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Background: Glioblastoma is the most common and aggressive primary tumor in adults. A narrative review of all the relevant papers known was conducted. Materials and methods: Reviews, clinical trials, and randomized controlled trials published from 1981 through September 2021 and written, or at least abstracted, in English were analyzed. Results: The standard of care for glioblastoma is the maximum safe resection possible, followed by radiation therapy and concurrent temozolomide (TMZ) and daily TMZ and tumor treatment fields (TTFields) after irradiation. There is no evidence to date of the benefit of brachytherapy, radiosurgery (SRS), fractional stereotactic radiotherapy (FSRT), and hyperfractionated radiotherapy over conventional external beam radiation therapy (EBRT) for the primary tumor. The assessment of age and performance status before treatment in the elderly enables hypofractionated radiotherapy. The research of tumor molecular signatures contributes to the choice of the best-targeted drug therapy. In recurrent glioblastoma, it is necessary to balance the risks and benefits of re-radiation and association with bevacizumab. Solid data confirming the role of immunotherapy in the treatment of malignant glioma are still lacking. Conclusions: Although the treatment of glioblastoma has evolved in terms of local control, mortality remains close to 12 months after diagnosis. To obtain better results and reduce recurrence, future research needs to investigate the frontiers of knowledge, such as the elucidation of the molecular mechanisms related to the tumor, the optimization of drugs to overcome the blood-brain barrier effectively, and the discovery of new therapies aimed at the heterogeneous profile of this neoplasm. [ABSTRACT FROM AUTHOR]

As the most common primary malignant brain tumor with a devastating survival perspective, glioblastoma treatment remains a major challenge in medicine. Among recent approaches, 5-aminolevulnic acid (5-ALA) mediated interstitial photodynamic therapy (iPDT) has shown promising results. 16 patients with de-novo glioblastoma treated with iPDT were retrospectively analyzed regarding survival and characteristic tissue regions discernible in recorded MRI data. These regions were segmented at different stages and analyzed, especially regarding their impact on survival. The iPDT cohort showed a median progression-free survival (PFS) of 16.4 months and a median overall survival (OS) of 28.0 months. 10 of 16 patients experienced prolonged survival (≥ 24 months). In comparison to other therapies, the iPDT cohort maintained a significantly prolonged PFS and OS. Known prognostic factors for survival after standard treatment were not found to be relevant for this cohort, such as necrosis-tumor ratio, tumor volume and post-treatment contrast enhancement. In this study, iPDT has shown its potential, especially by a large fraction of prolonged survival. Prognosis-related parameters can be derived from patient data and MR imaging data, but their interpretation has to be adapted in comparison to standard-of-care. [ABSTRACT FROM AUTHOR]

Craniotomy for tumor resection improves survival in adults aged ≥65 years with malignant glioma. However, the decision to attempt resection must be weighed against the near-term risks of surgery. This study examined risk factors associated with unfavorable 30-day outcomes following craniotomy for malignant glioma resection in older adult patients. The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 was queried for patients aged 65–89 years undergoing craniotomy for primary, supratentorial, malignant, intra-axial tumor resection. 30-day outcomes included mortality, life-threatening complication, unplanned readmission, reoperation, and change in living disposition. Independent risk factors were identified through multiple logistic regression. In total, 1016 cases met eligibility criteria. Death occurred in 35 cases (3.4%). 58 patients (5.7%) suffered at least one life-threatening complication. Risk factors for morbidity and mortality included frontal lobe tumor, corticosteroid use, dependent functional status, and underweight body mass index (BMI). Among 816 patients admitted from home, 33.9% experienced a change in living disposition, which was associated with advanced age, female sex, frontal lobe tumor, underweight BMI, and diabetes mellitus (among others). Readmission (11.8%) was most frequently attributed to altered mental status, seizure, or venous thromboembolism. Reoperation was rare (4.5%). Death and life-threatening morbidity were rare early outcomes for older adult patients undergoing malignant glioma resection. However, one in three patients admitted from home experienced a change in living disposition. Factors related to baseline state of health, tumor location, and corticosteroid regimen should be considered when anticipating the immediate postoperative course. [ABSTRACT FROM AUTHOR]

• The purpose is to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma. • PDT improved local tumor control and improved survival outcomes. • Patients treated with PDT had a higher rate of distant recurrence than local recurrence. For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma. Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery. In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months. PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions. [ABSTRACT FROM AUTHOR]

Highlights • Glioma stem cells would be responsible for treatment resistance of glioblastoma. • Glioma stem like cells, GSLCs, of A172 glioma are more resistant to anticancer drugs. • The GSLCs more highly express genes for protoporphyrin-IX biosynthesis. • The GSLCs more highly accumulate protoporphyrin-IX from exogenous ALA. • GSLCs are more sensitive to ALA-PDT than their matched non-GSLCs. Abstract Background Glioblastoma (GBM) is a highly malignant lethal brain cancer. Accumulated evidence suggests that elevated resistance of GBM to both chemo- and radio-therapy is, at least in part, due to the presence of a small population of glioma stem cells (GSC). In the present study, we aimed to determine the sensitivity of GSCs to 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). Methods For this purpose, we established GSC-enriched cell cultures (termed glioma stem-like cells or GSLCs) from A172 human GBM cell line. Under our cultivation conditions, GSLCs formed floating spheroid clusters that contained increased population of CD133/Sox2 expressing cells. Firstly, to compare the activity of protoporphyrin IX (PpIX) biosynthesis in the GSLCs and the parental A172 glioma cells, we examined the expression levels of biosynthesis enzymes and transporters for PpIX using qRT-PCR, and investigated the intracellular levels of PpIX with use of flow cytometry analysis. Then, we evaluated the sensitivity of these cells to ALA-PDT in vitro. Finally, to confirm the therapeutic impact of ALA-PDT on GSLCs with more clinically relevant model, we performed the same experiment using three different patient-derived glioma sphere lines, which cultivated them either in stem cell media or under differentiation conditions in the presence of serum. Results and Conclusion GSLCs expressed higher mRNA levels of PpIX biosynthesis enzymes and its transporters PEPT1/2 and ABCB6, when compared to the parental A172 glioma cells. Consistently, flow cytometry analysis revealed that upon incubation with ALA, GSLCs accumulate a higher level of PpIX. Finally, we showed that GSLCs were more sensitive to ALA-PDT than the original A172 cells, and confirmed that all patient-derived glioma sphere lines also showed significantly increased sensitivity to ALA-PDT if cultivated under the pro-stem cell condition. Our data indicate that ALA-PDT has potential as a novel clinically useful treatment that might eliminate GBM stem cells that are highly resistant to current chemo- and radio-therapy. [ABSTRACT FROM AUTHOR]

