Planning for brain surgery in brain tumors

A precise knowledge of the localization of an intracerebral mass is a basic requirement for the planning of neurosurgical operations. Stereotactic atlases offer the possibility to adapt pre-operative imaging data onto normal anatomical conditions in the CNS. These atlases, however, reflect the standard variants of the CNS and do not allow to draw conclusions on local and secondary changes of the anatomy caused by the presence of pathological processes. The physical model proposed in this paper provides an estimate of the displacement of brain areas by an intracerebral mass. The modeling of brain parenchyma deformation is based on the mechanics of deformed media. The implementation of the model is successful in the group of primary brain tumors and meningiomas, and uses empirically-obtained data of a prospectively-selected patient population. The aim of the proposed model is, as further step, the integration and adaptation in apposite software solutions for the stereotactic orientation in the CNS.     

Brachytherapy for brain tumors

Over the past several decades neurooncologists have attempted to find an adjuvant treatment that prolongs survival for patients with malignant brain tumors. Brachytherapy, radiotherapy delivered by placing radioactive sources directly into the tumor, was initially thought to be the solution to this problem. Initial single institution studies showed very promising results; however, this technique has failed to show a significant survival advantage in two randomized studies. Despite this, brachytherapy continues to be used in a number of centers throughout the world for the treatment of various types of brain tumors including low-grade gliomas, anaplastic astrocytomas, glioblastomas, meningiomas and metastases. This article reviews brachytherapys rationale, radiobiology, complications, indications, and results from numerous studies that have focused on its application for brain tumors with emphasis on its application for glial tumors.     

Reoperation for brain metastases

We report the results of reoperation for brain metastases in 21 patients with recurrent tumors following initial successful resection. The tumor recurrences were local (original site) in 14 patients, and occurred at other sites in the brain in the remaining seven. Time to CNS recurrence ranged from 3 to 30 months. At time of repeat craniotomy, disease was limited to the CNS in 12 (57%) of the patients. Median survival following second craniotomy was 9 months, and the actuarial 2-year survival was 25%. Neurological improvement was seen in two thirds of the patients; the median duration of neurological improvement was 6 months. There was no mortality, and only one patient developed increased deficit following surgery. We conclude that repeat resection of brain metastases is an important therapeutic option in selected patients, and should be considered in symptomatic patients with accessible mass lesions before the use of other experimental treatment.     

Radiotherapy for brain tumors

Over the last 2 years, several advances have been made in the field of radiotherapy for brain tumors. Key advances are summarized in this review. Crucial technologic advances, such as radiosurgery, fractionated stereotactic radiotherapy, and intensity-modulated radiotherapy, are discussed. Better understanding of the interaction between the processes of angiogenesis, apoptosis, cell-cycle regulation, and signal transduction and the effects of ionizing radiation has made it clear that many of these ‘new agents’ are, in fact, valuable modulators of the radiation response. Another exciting molecular discovery is the recognition of radiation-induced promoters that can be exploited to cause spatially and temporally configured expression of selected genes; this approach may represent the ideal application of conformal radiation techniques in the future, yielding welldefined genetic changes in specifically targeted tissues. The final ‘frontier’ covered in this review is the newer categories of radiosensitizers, ranging from topoisomerase-I inhibitors, to expanded metalloporphyrins, to oxygendissociating agents.     

非小细胞肺癌伴脑转移放疗疗效分析

目的探讨非小细胞肺癌(NSCLC)伴脑转移全脑放疗的时机及预后影响因素。方法搜集147例NSCLC伴脑转移并行全脑放疗患者的临床资料,结合随访资料进行单因素和多因素Cox比例风险模型回归分析。结果颅外转移为NSCLC脑转移患者预后的独立影响因素,比值比(OR)为1.924,95%可信区间(CI)为1.356-2.728。颅外转移、确诊脑转移到全脑放疗的时间是有脑转移症状NSCLC患者预后的独立影响因素,OR分别为1.691和2.964,95%CI分别为1.003～2.850和1.674-5.248。颅外转移是无脑转移症状NSCLC患者预后的独立影响因素,OR为1.793,95%CI为1.099-2.925。结论颅外转移是影响NSCLC伴脑转移患者预后的重要因素,及早行全脑放疗有助于提高有脑转移症状的NSCLC脑转移患者的生存期。     

Value of whole brain re-irradiation for brain metastases--single centre experience

