Desmoplastic Medulloblastoma Research Articles

Effects of cognitive-motor intervention for pediatric posterior fossa tumor survivors: results of a pilot study.

The purpose of this prospective pilot study was to evaluate the feasibility and effects of cognitive-motor intervention on the cognitive and motor abilities of pediatric survivors of posterior fossa tumors. The study involved patients aged 7 to 18 years with cognitive deficits who had completed primary treatment for posterior fossa tumors. 25 participants (Mage=11.3 ± 2.93, 64% male; 17 medulloblastoma, 1 ependymoma, 1 desmoplastic medulloblastoma, 6 piloid astrocytoma; 22 in remission (Mmonths =45), 3 in stabilization (Mmonths=49)) were recruited from the Research Institute for Brain Development and Peak Performance. The intervention consisted of two phases with a 3-month break for home training, and a total duration of 6 months. Each phase lasted 7 weeks and included two assessment procedures (pre- and post-intervention) and 10 training sessions over a period of 5 weeks (two 3-hour sessions per week). At baseline and pre- and post-intervention, all participants underwent a battery of cognitive and motor tests. Each training session included gross motor training (GMT), graphomotor training (GT), and cognitive-motor training (CMT). Statistical analysis was performed using the Friedman test for repeated measures and post-hoc Durbin-Conover test. The results indicated significant improvements in visuospatial working memory, visual attention, eye-hand coordination, semantic verbal fluency, auditory-motor synchronization, reaction time, and a decrease in the rate of ataxia. These improvements remained stable even in the absence of direct intervention. The findings demonstrate positive effects and feasibility of the intervention and suggest the need for further research in this area including randomized controlled feasibility studies with a larger sample.

Brain cancer in the ovary? A paediatric immature teratoma showing a focus with morphology of nodular desmoplastic medulloblastoma

Brain cancer in the ovary? A paediatric immature teratoma showing a focus with morphology of nodular desmoplastic medulloblastoma

Late effects of medulloblastoma treatment: multidisciplinary approach of survivors.

Medulloblastoma is one of the brain tumors with increased life expectancy due to improvements in treatment approaches. Besides the promising results, various undesirable effects can be encountered. This study's aim is to review long-term follow-up outcomes of our cases with medulloblastoma. Age at diagnosis, histological type of medulloblastoma, resection extension, chemotherapy and radiotherapy schemes, follow-up duration, and endocrinological, neuropsychiatric, cardiological, auditory, and visual examination results were evaluated in 20 patients diagnosed between 2007 and 2018 and followed 5 years and more. Twenty of 53 patients were included to the study. Eleven (55%) were male. Mean age at diagnosis was 6.95 years; mean age at the time of the study was 14 years. Mean follow-up time was 8.95 years. In terms of surgery, 14 (70%) were gross total, 1 (5%) was near total, and 2 (10%) were subtotal resection. In histopathological examination, 14 (70%) were classical medulloblastoma, 4 (20%) were desmoplastic medulloblastoma, and 1 (5%) was anaplastic medulloblastoma. With regard to endocrinological evaluation, 15 (75%) patients had hypothyroidism, 5 (25%) had growth hormone deficiency, 7 (35%) had clinical growth hormone deficiency, and 5 (25%) had sex hormone disorders. In neuropsychiatric examination, 11 (55%) patients had neurological sequelae, 18 (90%) patients had psychiatric issues, and 14 (70%) patients had two or more neuropsychiatric problems simultaneously. One (5%) patient had mitral valve insufficiency. Twelve patients (60%) had hearing loss. According to visual examination, 6 (30%) patients had refraction problem, 4 (20%) had cataract, and 1 (5%) had dry eye. Careful monitoring of long-term side effects is important for improving the quality of life of medulloblastoma patients. Besides endocrinological and other somatic sequelae of the disease and treatment, increased neuropsychiatric problems showed us that only cure is not the issue while treating childhood medulloblastoma.

