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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Neoadjuvant therapy with Toripalimab (240mg, Day 1, Q3W, 2 cycles);Adjuvant immunotherapy with Toripalimab (240mg, Day 1, Q3W, for a total of 15 cycles).
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).
Radical surgery performed 3-4 weeks after neoadjuvant therapy, following a re-evaluation of surgical indications by the surgeon.
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).
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.
The Fifth Affiliated Hospital,Sun Yat-sen University
Guangdong, China
RECRUITINGMain pathological response rate
The proportion of patients with residual living tumor cells in the tumor bed under microscopy after HE staining of the specimens organized is less than 10%.
Time frame: 1 week post-surgery
Progression-free survival
From random grouping to the time interval until tumor progression or death for any reason, or until the last follow-up time if there is no tumor progression.
Time frame: 2 years after enrollment treatment
Pathological complete response rate
The proportion of patients with no residual live tumor cells under the microscope.
Time frame: 1 week post-surgery
Objective response rate
Evaluate the proportion of patients with objective response (complete response and partial response) through imaging assessments such as MRI and CT.
Time frame: 3-4 weeks after neoadjuvant therapy
Overall survival
The time interval from random grouping to the time of death for any reason, or to the last follow-up time if there is no death.
Time frame: 2 years after enrollment treatment
Adverse Events Reporting
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 1 year
Head and Neck Cancer-Specific Quality of Life
Changes from baseline in head and neck cancer-specific symptoms and functions were assessed using the EORTC QLQ-H\&N35 module (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Cancer Module). The scores range from 0 to 100, with higher scores indicating a better quality of life outcome and lower scores indicating worse symptoms or functions.
Time frame: 1 year
Health-related Quality of Life
Changes from baseline in patient-reported quality of life were assessed using the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Version 3.0). The scores range from 0 to 100, with higher scores indicating a better quality of life outcome and lower scores indicating worse symptoms or functions.
Time frame: 1 year
Pathological tumor remission rate -2
The proportion of patients with tumor necrosis under a microscope, where the ratio of keratin fragments and giant cells/tissue cells in tissue sections is not less than 50%.
Time frame: 1 week post-surgery
Non-surgical delay rate
The proportion of patients whose surgical time is more than 4 weeks longer than planned.
Time frame: 8 weeks after two cycles of neoadjuvant therapy
R0 resection rate
The proportion of patients who achieved R0 resection (where the tumor is completely excised during surgery and the margin tissue pathology is negative) among all patients who underwent surgical resection.
Time frame: 1 week post-surgery
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