Cases Of Neuroblastoma Research Articles

Vascular encasement image defined risk factors independently predict surgical complications in neuroblastoma.

Specific image defined risk factors (IDRF) immediately prior to surgery may be more relevant to paediatric oncology surgeons than pre-neoadjuvant IDRFs at diagnosis. The aim of this study was to determine IDRF subtypes that independently predict postoperative complications. We searched the New Zealand Children's Cancer Registry for all cases of neuroblastoma treated at a single paediatric oncology centre between January 2007 and February 2021 and determined the IDRF status on pre-operative imaging at diagnosis and after neoadjuvant therapy. Surgical complications (Clavien-Dindo grade) were correlated with total number of IDRFs (pre- and post-chemotherapy) and three subsets: vascular encasement (VE), invasive (I), and extensive (E). Of 101 patients, 73 underwent surgical resection, and 32 (44%) had a surgical complication. Of the 54 IDRF-positive tumours, all were treated by neoadjuvant therapy and in 17, all IDRFs resolved. Complications correlated with the number of post-neoadjuvant therapy VE-IDRFs at OR 1.2 (95% CI 1.0-1.4, P = 0.02) and extensive IDRFs at OR 1.7 (95% CI 1.1-1.9, P = 0.02). Pre-neoadjuvant IDRF status was not independently associated with complications when controlling for post-neoadjuvant IDRF status. The total number of VE-IDRF reduced from 181 pre-neoadjuvant therapy to 86 post, with tumour encasing the aorta and/or vena cava being the most common. The vascular encasement and extensive subtypes of IDRF may be more useful prognostic indicators of surgical complications than the total number of IDRFs. This may have implications for reporting IDRF status on preoperative imaging and surgical planning but needs validation in larger cohort studies.

Adults and Adolescents With Neuroblastoma: An Analysis of the National Cancer Database.

Neuroblastoma, the most common extracranial solid tumor in children, is rare in adults. This study compares patient characteristics, disease patterns, and treatments among adults, adolescents, and children with neuroblastoma. We queried the National Cancer Database (2004-2019) for neuroblastoma cases. Patient and tumor characteristics, treatments, and 5-year overall survival (5-OS) were compared between adults (≥ 18 years), adolescents (10-17 years), and children (0-9 years). Kaplan-Meier curves and Cox regression assessed survival differences. Among 6350 neuroblastoma patients, 256 (4.0%) were adults, 222 (3.5%) were adolescents, and 5872 (92.5%) were children. Tumors were largest in adolescents (9.7 cm), followed by adults (8.0 cm) and children (6.7 cm) (p < 0.001). Adults were less likely to have tumors in the adrenal glands (34.0% vs. children: 54.7%, adolescents: 43.2%, p < 0.001) and had lower rates of metastasis (10.9% vs. 19.3% and 19.4%, p < 0.001). Compared to children, adults received less chemotherapy, immunotherapy, and bone marrow transplants (p < 0.001). 5-OS was worse in adults (65.8%), followed by adolescents (70.4%) and children (78.2%) (p < 0.001). After adjustment, adults (aHR: 2.27; 95% CI, 1.71-3.01) and adolescents (aHR: 2.02; 95% CI, 1.54-2.64) had higher hazards of death compared to children. Adults and adolescents with neuroblastoma have distinct clinical features and lower survival than children, underscoring the need for tailored treatment approaches for older patients. III.

Orbital neuroblastoma: A tale of two children

Neuroblastoma is frequently encountered in pediatric patients. Orbital neuroblastoma, primarily metastatic, carries a poorer prognosis with increasing age. Here, we present two cases of orbital metastatic neuroblastoma, focusing on their clinical and radiologic manifestations, treatment modalities, and a comprehensive literature review. This report underscores the critical role of ophthalmologists in facilitating early detection. Timely referral and collaboration among multidisciplinary teams are crucial, potentially life-saving measures, given the tumor’s diverse clinical presentations and aggressive progression.

Impact of the relationship between renal pedicles and tumors on surgical outcomes for non-high-risk abdominal neuroblastoma.

