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17
Kind of blue
- a systematic review and meta-analysis of music interventions in cancer treatment
by
Margrethe Langer Bro1,2
Kira Vibe Jespersen3
Julie Bolvig Hansen4,5
Peter Vuust3
Niels Abildgaard6
Jeppe Gram7
Christoffer Johansen8,9
Abstract: word count = 250
Full text: word count = 3324
1
The Danish National Academy of Music, Odense, Denmark
2
Institute of Regional Health Science, University of Southern Denmark, Odense, Denmark.
3
Center for Music in the Brain, Institute of Clinical Medicine, Aarhus University/The Royal
Academy of Music, Aarhus/Aalborg, Denmark
4
Departments of Sports Science and Clinical Biomechanics, The University of Southern
Denmark (SDU)
5
Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital,
Copenhagen, Denmark
6
Department of Haematology, Odense University Hospital, Denmark
7
Department of Endocrinology, Hospital of Southwest Denmark
8
Oncology Clinic, Rigshospitalet, University of Copenhagen, Denmark
9
Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark
Corresponding author: Margrethe Langer Bro. University of Southern Denmark, J. B.
Winsløws Vej 19, 5000 Odense, Denmark. E-mail: mlbro@health.sdu.dk. Tel +45 2231 0140
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/pon.4470
Objectives Music may be a valuable and low-cost coping strategy for cancer patients. We
conducted a systematic review and meta-analysis to identify the psychological and physical
effects of music interventions in cancer treatment.
Methods We included randomized, controlled trials with adult patients in active cancer
treatment exposed to different music interventions versus control conditions. Qualitative
studies and systematic reviews were excluded. We identified a total of 2624 records through
two systematic searches (June 2015, September 2016) in PubMed, Scopus, EMBASE,
Cinahl, Web of Science, Cochrane and PsycINFO and used Risk of Bias Assessment, GRADE
and Checklist for Reporting Music-Based Interventions to evaluate the music applied and
quality of the studies. We conducted meta-analyses using Review Manager (version 5.3).
PROSPERO reg. no. CRD42015026024.
Results We included 25 RCT´s (N=1784) of which 20 were eligible for the meta-analysis
(N=1565). Music reduced anxiety (SMD -0·80 [95% CI -1·35 to -0·25]), pain (SMD -0·88
[95% CI -1·45 to -0.32]), and improved mood (SMD -0·55 [95% CI -0·98 to -0·13]).
However, studies were hampered by heterogeneity with I2 varying between 54% and 96%.
Quality of the studies ranged from very low to low. The most effective mode of music
intervention appeared to be passive listening to self-selected, recorded music in a single
session design.
Conclusions Music may be a tool in reducing anxiety, pain and improving mood among
cancer patients in active treatment. However, methodological limitations in the studies
carried out so far prevent firm conclusions.
Music is increasingly offered as an adjunct to cancer treatment in the clinical setting [1-7].
Cancer affects all aspects of life, both in terms of somatic, psychological and social
dimensions, and these multi-dimensional problems are so immense and complex that they
require interdisciplinary approaches to meet the patient’s needs [8]. Music is observed as a
potential source for wellbeing for patients coping with a cancer diagnosis, during treatment
and in the aftermath [1-7].
Previous reviews of music, given at different time points of cancer treatment, have shown
that both somatic and psychological symptoms are positively affected by music [1-7].
However, these reviews applied different inclusion criteria for studies included. For example
the first and recently updated Cochrane meta-analysis included both randomized and quasi-
randomized studies [1]. Moreover, paediatric studies were not excluded from their analysis.
Consequently, inclusion of such ambiguous data may reduce the usefulness and impact of
their conclusions. One of the subsequent reviews published, included 17 studies in Chinese,
not available in English [3]; further one previous review conducted a screening strategy
focusing solely on anxiety by using the PEDro-scale to measure methodological quality,
which resulted in only four studies for meta-analysis [5]. Finally, a review published in 2014
included 21 RCTs and quasi-experimental studies across all age groups [6]. However, more
importantly, these reviews did not consider the qualities of the music, the patient´s musical
background or musical preferences as part of the evaluation of the effects of the music
intervention [1-7]. For example, it remains to be investigated how key elements of musical
structure such as tempo, rhythm, pitch, frequency spectrum and duration or type of music
influence the efficacy of the music provided.
