Neoadjuvant with low-dose radiotherapy, tislelizumab, albumin-bound paclitaxel, and cisplatin for resectable locally advanced head and neck squamous cell carcinoma: phase II single-arm trial

作者：Zhigang Liu, Zhigang Liu, Dong Wang, Muhua Yi, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Jianpeng Li, Jianpeng Li, Ye Liu, Jun Lai, Xianjuan Lv, Yongqiang Xu, Qiaodan Liu, Zhiqiang Wang, Zhutian Liu, Li Nie, Qinan Yang, Li Nie, Jiao Lei, Xiaotao Huang, Zhi‐Jie Liu, Zhi‐Jie Liu, Wen Jiang · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-59865-1 · 被引用次数：20 · 研究领域：Head and Neck Cancer Studies、Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of 23 patients (60.9%; 23/28, 82.1% of the total cohort underwent surgery). Secondary endpoints included MPR rate (21.7%, 5/23), R0 resection rate (100%), and objective response rate (64.3%; 18/28). Treatment-related adverse events were manageable, with grade 3 or 4 treatment-related adverse events occurring in 10 (35.7%) patients. No surgical delays were observed. Single-cell RNA sequencing revealed remodeling of the HNSCC tumor microenvironment, which may correlate with improved clinical outcomes. This trial met the pre-specified primary endpoint, demonstrating a high pCR rate with promising efficacy and manageable toxicity in locally advanced HNSCC. Neoadjuvant cancer therapeutic strategy has be...