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Medicines 2018, 5(2), 54; https://doi.org/10.3390/medicines5020054

Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck—A Low α/β?

Hall-Edwards Radiotherapy Research Group, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
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Received: 24 May 2018 / Revised: 9 June 2018 / Accepted: 11 June 2018 / Published: 13 June 2018
(This article belongs to the Special Issue Advances and Perspectives in Radiotherapy Treatments)
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Abstract

Background: The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. Methods: For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70 Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65 Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70 Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84 Gy in 70# over 46 days delivered without synchronous chemotherapy. Using the linear quadratic equation the above isoeffect relationships were expressed algebraically to determine values of α, α/β, and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule (α = 0.3 Gy−1, α/β = 10 Gy, and k = 0.42 Gy10day−1). Results: The values derived for α/β, α and k were 2 Gy, 0.20 and 0.21 Gy−1, and 0.65 and 0.71 Gy2day−1. Conclusions: Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomized trials examining the role of hypofractionated acceleration in SCCHN. View Full-Text
Keywords: head and neck cancer; chemoradiation; linear quadratic equation head and neck cancer; chemoradiation; linear quadratic equation
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Best, J.; Fong, C.; Benghiat, H.; Mehanna, H.; Glaholm, J.; Hartley, A. Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck—A Low α/β? Medicines 2018, 5, 54.

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