In this review and meta-analysis we aim to clarify how music interventions affect
psychological and physical symptoms in patients undergoing active cancer treatment by
including information on 1) the involvement of the patients undergoing the intervention, e.g.
passive listening or active participating, 2) how live versus recorded music influences the
effect, 3) whether music is applied one or more times; e.g., single- or multiple sessions, and
finally 4) how intervention content; e.g., repertoire, tempo, rhythm, harmony and tone
influence the outcome under study.
Search strategy
Two authors, (MLB and KVJ) conducted a systematic search in PubMed, Scopus, EMBASE,
Cinahl, Web of Science, Cochrane and PsycINFO and independently screened all titles and
abstracts evaluating full text articles for inclusion. Any disagreements were discussed and
clarified in consensus with a third author (CJ). Reference lists of reviews were hand-searched
for additional references. The research dates were June 26, 2015 and September 1, 2016 for
update search. The selection process is summarized in the Prisma flow diagram (Fig. 1) and
the search terms were: PubMed search strategy:
1 Neoplasms (MESH)
2 Cancer OR oncolog* OR Malignan* OR Neoplasm* OR Carcinoma* OR Tumo*
3 #1 OR #2
4 Music (MESH)
5 Music therapy (MESH)
6 Music*
7 #3 AND #4 OR #5 OR #6s
If sufficient data was available, we included the following outcomes for the meta-analysis:
In accordance with the recommendations of the Cochrane Handbook [9], a quality assessment
of the included articles was performed independently by two review authors (MLB and KVJ),
using the risk of bias assessment by Cochrane (Fig. 2*).
We used the GRADE scoring system, adopted by the Cochrane Collaboration [9], to rate the
overall quality of the evidence (Table. 3*). Further, we adapted the Guideline for Music-
based Interventions developed by Robb et al, [10] by adding information regarding the
Patients’ Perspective; e.g., musical background, preference and hearing ability (Table 1, full
version*). Musical background is defined as musical engagement and training, musical
culture and frequency of music listening.
Statistical analysis
We used Covidence [11] to extract the predefined outcomes from the included trials. For each
eligible study, mean (m) and standard deviation (SD) or standard error (SE) and relevant
demographic information were extracted. If data was not available, the authors of the trial
were contacted. Meta-analyses were conducted for all outcomes where one or more trial
reported data (Fig. 3a) (Fig. 3b-3j*). We calculated the pooled estimate by using the random
effects model in Review Manager 5.3. When multiple outcomes measures reported the same
outcome, standardized mean differences (SMDs) were used. Where only one study or a single
outcome measure was reported we used mean differences (MDs). Negative effect size
indicated a beneficial effect of the intervention. According to Cohen 1988 [9], an effect size
of 0.2 was considered a small effect, an effect size of 0.5 medium and an effect size of 0.8
was considered to be large.
RESULTS
Patients were passively listening to music in 15/25 studies; 13 studies applied recorded music
studies [12 - 16, 20, 23, 24, 27, 31 – 34] and 2 live music [22, 36]. Recorded music offered a
self-reflecting inner musical experience, whereas live music added a shared musical moment
together with the musician(s). Patients were active participating in the music intervention, in
10/25 studies; four recorded music studies [19, 21, 26, 28] and six live music studies [17,18,
25, 29, 30, 35]. Out of these, one three-armed study compared active participation with
passive listening versus control [28]. Recorded music offered a supportive dimension in
terms of verbal relaxation techniques, guided imagery and mood matching techniques,
whereas live music covered mutual and engaging involvement from singing along, clapping,
or tapping feet to improvising into a creative musical process. In all studies with active
participation, music therapists conducted the targeted interventions.
Psychological outcome
Anxiety (Fig. 3a, 4a*) Twelve studies focused on anxiety-reduction, mostly through recorded
music 11/12. Out of these, nine studies were eligible for meta-analysis showing an overall
statistically significant anxiety reduction (SMD -0·65 [CI 95%-1·20,-0·11]) [12, 14, 16, 17,
21, 26, 27, 31, 32]. The intervention design varied, e.g., 8/12 passive listening, 7/12 single
sessions. Keywords for music-choice were familiar, soothing, predictable and relaxing music.
