The future of personalised radiotherapy for head and neck cancer

Abstract

Radiotherapy has long been the mainstay of treatment for patients with head and neck cancer and has traditionally involved a stage-dependent strategy whereby all patients with the same TNM stage receive the same therapy. We believe there is a substantial opportunity to improve radiotherapy delivery beyond just technological and anatomical precision. In this Series paper, we explore several new ideas that could improve understanding of the phenotypic and genotypic differences that exist between patients and their tumours. We discuss how exploiting these differences and taking advantage of precision medicine tools-such as genomics, radiomics, and mathematical modelling-could open new doors to personalised radiotherapy adaptation and treatment. We propose a new treatment shift that moves away from an era of empirical dosing and fractionation to an era focused on the development of evidence to guide personalisation and biological adaptation of radiotherapy. We believe these approaches offer the potential to improve outcomes and reduce toxicity.

Figure 1:. Range of radiosensitivity index values in oropharyngeal and non-oropharyngeal squamous cell carcinomas of the head and neck

Adapted with permission from Scott and colleagues.

Figure 2:. Radiomic process in two patients with squamous cell carcinoma of the base of tongue and tonsil treated with definitive radiotherapy

Standard of care images are used for tumour delineation (segmentation) creating a volume of interest (third column). Quantitative features are then extracted from the volume of interest. The fourth column shows Hounsfield units heterogeneity and the fifth column shows standard uptake values, revealing significant intratumoural heterogeneity. These features can later be combined with clinical and genomic data to generate a predictive model (or decision support system) to guide therapy personalisation.

Figure 3:. Proliferation saturation index-dependent radiotherapy response

Tumour growth and standard fractionation radiotherapy is simulated for five tumours with different proportions of proliferating and quiescent cells (proliferation saturation index) at the beginning of treatment. Reproduced from Prokopiou and colleagues.