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Table 3 Imaging biomarkers for disease response assessment (semi-quantitative and quantitative) with examples of current evidence for their use that would support decision-making

From: Validated imaging biomarkers as decision-making tools in clinical trials and routine practice: current status and recommendations from the EIBALL* subcommittee of the European Society of Radiology (ESR)

  Biomarker SemiQ/Q Disease Question answered Utility of biomarker Data from Potential decision for
Non-malignant disease Volumetric high resolution CT density (quantitative interstitial lung disease, QILD) Q Scleroderma Response to cyclophosphamide 24-month changes in QILD scores in the whole lung correlated significantly 24-month changes in forced vital capacity (ρ  = − 0.37), diffusing capacity (ρ = − 0.22) and breathlessness (ρ = − 0.26) [164] Single centre Continue, change or stop treatment
Left Ventricular ejection fraction LVEF Q Pulmonary hypertension
Myocardial ischaemia/infarction
Right and left cardiac sufficiency
Improvement in cardiac function
Increases in 6-min walk distance were significant correlated with change in right ventricular ejection fraction and left ventricular end-diastolic volume [165]
Monitoring cardiac function [166]
Multicentre
Multicentre
Continue, change or stop treatment
Malignant disease RECIST/morphological volume Q Cancer Response Current guidelines for response assessment [167] Multicentre Continue, change or stop treatment
PERCIST/metabolic volume [168] Q Cancer Response Current guidelines for response assessment Multicentre Continue, change or stop treatment
Scoring systems for disease burden SQ Multiple sclerosis
Rheumatoid arthritis
Reduction in disease burden Effects on MRI lesions over 6–9 months predict the effects on relapses at 12–24 months) [169]
International consensus on scoring system [170]
Meta-analysis
Review
Continue, change or stop therapy
DSC-MRI SQ (rCBV) Brain cancer Differentiation of treatment effects and tumour progression In 2 meta-analyses MRI had high pooled sensitivities and specificities: 87% (95% CI, 0.82–0.91) to 90% (95% CI, 0.85-0.94) sensitivity and 86% (95% CI, 0.77–0.91) to 88% (95% CI, 0.83-0.92) specificity [171, 172] Meta-analysis Decision to treat
18F FDG-SUVmax [173] Q Multiple cancer types Response to therapy Rectal cancer-pooled sensitivity, 73%; pooled specificity, 77%; pooled AUC, 0.83 [174]
Intratreatment low SUVmax (persistent low or decrease of 18F-FDG uptake) predictive of loco-regional control in head and neck cancer [175]
Meta-analysis
Meta-analysis
Continue, change or stop therapy
Deauville or RECIL score on 18 F-FDG-PET SQ Lymphoma CR, PR, SD or PD [176] Assessment of tumour burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions [177] Multicentre Continue, change or stop therapy
Targeted agents
HER2
PSMA
SQ Breast cancer [178]
Prostate cancer [179]
Reduction in tumour cells expressing these antigens Tumour receptor specific
Effects of treatment on receptor expression
Single centre studies, review Continue, change or stop therapy
ADC [117] SQ
Q
Rectal cancer
Breast cancer
Response to neoadjuvant chemotherapy
Response to neoadjuvant chemotherapy
Additional value in both the prediction and detection of (complete) response to therapy compared with conventional sequences alone [180]
After 12 weeks of therapy, change in ADC predicts complete pathologic response to neoadjuvant chemotherapy (AUC = 0.61, p = 0.013) [181]
Review
Multicentre
Continue, change or stop therapy, proceed to surgery
CT perfusion/blood flow Q Oesophageal cancer Response to chemoradiotherapy Multivariate analysis identified blood flow as a significant independent predictor of response [182] Single centre Further treatment
DCE-MR parameters Q Multiple cancer types Response to therapy Particular benefit in assessing therapy response to antiangiogenic agents [183] Review Change therapeutic strategy
CT density HU Q Gastrointestinal stromal tumours Response to chemotherapy Decrease in tumour density of > 15% on CT had a sensitivity of 97% and a specificity of 100% in identifying PET responders versus 52% and 100% by RECIST [184]   Continue, change or stop therapy
  1. Biomarkers used visually in the clinic are given in italics, and those that are used quantitatively are in bold
  2. Abbreviations: ADC apparent diffusion coefficient, APT amide proton transfer, AUC area under curve, BI-RADS breast imaging reporting and data systems, CBV cerebral blood volume, CoV coefficient of variation, CR complete response, CT computerised tomography, DCE dynamic contrast enhanced, DFS disease-free survival, DOTATOC DOTA octreotitide, DOTATATE DOTA octreotate, DSC dynamic susceptibility contrast, ECG electro cardiogram, FDG fluorodeoxyglucose, FLT fluoro thymidine, HR hazard ratio, HU Hounsfield unit, ICC intraclass correlation, IQR interquartile range, LVEF left ventricular ejection fraction, MRF magnetic resonance fingerprinting, MRI magnetic resonance imaging, MTR magnetisation transfer ratio, NCCN National Comprehensive Cancer Network, OS overall survival, pCT perfusion computerised tomography, PERCIST positron emission tomography response criteria in solid tumours, PD progressive disease, PFS progression-free survival, PPV positive predictive value, PI-RADS prostate imaging reporting and data systems, PR partial response, PSMA prostate-specific membrane antigen, RECIL response evaluation in lymphoma, RECIST response evaluation criteria in solid tumours, ROC receiver operating characteristic, SD stable disease, SUV standardised uptake value, SWE shear wave elastography, US ultrasound