Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

Recent progress and novel approaches to treating atypical teratoid rhabdoid tumor.

Atypical teratoid rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) tumors that occur mostly in young children and have historically carried a very poor prognosis. While recent clinical trial results show that this tumor is curable, outcomes are still poor compared to other central nervous system embryonal tumors. We here review prior AT/RT clinical trials and highlight promising pre-clinical results that may inform novel clinical approaches to this aggressive cancer.

Strategies for the Treatment of Infantile Soft Tissue Sarcomas With BCOR Alterations.

BCOR alterations are described in ultra-rare infantile soft tissue sarcomas including primitive myxoid mesenchymal tumor of infancy and undifferentiated round cell sarcoma (URCS). Previous reports often describe dismal outcomes. Thus, we undertook a retrospective, multi-institutional study of infants with BCOR -rearranged soft tissue sarcomas. Nine patients aged 6 weeks to 15 months were identified. One tumor carried a BCOR :: CCNB3 fusion, whereas 7 tumors harbored internal tandem duplication of BCOR , including 4 cases classified as primitive myxoid mesenchymal tumor of infancy, 1 case as URCS, and 2 cases characterized by a "hybrid morphology" in our evaluation. Four patients underwent upfront surgery with residual disease that progressed locally after a median of 2.5 months. Locoregional recurrences were observed in hybrid patients, and the URCS case recurred with brain metastases. Complete radiographic responses after chemotherapy were achieved in patients treated with vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide, vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide (regimen I), and ifosfamide/carboplatin/etoposide. Seven patients received radiotherapy. With a median of 23.5 months off therapy, 8 patients are with no evidence of disease. In our study, observation was inadequate for the management of untreated postsurgical residual disease. Tumors demonstrated chemosensitivity with anthracycline-based regimens and ifosfamide/carboplatin/etoposide. Radiotherapy was required to achieve durable response in most patients.

Treatment of pediatric high-grade central nervous system tumors with high-dose methotrexate in combination with multiagent chemotherapy: A single-institution experience.

BACKGROUND: Effective treatment for pediatric embryonal brain tumors includes dose-intensive multiagent chemotherapy (DIMAC) followed by high-dose chemotherapy with stem cell rescue (HDCSCR). Use of repeated cycles of DIMAC including high-dose methotrexate (HDMTX) without HDCSCR has not been described. PROCEDURE: We retrospectively reviewed the responses/toxicities in 13 patients (aged 2-155 months, median 22 months) with central nervous system (CNS) tumors (atypical teratoid rhabdoid tumors, CNS embryonal tumors not otherwise specified, pineoblastoma, embryonal tumor with multilayered rosettes, and CNS sarcoma) treated over a 12-year period with repeated cycles of HDMTX followed by etoposide, cisplatin, cyclophosphamide, and vincristine. RESULTS: Six patients (46.2%) had disseminated disease at presentation and five (38.5%) had gross total resection. A total of 64 courses of therapy were administered with a median of five courses per patient.  Eight patients (61.5%) received radiation therapy (one at relapse). By completion of therapy, 11 patients (84.6%) achieved a response (six complete, five partial).  Six of the 13 patients (46.2%) remain alive with a median follow-up of 48 months (6-146).  Acute toxicities included fever/neutropenia (70.3%), bacteremia (15.6%), and grade 3 mucositis (18.8%).  Long-term complications included learning disability, seizure disorder, and brain necrosis, without treatment-related deaths. CONCLUSIONS: DIMAC with HDMTX without HDCSCR may be an effective treatment option for selected patients with embryonal or high-grade CNS tumors.

Myxoid glioneuronal tumor, PDGFRA p.K385-mutant: clinical, radiologic, and histopathologic features.

"Myxoid glioneuronal tumor, PDGFRA p.K385-mutant" is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow-up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports "myxoid glioneuronal tumor, PDGFRA p.K385-mutant" as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.

sCD36 sérico y variables cardiometabólicas en dos poblaciones peruanas: Carhuamayo (4100 msnm) y Mala (30 msnm) / Serum levels of sCD36 and cardiometabolic variables in two Peruvian towns: Carhuamayo (4100 masl) and Mala (30 masl)

Objetivo: Determinar los niveles séricos de sCD36, molécula relacionada al metabolismo lipídico, en poblaciones de la altura y del nivel del mar, y establecer la asociación de este parámetro con factores de riesgo cardiometabólico. Materiales y métodos: Participaron 45 personas de Carhuamayo (4100 msnm) y 40 personas de Mala (30 msnm). Se midió el peso, talla y presión arterial. Se determinó la hemoglobina en sangre total, y la glucosa, perfil lipídico y sCD36 en suero. Resultados: Se encontró en la población de Carhuamayo niveles de hemoglobina significativamente mayores, mientras que el peso, IMC y nivel de glucosa fueron significativamente menores que en Mala. No hubo diferencia significativa entre los niveles séricos de sCD36 de ambas poblaciones. Se observó una diferencia significativa entre los valores medios de sCD36 según el IMC, y una correlación positiva significativa entre sCD36 y el peso e IMC. Conclusiones: El nivel sérico observado de sCD36 es independiente de la altitud y puede ser considerado como marcador potencial de síndrome metabólico

