Metastatic medulloblastoma

The incidence of metastatic medulloblastoma is probably greater than the thirteen documented patients. Case reports of metastatic medulloblastoma must be carefully analysed. We have added two cases which conform to Weiss' criteria for metastatic disease. The direction and factors influencing spread have been discussed.     

成人髓母细胞瘤的诊断和治疗

目的 探讨成人髓母细胞瘤的临床特点、诊断和治疗方法.方法 回顾性分析我院2000 年8月至2008 年12 月期间收治的16 例成人髓母细胞瘤的临床及影像学表现、治疗措施与效果.结果 肿瘤全切除12 例,次全切除3 例,部分切除1 例,术后均行放疗,3 例同时行化疗.术后复发3 例,术后2 年生存率86.7%,5 年生存率66.7%.结论 成人髓母细胞瘤发生于后颅窝中线区者多见.手术切除及术后全脑脊髓放疗是主要治疗方法.复发者预后差.     

Radiation-induced medulloblastoma in an adult: a functional imaging study

We describe functional imaging findings using MRI, 1H-Magnetic resonance spectroscopy and positron emission tomography in a case of radiation-induced medulloblastoma following radiotherapy for pineal gland tumor. MRS showed a prominent choline peak; FDG, 11C-Met and 11C-Choline PET showed a minimal glucose, increased methionine and choline uptake.     

成人高级别脑胶质瘤术后替莫唑胺联合依托泊苷治疗的临床运用与观察

目的比较替莫唑胺联合依托泊苷与单用替莫唑胺在成人高级别脑胶质瘤术后综合治疗中的疗效差异。方法 42例成人高级别脑胶质瘤患者行手术切除病灶,术后随机分为两组,单药组(单用替莫唑胺)和联合治疗组(替莫唑胺联合依托泊苷)。比较两组患者的无进展生存期及不良反应。结果单药组和联合治疗组的中位无进展生存时间分别为17.5周和24.4周,6个月无进展生存率分别为31.8%和45.0%。联合治疗组的无进展生存期和6个月无进展生存率均要明显高于单药组(均P0.05)。同时,两组患者的不良反应无显著差异。结论在成人高级别脑胶质瘤术后综合治疗中,替莫唑胺联合依托泊苷的化疗疗效要优于单用替莫唑胺治疗,该方案值得临床推广。     

Long-term treatment with temozolomide in malignant glioma

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6 months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2 years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1 month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.     

Radiosurgery as adjuvant treatment of a recurrent adult medulloblastoma. Ultra-early response

The role of radiosurgery after multimodality treatment of recurrent desmoplastic adult medulloblastoma is analyzed. The ultra-early clinical and pathological response of this tumor to adjunctive radiosurgery is stressed.     

Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience

Purpose

Chemotherapy for relapsed medulloblastoma has been inadequate, and most patients succumb to disease.

Methods

We retrospectively reviewed nine cases of relapsed medulloblastoma treated with bevacizumab, irinotecan, ±?temozolomide. Patients received one to three prior therapeutic regimens. Five patients received 10 mg/kg bevacizumab and 125–150 mg/m² irinotecan IV every 2 weeks, with temozolomide, starting at a median dose of 150 mg/m² orally for 5 days monthly. Two patients received bevacizumab and irinotecan, but not temozolomide, due to provider preference. Two of nine patients received 15 mg/kg bevacizumab IV, 90 mg/m² irinotecan orally for five consecutive days, 100 mg/m²/day temozolomide IV for 5 days, and 1.5 mg/m² vincristine IV, each administered every 21 days.

Results

Median time to progression was 11 months. Median overall survival was 13 months. Objective tumor response at 3 months was 67 %, including six patients with partial response (PR) and three patients with stable disease (SD). At 6 months, objective response was 55 %, with two patients with PR and three with complete response. Additionally, one patient had SD and three had PD. Two patients remain alive and progression free at 15 and 55 months; another is alive with disease at 20 months. Toxicities included two patients with grade III neutropenia, two with grade III thrombocytopenia, one with grade III elevation of liver function tests, and one patient with grade III diarrhea.

Conclusions

The combination of bevacizumab and irinotecan, with or without temozolomide, produces objective responses with minimal toxicity in children with recurrent medulloblastoma. Prospective clinical trials are needed to evaluate the efficacy of this strategy.     

Dramatic response to temozolomide,irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases

There is little evidence to guide the choice of chemotherapeutic agents for osseous metastases in medulloblastoma. Recently, triple therapy with temozolomide, irinotecan, and bevacizumab has been reported to have efficacy in recurrent medulloblastoma, and this regimen alone and in combination with other agents has been tested in several early-phase clinical trials. Here we report a 20-year-old woman with multiply-relapsed medulloblastoma with numerous osseous metastases 8 years after original diagnosis who responded dramatically to temozolomide, irinotecan, and bevacizumab therapy. This case highlights the potential for this regimen in treating osseous metastases in medulloblastoma.     