To assess the impact of the relationship between renal pedicles and tumors on surgical outcomes in patients with non-high-risk abdominal neuroblastoma. We retrospectively analyzed cases of neuroblastoma without metastasis treated at our hospital between March 2002 and December 2023. Cases in which surgical resection was performed were divided into three groups according to imaging findings at the time of diagnosis and before surgery: Group E (tumor encasing renal pedicles), Group C (tumor in contact with renal pedicles), and Group S (tumor separated from renal pedicles). Among 256 neuroblastoma cases diagnosed during the study period, 27 non-high-risk cases that underwent surgery for partial abdominal tumor resection or greater were included. The numbers of cases in the S group, C group, and E group, respectively, were 7, 9, and 11 at diagnosis, and 8, 14, and 5 before surgery. Renal complications (combined concurrent renal resection and post-operative renal atrophy) were seen in five E group cases at the time of diagnosis, and two C group cases and three E group cases preoperatively. In non-high-risk abdominal neuroblastomas, tumors encased in the renal pedicles have the highest risk of renal complications, followed by tumors in contact with the renal pedicles.

Foetal paraspinal neuroblastoma: A case report of autopsy findings

Neuroblastoma is a rare tumour originating from neural crest cells, primarily occurring in the adrenal glands and sympathetic ganglia, with prenatal diagnosis often complicated by the difficulty in distinguishing it from other foetal abdominal or paraspinal masses. We present a case of foetal neuroblastoma in a 26-year old woman who, at 36 weeks of gestation, experienced absent foetal movements, leading to ultrasound confirmation of foetal demise with associated effusions. An emergency caesarean section revealed a stillborn male foetus with a previously undetected encapsulated mass in the posterior mediastinum, which was confirmed as neuroblastoma through histopathological analysis. This case highlights the challenges in prenatal diagnosis, as the tumour went unnoticed despite routine imaging. It contributes to the limited literature on foetal neuroblastoma, underscoring the need for further research on effective management strategies.

Risk of developing neuroblastoma influenced by maternal stressful life events during pregnancy and congenital pathologies.

A retrospective multicenter study to investigate the potential association between descriptive information related to pregnancy history and perinatal features and the risk of neuroblastoma (NB) in children. Data from 56 mothers during 105 pregnancies (56 cases of NB, 49 control siblings) were collected through face-to-face or telephone interviews with mothers of children diagnosed with NB, along with information extracted from Health System databases. Descriptive information related to (a) pregnancy history as maternal stressful life events with perceived distress during pregnancy, weight gain, alcohol and tobacco consumption, mode of delivery and gestational age; and (b) perinatal features as congenital pathologies, weight at birth and type of feeding were examined to identify potential risk factors for NB. Stressful life events during pregnancy and certain congenital pathologies were independently associated with NB risk. No significant associations were found between other features. Breastfeeding rates were similar between cases and controls. Our results underscore the importance of providing support and care to pregnant women to reduce potential stressors. Further research is needed to better understand the influence of dysbiosis and mitochondrial-nuclear communication impairment as underlying mechanisms of maternal stress during pregnancy and presence of congenital pathologies in order to confirm them as potential risk factors for NB.

Metanephrine mirage: distinguishing the phaeocopies, a case report and literature review

BackgroundWe present one of only seven reported cases of a catecholamine-secreting adrenal neuroblastoma in an adult. The case is used as a platform to discuss key biochemical, genomic and imaging considerations that are central to the successful, targeted management of catecholamine-secreting adrenal tumours.Case presentationA 63-year-old male was urgently reviewed at a tertiary hospital endocrinology outpatient clinic for a 12 cm right-sided adrenal incidentaloma. Plasma normetanephrine and 3-methoxytyramine levels were approximately 10 times the upper limit of normal at 9272 pmol/L (< 900) and 1023 pmol/L (< 110), respectively.The adrenal mass appeared to be inseparable from the liver on imaging, and thus was suspected to be an invasive malignant phaeochromocytoma. FDG positron emission tomography (PET)/CT demonstrated moderate to intense metabolic activity within the right adrenal mass. [68 Ga]Ga-DOTATATE (Ga-TATE) PET-CT demonstrated patchy, heterogenous somatostatin receptor (SSTR) expression in the adrenal lesion, at most Krenning 3 (intensity above liver).The patient underwent a right adrenalectomy and segment 6/7 liver resection. Histopathology revealed a 130 mm diameter neuroblastoma of the differentiating subtype with a low Mitosis-Karyorrhexis Index. There was lymphovascular invasion and tumour focally present at the resection margin, but no tumour in one periadrenal lymph node, and no tumour invasion in the adherent liver. Immunohistochemistry revealed ALK positivity (+ 3) and wild type ATRX.At nine months following adrenalectomy, the plasma normetanephrine level has reduced to 991 pmol/L (< 900). Post-operative GaTate PET/CT shows no definite abnormal SSTR-expressing lesions in the surgical bed or elsewhere. The patient has completed adjuvant radiotherapy and is a candidate for ALK-targeted therapy if required for recurrence in the future.ConclusionsNeuroblastomas may be misdiagnosed as phaeochromocytomas given the ability to secrete catecholamines and similarities in radiological appearance. Differentiating neuroblastomas from phaeochromocytomas and paragangliomas (PPGL) is critical, but clinically difficult. Genomics are central for management; diagnosing ALK-positive neuroblastoma triggers consideration of ALK-targeted therapy, which is not relevant for PPGL. A critical eye is required for the accurate diagnosis and management of malignant adrenal incidentalomas.

