MR Imaging and Clinical Characteristics of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters.

BACKGROUND AND PURPOSE: Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of the present study was to describe MR imaging and clinical characteristics of patients with DGONC. MATERIALS AND METHODS: Preoperative MR images of 9 patients with DGONC (median age at diagnosis, 9.9 years; range, 4.2-21.8 years) were reviewed. RESULTS: All tumors were located superficially in the frontal/temporal lobes and sharply delineated, displaying little mass effect. Near the circle of Willis, the tumors encompassed the arteries. All except one demonstrated characteristics of low-to-intermediate aggressiveness with high-to-intermediate T2WI and ADC signals and bone remodeling. Most tumors (n = 7) showed a homogeneous ground-glass aspect on T2-weighted and FLAIR images. On the basis of the original histopathologic diagnosis, 6 patients received postsurgical chemo-/radiotherapy, 2 were irradiated after surgery, and 1 patient underwent tumor resection only. At a median follow-up of 61 months (range, 10-154 months), 6 patients were alive in a first complete remission and 2 with stable disease 10 and 21 months after diagnosis. The only patient with progressive disease was lost to follow-up. Five-year overall and event-free survival was 100% and 86±13%, respectively. CONCLUSIONS: This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.

Imaging Characteristics of Wingless Pathway Subgroup Medulloblastomas: Results from the German HIT/SIOP-Trial Cohort.

BACKGROUND AND PURPOSE: In addition to the 4 histopathologically defined entities of medulloblastoma, 4 distinct genetically defined subgroups have been included in the World Health Organization classification of 2016. The smallest subgroup is the medulloblastoma with activated wingless pathway. The goal of this study was to identify a typical MR imaging morphology in a larger number of pediatric patients with wingless pathway medulloblastoma. MATERIALS AND METHODS: From January 2001 to October 2017, of 75 patients with histologically confirmed and molecularly subgrouped wingless pathway medulloblastomas recruited to the German Pediatric Brain Tumor (HIT) trials, 38 patients (median age, 12.8 ± 4.6 years at diagnosis; 24 [63.2%] female) had preoperative imaging that passed the entry criteria for this study. Images were rated by the local standardized imaging criteria of the National Reference Center of Neuroradiology. Additionally, a modified laterality score was used to determine tumor localization and extension. RESULTS: Twenty-eight of 38 (73.7%) were primary midline tumors but with a lateral tendency in 39.3%. One extensively eccentric midline tumor was rated by the laterality score as in an off-midline position. Five tumors were found in the cerebellopontine angle; 3, in the deep white matter; and 2, in a cerebellar hemisphere. Leptomeningeal dissemination was rare (11.5%). In 60.5%, intratumoral blood-degradation products were found, and 26.3% showed cysts with blood contents. CONCLUSIONS: According to our observations, wingless pathway medulloblastomas are not preferentially off-midline tumors as postulated in previous studies with smaller wingless pathway medulloblastoma cohorts. Dense intratumoral blood-degradation products and cysts with blood contents are frequently found and might help to differentiate wingless pathway medulloblastoma from other medulloblastoma subtypes.

Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study.

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. METHODS: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). RESULTS: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. CONCLUSIONS: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.

Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

BACKGROUND AND PURPOSE: HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non-brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY. MATERIALS AND METHODS: We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process. RESULTS: Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1). CONCLUSIONS: The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.

Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype.

BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study. RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%-100.0% and 62.6%-95.3%). WNT-activated nuclear ß-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2-22.3 cm3 versus 35.1-47.6 cm3; P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04). CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New "Leave Me Alone" Lesion with a Characteristic Imaging Pattern.

Multinodular and vacuolating neuronal tumor of the cerebrum is a recently reported benign, mixed glial neuronal lesion that is included in the 2016 updated World Health Organization classification of brain neoplasms as a unique cytoarchitectural pattern of gangliocytoma. We report 33 cases of presumed multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a remarkably similar pattern of imaging findings consisting of a subcortical cluster of nodular lesions located on the inner surface of an otherwise normal-appearing cortex, principally within the deep cortical ribbon and superficial subcortical white matter, which is hyperintense on FLAIR. Only 4 of our cases are biopsy-proven because most were asymptomatic and incidentally discovered. The remaining were followed for a minimum of 24 months (mean, 3 years) without interval change. We demonstrate that these are benign, nonaggressive lesions that do not require biopsy in asymptomatic patients and behave more like a malformative process than a true neoplasm.

Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

Hydrocephalus and hypothalamic involvement in pediatric patients with craniopharyngioma or cysts of Rathke's pouch: impact on long-term prognosis.

OBJECTIVE: Pediatric patients with sellar masses such as craniopharyngioma (CP) or cyst of Rathke's pouch (CRP) frequently suffer disease- and treatment-related sequelae. We analyzed the impact and prognostic relevance of initial hydrocephalus (HY) and hypothalamic involvement (HI) on long-term survival and functional capacity (FC) in children with CP or CRP. SUBJECTS AND METHODS: Using retrospective analysis of patient records, presence of initial HY or HI was assessed in 177 pediatric patients (163 CP and 14 CRP). Twenty-year overall survival (OS) and progression-free survival (PFS), FC, and BMI were analyzed with regard to initial HY, degree of resection, or HI. RESULTS: Of the 177 patients, 105 patients (103/163 CP and 2/14 CRP) presented with initial HY and 96 presented with HI. HY at diagnosis was associated (P=0.000) with papilledema, neurological deficits, and higher BMI at diagnosis and during follow-up. OS, PFS, and FC were not affected by HY at initial diagnosis. HI at diagnosis (96/177) had major negative impact on long-term prognosis. Sellar masses with HI were associated with lower OS (0.84±0.04; P=0.021), lower FC (P=0.003), and higher BMI at diagnosis and last follow-up (P=0.000) when compared with sellar masses without HI (OS: 0.94±0.05). PFS was not affected by HI or degree of resection. CONCLUSIONS: Initial HY has no impact on outcome in patients with sellar masses. OS and FC are impaired in survivors presenting with initial HI. PFS is not affected by HY, HI, or degree of resection. Accordingly, gross-total resection is not recommended in sellar masses with initial HI to prevent further hypothalamic damage.

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial.

Early studies with high-dose chemotherapy for treatment of relapsed cerebral PNET had shown modest efficacy but considerable toxicity. The HIT97 national trial tested a nonrandomized but stratified relapse protocol using either intensive chemotherapy, potentially high dose, or oral chemotherapy. 72 patients (59 disseminated) whose primary treatment had been surgery (97 %), radiotherapy (88 %), and/or chemotherapy (95 %) were enrolled in the intensive chemotherapy arm at diagnosis of relapse or resistance. As a window for this study they received two courses of a 96-hour infusion with carboplatin and etoposide. A response (complete or partial remission) was documented by MRI. Responders received two more cycles of this therapy and stem cell collection, before they received HDC (carboplatin, etoposide, thiotepa) and stem cell support. All possibilities of local therapy were to be explored and applied. After two courses of chemotherapy there was a 52 % response rate (41/72 patients). The median PFS and OS for all 72 patients were 11.6 and 21.1 months. Patients with medulloblastoma had a longer PFS and OS (12.6 and 22.6 months) than those with other PNETs (3.1 and 12.3 months). Favourable prognostic features were no new signs of clinical impairment and localised disease at relapse diagnosis. For the 27 patients who received HDC the median PFS and OS were 8.4 and 20.2 months, respectively. HDC did not benefit patients with resistant cerebral PNET and was associated with profound haematological and mucosal toxicity (90-100 % grade III, IV), infections (50 % grade III and IV) and severe ototoxicity (50 % grade III, 12.5 % grade IV). Treatment related mortality was 8 %. There was low long-term survival and only 2/72 patients are in continuous remission. Adding HDC in patients who responded to the initial courses of chemotherapy did not improve survival. Patients with relapsed cerebral PNET who respond to conventional chemotherapy do not profit from further augmentation to HDC.

MRI characteristics of ependymoblastoma: results from 22 centrally reviewed cases.

