Fowler Jack F, Harari Paul M, Leborgne Felix, Leborgne José H
Department of Human Oncology K4/316, University of Wisconsin, 600 Highland Ave., Madison, WI 53792, USA.
Radiother Oncol. 2003 Nov;69(2):161-8. doi: 10.1016/s0167-8140(03)00231-7.
To investigate whether a predictive estimate can be obtained for a 'tolerance level' of acute oral and pharyngeal mucosal reactions in patients receiving head and neck radiotherapy, using an objective set of dose and time data.
Several dozen radiotherapy schedules for treating head and neck cancer have been reviewed, together with published estimates of whether they were tolerated or (in a number of schedules) not. Those closest to the borderline were given detailed analysis. Total doses and biologically effective doses (BED or ERD) were calculated for a range of starting times of cellular repopulation and rates of daily proliferation. Starting times of proliferation from 5 to 10 days and daily cellular doubling rates of 1-3 days were considered. The standard published form of BED with its linear overall time factor was used: BED=nd(1 + d/(alpha/beta) - Ln2(T - T(k))/alpha T(p) (see text for parameters).
A clear progression from acceptable to intolerable mucosal reactions was found, which correlated with total biologically effective dose (BED in our published modeling), for all the head and neck cancer radiotherapy schedules available for study, when ranked into categories of 'intolerable' or 'tolerable'. A review of published mechanisms for mucosal reactions suggested that practical schedules used for treatment caused stimulated compensatory proliferation to start at about 7 days. The starting time of compensatory proliferation had little predictive value in our listing, so we chose the starting time of 7 days. Very short and very long daily doubling rates also had little reliability, so we suggest choosing a doubling time of 2.5 days as a datum. With these parameters a 'tolerance zone of uncertainty' could be identified which predicted acute-reaction acceptability or not of a schedule within a range of about 2-10 Gy in total BED. If concurrent chemoradiotherapy is used, our provisional suggestion is that this zone should be reduced by up to roughly 3-5 Gy10 in BED, with a request for further evidence.
It is suggested that total BED should be used, as specified above. Parameters of alpha=0.35 Gy-(1), alpha/beta=10 Gy, Tk=7 days and Tp=2.5 days are suggested. The 'acute/ tolerance zone' then turns out to be 59-61 Gy10 for radiation-only treatments. Further information about the decrement caused by concurrent head-and-neck cancer chemoradiotherapy, possibly 3-5 Gy10, is required.
利用一组客观的剂量和时间数据，研究对于接受头颈部放疗的患者，是否能够获得急性口腔和咽部黏膜反应“耐受水平”的预测估计值。
回顾了几十种治疗头颈部癌的放疗方案，以及已发表的关于这些方案是否被耐受（在一些方案中为不耐受）的估计。对那些最接近临界值的方案进行了详细分析。针对细胞再增殖的一系列起始时间和每日增殖率，计算了总剂量和生物等效剂量（BED或ERD）。考虑了从5至10天的增殖起始时间以及1至3天的每日细胞倍增率。使用了具有线性总时间因子的BED标准发表形式：BED = nd(1 + d/(α/β) - Ln2(T - T(k))/α T(p)（参数见正文）。
对于所有可供研究的头颈部癌放疗方案，当分为“不耐受”或“耐受”类别时，发现从可接受的黏膜反应到不可耐受的黏膜反应有明显进展，这与总生物等效剂量（我们发表的模型中的BED）相关。对已发表的黏膜反应机制的回顾表明，用于治疗的实际方案会使刺激的代偿性增殖在约7天开始。在我们的列表中，代偿性增殖的起始时间预测价值不大，因此我们选择7天作为起始时间。非常短和非常长的每日倍增率可靠性也很低，因此我们建议选择2.5天的倍增时间作为基准。利用这些参数，可以确定一个“不确定耐受区”，该区域可在总BED约2 - 10 Gy的范围内预测方案的急性反应可接受性。如果使用同步放化疗，我们的初步建议是，该区域应在BED中减少约3 - 5 Gy10，有待进一步证据。
建议使用上述规定的总BED。建议参数为α = 0.35 Gy⁻¹，α/β = 10 Gy，Tk = 7天，Tp = 2.5天。对于单纯放疗，“急性/耐受区”结果为59 - 61 Gy10。需要关于同步头颈部癌放化疗导致的减量的更多信息，可能为3 - 5 Gy10。
