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Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.
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Introdução: Os meduloblastomas são os tumores sólidos mais comuns da infância e classificados em 4 subgrupos moleculares: WNT, SHH, grupo 3 e grupo 4. Muitos estudos buscam desenvolvimento de novos quimioterápicos para os meduloblastomas através da identificação de genes cuja expressão sejam novos alvos moleculares para drogas, como receptores de membrana associados a replicação celular. Objetivo: Avaliar a associação da expressão de CD114 com a mortalidade de pacientes portadores de meduloblastoma. Métodos: Revisão feita colhendo informações publicadas em plataformas virtuais em português e inglês. Inicialmente foi realizada busca por descritores relacionados ao tema - neurocirurgia, oncologia cirúrgica, terapia de alvo molecular e meduloblastoma - e seus equivalentes em inglês - neurosurgery, surgical oncology, molecular targeted therapy e medulloblastoma - com busca AND ou OR, considerando o título e/ou resumo. Após, foram incluídos somente os que tinham maior relação ao tema, e realizada a leitura da íntegra dos textos. Finalmente foram referidos 2 artigos. Resultados: Há diferença na expressão do receptor de membrana CD114 entre o Grupo 3 e os demais grupos moleculares, além de diferença entre o subtipo molecular SHH γ e os subtipos moleculares Grupo 3 α e Grupo 3 ß. Não houve diferença estatisticamente significativa entre os demais grupos e subtipos. Em relação à mortalidade, esta revisão não demonstrou significância estatística na relação entre expressões baixas e elevadas desse gene e a mortalidade. Conclusão: Não há relação direta entre a expressão do receptor de membrana CD114 e a mortalidade em pacientes portadores de meduloblastoma. Entretanto, são necessários estudos adicionais sobre as vias de sinalização intracelulares associadas a esse receptor e ao seu gene, o CSF3R.
Introduction: Medulloblastomas are the most common solid tumors of childhood and classified into 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Many studies seek to develop new chemotherapy drugs for medulloblastomas by identifying genes whose expression is new molecular targets for drugs, such as membrane receptors associated with cell replication. Objective: To evaluate the association of CD114 expression with mortality in patients with medulloblastoma. Methods: Review carried out collecting information published on virtual platforms in Portuguese and English. Initially, a search was carried out for descriptors related to the topic - neurosurgery, surgical oncology, molecular targeted therapy and medulloblastoma, with AND or OR search, considering the title and/or summary. Afterwards, only those that were most related to the topic were included, and the texts read in full. Finally, 23 articles were referred. Results: There is a difference in the expression of the CD114 membrane receptor between Group 3 and the other molecular groups, in addition to a difference between the SHH γ molecular subtype and the Group 3 α and Group 3 ß molecular subtypes. There was no statistically significant difference between the other groups and subtypes. Regarding mortality, this review did not demonstrate statistical significance in the relationship between low and high expressions of this gene and mortality. Conclusion: There is no direct relationship between the expression of the CD114 membrane receptor and mortality in patients with medulloblastoma. However, additional studies are needed on the intracellular signaling pathways associated with this receptor and its gene, CSF3R.
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Objective:To analyze the MRI features of medulloblastoma (MB) in children, and screen out the key signs that can predict the risk of MB before surgery.Methods:Clinical and radiological data of 62 children with MB confirmed by pathology in Shenzhen Children′s Hospital from December 2012 to December 2021 were retrospectively analyzed. According to the diagnosis and treatment guidelines for children with MB (2021 edition), the patients were divided into standard risk group (43 cases) and high risk group (19 cases). MRI features of MB were observed and recorded, including tumor site, location of tumor center, tumor morphology, signal intensity of T 1WI, T 2WI and diffusion weighted imaging (DWI), enhancement pattern, cystic lesion size, location and number, peritumoral edema and hydrocephalus, and the maximum diameter of tumor was measured. The χ 2 test or Fisher exact probability method was used to compare the differences in age, gender and MRI signs between the two groups. The t test of two independent samples was used to compare the differences in the maximum diameter of tumors between the two groups. The indicators with statistically significant differences were included in binary logistic regression analysis to obtain independent influencing factors associated with the risk groups. The receiver operation characteristic curve was used to evaluate the diagnostic efficacy. Results:There were significant differences in age ( P=0.026), enhancement pattern ( P=0.018), cystic lesion size ( P=0.005), location ( P=0.011) and number ( P=0.003) between standard risk group and high risk group. There were no significant differences in gender, tumor site, location of tumor center, tumor morphology, signal intensity of T 1WI, T 2WI and DWI, peritumoral edema, hydrocephalus and maximum diameter of tumor between the two groups ( P>0.05). Binary logistic regression results showed the age (OR=0.207, 95%CI 0.040-0.983, P=0.042) and the number of cystic lesions (OR=0.215, 95%CI 0.073-0.630, P=0.005) were the protective factors for MB in high risk group, the enhancement pattern Ⅲ (OR=5.226, 95%CI 1.516-52.920, P=0.048) was the dangerous factor for MB in high risk group. The area under the curve of the combined diagnosis of high risk MB was 0.845 (95%CI 0.741-0.949). Conclusions:The age and MRI signs the pattern of tumor enhancement Ⅲ and the number of cystic lesion can be used to predict the risk grouping of MB preoperatively. When the child is younger and MB enhancement pattern is mainly peripheral enhancement without obvious cystic change, it may indicate high risk MB.
