11 research outputs found
Role of DNA Methylation Profile in Diagnosing Astroblastoma: A Case Report and Literature Review
Astroblastoma is a rare tumor of the central nervous system (CNS) with uncertain clinical behavior. Recently, DNA methylation profiling has been shown to provide a highly robust and reproducible approach for the classification of all CNS tumors across different age groups. By using DNA methylation profiling, a subset of CNS high-grade tumors with astroblastoma-like morphology characterized by the meningioma 1 gene (MN1) rearrangements, has been identified; they were termed “CNS high-grade neuroepithelial tumors with MN1 alteration” (CNS-HGNET-MN1). Here, we describe a case of CNS-HGNET-MN1 diagnosed by DNA methylation profiling, using Illumina Infinium HumanMethylationEPIC BeadChip (EPIC), that offers the opportunity to conduct a brief literature review. The patient presented with an episode of partial seizures involving the right hemisoma. A gross total resection was performed. No other treatment was proposed in light of the histological and molecular findings. After 21 months, the patient is disease-free in good clinical conditions. Also in view of this case, we recommend DNA-methylation profiling as an important tool for diagnosis and more effective patient stratification and management
Vemurafenib Treatment of Pleomorphic Xanthoastrocytoma in a Child With Down Syndrome
Brain tumors are the most common solid neoplasms of childhood, but they are very rarely reported in children with Down Syndrome (DS), who develop more commonly different types of malignancies. In particular, we hereby report the case of an 8-years-old child with DS that presented to our attention for neurological and endocrinological issues. Brain imaging revealed the presence of a mass that was partially resected revealing a histological diagnosis of Pleomorphic Xanthoastrocytoma (PXA), a rare WHO grade II tumor extending from the diencephalic region into the surrounding brain tissue. These tumors can harbor the BRAF mutation p.V600E, targetable by the specific inhibitor Vemurafenib. After confirming the presence of the mutation in the tumor, the patient was treated with Vemurafenib. The treatment proved to be effective, leading to a partial response and a stabilization of the disease. Usually, in patients with DS a reduction of the dose of chemotherapeutic drugs is necessary. Vemurafenib was instead well-tolerated as the only observed adverse effect was grade I skin toxicity. This is, to our knowledge, the first case of a PXA reported in a child with DS and the first DS patient treated with Vemurafenib
COLORECTAL CANCER WITH LIVER METASTASIS AND TREATMENT WITH ANTI-ANGIOGENIC DRUGS: RESPONSE EVALUATION WITH DIFFUSION-WEIGHTED MRI
Colorectal cancer is the third most common malignancy and the third leading cause of
cancer-related death worldwide. Recently, the introduction of novel drugs (antiangiogenic
drugs) has led to a significant improvement in the survival rates of patients
with metastatic colorectal cancer. The RECIST (Response Evaluation Criteria for Solid Tumors)
parameters cannot adequately detect important effects of treatment and response
to the application of these new drugs. New radiologic methods, such as diffusionweighted
MRI, could help to assess the quality and quantity of the response more accurately.
Diffusion-weighted MRI imaging is based on a technique sensitive to the Brownian
motion of water molecules over short distances.
