De-Escalation Surgery After Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

Официальное название

A Randomized Controlled Clinical Study of De-Escalation Surgery Following Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Обзор

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.

Вмешательства

• Процедура De-escalation surgery
  Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy.
• Процедура Standard Surgery
  Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.
• Лучевая терапия radiotherapy
  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
• Препарат adjuvant immunotherapy
  Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.

Первичные конечные точки

• 3-year overall survival (OS) rate [Срок оценки: 3 years]

Вторичные конечные точки (6)

• 5-year overall survival (OS) rate [Срок оценки: 5 years]
• 3-year and 5-year Event-free survival (EFS) rates [Срок оценки: 5 years]
• incidence of adverse events [Срок оценки: Through study completion, an average of 5 years]
• Surgical complications [Срок оценки: Perioperative]
• Totally quality of life, QoL [Срок оценки: 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 [Срок оценки: Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization]

Критерии участия

Критерии включения

• Age between 18 and 75 years inclusive, with no restriction on gender.
• Histologically confirmed primary squamous cell carcinoma of the head and neck (excluding nasopharyngeal carcinoma).
• Clinical stage III-IVa according to the AJCC 8th edition TNM staging system prior to immunotherapy; specifically, stage III-IVa for oropharyngeal squamous cell carcinoma (p16-negative) or stage III for oropharyngeal squamous cell carcinoma (p16-positive).
• ECOG performance status of 0 or 1.
• Life expectancy of ≥6 months.
• Received preoperative immune checkpoint inhibitor therapy, primarily with anti-PD-1 monoclonal antibodies or bispecific antibodies containing an anti-PD-1 arm, regardless of brand, with or without concurrent chemotherapy or targeted therapy, for no more than six cycles.
• Achieved complete response (CR) or partial response (PR) on imaging assessment after preoperative therapy, according to RECIST 1.1 criteria.
• Assessed as eligible for de-escalation surgery based on clinical evaluation by the surgeon. Examples include omission of surgery on the primary lesion; preservation of critical structures or functions, such as retaining the mandible initially planned for resection; avoidance of flap reconstruction; or limitation of tongue resection to less than half when hemi-glossectomy was initially indicated.
• No prior curative surgery or radiotherapy for the current tumor.
• Willing to undergo surgical treatment.
• No significant contraindications to surgery.
• Voluntary participation in the study, signed informed consent, good compliance, and willingness to cooperate with follow-up visits.

Критерии исключения

• Severe underlying diseases making the patient unable to tolerate surgery.
• Current tumor is recurrent.
• Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, or symptomatic congestive heart failure within 6 months before randomization.
• History of psychiatric drug abuse or drug addiction.
• Pregnant or breastfeeding women.
• Diagnosis of other malignancies within 5 years prior to study entry, except for locally treated and cured basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder carcinoma, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma.
• Any other severe physical or mental illness, or laboratory abnormalities that might increase the risk associated with participation or interfere with the study results, or any other conditions deemed unsuitable for participation by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Ninth Peolple's Hospital — Шанхай

Идентификаторы

NCT: NCT07320690 · JYKQ-2025-057 · NCRCO2025ZD-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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