Adult Medulloblastoma Research Articles

P23 * MANAGEMENT AND OUTCOME OF ADULT MEDULLOBLASTOMAS: ARE WE FOLLOWING RECOMMENDED GUIDELINES?

INTRODUCTION: Medulloblastomas are very rare tumours in adults compared to children. Clinical pathways for medulloblastoma are well established for children. The purpose of this study was to analyse clinical outcome of adult medulloblastomas. METHOD: Single centre retrospective case review from 1995 - 2012. Clinical, radiological and neuropathological data were gathered and analysed. RESULTS: 13 patients (9 male, 4 female) were identified; median age 24 years (range: 17-64). Annual incidence in our region is 0.2 cases per million per year. Headache was the most common presenting symptom, mean duration before diagnosis was 8 weeks. Tumours were located in lateral cerebellum (n = 10) and vermis (n = 3). All patients had localized disease at presentation and underwent surgical resection and tissue biobanking followed by cranio-spinal irradiation. Three patients also received adjuvant chemotherapy. MRI spine and CSF analysis were only completed after surgery in all cases. Median follow-up was 32 months (range: 3-126). Mean overall survival (OS) was 92 months (95%CI 62-122 months) with 5 year OS of 55%. Progression free survival (PFS) was 77% with median follow-up of 32 months falling to 56% at 5 years. Three of 13 cases (23%) recurred at a mean of 38 months. All patients who received adjuvant chemotherapy remained recurrence free. CONCLUSION: Diagnosis of adult medulloblastoma is often only made after surgery. Staging MRI should occur pre-operatively to minimize artifact. In our series, surgery and craniospinal radiotherapy was the primary treatment and the role of chemotherapy could be further beneficial. There may be a role for regional management of these very rare tumours.

Abstract 543: Identification of lincRNAs in the HOX domain in adult medulloblastoma by microarray analysis

Abstract Introduction: Medulloblastoma (MB) is defined at molecular level into at least four major subtypes: WNT, SHH, Group C and Group D. Previously, we have demonstrated that levels of HOX transcripts in medulloblastoma specimens correlate with their malignant phenotype. HOX gene regulation involves long noncoding RNAs (lncRNAs), the epigenetic activator of the Trithorax group (TrxG) and the epigenetic repressors of the polycomb group (PcG). Therefore, we performed transcriptoma profiling in adult MBs and normal cerebellum samples to elucidate potential epigenetic regulatory mechanisms involved in tumor progression. Methodology: We analyzed frozen tumor samples from 5 MB adult patients with different tumor subtypes and with ages ranging from 18-33 years and 3 control cerebellar tissues obtained from infants with ages from 23 weeks to six months. RNA was isolated and integrity was assessed using the Agilent 2100 Bioanalyzer. Two colors microarray-based gene expression analysis was performed according to the manufacture's instructions. Quality control and quantile normalization were done using R. Hierarchical clustering was performed using subsets of genes identified in previous studies analysis to classify the tumor samples. There was also considerable variability among the control samples which was separately studied using bootstrap analysis and rank based tests. Results The hierarchical clustering of samples considering the 200 most variable genes, followed by molecular analyses suggests the existence of at least three groups among the tumor specimens analyzed. Hierarchical clustering of samples using the Hox genes demonstrates that the HOX pattern expression might be related to defined medulloblastoma molecular subgroups. For example, in SHH, group C and group D, HOXA3, HOXA6 and HOXB4, are upregulated while HOXC4 is increased in the Wnt group. Interestingly, in control samples these HOX genes showed little variation. Hierarchical clustering of tumor samples using 1414 long intergenic noncoding RNAs (lincRNAs) from the chromosomal (7, 17, 12 and 2) of HOX genes shows similar grouping between control and tumor samples. Moreover five lincRNAs, whose distance from HOX is comparable with the distance from HOTAIR to HOX, were identified: three of these five are in HOX C, one in HOX B9 and another close to HOX D3 genes with the distance varying from 3,800 - 11,819 bp from HOX genes. In our analysis, HOTAIR showed little expression across the samples and HOX regulators (TrxG and PcG complexes) displayed variation in expression level among samples. We found that there is considerable heterogeneity among the control samples used in this study. Conclusion: This study suggests that lncRNAs might affect the expression of HOX gene products in adult medulloblastoma. Validation analyses and genetic studies are undergoing to elucidate the possible mechanisms of action of this class of ncRNAs during MB progression. Note: This abstract was not presented at the meeting. Citation Format: Julia B. Veiga, Ricardo Bonfim Silva, Kuruvilla Joseph Abraham, Daniela B. Pretti da Cunha Tirapelli, Fernando Silva Ramalho, Gerson Chadi, Jéssica Ruivo Maximino, Dimas B. Tadeu Covas, Angelo A. Cardoso, Carlos Gilberto B. Carlotti, Aparecida M. Fontes. Identification of lincRNAs in the HOX domain in adult medulloblastoma by microarray analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 543. doi:10.1158/1538-7445.AM2014-543

Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of CNS oncology

Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of CNS oncology

Patterns of care in adult medulloblastoma: results of an international online survey.

The literature on medulloblastoma in adults is generally limited to case reports and retrospective series, and there is no accepted standard of care. The Cooperative Trials Group for Neuro-Oncology (COGNO) sought to determine the range and consistency of clinicians' approaches to management as a basis for future trials. We aimed to identify current treatment strategies for adult medulloblastoma through an online survey launched at the 2012 Society of Neuro-Oncology meeting and by email invitation. Clinicians who had treated at least one adult patient with medulloblastoma, primitive neuroectodermal tumor (PNET), or pineoblastoma in the preceding year were asked about their most recent patient and invited to discuss their approach to a typical clinical scenario. Between November 2012 and January 2013, 45 clinicians (11 medical oncologists, 8 radiation oncologists, 5 pediatric oncologists, and 21 others) from Australia (24), United States (3), Europe (4) and other countries (14) completed the survey. Responding clinicians had treated 54 cases in the past 12 months. The most common histological type was medulloblastoma (64%), then PNET (20%). Most patients were male (68%), and had high-risk disease (65%). Complete surgical resection in 56 and 32% had molecular testing. Radiotherapy was predominantly cranio-spinal (92%) and given mostly post-resection (80%). Combination chemotherapy was more common than single-agent chemotherapy. The choice of chemotherapy varied considerably. There is substantial variation in the treatment of adult medulloblastoma, most pronounced in the choice of chemotherapeutic agents, highlighting the need for further collaborative research to guide evidence-based treatment strategies.

Shedding light on adult medulloblastoma: current management and opportunities for advances.

Few evidence-based guidelines are available for the treatment of adult medulloblastoma, an extremely rare disease. Therapeutic regimens, typically modeled following pediatric protocols, consist of surgical resection followed by radiotherapy with or without adjuvant chemotherapy. Because of the rarity of this disease in adults, any treatment undertaken is based mainly on small and retrospective studies. Unlike pediatric patients, adults with medulloblastoma have been treated according to risk-adapted therapeutic strategies in only a few prospective studies. Overall, approximately 30% of patients experience recurrence and die of disease-related causes. Although the patients could respond to second-line treatments, the prognosis of patients with recurrence remains dismal. An important challenge for the future will be the biologic characterization of medulloblastoma in adults, with the identification of specific genetic patterns of patients with different prognosis and different response to targeted treatments.

Therapeutic Opportunities for Medulloblastoma Come of Age

In this issue of Cancer Cell, Kool and colleagues reveal clear genetically defined subclasses of the sonic hedgehog (SHH) subclass of medulloblastoma. This molecular dissection of the SHH subclass is not simply a cutting-edge advance; the data have profound impact on clinical trial design and decision-making.

Analysis of pathologic characteristics and prognosis in different subtypes of adult medulloblastoma

To study the pathologic characteristics and prognosis in different subtypes of adult medulloblastoma (MB). The clinical information, imaging findings and pathologic characteristics of 151 cases of adult medulloblastomas were retrospectively reviewed and analyzed by chi-square test. The survival data were assessed using the Kaplan-Meier method. Amongst the 151 MB cases studied, there were 73 cases of classic MB, 36 cases of desmoplastic/nodular MB, 39 cases of anaplastic MB and 3 cases of large cell MB. The primary tumors were more frequently located in cerebral hemisphere in desmoplastic/nodular MB than in other subtypes (P=0.000).On the other hand, large cell/anaplastic MB were associated with more frequently local recurrence and distant metastasis (P=0.003). The post-operative overall survival time ranged from 6 to 150 months, with median survival being (103.3±5.7) months (95%CI, 92.52 to 115.09). The median survival of classic MB, desmoplastic/nodular MB and large cell/anaplastic MB was (110.7±7.8) months, (125.5±7.6) months and (57.6±7.6) months, respectively. The differences were statistically significant (P=0.000). The three variants of MB show different biologic behavior. Large cell/anaplastic MB represents an independent poor prognostic indicator in adults.

Adult medulloblastoma: feasibility and effectiveness of utilising high‐dose chemotherapy with autologous stem cell rescue in newly diagnosed patients

Adult medulloblastoma: feasibility and effectiveness of utilising high‐dose chemotherapy with autologous stem cell rescue in newly diagnosed patients

Prominent EMA ‘dots’ in tumour‐induced Bergmann gliosis

To describe an unusual pattern of epithelial membrane antigen (EMA) immunoreactivity in highly proliferative human Bergmann glia. An immunohistochemical study was performed of postmortem cerebellar tissue from 18 adult patients with cerebellar damage of various aetiologies and 15 biopsies of diverse adult and paediatric cerebellar tumours. We observed marked proliferation of Bergmann glia with unusual prominent dot-like cytoplasmic EMA immunoreactivity in a case with extensive leptomeningeal sarcomatosis. Similar staining was not observed in association with other types of cerebellar pathology, except for other neoplastic conditions, such as leptomeningeal carcinomatosis, adult medulloblastoma, and pilocytic astrocytoma in children. At an ultrastructural level, the index case showed prominent endoplasmic reticulum with some intermediate filaments and lipofuscin granules, but no structures related to cilia or microvilli were observed. We consider that prominent EMA dots in Bergmann glia might represent excessive activation induced by an overlying leptomeningeal tumour that stimulates the expression of early developmental antigens. This observation suggests modulation of the glial phenotype when exposed to a neoplastic microenvironment that, in turn, might influence the regenerative potential of Bergmann glia.

A Comparison of Clinical Outcomes of Adult and Pediatric Medulloblastoma

A Comparison of Clinical Outcomes of Adult and Pediatric Medulloblastoma

Management of recurrent medulloblastoma in adult patients: a systematic review and recommendations

Medulloblastoma accounts for almost one-third of pediatric central nervous system (CNS) cancers, but is very rare in the adult population. As a result, adult patients with medulloblastoma are often treated according to therapies developed for children with similarly staged disease at diagnosis, based on the assumption that adult and pediatric tumors have similar properties. The purpose of this review was to summarize the evidence and to make recommendations for the management of recurrent disease in adult patients with medulloblastoma. We conducted a systematic literature search to find publications addressing treatment of recurrent medulloblastoma in adults. Current treatment strategies for adult patients with relapsed medulloblastoma are based on the results of retrospective case series and published consensus recommendations, and include maximal safe re-resection where possible, combined with chemotherapy and/or re-irradiation. We describe the results of 13 publications involving 66 adult patients treated with high-dose chemotherapy (HDCT) plus stem cell transplantation for recurrent medulloblastoma. HDCT with stem cell transplantation may be a treatment option for a small proportion of adult patients who are unlikely to benefit from conventional chemotherapy and who are fit and have their disease recurrence contained within the CNS. Potential cases in which stem cell transplantation is being considered should be discussed at a multidisciplinary tumor board which includes involvement by hematologic oncologists and transplant specialists.

Comprehensive high-resolution genomic profiling and cytogenetics of two pediatric and one adult medulloblastoma

Medulloblastoma (WHO grade IV) is a rare, malignant, invasive, embryonal tumor which mainly occurs in children and represents less than 1% of all adult brain tumors. Systematic comprehensive genetic analyses on medulloblastomas are rare but necessary to provide more detailed information.Therefore, we performed comprehensive cytogenetic analyses (blood and tissue) of two pediatric and one adult medulloblastoma, using trypsin-Giemsa staining, spectral karyotyping (tissues only), SNP-arrays, and gene expression analyses.We confirmed frequently detected chromosomal aberrations in medulloblastoma, such as +7q, −8p/q, −9q, −11q, −12q, and +17q and identified novel genetic events. Applying SNP-array, we identified constitutional de novo losses 5q21.1, 15q11.2, 17q21.31, 19p12 (pediatric medulloblastoma), 9p21.1, 19p12, 19q13.3, 21q11.2 (adult medulloblastoma) and gains 16p11.1–16p11.2, 18p11.32, Yq11.223–Yq11.23 (pediatric medulloblastoma), Xp22.31 (adult medulloblastoma) possibly representing inherited causal events for medulloblastoma formation. We show evidence for somatic segmental uniparental disomy in regions 1p36, 6q16.3, 6q24.1, 14q21.2, 17p13.3, and 17q22 not previously described for primary medulloblastoma. Gene expression analysis supported classification of the adult medulloblastoma to the WNT-subgroup and classification of pediatric medulloblastomas to group 3 tumors.Analyses of tumors and matched normal tissues (blood) with a combination of complementary techniques will help to further elucidate potentially causal genetic events for medulloblastomas.

Adult primitive neuroectodermal tumors: the prognostic value of supratentorial location

Primitive neuroectodermal tumors (PNETs) are tumors which primarily consist of undifferentiated round neuroepithelial cells. Central nervous system PNETs can be divided into two genetically distinct groups: infratentorial PNET (iPNET)/medulloblastoma and supratentorial PNET (sPNET). Currently, the comparative outcome of adult patients with sPNETs and iPNETs is unknown. In this study we have utilized the Surveillance, Epidemiology, and End Results database to perform a comparative analysis of 103 cases of adult sPNET and 669 adult medulloblastoma cases. Additionally we have analyzed various factors to identify their prognostic significance and characterize the optimal treatment for these tumors. Patients with sPNETs were seen to have a significantly worse survival than those diagnosed with medulloblastomas (16 vs. 155 months, p < 0.0001). Elderly patients (15 vs. 114 months, p < 0.0001) and those over the age of 40 (68 vs. 147 months, p < 0.0001) experienced significantly worse survival than younger patients. In contrast, radiotherapy (143 vs. 26 months, p < 0.0001), surgical resection (116 vs. 22 months, p = 0.0010) and the extent of resection (EOR) (173 vs. 81 months, p = 0.0005) resulted in significantly improved patient survival. Multivariate analysis revealed age greater than 40 years (HR: 1.57; 95 % CI: 1.17-2.11; p = 0.0028) and sPNET pathology (HR: 3.41; 95 % CI: 2.47-4.72; p < 0.0001) to be poor prognostic factors for survival while radiotherapy (HR: 0.52; 95 % CI: 0.38-0.71; p < 0.0001) and the EOR (HR: 0.73; 95 % CI: 0.55-0.96; p = 0.023) were associated with significantly improved survival. The treatment of sPNETs should therefore include maximal surgical resection when feasible followed by radiotherapy as these treatments have been demonstrated to confer a survival benefit. Additional studies are needed to identify effective chemotherapeutics and specific treatment regimens for adults with sPNETs.

