TUMOR KINETICS IN HEAD AND NECK CANCER

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There is emerging clinical and laboratory evidence, much of it in cancers of the head and neck, that proliferation of tumor clonogenic cells during radiotherapy impairs local control and is an important mechanism of tumor therapeutic resistance. Recent studies have linked the pretreatment tumor potential doubling time with these intra-treatment proliferation rates. Thus, it is possible that a pretreatment determination of the potential doubling time might predict a given tumor's ability to repopulate during treatment. This, then, would allow selection of an accelerated course of radiotherapy for that subset of tumors with a high proliferative potential, leaving better tolerated, conventional fractionation schemes for tumors with lower proliferation rates. This study's primary purpose is to determine whether knowledge of the pretreatment tumor potential doubling time will allow selection of a subset of patients most likely to benefit from altered fractionation schedules. Modifications of the bromodeoxyuridine/delayed-biopsy technique will be used to determine pretreatment kinetics in human tumors of the head and neck. Cell kinetic parameters will include the DNA labelling index, length of the DNA synthetic phase and the potential doubling time. Secondary parameters will include the DNA index and S phase fraction. The patient population studied will be from RTOG protocol 90-03, a randomized trial with a total accrual goal of 648 patients that compares two accelerated, one conventional and one hyperfractionated radiotherapy schedule in patients with stage Ill and IV squamous cell carcinoma of the head and neck. Correlations between pretreatment kinetics and localregional control and survival will be investigated. The impact of fractionation schedule upon these correlations will also be studied.