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1.
Eur J Surg Oncol ; 50(6): 108321, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38598875

ABSTRACT

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.


Subject(s)
Liver Neoplasms , Neuroblastoma , Nomograms , Humans , Neuroblastoma/mortality , Neuroblastoma/pathology , Neuroblastoma/genetics , Neuroblastoma/secondary , Male , Female , Infant , Child, Preschool , Retrospective Studies , Liver Neoplasms/secondary , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Child , Survival Rate , Neoplasm Staging , Bone Neoplasms/secondary , Bone Neoplasms/mortality , China/epidemiology , N-Myc Proto-Oncogene Protein/genetics , Prognosis , Age Factors , Proportional Hazards Models
3.
Commun Biol ; 5(1): 42, 2022 01 12.
Article in English | MEDLINE | ID: mdl-35022561

ABSTRACT

The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression with poor survival and metastasis in primary NB, while TWIST2 correlates with good prognosis. Secondly, suppression of TWIST1 by CRISPR/Cas9 results in a reduction of tumor growth and metastasis colonization in immunocompromised mice. Moreover, TWIST1 knockout tumors display a less aggressive cellular morphology and a reduced disruption of the extracellular matrix (ECM) reticulin network. Additionally, we identify a TWIST1-mediated transcriptional program associated with dismal outcome in NB and involved in the control of pathways mainly linked to the signaling, migration, adhesion, the organization of the ECM, and the tumor cells versus tumor stroma crosstalk. Taken together, our findings confirm TWIST1 as promising therapeutic target in NB.


Subject(s)
Gene Expression Regulation, Neoplastic , Gene Expression , Neuroblastoma , Nuclear Proteins/genetics , Twist-Related Protein 1/genetics , Animals , Immunocompromised Host , Mice , Neuroblastoma/pathology , Neuroblastoma/secondary , Nuclear Proteins/metabolism , Twist-Related Protein 1/metabolism
5.
Acta Clin Belg ; 77(5): 868-873, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34779361

ABSTRACT

OBJECTIVES: For the detection of bone marrow (BM) metastases in patients with neuroblastoma, microscopic BM examination and [123I]MIBG scintigraphy are advised. The aims of this study were to assess the concordance of [123I]MIBG and microscopic BM examination (aspirate and biopsy) in detecting BM involvement and to compare invasive disease in BM biopsies and aspirates, both at diagnosis and before autologous stem cell collection (ASCC). METHODS: Fifty-five patients with stage 4 or stage 4S disease were included, and 37 of them received an autologous hematopoietic stem cell transplantation (AHSCT). The concordance rate was measured and paired binary data were analysed by the McNemar test to look for a systematic difference between diagnostic tests. RESULTS: At diagnosis and before ASCC, we found acceptable concordance rates for [123I]MIBG versus microscopic BM examination (77.1% and 85.3% respectively). Discordant results were found in both directions and at both time points. The concordance rate for biopsy versus aspirate at diagnosis was 80.6%, however, before ASCC a much higher concordance rate between both microscopic examinations was found (94.1%). While none of the aspirates showed neuroblastoma cells before ASCC, two biopsies still showed tumor invasion. CONCLUSION: For patients with neuroblastoma, a [123I]MIBG scintigraphy and a microscopic examination of BM aspirate and its biopsy should be used as complementary tools in the evaluation of BM involvement, and this both at diagnosis and during treatment (before ASCC).