Unusual Case of Recurrent Extraneural Metastatic Medulloblastoma in a Young Adult: Durable Complete Remission With Ewing Sarcoma Chemotherapy Regimen and Consolidation With Autologous Bone Marrow Transplantation and Local Radiation

Unusual Case of Recurrent Extraneural Metastatic Medulloblastoma in a Young Adult: Durable Complete Remission With Ewing Sarcoma Chemotherapy Regimen and Consolidation With Autologous Bone Marrow Transplantation and Local Radiation

Patterns of care study of adult medulloblastoma.

2086 Background: Medulloblastoma (MB) accounts for less than 1% of adult intracranial tumours. While pediatric MB has been investigated in several randomized studies, the evidence in adults is limited to case reports and retrospective series, with no accepted standard of care. The Australian Cooperative Trials Group for Neuro-Oncology (COGNO) sought to determine the range and consistency of clinicians’ approaches to management as a basis for future trials. Methods: We aimed to identify current treatment strategies for adult MB through an international electronic survey launched at the 2012 meeting of the Society of Neuro-Oncology and by email invitation. Clinicians who had treated at least 1 adult patient with MB, central primitive neuroectodermal tumor (cPNET), or pinealoblastoma in the preceding year were asked about their most recent patient and asked to discuss their approach to management of a typical clinical scenario. Results: Between Nov 2012 and Jan 2013, 45 clinicians (11 medical oncologists, 7 radiation oncologists, 5 pediatric oncologists, and 22 others) from Australia (n = 24), USA (n = 3), Europe (n = 4) and other countries (n = 14) completed the survey. Responding clinicians had treated 54 cases in the past 12 months. The commonest histological type was MB (64%), followed by cPNET (20%). Most patients were male (68%), and most had high-risk disease (65%). 56% had complete surgical resection and 32% had molecular testing. Radiotherapy was predominantly craniospinal (92%) and mostly post-resection (80%). Combination chemotherapy was more common than single agent. Vincristine, cisplatin, cyclophosphamide was the most common protocol (43%). Others included carboplatin, etoposide, ifosfamide (29%), vincristine, lomustine, cisplatin (19%), vincristine, lomustine, prednisone (5%). Further details will be presented at the 2013 ASCO Annual Meeting. Conclusions: Our study has shown substantial international variation in the treatment of adult MB, most pronounced in the choice of chemotherapeutic agents, highlighting the need for further collaborative research to guide evidence-based treatment strategies.

Chemotherapy for adult medulloblastoma: Is it necessary for all?

e13025 Background: Medulloblastome is rare in adults and treatment is usually extrapolated from the pediatric age group, the aim of our study is to highlight the importance of chemotherapy both in the concurrent and adjuvant setting in adult medulloblastoma. Methods: Fourty patients between 1995 and 2011 with diagnosis of medulloblastoma were treated at both the department of clinical oncology Cairo University or Nasser Institute Cancer Center, files reviewed for demographic characteristics, radiographic findings, extent of resection, staging, computerized tomography (CT) scans or magnetic resonance (MR), histopathology, treatment received, pattern of recurrence and treament received. All patients treated with craniospinal irradiation with total dose of 36Gy followed by a boost to the posterior fossa till 54Gy. Results: Fourty patient were identified from our medical records 24 (60%) male and 16 (40%) female, mean age 25 year (range = 18 - 45), 2 patients had residual tumor more than 2cm, one patient had leptomeningeal deposits, 13 patients had weekly vincristin 2 mg weekly followed by cisplatin vepside, 27 patients didn’t receive any form of chemotherapy. Five year overall and disease free survival for the whole group was 92% (95% CI: 88-142) , 66% (95% CI: 73-135) respectively, for patients received chemotherapy OAS and DFS was 80% (CI:71-138), and 68% (48-162) for patients didn‘t receive chemotherapy OAS and DFS was 90% (CI:81-161), and 67% (C: 58-101), No statistical significance difference of survival between the two groups. univariate analysis didnt show any statistical significance correlation with chemotherapy.G3 neutropenia was more in the chemotherapy group 6 patients vs. 1 patient in the chemotherapy group. Conclusions: Chemotherapy for adult medulloblastoma should be further investigated as good survival time can be achieved with radiotherapy alone. And recurrence can be still salvage with chemotherapy

A prospective phase II study to determine the efficacy of GDC 0449 (vismodegib) in adults with recurrent medulloblastoma (MB): A Pediatric Brain Tumor Consortium study (PBTC 25B).

