxiety (17%), tiredness (13%), lack of appetite (7%), shortness of breath (7%), nausea (3%), depression (3%), and discomfort (3%).

Significant differences in the main symptom intensity were observed between baseline (T1) and immediate post-intervention (T2) measurements in the MT + VR group (Wilcoxon signed-rank test, p < 0.05). When comparing between groups, the MT + VR condition showed significantly greater symptom reduction than the control condition immediately post-intervention, but this difference was not maintained at the 24-hour follow-up (T3) (Table 2). Figure 3 illustrates the pre-post changes in main symptom intensity for each condition and the between-group differences.

FIG. 3.

Changes in the guide symptom (ESAS-r) and differences by conditions.

Table 2.

Inferential Statistics by Conditions and Their Differences in Each Variable

Condition	Time	Median**	p value
Symptom guide (ESAS-r)
Receptive Music Therapy (RMT) + VR	Post-intervention (M1)	1.5	0*
	24 hours later (M2)	0	0.06
CONTROL	Post-intervention (M1)	0	0.94
	24 hours later (M2)	0	0.48
Prevalent symptoms (ESAS-r)
RMT + VR	Post-intervention (M1)	9	0*
	24 hours later (M2)	3	0.03*
CONTROL	Post-intervention (M1)	0.5	0.19
	24 hours later (M2)	0	0.28
Anxiety (STAI-S)
RMT + VR	Post-intervention (M1)	0.2	0*
	24 hours later (M2)	0.1	0.11
CONTROL	Post-intervention (M1)	0.5	0.45
	24 hours later (M2)	−0.5	0.74
Emotional distress (DME)
RMT + VR	24 hours later (M2)	1	0.08
CONTROL	24 hours later (M2)	−1	0.73

Differences between conditions
Outcome	Time	p value
Symptom guide (ESAS-r)	Post-intervention (M1)	0*
Symptom guide (ESAS-r)	24 hours later (M2)	0.17
Prevalent symptoms (ESAS-r)	Post intervention (M1)	0*
Prevalent symptoms (ESAS-r)	24 hours later (M2)	0.07
Anxiety (STAI-S)	Post-intervention (M1)	0.002*
Anxiety (STAI-S)	24 hours later (M2)	0.10
Emotional distress (DME)	24 hours later (M2)	0.26

*Wilcoxon test p < 0.05.

** for paired pre-post data.

ESAS-r, Edmonton Symptom Assessment System Revised; STAI-S, State-Trait Anxiety Inventory—State; VR, virtual reality.

Additionally, significant differences were found in the global ESAS-r score immediately post-intervention (T2) within the MT + VR group, with significant between-group differences favoring the MT + VR condition compared with control at this time point only (Table 2). For anxiety measured by the STAI, significant differences were also observed immediately post-intervention (T2) favoring the MT + VR group (Table 2). Emotional distress, which was only measured with the DME scale at baseline and 24 hours post-intervention, showed no significant differences between the two groups. Analysis of heart rate scores revealed no significant differences between groups at any time point.

Qualitative findings and patient experiences

Thirty responses were analyzed only from patients who received the intervention. From the open coding, 45 codes were identified, which were subsequently grouped into 3 categories: (1) affective states, (2) projections, and (3) transcendental experiences.

Affective states

The term “affective states” is used broadly to encompass all emotional experiences including emotion, arousal, stress responses, motivational drives, interpersonal stances, preferences, mood, attitudes and affective styles that have been reported by participants. This category includes 45 quotes, which were grouped into 4 codes: relaxation, tranquility, peace, happiness/sadness. The concept of relaxation was mentioned by 16 out of 30 patients and was associated with feelings of drowsiness or the desire to sleep, as well as the immersive quality of the experience. In some cases, relaxation was also linked to the ability to distract oneself from the illness.

Projections

In this study, we define projections as the human ability to create vivid and detailed mental images in the imagination. This category includes instances where patients describe images that were not actually reproduced by the helmet. There were 30 such cases, linked to places, people, and actions.

Regarding places, 14 out of 30 patients mentioned memories of locations they had previously visited, noting that some elements of those places appeared in the video they watched. Meanwhile, 7 out of 30 patients reported seeing themselves or others in the video. These others were generally relatives, and in two cases, they were deceased individuals. Lastly, 9 out of 30 patients imagined themselves performing various activities, mainly involving contact with nature, especially water.

