Joseph Nuradh, Kirkby Norman F, Hoskin Peter J, West Catharine M L, Choudhury Ananya, Dale Roger G
Ministry of Health, Colombo, Sri Lanka.
Sri Lanka Cancer Research Group, Maharagama, Sri Lanka.
Br J Radiol. 2020 Aug;93(1112):20190250. doi: 10.1259/bjr.20190250. Epub 2020 Jun 2.
As a fractionated course of radiotherapy proceeds tumour shrinkage leads to resolution of hypoxia and the initiation of accelerated proliferation of radioresistant cancer cells with better repair capacity. We hypothesise that, in tumours with significant hypoxia, improved tumour control could be achieved with biphasic fractionation schedules that either use acceleration after 3-4 weeks of conventional radiotherapy or deliver a higher proportional dose towards the end of a course of treatment. We conducted a modelling study based on the concept of biological effective dose (BED) comparing such novel regimens with conventional fractionation.
The comparator conventional fractionation schedule 70 Gy in 35 fractions delivered over 7 weeks was tested against the following novel regimens, both of which were designed to be isoeffective in terms of late normal tissue toxicity.40 Gy in 20 fractions over 4 weeks followed by 22.32 Gy in 6 consecutive daily fractions (delayed acceleration)30.4 Gy in 27 fractions over 4 weeks followed by 40 Gy in 15 fractions over 3 weeks (temporal dose redistribution)The delayed acceleration regimen is exactly identical to that of the comparator schedule over the first 28 days and the BED gains with the novel schedule are achieved during the second phase of treatment when reoxygenation is complete. For the temporal redistribution regimen, it was assumed that the reoxygenation fraction progressively increases during the first 4 weeks of treatment and an iterative approach was used to calculate the final tumour BED for varying hypoxic fractions.
Novel fractionation with delayed acceleration or temporal fractionation results in tumour BED gains equivalent to 3.5-8 Gy when delivered in 2 Gy fractions.
In hypoxic tumours, novel fractionation strategies result in significantly higher tumour BED in comparison to conventional fractionation.
We demonstrate that novel biphasic fractionation regimens could overcome the effects of tumour hypoxia resulting in biological dose escalation.
在分割放疗过程中，肿瘤缩小会导致缺氧情况缓解，并引发具有更好修复能力的放射抗性癌细胞加速增殖。我们假设，在缺氧显著的肿瘤中，采用双相分割方案可提高肿瘤控制率，该方案要么在传统放疗3 - 4周后采用加速放疗，要么在疗程结束时给予更高比例剂量。我们基于生物等效剂量（BED）的概念进行了一项建模研究，将此类新方案与传统分割方案进行比较。
将对照的传统分割方案（7周内分35次给予70 Gy）与以下两种新方案进行测试，这两种新方案在晚期正常组织毒性方面均设计为等效。4周内分20次给予40 Gy，随后连续6天每天给予22.32 Gy（延迟加速）；4周内分27次给予30.4 Gy，随后3周内分15次给予40 Gy（时间剂量重新分布）。延迟加速方案在最初28天与对照方案完全相同，新方案的BED增益在治疗的第二阶段实现，此时再氧合完成。对于时间重新分布方案，假设在治疗的前4周再氧合分数逐渐增加，并采用迭代方法计算不同缺氧分数下的最终肿瘤BED。
采用延迟加速或时间分割的新分割方案，以2 Gy分割给予时，肿瘤BED增益相当于3.5 - 8 Gy。
在缺氧肿瘤中，与传统分割相比，新的分割策略可使肿瘤BED显著更高。
我们证明，新的双相分割方案可克服肿瘤缺氧的影响，导致生物剂量增加。
