Childhood extracranial neoplasms: the role of imaging in drug development and clinical trials

Abstract

Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed.

Feasibility and applicability of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in routine assessments of children with high-grade gliomas

“…Children with high‐grade gliomas (HGGs) have 5‐year survival rates of 15–35%; development of novel agents for these patients is therefore an unmet need. Optimization of imaging response assessments is crucial to enhance paediatric drug development . Diffusion‐weighted (DW) and dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) can monitor and predict response to conventional and targeted agents in HGG patients …”

“…DW‐MRI informs on tissue cellularity and cellular membrane integrity . Malignant tumours are usually hypercellular, with low apparent diffusion coefficients (ADCs) .…”

“…DW‐MRI informs on tissue cellularity and cellular membrane integrity . Malignant tumours are usually hypercellular, with low apparent diffusion coefficients (ADCs) . DCE‐MRI assesses tumour vasculature by tracking intravenously administered contrast agent kinetics .…”

“…DCE‐MRI assesses tumour vasculature by tracking intravenously administered contrast agent kinetics . Malignant tumours often present friable and tortuous blood vessels, commonly with increased vascular perfusion and permeability . Importantly, DW‐MRI and DCE‐MRI allow for noninvasive quantitation of changes in tumour physiology that may serve as predictive and/or pharmacodynamic imaging biomarkers …”