Intracavitary Radiation Therapy for Recurrent Cystic Brain Tumors with Holmium-166-Chico : A Pilot Study

OBJECTIVE: Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS: Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS: There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION: Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

Chemotherapy for Malignant Gliomas Based on Histoculture Drug Response Assay : A Pilot Study

OBJECTIVE: The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials. METHODS: Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image. RESULTS: Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months (p=0.07). CONCLUSION: HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.

Radiosurgery for Recurrent Brain Metastases after Whole-Brain Radiotherapy : Factors Affecting Radiation-Induced Neurological Dysfunction

OBJECTIVE: We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. METHODS: In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was 12.4 cm3. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. RESULTS: Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age (6 months) toxicity occurred in 21%, respectively. Less acute toxicity was observed with small tumors (<10 cm3, p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gyxcm3) was a significant predictor of both acute and chronic CNS toxicities. CONCLUSION: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

Clinical Results of Cyberknife(R) Radiosurgery for Spinal Metastases

OBJECTIVE: Primary treatment of spinal metastasis has been external beam radiotherapy. Recent advance of technology enables radiosurgery to be extended to extracranial lesions. The purpose of this study was to determine the clinical effectiveness and safety of stereotactic radiosurgery using Cyberknife in spinal metastasis. METHODS: From June, 2002 to December, 2007, 129 patients with 167 spinal metastases were treated with Cyberknife. Most of the patients (94%) presented with pain and nine patients suffered from motor deficits. Twelve patients were asymptomatic. Fifty-three patients (32%) had previous radiation therapy. Using Cyberknife, 16-39 Gy in 1-5 fractions were delivered to spinal metastatic lesions. Radiation dose was not different regarding the tumor pathology or tumor volume. RESULTS: After six months follow-up, patient evaluation was possible in 108 lesions. Among them, significant pain relief was seen in 98 lesions (91%). Radiological data were obtained in 83 lesions. The mass size was decreased or stable in 75 lesions and increased in eight lesions. Radiological control failure cases were hepatocellular carcinoma (5 cases), lung cancer (1 case), breast cancer (1 case) and renal cell carcinoma (1 case). Treatment-related radiation injury was not detected. CONCLUSION: Cyberknife radiosurgery is clinically effective and safe for spinal metastases. It is true even in previously irradiated patients. Compared to conventional radiation therapy, Cyberknife shows higher pain control rate and its treatment process is more convenient for patients. Thus, it can be regarded as a primary treatment modality for spinal metastases.

The Role of Surgery in the Treatment of Spinal Myeloma

OBJECTIVE: Spinal myeloma has been treated with radiation therapy and chemotherapy. However, the role of surgery was not fully evaluated. This study is performed to evaluate the efficacy of surgery in the treatment of spinal myeloma. METHODS: 22 patients who were treated with surgery for spinal myeloma from August 1999 to April 2003 were analyzed. Radiological finding, surgical methods and result were reviewed in retrospective study. For compression fracture due to myeloma infiltration, percutaneous vertebroplasy(PVP) was done. Decompression surgery with or without fixation was performed for patients with neurologic deficit. The modalities of surgery consist of PVP (14 cases), corpectomy and fixation (7 cases), and laminectomy and epidural mass removal (3 cases). To evaluate clinical outcome, visual analogue pain score and Frankel neurological scale were used. RESULTS: In 14 cases of PVP, total 57 vertebral segments were treated including 21 thoracic vertebral bodies and 36 lumbar vertebral bodies. Pain relief was achieved in all cases. The pain score changed from 7.7 (preoperatively) to 2.5 (postoperatively). And pain relief effect was maintained over than one year. Frankel grade improved in decompression cases. CONCLUSION: Surgical treatment can alleviate pain and improve neurologic deficit immediately in spinal myeloma patients.

