Neuroblastoma is the most common pediatric solid tumor in the sympathetic nervous system and accounts for approximately 15% of childhood cancer‐related mortality (1). Seventy percent of patients with NB have metastatic disease. The time of diagnosis, which commonly involves the cortical bone and the bone marrow, implies a poor prognosis (2, 3). Several clinicohistopathological factors, including age, stage (distant metastases in lymph nodes, cortical bone, bone marrow, and liver), laboratory test parameters (neuron-specific enolase (NSE), lactic dehydrogenase (LDH)) and molecular pathology (the status of MYCN gene, chromosome1p36 and 11q) (4, 5).

Some authors suggest that any gene and chromosomal segmental alteration is associated with an increased risk of relapse and poor outcomes in neuroblastoma[6]. Currently, the most clinically useful genetic marker is an amplification of the MYCN oncogene (6). In approximately 25% of primary untreated patients amplification of the MYCN oncogene is frequently associated with a poor outcome (6). However, specific segmental chromosomal aberrations, such as 11q deletion,1p deletion and 17q gain, are also biological factors associated with poor prognosis (5). The 2-year event-free survival rate for 11q deletion cases was 30%, compared to 34% for MYCN-amplified patients and 100% for cases without these abnormalities (6). Helena Carén et al. revealed that the MYCN-amplified and 11q-deletion groups are significantly associated with poor prognosis (7). Deletion of the short arm of chromosome 1p36 is one of the most characteristic changes in neuroblastomas (8), suggesting that a tumor suppressor gene resides in this region (9). A strong correlation between 1p36 deletion, MYCN amplification, and advanced-stage disease (10). Chromosome 17q gain is observed in approximately half of all tumors and is associated with a low survival rate (11).

Nowadays, iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy is a mainstay method in pediatric NB (12). Nevertheless, ¹²³I-MIBG scintigraphy imaging has several disadvantages, such as no concentration of MIBG in 10% of tumors, limited spatial resolution, and limited sensitivity in small lesions. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) (¹⁸F-FDG PET/CT) is commonly used to complete the staging and prognosis prediction of neuroblastoma. Compared with ¹²³I-MIBG scintigraphy imaging, superiorities of PET are high ¹⁸F-FDG avidity of the bone marrow and better identification of FDG abnormalities in the bone marrow and bone (13, 14). Moreover, another critical advantage of PET/CT is that PET/CT can assess the whole body at once and find unintended distant lymph nodes, bone and skin metastases where traditional imaging or bone marrow biopsies are not usually performed (15). ¹⁸F-FDG PET/CT has an excellent overall diagnostic accuracy with high sensitivity and specificity in detecting bone-bone marrow involvement and soft-tissue lesions in pediatric neuroblastoma (13, 16, 17). ¹⁸F-FDG PET/CT scans may help assess the full extent of disease involvement, particularly at therapeutic decision points (18).

¹⁸F-FDG PET/CT can be used for tumor characterization and prognostic assessment in patients with neuroblastoma (18). Tumor metabolic activity was higher in higher-stage MYCN-amplified patients (19). However, little research has studied the relationship between the status of the MYCN gene and 1p and 11q chromosomal and ¹⁸F-FDG PET/CT metabolic parameters. This study aimed to explore the correlation between ¹⁸F-FDG PET/CT metabolism parameters and the status of the MYCN gene, chromosomal 1p and 11q in newly diagnosed pediatric neuroblastoma by reviewing our clinical experience.

¹²³I-MIBG scintigraphy and ⁶⁸Ga-1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid (DOTA) peptides are now the mainstay nuclear imaging agents for neuroblastoma (22). ¹²³I-MIBG imaging is primarily due to its structural similarity to norepinephrine, tissue that selectively concentrates ¹²³I-MIBG with abundant adrenergic innervation, and mostly neuroectodermal tissues, including neuroblastoma (23). High affinity binding of different ⁶⁸Ga-DOTA peptides to SSTR for PET/CT imaging (24, 25). Somatostatin receptors (SSTR) are expressed in 77%–89% of neuroblastoma cells. Most studies have confirmed the feasibility of ¹⁸F-FDG PET for neuroblastoma imaging, which is seen as an important and widespread alternative to ¹²³I-MIBG scanning, especially for non-MIBG uptake (26). ¹⁸F-FDG scan may be useful in assessing the full extent of disease involvement, particularly at therapeutic decision points (26). We report the ¹⁸F-FDG PET/CT metabolic parameters in newly diagnosed pediatric neuroblastoma and their association with the other indicators of disease clinical biological characteristics and survival status.