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol

PurposeMedulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients.MethodsAdult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed.ResultsForty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn’t statistically significant.ConclusionCombined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

MEDB-41. Identifying a subgroup of patients with early childhood sonic hedgehog-activated medulloblastoma with unfavorable prognosis after treatment with radiation-sparing regimens including intraventricular methotrexate

PURPOSE/METHODS: Clinical and molecular risk factors in 142 patients <5 years with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were investigated. Patients were diagnosed between 1992 and 2020 and treated with radiation-sparing approaches, 131 with intraventricular methotrexate. 14 patients with metastatic disease received high-dose chemotherapy. DNA methylation profiles of 77 sonic hedgehog (SHH)-activated medulloblastoma were reclassified according to the Heidelberg Brain Tumor Classifier Version 12.3. RESULTS: While metastatic disease or incomplete resection did not impact progression-free survival (PFS) and overall survival (OS), patients with MBEN had superior outcomes to DMB (5-year PFS 93% vs 71%, p=0.004; 5-year OS 100% vs 90%, p=0.026). Older patients had less favorable PFS (5-year PFS [>3 years] 47% vs 85% [<1 year] vs 84% [1-3 years], p<0.001). No TP53 mutations were detected (n=47). DNA methylation classification identified three subgroups: SHH-1v12.3 (n=39), SHH-2v12.3 (n=19), and SHH-3v12.3 (n=19), with distinct cytogenetic profiles (chromosome 2 gains in SHH-1v12.3, very few alterations in SHH-2v12.3, and chromosome 9q losses in SHH-3v12.3), age profiles (median age [years] SHH-1v12.3: 1.7, SHH-2v12.3: 0.9, SHH-3v12.3: 3.0, p<0.001), and histological distribution (SHH-2v12.3: 74% MBEN, SHH-1v12.3/SHH-3v12.3: 77%/79% DMB, p<0.001). PFS was more unfavorable in patients with SHH-3v12.3-medulloblastoma (5-year PFS 53% vs 86% [SHH-1v12.3] vs 95% [SHH-2v12.3], p=0.002), which remained the only risk factor on multivariable Cox regression for PFS. OS was comparable (5-year OS 94% [SHH-3v12.3] vs 97% [SHH-1v12.3] vs 100% [SHH-2v12.3], p=0.6). 8/9 patients with SHH-3v12.3-medulloblastoma received radiotherapy at relapse (6 craniospinal, 2 local [1 Gorlin syndrome, 1 BRCA2 germline mutation], 1 no radiotherapy [Gorlin syndrome]). CONCLUSION: We identify patients with an increased risk of relapse when treated with radiation-sparing approaches among children with early childhood SHH-medulloblastoma. If these tumors differ from SHH-3-medulloblastoma typically described in older children remains to be verified. Treatment recommendations need to consider cancer predisposition syndromes.

MEDB-34. A very rare case: medulloblastoma relapse with bone marrow infiltration in a toddler

We report about a female toddler congenitally deaf and diagnosed with a non-metastatic desmoplastic medulloblastoma (SHH activated, TP53-wt, variant in LDB1 gene). No tumor predisposition syndrome was found. After complete tumor resection the patient was treated according to I-HIT-MED-Guidance protocol. Five months later an asymptomatic localised relapse (same histology, PTEN frameshift deletion, TERT mutation, LDB1 mutation) detected by routine MRI was treated by complete resection, craniospinal irradiation and an antiangiogenic regimen adapted from the MEMMAT scheme including fenofibrate, thalidomide, celecoxib, topotecan, temozolomide, bevacizumab and intraventricular cytarabine. Before start of systemic treatment blood cell counts were normal. In the second cycle we had to interrupt chemotherapy due to a leukopenia while continuing the antiangiogenic treatment. In order to avoid relevant bone marrow toxicity chemotherapy doses were reduced. Nevertheless we had to stop the fourth cycle because of a severe pancytopenia. Same time the girl presented with fever, neck and leg pain. A full blood count showed: hemoglobin 6.92 g/dl, leukocytes 640/µl, platelets 8,000/µl. Suspecting an infection supported by the presence of a high CrP value of 230 mg/l the patient was treated with i.v. antibiotics. MRI showed an unspecific retropharyngeal soft tissue augmentation, a pleural effusion and high T2 signals in multiple vertebral bodies but no central tumor relapse. The bone marrow diagnostics revealed a diffuse medulloblastoma cell infiltration with the known PTEN frameshift deletion and LDB1 mutation. The liquor was tumor-cell free. We report on an extremely rare case of an early local relapse of desmoplastic medulloblastoma progressing to a diffuse bone marrow infiltration in a toddler. The girl died due to therapy resistance 9 weeks after bone marrow relapse. It remains unclear whether the fatal course was related to the hereditary deafness syndrome and the molecular alterations of the tumor.

LINC-11. Intrathecal methotrexate in a young child with medulloblastoma with extensive nodularity. An alternative to intra-ventricular route in Low and Middle Income Countries?

BACKGROUND: In places where determination of molecular subgrouping of Medulloblastoma is not available, histology remains standard for risk stratification and treatment. Young children with medulloblastoma treated with craniospinal irradiation show a negative impact in neurocognitive functions, thus avoiding radiation in this specific population is encouraged. High dose chemotherapy and stem cell rescue have been internationally used as a strategy to spare radiation in infants and young children with Medulloblastoma. German HIT protocol (SKK) reported a PFS 85±8 % and good cognitive outcome in patients with Desmoplastic Medulloblastoma treated with intra-ventricular (i.vtr.) methotrexate (MTX). SKK protocol includes 36 i.vtr. administrations of MTX through a subcutaneous reservoir. Complications related to the use of this kind of reservoir could be due to the lack of experienced staff. METHODS: We report a patient with localized Medulloblastoma with extensive nodullarity (MBEN) treated as per SKK using intrathecal route instead of i.vtr MTX. A 2.5 year old boy was diagnosed with MBEN, surgery was complete and no shunt was required. Spinal MRI and CSF cytology were negative. Patient received 3 cycles of SKK protocol and 2 cycles of modified SKK. During the first 3 cycles he received one dose of intrathecal MTX 8mg on weeks 1, 3, 5 and 7 (12 doses in all). Patient remains free of disease 2 years after chemotherapy completion and without signs of leukoencephalopathy on T2 weighted cranial MRI. DISCUSSION: Intrathecal administration of MTX is commonly used for the treatment of Acute Lymphoblastic Leukemia, the most common childhood cancer. Staff in Low and Middle Income Countries (LMIC) may be better trained for such procedure than using a ventricular access device. This strategy could be considered when using SKK protocol in selected young children with Demoplastic Medulloblastoma and MBEN in LMIC where centers with enough experience with ventricular access device placement and handling are scarce.

Survival Study in Pediatric Patients with Medulloblastoma in a General Hospital in Tehran, Iran

Abstract Brain tumours are the most common solid tumours that afflict the pediatric population. Me-dulloblastoma (MB) is the most common malignant brain tumour in children, constituting nearly 20% of all pediatric brain tumours. This study is an evaluation of overall survival rate of pediatric MB tumour patients after one year, three years, five years, and ten years according to case studies. From 22 June 2009 to 19 December 2019, a total of 22 patients ranging in age from 1 to 14 years old underwent tumour removal. These patients were followed to determine survival rate. Tumours were classified into three pathological subtypes: The first was classic MB, the second was desmoplastic nodular MB and MB with extensive nodularity, and the third was large cell and anaplastic MB. Patients who were 3 years old or older had a better survival rate than younger patients (log-rank test; p = 0.01). The survival probability in the older children group (55%) was significant compared to the group of younger children (29%). The Kaplan–Meier survival curves of the patients were significantly different. The ten-year survival rates in the average- and high-risk groups were 64.4% and 86.0%, respectively. After a follow-up of 120 months (median range = 60 months), recurrence or progression was observed in 22 patients and 15 patients were still alive. The estimated 10-year overall survival rates for all patients were 49.36 ± 38.33. MB patients’ survival rate was quite good in our hospital. More than half of the patients, most of whom had large cell anaplastic and classic type MB, survived the 10-year follow-up period without any problems.

Defining the Spectrum, Treatment and Outcome of Patients With Genetically Confirmed Gorlin Syndrome From the HIT-MED Cohort.

Gorlin syndrome is a genetic condition associated with the occurrence of SHH activated medulloblastoma, basal cell carcinoma, macrocephaly and other congenital anomalies. It is caused by heterozygous pathogenic variants in PTCH1 or SUFU. In this study we included 16 patients from the HIT2000, HIT2000interim, I-HIT-MED, observation registry and older registries such as HIT-SKK87, HIT-SKK92 (1987 – 2020) with genetically confirmed Gorlin syndrome, harboring 10 PTCH1 and 6 SUFU mutations. Nine patients presented with desmoplastic medulloblastomas (DMB), 6 with medulloblastomas with extensive nodularity (MBEN) and one patient with classic medulloblastoma (CMB); all tumors affected the cerebellum, vermis or the fourth ventricle. SHH activation was present in all investigated tumors (14/16); DNA methylation analysis (when available) classified 3 tumors as iSHH-I and 4 tumors as iSHH-II. Age at diagnosis ranged from 0.65 to 3.41 years. All but one patient received chemotherapy according to the HIT-SKK protocol. Ten patients were in complete remission after completion of primary therapy; four subsequently presented with PD. No patient received radiotherapy during initial treatment. Five patients acquired additional neoplasms, namely basal cell carcinomas, odontogenic tumors, ovarian fibromas and meningioma. Developmental delay was documented in 5/16 patients. Overall survival (OS) and progression-free survival (PFS) between patients with PTCH1 or SUFU mutations did not differ statistically (10y-OS 90% vs. 100%, p=0.414; 5y-PFS 88.9% ± 10.5% vs. 41.7% ± 22.2%, p=0.139). Comparing the Gorlin patients to all young, SHH activated MBs in the registries (10y-OS 93.3% ± 6.4% vs. 92.5% ± 3.3%, p=0.738; 10y-PFS 64.9%+-16.7% vs. 83.8%+-4.5%, p=0.228) as well as comparing Gorlin M0 SKK-treated patients to all young, SHH activated, M0, SKK-treated MBs in the HIT-MED database did not reveal significantly different clinical outcomes (10y-OS 88.9% ± 10.5% vs. 88% ± 4%, p=0.812; 5y-PFS 87.5% ± 11.7% vs. 77.7% ± 5.1%, p=0.746). Gorlin syndrome should be considered in young children with SHH activated medulloblastoma, especially DMB and MBEN but cannot be ruled out for CMB. Survival did not differ to patients with SHH-activated medulloblastoma with unknown germline status or between PTCH1 and SUFU mutated patients. Additional neoplasms, especially basal cell carcinomas, need to be expected and screened for. Genetic counselling should be provided for families with young medulloblastoma patients with SHH activation.

