A Rare Case of Abnormal Diffuse Brain Uptake on an 123I MIBG Scan in a Patient With High-Risk Neuroblastoma.

ABSTRACT: 123I-meta-iodobenzylguanidine (123I-MIBG) is extensively used for initial staging and response evaluation in children with neuroblastoma. Physiological uptake of 123I-MIBG occurs in the salivary glands, liver, adrenal gland, myocardium, bowel, and thyroid gland. 123I-MIBG cannot cross an intact blood-brain barrier. We present the rare case of a 3-year-old boy with neuroblastoma and meningeal metastases who underwent an 123I-MIBG scan for disease restaging that showed abnormal brain uptake. Abnormal MIBG uptake in the brain can occur if there is disruption of the blood-brain barrier either secondary to metastases or after damage to blood-brain barrier.

Prediction of High-Risk Neuroblastoma Among Neuroblastic Tumors Using Radiomics Features Derived from Magnetic Resonance Imaging: A Pilot Study.

PURPOSE: This study aimed to predict high-risk neuroblastoma among neuroblastic tumors using radiomics features extracted from MRI. MATERIALS AND METHODS: Pediatric patients (age≤18 years) diagnosed with neuroblastic tumors who had pre-treatment MR images available were enrolled from institution A from January 2010 to November 2019 (training set) and institution B from January 2016 to January 2022 (test set). Segmentation was performed with regions of interest manually drawn along tumor margins on the slice with the widest tumor area by two radiologists. First-order and texture features were extracted and intraclass correlation coefficients (ICCs) were calculated. Multivariate logistic regression (MLR) and random forest (RF) models from 10-fold cross-validation were built using these features. The trained MLR and RF models were tested in an external test set. RESULTS: Thirty-two patients (M:F=23:9, 26.0±26.7 months) were in the training set and 14 patients (M:F=10:4, 33.4±20.4 months) were in the test set with radiomics features (n=930) being extracted. For 10 of the most relevant features selected, intra- and inter-observer variability was moderate to excellent (ICCs 0.633-0.911, 0.695-0.985, respectively). The area under the receiver operating characteristic curve (AUC) was 0.94 (sensitivity 67%, specificity 91%, and accuracy 84%) for the MLR model and the average AUC was 0.83 (sensitivity 44%, specificity 87%, and accuracy 75%) for the RF model from 10-fold cross-validation. In the test set, AUCs of the MLR and RF models were 0.94 and 0.91, respectively. CONCLUSION: An MRI-based radiomics model can help predict high-risk neuroblastoma among neuroblastic tumors.

Primary Hepatic Neuroblastoma in a 5.5-Month-Old Boy: A Case Report.

The most frequent type of extracranial solid tumor in pediatric cases is neuroblastoma (NB), almost always arising in tissues with sympathetic innervation with only a few reported cases arising in other organs. NBs with hepatic involvement are typically metastatic lesions as primary hepatic NBs are extremely rare. This study presents a 5.5-month-old boy with primary hepatic NB. This case study describes a male 5.5-month-old preterm infant who presented with overt hepatomegaly. Laboratory tests showed an abnormally high level of alpha-fetoprotein. A sonography-guided liver needle biopsy was performed, so histopathological examination suggested the diagnosis of a small round-cell tumor. Immunohistochemical staining demonstrated evidence of neuronal differentiation in the tumor. The sum of these findings was in favor of the diagnosis of NB. Bone marrow aspiration and biopsy were normal. The full-body computed tomography scan revealed a large intrahepatic mass measuring 82×70×74 mm with mild peripheral enhancement. A metaiodobenzylguanidine (MIBG) scintiscan confirmed a huge round MIBG-avid hepatic lesion without other remarkable lesions at other sites in the body. Chemotherapy treatment was started for the patient, and after 4 sessions of chemotherapy, an ultrasound showed that the mass size had decreased to 55×36 mm. This report describes the first primary hepatic NB in a pediatric patient with detailed clinicopathological details. Primary hepatic NB is extremely rare. It is important to consider neuroendocrine tumors as a possibility when faced with a single hepatic tumor that has a similar histological appearance.

Differentiation of early relapse and late relapse in intermediate- and high-risk neuroblastoma with an 18F-FDG PET/CT-based radiomics nomogram.