In our study, 47 of 60 patients had molecular pathology results, including the status of MYCN gene and chromosomal 1p36 and 11q. We found that the rates of MYCN gene amplification, the chromosome 1p36 and 11q deletion were 34%, 38.3% and 36.2%, respectively, which is in general agreement with other reports on pediatric neuroblastoma (6, 10, 19, 27). In our study, we also found a correlation between MYCN gene amplification and chromosome 1p36 deletions (27, 28). In contrast, there was no correlation between MYCN gene amplification and chromosome 11q deletion and between chromosome 1p36 and 11q deletions.

Much research has found that MYCN gene amplification, chromosome 1p36 and 11q deletions can predict stage and prognosis in patients with neuroblastoma. In our study, MYCN gene amplification and chromosome 11q deletion predict high-risk stratification. What’s more, chromosomal deletion in 11q is highly correlated with lymph node metastasis and bone marrow involvement, suggesting a causal relationship between this region and the disease stage. Based on the Kaplan Meier method and log-rank test, chromosome11q deletion can affect PFS, and patients with chromosome 11q deletions are more likely to progress or die. These results are consistent with other reports of chromosome 11q mutations in pediatric neuroblastoma (27, 28). In addition, we also found that MYCN oncogene amplification is only found in patients with NB, about 100%.

¹⁸F-FDG PET/CT can be used for tumor characterization and prognostic assessment in patients with neuroblastoma (18). However, fewer reports have been reported on the ability of ¹⁸F-FDG PET/CT metabolic parameters in predicting the case of MYCN oncogene amplification, chromosome 1p36 and 11q deletion. In our study, the levels of LDH, NSE and LEGmax, SUVmax, SUVmean, TLG were higher in the MYCN gene amplification group than in the non-amplified group, and the differences were statistically significant in both groups, except for MTV. Meanwhile, the levels of LDH, the lesion MTV and TLG were higher in the chromosome 1p36 deletion group than in the non-deletion group. The differences were statistically significant in both groups. The lesion MTV was higher in the chromosome 11q deletion group than in the non-deletion group, and the difference between them was statistically significant.

Based on receiver operating characteristic (ROC) curve analysis, we obtained optimal threshold values of SUVmax 6.92, SUVmean 4.14, MTV 209.02 cm³, TLG 562.41, NSE 472.0 ng/ml, LDH 927.0 U/L and LEGmax 8.75cm, which can determine whether amplification of the MYCN gene occurred. Meanwhile, we also obtained optimal threshold values of MTV 229.52 cm³, TLG 982.43, LDH 792 U/L and LEGmax 7.99cm, these can determine whether a deletion of chromosome 1p36 has occurred. Surprisingly, there are no ¹⁸F-FDG PET/CT metabolic parameters and laboratory indicators that can effectively determine whether chromosome 11q is mutated.

In addition to gender (p=0.543), the age, the levels of LDH and NSE, the LEGmax, ¹⁸F-FDG PET/CT metabolic parameters (all p < 0.01), including SUVmax, SUVmean, MTV and TLG are all associated with PFS. In ¹⁸F-FDG PET/CT metabolic parameters, higher SUVmax, SUVmean, MTV and TLG were associated with worse PFS.

There are several limitations to our study. First, our results are inherently subject to selection bias as a retrospective study. Second, it may be that the small number of patients collected does not allow for a valid assessment of the differences in metabolic parameters of ¹⁸F-FDG PET/CT in multiple patients with simultaneous several molecular deletions. Third, we only performed correlation analyzes for PFS because of the short follow-up of patients (2-42 months; median time 9.5 months). It is also possible that the observation of the influence of the MYCN oncogene amplification and the chromosome 1p36 deletions on PFS was limited by the short follow-up period. Another shortcoming is that the status of chromosome 17q was not evaluated in our hospital.

The LDH levels, LEGmax, MTV and TLG can effectively predict the status of the MYCN oncogene and chromosome 1p36 in pediatric neuroblastoma and ganglioneuroblastoma. Those patients with chromosome 11q deletions are more likely to develop bone marrow involvement and lymph node metastases, showing a worse progression-free survival.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee of Cancer Hospital Affiliated to Shandong First Medical University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.

JR: acquisition of data, analysis of data, drafting of the manuscript. YZ: analysis of data and revision of the manuscript. ZF: revision of the manuscript, supervision. All authors contributed to the article and approved the submitted version.