An evaluation of genetic predisposition to congenital anomalies and pediatric cancer supports KAT6B as a novel neuroblastoma susceptibility gene

PurposeAlthough congenital anomalies are among the strongest risk factors for developing pediatric cancer, the genetic underpinnings remain unclear. Therefore, we evaluated germline susceptibility in children with congenital anomalies and cancer. MethodsThrough the Genetic Overlap Between Anomalies and Cancer in Kids Study, we recruited 47 participants with anomalies and cancer, along with their biological families. Genome sequencing was performed, focusing on single-nucleotide variants, indels, and structural variants. Pathogenic or likely pathogenic variants were identified by the American College of Medical Genetics and Genomics classification. ResultsWe identified pathogenic or likely pathogenic variants in 23.4% (11 of 47) of participants. These variants encompassed (1) 4 genes associated with both anomalies and cancer (WT1, USP9X, PTPN1, and LZTR1), (2) 2 established cancer predisposition genes (TP53 in 2 participants and PAX5), and (3) 4 genes that are associated with anomalies (MMUT, FBN1, COL3A1, and KAT6B). We further investigated the role of KAT6B on neuroblastoma in a gene-based analysis from 409 neuroblastoma cases and 952 controls. This analysis demonstrated a significant enrichment of rare, predicted deleterious variants (P = .017), with odds ratios ranging from 2 to 4 based on the conditions we applied. ConclusionThis study demonstrates a molecular diagnostic yield of 23.4% in participants with both anomalies and cancer. Additionally, the findings further implicate the role of KAT6B as a novel neuroblastoma predisposition gene.

The relative contributions of genetic and non‐genetic factors to the risk of neuroblastoma

ABSTRACTPrevious literature has well‐established genetic factors as being associated with neuroblastoma (NB). About 1%–2% of NB cases are familial, with 85% of these cases predisposed to mutations in the PHOX2B and ALK genes. The genetic basis of sporadic NB has been studied through genome‐wide association studies and next‐generation sequencing approaches. Particularly, germline variants, as well as copy number variations, confer increased risks of NB, often with effect estimates ≥1.5, underscoring the strong genetic contributions to NB. However, the strength of the association varied in non‐genetic factors. Some risk factors, such as birth defects, maternal illicit drug use, and early infections, had relatively stronger associations (effect estimates ≥1.5 or ≤0.67), while some other factors remain inconclusive. This suggests that certain non‐genetic factors may play a more prominent role in NB risk, while further research is needed to clarify the impact of others. We synthesized and critically evaluated existing literature on the risk factors of NB to provide an overview, analyze the current state of knowledge, and outline a research path to address the relative contributions of genetic and non‐genetic factors in NB. Future epidemiologic studies should incorporate novel methods for measuring genetic and non‐genetic factors to comprehensively assess the full extent of factors contributing to NB. Furthermore, the utilization of dried blood spots holds promise to overcome technical and recruitment challenges for future studies. These strategies will contribute to a more holistic understanding of NB etiology and potentially lead to improved prevention strategies.