Subject(s)
Bone Neoplasms , Neuroblastoma , 3-Iodobenzylguanidine , Bone Marrow/diagnostic imaging , Bone Marrow/pathology , Bone Marrow Examination , Bone Neoplasms/secondary , Humans , Iodine Radioisotopes , Neuroblastoma/diagnostic imaging , Neuroblastoma/pathology , Neuroblastoma/secondary , Radionuclide Imaging
7.
Technol Cancer Res Treat ; 20: 15330338211041454, 2021.
Article in English | MEDLINE | ID: mdl-34569870

ABSTRACT

Objective: The apoptotic and cytotoxic effects of arsenic trioxide (ATO) makes it a potentially suitable agent for the treatment of patients with neuroblastoma with poor prognosis; therefore, we try to evaluate the effectiveness and safety of ATO combined with reinduction/induction chemotherapy in children with recurrent/refractory or newly diagnosed stage 4 neuroblastoma. Methods: Retrospective analysis was performed on seven pediatric patients with recurrent /refractory or newly diagnosed stage 4 neuroblastoma treated with traditional reinduction/induction chemotherapy combined with ATO. Results: A total of 7 patients were treated synchronously with ATO and chemotherapy for up to nine courses; all patients received conventional chemotherapy plus a 0.16 mg/kg/day dose of intravenous ATO during reinduction/induction chemotherapy. Treatment was effective in five patients and ineffective in the other two patients. The overall response rate was 71.43% (5 of 7). The side effects of the ATO combination were minor, whereby only treatment in one patient was terminated at the sixth course due to a prolonged QT interval (0.51 s), which returned to normal after symptomatic treatment. Conclusions: ATO can be safely and effectively combined with chemotherapy drugs as a potential alternative means of treatment for high-risk stage 4 neuroblastoma, and we have observed that ATO can restore the sensitivity of chemotherapy in some patients who were resistant to previous chemotherapy. Further investigations and clinical data are required to confirm these observations.


Subject(s)
Abdominal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Neuroblastoma/drug therapy , Abdominal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arsenic Trioxide/administration & dosage , Child , Child, Preschool , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Etoposide/administration & dosage , Humans , Induction Chemotherapy/methods , Neoplasm Staging , Neuroblastoma/diagnostic imaging , Neuroblastoma/secondary , Positron Emission Tomography Computed Tomography , Retrospective Studies , Topotecan/administration & dosage , Treatment Outcome , Vincristine/administration & dosage
8.
Medicine (Baltimore) ; 100(17): e24399, 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33907087

ABSTRACT

ABSTRACT: Neuroblastoma (NB) metastasized into the mandible and spinal extradural region was rarely reported. We present a case with metastatic NB to the mandible and the spinal extradural regions. The patient received chemotherapy using NB 97 regimen and was tumor free after 8 months, but 9 months after the treatment, the patient presented with lower limb paralysis and persistent pain in maxillofacial region as well as swelling in the left mandibular area. Metastasis to the mandible and the spinal extradural regions was diagnosed based on the spinal and maxillofacial magnetic resonance imaging. Radiotherapy with a density of 2 Gy per day was given via a linear accelerator. The total dose of the intraspinal occupying lesion was subject to radiotherapy with a regimen of 30 Gy (10 fractions). For the management of the maxillofacial pain, tumor in the maxillofacial region was subject to a density of 50 Gy (25 fractions). The maxillofacial pain disappeared after a density of 10 Gy and soft tissue tumefaction was eliminated after a density of 50 Gy, and the maxillofacial appearance was much better than before. Finally, the patient died from tumor progression 2 years after diagnosis for NB.


Subject(s)
Adrenal Gland Neoplasms/pathology , Mandibular Neoplasms/secondary , Neuroblastoma/pathology , Neuroblastoma/secondary , Spinal Neoplasms/secondary , Child, Preschool , Epidural Space/pathology , Fatal Outcome , Female , Humans , Mandible/pathology
9.
Tumori ; 107(6): NP59-NP62, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33759659