BACKGROUND AND PURPOSE: Ependymoblastoma is a malignant embryonal tumor that develops in early childhood and has a dismal prognosis. Categorized by the World Health Organization as a subgroup of CNS-primitive neuroectodermal tumor, ependymoblastoma is histologically defined by "ependymoblastic rosettes." Because it is so rare, little is known about specific MR imaging characteristics of ependymoblastoma. We systematically analyzed and discussed MR imaging features of ependymoblastoma in a series of 22 consecutive patients. MATERIALS AND METHODS: Ependymoblastoma cases were obtained from the database of the German multicenter HIT trials between 2002 and 2013. All cases within this study were centrally reviewed for histopathology, MR imaging findings, and multimodal therapy. For systematic analysis of initial MR imaging scans at diagnosis, we applied standardized criteria for reference image evaluation of pediatric brain tumors. RESULTS: Ependymoblastomas are large tumors with well-defined tumor margins, iso- to hyperintense signal on T2WI, and diffusion restriction. Contrast enhancement is variable, with a tendency to mild or moderate enhancement. Subarachnoid spread is common in ependymoblastoma but can be absent initially. There was a male preponderance (1.75:1 ratio) for ependymoblastoma in our cohort. Mean age at diagnosis was 2.1 years. CONCLUSIONS: With this study, we add the largest case collection to the limited published database of MR imaging findings in ependymoblastoma, together with epidemiologic data. However, future studies are needed to systematically compare MR imaging findings of ependymoblastoma with other CNS-primitive neuroectodermal tumors and ependymoma, to delineate imaging criteria that might help distinguish these pediatric brain tumor entities.

Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group.

BACKGROUND: High-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated. PATIENTS AND METHODS: Between March 2007 and December 2012, six children with primary metastatic HGG (n = 4) or DIPG (n = 2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated. RESULTS: All patients received irradiation to the entire craniospinal axis (35.2 Gy, n = 5; 36 Gy, n = 1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m(2)/day, n = 5; 60 mg/m(2)/day, n = 1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0 ± 0.8 months (range 2.4-10.7 months) and median overall survival was 7.6 ± 3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (≥ grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases. CONCLUSION: Concurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study.

Feasibility of intensive multimodal therapy in infants affected by rhabdoid tumors - experience of the EU-RHAB registry.

Rhabdoid tumors mainly affect infants and other very young children with a marked vulnerability towards intensive therapy such as invasive surgery, high dose chemotherapy (HDCT) and dose intense radiotherapy. Radiotherapy (RT) is a promising option in rhabdoid tumors but its application in infants remains controversial. Neurocognitive and vascular side effects occur even long after completion of therapy. Therapeutic recommendations suggested by the European Rhabdoid Registry including RT, high dose chemotherapy (HDCT) and methotrexate (MTX) were developed by a consensus committee. Unique to our EU-RHAB database is the ability to analyze data of 64 of 81 registered infants (under one year of age) separate from older children. 20 (age at diagnoses 2-12 months) of these had received radiotherapy. To our knowledge, this is the first report specifically analyzing treatment data of infants suffering from malignant rhabdoid tumors. Our results suggest that radiotherapy significantly increases the mean survival time as well as the 3 year overall survival in infants. We detected a doubling of survival times in infants who received RT. Overall, our results suggest that infants benefit from RT with tolerable acute side effects. Severe long term sequelae likely due to intraventricular MTX and/or RT were reported in 4 patients (leukoencephalopathy). No differences in chemotherapy-related toxicity were observed between infants and children. We suggest that a nihilistic therapeutic approach towards young infants is not warranted and that RT may not be a priori rejected as a therapeutic option in infants.

Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH).

PURPOSE: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. PATIENTS AND METHODS: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. RESULTS: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 ± 5 % after EFRT and 65 ± 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. CONCLUSION: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative.

Cerebellar location may predict an unfavourable prognosis in paediatric high-grade glioma.

