This study is a prospective, multi-cohort, multi-center clinical trial targeting patients with intermediate-to-high-risk rhabdomyosarcoma who have not previously received systemic anti-tumor treatment. It aims to evaluate the efficacy and safety of all-trans retinoic acid combined with VAC chemotherapy.

Inclusion Criteria:

1. Age ≥ 14 years old and ≤ 60 years old;

2. Histologically confirmed medium to high risk rhabdomyosarcoma (excluding pleomorphic rhabdomyosarcoma);

3. The physical fitness status score of the Eastern Cancer Collaboration Group (ECOG) is 0-1;

4. Have not received any anti-tumor drug treatment in the past;

5. Expected survival time ≥ 3 months;

6. Possess sufficient organ and bone marrow function, with laboratory test values meeting the following requirements within 7 days prior to enrollment (no blood components, cell growth factors, albumin, or other corrective treatment drugs are allowed within 14 days prior to obtaining laboratory tests), as follows Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin (HGB) ≥ 100 g/L (no transfusion or erythropoietin dependence within 14 days) Liver function: serum total bilirubin ≤ 1.25 times the upper limit of normal (ULN); ALT and AST ≤ 2.5 x ULN (≤ 5x ULN for patients with liver metastases); Serum albumin ≥ 30 g/L; Alkaline phosphatase (ALP) ≤ 5 × ULN.

   Renal function: Serum creatinine (Cr) ≤ 1.25 × ULN, or creatinine clearance rate ≥ 60 mL/min (using the standard Cockcroft Gault formula): Urine routine results show urinary protein<2+; For patients whose baseline urine routine test shows urinary protein ≥ 2+, 24-hour urine collection should be performed with a 24-hour urine protein quantification of<1g.

   Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; If the subject is receiving anticoagulant therapy, as long as the INR is within the intended range of use of the anticoagulant drug.

7. For female subjects of childbearing age, a urine or serum pregnancy test should be conducted 3 days before receiving the first study drug and the result should be negative;

8. Participants and their sexual partners are required to use a medically approved contraceptive measure (such as intrauterine devices, birth control pills, or condoms) during the study treatment period and within 6 months after the end of the study treatment period.

Exclusion Criteria:

1. Previously received anti-tumor treatment other than surgery and radiation therapy for any malignant tumor;

2. Subjects who cannot accept or tolerate this chemotherapy regimen for various reasons;

3. Biopsy confirmed a patient with bone marrow infiltration;

4. Patients who have undergone major surgical procedures unrelated to medium to high risk rhabdomyosarcoma within the 4 weeks prior to enrollment, or who have not fully recovered from such surgical procedures;

5. Serious heart disease or discomfort, including but not limited to the following diseases:

   • Diagnosed history of heart failure or systolic dysfunction (LVEF<50%);
   • High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block (i.e. Mobitz II second or third degree atrioventricular block);
   • Angina requiring treatment with anti angina drugs;
   • Clinically significant heart valve disease;
   • ECG shows transmural myocardial infarction;
   • Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg)

6. Individuals with a known history of allergies to the components of this medication regimen;

7. The researcher believes that the patient is not suitable to participate in any other circumstances of this study.