Reactive oxygen species induced by indomethacin enhance accumulation of heme carrier protein 1 and hematoporphyrin accumulation in vitro and in vivo in a brain tumor model.

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.

P53-negative status and gross total resection as predictive factors for autologous tumor vaccine treatment in newly diagnosed glioblastoma patients.

Background: Among primary brain tumors, glioblastoma (GBM) is the most common and aggressive in adults, with limited treatment options. Our previous study showed that autologous formalin-fixed tumor vaccine (AFTV) contributed to prognostic improvements in newly diagnosed GBM patients. However, some patients died early despite the treatment. The discovery of predictive factors in the treatment was warranted for efficient patient recruitment and studies to overcome resistance mechanisms. Identifying prognostic factors will establish AFTV guidelines for patients who may respond to the therapy. Methods: Data from 58 patients with newly diagnosed GBM, including 29 who received standard therapy plus AFTV (AFTV group) and 29 who received standard treatment (control group) were analyzed. Several data including patient age, sex, the extent of removal, and various cell immunohistochemistry (IHC) parameters were also included in the analysis. Results: Both univariate and multivariate analyses revealed that gross total resection (GTR) and negative p53 were associated with a better prognosis only in the AFTV group. In the IHC parameters, CD8 staining status was also one of the predictive factors in the univariate analysis. For blood cell-related data, lymphocyte counts of 1100 or more and monocyte counts of 280 or more before chemo-radiotherapy were significant factors for good prognosis in the univariate analysis. Conclusions: A p53-negative status in IHC and GTR were the predictive factors for AFTV treatment in newly diagnosed GBM patients. Microenvironment-targeted treatment and pretreatment blood cell status may be key factors to enhance therapy effects.

Significance of perilesional T1 hyperintense areas in the differential diagnosis of primary adult-type diffuse glioma: A case report.

Perilesional T1 hyperintensity on magnetic resonance imaging (MRI) of intra-axial brain masses is an unusual feature of the perilesional area, characteristic of cavernous malformations (CMs) and metastatic brain tumors (METs). Here, we report a case of primary diffuse glioma with a perilesional T1 hyperintense area (HIA) on MRI. A 61-year-old woman with transient aphasia visited our hospital. Radiological examination revealed an intra-axial mass with acute/subacute hemorrhaging and calcification in the left frontal lobe. It was presumed to be a CM because of the perilesional T1 HIA. Gross total resection of the tumor was performed, and the pathological diagnosis was anaplastic oligodendroglioma, not otherwise specified by World Health Organization 2016 classification. Histopathological findings in the perilesional T1 HIA indicated hemorrhage involvement in the surrounding white matter. No recurrence appeared after radio-chemotherapy. Perilesional T1 HIAs, characteristic of CMs and METs, are also seen in primary diffuse gliomas. Therefore, caution should be taken when using this sign for the differential diagnosis of intracranial masses.

High-dose proton beam therapy versus conventional fractionated radiation therapy for newly diagnosed glioblastoma: a propensity score matching analysis.

BACKGROUND: High-dose proton beam therapy (PBT) uses excellent dose concentricity based on the unique characteristic termed the Bragg peak. PBT is a highly feasible treatment option that improves survival in select patients with newly diagnosed glioblastoma (GBM). However, selection bias remains an issue in prior studies that evaluated the efficacy of PBT. The aim of the present study was to compare the survival outcomes and toxicities of high-dose PBT and conventional radiation therapy (CRT) using propensity score-matched treatment cohorts. METHODS: The analysis included patients with newly diagnosed GBM treated with high-dose PBT of 96.6 Gy (RBE) or CRT of 60 Gy from 2010 to 2020. Propensity score generation and 1:1 matching of patients were performed based on the following covariates: age, sex, tumor location, extent of resection, chemotherapy, immunotherapy, and pre-radiation Karnofsky performance scale score. RESULTS: From a total of 235 patients, 26 were selected in each group by propensity score matching. The median overall survival (OS) of the PBT group was 28.3 months, while the median OS of the CRT group was 21.2 months. Although acute radiation-related toxicities were equivalent between the PBT and CRT groups, radiation necrosis as a late radiation-related toxicity was observed significantly more frequently in the PBT group. CONCLUSIONS: High-dose PBT provided significant survival benefits for patients with newly diagnosed GBM compared to CRT as shown by propensity score matching analysis. Radiation necrosis remains an issue in high-dose PBT; thus, the establishment of an effective treatment strategy centered on bevacizumab would be essential.