Mood (Fig. 4b, 4b*). Six studies investigated mood [18, 22, 25, 28, 29, 36] and four were
eligible for meta-analysis showing an overall statistically significant effect (SMD -0·55 [CI
Other psychological primary outcomes were measured in six trials without showing an
overall statistically significant effect; depression (Fig. 3c*) [15, 26] (SMD -0·89 [CI 95% -
2·92, 1·14]), spirit (Fig. 3d*) [35] (MD -2·69 [CL 95% -5·57, 0·19], distress (Fig. 3e*) [18,
26] (SMD -0·25 [CI 95% -1·03, 0·52]), Quality of Life (Fig. 3f*) [18, 23] (SMD -0·21 [CI
95% -0·55, 0·14] and relaxation (Fig. 3g*) [17] (MD 1·23 [CI 95% 0·42, 2·04]. Patients were
actively involved in four studies, and most studies used multiple session designs. Three
studies offered live music and three studies applied recorded music.
Physical outcomes
Pain (Fig. 3h, 4c*). Eight studies were eligible for meta-analysis. Except one study [26], pain
was significantly reduced by music (SMD -0·88 [CI 95% -1·45 to -0·32])[12, 13, 22, 29, 31,
33, 34]. Overall, the intervention design was similar across studies; e.g. passively listening in
6/8 studies and single sessions in 5 studies. Besides two studies [26, 29] applying patient
preferred live-music, the researchers had specific considerations on which recorded music
style, genre, volume and tempo, that could trigger pain-relief; e.g., slow (60-80 beats per
minute), sustained melodic quality and controlled volume and pitch [34], relaxing,
instrumental music [33] and classical, easy listening, inspirational new age music [12].
Other physical outcomes. Fatigue (Fig. 3i*) was measured in three studies [17, 26, 30]
without showing an overall statistically significant effect (SMD -0·22 [CI 95% -1·08, 0·63]).
In these studies, patients were actively involved by singing along [17], attending relaxation
techniques [26] or verbal interaction between songs [30]. Nausea (Fig. 3j*) was measured as
primary outcome in a three-armed study [23] without showing statistically significant effect
(MD 3·92 [CI 95% -2·22, 10·07]).
Overall, 16/25 trials found a significant effect on the primary outcome. The majority of
studies offering passively listening to music showed larger effect on primary outcome (11/15
studies) than those conducting active participating (5/10 studies). One may anticipate that
treatment modalities of the cancer disease; e.g., radiation therapy, surgery or chemotherapy
According to Table 1 (full version*), Intervention Theory and Schedule Delivery were well
described in most studies, whereas information about Music Repertoire was inadequate in
11/25 studies. Half of the studies excluded patients with hearing problems 12/25, whereas
only few investigated the patient’s musical background [22, 27, 34] preference [19, 24, 34]
and setting of the intervention [18, 21, 22, 32, 35].
DISCUSSION
Our systematic review and meta-analysis suggest that music can relieve anxiety and pain for
patients in active cancer treatment. However, the studies are hampered by small sample sizes
[12, 17 - 20, 22 - 26, 28 - 30, 32, 33, 35, 36], risk of underpowered studies [23-27, 30, 32],
heterogeneity in the interventions applied and overall low - to very low-rated quality of the
studies.
In studies investigating pain, single-sessions were applied in most studies [12, 29, 31, 33, 34]
except three [14, 23, 26], and patients were passively listening in six out of eight studies. In
these studies, intervention theory, design and content of the music were connected with the
patient´s music choice. However, the studies were small and the validity as well as reliability
of effect measures varied. Conversely, a significant decrease in a majority of anxiety-studies
was supported using STAI-scales [12, 14, 16, 20, 21, 31], large sample sizes [14, 16, 21, 31]
and partial coherence between intervention theory, exposure and musical content [12].
With regard to tempo [17] and music applied [16, 17] information was sparse, and three
articles investigating anxiety, pain and depression as primary endpoints, respectively, were
published based on the same material [13 - 15]. Overall, fewer than 100 patients were
included in studies before 2010, and there was no increasing tendency over time in
conducting power calculations.
