Challenges such as normal-tissue toxicity and radioresistance mar the otherwise notable advances in radiotherapy treatment planning and delivery that have been achieved over recent decades. These issues are particularly pronounced in patients with head-and-neck cancer (HNC) due to the proximity of malignancies to critical structures, which can lead to severe treatment-related morbidities. As a result, there is an unmet clinical need for treatment strategies that enable radiation dose de-escalation while maintaining efficacy.

A promising approach was explained in a talk at the ESTRO meets Asia meeting in Kuala Lumpur, Malaysia, in August. It involves the use of ultrasound-stimulated microbubbles (USMB), which modulate the tumour microenvironment (TME) in a highly localised manner by affecting the tumour microvasculature. Enhanced tumour control through the combination of USMB with radiotherapy has been demonstrated in various preclinical cancer models, and clinical trials of this treatment are underway for several cancer types, including HNC, although the mechanism responsible for the additive effects remains uncertain.

The effects of USMB and radiotherapy on the TME of two murine preclinical HNC models were assessed to provide additional evidence to elucidate the mechanism of action. Dynamic contrast-enhanced ultrasound and photoacoustic imaging, ex-vivo evaluation (histopathology and flow cytometry) and growth analysis were used to study the responses of the mouse oral carcinoma (MOC) 1 and 2 tumour models.

The results showed that control of tumour growth was significantly enhanced in both models when USMB was administered prior to radiotherapy, compared with radiotherapy alone. The combination therapy also influenced the TME, with increased tumour perfusion observed in both models. Notably, in the more aggressive and immunologically ‘cold’ MOC2 tumours, the combination therapy increased CD8 T-cell infiltration and promoted a tumour phenotype linked to improved treatment response and survival (reduced hypoxia and alterations in epithelial-to-mesenchymal transition-related protein expression).

These findings contribute to the growing understanding of this combination therapy and its potential clinical applications. Future research should focus on the potential use of USMB to de-escalate radiotherapy does and the deciphering of the molecular mechanisms to optimise and realise the potential of USMB-radiotherapy combination therapy.

Hannah Bargh-Dawson

PhD researcher

Institute of Cancer Research

London, UK

hannah.bargh-dawson@icr.ac.uk

@HannahBarghD