Management Of High-grade Gliomas Research Articles

Treatment of high-grade glioma with radiolabeled peptides

The management of high-grade glioma (HGG) patients in clinical routine represents a challenging task. HGG has a poor prognosis because of early recurrence or therapy-refractory disease following first-line standard therapy, which includes a multidisciplinary approach involving radical surgical resection followed by external beam radiation therapy in combination with chemotherapy. Glioma cells are known to express specific receptors or glycoproteins on their surface which can be used as biological targets for treatment. The application of radiopharmaceuticals consisting of a targeting and an effector domain has led to the introduction of new treatment approaches, aiming at a tumor-specific treatment sparing normal brain tissue. One of these new modalities is the peptide receptor radionuclide therapy (PRRT). Peptides labeled with radioactive nuclides can bind directly to the tumor cells and deliver high doses of radioactivity directly to the tumor tissue. This article reviews the literature for PRRT in HGG.

Carmustine-impregnated wafers and their impact in the management of high-grade glioma

Introduction: Carmustine-impregnated biodegradable wafers provide a locoregional adjunct to the treatment of patients with high-grade glial neoplasms. Their impact is that of delivering a chemotherapeutic agent directly to the tumor site at the time of neurosurgical intervention with a resulting increased local drug concentration and an ongoing therapeutic effect lasting several days to weeks.Areas covered: This manuscript reviews the preclinical and clinical studies that established carmustine-impregnated wafers as a locoregional therapy in the treatment of de novo as well as recurrent high-grade gliomas and compares it with other locoregional modalities currently under development. A pertinent English language literature search dating back to 1990 was undertaken.Expert opinion: Carmustine-impregnated wafers represent but one component of a multimodality armamentarium for the treatment of high-grade gliomas. The development of biodegradable compounds capable of incorporating additional therapeutic agents beyond carmustine is a subject of ongoing research. Integration of diverse treatment modalities into the management of complex high-grade cancers, taking advantage of predictive markers of efficacy, be they molecular or otherwise, will remain a major focus of clinical research in the second decade of this century.

MGMT immunoexpression in adamantinomatous craniopharyngiomas

At present, no effective medical treatment exists for recurrent and aggressive craniopharyngiomas that are resistant to conventional therapies, including surgery and adjuvant radiotherapy. Temozolomide is an alkylating chemotherapeutic agent used routinely in the management of high grade gliomas. The response to temozolomide is suggested to be dependent on the tumoral expression of O-6 methylguanine DNA methyltransferase (MGMT). Evidence supports that low MGMT immunoexpression correlates with positive response to temozolomide. Therefore, we aimed to assess MGMT immunoexpression in adamantinomatous craniopharyngiomas, in an effort to predict the likelihood of response to temozolomide. The MGMT immunostaining was performed on 23 adamantinomatous craniofaryngiomas operated at the Sisli Etfal Training and Research Hospital and identified by histological analysis. Paraffin embedded tissue sections were immunostained for MGMT and were evaluated semi-quantitatively. Of the 23 cases evaluated, 22 (96%) demonstrated negative (<10%) and 1 (4%) demonstrated low (10%) MGMT immunoexpression. Data from this study suggest a high proportion of adamantinomatous craniopharyngiomas exhibit negative/low MGMT immunoreactivity and could be treated with temozolomide, if conventional therapy fails.

Radiotherapy Planning in High-grade Gliomas: a Survey of Current UK Practice

Aims Primary brain tumours in adults are rare, with high-grade gliomas (HGG) being the most common and most aggressive type. The clinical management of rare tumours such as HGG can be heterogeneous across different cancer centres. The aim of this survey was to determine current UK practice in the primary management of HGG, particularly in light of the improved outcomes reported recently. Materials and methods In February 2009, a questionnaire was sent to 71 consultant clinical oncologists in the UK who were reported to have a neuro-oncology practice. Questions focussed on the radiotherapeutic management of HGG. Results In total, 46/71 (65%) completed questionnaires were returned; 31/46 (67%) routinely used magnetic resonance imaging/computed tomography fusion for radiotherapy planning; 34/36 (94%) routinely prescribed 60 Gy in 30 fractions in a single phase; 7/36 (19%) would consider 54–55 Gy in 30 fractions in selected clinical scenarios; 42/46 (91%) defined the planning target volume (PTV) as the gross tumour volume (GTV) + 2 – 3 cm margin and 42/46 (91%) outlined at least one ‘organ at risk’ (OAR). Accepted tolerance doses varied considerably, e.g. retina range: 30–54 Gy. Sixty-four per cent of clinicians (27/42) compromise the PTV and 30% (14/42) the GTV in order to keep OARs within preset tolerances. Nearly one-third (14/42) involve the patient in this decision-making process, e.g. weighing up the risk of late toxicity with the risks of reducing the dose to the PTV. Conclusion The results of this survey show areas of strong agreement as well as areas of variation in clinical practice of aspects of treatment planning for HGG between UK neuro-oncologists.

