Prognostic value of texture analysis of the primary tumour in high‐risk neuroblastoma: An ¹⁸F‐DOPA PET study

Abstract

Purpose To evaluate the prognostic value of texture analysis of the primary tumour with 18fluorine‐dihydroxyphenylalanine positron emission tomography/X‐ray computed tomography (18F‐DOPA PET/CT) in patients affected by high‐risk neuroblastoma (HR‐NBL). Methods We retrospectively analysed 18 patients with HR‐NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18F‐DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co‐occurrence (GLCM), run‐length (GLRLM), neighbouring difference (NGLDM) and zone‐length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole‐body metabolic burden (WBMB) score and the progression‐free/overall survival (PFS and OS). Results There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean: p = .004) and voxel heterogeneity (entropy: p = .026; GLCM_Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM_Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N‐myc proto‐oncogene protein (MYCN) amplification (p < .05) for both. Conclusions Textural parameters describing heterogeneity and metabolic intensity of the primary HR‐NBL are closely associated with its overall metastatic burden. In turn, the whole‐body tumour load appears to be one of the most relevant predictors of progression‐free and overall survival.

Improved risk stratification by PET-based intratumor heterogeneity in children with high-risk neuroblastoma

“…On the other hand, Histogram_Entropy measures the randomness of voxel distribution and has been established as an important biomarker reflecting heterogeneity in various MRI and PET studies ( 43 , 45 ). In accordance with previous studies ( 40 , 42 ), we found that high rad-risk, defined as patients with both a high GLRLM_RLNU and a high Histogram_Entropy, indicating a high intratumor heterogeneity, was the most significant independent factor for EFS after adjusting for clinicopathological factors.…”

“…A recent study reported that high intratumor metabolic heterogeneity on 18 F-FDG PET/CT was a strong prognostic factor in 38 children with newly diagnosed neuroblastoma (40), and it was the first report identifying metabolic heterogeneity as a prognostic biomarker of neuroblastoma. The authors used the area under the curve of the cumulative SUV-volume histograms (AUC-CSHs), which is a histogram-based first-order feature that describes the percentage associated with metastatic burden and had certain prognostic value (42). In the current study, we further expanded that intratumor heterogeneity was a prognostic biomarker in neuroblastoma, with a much larger cohort and a higher order of texture analysis, which further improves quantitative histogram approaches by introducing the spatial dimension.…”

“…In another recently published study of 18 children with high-risk neuroblastoma, Fiz et al. demonstrated that intratumor heterogeneity on 18fluorine-dihydroxyphenylalanine (18F-DOPA) PET/CT was closely associated with metastatic burden and had certain prognostic value ( 42 ). In the current study, we further expanded that intratumor heterogeneity was a prognostic biomarker in neuroblastoma, with a much larger cohort and a higher order of texture analysis, which further improves quantitative histogram approaches by introducing the spatial dimension.…”

Prognostic Values of Primary Tumor Textural Heterogeneity and Blood Biomarkers in High-risk Neuroblastoma

“…However, there are only a few studies investigating the prognostic value of PET textural features measuring tumor heterogeneity in neuroblastoma patients. According to the study of Fiz et al, 8 18F-dihydroxyphenylalanine PET textural parameters describing heterogeneity and metabolic intensity of the primary high-risk neuroblastoma were closely associated with its overall metastatic burden. Unlike this study, we examined the 18F-FDG PET texture features instead of 18F-dihydroxyphenylalanine PET.…”

“…Some studies have reported that intratumoural metabolic heterogeneity is correlated with treatment failure, the higher possibility of metastasis, and poor prognosis in various tumors, such as lung cancer, breast cancer, and cervical cancer 7 . However, there are not many studies investigating the prognostic value of intratumor metabolic heterogeneity on 18F-FDG PET/CT in high-risk neuroblastoma patients 8 …”