Receptive Music Therapy Effects on Anxiety, Depression, QoL, and EGF, IL-8, and NfL During the Breast Cancer Treatment.

Official title

Association of Receptive Music Therapy With Plasma Levels of Epidermal Growth Factor, Interleukin-8 and Neurofilament Light Chain in Women With Breast Cancer

Overview

The goal of this clinical study is to investigate whether receptive music therapy can help women with breast cancer by reducing anxiety and depression symptoms, improving quality of life, and influencing specific analytes in plasma, including epidermal growth factor (EGF), interleukin-8 (IL-8), and neurofilament light chain (NfL). Main Questions the Study Aims to Answer: GENERAL OBJECTIVE: To investigate the effect of receptive music therapy on anxiety and depression symptoms, quality of life, and the levels of epidermal growth factor, interleukin-8, and neurofilament light chain in plasma during treatment in women with breast cancer. SPECIFIC OBJECTIVES: * To determine whether there is a correlation between the levels of epidermal growth factor, interleukin-8, and neurofilament light chain in plasma and the severity of anxiety and depression symptoms. * To determine whether there is a correlation between the severity of anxiety and depression symptoms and quality of life. Participants will be randomly assigned to either a music group or a control group. The study will take place during the perioperative period and chemotherapy (in participants for whom chemotherapy will be indicated). At two (perioperative) or three (+ chemotherapy) time points, participants will: * Undergo assessments for anxiety, depression, and quality of life * Provide blood samples for analytes analysis (EGF, IL-8, NfL) * Receive music therapy sessions (for those in the intervention group) The scientific contribution of this study lies in understanding the relationship between the application of receptive music therapy and the plasma levels of epidermal growth factor, interleukin-8, and neurofilament light chain in women with breast cancer during the perioperative period and chemotherapy, as well as its association with the occurrence of pronounced anxiety and depression symptoms related to the malignant process. This study represents the first application of such research in this patient population and serves as a foundation for the future implementation of receptive music therapy in the complementary treatment of breast cancer.

Detailed description

The study will be conducted at the Center for Malignant Diseases at the University Hospital for Tumors, Sestre milosrdnice University Hospital Center in Zagreb, Croatia. The Ethics Committee of the Sestre milosrdnice University Hospital Center has approved the study.

This is a quantitative, randomized clinical trial involving a targeted group of female participants diagnosed with breast cancer (C50), aged 18-65, during the perioperative period of malignant neoplasm removal (segmentectomy or mastectomy with axillary lymph node dissection or sentinel lymph node biopsy; with possible breast reconstruction in the same surgery after mastectomy) and during systemic oncological treatment with adjuvant chemotherapy (anthracyclines or taxanes).

Study Design:

Participants will be randomly assigned to either an intervention or control group to assess the effects of receptive music therapy on anxiety and depression. Baseline stratification according to anxiety and depression levels will be conducted.

Intervention:

Both groups will undergo conventional medical treatments, including surgery and adjuvant chemotherapy. The intervention group will also receive receptive music therapy. Participants in this group will listen to selected classical instrumental music using audio devices and headphones.

Music Therapy Protocol:

* Perioperative period: Two 30-minute sessions per day for three days of hospitalization (morning and evening) * Chemotherapy period: One-hour sessions during the first three weeks of chemotherapy administration

The type of chemotherapy determines the frequency of music therapy: 4 cycles of taxanes (weekly) or 2 cycles of anthracyclines (every three weeks).

The control group will receive standard medical procedures without music therapy.

Music Selection:

The research team will select classical instrumental music based on specific musical parameters conducive to relaxation:

* Slow to moderate tempo (60-80 bpm) * Smooth rhythmic patterns without abrupt fluctuations * Gentle melodic progression without dissonant interval jumps * Consonant harmonic progressions * Gradual and predictable dynamic changes * Sound intensity between 65-80 dB, based on participant preference * Audio quality of at least 320 kbit/s

Headphones will enhance auditory focus and minimize environmental distractions.

