DISCUSSION
Several somatic genetic alterations, that provide critical prognostic information, have been described in NB. Among those, MYCN amplification is a crucial prognostic factor, being associated to advanced tumor stage and poor outcome, and is central to the risk stratification systems. According to the recommendations of the INRG Biology Committee, the methods accepted for detecting MYCN amplification are represented by FISH, Polymerase Chain Reaction (PCR), Array comparative genomic hybridization (aCGH) and Multiple Ligation dependent Probe Amplification (MLPA) on tumor tissue [17]. In clinical practice, the availability of tumor material is sometimes challenging even if biopsy remains the gold standard for the diagnosis of NB. Several minimally invasive surgical approaches have been adopted, including samples from fine-needle aspirates, but they result to be burdened by a significant risk of hetMNA, giving clinicians only partial information that could be misleading in the choice of the most appropriate therapeutic approach. Furthermore, MYCN amplification may rarely show hetMNA itself, making the sampling and following diagnosis even more challenging. Recently, other experimental methods to detect MYCN amplification by using cell-free DNA in serum and plasma have been developed in patient affected by NB [18, 19]. However, these approaches have not been validated yet in the current clinical practice. In this context, radiomics and radiogenomics, may play a significant role thanks to the quantitative noninvasive and repeatable analysis of standard clinical imaging that encompasses the whole tumor volume, taking into account the hetMNA. Radiomics features may be associated with specific molecular pathways or mutations, offering reliable predictive tools for clinicians in breast cancer [20], glioma [14], lung cancer [15, 21] and even in healthy tissue [22]. Furthermore, CT represent the most common modality used to diagnose and stage NB and for this reason the images are easily accessible even for retrospective analysis. Brisse and colleagues correlate semantic features to the genomic profile of NB, showing a significant relationships among the sympathetic origin of the tumor, its genomic profile and the outcome [23]. In our preliminary study we aimed to develop a radiomics single phase CT based predictive model as a convenient and reliable biomarker for MYCN amplification status in NB. The proposed radiomics signature was set up to differentiate among MYCN amplified and MYCN wild types tumors, representing a promising tool for prognostic prediction in a particularly innovative scenario. Wu and colleagues have recently published a similar model, achieving similar results in MYCN prediction using a combined clinical-radiomics modeling approach. Despite the similar structure of the two experiences, our model focuses only on one CT sequence, reducing the foreseen workload for a real-world application of our approach in clinical practice and is based on a lower number of radiomics features (2 versus 7), reducing the computational burden and offering a more immediate workflow [24].
In conclusion, this preliminary study suggests that standard post-contrast CT logistic radiogenomics classifier may help to identify MYCN amplification status, which may successfully integrate the traditional invasive MYCN status testing and provide survival predictions for patients presenting amplification. The limitations of this study are represented by the relatively small sample size, which cannot reflect the overall MYCN status population, and the retrospective and single-institution nature. Further prospective multicenter validation studies are necessary to confirm the generalizability of the observed results and to externally validate the proposed model.