BACKGROUND: High-grade glioma (HGG) of the cerebellum accounts for only 5% of paediatric HGG. Since little is known about these tumours, the present study aimed at their further characterisation. METHODS: Twenty-nine paediatric patients with centrally reviewed cerebellar HGG were identified from the HIT-GBM/HIT-HGG database. Clinical and epidemiological data were compared with those of 180 paediatric patients with cortical HGG. RESULTS: Patients with cerebellar tumours were younger (median age of 7.6 vs 11.7 years, P=0.028), but both groups did not differ significantly with regard to gender, tumour predisposing syndromes, secondary HGG, primary metastasis, tumour grading, extent of tumour resection, chemotherapy regimen, or radiotherapy. Except for an increased incidence of anaplastic pilocytic astrocytoma (APA) in the cerebellar subset (20.7% vs 3.3%; P<0.001), histological entities were similarly distributed in both groups. As expected, tumour grading had a prognostic relevance on survival. Compared with cortical HGG, overall survival in the cerebellar location was significantly worse (median overall survival: 0.92 ± 0.02 vs 2.03 ± 0.32 years; P=0.0064), and tumour location in the cerebellum had an independent poor prognostic significance as shown by Cox-regression analysis (P=0.019). CONCLUSION: High-grade glioma represents a group of tumours with an obviously site-specific heterogeneity associated with a worse survival in cerebellar location.

Craniospinal irradiation with concurrent temozolomide and nimotuzumab in a child with primary metastatic diffuse intrinsic pontine glioma. A compassionate use treatment.

Primary metastatic diffuse intrinsic pontine glioma (DIPG) is relatively rare and associated with a dismal prognosis. Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival. However, little is known about the feasibility and toxicity of this treatment approach. Here, we describe the case of an 8-year-old girl with primary metastatic DIPG who received craniospinal radiotherapy, a local boost, and concurrent temozolomide and nimotuzumab treatment based on an individual therapy recommendation. Radiotherapy could be completed without any interruption. However, concurrent temozolomide had to be disrupted several times due to considerable acute myelotoxicity (grade III-IV).Maintenance immunochemotherapy could be started with a delay of 5 days and was performed according to treatment schedule. The disease could be stabilized for a few months. A routine MRI scan finally depicted disease progression 5.7 months after the start of irradiation. The patient died 1.9 months later.

Bone involvement in atypical teratoid/rhabdoid tumors of the CNS.

SUMMARY: Destruction of the bony structures of the skull is rare in primary tumors of the CNS. In low-grade gliomas, modeling of the skull is caused by slow growth and chronic pressure. Bony destruction is exceptional even in highly malignant gliomas. Atypical teratoid/rhabdoid tumors of the CNS are highly malignant neoplasms diagnosed with an increasing frequency, mainly in young children. On imaging, these tumors exhibit distinct though not specific morphologic features including peripheral cysts, bleeding residues, and a distinct bandlike, wavy pattern of enhancement. A combination of these single characteristics together with a predilection for young age is suggestive of an atypical teratoid/rhabdoid tumor. We present 5 children with an atypical teratoid/rhabdoid tumor affecting the adjacent bone. These 5 patients were collected in our imaging data base for childhood atypical teratoid/rhabdoid tumor consisting of 91 children at the time of this evaluation and thus representing 6.6%. The mean age of children with bone involvement (4.8 years) was above the average age (2 years) of all children in the data base. We add this rare feature to the list of typical features in MR imaging and CT morphology of atypical teratoid/rhabdoid tumor.

Meningioma as second malignant neoplasm after oncological treatment during childhood.

A total of 38 patients (18 female/20 male) with childhood meningioma were recruited from the German registry HIT-Endo (1989-2009). In 5 cases meningioma occurred as second malignant neoplasm (SMN). Histologies were confirmed by reference assessment in all cases (SMN: 2 WHO I, 1 WHO II, 2 WHO III). The SMNs were diagnosed at a median age of 12.4 years with a median latency of 10.2 years after primary malignancy (PMN; 4 brain tumors, 1 lymphoblastic leukemia; median age at diagnosis 2.7 years). Meningioma occurred as SMN in the irradiated field of PMN (range 12-54 Gy). The outcome after treatment of SMN meningioma (surgery/irradiation) was favorable in terms of psychosocial status and functional capacity in 4 of 5 patients (1 death). We conclude that survivors of childhood cancer who were exposed to radiation therapy at young age harbor the risk of developing meningioma as a SMN at a particularly short latency period in case of high dose exposure.