Transcendental experiences

Transcendental experiences refer to experiences or moments in which a person feels a sense of deep connection, expanded awareness, and a feeling of transcending the usual boundaries of existence. These experiences are often characterized by a sense of unity, meaning, and transcendence beyond everyday experience. In a sample of 30 patients, 16 reported having such experiences. Some of these were linked to spirituality, described as a deep connection with something greater than oneself or with the entirety of existence. Others were connected to nature, where individuals reported feelings of calm, serenity, and satisfaction. These natural connections often generated a profound sense of well-being.

Discussion

To our knowledge, this is the first clinical trial to evaluate the combined effect of MT and VR in patients receiving palliative care. Our findings reveal statistically significant improvements immediately after the MT and VR intervention, including reductions in the primary symptom, decreased anxiety levels, and a lower overall symptom burden. These results suggest that combining MT and VR could offer a promising nonpharmacological approach to symptom management in palliative care settings.

Our trial addresses the critical gap identified in previous research by providing the first randomized controlled evaluation of combined MT + VR in palliative care, with detailed methodology, adequate sample size (n = 60), and consistent short-term results across all evaluated symptoms.

In our study, thematic analysis revealed that relaxation was the most frequently reported outcome. Patients described: “If you really get into the experience…it generates a change in the body and mind” (Patient 5), “I feel inner peace” (Patient 11), and “I feel that I float above the stones”(Patient 23). This aligns with findings from previous MT and VR studies.^8,12 This effect was largely attributed to the immersive nature of the intervention. These findings underscore the significance of immersion and mental imagery, core components of VR, in fostering a sense of presence and enhancing therapeutic outcomes.²³

Music was often described in relaxing, peaceful terms: “It gave me energy, I felt accompanied” (Patient 10), “The music was serene like the water, it relaxed me” (Patient 25). These descriptions align with the revitalization mechanism and musical entrainment strategy for affective self-regulation,²⁴ in which the therapist improvises by adjusting musical parameters to the patient’s rhythms.²⁵ This improvised approach contrasts with the use of prerecorded music in previous studies by Chirico et al.⁸ and Brungardt et al.¹² The combination of the immersive virtual environment and live musical improvisation appeared to facilitate relaxation within this MT + VR intervention.

Patients also reported projection and transcendental experiences. Some visualized deceased loved ones: “I was walking with my brother…we were laughing” (Patient 3, whose brother had died nine months earlier) while others described spiritual or existential connections: “Connected with life, feeling the immensity of everything” (Patient 20) and “I looked up to the sky and thought of the Virgin Mary” (Patient 23).

Musical selection was patient-directed, with participants choosing either instrumental or vocal music. The music therapist monitored patients’ facial expressions throughout the session to identify signs of relaxation, although these observations were not formally quantified. An interesting pattern emerged in the qualitative responses: patients who selected music with lyrics often referenced specific words or phrases from the songs when describing their experience. For example, one patient stated: “Beautiful. I keep the part of the lyrics ‘How can I still be singing…’ it took me to my situation” (Patient 2), while another noted: “The lyrics accompanied wonderfully, what it says ‘you have them by your side’” (Patient 7). In contrast, patients who chose instrumental music described their experiences in more general emotional or affective terms, without specific linguistic anchoring. Although our sample size (n = 60) precluded definitive conclusions about differential effects between instrumental and vocal music, these observations suggest that lyrics may frame or condition the subjective experience, and that systematic assessment of non-verbal indicators (such as facial expressions) could provide additional insights into real-time therapeutic responses. Both warrant further exploration in future studies.

Limitations

This study presents two important limitations. First, it is a single-center study conducted by one music therapist, which may introduce potential bias into the results. The findings could be influenced by factors unique to this specific setting or timeframe, limiting generalizability to other contexts. The individual researcher’s perspective may have unconsciously influenced methodological choices, data interpretation, and presentation of findings. Secondly, as a single-intervention study, our results only demonstrate short-term outcomes, leaving questions about the durability and long-term efficacy of the MT and VR combination therapy unanswered. Future multi-center trials with diverse practitioners and longitudinal designs would strengthen the evidence base for this promising intervention.

Implications

Improvement appears to be limited in duration, and it is crucial to ascertain whether the repetition of the experience or learning to replicate it without the presence of the music therapist can extend its effects, achieving the intervention’s effectiveness over a more extended period.

Conclusions

The results of the present study suggest that the combination of MT and VR improved the main symptom, prevalent symptoms, and anxiety in patients receiving palliative care. Patient perceptions emphasize the statistical results, adding valuable information about the factors that influenced those results and that were mainly related to the mechanisms of immersion, projection and musical entrainment.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research received external funding. It was the winner of the 17th Internal Competition for Scientific Research Projects 2021 80020210400003UA (SIGEVA project code) of Austral University.

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