The Sagittal Balance of Cervical Spine : Comprehensive Review of Recent Update

The cervical spine plays a critical role in supporting the skull, maintaining horizontal gaze, and facilitating walking. Its unique characteristics, including the widest range of motion among spinal segments, have led to extensive research on cervical sagittal alignment. Various parameters have been proposed to evaluate cervical alignment, with studies investigating their clinical significance, correlation with symptoms, and implications for surgical interventions. Recent findings suggest that cervical sagittal alignment not only impacts the cervical spine but also influences global spine-pelvic alignment through compensatory mechanisms. This comprehensive review examines classical and new parameters of cervical sagittal alignment and considers the dynamic and muscular factors associated with it.

Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). @*Materials and Methods@#In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). @*Results@#Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). @*Conclusion@#The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade IIIGliomas without 1p/19q Co-deletion: A Randomized, Open-Label,Phase 2 Study (KNOG-1101 Study) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We investigated the efficacy of temozolomide during and after radiotherapy in Korean adultswith anaplastic gliomas without 1p/19q co-deletion. @*Materials and Methods@#This was a randomized, open-label, phase 2 study and notably the first multicenter trial forKorean grade III glioma patients. Eligible patients were aged 18 years or older and hadnewly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative OncologyGroup performance status of 0-2. Patients were randomized 1:1 to receive radiotherapyalone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy withconcurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary endpointwas 2-year progression-free survival (PFS). Seventy patients (83.3%) were availablefor the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status. @*Results@#The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overallsurvival (OS) did not reach to significant difference between the groups. In multivariableanalysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidenceinterval [CI], 1.04 to 4.16). The IDH1mutation was the only significant prognostic factor forPFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverseevents over grade 3 were seen in 16 patients (40.0%) in the treatment group and werereversible. @*Conclusion@#Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed nonco-deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimenneeds further analysis with long-term follow-up at least more than 10 years.

Effect of Cumulative Dexamethasone Dose during Concomitant Chemoradiation on Lymphopenia in Patients with Newly Diagnosed Glioblastoma

Background@#Lymphopenia frequently occurs after concomitant chemoradiation (CCRT) in patients with glioblastoma (GBM) and is associated with worse overall survival (OS). A few studies have tried to identify risk factors for lymphopenia; however, the results were not clear. We aimed to identify potential risk factors for lymphopenia, focusing on the use of dexamethasone to control cerebral edema in patients with GBM. @*Methods@#The electronic medical records of 186 patients with newly diagnosed GBM treated at our institution between 2009 and 2017 were retrospectively examined. Acute lymphopenia was defined as total lymphocyte count less than 1,000 cells/μL at 4 weeks after completion of CCRT.Multivariate logistic regression analysis was used to identify independent risk factors for lymphopenia, and Cox regression analysis was used to identify independent risk factors for OS. @*Results@#Of the 125 eligible patients, 40 patients (32.0%) developed acute lymphopenia. Female sex and median daily dexamethasone dose ≥2 mg after initiation of CCRT were independent risk factors for acute lymphopenia on multivariate analysis. Acute lymphopenia, extent of surgical resection, and performance status were associated with OS; however, dexamethasone use itself was not an independent risk factor for poor OS. @*Conclusion@#Female sex, median daily dexamethasone dose ≥2 mg after initiation of CCRT until 4 weeks after completion of CCRT may be associated with acute lymphopenia. However, dexamethasone use itself did not affect OS in patients newly diagnosed with GBM. These results should be validated by further prospective studies controlling for other confounding factors.

Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

High-Dose Metformin Plus Temozolomide Shows Increased Anti-tumor Effects in Glioblastoma In Vitro and In vivo Compared with Monotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in Vitro and in vivo. MATERIALS AND METHODS: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5×105 U87 cells and treatedwith metformin, TMZ, and the combination for 4weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway. RESULTS: The combination of TMZ and metformin showed higher cytotoxicity than single agents in U87, U251, and A172 cell lines. A combination of high-dose metformin and TMZ showed the highest apoptotic activity. The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression. The median survival of each group was 43.6, 55.2, 53.2, 65.2, and 71.3 days for control, metformin treatment (2 mg/25 g/day or 10 mg/25 g/day), TMZ treatment (15 mg/kg/day), combination treatment with low-dose metformin and TMZ, and combination treatment with high-dose metformin and TMZ, respectively. Expression of fatty acid synthase (FASN) was significantly decreased in tumor specimens treated with metformin and TMZ. CONCLUSION: The combination of metformin and TMZ was superior to monotherapy using metformin or TMZ in terms of cell viability in Vitro and survival in vivo. The combination of high-dose metformin and TMZ inhibited FASN expression in an orthotopic model. Inhibition of FASN might be a potential therapeutic target of GBM.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence

BACKGROUND: The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence. METHODS: One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence. RESULTS: Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01). CONCLUSIONS: Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

Parasellar Extension Grades and Surgical Extent in Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas : A Single Surgeon's Consecutive Series with the Aspects of Reliability and Clinical Validity

OBJECTIVE: The inter-rater reliability of the modified Knosp's classification was measured before the analysis. The clinical validity of the parasellar extension grading system was evaluated by investigating the extents of resection and complication rates among the grades in the endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenomas. METHODS: From November 2008 to August 2015, of the 286 patients who underwent EETS by the senior author, 208 were pituitary adenoma cases (146 non-functioning pituitary adenomas, 10 adrenocorticotropic hormone-secreting adenomas, 31 growth hormone-secreting adenomas, 17 prolactin-secreting adenomas, and 4 thyroid-stimulating hormone-secreting adenomas; 23 microadenomas, 174 macroadenomas, and 11 giant adenomas). Two neurosurgeons and a neuroradiologist independently measured the degree of parasellar extension on the preoperative sellar MRI according to the modified Knosp's classification. Inter-rater reliability was statistically assessed by measuring the intraclass correlation coefficient. The extents of resection were evaluated by comparison of the pre- and post-operative MR images; the neurovascular complications were assessed by reviewing the patients' medical records. The extent of resection was measured in each parasellar extension grade; thereafter, their statistical differences were calculated. RESULTS: The intraclass correlation coefficient value of reliability across the three raters amounted to 0.862. The gross total removal (GTR) rates achieved in each grade were 70.0, 69.8, 62.9, 21.4, 37.5, and 4.3% in Grades 0, 1, 2, 3A, 3B, and 4, respectively. A significant difference in the extent of resection was observed only between Grades 2 and 3A. In addition, significantly higher complication rates were observed in the groups above Grade 3A. CONCLUSION: Although the modified Knosp's classification system appears to be complex, its inter-rater reliability proves to be excellent. Regarding the clinical validity of the parasellar extension grading system, Grades 3A, 3B, and 4 have a negative predictive value for the GTR rate, with higher complication rates.

Continuous Low-Dose Temozolomide Chemotherapy and Microvessel Density in Recurrent Glioblastoma

OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. METHODS: Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at 50 mg/m2/day until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). RESULTS: The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was 22.7+/-24.1/mm2 (mean+/-standard deviation), and this was lower than that of the initial tumor (61.4+/-32.7/mm2) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. CONCLUSION: The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.

Modified Graded Repair of Cerebrospinal Fluid Leaks in Endoscopic Endonasal Transsphenoidal Surgery

OBJECTIVE: Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time-consuming. METHODS: Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage. RESULTS: Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned. CONCLUSION: Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en-bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks.

Efficacy of Procarbazine, Lomustine, and Vincristine Chemotherapy for Recurrent Primary Central Nervous System Lymphomas

