title: Elevated cyclin D1 expression is predictive for a benefit from TPF induction chemotherapy in oral squamous cell carcinoma patients with advanced nodal disease.
abstract: Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients with cancer with biomarker detection. To investigate the prognostic and predictive values of cyclin D1 expression in patients with oral squamous cell carcinoma (OSCC) who were treated in a prospective, randomized, phase III trial evaluating standard treatment with surgery and postoperative radiotherapy preceded or not by induction docetaxel, cisplatin, and 5-fluorouracil (TPF), immunohistochemical staining for cyclin D1 was conducted in pretreatment biopsy specimens of 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Cyclin D1 index was estimated as the proportion of tumor cells with cyclin D1 nuclear staining. A low cyclin D1 expression predicted significantly better overall survival (OS; P = 0.001), disease-free survival (P = 0.005), locoregional recurrence-free survival (P = 0.003), and distant metastasis-free survival (DMFS; P = 0.002) compared with high cyclin D1 expression. Cyclin D1 expression levels were not predictive of benefit from induction TPF in the population overall. However, patients with nodal stage cN2 whose tumors had high cyclin D1 expression treated with TPF had significantly greater OS (P = 0.025) and DMFS (P = 0.025) when compared with high cyclin D1 cN2 patients treated with surgery upfront. Patients with low cyclin D1 level or patients with cN0 or cN1 disease did not benefit from induction chemotherapy. This study indicates that cN2 OSCC patients with high cyclin D1 expression can benefit from the addition of TPF induction chemotherapy to standard treatment. Cyclin D1 expression could be used as a biomarker in further validation studies to select cN2 patients that could benefit from induction therapy.
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lai-Ping
authors.initials: LP
authors.lastname: Zhong
authors.forename: Dong-Wang
authors.initials: DW
authors.lastname: Zhu
authors.forename: William N
authors.initials: WN
authors.lastname: William
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Cheng-Zhe
authors.initials: CZ
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Wang
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Chen-Ping
authors.initials: CP
authors.lastname: Zhang
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D043823:Taxoids; D019938:Cyclin D1; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil