Low-Dose Radiotherapy and Anti-PD-1 Immunotherapy as Neoadjuvant Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma
Sponsor: Rui You • ClinicalTrials.gov ID: NCT07371234
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Over 60% of head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at a locally advanced stage. While standard treatments involve surgery and chemoradiotherapy, prognosis remains poor, with 50-60% experiencing local recurrence within two years. Neoadjuvant therapy can potentially reduce tumor burden, preserve organs, and lower distant metastasis risk. Despite the KEYNOTE-689 trial showing that adjuvant two-cycle pembrolizumab increased major pathological response to 9.8% in stage III-IVB HNSCC, this result remains insufficient. More effective immunotherapy-based combinations are urgently needed to improve long-term survival after neoadjuvant treatment. Preclinical and clinical evidence indicates that low-dose radiotherapy can activate the tumor immune microenvironment and synergize with immunotherapy. Based on this rationale, the present clinical trial will evaluate a neoadjuvant regimen combining LDRT with two cycles of an anti-PD-1 inhibitor in patients with surgically resectable, locally advanced HNSCC.
Interventions
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Neoadjuvant and Adjuvant Immunotherapy
(Drug)
Neoadjuvant therapy with Toripalimab (240mg, Day 1, Q3W, 2 cycles);Adjuvant immunotherapy with Toripalimab (240mg, Day 1, Q3W, for a total of 15 cycles).
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Low-dose radiotherapy
(Radiation)
Low-dose radiotherapy (1 Gy/fraction, on Days 1, 8, and 15 of each cycle, Q3W, for 2 cycles; total dose: 6 Gy in 6 fractions).
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Surgery
(Procedure)
Radical surgery performed 3-4 weeks after neoadjuvant therapy, following a re-evaluation of surgical indications by the surgeon.
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Adjuvant Radiotherapy
(Radiation)
Low-risk group: 60 Gy in 30 fractions, using intensity-modulated radiation therapy (IMRT); High-risk group: 66 Gy in 33 fractions, or 70 Gy in 35 fractions for residual lesions, using intensity-modulated radiation therapy (IMRT).
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Adjuvant Cisplatin
(Drug)
High-risk group:Cisplatin 100 mg/m² is administered via intravenous infusion on Day 1 of every 21-day cycle during radiotherapy, for a total of 3 cycles.
Eligibility criteria
Conditions
Locations
- The Fifth Affiliated Hospital,Sun Yat-sen University — Guangdong, China
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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
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