BACKGROUND: Optimal treatment for recurrent primary central nervous system lymphomas (PCNSLs) has not been defined yet and there is no general consensus about the salvage chemotherapy after high-dose methotrexate (HD-MTX)-based chemotherapy. The purpose of the present study was to evaluate the efficacy and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy for recurrent PCNSLs. METHODS: We reviewed eight immunocompetent patients (five males/three females, mean age: 56 years) who received salvage PCV chemotherapy (procarbazine 60 mg/m2, days 8 through 21: CCNU 110 mg/m2, day 1: vincristine 2 mg, days 8 and 28) for recurrent PCNSL and two patients switched to PCV chemotherapy due to severe adverse effects of HD-MTX chemotherapy. Radiologic responses, survival, and adverse effects were analyzed. RESULTS: Of the eight recurrent PCNSLs, three patients (37.5%) showed radiologic complete response, one patient (12.5%) showed partial response, and four patients (50%) showed progressive disease after PCV chemotherapy. Median progression free survival (PFS) from the first administration of PCV to relapse or last follow-up was 7 months (range 5-32 months) and median overall survival was 8 months (range 2-41 months). The two patients who switched to PCV chemotherapy showed PFS of 9 and 5 months from the beginning of PCV to relapse. The common side effects were thrombocytopenia, neutropenia, and peripheral neuropathy. There were 4 grade III or IV myelo-suppression, but no fatal complications, including severe hemorrhage or infection, were observed. CONCLUSION: Salvage PCV chemotherapy has a moderate anti-lymphoma activity for recurrent PCNSLs after the HD-MTX-based chemotherapy with tolerable toxicity.

Primary Malignant Melanoma in the Pineal Region

A 59-year-old male patient had 5-month history of gait disturbance and memory impairment. His initial brain computed tomography scan showed 3.5x2.8 cm sized mass with high density in the pineal region. The tumor was hypointense on T2 weighted magnetic resonance images and hyperintense on T1 weighted magnetic resonance images with heterogenous enhancement of central portion. The tumor was totally removed via the occipital transtentorial approach. Black mass was observed in the operation field, and after surgery, histopathological examination confirmed the diagnosis of malignant melanoma. Whole spine magnetic resonance images and whole body 18-fluoro-deoxyglucose positron emission tomography could not demonstrate the primary site of this melanoma. Scrupulous physical examination of his skin and mucosa was done and dark pigmented lesion on his left leg was found, but additional studies including magnetic resonance images and skin biopsy showed negative finding. As a result, final diagnosis of primary pineal malignant melanoma was made. He underwent treatment with the whole brain radiotherapy and extended local boost irradiation without chemotherapy. His preoperative symptoms were disappeared, and no other specific neurological deficits were founded. His follow-up image studies showed no recurrence or distant metastasis until 26 weeks after surgery. Primary pineal malignant melanomas are extremely rare intracranial tumors, and only 17 cases have been reported since 1899. The most recent case report showed favorable outcome by subtotal tumor resection followed by whole brain and extended local irradiation without chemotherapy. Our case is another result to prove that total tumor resection with radiotherapy can be the current optimal treatment for primary malignant melanoma in the pineal region.

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

OBJECTIVE: To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). METHODS: A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. RESULTS: TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (> or =grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). CONCLUSION: For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.

Clinical Analysis of Intracranial Hemangiopericytoma

OBJECTIVE: Intracranial hemangiopericytomas (HPCs) are rare tumors with aggressive behavior, including local recurrence and distant metastasis. We conducted this retrospective study to evaluate the efficacy of grossly total resection and adjuvant radiotherapy (RT) for these tumors. METHODS: A total of 13 patients treated for intracranial HPC from January 1995 through May 2013 were included in this retrospective study. We analyzed the clinical presentations, radiologic appearances, treatment results, and follow-up outcomes, as well as reviewed other studies. RESULTS: The ages of the patients at the time of diagnosis ranged from 26 to 73 years (mean : 48 years). The majority of the patients were male (92.3%), and the majority of the tumors were located in the parasagittal and falx. The ratio of intracranial HPCs to meningiomas was 13 : 598 in same period, or 2.2%. Seven patients (53.8%) had anaplastic HPCs. Nine patients (69.2%) underwent gross total tumor resection in the first operation without mortality. Eleven patients (84.6%) underwent postoperative adjuvant RT. Follow-up period ranged from 13 to 185 months (mean : 54.3 months). The local recurrence rate was 46.2% (6/13), and there were no distant metastases. The 10-year survival rate after initial surgery was 83.9%. The initial mean Karnofsky performance scale (KPS) was 70.8 and the final mean KPS was 64.6. CONCLUSION: Gross total tumor resection upon initial surgery is very important. We believe that adjuvant RT is helpful even with maximal tumor resection. Molecular biologic analyses and chemotherapy studies are required to achieve better outcomes in recurrent intracranial HPCs.