OMIC-08. COMPOUND HETEROZYGOSITY OF POLE AND PMS2 LEADS TO CMMRD-LIKE PHENOTYPE- “POLYNCH” SYNDROME

Mono-allelic germline pathogenic variants (PV) in one of the mismatch repair (MMR) system genes cause Lynch syndrome, associated mainly with colon and endometrial cancer in adults. Germline PVs in DNA polymerase epsilon (POLE) are associated with a dominantly inherited syndrome which confers risk for polyposis and colon cancer. Brain tumors have been described as part of Lynch syndrome and POLE associated syndrome, mostly in adults. Constitutional mismatch repair deficiency (CMMRd) is caused by bi-allelic mutations in the MMR genes, associated with multiple café au lait macules (CAMs) and high incidence of pediatric cancer, including brain tumors. Both MMRD and POLE associated tumors have high tumor mutation burden (TMB), however, microsatellite status is usually unstable in MMR tumors, and stable in POLE. Germline POLE and CMMRd tumors have different mutational signatures, as is signature of MMR tumors with secondary somatic POLE. We describe a 4.5 y/o male who presented with a grossly metastatic SHH-activated, TP53-wildtype desmoplastic medulloblastoma. Physical examination was noted for CAMs. Family history was positive for a heterozygous POLE variant with variable clinical manifestations. Immunohistochemistry of the tumor showed loss of nuclear expression of the MMR gene PMS2, specifically in tumor cells. Analysis showed exceptionally high TMB (up to 276 Mut/Mb) and both the MMR and the POLE signatures. Germline analysis detected the familial POLE variant as well as a de novo heterozygous PMS2 PV. The phenotype of the patient together with the tumor’s features, led us to classify this case as a CMMRd-like. The patient had a partial response to intensive chemotherapy and is currently on immunotherapy without radiation. Collectively, our data suggest that heterozygous simultaneous germline mutations in MMR and polymerase genes can lead to novel “POLYNCH syndrome” that manifests with an ultra-hypermutant aggressive tumor and requires appropriate treatment and surveillance.

MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT

OBJECTIVETo avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy.PATIENTS AND METHODSEighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71).RESULTSPatients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) (n=42) had 93% 5-year PFS, 100% 5-year OS and 93% 5-year CSI-free survival. Patients with CMB/LCA (n=45) had 37% 5y-PFS, 62% 5y-OS and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in CMB/LCA patients. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH_INF subgroup. Group 3 patients (5y-PFS 36% [n=14]) relapsed more frequently than SHH_INF (5y-PFS 93% [n=28]) or Group 4 patients (5y-PFS 83% [n=6], p<0.001). SHH_INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I 73% vs. iSHH-II 83%, p=0.25, n=99). Mean IQ was 90 (radiotherapy-free survivors) vs. 74 (patients that received CSI) [p=0.012].CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH-subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in non-WNT/non-SHH CMB/LCA patients was not improved by local radiotherapy. Survival was more favorable in patients with Group 4 than in patients with Group 3 medulloblastoma.

Production of a SCID mouse model of medulloblastoma to explore the therapeutic value of targeting tumor driver genes.

Tumor driver genes are genes where structural or sequence mutations confer a selective advantage for cancer cells. The individualized targeting of tumor driver genes has become a topic of interest for tumor treatment. The prognosis for medulloblastoma (MB), a common type of malignant intracranial tumor found in children, is poor. The tumor driver genes and the corresponding targeted drugs remain to be studied. The present study analyzed tumor driver genes from tumor tissue and peripheral blood from one patient with nodular desmoplastic MB with Sonic Hedgehog activation and screened targeted drugs for the tumor driver genes. Additionally, MB tissue was successfully implanted into the SCID mouse which were then used for subsequent drug screening. The present study explored novel treatments for MB from the perspective of tumor driver genes, and may provide new ideas for choosing individualized targeted therapies for patients with MB.

MAGNETIC RESONANCE IMAGING FEATURES OF PEDIATRIC MEDULLOBLASTOMA IN RELATION TO PATHOLOGICAL SUBTYPES

Medulloblastma (MB) is a highly malignant (WHO grade IV), primitive cerebellar tumor of neuroectodermal origin. Medulloblastomas have been classified, based on histopathological, biological, and clinical characteristics, into classic medulloblastoma (CMB), desmoplastic nodular medulloblastoma (DNMB), medulloblastoma with extensive nodularity and anaplastic/large cell medulloblastoma.Medulloblastoma shows heterogenous tumor features in each subtype. Based on these heterogeneity, magnetic resonance imaging (MRI) could differentiate pathological subtypes according to each imaging features. This study aimed to assess the relation between Magnetic Resonance imaging features of pediatric medulloblastoma and pathological subtypes to improve treatment outcomes of the disease.All patients were subjected to the following:o History taking.o Thorough clinical examination.o Conventional MRI study of the brain.o Susceptibility-weighted imaging of the brain with post processing phase image. The study was applied on a 1.5 Tesla Magnetom Avanto Siemens (left handed system) machine using conventional MRI sequences in addition to DWI. Imaging evaluation depended on tumor location, tumor enhancement and degree of tumor restriction on DWI. Histo-pathology remains the gold standard in differentiating subtypes, however we can use MRI in early prediction of the subtypes and early planning for their management, regardless MRI very important role in post-surgical assessment and follow up.

