Woo-Youl Jang

Early prognostic factors related to progression and malignant transformation of low-grade gliomas

OBJECTIVE Low-grade gliomas (LGGs) are infiltrative tumors characterized by slow growth. However, during early period, LGGs can progress and transform into a malignant pathology. We analyzed the prognostic factors for progression and malignant transformation in LGGs. MATERIALS AND METHODS From 2000 to 2009, we operated on 86 patients: 42 oligodendrogliomas, 12 oligoastrocytomas, and 32 astrocytomas. The male:female ratio was 47:39, and the median age was 41 (±17.4) years. The mean follow-up period was 4.25 (±2.8) years. We analyzed the prognostic factors for progression-free survival (PFS), overall survival (OS), and malignant transformation, considering age, sex, KPS, clinical presentation, tumor location, radiologic pattern, extent of removal, pathologic subtype, and adjuvant treatment. RESULTS In univariate analysis, non-eloquent location, gross total removal, and oligodendroglial pathology statistically correlated with improved PFS and OS. In multivariate analysis, gross total removal correlated with longer PFS (p=0.043), and gemistocytic astrocytoma had a poor PFS (p=0.004). Younger age and non-eloquent area showed an improved OS (p=0.002 and 0.041), and astrocytic pathology showed a poor OS (p=0.01). Malignant transformation was pathologically diagnosed in 13 out of 86 patients (15%). Gemistocytic astrocytoma correlated independently with malignant transformation (p=0.022). CONCLUSION In LGGs, extent of removal associated with tumor progression. The pathology of astrocytoma, especially gemistocytic astrocytoma, was an independent prognostic factor for recurrence and malignant transformation.

Tumour-infiltrating T-cell subpopulations in glioblastomas

This study was designed to determine the incidence and prognostic value of various populations of tumour-infiltrating T cells in glioblastomas. We also evaluated the difference in T-cell populations after conventional treatment. Sixty-seven patients with glioblastomas underwent surgery between 2003 and April 2009. Immunohistochemical staining was performed for CD3, CD4, CD8 and FoxP3, and the average number and percentage of positive cells were calculated. In eight patients, the average number of subpopulations was compared between the specimens obtained during the first and second operations. Age, gender, Karnofsky performance status, Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) classes, extent of removal, treatment modality, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and immunopositivity for CD4, CD8 and FoxP3 were analyzed as prognostic factors. There was an average of 12.8 ± 1.8 CD31 T cells, 1.5 ± 0.5 CD41 T cells, 6.8 ± 1.3 CD81 T cells and 0.6 ± 0.2 FoxP3 cells. The percentage of positive T-cell subpopulations was 89.6%, 22.4%, 77.6% and 34.3% for CD3, CD4, CD8 and FoxP3, respectively. In eight patients, there was no difference in the subpopulations between the first and second operations. The median progression-free survival was 7.0 months (95% CI, 5.2–8.9 months) and the overall survival was 14.8 months (95% CI, 11–18.7 months). Univariate analysis showed a statistically significant difference in progression-free survival for CD8 (p = 0.02) and overall survival for RTOG-RPA classes (p = 0.003), the extent of removal (p = 0.01) and MGMT promoter methylation status (p = 0.005). Based on multivariate analysis, RTOG-RPA classes were significantly associated with longer overall survival. The intratumoural immune response occurred frequently in glioblastomas and there was a consistent response, even after conventional treatment. There was a statistically significant difference in progression-free survival for CD81 T cells in immunologically privileged central nervous system.

Characterization of Invading Glioma Cells Using Molecular Analysis of Leading-Edge Tissue

OBJECTIVE We have introduced a method of characterization of invading glioma cells by using molecular analysis of marginal invading tumor cells and molecular profiles of glioma tumor margin. METHODS Each of tumor core and marginal tissues was obtained in 22 glioma patients. Tumor core cells and marginal cells from each glial tumor were collected by laser capture microdissection or intraoperative microdissection under the operating microscope. Expression of MMP-2, MMP-9, CD44 and RHAMM mRNA by invading glioma cells compared with tumor core was confirmed by realtime-PCR of twenty-four glioma specimens. Clinical data also were reviewed for invasion and recurrence pattern of the gliomas radiologically and invasive rim pattern microscopically. RESULTS Overall results of the molecular analysis showed that relative overexpression of MMP-2, MMP-9 and RHAMM were noted at the invasive edge of human glioma specimens comparing to the tumor core but CD44 was highly expressed in the tumor core comparing to the margin. High marginal expression of MMP-2 and MMP-9 were noted in poorly ill-defined margin on the pathological finding. High marginal expression of CD44 and MMP-2 were demonstrated in the midline cross group on the radiological review, and that of RHAMM and MMP-2 were showed in the aggressive recurrence group. High expression of MMP-2 seems to be involved in the various invasion-related phenomenons. CONCLUSION Up-regulation of MMP-2, MMP-9, CD44 and RHAMM was noted in invasive edge of gliomas according to the various clinical situations.