Incidence and management of high grade glioma in Māori and non-Māori patients

A retrospective analysis of 301 patients was undertaken between 1993 and 2003 to evaluate the relationship of ethnicity with incidence, treatment and survival in patients undergoing surgery for high grade glioma (HGG) in New Zealand. There was no difference in age standardised incidence of HGG in Māori compared to non-Māori patients; 4.2/100,000 person years (95% confidence interval [CI] 2.6–6.9) versus 4.1 (95% CI 3.6–4.6). Māori were more likely to have complete tumour resection (odds ratio 3.59 (95% CI 1.01–12.76)) but waited 1.32 (95% CI 0.98–1.79) times longer for radiotherapy. Median survival was 29 weeks with poorer survival in Māori compared to non-Māori (hazard ratio 1.55 [95% CI 0.95–2.55]). We concluded that the incidence of HGG in Māori is similar to non-Maori. However, Māori with HGG have higher rates of complete resection but wait longer for radiotherapy and may have poorer overall survival than non-Māori.

Lycopene in treatment of high-grade gliomas: A pilot study

The therapeutic benefit of lycopene is well established for carcinoma prostate in various clinical trials and has been proposed for other malignancies including high-grade gliomas. Randomized placebo control study in the Department of Radiation Oncology of a teaching hospital. Fifty patients with high-grade gliomas were treated with surgery followed by adjuvant radiotherapy and concomitant paclitaxel. Patients were randomized to receive either oral lycopene (Group A) 8 mg daily with radiotherapy or placebo (Group B). Pre-and post-radiotherapy plasma lycopene levels were measured using high-precision liquid chromatography. McDonald's criteria were used for response assessment. Magnetic resonance imaging (MRI) of brain and Single Photon Emission Computed Tomograph (SPECT) were done three-monthly for two visits and six-monthly thereafter. Primary endpoint was response at six months post radiotherapy. Statistical Analysis Used : The data was analyzed using SPSS Software v10.0 (SPSS corporation Chicago IL) by applying Student's t-test, ANOVA F test, Chi-square test and Karl Pearson Correlation Coefficient. Median age was 38 years. The commonest histology was glioblastoma multiforme (n = 32). Pre- and post-treatment plasma lycopene levels in the patients in Gropu A were 152 ng/ml and 316 ng/ml and in the patients in Group B were 93 ng/ml and 98 ng/ml (P = 0.009). There was non-significant differences in favor of lycopene between Group A and Group B with higher overall response at six months (P = 0.100), response at last follow-up (P = 0.171) and time to progression (40.83 vs. 26.74 weeks, P = 0.089)., The follow-up duration was significantly higher for Group A than Group B (66.29 vs. 38.71 weeks, P = 0.05). Addition of nutrition supplements such as lycopene may have potential therapeutic benefit in the adjuvant management of high-grade gliomas.