A Case of Pituitary Fossa Chondrosarcoma Mimicking Sellar and Suprasellar Mass

We report a rare case of chondrosarcoma arising from the dorsum sellae as it mimicked sellar and suprasellar mass. A 36 year-old man visited our hospital for his decreasing visual acuity. Brain magnetic resonance(MR) image revealed round a sellar and suprasellar mass showing mottled enhancement with internal cystic material. The MR image favored the diagnosis of craniopharyngioma, most likely, while plain skull X-ray showed sellar floor erosion and widening, which favored pituitary adenoma. The patient underwent trans-sphenoidal approach less than a week of admission and evaluation because his visual acuity was at a risk of blindness. In the operation, sellar mass was totally removed but some of suprasellar mass was inevitably remained due to limited surgical field. The pathologic diagnosis was chondrosarcoma. Six months from the first operation, pterional approach was performed to remove the remaining suprasellar mass, which didn't come down to sellar area. Intraoperative findings confirmed that the mass was originated from dorsum sellae.

Brain Metastasis of Colorectal Cancer

PURPOSE: Brain metastasis is infrequent in colorectal cancer patients. The purpose of this study was to analyze the clinical characteristics including the survival, type of treatment, and metastatic patterns of brain metastasis in colorectal cancer. METHODS: Between January 1993 and September 2002, we analyzed 2,019 surgical patients with colorectal carcinoma operated at Korea Cancer Center Hospital. Among these patients, 13 patients were identified with metastatic colorectal cancer to the brain. The medical records of these patients were reviewed retrospectively and survival analysis was performed. RESULTS: During the study period, the incidence of brain metastasis of colorectal cancer was 0.6%. Male-to-female ratio was 1:1.6. Mean age was 55.2+/-9.7 years and median age was 56 years (34~67years). The most frequent primary tumor site was the rectum (11 cases, 84.6%). and the most frequent symptom of brain metastasis was headache. According to the TNM staging system, there were 1 case in stage II, 8 cases in stage III, and 4 cases in stage IV at the time of initial diagnosis of colorectal cancer. Brain metastases were often occurred concurrently with lung metastases (9 cases, 69.2%), otherwise solitary brain metastasis was found in 4 cases. Between the diagnosis of primary cancer and the diagnosis of brain metastasis, the mean interval was 25.9+/-6.9 months and the median interval was 16 months (5~97) in stage II and III patients. The mean survival time after the diagnosis of brain metastasis was 18.5 months for patients who underwent surgery and 3.3 months for patients who received non-surgical therapy. CONCLUSIONS: Brain metastasis of colorectal cancer is relatively uncommon and the incidence is significantly low, commonly more or less than 1%. It is often accompanied by pulmonary metastasis. The results of this study show that surgical resection may increase the survival of these patients. Though inability to the awareness of the possibility and early diagnosis of brain metastasis in colorectal cancer could affect the poor prognosis, aggressive treatment in suitable cases might enhance the survival for this group of patients.

Arsenic Trioxide, an Old Drug? or a New Drug? / Journal of the Korean Cancer Association, 대한암학회지

No abstract available.

Postoperative Brain Abscess Caused by Co-Infection of Aspergillus and Staphylococcus: Case Report

A staphylococcal brain abscess admixed with aspergillosis occurred after operation for the olfactory groove meningioma at remote site. We report the rare case and consider the clinical pathogenesis. Bifrontal craniotomy for the olfactory groove meningioma was done in a 61-year-old female. She was bedridden for one month after craniotomy. During that period, panhypopituitarism occurred and was corrected with hormonal replacement. Sore in the occipital scalp which had occurred during the bedridden state was cared by dressing. After 60 days of treatment, he was discharged with ambulatory status. During postoperative period, we found left parieto-occipital brain abscess in the brain computed tomography(CT) at 3 months. And then craniotomy and abscess resection was performed. Vancomycin and itraconazole antibiotic therapy was instituted after the identification of staphylococcus and aspergillus in the cystic fluid, and aspergillus hyphae in the solid wall portion of the abscess. After the confirmation of resolution of brain abscess on the postoperative 3 weeks' brain CT, the patient was discharged with oral itraconazole medication.