The most well documented mode of music intervention is passively listening to recorded
music in a single session design. The majority of studies offering passively listening to
music showed significant outcomes (11/15 studies) compared to those conducting active
participating (5/10 studies). The passive listening trials were more transparent with regard
to design, musical content, and most studies used recorded music. Further, no live music
Music is not just music. The understanding of the nature of musical sound is vital in order to
meet the individual cancer patient´s needs and hereby achieve the desired effect. One of the
reasons for this is that music has an arousal-regulating effect [38, 39]. Slow musical tempo is
found to decrease heart rate and blood pressure, while faster music increases these
measurements [40]. Further, especially self-selected favourite music can create positive
emotions, activate memories, affect heart rate, blood pressure and respiration and decrease
levels of pain [41, 42] and cortisol [43, 44]. Therefore, music tends to be a beneficial tool for
relief of anxiety and pain and for stress reduction with direct implication for cancer treatment
[45 – 48, 49]. This is essential knowledge in the understanding of how music interventions
may work.
Clinical implications:
Music is a valuable tool that is easy to use in the clinical setting. More high-quality
randomized controlled trials are needed to assess the effectiveness of music in cancer
treatment; however, such interventions would be meaningless unless the patient´s musical
perspective is included in their design
This is the first review comparing design, musical content, musical background, preference
and involvement of the patient with outcome-results. The fact that patient-preferred, recorded
music in a single session design seems to be the most well documented mode of intervention
gives a in-depth view on where to improve in design and transparency in multiple-session
studies applying live music. Bradt el al used broader inclusion criteria and they found that
multiple session music therapy studies were either as effective or more effective than music
medicine studies on QoL[1].
A possible limitation of our study might be not restricting the studies for meta-analysis based
on quality of evidence. However, we included al eligible studies in order to reveal the overall
quality of music interventions in active cancer treatment.
Conclusion
Music may be a tool in reducing anxiety, mood and pain among cancer patients in active
treatment. However, lack of transparency in music repertoire and methodological limitations
in the studies carried out so far refrain firm conclusions. When using the guidelines by Robb
et al, (2011), Gebauer et al, (2014) and adding the patient´s musical perspective; e.g.,
background, preference and hearing ability, the quality of future studies might increase. One
may anticipate that music might provide recovery of self-identity, meaning and coherence in
life and hereby add musical empowerment to the everyday life of the individual cancer
patient.
* online material
Acknowledgements
We would like to thank research librarian Peter Everfelt for his assistance with the search process.
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Figure Legends
Huang 1) Yes 4 tapes available: Folk- RECORDED 2) PASSIVE 30 min 1) Yes 3) No info
2010 tunes and Buddhist MUSIC (CD) 2) Yes
[34] hymns, harp and piano Headphones
music. Sedative music, Volume:
without lyrics, sustained Controlled
melodic quality,
controlled pitch, 60-80
Zimme USA Bot 40/40 Oncology Pain 1. RM Primary: Pain (MPQ) Primary: Decrease
rmann h Metastatic manageme 2. SC Secondary: VAS Secondary: NS
* disease nt Post-test measured after intervention
[33]
Smith* USA Bot 44/42 Oncology During 1. RM Primary: Anxiety (STAI) Primary: NS
[24] h Stage radiation 2. SC Post-test measured after 1 week of
unknown therapy interventions
Cassilet USA Bot 69/62 Haematologic During 1. LM Primary: Mood. POMS-short form Primary: NS
h h al high-dosis 2. SC Measured over whole in-patient stay. Secondary: Improvement
[25] Stage radiation Secondary: Mood. POMS-short form.
unknown therapy Measured before and after first MT and
with every 3rd day of inpatient stay.
autologous
stem cell
transplanta
tion
Clark USA Bot 68/63 Oncology Radiation 1. RM Primary: ND Secondary: NS
[26] h Stage I-IV therapy 2. SC Secondary: Anxiety & Depression
with or (HADS), Treatment-related distress &
without Pain (NRS), Fatigue (POMS).
surgery Post-test measured at mid-point and at the
and end of RT
chemother
apy
Hanser USA F 70/42 Metastatic Chemother 1. LM Primary: Psychological distress (HADS). Primary: NS
[18] breast cancer. apy and 2. SC Quality of life (FACT-G Secondary: Improvement
Stage IV other Spirituality (FACIT-sp)
therapies Secondary: Mood, Relaxation, Comfort
(VAS).