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

OBJECTIVE: This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma. METHODS: Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety. RESULTS: A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted. CONCLUSION: This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.

De Novo Aneurysm after Treatment of Glioblastoma

A rare case of spontaneous subarachnoid hemorrhage from newly developed cerebral aneurysm in glioblastoma patient is presented. A 57-year-old man was presented with headache and memory impairment. On the magnetic resonance image and the magnetic resonance angiography, a large enhancing mass was found at right frontal subcortex and intracranial aneurysm was not found. The mass was removed subtotally and revealed as glioblastoma. He took concurrent PCV chemotherapy and radiation therapy, but the mass recurred one month later after radiotherapy. He was then treated with temozolomide for 7 cycles. Three months after the completion of temozolomide therapy, he suffered from a subarachnoid hemorrhage due to a rupture of a small de novo aneurysm at distal anterior cerebral artery. He underwent an aneurysm clipping and discharged without neurologic complication.

Radiation-induced brain injury: retrospective analysis of twelve pathologically proven cases

PURPOSE: This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). MATERIALS AND METHODS: The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. RESULTS: Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose (BED)3 (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed or =6 months (p = 0.085). CONCLUSION: Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development.

The Clinical Features of Spinal Leptomeningeal Dissemination from Malignant Gliomas

OBJECTIVE: The incidence of leptomeningeal dissemination from malignant glioma is rare, so the clinical features of this are not well documented yet. We attempted to determine the clinical features of leptomeningeal dissemination from malignant gliomas. METHODS: We retrospectively analyzed 11 cases of leptomeningeal dissemination of malignant glioma, who were treated at our institution between 2006 and 2009. We investigated the clinical features of these patients by considering the following factors : tumor locations, the events of ventricular opening during surgery and the cerebrospinal fluid (CSF) profiles, including the cytology. RESULTS: The group was composed of 9 males and 2 females. The histological diagnosis of their initial intracranial tumors were 4 primary glioblastoma, 3 anaplastic astrocytoma, 1 anaplastic oligoastrocytoma, 2 ganglioglioma and 1 pleomorphic xanthoastrocyotma with anaplastic features. The mean age of the patients at the time of the initial presentation was 42.8+/-10.3 years. The mean time between surgery and the diagnosis of spinal dissemination was 12.3+/-7.9 (3-28) months. The mean overall survival after dissemination was 2.7+/-1.3 months. All our patients revealed a history of surgical opening of the ventricles. Elevated protein in the CSF was reported for eight patients who had their CSF profiles checked. CONCLUSION: We propose that in the malignant gliomas, the surgical opening of ventricles can cause the spinal leptomeningeal dissemination and the elevated protein content of CSF may be a candidate marker of leptomeningeal dissemination.

A Case of Pituitary Abscess that was Difficult to Diagnose due to Repeated Symptomatic Responses to Every Corticosteroid Administration

Pituitary abscess is a rare pathology, but it is a potentially life-threatening condition. Therefore, timely intervention, including antibiotics and an operation, can prevent the morbidity and mortality in such cases. A 31-year-old woman, who was 16 months after her second delivery, presented with intermittent headache for 3 months. Amenorrhea, polyuria and polydipsia were noticed and the endocrinological hormone studies were compatible with panhypopituitarism and diabetes insipidus. Pituitary MRI demonstrated a 2.3 cm sized cystic mass with an upper small nodular lesion. Her symptoms such as headache and fever were repeatedly improved whenever corticosteroid was administered, which led us to suspect the diagnosis of an inflammatory condition like lymphocytic hypophysitis. During the hormone replacement therapy, her cystic pituitary mass had grown and her symptoms progressively worsened for another two months. The patient underwent trans-sphenoidal exploration and she turned out to have a pituitary abscess. At the 3-month follow-up, amenorrhea was noticed and her residual function of the pituitary was tested by a combined pituitary stimulation test. The results were compatible with panhypopituitarism. She received levothyroxine 100 microg, prednisolone 5 mg and desmopressin spray and she is being observed at the out-patient clinic. The authors experienced a patient with primary pituitary abscess that was confirmed pathologically and we report on its clinical course with a literature review.