Background: Temozolomide (TMZ) is a first-line chemotherapeutic drug for malignant gliomas. Nonetheless, TMZ-induced side effects and drug resistance remain challenges. Our previous study showed the suppressive effects of honokiol on growth of gliomas.Purpose: This study was further aimed to evaluate if honokiol could enhance TMZ-induced insults toward malignant glioma cells and its possible mechanisms.Methods: Human U87 MG glioma cells were exposed to TMZ, honokiol, and a combination of TMZ and honokiol. Cell survival, apoptosis, necrosis, and proliferation were successively assayed. Fluorometric substrate assays were conducted to determine activities of caspase-3, -6, -8, and -9. Levels of Fas ligand, Bax, and cytochrome c were immunodetected. Translocation of Bax to mitochondria were examined using confocal microscopy. Mitochondrial function was evaluated by assaying the mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and complex I enzyme activity. Caspase-6 activity was suppressed using specific peptide inhibitors. The honokiol-induced effects were further confirmed using human U373 MG and murine GL261 cells.Results: Exposure of human U87 MG glioma cells to honokiol significantly increased TMZ-induced DNA fragmentation and cell apoptosis. Interestingly, honokiol enhanced intrinsic caspase-9 activity without affecting extrinsic Fas ligand levels and caspase-8 activity. Sequentially, TMZ-induced changes in Bax translocation, the MMP, mitochondrial complex I enzyme activity, intracellular ROS levels, and cytochrome c release were enhanced by honokiol. Consequently, honokiol amplified TMZ-induced activation of caspases-3 and -6 in human U87 MG cells. Fascinatingly, suppressing caspase-6 activity concurrently decreased honokiol-induced DNA fragmentation and cell apoptosis. The honokiol-involved improvement in TMZ-induced intrinsic apoptosis was also confirmed in human U373 MG and murine GL261 glioma cells.Conclusions: This study showed that honokiol can enhance TMZ-induced apoptotic insults to glioma cells via an intrinsic mitochondrion-dependent mechanism. Our results suggest the therapeutic potential of honokiol to attenuate TMZ-induced side effects. [ABSTRACT FROM AUTHOR]

Summary Background 5-Aminolevulinic Acid (5-ALA) induced fluorescence is useful in guiding glioma resection. The extent of 5-ALA accumulation is beyond gadolinium contrast enhancement. 1,2 Supratotal resection may be achieved, potentially granting patients with better survival. We present our experience on 5-ALA guided glioma resection in Chinese ethnics. Method Sixteen Patients ingested 5-ALA (Gliolan, Medas Germany) 20 mg/kg·m 2 4 h before surgery. The tumor resection was guided by fluorescence with neurosurgical microscope. Patient was monitored for general condition, especially for new neurological deficits. Postoperative MRI served as the assessment for extent of resection (EOR). Result High grade glioma was confirmed in 12 cases, low grade glioma in three and one inflammation. 5-ALA was used in ten patients with known malignant glioma, and in six patients with presumed diagnosis of malignant glioma. Fifteen cases had positive fluorescence. The intensity was strong in eight and moderate in seven cases. MRI suggested total resection was achieved in 9 patients, near total resection in two and five had subtotal resection. EOR was associated with duration between ingestion of 5-ALA and timing when microscope was brought in for visualization of fluorescence (p = 0.038). Two patients suffered from temporary visual field defects. One patient developed hemiparesis after surgery. Conclusion 5-ALA is a useful intra-operative guidance for resection. It increases the percentage of total removal of the tumor. It should be used within the window period of the action (4–12 h). [ABSTRACT FROM AUTHOR]

Background Oral 5-aminolevulinic acid (ALA) induces biosynthesis/accumulation of the natural photo-sensitizer protoporphyrin IX (PpIX) in cancer cells. ALA is used widely in photodynamic diagnosis (PDD) and therapy (PDT) during malignant glioma surgery, but few studies have examined the effects of photodynamics plus ALA on normal brain tissue in vivo. We investigated the effects of ALA-mediated PDD and PDT on normal brain tissue. Methods We established a rat model in which the brain surface was irradiated through the skull by light-emitting diode (635 nm) after ALA administration. Using this model, we investigated the effects of various amounts of light irradiation with various ALA doses on brain tissue. Results Neurological symptoms developed with administration of ALA at 240 or 120 mg/kg accompanied by irradiation at 100 or 400 J/cm 2 , respectively. Dye leakage occurred due to disruption of the blood–brain barrier (BBB) at 90 mg/kg and 100 J/cm 2 , respectively. Thickness of the cortex increased significantly at 240 mg/kg and 400 J/cm 2 , respectively. The number of neurons appeared to decrease at 200 mg/kg plus 400 J/cm 2 , respectively, and there was an increase in the number of cells that were positive for terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) staining. Conclusions ALA-mediated PDT is safe at doses of 90 mg/kg or less followed by light irradiation of 100 J/cm 2 in rat brains. At doses above this threshold, ALA-PDT led to irreversible BBB and brain damage in rats. [ABSTRACT FROM AUTHOR]