METTL3-induced lncARSR aggravates neuroblastoma tumorigenic properties through stabilizing PHOX2B

Neuroblastoma (NB), the most common extracranial solid tumor in pediatric patients, manifests with considerable variability across multiple primary sites. Despite this, the extent of genetic heterogeneity within these tumor foci and the identification of consistent oncogenic drivers remains largely unexplored. Of particular interest, genetic mutations in PHOX2B have been linked to familial cases of NB, yet the underlying molecular mechanisms are not fully delineated. In our research, we focus on unraveling the role of a novel functional long non-coding RNA (lncRNA) associated with PHOX2B in the context of NB. Using NB cell models with overexpressed PHOX2B, combined with lncRNA microarray analysis, we discovered that lncARSR is significantly upregulated in response to PHOX2B overexpression. Subsequent biological assays demonstrated that lncARSR promotes both the proliferation and metastasis of NB cells. Further molecular investigations revealed that lncARSR plays a crucial role in stabilizing PHOX2B expression within NB cells. Moreover, we identified that the expression of lncARSR is regulated by methylation through methyltransferase-like 3 (METTL3), which itself is positively correlated with PHOX2B expression. Rescue experiments underscored the functional importance of METTL3, lncARSR, and PHOX2B in NB cells. In summary, our findings provide new insights into the molecular functions of PHOX2B in the progression of neuroblastoma and propose a novel therapeutic target for this aggressive malignancy.

Outcome of radiotherapy for metastatic neuroblastoma

Background. Neuroblastoma (NB) is a prevalent solid extracranial tumor that primarily affects children. It is the third most common type of cancer in children, following leukemia and brain tumors. Aim. The study aimed to discuss the clinical outcomes after adjuvant radiotherapy to the primary site in case of metastatic NB after good response to chemotherapy. Methods. A retrospective clinical-dosimetric study of 25 patients metastatic NB treated with radiotherapy at Baghdad Radiotherapy and Nuclear Medicine Center, at Baghdad Medical City Complex, Baghdad, Iraq. Data collection begin from December 2023 and March 2024. Data were collected retrospectively with review of records. The following variables were studied: sex, age, date of diagnosis, site of primary tumor, site of metastasis, chemotherapy, surgery, RT, RT sites, doses of RT, fractions of RT, recurrence sites, date of relapse and survival outcome for each patient. Follow-up period include look up to metastasis, site of metastasis, recurrence, site of recurrence and survival rates. Results. In relation to sex, males (14, 56%) were more than females (11, 44%). The mean age of NB cases was 45.64±17.6 months. In NB, suprarenal masses were the most common site of primary in 21 (84%) of patients. The most common site of metastasis of NB was bone marrow in 12 (48). The multi sites of recurrence was the commonest presentation in 48%. The relapse-free survival (RFS) was 22.38 months. 5 out of 25 patients were alive whereas 20 (80%) of cases were dead. The median follow-up time was 6 years, and the OS of NB in this study after optimal treatment was 2.46 years (95%CI= 1.705-3.21) for survivors. The MS was 4.84 years. The OS was 6 yrs for those diagnosed at 2017, 2 yrs for those diagnosed at 2018, 1.5 yrs for those diagnosed at 2019, 1.75 yrs for those diagnosed at 2020, 3 yrs for those diagnosed at 2021 and 1.5 yrs for those diagnosed at 2022. There was a significant difference among doses (Log Rank (Mantel-Cox)= 11.425, p=0.044). Conclusions. This study is the first study in Iraq that examines the clinical results of radiotherapy on the primary site in cases of metastatic neuroblastoma following induction chemotherapy. The suprarenal masses of neuroblastoma are the most often occurring main site. The primary sites of metastases for neuroblastoma (NB) are the bone marrow and bones. Timely detection and proactive treatment of NB can improve overall results. Reoccurrence of skeletal issues and the infiltration of bone marrow are frequently observed. There were no significant differences observed in terms of relapse-free survival and overall survival based on factors such as sex, age, location of the main tumor, chemotherapy, radiation treatment, surgery, and radiation therapy dosages.

Molecular profiling of core immune-escape genes highlights TNFAIP3 as an immune-related prognostic biomarker in neuroblastoma.