OBJECTIVES: To develop and validate an 18F-FDG PET/CT-based radiomics nomogram for differentiating early relapse and late relapse of intermediate- and high-risk neuroblastoma (NB). METHODS: A total of eighty-five patients with relapsed NB who underwent 18F-FDG PET/CT were retrospectively evaluated. All selected patients were randomly assigned to the training set and the validation set in a 7:3 ratio. Tumors were segmented using the 3D slicer, followed by radiomics features extraction. Features selection was performed using random forest, and the radiomics score was constructed by logistic regression analysis. Clinical risk factors were identified, and the clinical model was constructed using logistic regression analysis. A radiomics nomogram was constructed by combining the radiomics score and clinical risk factors, and its performance was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Finally, the 12 most important radiomics features were used for modeling, with an area under the curve (AUC) of 0.835 and 0.824 in the training and validation sets, respectively. Age at diagnosis and International Neuroblastoma Pathology Classification were determined as clinical risk factors to construct the clinical model. In addition, the nomogram achieved an AUC of 0.902 and 0.889 for identifying early relapse in the training and validation sets, respectively, which is higher than the clinical model (AUC of 0.712 and 0.588, respectively). The predicted early relapse and actual early relapse in the calibration curves were in good agreement. The DCA showed that the radiomics nomogram was clinically useful. CONCLUSION: Our 18F-FDG PET/CT-based radiomics nomogram can well predict early relapse and late relapse of intermediate- and high-risk NB, which contributes to follow-up and management in clinical practice.

The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

Solitary Dural Metastasis From Neuroblastoma Detected by 123 I-MIBG SPECT/CT.

ABSTRACT: 123 I-MIBG SPECT/CT was performed for follow-up in an asymptomatic 8-year-old girl with a history of neuroblastoma. The images showed an unsuspected abnormal accumulation in the head, which was identified as a hyperdense lesion of the dura with increasing MIBG uptake, suggesting the possibility of metastasis from neuroblastoma. A brain MRI with contrast showed a remarkably enhanced lesion beside the confluence of sinuses, which mimicked meningioma. Results of the surgical pathology are consistent with the diagnosis of dural metastasis from neuroblastoma.

Pediatric neuroblastoma with intraspinal extension: the role of surgical management.

OBJECTIVE: Neuroblastoma with spinal involvement accounts for up to 30% of pediatric spinal tumors and can cause profound neurological deficits. Chemotherapy is the preferred treatment option, but in select patients resection may be indicated. The goal of this study was to identify preoperative factors that led to early surgical intervention, with a specific emphasis on identifying differences on long-term neurological function and spinal deformity in the recent treatment era. METHODS: A retrospective chart review was performed on all children diagnosed with neuroblastoma at a single institution from 2007 to 2020. Patient demographics, symptoms (motor deficit and sphincter dysfunction), and tumor characteristics (e.g., 123I metaiodobenzylguanidine [MIBG] avidity, MYCN amplification, chromosomal abnormality, pathology, catecholamine secretion, and stage) were recorded. Spine involvement included neural or vertebral extension, spinal cord compression, and/or T2 signal change on MRI. Survival, neurological status (motor deficit, sphincter dysfunction), and spine deformity at last follow-up were compared using univariate and multivariate analyses. The variables that contributed to neurological and deformity outcome were assessed with binomial logistic and linear regression models using R software. RESULTS: Seventy-seven of the 160 patients with neuroblastoma had spinal neuroblastoma, meaning either bone metastases alone (n = 43) or intraspinal extension with or without neurological deficit (n= 34). Most patients with spinal neuroblastoma were treated with chemotherapy and/or radiation therapy (97% and 57%, respectively). Resection of the spinal tumor was performed in 14 (18%) patients, all of whom also received chemotherapy. Between the surgical and nonsurgical patients, no baseline demographic differences were found. However, surgical patients were more likely to present with either motor deficits (50% vs 5%, p = 0.0011) or bladder/bowel dysfunction (14% vs 0%, p 0.035), and a shorter median time to onset of neurological symptoms (33 vs 80 days, p = 0.0096). Surgical patients also had a significantly shorter median overall survival (33.0 vs 54 months, p = 0.014). Of the 14 patients who underwent spine surgery, 2 patients underwent surgery at the time of diagnosis while the remaining 12 underwent initial chemotherapy followed later by resection. The 2 patients who underwent initial surgery had excellent outcomes, with neither long-term motor or bowel/bladder deficits nor spinal deformity. CONCLUSIONS: Surgical patients had shorter overall survival. However, the 2 patients with radiographic evidence of cord compression and acute neurological symptom onset who underwent initial, immediate surgery within 3 days of diagnosis had fewer long-term neurological deficits than surgical patients who underwent initial trials of chemotherapy. Thus, acute decompression may provide benefit in carefully selected patients with acute neurological deficits and cord compression on imaging.