Background Fluorescence image guided surgery (FIGS) with 5-aminolevulinic acid for malignant gliomas improves surgical outcome. One of the problems during FIGS is photobleaching under surgical microscopic white light. A solid laser-based white light source for neurosurgery that we developed does not include light with a wavelength of around 405 nm, which is strongly absorbed by protoporphyrin IX. In the present study, we examined the efficacy of this light source to prevent the photobleaching of protoporphyrin IX-induced fluorescence. Methods Filter papers transfused with protoporphyrin IX solution and a coronally sectioned F98 glioma rat model pretreated with 50 mg/kg 5-aminolevulinic acid were continuously exposed to white light. One group was exposed to conventional xenon-based white light and another group was exposed to laser-based white light. Fluorescence at a wavelength of 635 nm was measured with a radiospectrometer (in vitro study) and the relative fluorescence brightness was also measured in digital images (in vivo study) under excitation from violet blue light emitted from diodes every 5 min. Results and conclusion Estimated time for 50% photobleaching was prolonged about two times in the laser-based white light exposure group compared with that in the xenon-based white light exposure group (9.1/18.7 min). In the brain tumor rat model, it was also prolonged about 2.7 times (15.1/40.7 min). A laser-based white light source may inhibit photobleaching during FIGS for malignant gliomas. This light source for neurosurgical microscopy has the potential to prolong the prognosis of malignant glioma patients. [ABSTRACT FROM AUTHOR]

An innovative treatment modality for brain tumors is interstitial photodynamic therapy [1,2]. The analysis of patients undergoing iPDT contain the assessment of the outcome, and qualitative changes in the MRI due to iPDT have already been reported [1,3]. Patients with newly diagnosed malignant gliomas treated with 5-aminolevulinic acid mediated iPDT were retrospectively analyzed for PDT-induced effects. For this MRI Sequences (T1-weighted with/without contrast agent, T2-weighted, Diffusion-weighted) before iPDT, within 24h after iPDT, and follow up images were quantitatively analyzed concerning changes. Furthermore, observed conspicuities were analyzed in the temporal course after iPDT and spatially compared. Postoperative MRI after therapy showed, in most cases, a circumscribed heterogeneous region, which was best visible in the T2-weighted image. This region usually shows a larger extent than the treated contrast agent accumulating tumor volume in the T1-weighted MRI. MRI regions with restricted diffusion showed high overlap with this circumscribed region visible in T2-MRI. Overall, increased edema volumes were observed after treatment, which shrank in the temporal course during follow-up. The tumor contrast enhancement was only residually visible or in unspecific areas after iPDT that could not be associated with the contrast-enhanced volume before iPDT. Similar to a pseudoprogression, the contrast-enhanced volume increased again at the first follow-up but then shrank again in the temporal course. These analyses give insight into iPDT effects visible in MRI and, with further analysis, may also provide indications for direct treatment effect. [ABSTRACT FROM AUTHOR]

Brain tumor treatment via interstitial photodynamic therapy (iPDT) needs precise treatment light delivery, which is essential for the conduction of the therapy [1]. The light delivery and the resulting light dosimetry are highly dependent on the optical tissue properties of the tumor tissue and the surrounding brain tissue. Employing intraoperative spectral online monitoring (SOM), it looks possible to assess the treatment light transmittance between the used light applicators and monitor potential changes during therapy [2]. Changes have been observed during clinical iPDT-illumination and can be interpreted as changes in the optical tissue properties [2, 3]. In vitro experiments mimicking the clinical iPDT-illumination situation using liquid optical tissue phantoms, including blood, showed SOM intensity changes in transmittance. Due to simultaneous remission spectroscopy, this can be related to the deoxygenation of hemoglobin and its oxidation to methemoglobin (MetHb) [4]. The analysis of data from clinical iPDT-procedures confirmed this interpretation. Based on intraoperative SOM data, changes in the optical absorption coefficient have been calculated and correlated with newly diagnosed early visible intrinsic T1-hyperintensity in the treatment volume [3]. The intrinsic T1 hyperintensity is clinically an indicator of the formation of MetHb after silent hemorrhages, which may occur during iPDT. As the T1 hyperintensity was early visible in the MRI, the corresponding early appearance of MetHb was in context with the iPDT and consistent with the in vitro experiments. Further in vitro experiments showed that changes in optical tissue properties and hemoglobin oxidation is not only possible due to ROS production during iPDT but also due to a slight temperature increase during iPDT by 4°C [5]. These results give more insight into mechanisms occurring during iPDT irradiation, but the impact on treatment outcome has still to be assessed. [ABSTRACT FROM AUTHOR]

• Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. • Hypoxia-GSCs showed higher mRNA levels of FECH compared with Normoxia-GSCs. • Hypoxia-GSCs had lower intracellular PpⅨ accumulation that Normoxia-GSCs. • ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs. Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT). Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O 2 21%)-cultured cells (Normoxia-GSCs), and hypoxia (O 2 5%)-cultured cells (Hypoxia-GSCs). To compare the effects of different oxygen partial pressures on photoporphyrin Ⅸ (PpⅨ) biosynthetic activity, PpⅨ biosynthetic enzyme and transporter expression levels were examined by qRT-PCR; the intracellular PpⅨ concentration was determined using flow cytometry. Additionally, the sensitivity of these two groups of cells to ALA-PDT was evaluated in vitro. Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs. Hypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration. [ABSTRACT FROM AUTHOR]

BCNU wafers are a form of interstitial chemotherapy that is expected to improve the survival of patients with malignant glioma. However, their adverse events, especially brain edema, sometimes cause significant clinical symptoms. In this study, we performed a volumetric analysis of brain edema after the implantation of BCNU wafers and reported on the clinical course, and exacerbation factors of brain edema. Twelve patients who underwent surgical resection of supratentorial malignant glioma and BCNU wafer implantation, were enrolled. Radiographic quantitative analysis was conducted and compared with a historical control. The volume change in brain edema was divided into three groups and correlation with clinical symptoms was then evaluated. Compared with the control group, the brain edema in the BCNU wafer implantation group was significantly prolonged after surgery. Radiographic volumetric analysis revealed an increase of more than 25% at any time after surgery in four patients (33%) and a reduction of less than 25%, 1 month after surgery in three patients (25%). Grade 3 clinical deterioration related to brain edema occurred in two patients and Grade 2 in one patient. Univariate analysis revealed that the radiographic deterioration of brain edema had no correlation with age, sex, diagnosis, tumor grade, preoperative volume of brain edema and tumor, residual tumor volume, or number of BCNU wafers. Radiographic quantitative analysis of brain edema indicated that BCNU wafer implantation may induce the prolongation and enlargement of brain edema with or without neurological deterioration. Brain edema may be controlled by intensive perioperative treatment with diuretics and corticosteroids. [ABSTRACT FROM AUTHOR]

Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9 years, p = 0.0005) and second surgery (1.0 vs. 3.5 years, p < 0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4 years, p = 0.008) and OS (median 10.0 vs. 4.2 years, p = 0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population. [ABSTRACT FROM AUTHOR]

Background: Our previous study showed that honokiol, a bioactive polyphenol, can traverse the blood-brain barrier and kills neuroblastoma cells.Purpose: In this study, we further evaluated the preclinical effects of honokiol on development of malignant glioma and the possible mechanisms.Methods: Effects of honokiol on viability, caspase activities, apoptosis, and cell cycle arrest in human glioma U87 MG or U373MG cells were assayed. As to the mechanisms, levels of inactive or phosphorylated (p) p53, p21, CDK6, CDK4, cyclin D1, and E2F1 were immunodetected. Pifithrin-α (PFN-α), a p53 inhibitor, was pretreated into the cells. Finally, our in vitro findings were confirmed using intracranial nude mice implanted with U87 MG cells.Results: Exposure of human U87 MG glioma cells to honokiol decreased the cell viability. In parallel, honokiol induced activations of caspase-8, -9, and -3, apoptosis, and G1 cell cycle arrest. Treatment of U87 MG cells with honokiol increased p53 phosphorylation and p21 levels. Honokiol provoked signal-transducing downregulation of CDK6, CDK4, cyclin D1, phosphorylated (p)RB, and E2F1. Pretreatment of U87 MG cells with PFN-α significantly reversed honokiol-induced p53 phosphorylation and p21 augmentation. Honokiol-induced alterations in levels of CDK6, CDK4, cyclin D1, p-RB, and E2F1 were attenuated by PFN-α. Furthermore, honokiol could induce apoptotic insults to human U373MG glioma cells. In our in vivo model, administration of honokiol prolonged the survival rate of nude mice implanted with U87 MG cells and induced caspase-3 activation and chronological changes in p53, p21, CDK6, CDK4, cyclin D1, p-RB, and E2F1.Conclusions: Honokiol can repress human glioma growth by inducing apoptosis and cell cycle arrest in tumor cells though activating a p53/cyclin D1/CDK6/CDK4/E2F1-dependent pathway. Our results suggest the potential of honokiol in therapies for human malignant gliomas. [ABSTRACT FROM AUTHOR]

Aim To establish intensity-modulated radiotherapy (IMRT) planning procedures that spare the corticospinal tract by integrating diffusion tensor tractography into the treatment planning software. Background Organs at risk are generally contoured according to the outline of the organ as demonstrated by CT or MRI. But a part of the organ with specific function is difficult to protect, because such functional part of the organ cannot be delineated on CT or conventional sequence of MRI. Methods Diagnostic and treatment planning images of glioblastoma patients who had been treated by conventional 3-dimensional conformal radiotherapy were used for re-planning of IMRT. Three-dimensional fiber maps of the corticospinal tracts were created from the diffusion tensors obtained from the patients before the surgery, and were blended with the anatomical MR images (i.e. gadolinium-enhanced T1-weighted images or T2-weighted images). DICOM-formatted blended images were transferred and fused to the planning CT images. Then, IMRT plans were attempted. Results The corticospinal tracts could be contoured as organs at risk (OARs), because the blended images contained both anatomical information and fiber-tract maps. Other OARs were contoured in a way similar to that of ordinary IMRT planning. Gross tumor volumes, clinical target volumes, planning target volumes, and other OARs were contoured on the treatment planning software, and IMRT plans were made. Conclusions IMRT plans with diminished doses to the corticospinal tract were attained. This technique enabled us to spare specific neuron fibers as OARs which were formerly "invisible" and to reduce the probability of late morbidities. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the feasibility and efficacy of hypo-fractionated simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) using three-layered planning target volumes (PTV) for malignant gliomas. Materials and Methods: We conducted a retrospective analysis of 12 patients (WHO grade IV-10; III-2) postoperatively treated with SIB-IMRT with concurrent temozolomide. Three-layered PTVs were contoured based on gadolinium-enhanced magnetic resonance imaging as follows; high risk PTV (H-PTV) as the area of surgical bed including residual gross tumor with a 0.5 cm margin; low risk PTV (L-PTV) as the area surrounding the high risk PTV with 1.5 cm margin; moderate risk PTV (M-PTV) as a line at one-third the distance from high risk PTV to low risk PTV. Total dose to high risk PTV was 70 Gy in 8 and 62.5 Gy in 4 patients. Results: The median follow-up time was 52 months in surviving patients. The 2- and 5-year overall survival (OS) rates were 66.6% and 47.6%, respectively. The 2- and 5-year progression-free survival (PFS) rates were 57.1% and 45.7%, respectively. The median OS and PFS were 48 and 31 months, respectively. Six patients (50%) progressed: in-field only in one, out-ield or disseminated in 4, and both in one patient. All patients completed planned treatments without a toxicity-related gap. Asymptomatic radiation necrosis was observed in 4 patients at post-radiotherapy 9-31 months. Conclusion: An escalated dose of hypofractionated SIB-IMRT using three-layered PTVs can be safely performed in patients with malignant glioma, and might contribute to better tumor control and survival. [ABSTRACT FROM AUTHOR]