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Embryonal tumors are a heterogenous group of neoplasms mostly defined by recurrent genetic driver events. They have been, previously, broadly classified as either medulloblastoma or supratentorial primitive neuroectodermal tumors (PNETs). However, the application of DNA methylation/gene expression profiling in large series of neoplasms histologically defined as PNET, revealed tumors, which showed genetic events associated with glial tumors. These findings led to the definitive removal of the term “PNET” in the 2016 World Health Organization (WHO) classification of CNS tumors. Moreover, further studies on a large scale of methylation profiling have allowed the identification of new molecular-defined entities and have largely influenced the 5th edition of the WHO classification of CNS tumors (WHO CNS5) for both medulloblastomas and other CNS embryonal tumors. The importance of molecular characteristics in CNS embryonal tumors is well represented by the identification of different molecular groups and subgroups in medulloblastoma. So, in the CNS5, the emerged group 3 and group 4 belong to the classification, and the four molecular and morphologic types are now combined into a unique section. Among other embryonal tumors, two new recognized entities are introduced in CNS5: CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication (ITD). Embryonal tumor with multilayered rosettes (ETMR), already present in the previous classification now has a revised nomenclature as a result of the new DICER1 alteration, additional to the formerly known C19MC. Regarding atypical teratoid/rhabdoid tumor (AT/RT), three molecular subgroups are recognized in CNS5. The combination of histopathological and molecular features reflects the complexity of all these tumors and gives critical information in terms of prognosis and therapy. This encourages the use of a layered diagnostic report with the integrated diagnosis at the top, succeeded by layers including the histological, molecular, and other essential details.
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Background: Medulloblastoma is the commonest embryonal brain tumor in children. It has shown improved outcomes with combined modality treatment. We aimed to study patient characteristics and survival outcomes of patients with this disease across two tertiary care centers in India. Methods: We analyzed data of patients with histological diagnosis of medulloblastoma treated from January 2010 to January 2016. Patient characteristics and follow-up data were retrieved from hospital records. Descriptive statistics were used to describe clinical and pathological characteristics. Overall survival (OS) was calculated from date of diagnosis to death due to any cause. Relapse-free survival (RFS) was calculated from date of diagnosis to occurrence of relapse or death. Result: Out of 26 patients treated, 24 were children and 2 were adults. Median age was 10 years (range = 0.8–22 years). Twenty (76.9%) patients were male. Fifteen (57.7%) patients were stratified as high-risk (HR), rest 11 (42.3%) were categorized as average risk (AR). Histopathology showed classical variety in majority of patients except for 4 (15%) cases, 3 with desmoplastic and 1 with anaplastic subtype. Median follow-up was 49.7 months (range= 4.2–102.5 months). Overall, eight (30.8%) patients relapsed and six (23%) deaths occurred. Five (33.3%) patients in HR category and 3 (27.3%) patients in AR group showed relapse. Median RFS and OS were not yet reached. Five-year RFS was 69.2% whereas five-year OS was 76.9%. Conclusion: This study highlighted patient characteristics and treatment outcomes in Indian patients. With adherence to standard treatment, high remission rates and improvement in mortality rates were achieved.
