Background: Cyclin 01 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. Methodology and Findings: 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (nonneoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73％ vs 8％, p <0.001; 63％ vs 6％, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in nonneoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001). Conclusions: This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy.
Zhien Feng Lizhen Wang Bingshun Wang Guoxin Ren Tong Ji Wenyong Tu Xihu Yang Weiliu Qiu Li Mao Zhiyuan Zhang Wantao Chen Wei Guo Chenping Zhang Qin Xu Ping Zhang Jian Sun Hanguang Zhu Zhonghe Wang Jiang Li
Department of Oral and Maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, Nint Shanghai Key Laboratory of Stomatology, Shanghai, China Department of Oral Pathology, Shanghai Jiao Department of Blostatistlcs, Institute of Medical Science, Shanghai Jiao Tong University School of M Department of Oral and Maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, Nint Shanghai Key Laboratory of Stomatology, Shanghai, China Department of Oncology and Diagnostic Scienc