• 5-ALA was associated with low blood pressure in malignant glioma surgery. • Intraoperative hypotension was associated with increasing age. • RAS inhibitors boost the blood pressure-lowering effect of 5-ALA. • 5-ALA associated with low blood pressure may be mediated by NO in endothelial cells. Use of 5-aminolevulinic acid for photodynamic malignant tumor diagnosis reportedly causes intraoperative hypotension (systolic blood pressure < 70 mmHg) during urologic surgery. However, its association with intraoperative hypotension in malignant glioma surgery and underlying mechanisms has not yet been elucidated.. This study aimed to investigate whether 5-aminolevulinic acid administration is associated with intraoperative hypotension in malignant glioma surgery and explore the mechanisms of 5-aminolevulinic acid-induced hypotension in vitro. In this retrospective multicenter cohort study, we investigated intracellular nitric oxide as a candidate mediator of hypotension in response to 5-aminolevulinic acid in vitro in human umbilical vein endothelial cell cultures. Of 142 patients, 94 underwent 5-aminolevulinic acid-guided surgery. Systolic blood pressure was significantly lower throughout surgery with 5-aminolevulinic acid administration. 5-Aminolevulinic acid administration was an independent risk factor for intraoperative hypotension according to multivariable logistic regression analysis (89% vs. 56%; odds ratio = 6.72, 95% confidence interval [2.05–22.1], P = 002). In subgroup analysis of the 5-aminolevulinic acid group, increasing age and use of renin-angiotensin system inhibitors had a synergistic effect with 5-aminolevulinic acid on decreased blood pressure. In the vascular endothelial cell culture study, 5-aminolevulinic acid induced a significant increase in intracellular nitric oxide generation. 5-Aminolevulinic acid administration was associated with intraoperative hypotension in malignant glioma surgery, with increasing age and use of renin-angiotensin system inhibitors boosting the blood pressure-lowering effect of 5-aminolevulinic acid. According to in vitro results, the low blood pressure induced by 5-aminolevulinic acid may be mediated by a nitric oxide increase in vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Abstract: Bis-chloroethylnitrosourea (BCNU; Gliadel, Eisai, Tokyo, Japan) is the only therapeutic agent for local chemotherapy of malignant gliomas approved by the US Food and Drug Administration and the European Medicines Agency. In a small patient cohort, it has previously been shown that glioblastomas recur locally despite treatment with BCNU. This raises concern about local treatment with BCNU as a stand-alone measure. The goal of this study was to analyze the growth pattern of tumor recurrence in a larger patient group: 41 patients were included in this study. Tumor recurrences were morphologically categorized as: local, diffuse, distant or multilocular. Thirty-three of the tumors (80%) that recurred were local or diffuse. These results show that BCNU implantation does not provide lasting local tumor control. Our data support the need to incorporate BCNU in to multimodal therapy schemes. The improved survival rates of patients who receive concomitant local and systemic adjuvant treatment support using local therapy to bridge the therapy-free interval of the initial postoperative phase. [Copyright &y& Elsevier]

Rationale and Objectives: The aim of this study was to investigate the effect of scan duration on the measurement of blood flow (BF), blood volume (BV), and permeability–surface area product (PS) in patients undergoing computed tomography (CT) perfusion for brain tumors. Materials and Methods: CT perfusion scans were performed in 14 patients with malignant glioma. Patients were scanned for 150 seconds, and BF, BV, and PS were assessed for scan durations of 150, 120, 90, and 60 seconds. Systematic, random, and percentage errors associated with shorter scan durations were calculated. Repeated-measures analyses of variance with paired t tests were used to compare the perfusion values measured from different scan durations. Systematic and random errors were correlated with scan duration. Results: No effect of scan duration on BF and BV values was noted (P > .05). PS values were not affected by scan duration except in the tumor rim, in which they were significantly higher at 60 seconds (P < .01). Median percentage error was highest at 60 seconds for tumor core PS (median, 32.1%; interquartile range, 16.5%–43.0%). Tumor rim BV and PS and tumor core BF were correlated with scan durations (r = 0.42, −0.50, and −0.50, respectively; P < .01). Random errors were negatively correlated with scan durations for all tissue types (P ≤ .01) except for white matter BV. Conclusions: A scan duration of ≤60 seconds is not warranted for the measurement of PS in brain tumors. A scan duration of ≥90 seconds is recommended. [ABSTRACT FROM AUTHOR]

Abstract: Epilepsy surgery is common in the face of benign brain tumors, but rarely for patients with a history of malignant brain tumors. Seizures are a common sequelae in survivors of malignant pediatric brain tumors. Medical management alone may not adequately treat epilepsy, including in this group. We report four cases of patients who previously underwent gross total resection, radiation therapy, and chemotherapy for successful treatment of malignant brain neoplasia, yet suffered from medically intractable seizures. All underwent surgery for treatment of epilepsy with extension of the original resection. Despite the aggressive primary treatment of the neoplasm, and the potential for diffuse cerebral insults, all benefited from focal surgical resection. Aggressive surgical management of intractable epilepsy can be considered in survivors of malignant brain tumors. [Copyright &y& Elsevier]

Summary: Objectives: To investigate the safety and efficacy of photodynamic therapy (PDT) using talaporfin sodium in patients with surgically, completely unresectable malignant gliomas with invasion into the eloquent areas of the brain associated with language and motor functions. Materials and methods: Subjects consisted of consecutive 14 adult patients with malignant gliomas that were shown on preoperative diagnostic imaging to have invaded the eloquent areas of the brain. Of these, 6 patients had newly diagnosed tumors and 8 patients had recurrent tumors. In 15 craniotomy and tumor resection procedures, PDT was used as additional intraoperative treatment 24h after 40mg/m2 of talaporfin sodium had been injected intravenously. After the tumor bulk had been resected as extensively as possible either 1 or 2 sites of probable tumor invasion in the bottom of resection cavity were irradiated superficially with a 664-nm diode laser for 180s (27J/cm2) at a power density of 150mW/cm2. Results: PDT achieved a response rate of 80% at the treated sites in the 6 patients with newly diagnosed malignant gliomas. In these patients, the median progression-free survival time was 23 months. The median survival time in 3 patients who died was 26 months, and the remaining 3 patients survived for more than 3 years with a good Karnofsky Performance Scale (KPS). In the 8 patients with recurrent tumors who received PDT, their response rate was low (25.0%), their gliomas recurred 3 months after PDT, and their survival time was only 9 months following PDT. No adverse events directly attributable to PDT occurred in any patients. Protection against light was only required for approximately 3 days after PDT. Conclusion: We examined the safety and efficacy of PDT using talaporfin sodium as an additional intraoperative treatment for malignant glioma. PDT in addition to surgical resection achieved better therapeutic results than conventional protocols, especially in patients with newly diagnosed malignant gliomas. However, the current methodology has some limitations with respect to patients with recurrent tumors. Larger-scale studies are required to confirm the clinical feasibility of PDT plus surgery. [Copyright &y& Elsevier]