Performance status during and after radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma multiforme

For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70years or older with a newly diagnosed GBM were treated with radiotherapy (60Gy in 16 patients and 40Gy in four patients) plus concomitant and adjuvant temozolomide. We assessed age, the extent of tumor removal, and initial performance status as possible prognostic factors for OS and good performance status following treatment. The median OS was 11.8months (95% confidence interval [CI], 8.7-14.8). The median time for patients to reach an Eastern Cooperative Oncology Group (ECOG) performance status grade 2 was 3.0months (95% CI, 2.4-3.5), and the time to ECOG performance status grade 3 was 5.8months (95% CI, 1.6-9.9). World Health Organization grade III or grade IV toxicity was observed in four patients (20%), leucopenia and thrombocytopenia was noted in two patients, and major infection occurred in two patients. Univariate analysis showed a significantly longer OS (p=0.003) and a longer time with good performance status for gross total removal (GTR) (p=0.003). An initial good performance status was related to a good performance status during and after treatment (p=0.003). Based on multivariate analysis, GTR was significantly associated with a longer OS (hazard ratio [HR]=0.236; 95% CI, 0.060-0.922, p=0.038) and a good performance status (HR=0.124; 95% CI, 0.022-0.693, p=0.017). During and after treatment, elderly patients with GBM frequently exhibited an early deterioration of performance status. Therefore, in light of a rapidly fatal illness, elderly patients should be treated to preserve and respect their quality of life.

Intracranial Meningiomas, WHO Grade Il : Prognostic Implications of Clinicopathologic Features

Objective Intracranial meningiomas are primarily benign tumors with a good prognosis. Although WHO grade II meningiomas are rare (2-10%), WHO grade II meningiomas have higher recurrence and mortality rates than benign. We evaluated the patient recurrence rate and investigated the prognostic factors of WHO grade II meningiomas. Methods Between 1993 and 2005, 55 patients were diagnosed with WHO grade II meningiomas in our hospital. WHO grade II meningiomas (n=55) were compared with other WHO grades meningiomas (I, n=373; and III, n=20). The patients had a median age of 48.4 years (range, 14-17 years), a male-to-female ratio of 26 : 29, and a mean follow-up time of 45 months (range, 3-175 months). Results In WHO grade II meningiomas, only the extent of resection was a significant prognostic factor. Post-operative radiotherapy had no significant influence on tumor recurrence (p=0.053). The relative risk of recurrence was significantly higher in WHO grade II meningiomas with incomplete resection (10/27, RR=37%) than in WHO grade II meningiomas with complete resection (4/28, RR=14%) regardless of post-operative radiotherapy. In the incomplete resection group, Simpson grade III or IV had a significantly high risk of recurrence regardless of post-operative RT (n=3, RR=100%) However, if the degree of resection was Simpson grade II, the recurrence rate was similar to the complete resection group even though post-operative RT was not performed. Conclusion Complete resection was the most powerful independent predictive factor of the recurrence rate in WHO grade II meningiomas. Post-operative adjuvant RT was not a significant factor in this study.

The clinical experience of recurrent central nervous system hemangioblastomas

OBJECTIVE Hemangioblastomas (HBLs) of the central nervous system are benign vascular tumors that may occur sporadically or in von Hippel-Lindau disease (VHLD). We analyzed the clinical and radiological findings of HBLs focusing on recurrence. MATERIAL AND METHODS From 1998 to 2012, 36 patients with HBLs were treated. Twenty nine patients (80.6%, mean age 46.7 years) had sporadic HBLs and seven (19.4%, mean age 39 years) had HBLs associated with VHLD. Initially, the mass was totally removed in 32 patients, subtotally in one and partially in one, and gamma knife radiosurgery was done in two patients. The mean duration of follow-up was 48.4 months. We retrospectively analyzed the clinical and radiologic findings. RESULTS The location of cerebellum and brainstem was common. The HBLs of spinal cord and cerebral hemisphere were related with VHLD. The common radiologic findings of sporadic HBLs showed a cyst with a mural nodule in 15 patients (51.7%) and pure solid lesion in eight (27.6%). In HBLs related with VHLD, five of seven patients had multiple lesions and pure solid mass was common. Three (10.3%) and two (28.6%) patients showed recurrence in sporadic and VHLD-related HBLs, respectively. Two totally resected mural nodules on the cyst showed recurrence with similar radiologic findings 3 years later in sporadic HBLs. In recurred HBLs related with VHLD, one pure solid mass and one mural nodule on cyst showed the local recurrences after the total resection 8 years later and associated with distant recurrence. CONCLUSIONS All patients should be more specifically followed to detect local and distant recurrence, even if the clinical course was benign and mass was totally removed.