Modern treatment strategies in medulloblastoma

Chemotherapy has an important role in the modern treatment of children with medulloblastoma (MB). In patients at high risk, intense chemotherapy should improve the survival rate. In low-risk patients chemotherapy should allow the dose of craniospinal irradiation to be reduced, which in turn should improve the quality of life. In infants under 3 years of age radiotherapy should be delayed, or even replaced by postoperative chemotherapy. Chemotherapy is also necessary to prevent or treat systemic dissemination. The optimal timing of chemotherapy is a focus of contemporary research.     

Effects of palliative treatment with temozolomide in patients with high-grade gliomas

BACKGROUND AND PURPOSE: The aim of the study was to assess the results of treatment with temozolomide in patients with high-grade gliomas who no longer benefit from surgical treatment and radiotherapy. MATERIAL AND METHODS: The retrospective analysis included 51 patients treated between 2001 and 2007 in the Centre of Oncology in Kraków. Glioblastoma multiforme was histologically diagnosed in 24 (47%) patients; anaplastic astrocytomas and other grade III gliomas (according to WHO classification) were diagnosed in 27 (53%) patients. Patients received 1-11 cycles of treatment with temozolomide - 210 cycles were given in total. Forty-five patients were eligible for efficacy assessment because 6 patients received only one chemotherapy cycle (due to rapid progression of the glioma). RESULTS: According to the radiological assessment, 6 patients (13%) had an objective response and a further 16 patients (36%) had stabilization of the glioma. Subjective improvement was noted in 26 patients (58%), and neurological improvement was observed in 14 patients (31%). The median survival in the whole group was 41 weeks (40 weeks in patients with glioblastoma multiforme and 54 weeks in patients with anaplastic gliomas). One-year overall survival in the above-mentioned groups was 40.7%, 22%, and 50%, respectively. Two-year overall survival was 16%, 8%, and 20.9%, respectively. Adverse events were observed during 73 (35%) cycles of treatment and prompted a dose reduction in 12 (24.5%) patients. The most frequent adverse events were: thrombocytopenia, leukopenia, nausea and vomiting. Adverse events did not lead to treatment withdrawal in any patient. CONCLUSIONS: Objective benefit from the temozolomide treatment (stabilization or objective remission) was observed in 49% of patients irrespective of histological diagnosis. Tolerability of treatment with temozolomide in patients with high-grade gliomas is good.     

Lymph node metastasis of medulloblastoma in a young adult

Medulloblastoma is the commonest primary central nervous system malignancy in childhood, but is rare in adults. Rarer still is metastasis of such a tumour to a lymph node. This report describes such a case, and briefly discusses relevant pathophysiology and epidemiology.     

替莫唑胺胶囊治疗恶性脑胶质瘤30例疗效分析

目的评价替莫唑胺胶囊（TMZ）治疗人脑恶性胶质瘤的临床疗效及不良反应。方法2005年1月至2008年1月对一个单位30例术后确诊的恶性脑胶质瘤且使用TMZ化疗的患者进行随访,观察近期治疗反应、生存期,并分析常规病理和分子病理对治疗效果的影响。结果TMZ治疗结束时,30例患者客观有效率和疾病控制率分别为53．3％和80．0％,O^6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）对近期疗效无明显影响（P〉0．05）,而不同病理类型的近期疗效存在明显差异（P〈0．05）。随访期间共有12例患者死亡,生存期为0．7～3．7年,中位生存期为1．5年。MGMT阳性和阴性患者的中位生存期分别为1．3年和1．5年,无明显差异（P：0．31）。胶质母细胞瘤和间变型星形细胞瘤的中位生存期分别为1．3年和2．0年,亦无明显差异（P=0．28）。不良反应包括厌食、便秘等消化道症状11例（36．7％）,白细胞减少3例（10．0％）,假性进展2例（6．7％）。结论TMZ对恶性胶质瘤患者有较好的临床疗效,不良反应少,耐受性好,治疗方案简便,是一种理想的恶性胶质瘤术后辅助化疗药物。     

Diffusion-weighted MR imaging and pathologic findings in adult cerebellar medulloblastoma

OBJECTIVES, MATERIALS AND METHODS: The authors present the diffusion-weighted MR imaging and pathologic findings in two adult patients with cerebellar medulloblastoma. RESULTS: Both presented with a vermian mass of the posterior fossa with low signal on SE T1 weighted images, and moderate enhancement of the mass after gadolinium injection. The tumors were of high intensity on diffusion-weighted images with low ADC value. The ADC values (x10(-3) mm2/s) were respectively 0.60 +/- 0.06 and 0.59+/-0.11 (tumor), and 0.65 +/- 0.04 and 0.67 +/- 0.07 (cerebellar white matter). Tumors were highly cellular and composed of densely packed small round cells with hyperchromatic nuclei and scanty cytoplasm. CONCLUSION: diffusion-weighted MR imaging may be useful for the diagnosis of cerebellar medulloblastoma, due to their high cellularity and high nuclear-to-cytoplasmic ratio.     

