Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer

• Currently, treatment response monitoring in lung cancer is reliant on size change.
• With varied mechanisms of action, different therapeutic strategies produce changes in tumour biology that are often not accompanied by a reduction in size, despite improved patient outcome.
• Established and novel positron emission tomography and magnetic resonance imaging functional imaging techniques are able to monitor tumour biology, potentially offering both earlier and more accurate predictors of outcome than size change alone.
• Features evaluable with robust quantitative imaging techniques include metabolism, tissue water diffusion, perfusion, chemical composition and hypoxia.
• Knowledge of both the biological changes driving treatment response and the biophysical process to which each imaging modality relates is key in devising rational imaging strategies for any therapeutic regime.

Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing platform of antibody and small molecule therapies and immunotherapies. Although these therapies have varied mechanisms of action, they often induce changes in tumour architecture and microenvironment such that response is not always accompanied by early reduction in tumour mass, and evaluation by criteria other than size is needed to report more effectively on response. Functional imaging techniques, which probe the tumour and its microenvironment through novel positron emission tomography and magnetic resonance imaging techniques, offer more detailed insights into and quantitation of tumour response than is available on anatomical imaging alone. Use of these biomarkers, or other rational combinations as readouts of pathological response in NSCLC have potential to provide more accurate predictors of treatment outcomes. In this article, the robustness of the more commonly available positron emission tomography and magnetic resonance imaging biomarker indices is examined and the evidence for their application in NSCLC is reviewed.