Neuroblastoma with superficial soft tissue mass as the first symptom: case reports with atypical ultrasonic image and literature review.

Neuroblastoma is one of the most common tumors in children. Cases where an isolated soft-tissue metastasis mass is the initial symptom are rare, with only four such cases reported to date. We describe the imaging findings of ten cases of neuroblastoma patients in our hospital with superficial soft tissue mass (SSTM) as the primary symptom. The main ultrasound finding of SSTM was hypoechoic masses or scattered speck-like hyperechoic masses. However, when this type of SSTM is caused by soft tissue metastasis, the location is often atypical, and ultrasound findings are difficult to distinguish from other benign diseases. Therefore, this research should remind clinicians to recognize atypical presentations of this common childhood malignant tumor. Radiologists should also consider the possibility of neuroblastoma when finding this type of SSTM with atypical ultrasound features.

A narrative review of radiomics and deep learning advances in neuroblastoma: updates and challenges.

Neuroblastoma is an extremely heterogeneous tumor that commonly occurs in children. The diagnosis and treatment of this tumor pose considerable challenges due to its varied clinical presentations and intricate genetic aberrations. Presently, various imaging modalities, including computed tomography, magnetic resonance imaging, and positron emission tomography, are utilized to assess neuroblastoma. Nevertheless, these conventional imaging modalities have limitations in providing quantitative information for accurate diagnosis and prognosis. Radiomics, an emerging technique, can extract intricate medical imaging information that is imperceptible to the human eye and transform it into quantitative data. In conjunction with deep learning algorithms, radiomics holds great promise in complementing existing imaging modalities. The aim of this review is to showcase the potential of radiomics and deep learning advancements to enhance the diagnostic capabilities of current imaging modalities for neuroblastoma.

Solitary Neuroblastoma in the Scapula.

ABSTRACT: Majority of primary pediatric neuroblastomas occur in the abdomen, followed by posterior mediastinum. A 7-year-old girl presented worsening pain in the left shoulder, and a CT image of the chest revealed osseous destruction in the left scapula, suggestive of bone tumor. A biopsy was performed. Pathological result was consistent with neuroblastoma. A 123I scan with SPECT/CT images was performed, which showed only increased activity in the left scapula without any other foci of abnormal activity elsewhere.

MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma.

BACKGROUND: In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT). MATERIALS AND METHODS: Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position. RESULTS: The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from - 3.5 to 5.8 Gy for the pancreatic tail and - 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation. CONCLUSION: Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors.

BACKGROUND: Neuroblastoma (NB) and pheochromocytoma/paraganglioma (PHEO/PGL) are neuroendocrine tumors. Imaging of these neoplasms is performed by scintigraphy after injection of radiolabeled meta-iodobenzylguanidine (mIBG), a norepinephrine analog taken up by tumoral cells through monoamine transporters. The pharmacological induction of these transporters is a promising approach to improve the imaging and therapy (theranostics) of these tumors. METHODS: Transporters involved in mIBG internalization were identified by using transfected Human Embryonic Kidney (HEK) cells. Histone deacetylase inhibitors (HDACi) and inhibitors of the PI3K/AKT/mTOR pathway were tested in cell lines to study their effect on mIBG internalization. Studies in xenografted mice were performed to assess the effect of the most promising HDACi on 123I-mIBG uptake. RESULTS: Transfected HEK cells demonstrated that the norepinephrine and dopamine transporter (NET and DAT) avidly internalizes mIBG. Sodium-4-phenylbutyrate (an HDACi), CUDC-907 (a dual HDACi and PI3K inhibitor), BGT226 (a PI3K inhibitor) and VS-5584 and rapamycin (two inhibitors of mTOR) increased mIBG internalization in a neuroblastoma cell line (IGR-NB8) by 2.9-, 2.1-, 2.5-, 1.5- and 1.3-fold, respectively, compared with untreated cells. CUDC-907 also increased mIBG internalization in two other NB cell lines and in one PHEO cell line. We demonstrated that mIBG internalization occurs primarily through the NET. In xenografted mice with IGR-NB8 cells, oral treatment with 5 mg/kg of CUDC-907 increased the tumor uptake of 123I-mIBG by 2.3- and 1.9-fold at 4 and 24 h post-injection, respectively, compared to the untreated group. CONCLUSIONS: Upregulation of the NET by CUDC-907 lead to a better internalization of mIBG in vitro and in vivo.