Neuroblastoma (NB) is the most prevalent and deadliest pediatric solid tumor. With of over 50% of high-risk neuroblastoma cases relapse, the imperative for novel drug targets and therapeutic strategies is accentuated. In neuroblastoma, the existence of tumor-associated macrophages (TAMs) correlates with an unfavorable patient prognosis. However, the clinical relevance and prognostic implications of regulatory genes linked to TAMs infiltration in neuroblastoma remain unclear, and further study is required. We conducted a comprehensive analysis utilizing transcriptome expression profiles from three primary datasets associated with neuroblastoma (GSE45547, GSE49710, TARGET) to identify hub genes implicated in immune evasion within neuroblastoma. Subsequently, we utilized single-cell RNA sequencing analysis on 17 clinical neuroblastoma samples to investigate the expression and distribution of these hub genes, leading to the identification of TNFAIP3. The above three public databases were merged to allowed for the validation of TNFAIP3's molecular functions through GO and KEGG analysis. Furthermore, we assessed TNFAIP3's correlation with immune infiltration and its potential immunotherapeutic impact by multiple algorithms. Our single-cell transcriptome data revealed the role of TNFAIP3 in macrophage polarization. Finally, preliminary experimental verifications to confirm the biological functions of TNFAIP3-mediated TAMs in NB. A total of 6 genes related to immune evasion were screened and we found that TNFAIP3 exhibited notably higher expression in macrophages than other immune cell types, based on the scRNA-sequencing data. GO and KEGG analysis showed that low expression of TNFAIP3 significantly correlated with the activation of multiple oncogenic pathways as well as immune-related pathways. Then validation affirmed that individuals within the TNFAIP3 high-expression cohort could potentially derive greater advantages from immunotherapeutic interventions, alongside exhibiting heightened immune responsiveness. Deciphering the pseudotime trajectory of macrophages, we revealed the potential of TNFAIP3 in inducing the polarization of macrophages towards the M1 phenotype. Finally, we confirmed that patients in the TNFAIP3 high expression group might benefit more from immunotherapy or chemotherapy as substantiated by RT-qPCR and immunofluorescence examinations. Moreover, the role of TNFAIP3 in macrophage polarization was validated. Preliminary experiment showed that TNFAIP3-mediated TAMs inhibit the proliferation, migration and invasion capabilities of NB cells. Our results suggest that TNFAIP3 was first identified as a promising biomarker for immunotherapy and potential molecular target in NB. Besides, the presence of TNFAIP3 within TAMs may offer a novel therapeutic strategy for NB.

Analysis of imaging features of rare tumors in nasal cavity and paranasal sinus

Objective:To explore the imaging features of rare tumors of nasal cavity and sinuses, and to improve the understanding of these diseases, thereby aiding clinical diagnosis and treatment. Methods:The CT and MRI findings of 79 cases of rare neoplasm of nasal cavity and sinuses confirmed by pathology were retrospectively analyzed, and the imaging features were summarized. Results:Among the 79 cases, there were 16 cases of neuroendocrine carcinoma, most showing expansive and infiltrative bone destruction without hyperosteogeny and sclerosis. The sphenoid sinus exhibited a "pigeon" shape. In 28 cases of malignant melanoma, MRI signals were diverse, typical signals were rare, but mixed signals were more common. In 12 cases of rhabdomyosarcoma, MRI enhancement mostly showed "grape-like" enhancement and partial ring enhancement; There were 10 cases of olfactory neuroblastoma, the lesions were consistent with the distribution area of olfactory mucosa, most of them were lobulated, marginal nodules, and "flower ring" enhancement, and 2 cases grew across intracranial and external, with multiple cystic lesions and surrounding flaky edema bands. In 5 cases of solitary fibrous tumor, Benign tumors had regular shape and uniform density, while malignant tumors had irregular shape and uneven density, The enhancement was obviously uneven and showed a "pattern" change. There were 2 cases of sarcomatoid carcinoma, both with lobed appearance, uneven density, lamellar low-density shadow, and osteolytic bone destruction. In 4 cases of schwannoma, the enhancement showed obvious inhomogeneous enhancement. One case showed cystic necrosis, one case showed calcification, and the surrounding structure was compressed without damage. There was 1 case of neurofibroma, with many cystic components, low signal separation and compartmentalized enhancement. One case of paraganglioma showed moderate enhancement in the arterial phase and progressive enhancement in the venous phase, accompanied by significant swelling bone destruction. Conclusion:Rare tumors of nasal cavity and paranasal sinuses have distinctive imaging features. CT and MRI can effectively show the extent of the lesions and the degree of infiltration into adjacent tissues and organs, which is helpful for early clinical diagnosis and staging. However, definitive diagnosis still depends on pathology and immunohistochemistry.

