Abstract
Radiotherapy is recognized globally as a mainstay of treatment in most solid tumors and is essential in both curative and palliative settings. Ionizing radiation is frequently combined with surgery, either preoperatively or postoperatively, and with systemic chemotherapy. Recent advances in imaging have enabled precise targeting of solid lesions yet substantial intratumoral heterogeneity means that treatment planning and monitoring remains a clinical challenge as therapy response can take weeks to manifest on conventional imaging and early indications of progression can be misleading. Photoacoustic imaging (PAI) is an emerging modality for molecular imaging of cancer, enabling non-invasive assessment of endogenous tissue chromophores with optical contrast at unprecedented spatio-temporal resolution. Preclinical studies in mouse models have shown that PAI could be used to assess response to radiotherapy and chemoradiotherapy based on changes in the tumor vascular architecture and blood oxygen saturation, which are closely linked to tumor hypoxia. Given the strong relationship between hypoxia and radio-resistance, PAI assessment of the tumor microenvironment has the potential to be applied longitudinally during radiotherapy to detect resistance at much earlier time-points than currently achieved by size measurements and tailor treatments based on tumor oxygen availability and vascular heterogeneity. Here, we review the current state-of-the-art in PAI in the context of radiotherapy research. Based on these studies, we identify promising applications of PAI in radiation oncology and discuss the future potential and outstanding challenges in the development of translational PAI biomarkers of early response to radiotherapy.
Highlights
External X-ray beam radiotherapy (EBRT) is a common and effective treatment for many solid tumors, used as a standalone method or in combination with other treatments, from first line to palliative setting [1]
In conventionally fractionated EBRT, small fractions of radiation dose are delivered to the tumor over several weeks and optimized to spare surrounding healthy tissue [1]
Response to EBRT is typically assessed by the response evaluation criteria in solid tumors (RECIST) [6] and its derivatives [7, 8] in clinical trials
Summary
External X-ray beam radiotherapy (EBRT) is a common and effective treatment for many solid tumors, used as a standalone method or in combination with other treatments, from first line to palliative setting [1]. Magnetic resonance imaging (MRI) has shown potential as a non-ionizing modality for defining sub-volumes for escalation of radiation dose based on diffusion [27, 28] and perfusion [29–31] biomarkers, or for predicting response with oxygen-sensitive MRI techniques using tissue and blood oxygen level dependent (TOLD/BOLD) signals with oxygen [32] or carbogen gas breathing challenge [33], reviewed elsewhere [34].
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