This study aims to evaluate the safety and efficacy of hypofractionated radiotherapy in patients with postoperative intermediate-risk head and neck squamous cell carcinoma.

After being informed about the study and potential risks, all patients giving written informed consent will undergo a screening period of up to 28 days to determine eligibility for study entry. Eligible patients will then receive hypofractionated radiotherapy (PGTVtb/PGTVnd-tb: 45 Gy in 15 fractions of 3.0 Gy; PTV1: 40.5 Gy in 15 fractions of 2.7 Gy, once daily, 5 days per week for 3 weeks.).

Inclusion Criteria:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Histologically or cytologically confirmed stage II-IVA head and neck squamous cell carcinoma (AJCC 8th edition), including oral cavity, oropharynx, hypopharynx, larynx, or cervical lymph node metastasis from unknown primary
• R0 resection and standard neck dissection per surgical evaluation
• Negative surgical margins and no extranodal extension in metastatic lymph nodes on postoperative pathology
• Presence of at least one intermediate-risk factor: close margins (<5 mm), pT3-4, pN2, lymphovascular invasion, perineural invasion, poor differentiation, or for oral cavity cancer T2 with depth of invasion >5 mm
• Adequate organ function (without blood transfusion or growth factors within 14 days):
• White blood cell count ≥ 2.0 × 10^9/L
• Absolute neutrophil count ≥ 1.0 × 10^9/L
• Platelet count ≥ 80 × 10^9/L
• Hemoglobin ≥ 90 g/L
• Willing and able to comply with study and follow-up procedures
• Voluntary participation with written informed consent

Exclusion Criteria:

• Prior radiotherapy or surgery to the head and neck region
• Primary head and neck cancer arising from other sites such as paranasal sinuses, nasopharynx, glottic larynx, skin, or salivary glands
• Concurrent other anti-tumor therapy
• Prior neoadjuvant drug therapy
• Evidence of tumor progression on imaging within 28 days before enrollment
• History of severe infection within 1 month before enrollment, including but not limited to infection complications requiring hospitalization, bacteremia, severe pneumonia; any active infection, or unexplained fever >38.5°C during screening or before first dose
• Severe cardiovascular disease: grade II or higher myocardial ischemia or infarction, uncontrolled arrhythmia (including QTc interval ≥450 ms for males or ≥470 ms for females); New York Heart Association (NYHA) class III-IV heart failure, or left ventricular ejection fraction (LVEF) ≤50% on echocardiography
• History of other malignancy within 5 years (except adequately treated in situ cervical cancer or basal cell/squamous cell carcinoma of the skin)
• History of psychoactive substance abuse that cannot be abstained from, or mental disorders

Individual participant data (IPD) will be shared with other researchers upon reasonable request. The data to be shared include de-identified participant data related to the study outcomes, including demographic data, efficacy outcomes (DFS, LRC, OS), safety data (adverse events), and quality of life assessments (EORTC QLQ-C30, QLQ-H&N35, MDADI).

Data will become available within 6 months after publication of the primary results and will be available for up to 5 years following publication.

Access to IPD will be granted to qualified researchers who submit a methodologically sound research proposal. Requests should be sent to the Principal Investigator (drzye1983@163.com). A data use agreement must be signed before data are released. Data will be provided in a de-identified format to protect participant privacy.