CCND1 as a Predictive Biomarker of Neoadjuvant Chemotherapy in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma
Open Access
- 31 October 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (10), e26399
- https://doi.org/10.1371/journal.pone.0026399
Abstract
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. 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). 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.Keywords
This publication has 32 references indexed in Scilit:
- Inhibition of cyclin D1 expression by cyclin D1 shRNAs in human oral squamous cell carcinoma cells is associated with increased cisplatin chemosensitivityInternational Journal of Cancer, 2008
- Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy?Journal of Clinical Oncology, 2008
- Neoadjuvant Cisplatin Chemotherapy Before Chemoradiation: A Flawed Paradigm?Journal of Clinical Oncology, 2007
- An Integrated Genomic-Based Approach to Individualized Treatment of Patients With Advanced-Stage Ovarian CancerJournal of Clinical Oncology, 2007
- Prognostic value of the epidermal growth factor receptor (EGRF) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapyEuropean Journal Of Cancer, 2005
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplificationOncogene, 1998
- First-Line Chemotherapy Improves the Resection Rate and Long-Term Survival of Locally Advanced (T4, any N, M0) Squamous Cell Carcinoma of the Thoracic EsophagusAnnals of Surgery, 1997
- Evidence-Based Recommendations Against Neoadjuvant Chemotherapy for Routine Management of Patients with Squamous Cell Head and Neck CancerCancer Investigation, 1994
- Induction Chemotherapy plus Radiation Compared with Surgery plus Radiation in Patients with Advanced Laryngeal CancerNew England Journal of Medicine, 1991