IN-VIVO MEASUREMENT OF THE POTENTIAL DOUBLING TIME BY FLOW-CYTOMETRICIN OROPHARYNGEAL CANCER TREATED BY CONVENTIONAL RADIOTHERAPY

Purpose: Experimental and clinical studies suggest that the Pre-treatm ent potential doubling time could be predictive of tumor control in pa tients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is requ ired. Methods and Materials: To test this hypothesis, we studied prosp ectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were o btained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient. Results: Three parameters were significantly associated with an increased risk of rel apse namely the tumors size (T4; p < 0.01), the nodal status (greater- than-or-equal-to N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and pote ntial doubling time were not significantly associated with an increase d risk of relapse. However when considering only the T2 subgroup of pa tients, high labeling indexes and short potential doubling time were a ssociated with an increased risk of relapse: the mean pre-treatment po tential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurr ence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02). Conclusion: Factors other than proliferation play a role i n determining the outcome of oropharyngeal cancers treated by conventi onal radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurren ce in the T2 subgroup of patients. The finding of significance for pot ential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneneous nature of these tumors with regard to prognostic variables.