Long non-coding RNA MALAT 1 and PHOX2B expression in olfactory neuroblastomas and sympathetic neuroblastomas

Long noncoding RNAs (lncRNAs) participate in transcriptional, epigenetic, and post-transcriptional regulation of gene expression and may influence carcinogenesis. MALAT1 is a lncRNA that is expressed in endocrine and many other neoplasms and it has been shown to have oncogenic and/or tumor suppressor effects in tumor development. Olfactory neuroblastomas arise in the nasal cavity while sympathetic neuroblastomas are present mainly in the adrenal and periadrenal regions. These neoplasms have overlapping histopathological features. Rare cases of sympathetic neuroblastomas metastatic to the nasal cavity have been reported. PHOX2B has been shown to be relatively specific for sympathetic neuroblastomas, but only a limited number of cases of olfactory neuroblastomas have been examined for PHOX2B expression. This study aimed to explore the potential utilization of MALAT1 and PHOX2B in distinguishing these two entities. Tissue microarrays (TMA) were created for olfactory neuroblastomas (n = 26) and sympathetic neuroblastomas (n = 52). MALAT1 lncRNA expression was assessed by in situ hybridization using RNAScope technology. TMA slides were scanned by Vectra multispectral imaging system and image analysis and quantification were performed with inForm software. PHOX2B expression was analyzed by immunohistochemistry. MALAT1 showed predominantly nuclear expression in both tumor types and MALAT1 expression was 2-fold higher in olfactory neuroblastomas compared to sympathetic neuroblastomas (p < 0.0001). PHOX2B showed nuclear staining in most sympathetic neuroblastomas (51/52, 98 %) while only 1 olfactory neuroblastoma (3.8 %) was focally positive for this marker. These findings suggest immunostaining of PHOX2B could be an excellent marker in distinguishing between these two tumor types.

Case of recurrence olfactory neuroblastoma presented with ACTH dependent Cushing syndrome

Case of recurrence olfactory neuroblastoma presented with ACTH dependent Cushing syndrome

Feasibility of tumor-informed circulating tumor DNA (ctDNA) for molecular residual disease (MRD) assessment in pediatric patients with solid tumors.

10058 Background: Circulating Tumor DNA (ctDNA) is a noninvasive biomarker which has been validated as a prognostic tool in multiple adult cancers. There is evolving evidence that ctDNA may be prognostic in pediatric solid tumors, but experience with commercially available assays in pediatric patients is scarce. Signatera is a ctDNA assay which utilizes whole exome sequencing of tumor and whole blood to identify 16 tumor-specific, clonal, somatic variants. These variants are then monitored in plasma as a molecular residual disease (MRD) assessment. Methods: From November 2021 through August 2023, 30 patients were enrolled on a single center study evaluating the feasibility and utility of Signatera MRD monitoring in pediatric patients with solid tumors. Patients 6 months to 25 years of age with any malignant extracranial solid tumor including lymphoma were eligible. Peripheral blood has been collected every 3 weeks to 3 months while on therapy and every 3 to 6 months while off therapy for up to 2 years. A minimum of 22mL of blood was required for the first draw, and 16mL for subsequent draws. Timing of blood draws was aligned with standard of care blood draws when possible. Results of ctDNA MRD were compared with imaging obtained for disease response and surveillance as standard of care. Results: The cohort consisted of 6 cases of neuroblastoma, 6 osteosarcomas, 4 Wilms tumors, 4 carcinomas, 3 soft tissue sarcomas, 2 Ewing sarcomas, 2 germ cell tumors, 2 lymphomas, and one hepatoblastoma. Of 30 patients enrolled, a tumor-informed ctDNA assay was successfully created for 27 (90%). Of 25 patients who had radiographic evidence of disease at any time of monitoring, 23 (92%) had simultaneous detectable ctDNA. Seven patients have had disease recurrence, of whom all seven had detectable ctDNA at or preceding time of recurrence. Conclusions: Signatera tumor-informed ctDNA assay is a feasible noninvasive tool which may be utilized in parallel with standard of care imaging to monitor for disease recurrence in pediatric patients with extracranial solid tumors. Additional analysis of a larger patient cohort is needed to identify tumor types and clinical scenarios for which its application is most useful.