Prediction of MYCN Gene Amplification in Pediatric Neuroblastomas: Development of a Deep Learning-Based Tool for Automatic Tumor Segmentation and Comparative Analysis of Computed Tomography-Based Radiomics Features Harmonization.

OBJECTIVE: MYCN oncogene amplification is closely linked to high-grade neuroblastoma with poor prognosis. Accurate quantification is essential for risk assessment, which guides clinical decision making and disease management. This study proposes an end-to-end deep-learning framework for automatic tumor segmentation of pediatric neuroblastomas and radiomics features-based classification of MYCN gene amplification. METHODS: Data from pretreatment contrast-enhanced computed tomography scans and MYCN status from 47 cases of pediatric neuroblastomas treated at a tertiary children's hospital from 2009 to 2020 were reviewed. Automated tumor segmentation and grading pipeline includes (1) a modified U-Net for tumor segmentation; (2) extraction of radiomic textural features; (3) feature-based ComBat harmonization for removal of variabilities across scanners; (4) feature selection using 2 approaches, namely, ( a ) an ensemble approach and ( b ) stepwise forward-and-backward selection method using logistic regression classifier; and (5) radiomics features-based classification of MYCN gene amplification using machine learning classifiers. RESULTS: Median train/test Dice score for modified U-Net was 0.728/0.680. The top 3 features from the ensemble approach were neighborhood gray-tone difference matrix (NGTDM) busyness, NGTDM strength, and gray-level run-length matrix (GLRLM) low gray-level run emphasis, whereas those from the stepwise approach were GLRLM low gray-level run emphasis, GLRLM high gray-level run emphasis, and NGTDM coarseness. The top-performing tumor classification algorithm achieved a weighted F1 score of 97%, an area under the receiver operating characteristic curve of 96.9%, an accuracy of 96.97%, and a negative predictive value of 100%. Harmonization-based tumor classification improved the accuracy by 2% to 3% for all classifiers. CONCLUSION: The proposed end-to-end framework achieved high accuracy for MYCN gene amplification status classification.

Neck stiffness and bone osteolytic lesion in a 3-years old child: a case report.

BACKGROUND: Neuroblastoma is the most frequent extracranial solid tumor occurring in childhood, representing approximately 28% of all cancers diagnosed in infants. Signs and symptoms of neuroblastoma vary with the site of development of the tumor and can mimic other diseases due to its extreme clinical variability. However, torticollis is not reported in the medical literature as a leading symptom of neuroblastoma. CASE PRESENTATION: Here we report the case of a 3 years-old girl with fever and neck stiffness. Blood tests revealed a mild anemia and a rise in inflammatory markers. CT-scan showed a solid, heterogeneous, predominantly hypodense surrenal mass with eccentric calcification and extensive inhomogeneity of the vertebral metamers. Blood tests revealed raised serum levels of Neuron-Specific Enolase. At the 24-hours urine collection urinary catecholamines were greatly increased. A course of chemotherapy for neuroblastoma was promptly started with immediate clinical improvement. CONCLUSIONS: This case shows that the presence of torticollis could be a chief complaint of neuroblastoma. To our knowledge, neuroblastoma is not mentioned among life-threatening underlying conditions of torticollis in most recent literature reviews.

Diagnostic value of CT and MRI combined with serum LDH, NSE, CEA, and MYCN in pediatric neuroblastoma.