2035 Background: Almost 80% of adult medulloblastoma are of the SHH subtype. Second line therapy for adult MB is limited; therefore we tested the efficacy of vismodegib, a small molecule inhibitor of Smoothened (SMO) among patients with this disease. Methods: Adult patients with refractory or recurrent MB and who had measureable disease were enrolled on the study. Immunohistochemistry (IHC) was used to stratify patients to Stratum A (non-SHH group); Stratum B (SHH tumors) and Stratum C (indeterminate). All patients were treated with vismodegib at 150 mg/day PO daily. Tumor response, which had to be maintained for 8 weeks to meet protocol definition of sustained response, was assessed using RECIST criteria and central imaging review. Separate but identical Simon 2-stage MinMax designs (α = 0.10) were used in strata A and B to test for evidence that sustained response rates exceeded 5% with 90% power to detect 25% sustained response rates. Thus, 3/20 sustained responses were needed to declare potential activity of vismodegib. Results: 32 patients with a median age of 30 years (range 22.4-51.9) were enrolled on the study [Stratum A (n = 8); Stratum B (n = 20); Stratum C (n = 4)], including 18 males and 14 females. No responses were observed in Strata A or C and the median duration of treatment was 1.5 months (range 0.66-2.33). Three of 20 patients enrolled on Stratum B had sustained responses. The median duration of therapy for Stratum B patients was 2.76 months (range 0.33- 13.61). Six patients were on treatment for ≥6.44 months and 3 remain on treatment after 5.42, 9.34 and 13.61 months. During course 1, 2 patients experienced grade 3 decrease in lymphocytes; 1 experienced a grade 4 thromboembolic event; and 2 experienced grade 3 toxicities (back pain &amp; syncope). During course 2, 3 patients experienced grade 3 toxicities (decrease in lymphocytes; myalgia &amp; seizure). One other patient experienced grade 3 hypophosphatemia in courses 1 and 2. Conclusions: Vismodegib has activity against recurrent or refractory adult ‘SHH-subtype’ medulloblastoma and should be considered as a therapeutic option for newly diagnosed patients with this disease. Clinical trial information: NCT00939484.

Local perspective on a rare brain tumour: adult medulloblastoma

Little contemporary data are available regarding Australian patterns of care in adult medulloblastoma. It is unclear whether treatment, extrapolated from paediatric protocols despite known differences between the two groups, results in comparable efficacy. To perform a retrospective review of patterns of care in adult medulloblastoma, especially with respect to adjuvant chemotherapy, in Australian patients. All medulloblastoma patients aged 15 years or older at two neuro-oncology institutions were identified from January 1995-May 2011. Patients with supratentorial or peripheral tumours were excluded. Standardised data were extracted from each institution regarding symptoms, disease staging, treatments received, toxicities and survival outcomes. Seventeen eligible patients were identified. Median age was 37 years (range 20-67 years). All had good performance status (Eastern Cooperative Oncology Group 0-1). There were 11 standard-risk de novo patients, three high-risk de novo patients and three patients with recurrent disease. Median overall survival (OS) had not been reached for standard-risk patients with median follow up of 58 months. The median OS for high-risk de novo patients was 21 months, while the median OS was 15 months for patients with recurrent disease. Treatment was well tolerated, with haematological toxicities being most common. Combined modality therapy (surgery followed by postoperative radiotherapy and adjuvant chemotherapy) was well tolerated and associated with good outcomes in standard-risk de novo patients. High-risk and recurrent disease patients do extremely poorly regardless of treatment and better treatment strategies are needed in these patients.