Factors Involved in Preoperative Edema in High-Grade Gliomas.

Background Expansion of preoperative edema (PE) is an independent poor prognostic factor in high-grade gliomas. Evaluation of PE provides important information that can be readily obtained from magnetic resonance imaging (MRI), but there are few reports on factors associated with PE. The goal of this study was to identify factors contributing to PE in Grade 3 (G3) and Grade 4 (G4) gliomas. Methodology PE was measured in 141 pathologically proven G3 and G4 gliomas, and factors with a potential relationship with PE were examined in univariate and multivariate analyses. The following eight explanatory variables were used: age, sex, Karnofsky performance status (KPS), location of the glioma, tumor diameter, pathological grade, isocitrate dehydrogenase (IDH)-1-R132H status, and Ki-67 index. Overall survival (OS) and progression-free survival (PFS) were calculated in groups divided by PE (<1 vs. ≥1 cm) and by factors with a significant correlation with PE in multivariate analysis. Results In univariate analysis, age (p = 0.013), KPS (p = 0.012), pathology grade (p = 0.004), and IDH1-R132H status (p = 0.0003) were significantly correlated with PE. In multivariate analysis, only IDH1-R132H status showed a significant correlation (p = 0.036), with a regression coefficient of -0.42. The median follow-up period in survivors was 38.9 months (range: 1.2-131.7 months). The one-, two-, and three-year OS rates for PE <1 vs. ≥1 cm were 77% vs. 68%, 67% vs. 44%, and 63% vs. 24% (p = 0.0001), respectively, and those for IDH1-R132H mutated vs. wild-type cases were 85% vs. 67%, 85% vs. 40%, and 81% vs. 21% (p < 0.0001), respectively. The one-, two-, and three-year PFS rates for PE <1 vs. ≥1 cm were 77% vs. 49%, 64% vs. 24%, and 50% vs. 18% (p = 0.0002), respectively, and those for IDH1-R132H mutated vs. wild-type cases were 85% vs. 48%, 77% vs. 23%, and 73% vs. 14% (p < 0.0001), respectively. Conclusions IDH1-R132H status was found to be a significant contributor to PE. Cases with PE <1 cm and those with the IDH1-R132H mutation clearly had a better prognosis.

Levetiracetam Versus Levetiracetam Plus Sodium Channel Blockers for Postoperative Epileptic Seizure Prevention in Brain Tumor Patients.

Background Brain tumor patients tend to develop postoperative epileptic seizures, which can lead to an unfavorable outcome. Although the incidence of postoperative epileptic seizures and adverse events are improved with the advent of levetiracetam (LEV), postoperative epilepsy occurs at a frequency of 4.6% or higher. In brain tumor patients, the addition of sodium channel blockers (SCBs) to LEV significantly reduces seizures, though confirmed in a non-postoperative study. Thus, the combination of SCBs with LEV might be promising. Objective In this prospective randomized controlled trial we investigated the safety, evaluated by adverse events during one and two weeks after surgery, and the efficacy, evaluated by the incidence of early epilepsy, including non-convulsive status epilepticus (NCSE), of using LEV alone or SCBs added to LEV in patients who underwent craniotomy or biopsy for brain tumors or brain mass lesions. Methods Patients with brain tumors or brain mass lesions undergoing surgical interventions, excluding endoscopic endonasal surgery (EES), with a diagnosis of epilepsy were eligible for this study. Patients are randomized into either Group A or B (B1 or B2) after the informed consents are taken; LEV alone in Group A patients, while LEV and SCBs in Group B patients (GroupB1, intravenous fosphenytoin plus oral lacosamide (LCM) and GroupB2, intravenous LCM plus oral LCM) were administered postoperatively. Fifty-three patients were enrolled during the first two and a half years of the study and four of them were excluded, resulting in the accumulation of 49 patients' data. Results Postoperative epileptic seizures occurred only in three out of 49 patients during the first week (6.1%) and in seven patients within two weeks after surgery (14.3%, including the three patients during the first week). In Group A, epileptic seizures occurred in two out of 26 patients during the first week (7.7%) and in five patients within two weeks (19.2%) after surgery. In Group B, epileptic seizures occurred in one out of 23 patients during the first week (4.3%) and in two patients during the first two weeks (8.7%). Low complication grade of epileptic seizures was observed in Group B rather than in Group A, however, without significant difference (p=0.256). There was no difference in the frequency of adverse effects in each group. Conclusion Although not statistically significant, the incidence of epileptic seizures within one week after surgery was lesser in LEV+SCBs groups than in LEV alone. No hepatic damage or renal function worsening occurred with the addition of LCM, suggesting the safety of LEV+SCBs therapy.