Chemotherapy as initial treatment in gliomatosis cerebri: results with temozolomide

The optimal therapy for gliomatosis cerebri is unclear, and the rate of response to chemotherapy is not known. Eleven radiotherapy-naive patients received a median number of 10 treatment cycles of temozolomide. An objective response was documented in 45%, and the median time to tumor progression was 13 months with a progression-free survival of 55% at 12 months. These results indicate that radiotherapy to extensive brain regions can be deferred until progressive disease is observed.     

Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma

Medulloblastoma (MB) represents approximately 4% of adult brain tumours, and as such is a poorly studied disease. Although many adult MB are treated using paediatric MB protocols, the reported outcomes are inferior to those observed in children. It remains unclear whether biologic differences underlie these clinical observations. We investigated the molecular characteristics of 31 adult MB. Twelve and 19 adult MB were respectively examined using Affymetrix-HG-U133-plus-2.0-genechips and immunohistochemical analyses. 26/31 (84%) of adult MB examined by gene expression and/or immunohistochemical analysis showed evidence of sonic hedgehog (SHH) pathway activation. A comparison of adult and paediatric MB showed that most adult tumours cluster within the SHH-active subgroup of paediatric MB. The preponderance of SHH activity in adult MB tumours was also shown by positive SFRP1 immunostaining in 16/19 adult paraffin-embedded adult MB tumour blocks. A smaller proportion of adult tumours exhibited evidence of WNT pathway activation, as confirmed by nuclear β-catenin staining (9.7%; 3/31). Notably, we found PTCH1 gene mutation in 4/8 samples tested. Similar to children, adult MB has abnormalities in developmental signalling pathways including SHH and WNT. Importantly, we found a preponderance of SHH pathway activation amongst MB tumours in adults. This SHH signature does not appear to correlate with a long-term favourable outcome. Differences in molecular profiles exist between adult and paediatric SHH-driven MB and further investigations are needed to better characterize age-related molecular profiles in this subgroup.     

Anaplasia is rare and does not influence prognosis in adult medulloblastoma

Histopathologic grading based on increasing anaplasia predicts clinical behavior of pediatric medulloblastomas. The present study was aimed at grading 86 medulloblastomas of adult patients (aged 18 and older) by anaplasia and analyzing the predictive power. Nodularity, desmoplasia, nuclear size, nuclear pleomorphism, necrosis, and endothelial proliferations have been evaluated. Morphometric analysis of nuclear size was performed using the Eclipse Net program. Patients treated with standard postoperative radiotherapy (35 Gy to craniospinal axis and 50 Gy to posterior fossa) were considered for correlation with survival. Pathologic data and total survival were compared by Kaplan-Meier and logrank analysis. No correlation was found between total survival duration and individual pathologic features. Cooccurrence of nuclear pleomorphism, large nuclear diameter, microvascular proliferations, and necroses did not predict outcome. Severe nuclear pleomorphism was found in 4 of 86 cases; the only large-cell medulloblastoma was from an 18-year-old patient. Histopathologic factors have no clinical use for stratification of patients in risk groups. The histologic spectrum of medulloblastoma in adults is different from that in children.     

Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma

We surveyed neuro-oncologists regarding patients treated with temozolomide for at least 12 cycles or 12 months. Patients receiving first-line temozolomide for a median 13 cycles had a median progression-free survival (PFS) of 14 months. Patients with recurrent disease receiving a median 14 cycles had a median PFS of 15.5 months. A small percentage of patients experienced grade III to IV toxicity. These results suggest that long-term treatment with temozolomide is feasible and well tolerated.     

Neurobehavioural treatment for obsessive-compulsive disorder in an adult with traumatic brain injury

Although obsessive-compulsive disorder has been reported as one of many anxiety-related sequelae of brain injury, few empirical data of its responsiveness to psychological intervention are available. In this study, a single participant changing criterion experimental design was used to evaluate a neurobehavioural intervention for compulsive behaviour of an adult with severe traumatic brain injury. The participant, a man aged 24 years, had sustained frontal-temporal lobe brain trauma 12 months earlier, and presented with compulsive counting and voiding of bladder. The neurobehavioural intervention consisted of regular in-home consultations, self-regulation procedures including self-recording of compulsive behaviour, stress-coping strategies, errorless remediation, social reinforcement, and gradual fading of intervention. Baseline showed counting occurred on average 80% of daily hourly intervals, and voiding 12 times per day. Intervention produced elimination of compulsive counting, acceptable voiding at 8 times per day, and reports of the participant's satisfaction with intervention methods and outcomes. At 6 months follow-up, counting remained at zero levels, and voiding had decreased further to 7 times per day.