Dosimetry of the Low Fluence Fast Neutron Beams for Boron Neutron Capture Therapy / 대한방사선종양학회지

PURPOSE: For the research of Boron Neutron Capture Therapy (BNCT), fast neutrons generated from the MC-50 cyclotron with maximum energy of 34.4 MeV in Korea Cancer Center Hospital were moderated by 70 cm paraffin and then the dose characteristics were investigated. Using these results, we hope to establish the protocol about dose measurement of epi-thermal neutron, to make a basis of dose characteristic of epi-thermal neutron emitted from nuclear reactor, and to find feasibility about accelerator-based BNCT. METHOD AND MATERIALS: For measuring the absorbed dose and dose distribution of fast neutron beams, we used Unidos 10005 (PTW, Germany) electrometer and IC-17 (Far West, USA), IC-18, EIC-1 ion chambers manufactured by A-150 plastic and used IC-17M ion chamber manufactured by magnesium for gamma dose. There chambers were flushed with tissue equivalent gas and argon gas and then the flow rate was 5 cc per minute. Using Monte Carlo N-Particle (MCNP) code, transport program in mixed field with neutron, photon, electron, two dimensional dose and energy fluence distribution was calculated and there results were compared with measured results. RESULTS: The absorbed dose of fast neutron beams was 6.47x10-3 cGy per 1 MU at the 4 cm depth of the water phantom, which is assumed to be effective depth for BNCT. The magnitude of gamma contamination intermingled with fast neutron beams was 65.2+/-0.9% at the same depth. In the dose distribution according to the depth of water, the neutron dose decreased linearly and the gamma dose decreased exponentially as the depth was deepened. The factor expressed energy level, D20/D10, of the total dose was 0.718. CONCLUSION: Through the direct measurement using the two ion chambers, which is made different wall materials, and computer calculation of isodose distribution using MCNP simulation method, we have found the dose characteristics of low fluence fast neutron beams. If the power supply and the target material, which generate high voltage and current, will be developed and gamma contamination was reduced by lead or bismuth, we think, it may be possible to accelerator-based BNCT.

Growth Suppression by Adenovirus-mediated Gene Transfer of p16/INK4a in Glioma Cell Lines

No abstract available.

Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.

Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.

Percutaneous Vertebroplasty in Spinal Metastasis and Myeloma:25 Cases Experience

No abstract available.

Epidural Granulocytic Sarcoma Causing Cord Compression at Thoracic Region in Acute Myelogenous Leukemia: A Case Report

No abstract available.

Clinical Analysis of 178 Metastatic Brain Tumors

OBJECTIVE: A retrospective clinical analysis for metastatic brain tumors was undertaken to understand demographic feature, to determine the survival rate, prognostic factors and to decide the role of surgery. PATIENTS AND METHODS: From 1987 to 1994, 178 patients with brain metastases were treated at our hospital. Data regarding the primary disease and characteristics of brain metastases were retrospectively collected. We used Kaplan-Meier method to assess survival rate, and log-rank test to compare survival rates between subgroups. RESULTS: The most common age at the time of diagnosis was sixth and seventh decade(62%). The male to female ratio was 97:81. The supratentorial lesions were in 128(77%, n=67) and multiple lesions were in 84(55%, n=52). The most common primary cancer was lung cancer(80, 45%), and metastases of unknown origin(28, 16%), breast(27, 15%), head and neck(11, 6%), colorectal cancer(7, 4%), and stomach cancer(6, 3%). The time to metastasis was shortest in lung cancer(15 months), and longest in head and neck cancer(61 months). The overall 1 year survival rate(1YSR) was 25.4% and median survival time(MST) was 5.6 months. There was no statistically significant difference in MST and 1YSR between single and multiple metastases. The 1YSR of metastatic brain tumor from head and neck cancer was 62.5% and that from breast, lung, and GI tract was 37.7%, 25.7%, and 8.3% respectively. The overall 1YSR and MST of resected group in single metastasis(n=0, resection plus whole brain radiation therapy; WBRT) were 33.3% and 6.6 months, and those of non-resected group(n=5, WBRT) were 31.5% and 5.6 months. The 1YSR and MST of resected group in single metastasis from lung cancer(n=) were 37.5% and 8.4 months, and those of non-resected group(n=6) were 25% and 4.8 months. But there were no statistically significant differences. Karnofsky performance scale score was improved in 37% of resected group, compared with 24% of non-resected group. CONCLUSION: Surgical removal of metastatic brain tumor in selected patients results in increased survival time and better quality of life. For the statistical significance, multi-institutional well-designed prospective randomized study is needed.

