Radiobiological Modelling of the Therapeutic Ratio for the Addition of Synchronous Chemotherapy to Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Abstract 

Aims

To model the therapeutic gain from the addition of synchronous chemotherapy to radiotherapy in locally advanced head and neck cancer.

Materials and methods

Refinements to previous methodology, including the derivation of weighted estimates of key parameters from randomised studies and the use of the expected mucosal biologically effective dose concept, have been used to produce an evidence-based assessment of the benefit from the addition of chemotherapy when considering acute grade 3 mucositis and rates of 5-year local control.

Results

For a value of α=0.3Gy⁻¹ the additional contribution from chemotherapy to local control was estimated to be 9.3Gy₁₀ and to grade 3 mucositis 6.4Gy₁₀. The additional expected mucosal biologically effective dose if radiotherapy dose escalation had been used instead of chemotherapy would have been 11.6Gy₁₀. Therefore, the mucosal sparing by using synchronous chemotherapy rather than radiotherapy dose escalation was found to be 5.2Gy₁₀ or the equivalent dose in 2Gy fractions 4.3Gy EQD₂.

Conclusion

This modelling suggests a small therapeutic gain for the use of synchronous chemotherapy instead of radiotherapy dose escalation. This conclusion is dependent on the linear quadratic model and takes no account of late side-effects. This gain would be greater for agents that enhance the mucosal reaction to a lesser degree. This gain may be less when data for radiotherapy dose escalation to smaller high dose volumes using intensity-modulated radiotherapy are considered.

Key words: Chemoradiation, head and neck cancer, radiobiological modelling, squamous cell carcinoma, therapeutic ratio