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Because the rate of distant metastasis is significant, particularly in patients with advanced nodal involvement, there is a rationale for developing a successful systemic treatment. Newer drug combinations, usually containing cisplatin, have shown high complete response rates in nonkeratinizing head and neck cancers and may improve results of treatment. They should be tested in advanced cases in prospective clinical trials. [ref: 20,50,52,55,67] Concurrent radiation therapy and weekly docetaxel in elderly patients with oropharyngeal carcinoma.

Sequelae of Treatment

High-dose irradiation for base of tongue cancer causes acute side effects, such as severe mucositis, difficulty in swallowing, loss of taste, xerostomia, and weight loss. Patients must be observed carefully, and nasogastric intubation may become necessary to ensure adequate hydration and caloric intake. Late complications of high doses of irradiation occur in one fourth of the patients and cause significant morbidity (Table 40-5). Necrosis of bone and cartilage with associated pain is a difficult management problem and can necessitate removal of the mandible. Adverse sequelae of doses of irradiation greater than 70 Gy in 7 weeks can be avoided by using compensating filters to ensure dose homogeneity, high-energy x-rays to spare the mandible, temporomandibular joints, and subcutaneous tissues, as well as by using altered fractionation schedules. Moderate doses of adjuvant irradiation of 50 to 60 Gy delivered in 5 to 6 weeks in combination with conservation surgery may reduce the incidence of late radiation complications without compromising tumor control, although producing more functional impairment. [ref: 31] Effects of swallowing therapy on oropharyngeal function in head and neck cancer patients.

Surgery for base of tongue cancer is associated with an operative mortality that ranges from 4% to 7%, which must be weighed against the possibility of improved tumor control and reduction in late radiation-induced sequelae. [ref: 23,42] Because of the proximity of pharyngeal and cutaneous suture lines to the carotid artery, formation of pharyngocutaneous fistulas with carotid artery rupture is a major concern.

Clinical Trials

Prospective clinical trials with combinations of irradiation and surgery for base of tongue cancer have been few and unilluminating. Lawrence and associates [ref: 44] studied the use of 14 Gy preoperatively in two equal fractions completed 24 hours before surgery in 69 patients with head and neck cancer, including tongue, tonsil, soft palate, and hypopharyngeal primary tumors. They compared this group with 74 patients receiving surgery alone and found no difference in local control, morbidity, or mortality.

Strong and colleagues [ref: 72] compared 100 patients with stage II and III cancers of the oropharynx treated with 20 Gy preoperatively in 5 days and surgery within 30 days with those receiving surgery alone. There was no difference in the 5-year survival rate, which was 40% for the two groups. However, both groups had unacceptably high rates (56%) of recurrence in the neck after treatment.

Despite the lack of convincing prospective randomized trials, adjuvant postoperative radiation therapy, allowing safer delivery of higher doses, has become standard treatment in moderately advanced and advanced, operable carcinoma of the base of tongue, decreasing the subsequent T and N failure. [ref: 66,75]

A prospective randomized trial by the Radiation Therapy Oncology Group (RTOG) comparing split-course radiation therapy to a dose of 60 Gy with continuous-course therapy to a dose of 66 Gy did not demonstrate any significant difference in local tumor control between the treatment arms. In this study, 89% of patients had T2 or T3 disease, 75% had N+, and 60% had N3 disease. All five T1 and seven of 10 T2 patients had initial tumor control. When both primary and regional disease were considered, however, only 38% of patients became free of locoregional tumor. Five-year survival results in this group of patients were poor, with only 15% surviving. The overall locoregional failure rates were 84% in the continuous-course group and 73% in the split-course group. These results suggest that external irradiation alone to these doses is insufficient for advanced base of tongue carcinoma. However, the adequacy of the fields and their reproducibility could be questioned because of small size and lack of external landmarks. [ref: 49]

The first prospective randomized trial to demonstrate the superiority of hyperfractionation over standard fractionation for oropharyngeal cancer was reported by Horiot and colleagues [ref: 36] for the European Organization for Research on Treatment of Cancer. They reported a significant improvement in 5-year locoregional tumor control rates for 1.15-Gy twice-daily treatment to 80.5 Gy versus 2 Gy per day irradiation to 70 Gy (57% and 37%, respectively) with no difference in late complications. However, base of tongue cancer was excluded from this trial.

A large RTOG trial (RTOG 90-03) nearing completion compares standard fractionation to hyperfractionation, accelerated hyperfractionation with a split, and standard fractionation plus a concomitant boost in patients with head and neck cancers including base of tongue. If these results confirm and extend those of Horiot, then better selection factors for treating cancers of the head and neck with altered fractionation schedules will have been established.