Estimate of the accelerated proliferation by protein tyrosine phosphatase (PTEN) over expression in postoperative radiotherapy of head and neck squamous cell carcinoma

PURPOSE: To estimate the impact of PTEN expression in terms of effective doubling time (T(d)) and dose per fraction which compensates the accelerated proliferation during the radiotherapy (D(prolif)) when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data were carried out from a recent paper comparing the local control rate (LCR) for patients with HNSCC that underwent a conventional (p-CF) or accelerated radiotherapy (p-CAIR) and a pretreatment assessment of PTEN expression. The impact of PTEN over expression was assessed using the Clinical Efficacy Factor (C) and assuming a plausible range of intrinsic radiosensitivity (α). Statistical analysis was made by evaluating the LCR from Kaplan-Meier curves and log-rank test with significance of 0.05. RESULTS: C indexes were 1.46 and 0.23 for the high- versus low-PTEN group, corresponding to a considerable reduction of doubling time of more than six times (6.6 versus 42.2 days). The median estimate of D(prolif) was 0.51 versus 0.08 Gy/day if referred to a median value in the adopted range of α. CONCLUSIONS: The PTEN expression has a significant implication on the clinical management of these patient groups. Our data support the hypothesis that the high-PTEN group would benefit from a hypo-fractionation with a reduction of the OTT to compensate for the increase in the proliferation rate, while the low-PTEN group could benefits from a hyper-fractionation which would result in a reduced toxicity for all the organs at risk.