Predictive value of potential doubling time in head and neck cancer patients treated by conventional radiotherapy

The goal of this study was to investigate the clinical utility of pretreatment measurements of tumor cell kinetics to predict the outcome of patients with squamous cell carcinoma of the head and neck receiving conventional radiotherapy.

All patients received between 64 and 70 Gy as 2 Gy fractions, five fractions per week. Cell kinetics were assayed rapidly and quantitatively using flow cytometric evaluation of iododeoxyuridine (IdUrd) incorporation, in vivo, from a biopsy removed several hours after the administration of the DNA precursor to the patient prior to the start of treatment.

The measured proliferation parameters were not related to the clinicopathological features of the tumors, emphasizing the independent nature of these parameters. In univariate analysis, nodal involvement was the most important clinical feature of the tumors related to local control followed by Tpot, DNA aneuploidy, and attainment of complete regression at 6 weeks. Of these only Tpot and nodal status maintained significance in multivariate analysis, with respect to loco-regional control. In subgroup analysis, Tpot was able to stratify patients into high or low rate of loco-regional control in node negative patients, in aneuploid tumors and in patients who did achieve complete regression at 6 weeks. For cause specific survival, N-stage was the only parameter that significantly discriminated the prognosis in these patients.

The conclusion of this study is that Tpot provides clinically important information that can predict patients with a low probability of achieving long-term local control with conventional fractionation. Further improvements to the methodology to address the shortcomings of analyzing diploid tumors may increase the predictive power of the measurement.