Glioblastoma multiforme in four siblings: A cytogenetic and molecular genetic study

Summary The familial occurrence of gliomas, in the absence of well-defined neurological tumor syndromes such as the neurofibromatoses, is uncommon. We present a family of ten children in which the four eldest suffered from gliomas. Three of these siblings had histologically verified glioblastoma multiforme, and one patient also had an intestinal non-Hodgkin's lymphoma, but there were no stigmata or family history of a neurological tumor syndrome. Cytogenetic studies of the proband revealed a normal karyotype. Molecular genetic analysis of the proband's glioblastoma revealed two mutations in the p53 tumor suppressor gene, but these were not present in the germline DNA, mutations were not detected in the MTS1 gene in the tumors or in the germline DNA. These findings suggest that a genetic factor may be responsible for the clustering of glial tumors in this family, but it is unlikely that the genetic alteration is mutation of the p53 gene. The data are discussed in light of the literature on familial brain tumors.     

An integrated approach to the treatment of chiasmatic-hypothalamic gliomas

The treatment of visual pathway gliomas is controversial. The many retrospective studies reporting outcome data for patients with chiasmatic/hypothalamic gliomas are difficult to interpret for several reasons. First the natural history of these tumors is erratic with some reports suggesting that most visual pathway gliomas are hamartomas and follow an indolent course, and others reporting 10-year survival rates of close to 60%. Second, earlier studies did not clearly indicate which patients had neurofibromatosis type 1 (NF1) and recent evidence suggests that the natural history of optic gliomas is more favorable in patients with NFL Third the methods and accuracy of diagnosis have changed dramatically and patients diagnosed before and after the[/p] advent of CT/MR imaging have often been included in the same series.While surgical resection is usually not a viable option for definitive treatment of these tumors, recent studies have shown favorable results after subtotal resection in selected patients. The efficacy of radiotherapy has not been unequivocally demonstrated and treatment-related morbidity has become a major concern, in particular, adverse effects on cognition and growth. Chemotherapy has been advanced as an viable alternative to avoid or delay the adverse affects of RT, but the long-term outcome benefits and adverse effects of treatment are just being defined. Despite the limitations of currently available information, sufficient data are now available to rational management quotelines for the majority of children with chiasmatic/hypothalamic gliomas.     

Recent trends in the radiotherapy of pediatric gliomas

The management of pediatric gliomas is controversial, and is greatly influenced by the site of origin of the tumor. For example, cerebellar low grade tumors are often cured by surgery alone. This is in contrast to the hypothalamic and optic system tumors which are usually not amenable to complete resection. For the low grade astrocytomas, the usual indications for adjuvant treatment include: recurrent tumors after initial complete resection or symptomatic tumors that have been incompletely excised. In addition, treatment is generally indicated in tumors with growth on follow-up imaging, even in the absence of symptoms. In selecting the optimal treatment, the relative efficacies of surgery, chemotherapy and irradiation must be balanced by the potential complications of therapy. The potential risks of delayed intervention include irreversible neurologic impairment and potential lower probability of tumor control. This chapter reviews recent trends in the radiotherapeutic management of pediatric low-grade and malignant astrocytomas, particularly the new more conformal techniques that hold the promise of reduced toxicity in children requiring irradiation.     

Treatment of infants with malignant gliomas: The Pediatric Oncology Group Experience

Although survivals of infants with malignant brain tumors are worse than any other age group, one possible exception to this rule are the malignant gliomas. Eighteen children less than 3 years of age with malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma and malignant glioma) were treated on the Pediatric Oncology Group regimen of prolonged postoperative chemotherapy and delayed irradiation, (1986–1990). Of 10 children evaluable for neuroradiologic response, 6 had partial responses (> 50% reduction) to two cycles of cyclophosphamide and vincristine. Progression free survivals at l, 3 and 5 years were 54.25% ± 12, 43% ± 16 and 43% ± 23 respectively. Survivals at 5 years were 50% ± 14. Four children were not irradiated after 24 months of chemotherapy due to parental refusal and none have developed recurrent disease. Neither degree of surgical resection, presence or absence of metastases, nor pathology influenced survival but this may reflect small sample size. This study suggests that some malignant gliomas in infants are chemotherapy sensitive and may be associated with a good prognosis. Why infants with these high-grade gliomas fare better than adults is not clear. It is likely that there is something intrinsically different about them that cannot be identified on routine pathologic examination.     

Subvoxel image registration of multislice (2D) magnetic resonance images in patients with high-grade gliomas of the brain

AIMS: To implement a multislice two-dimensional (2D) T2-weighted sequence suitable for subvoxel image registration and to assess its usefulness in detecting change in high-grade intracranial gliomas. MATERIALS AND METHODS: Twenty patients with high-grade gliomas were studied on two or more occasions. T2-weighted multislice pulse sequences with a Gaussian slice profile, 50% overlapping slices and nearly isotropic voxels were acquired. The images were registered and subtraction images were produced. The images were compared with three-dimensional (3D) T1-weighted registered images and conventional unregistered T2-weighted images. All images were scored for changes in the lesions and ventricular system. RESULTS: The 2D and 3D registered subtraction images were the most sensitive for detecting changes in both the lesions and other regions in the brain. The mean rank scores were significantly higher for the lesions (chi2=86.742; df=5, n=38, P<0.0001) and for the ventricles (chi2=63.837; df=5, n=35, P<0.0001) compared with the unregistered and registered anatomical images. The subtraction images were also most sensitive for detecting signal intensity changes irrespective of the direction of change. CONCLUSION: Rigid body subvoxel registration can be successfully performed with both multislice 2D and 3D imaging. In principle, virtually all forms of clinical MR images of the brain can be accurately registered and subtracted.     

脑胶质瘤的放射治疗进展

 脑胶质瘤治疗以外科手术为主，由于肿瘤侵蚀性强，与脑组织无明显分界，手术难以彻底切除，易复发，生存期短，死亡率高。因此，术后辅助放射治疗占有重要地位。而脑胶质瘤的预后受患者的年龄、Karnofsky评分、病理类型和侵犯范围等因素的影响，其疗效仍不理想。为探索脑胶质瘤放射治疗的疗效，近年来放射治疗的新设备、新技术不断改善和进步，为脑胶质瘤的放射治疗提供了条件。主要阐述了高分级与低分级脑胶质瘤放射治疗以及放疗联合化疗的现状和进展。     

CI-980 for the Treatment of Recurrent or Progressive Malignant Gliomas: National Central Nervous System Consortium Phase I-II Evaluation of CI-980

Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma.

Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses.

Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m², given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m² per cycle. Treatment response was based on serial MRI imaging characteristics.

Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI=0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen.

Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.     

X刀治疗脑胶质瘤的方法及结果分析

 本文报告了我院从1995年3月到1996年5月，采用德国BrainScanX刀治疗系统治疗脑胶质瘤病人45例，经过6～12个月的随访，结果表明，总的治疗有效率达到75．56％，半年以上的生存率为77．78％，颅内压增高等严重并发症的发生率为22．22％。作者总结了适应症选择的标准、治疗计划设计优化的原则、疗效判断标准、X刀后病理和影像变化的特声、以及与并发症发生有关因素等方面的经验和体会。