Evaluation of dysphagia-optimising radiotherapy techniques in locally advanced oropharyngeal cancer

Radiation-associated dysphagia (RAD) following chemoradiation in locally advanced oropharyngeal cancers (LA-OPC) can have a devastating impact on patients' quality of life (QoL). Establishing efficient swallow-sparing radiotherapy (RT) techniques is, therefore, of paramount importance in an era where health-related QoL measures are increasingly influential determinants of curative management strategies. Dysphagia-optimised intensity-modulated RT (Do-IMRT) is a novel planning technique that limits dose delivered to the pharyngeal constrictor muscles (PCM), a key swallowing structure implicated in RAD. A retrospective comparison planning study is presented which specifically investigated the swallow-sparing benefits of Do-IMRT over standard IMRT (S-IMRT) in LA-OPC. It is demonstrated that Do-IMRT significantly reduces the probability of persistent swallowing dysfunction, without compromising on dose to high-dose target volume or organs at risk (OAR). Prospective validation of the benefits of Do-IMRT is currently under investigation within the context of the Dysphagia-at-risk structures (DARS) trial, a national phase 3 randomised study. Intensity-modulated proton therapy (IMPT), with its sharp dose fall-off, holds great promise as a toxicity-mitigating strategy. The benefits of IMPT in reducing RAD in LA-OPC relative to IMRT, however, remain investigational. The role of IMPT, using different beam arrangements and optimisation techniques, in reducing the estimated risk of RAD was evaluated in a retrospective comparison planning study. It is shown that robustly optimised dysphagia-optimised IMPT (Do-IMPT-RO) could improve long-term swallowing function in selected patients with LA-OPC, compared to Do-IMRT. It is also demonstrated that the robustness of Do-IMRT-RO plans are not affected in the presence of range and set up uncertainties, unlike conventional planning target volume (PTV)-based Do-IMPT optimisation technique. The perceived advantage of dysphagia-optimising RT techniques is contingent on contouring accuracy of PCM, an OAR not delineated routinely in the United Kingdom (UK). Heterogeneity in delineation between oncologists may lead to differences in the reported dose-volume parameters, and this can have implications on subsequent toxicity outcomes. Inter-observer variability (IOV) in PCM contouring in the UK and subsequent potential impact on functional outcomes was studied within the context of a pre-trial RT quality assurance programme for DARS study. It is shown that there is IOV in the delineation of PCM amongst oncologists, but the impact of the variability on dose delivered to this structure was not significantly impacted upon in the pre-trial benchmark case