Burns* USA Bot 49/30 Acute Intensive 1. RM Primary: Anxiety STAI-YI (STAI-YU) Primary: NS
[19] h leukemia myelosupp 2. SC (and Feasibility**) Secondary: NS
Stage resive Secondary: Affect (PANAS)
unknown chemother Fatigue (FACIT-F)
apy Anxiety (STAI-YI)
Time of measuring post-test unclear
Bulfone Italy F 60/60 Breast Waiting 1. RM Primary: Anxiety (STAI) Primary: Reduction
* Stage I-II for 2.SC Post-test measured after intervention
[20] adjuvant
chemother
apy
Huang Taiwan Bot 129/12 Various Cancer 1. RM Primary: Cancer related Pain. (dual VAS Primary: Decrease
[34] h 6 Stage I-IV pain 2. SC (rest) scale -sensation and stress) Distress: Decrease
Waitlist-control Post-test measured after intervention Sensation: Decrease
design
Zhou‡ China F 120/10 Breast Radical 1. RM 1. Depression (ZSDS Chinese version) 1. Reduction
[15] 5 Mixed stages mastectom 2. SC 2. Duration of hospital stay 2. Shorter
y Three post-tests measured day before
discharge and on the day for first and
second chemotherapy.
O- Germany Bot 100/97 Various Radiation 1.RM Primary: Anxiety (STAI) Primary: NS
Callahg h Stage therapy 2.SC Post-test measured after intervention
an unknown
[27]
Cook USA Bot 34/17 Haematologic Hospitalize 1. LM Primary: Meaning of life, peace & faith. Primary: Faith: Increase
[35] h al & d cancer 2. Waitlist control Spirituality (FACIT-sp) Peace: Increase.
Oncology patients group Post-test measured three days after final
Stage intervention.
unknown
Roseno USA Bot 18/18 Leukemia Recoverin 1.LM Primary: Fatigue (BFI) Primary: NS
w h Stage g from 2. SC Post-test measured after intervention
[30] unknown bone Waitlist-design
marrow
transplants
Yates† USA Bot 26/22 Oncology Post- 1. LM Primary: Mood (QMS) Primary: Improvement in
[36] h Stage surgical 2. SC Post-test measured after intervention one (relaxed) out of 6
unknown (drowsy, depressed.
aggressive, confused,
LM=live music. RM=recorded music. SC=standard care. NS=not significant. ND=not determined. MPQ=McGill pain questionnaire. VAS=visual analogue scale. STAI-Y1,
STAI-Y2=state-trait anxiety inventory. POMS=profile of mood state. HADS=hospital, anxiety, depression scale. NRS=numeric rating scale. FACT-G=functional assessment
of cancer therapy-general. FACIT-sp=functional assessment of chronic illness therapy-spiritual wellbeing. SBP=systolic blood pressure. DPB=diastolic blood pressure.
PANAS=Positive and negative affect schedule. FACIT-F=functional assessment of chronis illness therapy-fatigue scale. MAP=mean arterial pressure. HR=heart rate. SF-
MPQ=short-form of McGill Pain Questionnaire includes VAS & PPI=pain intensity. ZSDS=self-rating depression scale. POMS-SF=profile of mood state. FACT-
BMT=functional assessment of cancer therapy - bone marrow transplant subscale. MDASI= Anderson symptom inventory. I-PANAS-SF=positive and negative affect
schedule short-form. The Rhodes INVR=index of nausea, vomiting, retching. EORTC-QLQ-30=European organization for research and treatment of cancer quality of life
questionnaire. EORTC-BR23=…for breast cancer women. BFI=brief fatigue inventory. QMS=quick mood scale. TRSC: Therapy-Related Symptoms Checklist
* not included in meta-analysis results because SD was not given
† not included in meta-analysis. Yates reported sub score raw data to author, however no overall score is available in QMS.
‡ Li, Li and Zhou are included in meta-analysis with one data-set only. They published data from identical data-set.
**Not included in this review