Bevacizumab in adult malignant brainstem gliomas

Torcuator et al. recently presented a case report in the Journal of Neuro-Oncology regarding an adult Brainstem glioma (BSG) treated with Bevacizumab and Irinotecan. The authors speak about clinical benefit and sustained radiographic response in an adult patient with diffuse BSG. They noted initial discordance between clinical improvement and increased enhancement on MRI, an enhancement which decreased in subsequent scans [1]. However, the report lacks clarity in terms of the neuro-radiographic characteristics on MRI which are correlated with high grade tumors, as well as the presence/absence of several other prognostic factors which may have an impact on clinical response and survival. Unfortunately, the data concerning BSG in the pre-MRI era are mostly reported in neurosurgical series where both pediatric and adult patients are grouped together [2]. Several of the author’s observations on the prognosis of the disease seem to stem from this. Recent studies in adults have shown that adult patients with BSGs tend to do better than children. Those patients who do better present without necrosis on MRI, low-grade histology and longer duration of symptoms ([4 months) prior to diagnosis. [2–5]. Table 1 presents a summary of the more important prognostic factors. Despite all these controversies, if, according to the authors, this patient had a high grade tumor on MRI and poor prognostic factors, then the response to bevacizumab and irinotecan can be considered truly impressive. But discordance between clinical and radiological responses in these tumors is not uncommon. The authors mention the importance of anti-edema effect of Bevacizumab. VEGF (Vascular Endothelial Growth Factor) inhibitors, as important determinants of capillary permeability, may be responsible for decreased enhancement (and vasogenic edema) which could result in transient improvement even in the absence of a substantial impact on the tumor burden [2, 6]. At our institution we have treated one adult affected by malignant infiltrative diffuse BSG who presented with shorter duration of symptoms (\3 months), cranial nerve deficits and heterogeneous contrast enhancement in the pons and medulla with a rim of necrosis (high grade using MRI). This case of malignant BSG was treated with Bevacizumab and concomitant Temozolomide and radiation because the treatment protocol (later published by Narayana et al. [7]) was already open at our institution and preliminary results were proving Bevacizumab to be safe with radiation and Temozolomide in the upfront management of high grade gliomas. At 6-month follow up, contrast enhancement disappeared, marked reduction was observed in non-enhanced tumor volume and perfusion drop off. At 30-month follow up, the patient is alive and stable with no new neurological symptoms. Nonetheless, given the enthusiasm for the use of Bevacizumab in adult BSGs, response should be interpreted in the context of prognostic factors if no biopsy is available for these tumors. S. Raza (&) Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY 10016, USA e-mail: shahzad.raza@nyumc.org

49. Incidence and Management of High Grade Glioma in Mäori and Non-Mäori

49. Incidence and Management of High Grade Glioma in Mäori and Non-Mäori

Feasibility of Using Bevacizumab With Radiation Therapy and Temozolomide in Newly Diagnosed High-Grade Glioma

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

Therapeutic Application of Noncytotoxic Molecular Targeted Therapy in Gliomas: Growth Factor Receptors and Angiogenesis Inhibitors

Growth factor receptors and angiogenesis play major roles in the oncogenesis of gliomas. Over the last several years, several noncytotoxic molecular targeted therapies have been developed against growth factor receptors and tumor angiogenesis. In gliomas, two main anti-growth factor receptor strategies have been evaluated in phase I/II clinical trials: (a) small molecule tyrosine kinase inhibitors (TKIs) and (b) monoclonal antibodies that target growth factors or growth factor receptors other than vascular endothelial growth factor (VEGF). Up to now, few glioma patients have responded to small TKIs (0%-14%) or monoclonal antibodies (three case reports) delivered as a single agent. Greater doses, combined therapies, as well as the identification of molecular biomarkers predictive of response and resistance are important in order to optimize drug delivery and improve efficacy. Antiangiogenic therapies are promising for the treatment of gliomas. Thalidomide and metronomic chemotherapy were the first antiangiogenic strategies evaluated, but they have shown only modest activity. Recent studies of bevacizumab, an anti-VEGF antibody, and irinotecan, a topoisomerase I inhibitor, have demonstrated a high response rate, suggesting that targeted antiangiogenic therapies may play a significant role in the management of high-grade gliomas in the future. However, the toxicity profiles of these agents are not fully defined and the radiological evaluation of possible tumor response is challenging. Clinical evaluation of several VEGF receptor TKIs is currently ongoing; one of these inhibitors, cediranib, has already demonstrated interesting activity as a single agent. The integrin inhibitor cilengitide represents another promising strategy.

