Quantitative PET-based biomarkers in lymphoma: getting ready for primetime

The use of functional quantitative biomarkers extracted from routine PET-CT scans to characterize clinical responses in patients with lymphoma is gaining increased attention, and these biomarkers can outperform established clinical risk factors. Total metabolic tumour volume enables individualized estimation of survival outcomes in patients with lymphoma and has shown the potential to predict response to therapy suitable for risk-adapted treatment approaches in clinical trials. The deployment of machine learning tools in molecular imaging research can assist in recognizing complex patterns and, with image classification, in tumour identification and segmentation of data from PET-CT scans. Initial studies using fully automated approaches to calculate metabolic tumour volume and other PET-based biomarkers have demonstrated appropriate correlation with calculations from experts, warranting further testing in large-scale studies. The extraction of computer-based quantitative tumour characterization through radiomics can provide a comprehensive view of phenotypic heterogeneity that better captures the molecular and functional features of the disease. Additionally, radiomics can be integrated with genomic data to provide more accurate prognostic information. Further improvements in PET-based biomarkers are imminent, although their incorporation into clinical decision-making currently has methodological shortcomings that need to be addressed with confirmatory prospective validation in selected patient populations. In this Review, we discuss the current knowledge, challenges and opportunities in the integration of quantitative PET-based biomarkers in clinical trials and the routine management of patients with lymphoma. Despite advances in drug development for patients with lymphoma over the past decades, the identification of biomarkers for treatment selection remains an unmet need. The authors of this Review provide an overview of quantitative PET-based biomarkers in this patient population and discuss the challenges and opportunities in the integration of these biomarkers in clinical trials and the routine management of patients with lymphoma.