Five-Element Music Therapy for Psychological Distress in Pancreatic Cancer Chemotherapy (FEMT-PC)

Background Pancreatic cancer patients have a high prevalence of anxiety and depression, with rates reaching 70% for depression and 80% for anxiety after diagnosis; however, 73% of those with Psychological Distress do not receive effective intervention. Psychological Distress promotes pancreatic cancer progression through sympathetic-exosome pathways, establishing an "emotion-tumor" vicious cycle. Although the NALIRIFOX or AG regimen extends survival, the incidence of grade ≥3 adverse events reaches 73.1%, and chemotherapy toxicities interact bidirectionally with Psychological Distress. Music therapy has been recommended by NCCN and other guidelines for improving Psychological Distress in cancer patients. Ziwu Liuzhu Five-Element Music Therapy integrates five-element music with chronomedicine, delivering music at specific time periods to enhance therapeutic efficacy; however, high-level evidence is lacking for pancreatic cancer patients undergoing chemotherapy.

Study Objectives This study aims to: (1) demonstrate that Ziwu Liuzhu Five-Element Music Therapy is non-inferior to Mindfulness-Based Stress Reduction in reducing anxiety in pancreatic cancer patients during chemotherapy; (2) evaluate its effects on depression, quality of life, and biomarkers.

Study Design This is a multicenter, prospective, parallel-group, non-inferiority randomized controlled trial with a 1:1 allocation ratio to either the Ziwu Liuzhu Five-Element Music Therapy group or the MBSR group.

Participants Inclusion criteria: age ≥18 years; histologically confirmed pancreatic cancer; first-line chemotherapy with NALIRIFOX or AG (nab-paclitaxel + gemcitabine) regimen; ECOG PS ≤2; life expectancy >3 months; HAMA score 7-23 (mild-to-moderate anxiety); voluntary signed informed consent. A total of 320 participants (160 per group) are planned for enrollment.

Exclusion criteria: severe psychiatric disorders, cognitive impairment, suicidal ideation, or unstable antipsychotic medication dosage; chemotherapy-related acute unstable conditions; severe hearing impairment or intolerance to music; concurrent participation in other clinical trials; regular mindfulness or yoga practice history (≥2 times/week for ≥3 months).

Intervention

The intervention group receives an 8-week Ziwu Liuzhu Five-Element Music Therapy program:

Si Period (9:00-11:00, Spleen meridian): Gong mode (e.g., "Spring River Moonlight"), 20 minutes after breakfast, once daily, 20 minutes per session.

Wu Period (11:00-13:00, Heart meridian): Zhi mode (e.g., "Purple Bamboo Tune"), before lunchtime rest, once daily, 20 minutes per session.

You Period (17:00-19:00, Kidney meridian): Yu mode (e.g., "Three Variations of Plum Blossom"), during dinner, once daily, 20 minutes per session.

During hospitalization, bedside guidance is provided by the responsible nurse. At home, exercises are supervised via video, with daily check-in recording.

The control group receives an 8-week standard Mindfulness-Based Stress Reduction program: weekly online group sessions (60 minutes/session) + twice-daily home audio-guided practice (20 minutes/session)..

Outcome Measures Primary outcome: HADS-Anxiety score (T0, T1, T2). Secondary outcomes: HADS-Depression score, EORTC QLQ-C30 quality of life score (T0, T1, T2).

Exploratory outcomes: NLR, MLR, albumin, total protein, hemoglobin, glucose (prior to each chemotherapy cycle).

Statistical Analysis Non-inferiority testing with one-sided α = 0.025. Linear mixed-effects models are used to analyze HADS-A change scores. Non-inferiority is claimed if the upper bound of the 97.5% confidence interval for the between-group difference is less than the prespecified non-inferiority margin (1.225 points). Intention-to-treat analysis is primary; per-protocol analysis is sensitivity.

Ethics and Registration This study has been approved by the Medical Ethics Committee of Tianjin Medical University Cancer Institute & Hospital. All participants will provide written informed consent.