[Controlled clinical trials of hyperfractionated and accelerated radiotherapy in otorhinolaryngologic cancers]

From 1978 to March 1998, (1,867 patients) were accrued in head and neck trials comparing hyperfractionation (HF) and accelerated fractionation (AF) to classical fractionation (CF). Two randomized trials (867 pts) led to positive conclusions in favour of the HF & AF arms: 1) EORTC trial 22791 (356 patients, 1980-87) compared CF (70 Gy/35-40 fr/7-8 wks) to HF (80.5 Gy/70 fr/7 wks, using 2 fr x 1.15 Gy/day) in T2 T3, N0-N1 < 3 cm in oropharyngeal carcinoma. Locoregional control (LRC) was higher (p = 0.01) in HF versus CF. At 5 years, 56% of the patients are LRC free with HF versus 38% with CF on the latest update (February 1998). This improvement of LRC also resulted in a significant overall survival (p = 0.05). There was no difference in late normal tissue damage between the two treatment modalities. Overall, this is the largest improvement documented in a randomised trial for oropharyngeal cancers during the past decade. 2) EORTC trial 22851 (511 patients, 1985-1995) compared AF (72 Gy/45 fr/5 wks) to CF (70 Gy/35 fr/7 wks) in T2 T3 T4 head & neck cancers (hypopharynx excluded). Acute and late toxicity were increased in the AF arm. Late severe sequelae occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord. The AF arm is significantly better for locoregional control (p = 0.017) and for time to progression (p = 0.012) resulting in a 15% locoregional gain at 5 years over the CF arm. This improvement is of larger magnitude in patients with poorer prognosis (N3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent pronostic factor for local control (p = 0.03). Specific survival shows a non significant advantage (p = 0.06) in favour of the AF arm. This trial shows that accelerated radiotherapy is able to improve locoregional control in a large variety of head and neck squamous cell carcinomas. A less toxic scheme should however be investigated before moving AF schemes in standard practice. To conclude, these two schemes derived from experimental radiobiology concepts resulted in a significant improvement of locoregional control. Hyperfractionation resulted in an improved locoregional and survival benefit. Although HF is presently the most reliable regimen to improve locoregional control, the validity of the concept of AF is also confirmed. Better schemes of AF should now be evaluated to reduce late toxicity.