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Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.
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Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.
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We provided inpatient rehabilitation treatment and return-to-school guidance to a junior high school student with medulloblastoma and pervasive developmental disorder (autism spectrum disorder). Here we describe the rehabilitation treatment for patients with physical and developmental disabilities. A 13-year-old boy who was diagnosed with pervasive developmental disorder at 4 years of age was able to perform activities of daily living independently and attend junior high school. However, he was admitted to our hospital with new-onset ataxia. Magnetic resonance imaging revealed a cerebellar tumor. After total tumor excision was performed, pathological analysis revealed medulloblastoma, which was treated initially with radiation therapy and then chemotherapy for 1 year. Rehabilitation was initiated 2 days post-surgery. We evaluated his communication abilities. He showed stereotypical behavior owing to the autism spectrum disorder；therefore, we performed low-intensity repetitive exercises. The functional independence measure score at discharge was 67/126 (motor 44/91, cognitive 23/35). We taught his teachers how to properly assist him, and he successfully returned to school post-discharge. Although this was a case in which the child had multiple disabilities, ataxia caused by the medulloblastoma aggravated his developmental disability. Thus, understanding the characteristics of communication and its strengths was vital in determining a treatment plan that enabled his return to school.
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We provided inpatient rehabilitation treatment and return-to-school guidance to a junior high school student with medulloblastoma and pervasive developmental disorder (autism spectrum disorder). Here we describe the rehabilitation treatment for patients with physical and developmental disabilities. A 13-year-old boy who was diagnosed with pervasive developmental disorder at 4 years of age was able to perform activities of daily living independently and attend junior high school. However, he was admitted to our hospital with new-onset ataxia. Magnetic resonance imaging revealed a cerebellar tumor. After total tumor excision was performed, pathological analysis revealed medulloblastoma, which was treated initially with radiation therapy and then chemotherapy for 1 year. Rehabilitation was initiated 2 days post-surgery. We evaluated his communication abilities. He showed stereotypical behavior owing to the autism spectrum disorder；therefore, we performed low-intensity repetitive exercises. The functional independence measure score at discharge was 67/126 (motor 44/91, cognitive 23/35). We taught his teachers how to properly assist him, and he successfully returned to school post-discharge. Although this was a case in which the child had multiple disabilities, ataxia caused by the medulloblastoma aggravated his developmental disability. Thus, understanding the characteristics of communication and its strengths was vital in determining a treatment plan that enabled his return to school.
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Objective:To investigate the values of Ki-67 expression level and 4 molecular types for risk classification of prognosis in patients with medulloblastoma (MB).Methods:A retrospective study of 92 MB patients who underwent surgery and were confirmed by postoperative pathology in the First Affiliated Hospital of Zhengzhou University from January 2009 to January 2018 was performed. The clinical data and survival data of the patients were collected and sorted out. