This is a multicenter, randomized, open-label, non-inferiority clinical trial designed to evaluate whether downgraded surgery-guided by post-immunotherapy tumor boundaries-can achieve comparable 3-year overall survival (OS) to standard surgery in patients with Stage III-IVa locally advanced head and neck squamous cell carcinoma (HNSCC) who have responded to neoadjuvant immunotherapy. A total of 356 patients will be randomized 1:1 to receive either downgraded or standard surgery, followed by risk-adapted adjuvant therapy. The primary endpoint is 3-year OS, with secondary endpoints including disease-free survival, quality of life, complication rates, and cost-effectiveness. The study hypothesizes that downgraded surgery will preserve organ function and quality of life without compromising survival outcomes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
356
Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy.
Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.
Radiotherapy is recommended within 6 weeks after surgery. Patients achieving a pathological complete response (pCR) may be exempted. For the primary tumor and involved nodes, 60-70 Gy in 30-35 fractions is delivered once daily, Monday to Friday (low risk: 60 Gy; high risk: 66 Gy; residual disease: 70 Gy). Suspected subclinical areas receive 45-50 Gy (2 Gy/f) or 54-63 Gy (1.6-1.8 Gy/f). Concurrent cisplatin is given when extracapsular nodal extension or positive/close margins (\<1 mm) are present: 100 mg/m² every 3 weeks ×3, with renal function-based dose adjustment. For patients unsuitable for cisplatin, cetuximab is administered at 400 mg/m² in the first week, then 250 mg/m² weekly.
Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.
Shanghai Ninth Peolple's Hospital
Shanghai, Shanghai Municipality, China
3-year overall survival (OS) rate
The proportion of subjects in the intention-to-treat population who are alive at 3 years after randomization.
Time frame: 3 years
5-year overall survival (OS) rate
The proportion of subjects in the intention-to-treat population who are alive at 5 years after randomization.
Time frame: 5 years
3-year and 5-year Event-free survival (EFS) rates
The proportion of subjects in the intention-to-treat population who have not experienced any EFS events at 3 and 5 years after randomization. EFS time is defined as the duration from randomization to the first occurrence of any of the following events: (1) disease recurrence or metastasis in patients who underwent surgery; (2) disease progression per RECIST 1.1, or recurrence/metastasis after non-surgical treatment (e.g., radiotherapy) following neoadjuvant therapy; (3) occurrence of a second primary tumor; or (4) death from any cause. Patients who did not undergo surgery due to clinical complete response (CR) or near CR, as well as those who declined surgery but received other antitumor therapies without experiencing progression, recurrence/metastasis, or death, or who had positive surgical margins without radiographic evidence of progression, are not considered to have reached an EFS event.
Time frame: 5 years
incidence of adverse events
Adverse events observed will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Time frame: Through study completion, an average of 5 years
Surgical complications
Surgical complications in this study will be assessed according to the Clavien-Dindo classification system, and detailed information on all complications occurring during the perioperative period will be recorded in the eCRF.
Time frame: Perioperative
Totally quality of life, QoL
Totally Health status and quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Lifer Questionnaire Core 30 (EORTC QLQ-C30) questionnaires.
Time frame: Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization
Quality of life for HNSCC patients
Health status and quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Lifer Questionnaire Head and Neck 35 (EORTC QLQ-H\&N35) questionnaires
Time frame: Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization
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