The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis

Purpose: The aim of this study was to assess the potential of pre-treatment cell kinetic parameters to predict outcome in head and neck cancer patient s treated by conventional radiotherapy. Materials and methods: Data from 11 different centers were pooled. Inclusio n criteria were such that the patients received radiotherapy alone, and tha t the radiotherapy was given in an overall time of at least 6 weeks with a dose of at least 60 Gy. All patients received a tracer dose of either iodod eoxyuridine (IdUrd) or bromodeoxyuridine (:BrdUrd) intravenously prior to t reatment and a tumor biopsy was taken several hours later. The cell kinetic parameters labeling index (:LI), DNA synthesis time (Ts) and potential dou bling time (Tpot) were subsequently calculated from flow cytometry data, ob tained on the biopsies using antibodies against I/BrdUrd incorporated into DNA. Each center carried out their own flow cytometry analysis. Results: From the 11 centers, a total of 476 patients conforming to the inc lusion criteria were analyzed. Median values for overall time and total dos e were 49 days and 69 Gy, respectively. Fifty one percent of patients had l ocal recurrences and 53% patients had died, the majority from their disease . Median follow-up was 20 months; being 30 months for surviving patients. M ultivariate analysis revealed that T-stage, maximum tumor diameter, differe ntiation grade, N-stage, tumor localization and overall time correlated wit h locoregional control, in decreasing order of significance. For the cell k inetic parameters, univariate analysis showed that only LI was significantl y associated with local control (P = 0.02), with higher values correlating with a worse outcome. Ts showed some evidence that patients with longer val ues did worse, but this was not significant (P = 0.06). Tpot showed no tren d (P = 0.8). When assessing survival in a univariate analysis, neither LI n or Tpot associated with outcome (P = 0.4, 0.4, respectively). Surprisingly, Ts did correlate with survival, with longer values being worse (P = 0.02). In the multivariate analysis of local control, LI lost its significance (P = 0.16). Conclusions: The only pretreatment kinetic parameter for which some evidenc e was found for an association with local control (the best end-pomt for te sting the present hypothesis) was LI, not Tpot, and this evidence disappear ed in a multivariate analysis. It therefore appears that pretreatment cell kinetic measurements carried out using flow cytometry, only provide a relat ively weak predictor of outcome after radiotherapy in head and neck cancer. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.