This article describes our experience with this method in patients with liver metastasis
from colorectal cancer after treatment with bevacizumab
The Prognostic Role of the C-Reactive Protein and Serum Lactate Dehydrogenase in a Pediatric Series of Bone Ewing Sarcoma
Background: Ewing sarcoma (ES) is a rare and aggressive pediatric cancer. Numerous studies have attempted to identify new prognostic biomarkers. The predictive value of serum LDH and CRP has not been clearly described, to date. Methods: The objective of our retrospective study was to investigate the prognostic value of LDH and CRP levels and their association with overall survival in a series of ES patients. Results: Between 2004 and 2019, 89 ES patients were included. In a univariable analysis, high levels of LDH and CRP were associated with the worst prognosis. In a multivariable analysis, only higher LDH values remained associated with a lower survival. The high-LDH-level group experienced all 21 deaths registered in our population (24%) and about 90% of disease progressions. The 5-year overall survival was 66.4% in the high-LDH-level group, while no deaths were observed in the low-LDH-level group. The 5-year progression-free survival was 57.9% in the high-LDH-level group versus 80.4% in the low-LDH-level group. Conclusions: In our study, LDH levels at diagnosis were strongly correlated with the prognosis, and they might be considered a prognostic factor in Ewing sarcoma. The LDH value, along with its very low cost and its reproducibility in almost all centers, make it suitable as a potential prognostic biomarker in clinical practice
Peripheral Nervous System Involvement in Non-Primary Pediatric Cancer. From Neurotoxicity to Possible Etiologies
Peripheral neuropathy is a well described complication in children with cancer. Oncologists are generally well aware of the toxicity of the main agents, but fear the side effects of new drugs. As chemotherapeutic agents have been correlated with the activation of the immune system such as in Chemotherapy Induced Peripheral Neuropathy (CIPN), an abnormal response can lead to Autoimmune Peripheral Neuropathy (APN). Although less frequent but more severe, Radiation Induced Peripheral Neuropathy may be related to irreversible peripheral nervous system (PNS). Pediatric cancer patients also have a higher risk of entering a Pediatric Intensive Care Unit for complications related to therapy and disease. Injury to peripheral nerves is cumulative, and frequently, the additional stress of a malignancy and its therapy can unmask a subclinical neuropathy. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication along with patient factors, namely age and inherited susceptibilities. The recent identification of individual genetic variations has advanced the understanding of physiopathological mechanisms and may direct future treatment approaches. More research is needed on pharmacological agents for the prevention or treatment of the condition as well as rehabilitation interventions, in order to allow for the simultaneous delivery of optimal cancer therapy and the mitigation of toxicity associated with pain and functional impairment. The aim of this paper is to review literature data regarding PNS complications in non-primary pediatric cancer
Long-term response to crizotinib in a 17-year-old boy with treatment-naĂŻve ALK-positive non-small-cell lung cancer
Background: Lung cancer is the leading cause of cancer-related death. NSCLC accounts for 80-90% of cases. In young patients, adenocarcinoma is the most frequent histotype and 3-7% expresses the rearrangement of ALK oncogene, sensitive to TKIs. Crizotinib is the first ALK inhibitor approved by the FDA. Case: We present a case of a 17-year-old male with metastatic treatment-naïve ALK-positive adenocarcinoma. He was treated with crizotinib and obtained a prolonged response with PFS of 33 months. Conclusion: Crizotinib can be extremely effective in adolescents with treatment-naïve ALK-positive NSCLC but fail to prevent a central nervous system relapse. Resistance mechanisms need to be investigated
Short and Long-Term Toxicity in Pediatric Cancer Treatment: Central Nervous System Damage
Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS solid malign tumors. The effects on the CNS are disabling and often permanent with limited treatments, thus it is important that clinicians recognize the effects of cancer therapy on the CNS. Knowledge of these conditions can help the practitioner be more vigilant for signs and symptoms of potential neurological complications during the management of pediatric cancers. As early detection and more effective anticancer therapies extend the survival of cancer patients, treatment-related CNS toxicity becomes increasingly vital. This review highlights major neurotoxicities due to pediatric cancer treatments and new therapeutic strategies; CNS primary tumors, the most frequent solid tumors in childhood, are excluded because of their intrinsic neurological morbidity
Molecular Characterization of Medulloblastoma in a Patient with Neurofibromatosis Type 1: Case Report and Literature Review
Brain tumors are the most common solid neoplasms of childhood. They are frequently reported in children with Neurofibromatosis type 1 (NF1). The most frequent central nervous system malignancies described in NF1 are optic pathway gliomas and brainstem gliomas. Medulloblastoma (MB) in NF1 patients is extremely rare, and to our knowledge, only 10 cases without molecular characterization are described in the literature to date. We report the case of a 14-year-old girl with NF1 that came to our attention for an incidental finding of a lesion arising from cerebellar vermis. The mass was completely resected, revealing a localized classic medulloblastoma (MB), subgroup 4. She was treated as a standard-risk MB with a dose-adapted personalized protocol. The treatment proved to be effective, with minor toxicity. Brain and spine MRI one year after diagnosis confirmed the complete remission of the disease. To our knowledge, this is the only case of MB reported in a patient with NF1 with molecular characterization by the methylation profile. The association between NF1 and MB, although uncommon, may not be an accidental occurrence
Medulloblastoma Associated with Down Syndrome: From a Rare Event Leading to a Pathogenic Hypothesis
Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB development via inhibition of neuroectodermal differentiation. Moreover, the NOTCH/WNT dysregulation in DS, which is probably associated with an increased risk of leukemia, suggests a pivotal role of this pathway alteration in the pathogenesis of MB; therefore, this condition should be further investigated in future studies by molecular characterizations