AimsThere is controversy in published studies regarding the role of repeat whole brain radiation (WBRT) for previously irradiated brain metastases. The aim of our retrospective study was to document the practice at Princess Margaret Hospital with respect to the re-irradiation of patients with progressive or recurrent brain metastatic disease after initial WBRT.Materials and methodsA comprehensive computerised database was used to identify patients treated for brain metastases with more than one course of WBRT between 1997 and 2003. Seventy-two patients were treated with WBRT for brain metastases and retreated with WBRT at a later date. The records of these patients were reviewed.ResultsThe median age was 56.5 years. The most common primary sites were lung (51 patients) and breast (17 patients). The most frequent dose used for the initial radiotherapy was 20 Gy/5 fractions (62 patients). The most common doses of re-irradiation were 25 Gy/10 fractions (22 patients), 20 Gy/10 fractions (12 patients), 15 Gy/5 fractions (11 patients) and 20 Gy/8 fractions (10 patients). Thirty-one per cent of patients experienced a partial clinical response after re-irradiation, as judged by follow-up clinical notes; 27% remained stable; 32% deteriorated after re-irradiation. Patients who had Eastern Cooperative Oncology Group performance status 0–1 at the time of retreatment lived longer. In responders, the mean duration of response was 5.1 months. The median survival after re-irradiation was 4.1 months. One patient was reported as having memory impairment and pituitary insufficiency after 5 months of progression-free survival.ConclusionRepeat radiotherapy may be a useful treatment in carefully selected patients. With increased survival and better systemic options for patients with metastatic disease, more patients may be candidates for consideration of repeat WBRT for recurrent brain metastases, but prospective studies are needed to more clearly document their outcomes.     

Subacute brain atrophy after radiation therapy for malignant brain tumor

Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.     

Whole brain radiotherapy for the treatment of multiple brain metastases

BACKGROUND： Brain radiotherapy is used to treat cancer patients who have brain metastases resulting from various primary malignancies. OBJECTIVES： To assess the effectiveness and adverse effects of whole brain radiotherapy （WBRT） in adult patients with multiple metastases to the brain. SEARCH STRATEGY： CENTRAL （The Cochrane Library）, MEDLINE, EMBASE, CANCERLIT, and CINAHL were searched. SELECTION CRITERIA： Randomized controlled trials （RCTs） in which adult patients with multiple metastases to the brain from any primary cancer and treated with WBRT were included. Trials of prophylactic WBRT were excluded as well as trials that dealt with surgery or WBRT, or both, for the treatment of a single brain metastasis. DATA COLLECTION AND ANALYSIS：     

Surgical resection followed by whole brain radiotherapy versus whole brain radiotherapy alone for single brain metastasis

PURPOSE: To compare the outcome of surgical resection followed by whole brain radiotherapy (WBRT) with WBRT alone in patients treated for single brain metastasis. METHODS AND MATERIALS: The data from 195 patients with single brain metastases were retrospectively evaluated. Of the 195 patients, 99 underwent resection of the metastasis followed by WBRT and 96 underwent WBRT alone. Seven additional potential prognostic factors were investigated: age, gender, Eastern Cooperative Oncology Group performance score, tumor type, interval between initial tumor diagnosis and WBRT, extracranial metastases, and recursive partitioning analysis class. Both treatment groups were well balanced for these factors. RESULTS: On multivariate analysis, improved survival was associated with resection (relative risk [RR], 1.20; 95% confidence interval [CI], 1.11-1.31; p < 0.001), lower recursive partitioning analysis class (RR, 1.58; 95% CI, 1.22-2.06; p < 0.001), age < or = 61 years (RR, 1.79; 95% CI, 1.23-2.61; p = 0.002), Eastern Cooperative Oncology Group performance score of 0-1 (RR, 2.47; 95% CI, 1.70-3.59; p < 0.001), and the absence of extracranial metastases (RR, 1.99; 95% CI, 1.41-2.79; p < 0.001). Improved local control was associated with resection (RR, 1.25; 95% CI, 1.11-1.41; p < 0.001) and age < or = 61 years (RR, 1.77; 95% CI, 1.09-2.88; p = 0.020). Improved brain control distant from the original site was associated with lower recursive partitioning analysis class (RR, 1.65; 95% CI, 1.03-2.69; p < 0.035), age < or = 61 years (RR, 1.81; 95% CI, 1.12-2.96; p = 0.016), and the absence of extracranial metastases (RR, 2.42; 95% CI, 1.52-3.88; p < 0.001). Improved control within the entire brain was associated with surgery (RR, 1.24; 95% CI, 1.12-1.38; p < 0.001) and age < or = 61 years (RR, 1.83; 95% CI, 1.21-2.77; p = 0.004). CONCLUSION: In patients with a single brain metastasis, the addition of resection to WBRT improved survival, local control at the original metastatic site, and control within the entire brain, but did not prevent the development of new brain metastases distant to the original site.     

Radiotherapy for metastatic brain tumors

Radiation therapy has been the most important treatment for patients with brain metastases. With the development of stereotactic irradiation, conventional radiotherapy is being employed less often. However, whole-brain radiation therapy (WBRT) is still the mainstay of treatment for multiple brain metastases. This article reviews the results of conventional radiotherapy for brain metastases, and discusses optimal treatment, including fractionation schedules and combination with stereotactic irradiation, and the effects on neurocognitive functions. The authors conclude that WBRT with 30 Gy in ten fractions is no longer optimal for every patient with multiple brain metastases. WBRT employing appropriate fractionation schedules with or without stereotactic boost should be considered, depending on the patient’s condition, disease status, and expected period of life.     

Gene therapy for brain tumors

‘Gene therapy’ can be defined as the transfer of genetic material into a patient’s cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug (‘suicide gene’) therapy, oncolytic therapy, replacement/ therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.