3D Quantitative tumour burden analysis in patients with hepatocellular carcinoma before TACE: comparing single-lesion vs. multi-lesion imaging biomarkers as predictors of patient survival

Abstract

Objectives: To compare the ability of single- vs. multi-lesion assessment on baseline MRI using 1D- and 3D-based measurements to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) before transarterial chemoembolization (TACE).

Methods: This retrospective analysis included 122 patients. A quantitative 3D analysis was performed on baseline MRI to calculate enhancing tumour volume (ETV [cm(3)]) and enhancing tumour burden (ETB [%]) (ratio between ETV [cm(3)] and liver volume). Furthermore, enhancing and overall tumour diameters were measured. Patients were stratified into two groups using thresholds derived from the BCLC staging system. Statistical analysis included Kaplan-Meier plots, uni- and multivariate cox proportional hazard ratios (HR) and concordances.

Results: All methods achieved good separation of the survival curves (p < 0.05). Multivariate analysis showed an HR of 5.2 (95 % CI 3.1-8.8, p < 0.001) for ETV [cm(3)] and HR 6.6 (95 % CI 3.7-11.5, p < 0.001) for ETB [%] vs. HR 2.6 (95 % CI 1.2-5.6, p = 0.012) for overall diameter and HR 3.0 (95 % CI 1.5-6.3, p = 0.003) for enhancing diameter. Concordances were highest for ETB [%], with no added predictive power for multi-lesion assessment (difference between concordances not significant).

Conclusion: 3D quantitative assessment is a stronger predictor of survival as compared to diameter-based measurements. Assessing multiple lesions provides no substantial improvement in predicting OS than evaluating the dominant lesion alone.

Key points: • 3D quantitative tumour assessment on baseline MRI predicts survival in HCC patients. • 3D quantitative tumour assessment predicts survival better than any current radiological method. • Multiple lesion assessment provides no improvement than evaluating the dominant lesion alone. • Measuring enhancing tumour volume in proportion to liver volume reflects tumour burden.

Keywords: 3D; HCC; Segmentation; TACE; Tumour burden.

Fig. 1

Exclusion criteria flowchart. A total of 142 patients were excluded because of portal vein invasion; 28 patients were excluded because of missing or inadequate MRI results. In addition, a total of 8 patients were excluded because of infiltrative HCC

Fig. 2

MRI assessment techniques. a 1D measurements of the overall tumour diameter as shown by a fine red line. b 1D measurement of the enhancing tumour diameter as shown by a fine red line. Enhancement was defined as areas with hyperintense MR signal in the arterial phase of the T1-weightedMRI sequence that were not seen in the pre-contrast phase. c Segmentation masks (3D rendering in red) representing total tumour volume (TTV). A fine yellow line as created by semiautomatic liver segmentation illustrates the liver contour. d Quantification of the enhancing tumour volume (ETV). Red represents maximum enhancement and blue represents no enhancement, normalized by the ROI. Green box 3D ROI used as the reference background of image intensity

Fig. 3

Definition of thresholds. Cut-offs derive from unidimensional values that were extrapolated using the equation for the calculation of spheroid volumes (see figure). For single lesions, this was 5 cm for diameter and 65 cm³ for volumes. For multiple lesions, this was 3 lesions each 3 cm in diameter and for volumes 45 cm³

Fig. 4

OS curves for the respective thresholds for utilized image assessment techniques. Kaplan–Meier analysis results are shown for each subgroup and technique on the basis of cut-off values. According to the analysis, all radiological methods provided a good separation of the survival curves (P < 0.05)

Fig. 5

Boxplots showing overall survival for high and low tumour burden groups stratified according to each of the used method