Abstract: CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan), a novel synthetic water-soluble camptothecin derivative, is known to have a significant anticancer effect in vitro on human glioma cell lines, including U87MG and U251MG. In the present study, we evaluated the in vivo antitumor effect of CKD-602 in a mouse glioma model. Nude mice with established U87MG glioma were treated with a dose of CKD-602 of 0mg/kg (control group, injection with saline only; n =5), 40mg/kg (group A) or 60mg/kg (group B). Thereafter, the dose was repeated once every 4days for a total of four doses. Tumor volume was measured histologically and apoptosis was detected using the terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) assay and immunofluorescence analysis with cleaved caspase-3. Mean tumor volume in each group was: control, 145.35mm3; group A, 76.51mm3; group B, 73.99mm3). Tumor volume was significantly smaller in both groups A and B compared with the control group (group A, p <0.01; group B, p <0.05). Apoptosis of tumor cells was evident to a greater extent in groups A and B relative to the control group, but there were no significant differences in tumor volume or apoptotic index between groups A and B. These results suggest that CKD-602 has a significant anticancer effect on glioma cells in vivo. [Copyright &y& Elsevier]

Abstract: In 1995 a government-supported Universal National Health care system was implemented in Taiwan, which in 2008 was available to 98% of the population. This system offers affordable, rapid medical attention. A multi-center retrospective study was conducted to assess the prognosis of malignant glioma patients under this system. In 2005 and 2006, patients at 14 independent neuro-oncology centers with newly diagnosed malignant glioma were enrolled. The patient profile, pathology, treatment modalities, and prognosis were collected by questionnaire at each center. The Taiwan Neuro-Oncology Society was responsible for the data analysis. The overall median survival period, 1-year survival rate, and 2-year survival rate for patients with World Health Organization grade III glioma were 33.8 months, 81.4%, and 58.2%, respectively, and 15 months, 57.3%, and 33.9% in patients with grade IV glioma. The median survival period, 1-year survival rate, and 2-year-survival rate in patients receiving temozolomide adjuvant therapy was 36 months, 84.2%, and 61.8%, respectively, for patients with grade III glioma and 19.8 months, 73.1%, and 43.7%, for patients with grade IV glioma. The universal health care system in Taiwan offers a comparable prognosis with an affordable premium relative to other large series in developed countries. [Copyright &y& Elsevier]

Abstract: Gliadel® (Eisai Inc., Woodcliff Lake, NJ, USA) is the only therapeutic agent approved by the Food and Drug Administration and the European Medicines Agency for local chemotherapy of malignant gliomas. With increasing use of this treatment, characteristic side effects have become evident. While most side effects can be managed conservatively, cyst formation requires further intervention. From 2004 to 2009 at our institution 88 patients with malignant gliomas were treated with Gliadel®. Ten patients (11%) developed a space-occupying cyst in the resection cavity, seven of which caused clinical symptoms of mass effect that was most prominent 2weeks after Gliadel® implantation (median=16, range=9–30). Despite dexamethasone treatment symptoms progressed, necessitating various surgical interventions. In four patients the cysts were drained percutaneously through a burrhole using a 19-gauge needle. If puncture was not possible (three patients) or not sufficient (two patients), an Ommaya reservoir was implanted for repetitive drainage. In two patients this treatment was combined with open decompression of the cyst. On average, cysts were drained three times. Eventually the symptoms subsided, corresponding to shrinkage of the cysts as shown on follow-up imaging. We describe a serious side effect of local chemotherapy, which may cause rapid clinical deterioration and require direct intervention. While reservoir implantation apparently represents a more elegant treatment option, our experience shows that draining the cyst, even only a few times, sufficiently ameliorates the symptoms and subsequently reverses and halts further cyst enlargement. [Copyright &y& Elsevier]

Abstract: We report the clinical, EEG and neuroradiologic findings from three adult patients who developed new-onset seizure disorders as early clinical manifestations of de novo high grade glioma. The malignancies could not be recognised at the time of the first epileptic seizure because of minimal non-specific brain abnormalities, which showed no signs of necrosis or significant contrast enhancement on computed tomography and magnetic resonance imaging. Focal EEG abnormalities were recorded in all cases and appeared consistent with the neuroradiologic findings. The patients regained normal neurological status after the first seizure but rapidly developed space-occupying necrotic lesions. Two patients underwent surgery and received histological diagnoses of the tumours. Another patient was finally diagnosed with a malignant glioma based on the neuroradiologic picture and rapid progression of the cerebral lesion. It should be noted that in adult patients, new-onset epileptic seizures might reveal the presence of malignant gliomas at a very early stage in the tumour formation process. This report indicates that typical anatomoradiologic features of de novo high grade glioma, such as necrosis and rim-contrast enhancement, could be absent at the time of the first epileptic seizure but become clear within a short period after clinical presentation. [ABSTRACT FROM AUTHOR]

Abstract: We report on the safety and feasibility of autologous tumor cell vaccination combined with infusion of granulocyte-macrophage colony-stimulating factor by a programmable pump in the treatment of recurrent malignant gliomas. The programmable pump is a promising tool used to infuse cytokines subcutaneously for vaccination. Our trial enrolled nine patients who had undergone surgery, radiation and had been successfully weaned off steroids. Unfortunately, only five patients completed the protocol and were monitored for side effects, local reactions, delayed-type hypersensitivity (DTH) responses and survival. The treatment was well tolerated. Two patients developed DTH reactions after vaccination and three patients had an unusually long survival without any other treatment. Despite the few patients treated, the results of this trial are encouraging. This study also highlights the specific difficulties encountered in vaccination programs for the treatment of glioma. [Copyright &y& Elsevier]