Clinical Analysis on Open Thoracic Cordotomy of the Cancer Pain

Patients with pain syndromes resulting from recurrent or metastatic cancer should be evaluated carefully to determine the cause of their pain and the need for appropriate antitumor treatment. The most effective ablative pain control procedure at the current time is cordotomy, which is indicated in patients with unilateral pain. The authors results of 12 antero-lateral thoracic cordotomies performed for intractable cancer pain between 1996-1998. The follow-up of these patients was continued for at least 12 months or until death to determine the late success of this procedure. Excellent surgical results were obtained in 100% after one week and in 50% in 6 months after operation. The operation was considered to be successful for patients with malignant disease of short life expectancy.

Three Cases of Primary Spinal Malignant Schwannomas: Case Reports

Malignant peripheral nerve sheath spinal tumours are relatively rare. A primary spinal location at the first onset is rarely reported in the literature, thus the clinical features and therapeutic results of these spinal malignant tumours are not defined. We describle three patients with primary spinal malignant schwannomas and stress the surgical mananement of these cases.

Brain Stem Gliomas in Adult: Correlation between MRI, Clinical Findings and Outcome: Preliminary Report

An analysis of 13 patients with brain stem glioma in adult, treated between 1988 and 1995, was undertaken. The purpose of this study is to establish the correlations between the MRI appearance, clinical findings and the prognosis. Based on the MRI appearance of the tumor at the time of clinical diagnosis, tumors were divided into four types: intrinsic diffuse, intrinsic focal, intrinsic cervicomedullary and exophytic type. Five patients were diagnosed pathologically by means of stereotactic biopsy(2 patients) and open surgery(3 patients), the rest were diagnosed on the basis of MRI appearance. All patients had received radiation therapy, and 11 patients had received chemotherapy during or immediately after radiation therapy. The methods of radiation therapy were either conventional or hyperfractionated type. The histological features were not always correlated with the prognosis. MRI and clinical findings could suggest the prognosis and probably the histological nature of the tumors. Moreover, response to initial radiotherapy and chemotherapy was considered to be a good prognostic factor. Seven of the 13 patients had response to the initial radiotherapy and chemotherapy. The poor prognostic factors determined in our study were 1) diffuse type 2) rapid growing with rim enhancement in spite of initial radiotherapy and chemotherapy 3) malignant pathologic finding 4) intratumoral necrosis after radiotherapy 5) multiple site involvement. The good prognostic factors were 1) intrinsic focal type 2) intrinsic cervicomedullary type 3) no cranial nerve involvement 4) good response to initial radiotherapy and chemotherapy.

Molecular Profiling of Human Gliomas by cDNA Expression Array

Extensive research in this decade has led to detailed understanding of genetic changes underlying human cancers. Two major tumorigenic events are mutation and amplification of oncogenes and inactivation of tumor suppressor genes. These events then trigger a series of signal transduction cascades, activating expression of downstream genes that control various cellular activities including cell cycle progression, DNA synthesis, programmed cell death, DNA repair, and cell migration. Investigations of these molecular pathways has led to the identification of many targets for therapeutic intervention. Knowledge of the expression patterns and functions of all human genes wil l provide a frame work for future molecular, genetic medicine. During the past ten years, the human genome project has generated an enormous amount of sequencing information, and sequencing of the entire human genome may be completed by the year 2003 (1,2). One can envision that this will irreversibly transform the methodology of medical research and the practice of medicine. The search for new genes, which currently consumes the effort of many talented scientists, will become past history. Additionally, studying one gene at a time will be replaced by studying large number of genes simultaneously(3). Reductionistic approaches to human disease will be replaced by systemic approach. As a prelude to this revolution, tools used for parallel analysis of gene expression in the format of ordered gene arrays have been developed and are under continued expansion. In this technical tip, we will introduce the Atlas Human cDNA Expression Array system developed by Clontech Laboratories, Inc.(4). With this technology, a conventional laboratory can profile the expression of 588 human genes simultaneously in one simple experiment without the using of expensive equipment. We will demonstrate the profiling of 588 genes in a human glioblastoma cell line to exemplify the utility of this technique.