Survival in adult and pediatric patients with medulloblastoma: A 2018 SEER-based analysis.

e14529 Background: Medulloblastoma (MB) is a malignant neuroectodermal tumor accounting for 30% of pediatric and only 1% of adult brain tumors. In previous studies comparing survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database no difference has been found. However, diagnostic subgroup analyses have been limited. Methods: We examined survival in children (age 0-19) and adults (20-79) coded as MB in the 2018 SEER database (2000-2016). We used Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n = 1,728). ICD 9473, supratentorial PNET (sPNET, n = 97) is biologically distinct and therefore it was analyzed separately. Results: We found that 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n = 488, 79.1%) (HR = 0.97, CI: 0.79 – 1.17, p = 0.50). Furthermore, subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n = 222, p = 0.09), large cell MB (n = 73, p = 0.46), or MB NOS (n = 1330, p = 0.10). Yet, children with sPNET had improved 5-year survival (n = 65, 72.3%) compared to adults (n = 29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p = 0.02,). These findings indicate that while survival in patients with MB is similar across age groups, children with sPNET have improved outcomes. Conclusions: In summary, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment (chemotherapy or radiation). For sPNET, the apparent improved outcomes for children merit further detailed investigation and will be re-evaluated using the new 2016 World Health Organization classification.

Paediatric desmoplastic medulloblastoma – Surgical treatment, adjuvant therapy, outcome survival (case series study)

Paediatric desmoplastic medulloblastoma – Surgical treatment, adjuvant therapy, outcome survival (case series study)

СONGENITAL MEDULLOBLASTOMA: PRENATAL AND POSTNATAL MRI FINDINGS

Background . Medulloblastoma represents the most common malignant pediatric brain neoplasm accounting for 15–20 % of brain tumors in childhood. However, congenital medulloblastomas are extremely rare and mostly diagnosed postnatally. to the best of our knowledge, only one case was reported where this tumor was detected antenatally by ultrasound. MRI features of fetal medulloblastoma have not been described to date. M aterial and methods. We present MRI findings of fetal medulloblastoma progression from the 31 st week of gestation until 5.5 months of postnatal life. Histopathological, genetic and molecular parameters were studied. after partial tumor removal and chemotherapy, MRI images demonstrated complete tumor response to therapy. the follow-up period was 1.5 years. Results . Fetal MRI performed on the 31st gestational week revealed a midline cerebellar lesion of ≤2 cm in size with minor t2 hypointensity and t1 hyperintensity. additionally, a restricted diffusion on aDc-maps depicted the lesion most conspicuously. the advantage of DWI over traditional t1- and t2-VI was associated with a relatively lower diffusion coefficient in the tumor (0.63×10 –3 mm 2 /s) compared with the surrounding medulla (0.98×10 -3 mm 2 /s). Histopathological, genetic and molecular studies revealed desmoplastic medulloblastoma with high nodularity, cMYc/NMYc-negative, МхR+. combined treatment using 5 cycles of HIt-sKK chemotherapy by HIt MED 2014 protocol (version 2017) in a highly specialized pediatric oncology center resulted in a stable tumor remission . Conclusion. Fetal MRI with DWI is the most effective approach for early detection of congenital medullobastoma. Early prenatal diagnosis, as well as postnatal verification and classification of congenital medulloblastomas is critical for timely treatment planning and good outcome.

Correlation between MRI characteristics of medulloblastoma with histopathological subtypes and 2-year survival.

