title: CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Cyclin D1 (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.
  
  
  RESULTS
  224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant 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 non-neoadjuvant 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.
authors: Department of Oral and Maxillofacial Surgery, Shanghai Jiao Tong University School of Medicine, Ninth People's Hospital, Shanghai, China.
authors: Zhien
authors: Z
authors: Feng
authors: Wei
authors: W
authors: Guo
authors: Chenping
authors: C
authors: Zhang
authors: Qin
authors: Q
authors: Xu
authors: Ping
authors: P
authors: Zhang
authors: Jian
authors: J
authors: Sun
authors: Hanguang
authors: H
authors: Zhu
authors: Zhonghe
authors: Z
authors: Wang
authors: Jiang
authors: J
authors: Li
authors: Lizhen
authors: L
authors: Wang
authors: Bingshun
authors: B
authors: Wang
authors: Guoxin
authors: G
authors: Ren
authors: Tong
authors: T
authors: Ji
authors: Wenyong
authors: W
authors: Tu
authors: Xihu
authors: X
authors: Yang
authors: Weiliu
authors: W
authors: Qiu
authors: Li
authors: L
authors: Mao
authors: Zhiyuan
authors: Z
authors: Zhang
authors: Wantao
authors: W
authors: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D002945:Cisplatin / Q000627:therapeutic use; D019938:Cyclin D1 / Q000378:metabolism*; D003710:Demography; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1; D002945:Cisplatin