Induction Chemoimmunotherapy Followed by Deescalated Definitive Radiotherapy in Head and Neck Cancer

Overview

This study aims to evaluate whether reducing the intensity of radiotherapy (de-escalated radiotherapy) after induction chemoimmunotherapy is not inferior to standard-dose radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The study is a multicenter, prospective, phase II, randomized, non-inferiority controlled trial. A total of 180 participants who achieve deep tumor response (≥50% regression) after 2-3 cycles of induction chemotherapy plus PD-1 inhibitor (camrelizumab) will be randomized 1:1 to receive either de-escalated radiotherapy (experimental group) or standard radiotherapy (control group). Additional maintenance camrelizumab for 8 cycles after radiotherapy will be administered for both groups. The primary outcome is 2-year progression-free survival (PFS). Secondary outcomes include overall survival, local-regional control, distant metastasis-free survival, treatment-related adverse events, and quality of life. The study is expected to start in June 2026 and complete in December 2031.

Background Induction chemoimmunotherapy has demonstrated marked response rates in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Conventional "expanded and escalated " radiotherapy to lymph node regions may reduce the systemic immune responses. Therefore, de-escalated radiotherapy after a good response to induction therapy may reduce accumulated toxicity while preserving efficacy and maintain the functional state of anti-tumor immune niche. Objectives Primary: To determine if de-escalated radiotherapy is non-inferior to standard radiotherapy for 2-year PFS in LA-HNSCC patients with deep response (≥50% tumor regression) after induction chemoimmunotherapy. Secondary: To compare overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), treatment-related adverse events (AEs, irAEs, SAEs), and quality of life (ECOG, EQ-5D-5L, MDADI) between the two groups. Study Design Multicenter (8 sites in China), prospective, phase II, randomized (1:1), open-label, non-inferiority trial. Eligibility Criteria: * Age 18-75 years * Histologically confirmed HNSCC (non-nasopharyngeal), HPV/P16 negative * AJCC 8th stage T1-2N2-3M0 or T3-4N0-3M0 * ECOG 0-1 * Completed 2-3 cycles of induction chemotherapy (platinum-based) plus PD-1 inhibitor, achieving deep response (≥50% tumor reduction by RECIST) assessed by MDT * Adequate organ function * No prior immunotherapy Interventions: Induction (all patients) : 2-3 cycles of chemotherapy (cisplatin/carboplatin based) + PD-1 inhibitor. Randomization (1:1): * Experimental (de-escalated RT): GTV (post-induction residual): 60 Gy/25 fractions GTVtb (pre-induction tumor bed): not specified CTV1 (GTVtb + 1 cm): 50 Gy/25 fractions CTV2 (high-risk nodal stations + one station beyond): 45 Gy/25 fractions * Control (standard RT): GTV (post-induction residual): 69.96 Gy/33 fractions GTVtb (pre-induction tumor bed): not specified CTV1 (GTVtb + 1-1.5 cm + high-risk nodal stations): 60.06 Gy/33 fractions CTV2 (intermediate/low-risk nodal stations): 50.96 Gy/28 fractions * Maintenance: Camrelizumab 200 mg IV Q3W for 8 cycles Follow-up: Every 3 months for 2 years post-RT. Sample Size: 180 participants, 90 patients in each arm. Statistical Analysis: Baseline comparisons using Mann-Whitney U test; survival analysis using log-rank test and Cox regression; non-inferiority testing for PFS. Study Period: June 2026 (anticipated start) to December 2031 (completion). Ethics: Approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences (26/057-0382). Written informed consent will be obtained from all participants.