An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity.

PURPOSE: To analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity.

METHODS AND MATERIALS: Between October 1964 and November 1993, 134 patients with 135 previously untreated primary invasive squamous cell carcinomas of the oral cavity (excluding the lip) were treated postoperatively with continuous courses of external-beam irradiation at the University of Florida. All patients had a minimum follow-up of 2 years (analysis, December 1995). No patient was lost to follow-up.

RESULTS: The 10-year actuarial rates of primary site, neck, and local-regional control were 79%, 88%, and 71%, respectively. Recurrence of cancer above the clavicles developed in 35 patients. Ninety-four percent of the recurrences were within the primary field of irradiation (anterior to the plane of the spinal cord); there were 24 recurrences at the primary site and nine in the upper neck alone. There were no failures in the neck area behind the plane of the spinal cord (i.e., the "posterior strip"). Two failures occurred in the low neck below the level of the thyroid notch. In univariate analyses, factors that affected local-regional control included pathologic stage (I-II vs. III-IV, p = 0.04), margin status (invasive cancer at the margin vs. other, p = 0.0007), multifocal tumor (p = 0.05), perineural invasion (p = 0.04), and number of indications for postoperative irradiation (p = 0.05). Extracapsular nodal extension was marginally significant (p = 0.07). In multivariate analysis, positive margins and number of indications remained significant. These factors were used to define relatively favorable (< 4 indications, margins not positive) and unfavorable (> or = 4 indications and/or margins positive for invasive cancer) groups. For both favorable and unfavorable groups, there were nonsignificant trends toward improved local-regional control for patients who began irradiation within 45-50 days, compared with those whose irradiation began later. There were also nonsignificant trends toward improved control for patients treated with shorter overall irradiation treatment courses. An analysis was also performed on the effects of duration of the overall "treatment package" (from the date of surgery until the last day of irradiation). For patients with unfavorable tumors, there was a significantly higher probability of local-regional control for patients whose overall "treatment package" was < or = 100 days (60% vs. 14%, p = 0.04). The 5-year rate of distant metastasis as the sole site of failure was 8% and was predicted by pathologic N stage (N0-N1, 3%; N2-N3, 16%, p = 0.02), as well as the presence (20%) or absence (6%) of extracapsular nodal extension (p = 0.06). The 5-year freedom-from-relapse rate was 63%. The 5-year survival and cause-specific survival rates were 50% and 67%, respectively. Four severe radiation injuries occurred (3%).

CONCLUSION: This paper provides data that define relatively favorable and unfavorable groups of patients in the postoperative setting. Patients with four or more indications for irradiation and/or invasive cancer at the surgical margins have a worse outcome than patients who do not have these negative factors; this is true in spite of the fact that the unfavorable group received higher doses of radiation. Attention should be focused on not only the interval between surgery and irradiation, but also time-dose parameters and the overall duration of the treatment "package."