Clinical analysis of resection and dura skull base reconstruction of cranionasal communication tumor in 31 cases

Objective:To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Methods:Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. Results:A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesions（one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade Ⅰ, three cases of schwannoma, four cases of pituitary tumor） and 14 malignant lesions（one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinoma） . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 cases（fascia lata in 5 cases and nasal mucosa in 3 cases）. Twenty-three cases were repaired with pedicled flaps（septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 cases）. Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Conclusion:Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.

Infiltration of Round Blue Cell Tumors in Bone Marrow

Objective: To identify different types of round blue cell tumors on bone marrow biopsy and their pattern of marrow infiltration. Methodology: This cross-sectional descriptive study was conducted at the Department of Hematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2021 to December 2021. A total of 60 diagnosed cases of round blue cell tumors were included. Patients with acute lymphoblastic leukemia (ALL) and those receiving treatment for round blue cell tumors were excluded. Bone marrow aspiration and biopsy were performed. Peripheral film results, clinical observations, and patterns of marrow infiltration of round blue cell malignancies were analyzed using Statistical Package for the Social Sciences (SPSS) version 23. Results: The study revealed a male to female ratio of 2:1, with 40 (66.6%) males and 20 (33.3%) females. The overall average age was 5.69 ± 5.0 years. Ewing sarcoma and rhabdomyosarcoma patients did not exhibit infiltration, while three instances of retinoblastoma (9.37%) and two cases of neuroblastoma (10.52%) did. Immunohistochemistry (IHC) results for synaptophysin and chromogranin were positive for retinoblastoma and neuroblastoma, while S100 results were positive for neuroblastoma infiltration and negative for retinoblastoma. Both retinoblastoma and neuroblastoma showed diffuse, focal, and interstitial patterns of infiltration on trephine biopsy. Conclusion: Small round blue cell tumors were noted in bone marrow infiltration in 5 (8.33%) cases. Early detection of malignant cancers necessitates appropriate medical care, and in more severe cases, the need for neoadjuvant chemotherapy.

Abstract 6374: Socio-demographic predictors of recruitment in neuroblastoma therapeutic clinical trials

Abstract The generalizability of clinical trial outcomes hinges upon the equitable access and enrollment of diverse patient populations. Yet, disparities persist that may influence enrollment patterns. In neuroblastoma, the impact of ethnicity, socioeconomic status (SES), distance to care, and age at diagnosis on enrollment in therapeutic trials remains underexplored. We aimed to investigate these factors in neuroblastoma patients to identify potential disparities in clinical trial participation. We utilized the Childhood Cancer Research Network data, selecting neuroblastoma cases from 2008-2015, excluding those &amp;gt;21 years old or with incomplete data. We focused on factors influencing enrollment in therapeutic trials (ANBL0032, ANBL0421, ANBL0531, ANBL0532, ANBL0621, ANBL0931, ANBL1021, ANBL1221, ANBL1232). Key predictors examined were ethnicity, age at diagnosis, SES (via Yost Index), and distance to care from home to treatment hospital. We employed Poisson regression to calculate adjusted risk ratios (aRR) and 95% confidence intervals for trial participation. Analyzing 3,148 neuroblastoma cases from the CCRN registry, the ethnic composition was as follows: 68% were non-Hispanic White, 14% Hispanic, and 10% NH Black and SES distribution was even across quintiles. Age at diagnosis was a significant factor in trial enrollment: children &amp;gt;2 years were 94% more likely to enroll than those under 2 years (p &amp;lt; 0.001). Race, ethnicity, SES, and distance to care showed no significant effect on enrollment, all with non-significant p-values. In CCRN, neuroblastoma patient's age at diagnosis was a determinant in therapeutic trial enrollment, providing insight into design strategies to encourage trial participation. While common barriers like race, ethnicity, SES, and distance to care did not impact enrollment in our cohort, the significant role of age highlights an area where focused efforts can ensure that all age groups have equitable access to the potential benefits of therapeutic trials. Category N aRR (95% CI) p-value Race and Ethnicity Non-Hispanic (NH) White 2139 ref Hispanic (All races) 436 0.93 (0.81, 1.08) 0.36 NH Black 320 1.07 (0.93, 1.23) 0.33 NH Asian/Pacific Islander 98 1.14 (0.89, 1.47) 0.30 NH American Indian/Alaska Native 17 0.95 (0.48, 1.88) 0.89 Other 138 0.94 (0.75, 1.17) 0.55 SES (Yost Index) Quintile 1 493 0.88 (0.75, 1.02) 0.09 Quintile 2 524 0.95 (0.83, 1.10) 0.53 Quintile 3 606 0.98 (0.86, 1.11) 0.71 Quintile 4 554 0.92 (0.80, 1.06) 0.24 Quintile 5 563 ref Age at Diagnosis &amp;lt;2 year 1790 ref &amp;gt;2 years 1354 1.94 (1.76, 2.12) &amp;lt;0.001 Distance to Care 0-25 miles 1520 ref &amp;gt;25-50 miles 535 1.05 (0.93, 1.18) 0.36 &amp;gt;50-100 miles 412 0.97 (0.85, 1.11) 0.91 &amp;gt;100-250 miles 239 0.99 (0.87, 1.13) 0.60 &amp;gt;250 miles 82 0.99 (0.77, 1.28) 0.97 Citation Format: DeVon Hunter-Schlichting, Jeannette Sample, Kate Knowles, David Van Riper, Logan Spector, Erin Marcotte. Socio-demographic predictors of recruitment in neuroblastoma therapeutic clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6374.