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and the log-rank test was performed. Risk stratification of prognosis of patients was performed according to the Ki-67 expression level combined with molecular typing, the low-risk group had Ki-67 positive index ≤50% and WNT or SHH subtype, the medium-risk group had Ki-67 positive index ≤50% and GROUP 3 or GROUP 4 subtype, or Ki-67 positive index >50% and WNT or SHH subtype), and the high-risk group had Ki-67 positive index >50% and GROUP 3 or GROUP 4 subtype. The differences in OS and PFS among different risk groups were compared. A multivariate Cox proportional hazards model was used to assess factors affecting the survival of patients.Results:There were 50 cases (54.3%) with Ki-67 positive index ≤50% and 42 cases (45.7%) with Ki-67 positive index >50%. The 5-year PFS rate and OS rate of patients with Ki-67 positive index ≤50% were 46.9% and 63.1%, and patients with Ki-67 positive index >50% were 28.5% and 32.0%, there were statistical differences in PFS and OS between the two groups ( P values were 0.020 and 0.028). There were 16 cases (17.4%) of WNT subtype, 14 cases (15.2%) of SHH subtype, 40 cases (43.5%) of GROUP 3 subtype and 22 cases (23.9%) of GROUP 4 subtype, their 5-year PFS rates were 78.0%, 76.0%, 19.2% and 19.9%, respectively, and their 5-year OS rates were 82.1%, 76.0%, 40.2% and 0, respectively. MB patients with GROUP 3 or GROUP 4 subtype had poorer PFS and OS than patients with WNT or SHH subtype ( P values were 0.003 and 0.039). Ki-67 expression level and molecular typing were combined to carry out risk classification of prognosis. There were 12 cases (13.0%) in the low-risk group, 56 cases (60.9%) in the medium-risk group, and 24 cases (26.1%) in the high-risk group . There were statistical differences in PFS and OS among MB patients in low-, medium- and high-risk groups (both P < 0.001). Multivariate Cox regression analysis showed that radiotherapy and risk classification of prognosis as medium risk and low risk were independent protective factors for PFS (radiotherapy vs. no radiotherapy: OR = 0.263, 95% CI 0.124-0.556, P < 0.001; medium-risk group vs. high-risk group: OR = 0.069, 95% CI 0.008-0.581, P = 0.014; low-risk group vs. high-risk group: OR = 0.260, 95% CI 0.131-0.514, P < 0.001); radiotherapy and risk classification of prognosis as low risk were independent protective factors for OS (radiotherapy vs. no radiotherapy: OR = 0.221, 95% CI 0.097-0.503, P < 0.001; low-risk group vs. high-risk group: OR = 0.328, 95% CI 0.150-0.717, P = 0.005). Conclusions:The expression level of Ki-67 and 4 molecular types are related to the prognosis of MB patients. The combination of the two can be used to classify the prognosis risk of MB patients, which has reference significance for the prediction of prognosis of patients and the selection of individualized treatment plans.
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ABSTRACT Objective: To describe the clinical, demographic, anatomopathological, molecular, and survival characteristics of patients with medulloblastoma. Methods: Retrospective study based on patient information obtained from the review of medical records. Overall and event-free survival were analyzed using the Kaplan-Meier estimator, and the curves were compared by the log-rank test. Results: Among the patients investigated, 70 were male (66%), and age at diagnosis ranged from 2 months to 22 years. The most frequent signs and symptoms were headache (80.8%) and vomiting (75.8%). Regarding treatment, most patients (63.2%) underwent complete surgical resection, with a predominance of classic histology (63.2%). The 5-year overall survival rate was 67.9%, and the 10-year rate was 64.2%. Patients with molecular profile characteristic of the wingless (WNT) subgroup had a better prognosis, with 5-year overall survival of 75%. Conclusions: The clinical, demographic, anatomopathological, and molecular characteristics of patients with medulloblastoma described in the present study were mostly similar to those reported in the literature. Patients submitted to complete tumor resection had better clinical outcomes than those who underwent incomplete resection/biopsy. Patients classified as high-risk showed worse overall and event-free survival than those in the standard-risk group, and the presence of metastasis at diagnosis was associated with recurrence.
RESUMO Objetivo: Descrever as características clínicas, demográficas, anatomopatológicas, moleculares e de sobrevida de pacientes portadores de meduloblastoma. Métodos: Estudo retrospectivo, no qual as informações dos pacientes foram obtidas pela revisão dos prontuários médicos. Análises de sobrevida global e de sobrevida livre de eventos foram realizadas por meio da construção de curvas de Kaplan-Meier e a comparação entre as curvas foi feita pelo teste log-rank. Resultados: Entre os pacientes analisados, 70 pertenciam ao sexo masculino (66%) e a idade ao diagnóstico variou de dois meses a 22 anos. Os sinais e sintomas de maior frequência foram cefaleia (80,8%) e vômitos (75,8%). Em relação ao tratamento, a maioria (63,2%) dos pacientes foi submetida à ressecção cirúrgica total e apresentava como histologia predominante a forma clássica (63,2%). A taxa de sobrevida global em cinco anos foi de 67,9% e, em 10 anos, de 64,2%. Os pacientes com perfil molecular característico do subgrupo wingless (WNT) apresentaram melhor prognóstico, com sobrevida global em cinco anos de 75%. Conclusões: As características clínicas, demográficas, anatomopatológicas e moleculares dos pacientes com meduloblastoma descritas no presente estudo foram majoritariamente semelhantes às descritas na literatura. Pacientes submetidos à ressecção completa do tumor tiveram melhor evolução clínica do que aqueles com ressecção incompleta/biópsia. Pacientes estratificados como de alto risco apresentaram pior sobrevida global e livre de eventos do que o grupo standard e a presença de metástases ao diagnóstico se mostrou associada à ocorrência de recidiva da doença.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Young Adult , Cerebellar Neoplasms/pathology , Medulloblastoma/pathology , Cerebellar Neoplasms/surgery , Cerebellar Neoplasms/mortality , Retrospective Studies , Risk Assessment , Disease-Free Survival , Progression-Free Survival , Medulloblastoma/surgery , Medulloblastoma/mortalityABSTRACT
Congenital medulloblastoma is a rare brain tumor that appears in less than 1% of pediatric patients. Congenital medulloblastoma has a poor prognosis and should be suspected in patients with clinical manifestations of hyporeactivity, slow suction reflexes, and the presence of hydrocephalus. Herein we present the case of a 12-day-old female newborn who developed non-communicative hydrocephalus, hyporeactivity, and hyporeflexia. Magnetic resonance imaging of her brain showed a heterogeneous and cystic mass on the posterior cranial fossa. A suboccipital craniotomy was performed. The histopathologic analysis reported a congenital medulloblastoma. She remained in hospital until her death at 112 days old. This is one of the first case reports with clinical-radiological and pathological documentation. Awareness of this diagnosis can allow prenatal intervention, rendering a better prognosis. This case report exemplifies the importance of good prenatal follow-up.
Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Cerebellar Neoplasms/congenital , Medulloblastoma/congenital , Prenatal Diagnosis , Fatal OutcomeABSTRACT
Objective:To explore the value of the model based on multi-sequence magnetic resonance imaging (MRI) radiomics and clinical features in predicting molecular subtypes of pediatric medulloblastoma (MB).Methods:MRI imaging data and clinical data of 100 children with primary MB admitted in the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were analyzed retrospectively.Fifty children with primary MB were allocated to training cohort, and those of the other 50 were allocated to testing cohort by using simple random sampling method.In the training cohort, there were 5 cases of WNT-activated MB (Wingless, WNT), 5 cases of SHH-activated MB (Sonic hedgehog, SHH), 28 cases of non-WNT/non-SHH medulloblastoma Group3 (Group3), 12 cases of non-WNT/non-SHH medulloblastoma Group4 (Group4). The testing cohort included 11 cases of WNT, 3 cases of SHH, 24 cases of Group3 and 12 cases of Group4.The robust and non-redundant features were selected from 5 929 three-dimensional radiomic features extracted from the manually delineated tumor area, and Boruta algorithm was used to further select the optimal features.Based on the selected features, a random forest prediction model was constructed using the training cohort (50 cases), which was further used to evaluate the testing cohort (50 cases). Combined with radiomic features and clinical features, a joint random forest prediction, clinical-radiomic model was constructed.Results:A radiomic model containing 13 optimal radiomics features was used to predict molecular subtypes of MB.The area under curve(AUC) of receiver operating characteristic (ROC) curve for WNT, SHH, Group3 and Group4 MB cases in the testing cohort was 0.923 1, 0.673 7, 0.519 2 and 0.705 0, respectively.Incorporating clinical features into the radiomic model improved AUC for WNT and SHH at 0.944 1 and 0.819 1, respectively.Conclusions:The multi-sequence clinical radiomic model has a high predictive value for pediatric MB with the molecular subtypes of WNT and SHH, which provides decision-making supports for individualized diagnosis and treatment of pediatric MB.