Abstract 4591: Whole genome sequencing of SHH medulloblastomas predicts molecular groups of responders and non-responders to SMO-inhibition .

Abstract Recently, we and others analyzed large series of pediatric medulloblastomas (MB) and identified a number of recurrent aberrations in each of the four major subgroups (WNT, SHH, Group 3 and Group 4). However, due to their infrequent occurrence not much is known about genetic aberrations in adult MBs. We now have analyzed a large series of adult SHH MBs (age ≥ 16) by whole genome sequencing and compared them with pediatric SHH MBs. We sequenced tumor and blood of 26 adult SHH MBs and compared them with 30 pediatric SHH MBs. A replication cohort of 28 adult and 29 pediatric SHH MBs was sequenced for 414 genes by targeted sequencing. We also performed expression profiling and DNA methylation analyses on most of these cases. Whole genome sequencing revealed a clear correlation between mutation rate and age of the patient (r = 0.69). Furthermore, the genomic data showed that SHH MBs can be split up in three distinct subgroups: infants, children and adults. They all have mutations in the SHH pathway, mostly in PTCH1 (infants and adults), SUFU (infants) and SMO (adults). Children almost completely lack the classical upstream SHH pathway mutations but instead have more downstream aberrations such as MYCN and GLI2 mplifications, and have frequent TP53 mutations, often in the germline, whilst all of these were extraordinarily rare in infants and adults. We also identified several recurrent mutations in adult MBs that were not found in pediatric MBs. Moreover, the three SHH subgroups were different in their transcriptome and methylome with the TP53 mutated SHH MBs in children being more similar to adult MBs. Collectively, this data will help to better understand the biology of pediatric and adult SHH-medulloblastoma, but most importantly may help selecting patients for targeted SHH inhibition and new treatment strategies for TP53 mutated SHH MBs in a clinical setting. Citation Format: Marcel Kool, David TW Jones, Natalie Jaeger, Paul A. Northcott, Volker Hovestadt, Ulrich Schueller, Marc Remke, Yoon-Jae Cho, Scott Pomeroy, Michael D. Taylor, Roland Eils, Andrey Korshunov, Peter Lichter, Stefan M. Pfister. Whole genome sequencing of SHH medulloblastomas predicts molecular groups of responders and non-responders to SMO-inhibition . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4591. doi:10.1158/1538-7445.AM2013-4591

Retreatment of recurrent adult medulloblastoma with radiotherapy: a case report and review of the literature

IntroductionMedulloblastoma, the most frequent brain tumor in childhood, also occurs with a wide range of characteristics in adult patients. Late relapse is common in adult medulloblastoma, and the overall survival of relapsed patients usually ranges from 12 to 15 months. Treatment at recurrence is still debated and after reoperation includes stereotactic or normofractionated radiotherapy, and high-dose chemotherapy with autologous bone marrow transplantation.Case presentationWe report on the case of a 31-year-old Caucasian woman who underwent re-irradiation for a recurrence of medulloblastoma at nine years after first irradiation (56Gy), focusing on the radiobiological background and a review of previous studies involving re-irradiation of recurrent medulloblastoma. After surgical excision of the relapsed tumor and medical multi-agent treatment, the site of recurrence was treated using three-dimensional conformal radiotherapy to a total dose of 52.8Gy (1.2Gy/fraction/twice daily). A total biological equivalent dose of 224.6Gy (α:β = 2 Gy) was delivered to the posterior fossa (first and second treatments). No radionecrosis or local recurrence was evident at 18 months after re-irradiation.ConclusionRe-irradiation can be considered a possible and safe treatment in selected cases of recurrent medulloblastoma in adults. The reported radiobiological considerations could be useful in other cases involving re-irradiation of brain tumors.