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.