Predictive factors related to symptomatic venous infarction after meningioma surgery.

Abstract Introduction. The incidence of venous infarction after surgical resection of meningioma is low, but its occurrence can necessitate additional surgical procedures and long hospital stay. In this study, we evaluated variables associated with venous infarction after meningioma surgery. Methods. Among 825 patients with intracranial meningiomas who underwent microsurgical resection between January 1993 and March 2011, 27 (3.3%) presented with neurological deterioration due to postoperative venous infarction. The following factors were included in the statistical analysis to determine their association with venous infarction: sex, age, location, relation to venous sinus, peritumoural oedema, size and degree of resection. Results. Incidence of venous infarction was 6.8% with large meningiomas (size ≥ 4 cm), but with small (size < 4 cm) was reduced to 1.2% (p < 0.001). Meningiomas with perilesional edema elicited venous infarction more frequently than those without (5.1% vs. 2.3%, p = 0.030). Venous infarction was also determined to occur at 5.5% frequency in superficial meningiomas, such as parasagittal, falx and convexity, but only at 0.5% frequency in deep locations (p = 0.001). Venous infarction additionally occurred less often in meningiomas at a distance from the midline venous sinus than in those nearby, such as parasagittal and falx (2.2% vs. 6.6%, p = 0.004). Conclusions. To prevent venous infarction after meningioma surgery, it is essential to maintain the intervening arachnoid plane as much as possible; this is especially important in meningiomas larger than 4 cm, combined with peritumoural edema or positioned superficially around the midline venous sinus.

Intramedullary subependymoma of the thoracic spinal cord

We report a rare case of a thoracic intramedullary subependymoma in a 37-year-old woman. The patient developed a monoparesis of the right leg after a subtotal resection of the tumor. During the 30 months of follow-up the neurological deficit improved and the patient remained symptom free without progression of the remnant tumor. A complete resection of the tumor is usually curative with improved function. However, aggressive surgery may cause either worsening of an existing deficit or the development of new deficits. In patients with poor delineation between the tumor and the spinal cord, subtotal removal and close follow-up should be considered.

Alternative Treatment of Stereotactic Cyst Aspiration and Radiosurgery for Cystic Brain Metastases

Background: Surgical removal is the first choice of treatment for large cystic brain metastases. However, some patients cannot undergo surgical resection due to their general condition and/or the tumor location. Aims: In this study, we investigated the feasibility and safety of stereotactic cyst aspiration and gamma knife radiosurgery (GKR) as an alternative treatment for these lesions and followed the volumetric changes in cystic and solid portions. Methods: Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS). Results: Before aspiration, the mean total tumor volume was 32.7 cm3 (range, 12.1-103.3) and cystic volume was 18.6 cm3 (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm3 (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm3 (range, 3.7-38.1) and cystic volume was 2.0 cm3 (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (±1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (±0.42) and 6.8 (±0.38) months. Conclusions: Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time.

Leptomeningeal Dissemination of a Low-Grade Brainstem Glioma without Local Recurrence

It is rare for low-grade gliomas to disseminate to the leptomeninges. However, low-grade gliomas with dissemination to the leptomeninges have been occasionally reported in children, and have generally been associated with local recurrence. A 16-year-old boy sought evaluation for diplopia and gait disturbance. A brain magnetic resonance imaging (MRI) revealed pontine mass, which was proved to be fibrillary astrocytoma on biopsy, later. Radiation therapy (5400 cGy) was given and the patients symptoms were improved. He was followed-up radiologically for brain lesion. Seven months after diagnosis he complained of back pain and gait disturbance. A brain MRI showed a newly-developed lesion at the left cerebellopontine angle without an interval change in the primary lesion. A spinal MRI demonstrated leptomeningeal dissemination of the entire spine. Radiation therapy (3750 cGy) to the spine, and adjuvant chemotherapy with a carboplatin plus vincristine regimen were administered. However, he had a progressive course with tumoral hemorrhage and expired 13 months after diagnosis. We report an unusual case of a low-grade brainstem glioma with spinal dissemination, but without local recurrence, and a progressive course associated with hemorrhage.