Perioperative Deep Vein Thrombosis and D-dimer Measurement in Patients with Brain Tumor.

We investigated the appropriate D-dimer cutoff value for each brain tumor type for acute or subacute deep vein thrombosis (DVT) following transcranial brain tumor surgery.In this single-center retrospective study, a cumulative total of 128 patients who underwent transcranial brain tumor surgery were enrolled and classified into the glioma group, the other intracranial malignant tumor group, and the intracranial benign tumor group. Venous ultrasonography was performed if the D-dimer plasma levels were positive (≥1 µg/mL) before surgery and on postoperative day (POD) 3 or 7.Of the 128 cases, DVT developed in 32 (25.0%). Among those, acute or subacute DVT was diagnosed in 22 cases on POD 3 and in 8 cases on POD 7. Compared with DVT-negative cases on POD 3, acute or subacute DVT-positive cases on POD 3 revealed a significant increase in the D-dimer level in all groups combined and in the benign tumor group but not in the glioma group. With regard to DVT on POD 3 in all groups, the receiver operating characteristic curve for the D-dimer level on POD 3 demonstrated a cutoff value of 3.3 µg/mL (sensitivity [0.636] and specificity [0.750]). However, if this cutoff value was used in practice, eight cases would be false-negative with a minimum D-dimer level of 1.5 µg/mL.The D-dimer cutoff value for acute or subacute DVT on POD 3 could be set to 3.3 µg/mL; however, the setting resulted in several false-negative cases. Practically, 1.5 µg/mL of the D-dimer cutoff value on POD 3 might be appropriate to avoid false-negative results.

Timing of bevacizumab administration after biopsy for unresectable newly diagnosed glioblastoma.

Background: Recent studies have revealed that bevacizumab (BEV) can improve the survival of patients with newly diagnosed unresectable glioblastoma (GBM) with poor performance status. For patients who develop early clinical deterioration, early initiation of BEV would be beneficial. However, the safety and feasibility of early initiation of BEV remain to be determined because of the lack of studies addressing adverse events associated with BEV initiation <28 days after surgery. The aim of this study was to analyze the risks and benefits of early BEV administration after biopsy in patients with newly diagnosed GBM. Methods: Thirty-one consecutive patients with newly diagnosed GBM who underwent biopsy followed by BEV administration were investigated. The relationships between the timing of BEV administration and treatment response, survival outcome, and adverse events were analyzed. Results: Response rates based on the RANO criteria and overall survival times were similar between the early and standard BEV groups. No wound dehiscence was observed in the early BEV group, and only one case was observed in the standard BEV group. Patients in the early BEV group were more likely to have undergone biopsy with a smaller skin incision than those in the standard BEV group. Equivalent treatment effects of BEV were achieved in patients who developed early clinical deterioration and those without clinical deterioration. Conclusion: Early BEV administration is effective in controlling early clinical deterioration and does not increase the risk of wound-healing complications. Further studies with larger numbers of patients are needed to validate our results.

Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis.

Background and objective Postoperative radiotherapy is usually indicated for both grade 3 glioma and grade 4 glioblastoma. However, the treatment results and tumor features of grade 3 glioma clearly differ from those of glioblastoma. There is limited information on outcomes and tumor progression for grade 3 glioma. In this study, we evaluate the result of postoperative radiotherapy for grade 3 glioma and focus on the correlation of MRI findings with prognosis. Methods In this study, 99 of 110 patients with grade 3 glioma who received postoperative radiotherapy and were followed up for more than one year were retrospectively analyzed. The total irradiation dose was 60.0 Gy in 30 fractions, and daily temozolomide or two cycles of nimustine (ACNU) was concurrently administered during radiotherapy. The median follow-up period was 46 months (range: 2-151 months). Results In multivariate analysis, pathology [anaplastic oligodendroglioma (AO) vs. anaplastic astrocytoma (AA)], the status of surgical resection (biopsy vs. partial resection or more), and contrast enhancement (enhanced by MRI image or not) were significant factors for overall survival (OS). The five-year OS for AO vs. AA cases were 76.8% vs. 46.1%, total to partial resection vs. biopsy cases were 72.7% vs. 21.0%, and non-enhanced vs. enhanced cases were 82.5% vs. 45.6%, respectively. In multivariate analysis, the status of surgical resection and longer extension of preoperative edema (PE) were significant factors for progression-free survival (PFS). The five-year PFS for the total to partial resection vs. biopsy cases were 52.9% vs. 10.7%, and non-extensive PE vs. extensive PE (EPE) cases were 62.2% vs. 19.1%, respectively. Conclusion Our results suggest that a contrast-enhanced tumor on MRI and a longer PE may also be significantly associated with OS and PFS among grade 3 glioma patients.