BACKGROUND: To analyze the diagnostic value of computed tomography (CT), magnetic resonance imaging (MRI) combined with serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and N-myc (MYCN) in the diagnosis of pediatric neuroblastoma. METHODS: Fifty-two children diagnosed with neuroblastoma were selected as the neuroblastoma group. During the same period, 52 children who visited our hospital with abdominal distension, diarrhea, constipation, and vomiting but were finally excluded from neuroblastoma were selected as the control group. CT and MRI were performed on all children. RESULTS: Fifty-two cases of neuroblastoma of the central nervous system were confirmed by pathological examination. The levels of LDH, NSE, CEA, and MYCN in the neuroblastoma group were clearly higher than those in the control group (P < 0.05). The results of CT and MRI combined with serum LDH, NSE, CEA, and MYCN were false positive in 10 cases and false negative in 6 cases, which were consistent with the pathological results. The sensitivity of CT and MRI combined with serum LDH, NSE, CEA, and MYCN in the diagnosis of neuroblastoma was notably higher than that of the three alone (P < 0.05). CONCLUSION: The imaging findings of CT and MRI in children with central nervous system neuroblastoma were definitely characteristic. MRI had higher diagnostic value than CT. The diagnostic value of CT and MRI combined with serum LDH, NSE, CEA, and MYCN was improved to some extent.

Image-defined risk factors in localized thoracic neuroblastoma and ganglioneuroma.

BACKGROUND: The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection. METHODS: Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included. Imaging at diagnosis and operative reports were reviewed retrospectively. IDRFs were assessed centrally and correlated to International Neuroblastoma Staging System (INSS) stage and extent of tumor resection. Additionally, we analyzed data on surgery-related complications. RESULTS: Imaging series of 88 patients were available for central review. In 18 children, no IDRF was present, 28 exhibited one IDRF, 42 two or more IDRFs, resulting in 70 patients with L2 disease. The most frequently observed IDRF was encasement of any vessel (n = 38). Initial surgical resection was aimed for in 45 patients (L1: n = 11; L2: n = 34). Complete and gross total resection rates were higher children with L2 NB (n = 8/25 L1, n = 17/25 L2 vs. n = 2/15 L1, n = 13/15 L2, respectively). The proportion of surgical complications was very similar between INRGSS L1 and L2 (n = 4/11 vs. n = 17/34). All complications were manageable, and no surgery-related deaths were observed. CONCLUSION: In this retrospective cohort, the extent of resection and the rate of surgical complications did not differ substantially between patients classified as L1/L2, indicating that INRGSS L2 does not equate unresectability. It appeared that individual IDRFs differ in value. Larger studies are needed to assess the significance and therapeutic/prognostic impact of such findings.

An Optimal Radiomics Nomogram Based on 18F-FDG PET/CT for Identifying Event-Free Survival in Pediatric Neuroblastoma.

RATIONALE AND OBJECTIVES: To investigate whether the 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomics features that combine tumor and bone marrow can more accurately identify event-free survival (EFS) in pediatric neuroblastoma. MATERIALS AND METHODS: A total of 126 patients with neuroblastoma were retrospectively included and randomly divided into the training and validation cohorts (7:3 ratio). Radiomics features were extracted to develop a tumor- and bone marrow-based radiomics risk score (RRS). The Kaplan-Meier method was used to evaluate the effectiveness of RRS in EFS risk stratification. Univariate and multivariate Cox regression analyses were used to determine independent clinical risk factors and construct the clinical models. The conventional PET model was constructed based on conventional PET parameters, and the noninvasive combined model integrated the RRS and the noninvasive independent clinical risk factors. The performance of the models was evaluated using C-index, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 15 radiomics features were selected to build the RRS. According to Kaplan-Meier analysis, there was a significant difference in EFS between the low-risk and high-risk groups as defined by the value of RRS (P < .05). The noninvasive combined model combining RRS and the International Neuroblastoma Risk Group stage achieved the best prognostic prediction of EFS, with a C-index of 0.810 and 0.783 in the training and validation cohorts, respectively. The calibration curves and DCA indicated that the noninvasive combined model had good consistency and clinical utility. CONCLUSION: The 18F-FDG PET/CT-based radiomics of neuroblastoma allows a reliable evaluation of EFS. The performance of the noninvasive combined model was superior to the clinical and conventional PET models.