Abstract 2865: Efficacy of MDM2 and epigenetic inhibitors treatments for neuroblastoma

Abstract Pediatric Neuroblastoma (NB) is one of the most prevalent solid tumors in children that arise from embryonic neural crest cells and poses a significant challenge in the field of oncology. There are about 700 to 800 new cases of neuroblastoma diagnosed each year in the United States, and accounts for approximately 15% of all childhood cancer mortalities. Since this malignancy predominantly affects infants and young children, it is imperative to decipher the underlying molecular factors driving its pathogenesis. The novel molecular therapeutic approach includes the use of epigenetic modifiers as drugs. This approach aims to reverse significant epigenetic events underlying cancer pathogenesis, particularly abnormalities in histone modifications and DNA methylation. The reduction of both DNA and histone methylation levels leads to the reactivation of tumor suppressor genes and inhibits cancer cell proliferation and cell growth. In this study, we used selective and reversible small molecule agents such as MDM2 inhibitor (RG7388) and epigenetic modifiers (CM272 and SAHA) to block cell proliferation by inducing cell cycle arrest via enforcing Epigenetic alterations. Our initial experiments were designed to understand the effects of RG7388, CM272, and SAHA treatments on NB and their impact on cell cycle progression. It was hypothesized that the decrease in DNA methylation and increase in histone modification- augment p21 expression via the use of MDM2 inhibitors and epigenetic modifiers. To test this hypothesis, the NB cells (SK-N-SK and IMR-32) were treated with RG7388, CM272, and SAHA for 24 hours. The extent of Cell death was determined for NB cells by using the Trypan Blue Dye Exclusion (TBDE) method, and CellTiter-Glo® Luminescent Cell Viability Assay. Induction of apoptosis was determined by using the Immunofluorescence staining method with DEVD-amc substrate. The results of our study suggested that RG7388, CM272, and SAHA were able to induce cell death in the SK-N-SH cells following 24-hour treatment. Furthermore, we analyzed the levels of Tumor suppressor (p53), cell cycle arrest (p21, p27, AurkB, CDC25A, CyclinD) cell death (Bax, Bcl2, LC3, Beclin, PARP, Cleaved PARP, RIP1, RIP3, MLKL, p-AKT), and Epigenetic biomarker (DNMT1, DNMT3A, DNMT3B, acetyl histoneH3, H4, and H2b) protein expression levels using western blot analysis. The results showed significant elevation of p53, p21, p27, and acetylation of histone family biomarkers after treatment when compared with the control group. In summary, our results indicate that RG7388, CM272, and SAHA treatments can effectively induce cellular responses and prevent cell growth and progression by enforcing epigenetic changes in the NB cells. (This research was supported by the National Pediatric Cancer Foundation, Tampa, Florida, and the Royal Dames of Cancer Research Inc. of Ft. Lauderdale, Florida) Citation Format: Tahani Momenah, Umamaheswari Natarajan, Shyam Jaganathan, Appu Rathinavelu. Efficacy of MDM2 and epigenetic inhibitors treatments for neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2865.