Frequently asked questions in the medical management of high-grade glioma: a short guide with practical answers

Frequently asked questions in the medical management of high-grade glioma: a short guide with practical answers R. Stupp, A. F. Hottinger, M. J. van den Bent, P.-Y. Dietrich & A. A. Brandes Centre Hospitalier Universitaire Vaudois and University of Lausanne; Hopitaux Universitaire Genevois and University of Geneva, Switzerland; Erasmus University/Daniel de Hoed Cancer Center, Rotterdam, The Netherlands; Bellaria-Maggiore Hospital, Azienda USL of Bologna, Bologna, Italy

Psychosocial and supportive-care needs in high-grade glioma

The diagnosis and management of high-grade glioma has profound effects on patients and their families. Guidance issued by the UK National Institute of Health and Clinical Excellence in 2006 highlighted the lack of good studies of palliative care for patients with this disease. We describe new studies published from 2000 to 2007. High-grade glioma is undoubtedly a challenging research area, and many studies are poorly defined and have small and biased samples. Nevertheless the data reveal this to be a heterogeneous group of patients with complex needs that differ from those of patients with other cancers. Improvements in care require a united input from neurology and neurosurgery, oncology, and palliative care. The main research priorities are the development and assessment of psychosocial or supportive interventions and the investigation of service provision of specialist palliative and end-of-life care, which have hitherto been neglected.

Pretherapeutic prognostic impact of FDG-PET in high-grade gliomas: A multivariate analysis including all consensual prognostics factors

2080 Background: The prognostic value of positron emission tomography with [18F]-fluoro-2-deoxy-D-glucose (FDG-PET) has been previously reported in high-grade gliomas (HGG) with inconstant results using different statistical methods in nonhomogeneous population. Indeed, most of these studies are based on univariate or limited multivariate analysis, not including all consensual prognostics factors. The objective of this study was to determine the independent prognostic value of pretherapeutic FDG-PET on overall (OS) and event-free survival (EFS) in HGG. Methods: We retrospectively included 41 histologically-proven HGG: 31 glioblastomas multiforme, WHO grade IV (GBM) and 10 anaplasic gliomas, WHO grade III (AG). Pretherapeutic FDG-PET was performed on hybrid PET/computerized tomography. The uptake of FDG was assessed by a five visual-step metabolic grading (MG), and the ratio between tumour and controlateral maximal standardized uptake value (T/CL). OS and EFS following PET were determined by Kaplan-Meier analysis and correlated with FDG uptake by univariate and multivariate analysis (MVA) using log-rank test and Cox Regression. MVA included FDG uptake, age, Karnofsky performance status (KPS), extend of surgery, histologic grade (HG), and first-line chemotherapy in GBM. A second MVA was performed with FDG uptake and RPA (recursive partitioning analysis) classification of the RTOG. Results: Median OS and EFS of were respectively 18.4 and 9.2 months, significantly higher for AG than GBM (respectively p=0.040 and p=0.027). MG was nearly correlated with OS in the whole group and in the GBM (respectively p=0.077 and 0.059). T/CL ratio was significantly correlated with OS (p=0.003) and nearly significantly with EFS (p=0.052), independently from age, KPS, histological grade, surgery and RPA classification. In GBMs subgroup, T/CL ratio still predicted OS (p=0.018), independently from age, KPS, surgery, RPA classification and 1st-line chemotherapy. Conclusions: On preoperative FDG-PET, the ratio between tumour and controlateral uptake can provide additional prognostic information in the management of HGG, independently from consensual prognostic factors. No significant financial relationships to disclose.

Heavy element enhanced synchrotron stereotactic radiotherapy as a promising brain tumour treatment

Synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumours followed by stereotactic irradiation, in CT mode, with monochromatic X-rays from a synchrotron source, tuned at an optimal energy. The irradiation geometry, characteristic X-rays, photoelectrons, and Auger electrons generated on high-Z atoms by kilovoltage X-rays produce a localized dose enhancement. Two complimentary SSR approaches have been successfully developed in the past 5 years in our team, and may be promising in high-grade glioma management: iodine-enhanced SSR, with an iodinated contrast agent; and Pt-enhanced SSR; a concomitant radio-chemotherapy treatment with locoregional injection of platinated chemotherapy drugs. The results for iodine-enhanced SSR using contrast agents are presented in this paper. IUdR-enhanced SSR was also tested in this study. Up to 15 Gy, intracarotid infusion of iodine significantly improved the rats' survival compared to irradiation alone. SSR provides the most protracted survivals of F98 glioma-bearing rats. The technique is currently transferred to clinical trials. Iodine-enhanced SSR will be implemented first, because of its simplicity; and pave the way for Pt-enhanced SSR, the most efficient technique, but still needing to be improved in terms of intrinsic toxicity.