Peritumoral edema status of glioblastoma identifies patients reaching long-term disease control with specific progression patterns after tumor resection and high-dose proton boost.

BACKGROUND: Glioblastoma peritumoral edema (PE) extent is associated with survival and progression pattern after tumor resection and radiotherapy (RT). To increase tumor control, proton beam was adopted to give high-dose boost (> 90 Gy). However, the correlation between PE extent and prognosis of glioblastoma after postoperative high-dose proton boost (HDPB) therapy stays unknown. We intend to utilize the PE status to classify the survival and progression patterns. METHODS: Patients receiving HDPB (96.6 GyE) were retrospectively evaluated. Limited peritumoral edema (LPE) was defined as PE extent < 3 cm with a ratio of PE extent to tumor maximum diameter of < 0.75. Extended progressive disease (EPD) was defined as progression of tumors extending > 1 cm from the tumor bed edge. RESULTS: After long-term follow-up (median 88.7, range 63.6-113.8 months) for surviving patients with (n = 13) and without (n = 32) LPE, the median overall survival (OS) and progression-free survival (PFS) were 77.2 vs. 16.7 months (p = 0.004) and 13.6 vs. 8.6 months (p = 0.02), respectively. In multivariate analyses combined with factors of performance, age, tumor maximum diameter, and tumor resection extent, LPE remained a significant factor for favorable OS and PFS. The rates of 5-year complete response, EPD, and distant metastasis with and without LPE were 38.5% vs. 3.2% (p = 0.005), 7.7% vs. 40.6% (p = 0.04), and 0% vs. 34.4% (p = 0.02), respectively. CONCLUSIONS: The LPE status effectively identified patients with relative long-term control and specific progression patterns after postoperative HDPB for glioblastoma.

Maximum resection and immunotherapy improve glioblastoma patient survival: a retrospective single-institution prognostic analysis.

Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. In this retrospective study we analyzed the prognostic factors of 277 newly diagnosed GBM patients over 11 years of consecutive cases at our institution to evaluate the effect of these methods on prognosis. Various data, including the extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. The median overall survival (OS) of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases was 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative magnetic resonance imaging (MRI) use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and a combination of immunotherapies, including autologous formalin-fixed tumor vaccine, were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS % values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. In conclusion, GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.

Malignant transformation of pleomorphic xanthoastrocytoma and differential diagnosis: case report.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization's (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA. CASE PRESENTATION: Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA. CONCLUSIONS: This case highlights the complexities of differential diagnosis based on the World Health Organization's 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.

Evaluation of the extent of resection and detection of ischemic lesions with intraoperative MRI in glioma surgery: is intraoperative MRI superior to early postoperative MRI?