ABSTRACT

BACKGROUND: Although most breast masses in children are benign, breast cancer must be considered in the differential diagnosis. The majority are represented by sarcomas and secondary lesions. Literature reports only four cases of neuroblastoma breast metastasis, with no emphasis on radiologic features. Our work aims to furnish a description of radiologic and sonographic features of neuroblastoma metastasis in the breast. CASE DESCRIPTION: A 15-year-old girl had a round nodular mass in the outer upper quadrant of the left breast that had rapidly enlarged over the last month. An ultrasound showed two subcutaneous nodules (3.8 cm and 1.3 cm in maximum diameter), with an irregular shape, heterogeneous echogenicity (isohypoechoic), and hyperechoic foci with a posterior acoustic shadow inside. Overall, the features were highly suspicious of secondary malignant lesions. Computed tomographic scan was performed and found a large retroperitoneal mass and multiple mixed secondary lesions to the spine and hip. A 14G core needle biopsy of breast masses was performed and showed a secondary localization of neuroblastoma. CONCLUSIONS: In adolescents, metastases are the most frequent cause of malignant breast masses. Ultrasound examination should be preferred as the first imaging tool. For the differential diagnosis of breast metastasis with benign masses, a rapid enlargement, a heterogeneous echogenicity, and intralesional hyperechogenic foci could be considered features of malignancy.


Subject(s)
Breast Neoplasms/pathology , Neoplasms, Second Primary/pathology , Neuroblastoma/secondary , Ultrasonography, Mammary/methods , Adolescent , Breast Neoplasms/diagnostic imaging , Female , Humans , Neoplasms, Second Primary/diagnostic imaging , Neuroblastoma/diagnostic imaging
10.
Head Neck Pathol ; 15(3): 757-768, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33394374

ABSTRACT

Neuroblastoma is the most common extracranial solid cancer of infancy, occurring mainly in the adrenal gland, with high metastatic potential. However, involvement of the head and neck region is rare. Here, we present two cases of metastatic neuroblastoma of childhood, in which a mandibular swelling was the first sign of disseminated disease. Case 1 describes a 4-year-old boy with a 2-week history of painful swelling in the left mandibular region, body soreness and weakness. Panoramic radiography and computed tomography showed a destructive lesion in the left mandibular ramus. Case 2 describes a 3-year-old boy with a 1-month history of swelling in the right mandibular area. Panoramic radiograph and cone-beam computed tomography showed a destructive lesion in the right body and ramus of the mandible, displacing tooth germs, with the destruction of vestibular and lingual bone cortices. In both cases, microscopic analyses revealed a diffuse proliferation of small, round, and blue cells with hyperchromatic nuclei and scant cytoplasm. While Case 1 was more undifferentiated, Case 2 presented eosinophilic areas suggestive of neuropil. A large immunohistochemical panel was performed, showing expression of neural markers such as CD56, neuron-specific enolase (in Case 2), chromogranin, and synaptophysin. Both lesions presented a high proliferation index (Ki67 > 70% and 80%, respectively). Positron emission tomography-computed tomography revealed ipsilateral adrenal primary lesions in both cases, with multiple bone metastatic lesions. Besides the mandible, multiple sites of the axial and appendicular skeleton were affected. Treatment consisted of induction chemotherapy, adrenalectomy, consolidation chemoradiotherapy, and post-consolidation therapy.


Subject(s)
Adrenal Gland Neoplasms/pathology , Mandibular Neoplasms/secondary , Neuroblastoma/secondary , Child, Preschool , Humans , Male
13.
Biomed Pharmacother ; 129: 110268, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32563146