Heavy-atom enhanced synchrotron stereotactic radiotherapy of brain tumors: from DNA to preclinical studies

Gliomas are the most frequent primary brain tumors in adults. Despite multimodality treatment strategies that combine surgery, chemotherapy and radiotherapy, high grade gliomas are almost uniformly fatal. Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a novel therapeutic modality proposed to increase the toxicity to the tumor while protecting the surrounding healthy tissue. It consists in selective accumulation of high-Z elements in tumor followed by stereotactic irradiation, in tomography mode, with monochromatic X-rays from a synchrotron source, tuned at an optimal energy. Two complimentary SSR approaches have been successfully developed in the past 5 years, and may be promising in high-grade glioma management: iodine-enhanced SSR , with an iodinated contrast agent; and Pt-enhanced SSR , , a concomitant radio-chemotherapy treatment with locoregional injection of platinated chemotherapy drugs. Several in vitro and in vivo experiments have been carried out at the European Synchrotron Radiation Facility, either with iodine or platinum. In vivo experiments are performed on F98 glioma-bearing rats. The F98 glioma model simulates several characteristics of human glioblastoma including lethality following treatment with a variety of therapeutic modalities. Recently, we have shown that a significant increase in survival time is obtained when the platinated drug (cisplatin or carboplatin) is infused intratumoraly followed by X-rays irradiation. Furthermore, a significant percent of animals are cured. To optimise the treatment, work is in progress in order to determine and increase the incorporation of heavy-atoms in tumoral cells and also to improve the intracerebral drug distribution by developing new injection methods and using different chemotherapeutic drugs including oxaliplatin, chlorotertpyridineplatinum and 5-iodo-2’-deoxyuridine. In addition, efforts will be made to have a better understanding of the biological consequences at the molecular and cellular level of the SSR treatment. 1 - Adam JF et al, International Journal of Radiation Oncology, Biology, Physics 2006; 64:603-611. 2 Biston MC et al, Cancer Research 2004; 64:2317-2323. 3 Rousseau J et al, Clinical Cancer Research 2007;13:5195-5201.

The Role of Surgery in High-grade Glioma – Is Surgical Resection Justified? A Review of the Current Knowledge

The aims of this article were to review the role of surgical resection in the management of high-grade gliomas and to determine whether there is any survival benefit from surgical resection. A literature review of the influence of surgical resection on outcome was carried out. Relevant original and review papers were obtained through a PubMed search using the following keywords: glioma, resection, prognosis and outcome. Presently, there is a lack of evidence to support a survival benefit with aggressive glioma resection, but this should not detract patients from undergoing surgery as there are many other clinical benefits of glioma excision. In addition, limiting surgical morbidity through the use of adjuvant techniques such as intraoperative magnetic resonance imaging (MRI), functional MRI and awake craniotomy is becoming increasingly important. Ideally, a randomised controlled trial would be the best way to resolve the issue of whether (and to what extent) surgical resection leads to improvements in patient outcome and survival, but this would not be ethical. The second best option would be well-controlled retrospective studies with a multivariate analysis of all potential confounding factors.

Improvements in Quality of Care Resulting From a Formal Multidisciplinary Tumour Clinic in the Management of High-grade Glioma