Rhombencephalitis and longitudinal extensive myelitis associated with dinutuximab use in high-risk neuroblastoma.

BACKGROUND: Dinutuximab is a monoclonal antibody that targets the GD2 antigen used in the treatment of high-risk neuroblastoma. Dinutuximab-associated rhombencephalitis and myelitis is a rare, steroid-responsive, serious, but reversible pathology. To date, three transverse myelitis cases and one rhombencephalitis case due to dinutuximab have already been reported. Moreover, a recently published article identified five inflammatory CNS demyelination cases (four myelitis and one rhombencephalitis). We present a 5-year-old patient with rhombencephalitis and myelitis following dinutuximab-beta treatment. CASE: A 5-year-old patient with a left-sided retroperitoneal mass infiltrating the left kidney and multiple lytic bone lesions was diagnosed with neuroblastoma with a percutaneous biopsy from the abdominal mass. Surgery was performed after a prominent treatment response was detected on the abdominal CT. Radiotherapy was applied to the abdomen. While she was still undergoing maintenance treatment with 13-cis retinoic acid, a metaiodobenzylguanidine (MIBG) scan detected new bone lesions, and brain MRG identified pachymeningeal involvement. A new chemotherapy regimen was started and decreased MIBG uptake was seen in all previous bone lesions. However, newly developed eighth rib metastasis was seen in the following MIBG scan. Autologous stem cell transplantation was done. Soon after, dinutuximab-beta, together with temozolomide and irinotecan, was initiated. Following the third cycle hypotension, somnolence, paraparesis, and unilateral fixed dilated pupil were developed. Afterward, hemiballismus-like irregular limb movements were observed. Work-up studies were unremarkable, except for hypodensity in the brain stem on the brain CT. MRI revealed T2 hyperintensity of the brainstem and spinal cord extending from the cervicomedullary junction to the T7 level. Moreover, incomplete contrast enhancement and facilitated diffusion were observed. Imaging findings suggested demyelination. Steroids and intravenous immune globulin (IVIG) treatment were initiated. Both imaging abnormalities and clinical symptoms resolved partially at one month and disappeared at six months. CONCLUSIONS: Awareness of the radiological findings of dinutuximab toxicity will lead to prompt diagnosis and treatment.

Association of Computed Tomography Radiomics Signature with Progression-free Survival in Neuroblastoma Patients.

AIMS: To investigate the association of computed tomography radiomics signature with progression-free survival (PFS) in neuroblastoma patients. MATERIALS AND METHODS: We retrospectively included 167 neuroblastoma patients who were divided into a training set and a test set through stratified sampling at a ratio of 7:3. Regions of interest of the primary tumours were delineated on pretreatment contrast-enhanced computed tomography images and radiomics features were extracted from them. The intraclass correlation coefficient, Pearson correlation coefficient, and least absolute shrinkage and selection operator Cox regression algorithm were applied to select radiomics features and construct the radiomics signature. The effectiveness of the signature in predicting PFS was evaluated using the concordance index (C-index) and 95% confidence interval in both the training and the test sets. The time-dependent receiver operator characteristic curve of the radiomics signature was plotted and the area under the curve (AUC) was calculated. A calibration curve was used to assess the difference between the predicted probability of the radiomics signature and the observed probability at different time points. RESULTS: The radiomics signature was composed of six features, which achieved a C-index of 0.733 (95% confidence interval 0.664-0.803) in the training set and 0.734 (95% confidence interval 0.608-0.861) in the test set. In the training set, the radiomics signature yielded an AUC of 0.707, 0.737, 0.788, 0.859 and 0.829 for 1-, 2-, 3-, 4- and 5-year PFS, respectively. Similarly, the radiomics signature exhibited an AUC of 0.738, 0.807, 0.761, 0.787 and 0.818 for 1-, 2-, 3-, 4- and 5-year PFS, respectively, in the test set. The calibration curves showed no significant difference between the predicted probability of the radiomics signature and the observed probability for up to 5 years. CONCLUSIONS: Computed tomography radiomics features exhibit a significant correlation with the PFS of neuroblastoma patients, particularly in terms of long-term outcomes.