Objectives: To determine the serum levels of sCD36, a lipid metabolism-related molecule, in high-altitude and sea-level populations, and to establish the association of this parameter with cardiometabolic risk factors. Materials and methods: The study population consisted of 45 people from Carhuamayo (4100 masl) and 40 people from Mala (30 masl). Weight, height and blood pressure were measured. Hemoglobin was determined in whole blood, and glucose, lipid profile and sCD36 in serum. Results: It has been found that hemoglobin levels in the population of Carhuamayo were significantly higher, while weight, BMI and glucose level were significantly lower than those in the population of Mala. There was no significant difference between serum levels of sCD36 in both populations. A significant difference was observed between sCD36 mean serum levels of both populations based on the BMI, and a significant positive correlation between sCD36 and the weight and BMI. Conclusions: The observed sCD36 serum level is not related to the altitude and can be considered as a potential marker of metabolic syndrome

Distribución del polimorfismo Q192R del gen de la paraoxonasa 1 en una población del distrito de Junín (Región Junín, Perú) / Distribution of the Q192R polymorphism of the paraoxonase 1 gene in a population of the district of Junín (Junín region, Peru)

Objetivo: La paraoxonasa 1 (PON1), una esterasa asociada a las lipoproteínas de alta densidad (HDL), presenta diversos polimorfismos: el polimorfismo PON1 Q192R (región codificante) es el responsable de las variaciones de la actividad paraoxonasa de la enzima. El alelo PON1 192R es considerado un factor de riesgo para desarrollar trastornos cardiometabólicos en algunas poblaciones. El objetivo del presente estudio es determinar la distribución de los polimorfismos PON1 Q192R, y su asociación con el perfil lipidíco y APO A1 en una población andina. Materiales y métodos: Estudio descriptivo, transversal, en el que participaron 79 personas adultas (26 hombres y 53 mujeres), clínicamente sanas, residentes del distrito de Junín a 4105 msnm. Se empleó la técnica PCR/RFLP para el análisis del sitio polimórfico Q192R del gen PON1, y se determinaron los valores séricos del perfil lipídico y APO A1, y las actividades paraoxonasa y arilesterasa de la enzima. Resultados: La distribución de los genotipos para PON1192 fue: QQ 13,9%, QR 45,6% y RR 40,5%, y el alelo más frecuente fue 192R 63%. Las actividades paraoxonasa basal y estimulada fueron diferentes según sus genotipos, mientras que la actividad esterasa de la enzima no estuvo influenciada por el polimorfismo. Por otra parte, no se encontró asociación entre el polimorfismo PON1 Q192R y el perfil lipídico y APO A1. Conclusiones: La alta prevalencia del alelo PON1 192R en la población estudiada probablemente indique un papel importante en el desarrollo de enfermedades cardiometabólica

Objective: Paraoxonase 1 (PON1), an esterase associated with high-density lipoproteins (HDL), has several polymorphisms: the PON1 Q192R polymorphism (coding region) is responsible for variations in the paraoxonase activity of the enzyme. The PON1 192R allele is considered a risk factor for developing cardiometabolic disorders in some populations. The aim of the present study is to determine the distribution of the PON1 Q192R polymorphism and its association with the lipid profile and APO A1 in an Andean population. Materials and methods: A descriptive, cross-sectional study involving 79 healthy adults (26 males and 53 females), residents of the district of Junín at 4105 m.a.s.l. The PCR/RFLP technique was used for the analysis of the PON1 Q192R polymorphism. The serum values of the lipid profile and APO A1, and the paraoxonase and arylesterase activities of the enzyme were determined. Results: The distribution of the genotypes for PON1192 was QQ 13.9%, QR 45.6% and RR 40.5%, and the most frequent allele was 192R 63%. The baseline and stimulated paraoxonase activities were different based on their genotypes, while the esterase activity of the enzyme was not influenced by the polymorphism. On the other hand, no association was found between the PON1 Q192R polymorphism and the lipid profile and APO A1. Conclusions: The high prevalence of the PON1 192R allele among the studied population probably indicates an important role in the development of cardiometabolic diseases

Barriers to the Use of Psychosocial Support Services Among Adolescent and Young Adult Survivors of Pediatric Cancer.

Purpose: Adolescent and young adult (AYA) survivors of pediatric cancer commonly report both functional and emotional difficulties, yet many of their mental health needs are not met. Given the unique needs of these survivors, this study examined barriers to psychosocial support service utilization in this population, including accessibility, personal preferences, and practical barriers such as insurance and transportation. Methods: Thirty-six adolescent and young adult survivors of pediatric cancer (aged 15-29) with mental health difficulties (i.e., anxiety or depression) completed surveys assessing access and utilization of services and barriers to utilization. Services assessed included the use of mental health professionals, a pastor or someone in a place of worship, and support groups. Results: Half of the participants utilized a mental health professional, but other forms of support were used less frequently. Utilization of services was related to insurance status and use of prescription medication. Greater time since completion of treatment was a barrier to utilizing psychosocial support services. Conclusion: Use of psychosocial support services is linked closely with use of other healthcare services, including taking prescription medication for mood difficulties. Results have implications for how primary care and oncology providers address barriers to these services among AYA survivors of pediatric cancer.