OBJECTIVE: MRI scans obtained within 48-72 hours (early postoperative MRI [epMRI]), prior to any postoperative reactive changes, are recommended for the accurate assessment of the extent of resection (EOR) after glioma surgery. Diffusion-weighted imaging (DWI) enables ischemic lesions to be detected and distinguished from the residual tumor. Prior studies, however, revealed that postoperative reactive changes were often present, even in epMRI. Although intraoperative MRI (iMRI) is widely used to maximize safe resection during glioma surgery, it is unclear whether iMRI is superior to epMRI when evaluating the EOR, because it theoretically shows fewer postoperative reactive changes. In addition, the ability to detect ischemic lesions using iMRI has not been investigated. METHODS: The authors retrospectively analyzed prospectively collected data in 30 patients with glioma (22 and 8 patients with enhancing and nonenhancing lesions, respectively) who underwent tumor resection. These patients had received preoperative MRI within 24 hours prior to surgery, postresection radiological evaluation with iMRI during surgery, and epMRI within 24 hours after surgery, with all neuroimaging performed using identical 1.5T MRI scanners. The authors compared iMRI or epMRI with preoperative MRI, and defined a postoperative reactive change as a new postoperative enhancement or T2 high-intensity area (HIA), if this lesion was outside of the preoperative original tumor location. In addition, postoperative ischemia was evaluated on DWI. The iMRI and epMRI findings were compared in terms of 1) postoperative reactive changes, 2) evaluation of the EOR, and 3) presence of ischemic lesion on DWI. RESULTS: In patients with enhancing lesions, a new enhancement was seen in 8 of 22 patients (36.4%) on iMRI and in 12 of 22 patients (54.5%) on epMRI. In patients with nonenhancing lesions, a new T2 HIA was seen in 4 of 8 patients (50.0%) on iMRI and in 7 of 8 patients (87.5%) on epMRI. A discrepancy between the EOR measured on iMRI and epMRI was noted in 5 of the 22 patients (22.7%) with enhancing lesions, and in 3 of the 8 patients (37.5%) with nonenhancing lesions. The occurrence of ischemic lesions on DWI was found in 5 of 30 patients (16.7%) on iMRI, whereas it was found in 16 of 30 patients (53.3%) on epMRI (p = 0.003); ischemic lesions were underestimated on iMRI in 11 patients. CONCLUSIONS: Overall, given the lower incidence of postoperative reactive changes on iMRI, it was superior to epMRI in evaluating the EOR in patients with glioma, both with enhancing and nonenhancing lesions. However, because ischemic lesions can be overlooked on iMRI, the authors recommend only the additional DWI scan during the early postoperative period. Clinicians need to be mindful about not overestimating the presence of residual tumor on epMRI due to the high incidence of postoperative reactive changes.

Diffusely Infiltrating Cerebellar Anaplastic Astrocytoma Effectively Controlled with Bevacizumab: Case Report and Literature Review.

BACKGROUND: Gliomas that show extensive diffuse infiltration from the cerebellum to the brainstem without masslike expansion are extremely rare. The efficacy of bevacizumab treatment for diffusely infiltrating gliomas remains uncertain. CASE DESCRIPTION: A 75-year-old man presented with a cerebellar anaplastic astrocytoma showing diffuse infiltration to the brainstem without a definite mass. He had experienced rapidly progressive nausea and dysarthria, as well as vertigo and headache for 2 months. Magnetic resonance imaging (MRI) revealed a poorly demarcated T2 high-intensity area in the right cerebellum and brainstem. The tumor in the right cerebellum showed sparse enhancement with gadolinium (Gd). Suboccipital decompressive craniotomy and partial removal of the tumor was emergently performed because of the rapid progression of symptoms and severe tonsillar herniation demonstrated on MRI. The pathologic diagnosis was anaplastic astrocytoma, and genomic analyses revealed no mutation in IDH1, H3F3A, or BRAF. During concomitant chemoradiotherapy with temozolomide, rapid worsening of the neurologic symptoms developed and significant enlargement of the T2 high-intensity area extending to the cerebral peduncle was seen, as well as a new Gd-enhancing lesion in the midbrain. After administration of bevacizumab, the neurologic symptoms gradually improved, the T2 high-intensity area decreased, and the Gd-enhancing lesion disappeared. At follow-up 2 years after the operation, no worsening of neurologic symptoms was seen and the residual T2 high-intensity area remained unchanged on MRI. CONCLUSIONS: Bevacizumab treatment may be a salvage treatment option for patients with diffusely infiltrating cerebellar gliomas that exhibits rapid progression during standard treatment.

Prognostic analysis of patients who underwent gross total resection of newly diagnosed glioblastoma.

Despite cumulative evidence supporting the idea that gross total resection (GTR) contributes to prolonged survival of patients with glioblastoma (GBM), the survival outcome of such patients remains unsatisfactory. To develop more effective postoperative therapeutic strategies for patients who underwent GTR, identification of prognostic factors influencing survival is urgently needed. Here we retrospectively analyzed prognostic factors for patients who underwent GTR of newly diagnosed GBM, with a particular focus on the influence of the subventricular zone (SVZ) as the tumor location. Forty-eight consecutive patients with newly diagnosed GBM who underwent GTR during the initial operation were investigated. Tumor involvement of the SVZ was significantly associated with overall survival (OS). The SVZ-positive group had a significantly shorter median OS of 12.2 months, compared to 34.9 months for the SVZ-negative group. The occurrence of leptomeningeal dissemination was significantly influenced by tumor involvement of the SVZ, but was not significantly influenced by ventricular opening during surgery. We observed a statistically significant difference in OS according to radiation modality. The median OS was 36.9 months for patients treated with high-dose proton beam therapy, compared with 26.2 months for patients treated with conventional radiotherapy. We demonstrated that tumor involvement of the SVZ was associated with poor survival of patients who underwent GTR of newly diagnosed GBM, suggesting the potential need for therapeutic strategies that specifically target tumors in the SVZ. Further prospective studies to evaluate whether radiotherapy targeting the SVZ improves survival of patients with tumor involvement of the SVZ who had undergone GTR are warranted.

