Radiobiologically derived biphasic fractionation schemes to overcome the effects of tumour hypoxia
AffiliationMinistry of Health, Colombo, Sri Lanka.
MetadataShow full item record
AbstractOBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In hypoxic tumours, novel fractionation strategies result in significantly higher tumour BED in comparison to conventional fractionation. ADVANCES IN KNOWLEDGE: We demonstrate that novel biphasic fractionation regimens could overcome the effects of tumour hypoxia resulting in biological dose escalation.
CitationN. Joseph, N. F. Kirkby, P. J. Hoskin et al. Radiobiologically derived biphasic fractionation schemes to overcome the effects of tumour hypoxia. Br J Radiol. 2020:20190250.
JournalBritish Journal of Radiology
- Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlates with reoxygenation.
- Authors: Petersen C, Zips D, Krause M, Schöne K, Eicheler W, Hoinkis C, Thames HD, Baumann M
- Issue date: 2001 Oct 1
- Impact of SBRT fractionation in hypoxia dose painting - Accounting for heterogeneous and dynamic tumor oxygenation.
- Authors: Kjellsson Lindblom E, Ureba A, Dasu A, Wersäll P, Even AJG, van Elmpt W, Lambin P, Toma-Dasu I
- Issue date: 2019 May
- Modelling the interplay between hypoxia and proliferation in radiotherapy tumour response.
- Authors: Jeong J, Shoghi KI, Deasy JO
- Issue date: 2013 Jul 21
- Radiobiological prediction of normal tissue toxicities and tumour response in the radiotherapy of advanced non-small-cell lung cancer.
- Authors: Singer JM, Price P, Dale RG
- Issue date: 1998 Dec
- The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate.
- Authors: Sminia P, Schneider CJ, Fowler JF
- Issue date: 2002 Mar 1