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Objective:To analyze the clinical characteristics of children with medulloblastoma (MB) complicated with incomplete intestinal obstruction, and to explore the possible pathogenesis of intestinal obstruction in children with MB.Methods:A total of 409 children with MB admitted to the Department of Pediatrics of Beijing Shijitan Hospital, Capital Medical University from October 2014 to January 2019 were recruited into this study, and the clinical data of children with incomplete intestinal obstruction were collected and analyzed retrospectively.A comparison was performed between these children and those without intestinal obstruction who were treated at the same time.The chi- squared test and Logistic regression analysis were adopted to explore the pathogenesis of intestinal obstruction.The overall survival (OS) rate was calculated with the Kaplan-Meier method. Results:There were 11 cases of 409 children with MB complicated with incomplete intestinal obstruction in total, with the morbidity of 2.7%, they were all over 3 years old, with the median age of 8.7 years, and a male-to-female ratio of 4.5∶1.The incomplete intestinal obstruction in all cases occurred during the first cycle of maintenance chemotherapy after radiotherapy.All these patients could be reco-vered after conservative treatment, and no incomplete intestinal obstruction occurred in the subsequent chemotherapy.The results of Logistic regression analysis showed that there was a correlation between age and the development of incomplete intestinal obstruction ( P<0.05). The 2-year OS rate of MB patients complicated with incomplete intestinal obstruction was (87.5±11.7)%, and that of patients without incomplete intestinal obstruction during the same period was (92.8±1.6)%, which showed that the difference between the two group was not statistically significant ( P>0.05). Conclusions:Incomplete intestinal obstruction would occur in all MB patients within 2 months after radiotherapy, and children more than 3 years old are more prone to suffer from this disease.Therefore, it can be supposed that gastrointestinal mucosa was damaged under the double attack of radiotherapy and Vincristine, which slowed down the intestinal peristalsis, thus inducing intestinal obstruction.
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Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.
Subject(s)
Child , Humans , Cerebellar Neoplasms , Hodgkin Disease/radiotherapy , Hypothyroidism/prevention & control , Medulloblastoma/radiotherapy , Prospective Studies , ThyrotropinABSTRACT
One of the most invasive malignant tumors of the cerebellum is medulloblastoma, which is also the most common malignant tumor of the brain in children. Patients with a recurrent disease following initial treatment have the most unfavorable prognosis. The most common metastasis locations are the spine, the posterior fossa, the bones, and the supratentorium. Late medulloblastoma metastasis in the supratentorial intraventricular region is uncommon. We report here a case with supratentorial seeding.
Subject(s)
Humans , Female , Child, Preschool , Supratentorial Neoplasms/secondary , Medulloblastoma/surgery , Medulloblastoma/pathology , Neoplasm Metastasis , Recurrence , Supratentorial Neoplasms/pathology , Supratentorial Neoplasms/therapy , Medulloblastoma/diagnostic imagingABSTRACT
Brain tumors, the second common cancer following hematological malignancies account for up to 21% of all malignancies below 14 years of age. Medulloblastoma is a common form of Primitive neuro ectodermal tumor and likely arise from either the external granular layer (e.g., desmoplastic variant) or the subependymal matrix cells of the fourth ventricle (e.g., classic variant), or both. The clinical course of the disease is aggressive in children than in adults. The tumor can invade the CSF through the ventricles or even cause metastases to bones and lymph node. With the emergence of advanced technologies and treatment facilities, the morbidity and mortality of the disease is greatly improved with a five-year survival of up to 75%. However, the presence of disease in children <3 years or evidence of dissemination on diagnosis carries poor prognosis. Here we are discussing a case of 5-year-old girl who presented to OPD with vomiting for 1 month.
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Resumen: La tomografía por emisión de positrones/tomografía computada (PET/CT) por sus siglas en inglés, es una modalidad de imagen única que proporciona evidencia in vivo de actividades tanto bioquímicas como fisiológicas en diferentes órganos y estructuras del cuerpo. El meduloblastoma es el tumor maligno más frecuente del sistema nervioso central (SNC) en pacientes pediátricos, por este motivo el PET/CT juega un papel importante en el manejo de estos pacientes ya que proporciona información sobre el grado y extensión del tumor, así como a determinar el sitio adecuado para la toma de biopsia, valorar la respuesta al tratamiento y determinar el pronóstico del paciente. Existen diferentes radiofármacos para la evaluación de los tumores de sistema nervioso central, pero se ha estudiado que el 18F-FDG (flúor-2-fluoro-2-desoxi-D-glucosa) y el 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) nos ayudan a evaluar y dar seguimiento a pacientes con diagnóstico de meduloblastoma. El meduloblastoma tiene una sobreexpresión de transportadores de glucosa, principalmente tipo 1 y sobreexpresión de receptores de somatostatina predominantemente tipo 2, lo cual permite que exista una gran afinidad por estos radiofármacos.