There is increasing belief that a formal protocol-based multidisciplinary care model should be adopted as an optimal care model in oncology. However, there is minimal outcome evidence to demonstrate an improvement in patient care. The aim of this study was to compare clinical quality outcomes between patients with high-grade glioma managed at one hospital using a formal neuro-oncology multidisciplinary tumour clinic (MTC) and a second hospital with a traditional on-call referral pattern (non-MTC). Patients with high-grade glioma managed radically with radiation therapy at 2 Singapore hospitals from May 2002 to May 2006 were entered into a prospective database. Patients were grouped into management via MTC or non-MTC. Four clinical quality indicators were chosen retrospectively to assess the variation in practice: a) Use of computed tomography (CT) or magnetic resonance (MR) imaging post-resection (POI) for assessment of residual disease; b) Commencement of radiation therapy (RT) within 28 days of surgery; c) Adjuvant chemotherapy use for glioblastoma multiforme (CTGBM) and d) Median survival. Sixty-seven patients were managed radically, with 47 by MTC and by 20 by non-MTC. MTC patients were more likely to have POI (P = 0.042), and CTGBM (P = 0.025). Although the RT start time was similar for the whole cohort (60% versus 45%: P = 0.296); for GBM patients, the RT start was earlier (63% vs 33% P = 0.024). The median survival for the MTC group was 18.7 months versus 11.9 months for the non-MTC group (P = 0.11). Clinical quality outcomes were significantly improved in patients with high-grade glioma managed in this neuro-oncology MTC.

Dose and duration of dexamethasone in patients with high grade gliomas (HGG): Relationship to steroid myopathy (SM)

18517 Background: Steroids are critical in the management of HGG due to their ability to control peri-tumoral edema. Myopathy is a disabling complication of steroids leading to loss of ambulation and respiratory compromise. We sought to describe the use of steroids in the first 8 months after the diagnosis of HGG and its relationship to SM. Methods: Charts of all adults with HGG diagnosed and treated at Johns Hopkins Hospital from June 2004 to May 2005 were reviewed. Patients who died in less than 8 months were excluded. Starting steroid dose, subsequent documented doses, initial date and dates of change were recorded. Only charts with the phrase “steroid myopathy” were defined as SM positive. Results: Twenty-eight patients met all inclusion criteria. The mean age was 57.2 ± 8.7 years and 19 (67.8%) were males. All patients (100%) received steroids. Dexamethasone was used exclusively. Ninety-three percent of patients received &gt;16mg/day and 36% were on &gt;16mg/day for at least a month. The average daily dose was 15.3 ± 7.1 mg. Mean cumulative dose was 2.8 ± 1.8 grams. The median peak dose was 40mg/day (range 16–120mg/day). Median days on steroids was 224 days (range 5–224 days) from diagnosis and 67.8% of patients were on continuous steroids for 8 months. Eleven (39% [95% CI: 22%-59%]) of the 28 patients were defined as SM. Seven of the 11 (63.6%) SM patients required wheelchairs versus two (11.8%) without SM (p = 0.004). Days on steroid was significantly longer (p = 0.012) in the SM group (214 ± 32 days) versus the non-SM group (155 ± 81days). No strong evidence supported differences between groups in total dose, average daily dose, peak dose or days on high dose steroids. Conclusions: Patients with HGG are exposed to high doses of steroids for long periods. SM was noted in 39% of our patients and most required wheelchairs within 8 months of diagnosis. These figures are likely significant underestimates given the amount of steroids administered and the retrospective nature of this study. Our data confirm prior reports of an association between duration of steroid use and SM. The findings highlight the need to prevent SM using alternate dosing schedules and agents and to develop effective treatment interventions for SM. No significant financial relationships to disclose.

Photodynamic Therapy and Detection of High-Grade Gliomas

The first reported use of photodynamic therapy (PDT) for the treatment of high-grade gliomas occurred in 1981. In the intervening years there have been relatively few clinical trials to investigate the efficacy of this therapeutic modality for the treatment of gliomas. This is due, in part, to the rarity of the disease, and the ever growing list of novel therapies that PDT must compete against. These factors make accrual of patients for clinical trials a difficult proposition. During the mid-1990s, a number of reviews were published that effectively summarized the status of PDT for the management of high-grade gliomas. The intent of the present work is to provide an update of recent developments (1996-2004) in PDT and photodynamic detection (PDD) of gliomas, in particular, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA).

Surgical management of high-grade gliomas

High-grade gliomas, in particular anaplastic astrocytoma and glioblastoma multiforme, represent two of the most devastating forms of brain cancer. In spite of the poor prognosis, new treatments and emerging therapies are making an impact on this disease. This review discusses the role of the surgical management of high-grade gliomas and provides an overview of the currently available therapies which depend on surgical intervention. At the same time, cutting-edge clinical trials for patients with malignant brain tumors are reviewed to provide further insights into potential future therapies.