Data Collection and Assessment:

Participants will provide Informed Consent Form and demographic information (age, marital status, education, employment, prior musical training). Clinical data will be collected, and validated psychological instruments will assess anxiety, depression, and quality of life at three time points:

1. Day 1 of hospitalization (before the first music therapy session in the intervention group) 2. Day 3 of hospitalization 3. Three weeks after chemotherapy initiation (after the last music therapy session in the intervention group, in participants for whom chemotherapy will be indicated)

The following instruments will be used:

1. Hospital Anxiety and Depression Scale (HADS) 2. Beck Depression Inventory-II (BDI-II) 3. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) 4. Adaptive Functions of Music Listening Scale (administered during music listening in the intervention group or standard medical procedures in the control group)

Blood samples will be collected at the same three time points to measure:

* Epidermal Growth Factor (EGF) * Interleukin-8 (IL-8) * Neurofilament Light Chain (NfL)

The measurement of analytes (potential biological markers) from blood will be performed using the ELISA method in the Laboratory for Neurodevelopmental Pathology, led by Professor Goran Šimić, PhD, MD, at the Croatian Institute for Brain Research. Statistical analysis will include descriptive statistics and methods for testing differences between groups, as well as normality testing, which will determine the use of parametric or non-parametric statistical tests. Regression analysis will measure the association of EGF, IL-8, and NfL levels concerning the intervention effect.

Interventions

• Other Music intervention
  The protocol for the application of receptive music therapy in the intervention group will involve listening to music using a music playback device and headphones. Receptive music therapy will be applied twice daily for 30 minutes during the 3-day hospitalization period (in the morning and evening), and for 1 hour during the first three weeks of chemotherapy. The selection of music will be made by the researcher. Classical instrumental music pieces will be chosen based on musical components suc

Primary outcome measures

• Plasma levels of Epidermal Growth Factor (EGF) [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]
• Plasma Levels of Interleukin-8 (IL-8) [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]
• Plasma Levels of Neurofilament Light Chain (NfL) [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]

Secondary outcome measures (4)

• Anxiety and Depression Symptoms (HADS) [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]
• Depression Symptoms (BDI-II) [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]
• Quality of Life Score (EORTC QLQ-C30 and EORTC QLQ-BR23) [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]
• Adaptive Functions of Music Listening Scale (AFML) Scores [Time frame: Change from Baseline (Day 1 of hospitalization) to Day 3 of hospitalization, after Week 3 of chemotherapy (where applicable - in participants for whom chemotherapy will be indicated; this time point is approximately 2-3 months post-surgery).]

Eligibility criteria

Inclusion criteria

• Diagnosis of Breast Cancer (Ca mammae, C50),
• Age: 18-65 years
• Treatment at the University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
• Hospitalization during perioperative period while undergoing primary surgical removal of malignant neoplasm (segmentectomy or mastectomy with axillary lymph node dissection or sentinel lymph node biopsy; including possible reconstruction in the same surgery after mastectomy)
• Administration of systemic oncological treatment - adjuvant chemotherapy (anthracycline or taxane-based cytostatics)
• First occurrence of malignant disease
• Early invasive breast cancer
• Absence of metastases
• Possible positive axillary lymph nodes
• No history of hearing impairment

Exclusion criteria

• Presence of primary malignant process in other organs
• Ductal carcinoma in situ
• Previous malignant disease
• Recurrence of Breast Cancer
• Prior chemotherapy
• Neoadjuvant chemotherapy
• Diagnosis of anxiety and depressive disorders in the past three years
• Other severe psychiatric disorders (bipolar disorder, schizophrenia)
• Use of psychopharmacotherapy
• Inability to read and write in Croatian
• Presence of intellectual disabilities
• Professional musicians (classical music)
• Use of a hearing aid

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

Croatia · 1 center

• University Hospital for Tumors, Sestre Milosrdnice University Hospital Center Zagreb, Croa — Zagreb

Publications

• Galvez-Contreras AY, Campos-Ordonez T, Lopez-Virgen V, Gomez-Plascencia J, Ramos-Zuniga R, Gonzalez-Perez O. Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders. Cytokine Growth Factor Rev. 2016 Dec;32:85-96. doi: 10.1016/j.cytogfr.2016.08.004. Epub 2016 Sep 8. PMID 27618303
• Ma Y, Ren Y, Dai ZJ, Wu CJ, Ji YH, Xu J. IL-6, IL-8 and TNF-alpha levels correlate with disease stage in breast cancer patients. Adv Clin Exp Med. 2017 May-Jun;26(3):421-426. doi: 10.17219/acem/62120. PMID 28791816
• Nightingale CL, Rodriguez C, Carnaby G. The impact of music interventions on anxiety for adult cancer patients: a meta-analysis and systematic review. Integr Cancer Ther. 2013 Sep;12(5):393-403. doi: 10.1177/1534735413485817. Epub 2013 Apr 26. PMID 23625027

Identifiers

NCT: NCT07483034 · 90Z19012

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