Abstract: PET/CT (positron emission tomography/computed tomography, for its acronym in English) is a unique imaging method that provides in vivo evidence of both biochemical and physiological activities of the brain, spinal cord and tumors that involve these structures. Medulloblastoma is the most common malignant tumor of the central nervous system (CNS) in pediatric patients, so PET/CT plays an important role as it provides information on the grade and extent of the tumor, as well as to determine the appropriate site for the biopsy, assessing the response to the treatment and the patient's prognosis. There are different radiopharmaceuticals for the evaluation of central nervous system tumors, but 18F FDG (Fluor-2-fluoro-2-desoxy-D-glucose) and 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) have been studied to help us evaluate and follow up patients diagnosed with medulloblastoma. Medulloblastoma has an overexpression of glucose transporters, mainly type 1, and an overexpression of predominantly type 2 somatostatin receptors, which allows a high affinity for these radiopharmaceuticals.
ABSTRACT
Abstract Several factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Being a special atypical subtype of invasive carcinoma, it most frequently affects women of advanced age and represents 1 to 7% of all breast cancers. The reported case aims to show the rarity of the occurrence of desmoplastic medulloblastoma and mammary mucinous carcinoma in a young patient in a short period of time, in different sites, without direct anatomical attachment and without occurrence of metastasis. Initially, this patient had a desmoplastic medulloblastoma and was treated with lumpectomy and radiotherapy. After 13 months, the patient was diagnosed with a mucinous breast carcinoma, underwent mastectomy, adjuvant chemotherapy and is currently undergoing endocrinotherapy. We conclude, based on the metachronous characteristic of the neoplasia and clinical characteristics, that the patient is likely to have Li-Fraumeni syndrome, an autosomal dominant disease with mutation of the TP53 gene, which is the the main involved. Because the patient does not present all the characteristics of the phenotype of the syndrome, she can thus be classified as having Li-Fraumeni variant or Li-Fraumeni-like syndrome.
Resumo Diversos fatores desencadeiam o desenvolvimento de mutações genéticas que são responsáveis por originar uma neoplasia. O meduloblastoma é uma neoplasia cerebelar maligna e invasiva que acomete crianças e adultos jovens. O carcinoma mucinoso é um tipo de câncer de mama especial por ser um subtipo atípico de carcinoma invasivo, que acomete com maior frequência mulheres de idade avançada e representa entre 1 a 7% do total de neoplasias mamárias. O caso relatado tem como objetivo mostrar a raridade da ocorrência do meduloblastoma desmoplásico e carcinoma mucinoso mamário em uma paciente jovem em um curto período de tempo, em diferentes sítios sem ligação anatômica direta e sem ocorrência de metástase. Inicialmente, esta paciente possuía um meduloblastoma desmoplásico e foi tratada com tumorectomia e radioterapia. Após 13 meses, a paciente foi diagnosticada com carcinoma mucinoso de mama, sendo submetida a mastectomia, quimioterapia adjuvante e atualmente está sendo tratada com endocrinoterapia. Concluímos, com base na característica metacrônica da neoplasia e características clínicas, que a paciente apresenta a síndrome de Li-Fraumeni, doença autossômica dominante com mutação do gene TP53, que é o principal gene envolvido nesta síndrome. Por não apresentar as características completas do fenótipo da síndrome, a paciente pode assim ser classificada como portadora de uma variante da síndorme de Li-Fraumeni ou síndrome do tipo Li-Fraumeni.
Subject(s)
Humans , Female , Adult , Li-Fraumeni Syndrome/diagnosis , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Magnetic Resonance Imaging , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/pathology , Cerebellar Neoplasms/diagnostic imaging , Li-Fraumeni Syndrome/genetics , Combined Modality Therapy , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/pathology , Diagnosis, Differential , Medulloblastoma/diagnosis , Medulloblastoma/genetics , Medulloblastoma/pathology , Medulloblastoma/diagnostic imaging , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathologyABSTRACT
La población pediátrica es, de lejos, la más afectada por las lesiones del cuarto (IV) ventrículo. La gran mayoría presentan un patrón radiológico similar; actualmente, con las secuencias de difusión, espectroscopia y mapas de ADC, se puede inferir la compatibilidad de los hallazgos visualizados con alguna de las patologías que se revisarán en el presente trabajo
The pediatric population is by far the most affected by lesions of the fourth (IV) ventricle. The vast majority present a similar radiological pattern, for which today, with the diffusion sequences, spectroscopy and ADC maps, it can be inferred that the visualized findings are more likely compatible with some of the pathologies that we will review later