A patient, admitted to our center with chronic intense headaches, vomiting, and diplopia, underwent neurologic examination that revealed a right sixth nerve palsy and bilateral papilledema secondary to elevated intracranial pressure. CT and MRI scans revealed an expansive, well-demarcated mass in the right frontal region with displacement and compression of the midline and ventricular system. Subsequent imaging studies were consistent with high-grade glioblastoma multiforme (GBM). Macroscopically complete resection was carried out through right frontotemporal craniotomy and right frontal lobectomy. Surgical biopsy findings, confirmed by histopathology, were consistent with glioblastoma multiforme. Carmustine wafers (N=24) were implanted, and a lumbar drain was inserted to protect the sutures and removed after 5 days. Two weeks after resection, a neurostimulator was placed in the epidural space for radiosensitizing tumor bed cells. Adjuvant radiotherapy (total 60 Gy) with spinal cord stimulation and concomitant temozolomide (75 mg/m2 daily) was followed by 6 cycles of monthly temozolomide (150 mg/m2, 5 d/mo). Over the course of treatment, the patient developed a wound infection that was successfully resolved, and displayed a left hemiparesis postsurgery that developed into a hand paresis over the subsequent weeks. The patient progressed favorably and remained disease-free more than 18 months postsurgery. After this period, a disseminated relapse occurred, and the patient died 2 months later. Local treatment with a high dose of BCNU wafers seemed to improve tumor control for more than 18 months postsurgery. Use of high-dose local chemotherapy with carmustine wafers in a Large tumor cavity may be safe and effective as part of a multimodal treatment strategy. [ABSTRACT FROM AUTHOR]

Objectives: Recently, it was revealed that carnosine inhibits growth of cells isolated from human malignant glioma. In order to understand how this effect is mediated, experiments were performed that addressed a possible influence of carnosine on energy metabolism. Methods: Cells from the glioma line T98G and primary cultured cells from human malignant glioma were cultivated in the presence of carnosine and inhibitors of cellular energy metabolism. As a specific inhibitor for anaerobic glycolysis, oxamate, and as an inhibitor for mitochondrial oxidative phosphorylation, potassium cyanide, were used, and the influence on ATP production was determined using cell-based assays. Results: The experiments identified glycolysis as crucial for ATP production in gliomas. In addition, ATP production by mitochondrial activity did not significantly contribute to ATP production and carnosine was identified to be an inhibitor of the vital anaerobic glycolysis. Discussion: Carnosine might be considered as a potential drug for the treatment of malignant glioma or other tumors since it inhibits the glycolytic energy metabolism that is crucial for cancer cells and malignant gliomas as shown in the current study. This is especially interesting since the dipeptide is a naturally occurring substance that should be well tolerated. [ABSTRACT FROM AUTHOR]

We describe herein a malignant glioma arising at the site of the resected hemangioblastoma after irradiation in a patient with von Hippel-Lindau disease (VHL). The patient was a 25 year-old male with multiple hemangioblastomas at the cerebellum and spinal cord, multiple pancreatic cysts and a renal cell carcinoma; he was diagnosed as having VHL disease. The largest hemangioblastoma at the right cerebellar hemisphere was completely removed, and he received high-dose irradiation postoperatively. The tumor recurred at the same site 7 years later, which was a malignant glioma with no evidence of hemangioblastoma. The malignant glioma showed molecular genetic profiles of radiation-induced tumors because of its diffuse p53 immunostaining and the loss of p16 immunoreactivity. The genetic study to find the loss of heterozygosity (LOH) of VHL gene revealed that only the cerebellar hemangioblastoma showed allelic losses for the gene. To the best of our knowledge, this report is the first to show a malignant glioma that developed in a patient with VHL disease after radiation therapy at the site of an excised hemangioblastoma. This report also suggests that radiation therapy should be performed very carefully in VHL patients with hemangioblastomas. [ABSTRACT FROM AUTHOR]

Abstract: Neuroglobin is a recently identified globin molecule that is expressed predominantly in the vertebrate brain. Neuroglobin expression increases in oxygen-deprived neurons, suggesting it protects neurons from ischemic cell death. We report that neuroglobin transcript and protein are expressed in human glioblastoma cells, and that this expression increases in hypoxia in vitro. We also show that neuroglobin is up-regulated in hypoxic microregions of glioblastoma tumor xenografts. Our finding of hypoxic up-regulation of neuroglobin in human glioblastoma cells may provide insight into how tumor cells adapt to and survive in hypoxic microenvironments. [Copyright &y& Elsevier]

Summary: Object: The usefulness of photodynamic therapy (PDT) as a local therapy for malignant glioma was evaluated by investigating histological changes in a rat C6 glioma model treated with a combination of talaporfin sodium, a water-soluble photosensitizer derived from chlorophyll and exposure to a diode laser. Methods: Glioma cells (C6) at the confluence stage were transplanted stereotactically into the right frontal lobe of SD rats. Five days later, the rats underwent right frontal craniotomy and intravenous administration of talaporfin sodium. One hour after talaporfin sodium administration, each rat was irradiated by a 664nm diode laser beam. The brain was removed 1, 3 or 6h after laser irradiation for histological examination of tumor-affected brain tissue and surrounding normal brain tissue. Results: In addition to the tumor mass, tumor cells invading surrounding edematous brain tissue were seen in untreated rats, ranging from the brain surface to a depth of 2mm. One hour after PDT, coagulation necrosis as well as disappearance of indication of cell viability such as disappearance of tumor cell processes and foamy changes of cytoplasm were noted in the tumor tissue at a depth of 0.5mm, accompanied by reduction of cytoplasmic glial fibrillary acidic protein (GFAP) expression and appearance of granular M30 cytodeath positivity. Three hours later, the cytoplasm of the residual tumor cells showed disappearance of GFAP expression and increased expression of M30 cytodeath. Six hours later, the foamy cytoplasm of swollen tumor cells demonstrated strong positivity for M30 cytodeath. Conclusion: PDT using talaporfin sodium induced coagulation necrosis and apoptosis in rats with C6 glioma. [Copyright &y& Elsevier]

Abstract: Introduction: Central nervous system (CNS) tumors cause a significant amount of morbidity and mortality. More research is needed to improve the prognosis of patients with CNS tumors, and especially for those with malignant gliomas. The advances over the last several years in the treatment of adult central nervous system tumors are reviewed here. Materials and methods: Phase II and Phase III trials published in major peer-reviewed journals between 2005 and 2006 were examined. Adult central nervous system tumors including malignant glioma, low-grade glioma, primary central nervous system lymphoma, brain metastases, and neoplastic meningitis, were included. Results: Phase II treatment trials for patients with gliomas dominated the literature in the time-period examined. Trials primarily addressed radiotherapy as well as chemotherapy in the treatment of gliomas. A number of trials examined targeted agents as single agents and in combination with systemic therapy in glioma patients. A few studies evaluated the role of chemotherapy and radiation in metastatic disease and primary CNS lymphoma. Conclusions: Temozolomide is now the new standard of care in combination with radiation therapy for newly diagnosed glioblastomas. The optimal dosing and length of adjuvant temozolomide treatment remains unclear, and there remains no current role for neo-adjuvant therapy. Targeted agents that can be used in the salvage or front-line setting, alone or in combination with systemic therapy, will likely be the focus of future research. For metastatic brain tumors, more studies are needed to examine the exact role of radiosurgery, whole brain radiation, and the role of other therapies such as temozolomide or targeted agents. For primary CNS lymphomas, the role of various high-dose methotrexate regimens is being actively investigated. [Copyright &y& Elsevier]

