Use of new imaging techniques to predict tumour response to therapy

Summary

Imaging of tumour response to therapy has steadily evolved over the past few years as a result of advances in existing imaging modalities and the introduction of new functional techniques. The use of imaging as an early surrogate biomarker of response is appealing, because it might allow for a window of opportunity during which treatment regimens can be tailored accordingly, depending on the expected response. The clinical effect of this would ultimately result in a reduction in morbidity and undue costs. The aim of this review is to describe the potential of various new imaging techniques as biomarkers of early tumour response. We have reviewed the literature and identified studies that have assessed these techniques, such as diffusion-weighted MRI, dynamic contrast-enhanced MRI, magnetic resonance spectroscopy, and 18-fluorodeoxyglucose-PET as early response indicators, and highlight the current clinical awareness of their use.

Introduction

The ability to rapidly and accurately predict the response of a tumour to therapy would have immense value in clinical practice. Persisting with ineffective treatment is associated with increased toxic effects and morbidity, accelerated tumour growth, a delay in commencing alternative, potentially effective treatment, and unnecessary expense. Additionally, because of tumour heterogeneity, all cancers of a particular type rarely respond to the recommended therapy,¹ emphasising the urgent need for a reliable, accurate, and early predictor of tumour response, which would enable the development of individualised regimens.

Imaging has a fundamental role in oncology, especially in the assessment of tumour response to therapy. By using tumour shrinkage as a standard endpoint of response, current conventional imaging follow-up is based on morphological criteria, with changes in tumour dimension determining response or progression. Unfortunately, this traditional method of quantifying tumour response is hampered by various limitations of using size change as a response variable. For example, observer variation can lead to inaccuracy, and infiltrative, irregular lesions can be difficult or almost impossible to measure. Crucially, changes in gross tumour size are notably delayed and substantially lag behind the biological and molecular changes that are known to occur early in responders.2, 3

New functional and metabolic imaging techniques that have the ability to integrate pathological, physiological, and morphological changes, offer substantial potential as early predictors of therapy response (figure 1). These include diffusion-weighted MRI (DW-MRI), which assesses water motion and tumour cellularity, dynamic contrast-enhanced MRI (DCE-MRI), which assesses the biodistribution of contrast within tumours, magnetic resonance spectroscopy (MRS), which analyses the relative amount of chemical components within biological tissues, and 18-fluorodeoxyglucose-PET ([¹⁸F]FDG-PET), which provides an indication of the metabolic and proliferative activity within tumours. Recent advances in the development of these functional techniques have provided an ability to detect microscopic changes in tumour microenvironment and tissue cytoarchitecture, allowing earlier assessment of therapy response by observing alterations in perfusion, oxygenation, and metabolism.

The concept of an imaging biomarker is especially attractive, because it can allow for customised treatment regimens according to the predicted response, and aid the development of improved clinical trials of new therapeutic agents by providing an accurate response indicator. Another appealing factor is the ability of several of these imaging modalities to capture and quantify regional tumour heterogeneity and the changes that occur after treatment. This review aims to highlight the use of these emerging techniques in oncology, with emphasis on the current understanding of their clinical usefulness as predictors or early biomarkers of response.