Objectives:The objective of this study is to describe the imaging features of medulloblastoma (MB) and correlate the MR characteristics with the different histological subtype of MB with 2-year survival.Materials and Methods:This is a retrospective descriptive study. A total of 29 patients diagnosed with MB from January 2005 to December 2015 were included in this study. The MRI brain and spine studies of these patients were retrieved and reviewed by a pediatric radiologist and a neuroradiologist independently, both blinded from the histological type of the MB. The HPE slides were also retrieved and reviewed by a pathologist.Results:80% of desmoplastic MB showed the presence of intracranial leptomeningeal seeding and 57.1% of anaplastic MB showed the presence of necrosis. The presence of intracranial leptomeningeal seeding (P = 0.002) and necrosis (P = 0.019) was predictive of the histological subtypes. There is a significant correlation between the enhancement pattern and the 2-year outcome (P = 0.03) with 6 out of 8 patients whose tumors showed minimal enhancement having disease progression within 2 years. A significant correlation was also seen between the presence of necrosis with a poorer outcome (P = 0.03) and between the HPE subtype and 2-year outcome (P = 0.03) with anaplastic MB having the poorest prognosis.Conclusion:MR imaging features of intracranial leptomeningeal seeding and the presence of necrosis were correlated with a specific histologic subtype of MB. The enhancement pattern as well as necrosis correlated with 2-year poorer outcome of the disease.

Adjuvant chemotherapy to improve survival in average-risk adult medulloblastoma patients: Long-term results.

2037 Background: Medulloblastoma is extremely rare in adults and, therefore, it is difficult to accrual patients in clinical trials. Radical surgery and radiotherapy (RT) provide a significant control of disease. Nevertheless, about 25% of average-risk patients have a relapse and die because of disease progression. The role of chemotherapy (CT) after standard RT for average-risk adult patients remains controversial. Methods: We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016. Median age was 29 years (range 16-61), M/F ratio was 26 (54.2%)/22 (45.8%). Fifteen patients had classic medulloblastoma (31.3%), 15 patients had desmoplastic medulloblastoma (31.3%), 5 patients had extensive nodularity (10.4%) and 2 patients had large cells/anaplastic histology (4.2%). The patients were homogeneously distributed in the two groups: 24 (50%) received adjuvant RT alone and 24 (50%) received RT + CT that consisted in a platinum-etoposide based combination. Results: After a median follow-up of 12.5 years, CT increases progression-free survival rate at 15 years (PFS-15 82.3 ± 8.0% in RT-CT group vs. 38.5% ± 13.0% in RT group p = 0.05) and overall survival rate at 15 years (OS-15 89.3% 7.2% vs. 52.0% 13.1%, p = 0.02). Among patients receiving CT, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia; 6 cases of G3 neutropenia (25%) and 3 cases of G4 neutropenia (13%), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%). Conclusions: Our study with a long follow up period suggests that adding adjuvant chemotherapy to RT might improve PFS and OS in average-risk adult medulloblastoma patients.

Multi-nodular Desmoplastic Medulloblastoma in a Child: A Rare Radiological Physiognomy

Introduction: Nodular desmoplastic variant of medulloblastoma although very common, can present with very challenging radiological feature that mimics others lesions in the inferior and lower vermis in children. We present a case of rare radiological appearance of desmoplastic medullobastoma. Case Presentation: A one year and nine months old male presented with unstable walking and projectile vomiting of two weeks’ duration. He was apparently walking well prior this illness. The vomiting was usually in the morning and associated with headaches. Radiological imaging revealed very unusual masses in the cerebellum vermin region with obvious bilateral ventricular enlargement as well as the third ventricle, indicating hydrocephalus. Surgery was successful carried out and microscopic as well as immunohistochemistry confirmed desmoplastic medullobastoma. Conclusion: Desmoplastic medulloblastoma although not very rare can be very problematic in terms of radiological diagnosis. We are of the option that our imaging finding will throw more light on the radiological features of this tumor.

Primary desmoplastic medulloblastoma of the ovary: report of a case

Primary desmoplastic medulloblastoma of the ovary: report of a case