ABSTRACT

The dysregulation of non-coding RNAs (ncRNAs) often caused aberrant cell behaviors. In the present study, we focused on the role of long noncoding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in the development of neuroblastoma (NB). The enrichment of NORAD, miRNA-144-3p (miR-144-3p) and histone deacetylase 8 (HDAC8) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, chemoresistance, apoptosis, metastasis and autophagy of NB cells were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell migration and invasion assays and Western blot assay, respectively. The target relationship between miR-144-3p and NORAD or HDAC8 was predicted by Starbase software and validated through dual-luciferase reporter assay, RIP and RNA-pull down assays. The protein expression of HDAC8 was measured by Western blot assay. Murine xenograft model was used to verify the function of NORAD in vivo. We found that the level of NORAD was up-regulated in NB tissues and cells, and the level of NORAD was negatively correlated with the prognosis of NB patients. NORAD promoted the proliferation, metastasis and doxorubicin (DOX) resistance while inhibited the apoptosis and autophagy of NB cells. MiR-144-3p was a target of NORAD in NB cells, and NORAD accelerated the progression and DOX resistance of NB through sponging miR-144-3p. HDAC8 was a direct target of miR-144-3p in NB cells, and miR-144-3p suppressed the progression of NB through down-regulating HDAC8. NORAD up-regulated the expression of HDAC8 through sponging miR-144-3p in NB cells. NORAD accelerated the growth of NB tumors at least partly through miR-144-3p/HDAC8 signaling in vivo. In conclusion, NORAD promoted the progression and DOX resistance of NB through miR-144-3p/HDAC8 axis in vivo and in vitro.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Histone Deacetylases/metabolism , MicroRNAs/metabolism , Neuroblastoma/drug therapy , RNA, Long Noncoding/metabolism , Repressor Proteins/metabolism , Animals , Apoptosis/drug effects , Autophagy/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Child, Preschool , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Neoplastic , Histone Deacetylases/genetics , Humans , Male , Mice , MicroRNAs/genetics , Neuroblastoma/enzymology , Neuroblastoma/genetics , Neuroblastoma/secondary , RNA, Long Noncoding/genetics , Repressor Proteins/genetics , Signal Transduction , Tumor Burden/drug effects , Up-Regulation , Xenograft Model Antitumor Assays
14.
Rom J Ophthalmol ; 64(1): 75-77, 2020.
Article in English | MEDLINE | ID: mdl-32292863

ABSTRACT

A 2-year-old female patient with a recent history of head trauma was admitted to the Ophthalmology Clinic with left exophthalmos. A differential diagnosis between traumatic and tumoral etiology was made. The orbitocranial MRI and fine needle ganglion biopsy settled the malignant etiology of the exophthalmia. Further investigations at the Pediatric Oncology Clinic decided on the diagnosis of orbital metastatic neuroblastoma. This case report presented an unusual association: orbital metastatic neuroblastoma becoming clinically positive soon after a head trauma.


Subject(s)
Abdominal Neoplasms/pathology , Brain Injuries/diagnosis , Exophthalmos/diagnosis , Neuroblastoma/secondary , Orbital Neoplasms/secondary , Abdominal Neoplasms/diagnostic imaging , Abdominal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy, Fine-Needle , Child, Preschool , Diagnosis, Differential , Fatal Outcome , Female , Humans , Magnetic Resonance Imaging , Neuroblastoma/diagnostic imaging , Neuroblastoma/drug therapy , Orbital Neoplasms/diagnostic imaging , Orbital Neoplasms/drug therapy , Tomography, X-Ray Computed
16.
Crit Rev Oncol Hematol ; 149: 102924, 2020 May.
Article in English | MEDLINE | ID: mdl-32172225

ABSTRACT

Neuroblastoma is the most common extracranial solid tumor, arising from primitive sympathetic ganglion cells, in pediatric patients. The unique features of neuroblastoma include variable clinical behaviors, such as rapid progression to death and maturation to benign ganglioneuroma, followed by regression. Radiation therapy (RT) is usually administered to both the primary tumor bed and persistent metastatic sites after induction chemotherapy for high-risk neuroblastoma. RT to the tumor bed after surgical resection contributes significantly to local disease control and prevention of local relapse, confirming the role of RT. Palliative radiotherapy for metastatic neuroblastoma is also effective and safe and mainly provides symptomatic relief. The late side effects of RT in neuroblastoma patients include growth and developmental failure, hypothyroidism, gastrointestinal dysfunction, neurocognitive defects, pulmonary and cardiac abnormalities, infertility, and secondary cancers. In this article, we reviewed the role and toxicity of RT in neuroblastoma patients.