Abstract: Introduction: Chemotherapy, immunotherapy, and biological response modifiers were tested in clinical trials for brain tumors. Results of these studies published in 2003 and 2004 are reviewed. Materials and methods: Major peer-reviewed journals in the disciplines of neurosurgery, neurology, medical oncology, and radiation oncology were surveyed. Results of phase II and phase III clinical trials testing chemotherapy, gene therapy, immunotherapy, and radiosensitizers for adults and children with malignant and low-grade glioma, primary central nervous system lymphoma (PCNSL), brain metastasis, medulloblastoma/primitive neuroectodermal tumor (PNET), and germ cell tumors were reviewed. Results: Nitrosourea and temozolomide were tested as monotherapy or in combination with other agents as neoadjuvant, concurrent, and adjuvant treatment with radiotherapy for newly diagnosed malignant glioma in adults, including high-risk treatment groups, such as the elderly. Trials for recurrent malignant glioma included novel therapies, dendritic vaccine therapy, gene therapy and immunotherapy. High-dose chemotherapy with bone marrow rescue was tested in anaplastic oligodendroglioma (AO). Seven additional studies were performed to treat recurrent oligodendroglioma (O). Nine clinical trials for PCNSL emphasized the use of high-dose systemic methotrexate, temozolomide, and rituxin. Chemotherapy and immunotherapy were used to treat low-grade glioma in 7 studies. Intra-arterial and (IT) chemotherapy were used for metastatic disease. Treatment protocols for children were compared using multi-agent chemotherapy for malignant glioma, brainstem glioma, medulloblastoma, and germ cell tumors. Conclusion: Multi-agent chemotherapy is successful for some pediatric brain tumors and PCNSL in adults. Vaccine, immunotherapy, and other gene therapies are still under investigation. Temozolomide and nitrosourea, specifically degradable polymer wafers, had the best results for malignant gliomas in adults. Treatment standards have been established for medulloblastoma/PNET. Treating malignant glioma in children remains problematic. [Copyright &y& Elsevier]

Summary: The prognostic significance of the histologic type and grade of gliomas at initial surgery is well established, but the value of histologic findings in resections after radiotherapy is unclear. Despite this uncertainty, pathologic interpretation of specimens after radiotherapy influences immediate treatment decisions. It is important to determine if, and to what extent, treatment decisions should be based on this information. We aimed to determine the prognostic value of pathologic evaluation in postradiation specimens from 54 patients with similar clinical features who underwent a second surgery for the treatment of radiologic worsening after external beam radiotherapy. We categorized the specimens from the second surgery as either recurrent tumor (category 1) or radionecrosis (category 2). Patients in category 1 had actively proliferating neoplasms with classical features of glioblastoma, whereas patients in category 2 had no evidence of tumor in their surgical specimens. Cases in which a clear-cut definition could not be made were labeled indeterminate (category 3). Despite the morphological evidence of tumor, there were no significant differences between categories 1 and 2 in any of the survival parameters tested. The only difference between groups was higher frequency of iodine 125 (125I) placement at second surgery in category 1 patients (P < .028). Patients in category 1 with or without 125I treatment had similar survival characteristics. We conclude that histopathologic evaluation of postradiotherapy specimens was not helpful in predicting outcome or dictating further management. A comprehensive prospective study with advanced radiologic, pathologic, and molecular analyses may be more useful to determine prognostically valuable parameters. [Copyright &y& Elsevier]

Despite poor prognosis of patients with glioblastoma multiforme, improved multimodality treatment and chemotherapy and improved chemotherapeutic options are beginning to have an increased impact. Multimodality treatment involving surgery, radiation therapy, and chemotherapy is an accepted therapeutic strategy for glioblastoma multiforme. Meta-analyses have shown a survival benefit for patients receiving chemotherapy and radiation therapy when compared with patients receiving radiation therapy alone. Conventional systemic chemotherapy is being complimented by tumor-directed therapies, such as chemotherapy wafers, convection-enhanced delivery, and intra-arterial delivery with blood-brain barrier disruption, to increase local delivery to gliomas.

• We developed a mirror reflecting system against blinds spots in PDT for malignant glioma. • The energy efficiency was approximately 70 %, and 9 patients were treated without complication. • Recurrence did not occur in the site where mirror irradiation was performed. Intraoperative photodynamic therapy (PDT) using talaporfin sodium for malignant glioma is effective both in the experimental and in the clinical setting. Because the irradiation unit is fixed to the objective lens of the operating microscope, blind spots for irradiation exist. To overcome this problem, we developed a mirror reflecting system using a modified dental mirror. The developed mirror is made of stainless steel, has a mirror-polished surface, and is rhodium coated on 1 side, which is the reflecting surface. The reflection rate was measured using He-Ne laser irradiation. The reflection intensity was measured using a laser power meter when the incident angle to the mirror was changed to 60°, 45°, and 30°, and the reflectance was calculated by the direct received light intensity from the laser. After confirming the safety of the fundamental experiment, PDT was performed with this developed mirror on 9 patients with malignant glioma (4 with recurrence and 5 newly diagnosed). The energy efficiency of the mirror was approximately 70 %, and apparent irregular reflection was not observed. Even during clinical use, apparent complications, such as irregular reflection, did not occur upon using the mirror in any of the patients. In all patients, recurrence did not occur in the site where mirror irradiation was performed, but in a deep site or a distant site to which sufficient laser irradiation did not reach. PDT using our newly developed mirror involves few instrumental changes compared with the conventional irradiation method, and is effective, safe, and inexpensive. [ABSTRACT FROM AUTHOR]