Proton Beam Therapy for Pediatric Brain Tumor.

Cancer is a major cause of childhood death, with central nervous system (CNS) neoplasms being the second most common pediatric malignancy, following hematological cancer. Treatment of pediatric CNS malignancies requires multimodal treatment using a combination of surgery, chemotherapy, and radiotherapy, and advances in these treatments have given favorable results and longer survival. However, treatment-related toxicities have also occurred, particularly for radiotherapy, after which secondary cancer, reduced function of irradiated organs, and retarded growth are significant problems. Proton beam therapy (PBT) is a particle radiotherapy with excellent dose localization that permits treatment of liver and lung cancer by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. Thus, PBT has the potential advantages for pediatric cancer. In this context, we review the current knowledge on PBT for treatment of pediatric CNS malignancies.

Early Postoperative Expansion of Parenchymal High-intensity Areas on T2-weighted Imaging Predicts Delayed Cerebral Edema Caused by Carmustine Wafer Implantation in Patients with High-grade Glioma.

BACKGROUND: Carmustine (BCNU) wafer (Gliadel(®) Wafer) implantation after tumor resection is an approved treatment for high-grade glioma (HGG). These wafers change various characteristics on early postoperative magnetic resonance imaging (ep-MRI) including slight expansion of high-intensity areas on T2-weighted imaging (ep-T2-HIAs) into adjacent parenchyma without restricted diffusivity. We assessed the frequency of the ep-T2-HIAs after BCNU wafer implantation in HGG patients. Moreover, we focused on ep-T2-HIA expansion and its relation to delayed cerebral edema. METHODS: Twenty-five consecutive HGG patients who underwent BCNU wafer implantation were assessed. First, patients were divided into ep-T2-HIA and non-ep-T2-HIA groups, and the incidence of delayed adverse effects was compared between the two groups. Subsequently, the patients were divided into delayed edema and non-delayed edema groups, and pre-, intra-, and postoperative data were compared between the two groups. RESULTS: The ep-T2-HIA expansion and the delayed edema were evident in 9 cases (36%) and 12 cases (48%), respectively. In comparison of the ep-T2-HIA and non-ep-T2-HIA groups, delayed edema was the only delayed adverse effect associated with ep-T2-HIA expansion (P = 0.004). Univariate analysis showed a significantly higher ratio of delayed edema in the subgroups with maximal diameter of removed cavity ≤40 mm (P = 0.047) and the ep-T2-HIA expansion in comparison of the delayed edema and non-delayed edema groups. Multivariate analysis showed that the ep-T2-HIA expansion was the only independent factor associated with delayed edema (P = 0.021). CONCLUSION: In BCNU wafer implantation cases, ep-T2-HIA expansion was a predictive factor for delayed cerebral edema.

Intraparenchymal brain lesion biopsy guided by a rigid endoscope and navigation system.

BACKGROUND: The authors report a continuous case series of navigation-guided rigid endoscopic biopsy via the transcortical route for intraparenchymal brain lesions to assess the feasibility and efficacy of the method. METHODS: Thirty-four patients with intraparenchymal brain lesions found on neurovisualization underwent navigation-guided rigid endoscopic biopsy. Most of the preoperative diagnoses were glioma WHO Grade II-IV (16 cases) or malignant lymphoma (15 cases). Intraoperative photodynamic diagnosis and intraoperative pathological diagnosis were used in 28 and 29 cases, respectively. In 2 cases with small and deep lesions, intraoperative magnetic resonance imaging was used for confirming the accuracy of the biopsy point. RESULTS: The sampling accuracy determined by postoperative imaging and the definitive diagnosis ratio were 94% (32 out of 34 cases) and 97% (33 out of 34 cases), respectively. There was no postoperative mortality. In 2 patients, mild postoperative permanent morbidity (5.9%), presumably related to this technique, was observed in the early cases in the current group (34 case series). CONCLUSION: The method was estimated as safe and feasible for diagnostic tissue sampling of intraparenchymal brain lesions.