Horiot J C
Service de Radiothérapie, Centre de Lutte Contre le Cancer Georges-François Leclerc, Dijon, France.
Bull Acad Natl Med. 1998;182(6):1247-60; discussion 1261.
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.
从1978年至1998年3月，（1867例患者）被纳入头颈部试验，比较超分割放疗（HF）、加速分割放疗（AF）与传统分割放疗（CF）。两项随机试验（867例患者）得出了支持HF和AF组的阳性结论：1）欧洲癌症研究与治疗组织（EORTC）试验22791（356例患者，1980 - 1987年）比较了口咽癌T2、T3、N0 - N1且肿瘤直径＜3 cm患者的CF方案（70 Gy/35 - 40次分割/7 - 8周）与HF方案（80.5 Gy/70次分割/7周，采用每日2次分割，每次1.15 Gy）。HF组的局部区域控制（LRC）高于CF组（p = 0.01）。在最新更新（1998年2月）时，5年时HF组56%的患者无局部区域复发，而CF组为38%。LRC的这种改善也带来了显著的总生存期改善（p = 0.05）。两种治疗方式在晚期正常组织损伤方面无差异。总体而言，这是过去十年中口咽癌随机试验记录的最大改善。2）EORTC试验22851（511例患者，1985 - 1995年）比较了T2、T3、T4头颈部癌（下咽癌除外）的AF方案（72 Gy/45次分割/5周）与CF方案（70 Gy/35次分割/7周）。AF组的急性和晚期毒性增加。AF组14%的患者出现晚期严重后遗症，而CF组为4%。脊髓照射剂量达42 Gy和48 Gy后发生了2例放射性脊髓炎。AF组在局部区域控制（p = 0.017）和疾病进展时间（p = 0.012）方面显著更好，5年时比CF组的局部区域控制率提高了15%。与预后较好的患者相比，这种改善在预后较差的患者（N3任何T、T4任何N）中幅度更大。多因素分析证实AF是局部控制的独立预后因素（p = 0.03）。特定生存期显示AF组有非显著优势（p = 0.06）。该试验表明加速放疗能够改善多种头颈部鳞状细胞癌的局部区域控制。然而，在将AF方案应用于标准实践之前，应研究毒性更低的方案。总之，这两种源自实验放射生物学概念的方案显著改善了局部区域控制。超分割放疗带来了局部区域和生存获益的改善。虽然目前HF是改善局部区域控制最可靠的方案，但AF概念的有效性也得到了证实。现在应评估更好的AF方案以降低晚期毒性。
