A review of the biological and clinical implications of RAS-MAPK pathway alterations in neuroblastoma

Neuroblastoma is the most common extra-cranial solid tumor in children, representing approximately 8% of all malignant childhood tumors and 15% of pediatric cancer-related deaths. Recent sequencing and transcriptomics studies have demonstrated the RAS-MAPK pathway’s contribution to the development and progression of neuroblastoma. This review compiles up-to-date evidence of this pathway’s involvement in neuroblastoma. We discuss the RAS-MAPK pathway’s general functioning, the clinical implications of its deregulation in neuroblastoma, and current promising therapeutics targeting proteins involved in signaling.

Spinal Deformities after Childhood Tumors

Childhood tumors of the central nervous system (CNS) and other entities affecting the spine are rare. Treatment options vary from surgical biopsy to partial, subtotal, and total resection, to radiation, to chemotherapy. The aim of this study is to investigate spinal deformity and subsequent surgical interventions in this patient cohort. A retrospective review at our institution identified children with CNS tumors, spinal tumors, and juxta-spinal tumors, as well as spinal deformities. Tumor entity, treatment, mobilization, and radiographic images were analyzed relative to the spinal deformity, using curve angles in two planes. Conservative or surgical interventions such as orthotic braces, growth-friendly spinal implants, and spinal fusions were evaluated and analyzed with respect to treatment results. Tumor entities in the 76 patients of this study included CNS tumors (n = 41), neurofibromatosis with spinal or paraspinal tumors (n = 14), bone tumors (n = 12), embryonal tumors (n = 7), and others (n = 2). The initial treatment consisted of surgical biopsy (n = 5), partial, subtotal, or total surgical resection (n = 59), or none (n = 12), followed by chemotherapy, radiotherapy, or both (n = 40). Out of 65 evaluated patients, 25 revealed a moderate or severe scoliotic deformity of 71° (range 21–116°), pathological thoracic kyphosis of 66° (range 50–130°), and lordosis of 61° (range 41–97°). Surgical treatment was performed on 21 patients with implantation of growth-friendly spinal implants (n = 9) as well as twelve dorsal spinal fusions (two with prior halo distraction). Surgical interventions significantly improved spinal deformities without additional neurological impairment. With the increasing number of children surviving rare tumors, attention should be focused on long-term problems such as spinal deformities and consequent disabilities. A significant number of children with CNS tumors, spinal tumors or juxta-spinal tumors required surgical intervention. Early information about spinal deformities and a close follow-up are mandatory for this patient group.

Assessment of the results and the haematologic side effects of the 3D conformal and the IMRT/ARC therapies delivered during the craniospinal irradiation of childhood tumors, in a follow-up period of 5 years

Objectives The craniospinal irradiation (CSI) of childhood tumors with Rapidarc technique is a new way of treatment. Our objective was to compare the acute haematologic toxicity pattern during 3D conformal radiotherapy with the application of the novel techniques. Materials and methods Data from patients treated between 2007 and 2014 has been collected and seven patients were identified in each of both treatment groups. The acute blood toxicity results were obtained, after establishing a general linear model, by using the SPSS software. Furthermore, the dose exposure of the organs-at-risk has been compared. Patients have been followed-up for a minimum of five years, then progression-free survival and overall survival data were assessed. Results After the assessment of the laboratory parameters of the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side-effects during the IMRT/ARC and the 3D conformal treatment. Laboratory parameters significantly decreased compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival and overall survival, and no signs of serious irradiation organ toxicity were observed during the follow-up period in either of the groups. Conclusion Rapidarc technique can be used safely even for the treatment of childhood tumors, as the extent of normal tissue dose exposures and that of acute hematological side effects is not higher.

Differential diagnosis of kidney formation as a model of the interaction of regional clinics with the federal center

Malignant kidney tumors make up 6 % of all childhood tumors and require careful differential diagnosis with other diseases. This article discusses the differential diagnosis of nephroblastoma and kidney tuberculosis.Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.