Subject(s)
Induction Chemotherapy/methods , Neuroblastoma/radiotherapy , Palliative Care/methods , Soft Tissue Neoplasms/radiotherapy , Child , Cranial Irradiation , Humans , Infant , Neoplasm Recurrence, Local , Neuroblastoma/pathology , Neuroblastoma/secondary , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/secondary , Treatment Outcome
17.
J Pediatr Surg ; 55(1): 130-134, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31685267

ABSTRACT

BACKGROUND/PURPOSE: MYCN-amplification in neuroblastoma is associated with an aggressive clinical phenotype. We evaluated the association of MYCN amplification with tumor response to neoadjuvant chemotherapy. METHODS: Primary tumor response, assessed by percentage volume change on CT scan and degree of tumor resection, assessed by the operating surgeon, were retrospectively compared in 84 high-risk neuroblastoma patients. There were thirty-four (40%) with MYCN-amplified tumors and fifty (60%) with non-amplified tumors treated at our institution from 1999 to 2016. Metastatic disease response was assessed on MIBG scan by change in Curie score. RESULTS: MYCN-amplification was associated with a greater mean percentage reduction in primary tumor volume after neoadjuvant chemotherapy (72.27% versus 46.83% [non-amplified tumors], p = 0.001). The percentage of patients with a Curie score > 2 at diagnosis who then had a score ≤ 2 after neoadjuvant chemotherapy was not significantly different (8 [61.5%] and 8 [34.8%], respectively, p = 0.37). Twenty-eight (85.7%) patients with MYCN-amplification had ≥90% surgical resection compared to 45 (91.84%) patients with non-amplified tumors (p = 0.303). CONCLUSIONS: MYCN-amplification in high-risk neuroblastoma was associated with a better response of the primary tumor to neoadjuvant chemotherapy, but not metastatic sites, than in patients with non-amplified tumors. This did not significantly impact the ability to resect ≥90% of the primary tumor/locoregional disease. TYPE OF STUDY: Treatment Study LEVEL OF EVIDENCE: Level III.


Subject(s)
Antineoplastic Agents/therapeutic use , N-Myc Proto-Oncogene Protein/genetics , Neuroblastoma/genetics , Neuroblastoma/therapy , Chemotherapy, Adjuvant , Child, Preschool , Female , Gene Amplification , Humans , Infant , Male , Neoadjuvant Therapy , Neoplasm Staging , Neoplasm, Residual , Neuroblastoma/pathology , Neuroblastoma/secondary , Retrospective Studies , Tomography, X-Ray Computed , Tumor Burden
20.
Medicine (Baltimore) ; 98(36): e17038, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31490393

ABSTRACT

RATIONALE: Neuroblastoma is one of the most common tumors found in children, and mostly arises in the adrenal gland and paravertebral regions. Orbital neuroblastoma metastasis is relatively rare, and is associated with poor prognosis. Since the symptoms and signs of orbital neuroblastoma are not specific, its diagnosis remains challenging. PATIENT CONCERNS: A 3-year-old girl presented with periorbital ecchymoses (raccoon eyes) and proptosis for 40 days. DIAGNOSES: Abdominal magnetic resonance imaging (MRI) and sonography analysis revealed a large mass in the left adrenal gland (primary tumor). The computed tomography and MRI further revealed multiple soft tissue masses in the skull and both orbits with erosion of the adjacent bones (the metastasis). The histological analysis of the tumor removed from the right orbit confirmed the diagnosis of neuroblastoma. INTERVENTIONS: The mass on the right face was surgically removed. OUTCOMES: The patient exhibited no deteriorative signs at the 6-month follow-up. LESSONS: Clinical manifestations, such as periorbital ecchymoses and proptosis, in combination with radiological analysis and histological findings, are important for the diagnosis of orbital neuroblastoma metastasis.


Subject(s)
Adrenal Gland Neoplasms/diagnostic imaging , Ecchymosis/etiology , Exophthalmos/etiology , Neuroblastoma/diagnostic imaging , Orbital Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/pathology , Adrenal Glands/pathology , Child, Preschool , Female , Humans , Neuroblastoma/complications , Neuroblastoma/pathology , Neuroblastoma/secondary , Orbital Neoplasms/complications , Orbital Neoplasms/pathology , Orbital Neoplasms/secondary
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