Five-Element Music Therapy for Psychological Distress in Pancreatic Cancer Chemotherapy

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. PsychologicalDistress promotes pancreatic cancer progression through sympathetic‐exosome pathways,establishing an "emotion‐tumor" vicious cycle. Although the NALIRIFOX or AG regimenextends survival, the incidence of grade ≥3 adverse events reaches 73.1%, andchemotherapy toxicities interact bidirectionally with Psychological Distress. Musictherapy has been recommended by NCCN and other guidelines for improving PsychologicalDistress in cancer patients. Ziwu Liuzhu Five‐Element Music Therapy integratesfive‐element music with chronomedicine, delivering music at specific time periods toenhance therapeutic efficacy; however, high‐level evidence is lacking for pancreaticcancer patients undergoing chemotherapy.Study Objectives This study aims to: (1) demonstrate that Ziwu Liuzhu Five‐Element MusicTherapy is non‐inferior to Mindfulness‐Based Stress Reduction in reducing anxiety inpancreatic 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‐inferiorityrandomized controlled trial with a 1:1 allocation ratio to either the Ziwu LiuzhuFive‐Element Music Therapy group or the MBSR group.Participants Inclusion criteria: age ≥18 years; histologically confirmed pancreaticcancer; first‐line chemotherapy with NALIRIFOX or AG (nab‐paclitaxel + gemcitabine)regimen; ECOG PS ≤2; life expectancy >3 months; HAMA score 7‐23 (mild‐to‐moderateanxiety); voluntary signed informed consent. A total of 320 participants (160 per group)are planned for enrollment.Exclusion criteria: severe psychiatric disorders, cognitive impairment, suicidalideation, or unstable antipsychotic medication dosage; chemotherapy‐related acuteunstable conditions; severe hearing impairment or intolerance to music; concurrentparticipation in other clinical trials; regular mindfulness or yoga practice history (≥2times/week for ≥3 months).InterventionThe 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"), 20minutes after breakfast, once daily, 20 minutes per session.Wu Period (11:00‐13:00, Heart meridian): Zhi mode (e.g., "Purple Bamboo Tune"), beforelunchtime rest, once daily, 20 minutes per session.You Period (17:00‐19:00, Kidney meridian): Yu mode (e.g., "Three Variations of PlumBlossom"), 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‐guidedpractice (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 toeach chemotherapy cycle).Statistical Analysis Non‐inferiority testing with one‐sided α = 0.025. Linearmixed‐effects models are used to analyze HADS‐A change scores. Non‐inferiority is claimedif the upper bound of the 97.5% confidence interval for the between‐group difference isless than the prespecified non‐inferiority margin (1.225 points). Intention‐to‐treatanalysis is primary; per‐protocol analysis is sensitivity.Ethics and Registration This study has been approved by the Medical Ethics Committee ofTianjin Medical University Cancer Institute & Hospital. All participants will providewritten informed consent.