This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors.

Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving > 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk.

The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of < or = 54 Gy had a significantly higher primary failure rate than those receiving > or = 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at > or = 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, > or = 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status > or = 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received > or = 63 Gy.

With daily fractions of 1.7 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio.