Stuschke M, Thames H D
Department of Radiotherapy, University Hospital Charité, Humboldt University, Berlin, Germany.
Radiother Oncol. 1999 May;51(2):113-21. doi: 10.1016/s0167-8140(99)00042-0.
A therapeutic benefit can be achieved by hyperfractionation (HF) if tumours have small fractionation sensitivities characterized by alpha/beta values greater than those for late effects of dose limiting normal tissues. It is the purpose of the present paper to estimate alpha/beta values for head and neck carcinomas from randomized HF trials.
Maximum likelihood estimates the alpha/beta ratio were obtained from tumour control data from the randomized HF trials using the LQ model and a logit or probit type dose-response curve. A joint analysis of five randomized HF trials for head and neck carcinomas was performed to estimate overall alpha/beta and gamma50 values for tumour control. In addition, alpha/beta ratios for the individual trials were estimated using fixed gamma50 values (characteristic quantifying the steepness of dose-response curves) between 1.4 and 5 for tumours.
An overall gamma50 of 3.1 (1.5-4.7) was estimated for the dose-tumour control relation from the HF trials, assuming a logit or probit dose-response curve. The tumours showed small fractionation sensitivities characterized by an overall alpha/beta of 10.5 (6.5-29) Gy. One trial allowed quantitative estimation of the alpha/beta values for late normal tissue damage: The alpha/beta estimate for late effects of grade 2 + was 4.0 (3.3-5.0) Gy, assuming a fixed gamma50 of 5 and was even smaller for smaller gamma50 values.
Head and neck carcinomas showed small fractionation sensitivities with alpha/beta values greater than those typical for bone, soft tissues, and skin, as well as steep dose response curves. Thus, important prerequisites for improving the therapeutic benefit of radiotherapy of head and neck carcinomas by HF are fulfilled for patients who met the accession criteria of the trials.
如果肿瘤具有较小的分次敏感性，其α/β值大于剂量限制正常组织晚期效应的α/β值，那么通过超分割放疗（HF）可实现治疗益处。本文旨在从随机HF试验中估算头颈部癌的α/β值。
使用LQ模型以及logit或probit型剂量反应曲线，从随机HF试验的肿瘤控制数据中获得α/β比值的最大似然估计值。对头颈部癌的五项随机HF试验进行联合分析，以估算肿瘤控制的总体α/β值和γ50值。此外，使用肿瘤的γ50固定值（用于量化剂量反应曲线的陡度）在1.4至5之间估算各个试验的α/β比值。
假设采用logit或probit剂量反应曲线，从HF试验估算出剂量-肿瘤控制关系的总体γ50为3.1（1.5 - 4.7）。肿瘤显示出较小的分次敏感性，总体α/β为10.5（6.5 - 29）Gy。一项试验允许对晚期正常组织损伤的α/β值进行定量估计：假设γ50固定为5，2级及以上晚期效应的α/β估计值为4.0（3.3 - 5.0）Gy，对于较小的γ50值，该值甚至更小。
头颈部癌显示出较小的分次敏感性，其α/β值大于骨骼、软组织和皮肤的典型值，并且剂量反应曲线较陡。因此，对于符合试验纳入标准的患者，通过HF提高头颈部癌放疗治疗益处的重要前提条件得到了满足。
