ACCELERATED RADIATION-THERAPY FOR LOCALLY ADVANCED SQUAMOUS-CELL CARCINOMAS OF THE ORAL CAVITY AND OROPHARYNX SELECTED ACCORDING TO TUMOR-CELL KINETICS - A PHASE-II MULTICENTER STUDY

Purpose: A Phase II multicenter trial testing an accelerated regimen o f radiotherapy in locally advanced and inoperable cancers of the head and neck, in patients selected on the basis of 5-bromo-2-deoxyuridine/ DNA flow cytometry-derived tumor potential doubling time (T-pot). Meth ods and Materials: From September 1992 to September 1993, 23 patients consecutively diagnosed to have locally advanced, inoperable carcinoma s of the oral cavity and the oropharynx, with T-pot of less than or eq ual to 5 days, received an accelerated radiotherapy regimen (AF) based on a modification of the concomitant boost technique: 2 Gy/fraction o nce a day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fract ion twice a day, with a 6-h interval, one of the two fractions being d elivered as a concomitant boost to reduced fields, up to 66 Gy total d ose (off-cord reduction at 46 Gy), shortening the overall treatment ti me to 4.5 weeks. A contemporary control group of 46 patients with T-po t of >5 days or unknown was treated with conventional fractionation (C F): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5 weeks, with fields shrinkage after 46 Gy. Results: All patients completed th e accelerated regimen according to protocol and in the prescribed over all treatment time. Immediate tolerance was fairly good: 65% of the pa tients in the AF group experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms related to mucosal reactions seemed to per sist longer in AF than in CF patients. The crude proportion of mild (G rades 1 and 3) late effects on skin (p < 0.01) and salivary glands (p < 0.05) was higher in AF than in CF patients, although these reactions did not exceed the limits of tolerance. Three patients in the AF and 1 in the CF arm experienced a late Grade 4 bone complication. Actuaria l estimates of severe (Grades 3 and 4) late complications showed a 2-y ear hazard of 33.3% in the AF arm and 49.7% in CF (p = NS). The actuar ial 2-year local control rate of the AF patients was 49.4%, while actu arial 2-year overall survival for the same patients was 43.5%.Conclusi on: The results suggested that this accelerated regimen is worth testi ng in a controlled randomized trial to compare different accelerated s chedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA h ow cytometry technique as a suitable method of evaluating tumor cell k inetics in multicenter clinical studies, on condition that all measure ments are carried out by one most experienced laboratory. Copyright (C ) 1996 Elsevier Science Inc.