Gamma Knife Irradiation Research Articles

Prospective evaluation of preoperative stereotactic radiosurgery followed by delayed resection of a high grade arteriovenous malformation

Reports of the utility of preoperative radiation for shrinking large arteriovenous malformations (AVM) in preparation for resection have produced conflicting results, and to our knowledge no prospective studies are available. A 28-year-old man presented with a ruptured right temporal Spetzler-Martin Grade 5 AVM with deep venous drainage, involvement of the internal capsule, deep perforator supply, and a diffuse nidus. He underwent staged embolization, a single Gamma Knife (Elekta AB, Stockholm, Sweden) radiation treatment to the deepest portion of the nidus followed by complete surgical resection 3years later. He suffered no long-term neurological deficits and has since returned to work symptom-free (modified Rankin Scale score 0). Preoperative radiosurgery is an effective method for downgrading high-grade AVM in preparation for surgery by targeting the deeper portions that abut or involve eloquent territory. To our knowledge this is the first such successful prospective report in the literature.

Psychological reserves of patients with laryngeal cancer

Aim. To reveal the psychological features of the patients, suffering from laryngeal cancer depending of surgical treatment type and extent. Methods. 109 patients of the clinical oncological hospital were included. The first group included 88 patients who underwent surgery: larynx resection - 35 patients, laryngectomy - 40 patients, and 13 patients in whom voice rehabilitation by imposing a shunt between a trachea and a gullet and vocal prosthesis introduction were performed. The second group included patients of radiological department who have refused surgery (21 patients) and were receiving radical gamma-knife radiotherapy. The psychological techniques were applied to assess the types of reaction to illness and intensity of psychopathological symptoms. Results. The psychological traits of patients in whom a tracheaesophagal shunt was formed, can describe them as socially adapted, patient with low anxiety level. Due to vocal prosthesis they can communicate, that is resulted in features of their behavior. Among compared groups, there were statistically significant differences in the extent of «projection» psychological protection mechanism and the degree of phobic disorders. Conclusion. It is necessary to create a rehabilitation complex for psychological rehabilitation of patients with laryngeal cancer. Further studies will help to understand, why they refuse surgery and to help them to complete a correct apprehension of illness basing on true data about their disease.

A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) includes a spectrum of radiosensitive and radioresistant tumors. However, little is known about the molecular determinants of cellular radiation responses. We examined clinical outcomes after gamma knife radiotherapy for NSCLC intracranial metastases to evaluate the use of this model for determining radiosensitive tumor genotypes. Between 2005 and 2012, 239 patients with NSCLC were enrolled in a prospective gamma knife data repository. Molecular pathology regarding EGF receptor (EGFR), ALK, and KRAS mutation status was available for 81 patients. Local and distant brain control was determined for 79 patients with 469 brain metastases. Modified Cox proportional hazards models were established to evaluate local control for treated lesions after serial gamma knife treatments. In total, 11% of patients developed in-field recurrence. No patients with metastases from tumors with EGFR mutations (0/164 lesions) or EML4-ALK translocations (0/61 lesions) recurred in-field. In contrast, 19% of patients without these mutations and 18% of patients with KRAS mutations recurred in-field (10/139 and 3/105 lesions, respectively). Rates of distant brain recurrence did not significantly differ across tumor genotypes. The predicted median in-field local control was significantly longer for EGFR-mutant and ALK-translocated tumors compared with other patients with NSCLC (P < 0.001), whereas distant brain recurrence time was equivalent (P = 0.97). On multivariate analysis, EGFR mutation, ALK translocation, and metastasis size were independent predictors for superior local control after gamma knife treatment. This study suggests that EGFR kinase domain mutations and EML4-ALK translocations are radiosensitive NSCLC genotypes, and proposes a novel model to identify radiosensitive subtypes of NSCLC.

Brain Metastases in Women With Epithelial Ovarian Cancer: Multimodal Treatment Including Surgery or Gamma-Knife Radiation Is Associated With Prolonged Survival

ObjectiveTo explore the impact of treatment modality on survival in patients with brain metastases from epithelial ovarian cancer. MethodsWe conducted a retrospective review of cases of ovarian cancer with brain metastases treated at institutions in three countries (Canada, China, and India) and conducted a search for studies regarding brain metastases in ovarian cancer reporting survival related to treatment modality. Survival was analyzed according to treatment regimens involving (1) some form of surgical excision or gamma-knife radiation with or without other modalities, (2) other modalities without surgery or gamma-knife radiation, or (3) palliation only. ResultsTwelve patients (mean age 56 years) with detailed treatment/outcome data were included; five were from China, four from Canada, and three from India. Median time from diagnosis of ovarian cancer to brain metastasis was 19 months (range 10 to 37 months), and overall median survival time from diagnosis of ovarian cancer was 38 months (13 to 82 months). Median survival time from diagnosis of brain metastasis was 17 months (1 to 45 months). Among patients who had multimodal treatment including gamma-knife radiotherapy or surgical excision, the median survival time after the identification of brain metastasis was 25.6 months, compared with 6.0 months in patients whose treatment did not include this type of focused localized modality (P = 0.006). Analysis of 20 studies also indicated that use of gamma-knife radiotherapy and excisional surgery in multi-modal treatment resulted in improved median survival interval (25 months vs. 6.0 months, P < 0.001). ConclusionIn the subset of patients with brain metastases from ovarian cancer, prolonged survival may result from use of multidisciplinary therapy, particularly if metastases are amenable to localized treatments such as gamma-knife radiotherapy and surgical excision.

Detection of Meningioma Metastasis to Liver and Lung Using Somatostatin Receptor Scintigraphy

Extracranial meningioma metastasis is rare. We report a case of a 74-year-old Caucasian man with intracranial recurrence of atypical meningioma treated with a combination of surgical resection and gamma knife radiotherapy over a 4-year period. Somatostatin receptor scintigraphy using (111)In pentreotide for surveillance of tumor recurrence showed multiple pulmonary and hepatic metastases.

SU-E-T-571: Comparison of Collapsed Cone Convolution with the Traditional Tissue Maximum Ratio Algorithms for Dose Calculation in a Gamma Knife Radiation Treatment Planning System

Purpose: Advanced treatment delivery techniques in radiosurgery require improved treatment planning system (TPS). The aim of this study was to compare the traditional tissue maximum ratio calculation method (TMR) with recently developed by Elekta collapsed cone convolution (CCC) algorithm for dose calculation in Gamma Plan TPS. Methods: The possibility of this study was a consequence of the untraditional approach to the Gamma Knife treatments at Cleveland Clinic using both MR and CT studies for the absolute majority of the treatments. The basis for the plan data were approximately 1000 clinical cases treated on Perfexion Gamma Knife using TMR classic and complete MR/CT studies. Dose characteristics like D95 (dose received by 95% of target), D50 (dose received by 50% of target), minimum dose, maximum dose, average dose, integral dose, average target density, shortest distance to skull surface, and average axial skull radii were calculated for both algorithms and analyzed. The shot time and configuration were fixated according to the original plan made with TMR Classic. Convolution dose calculations were enabled by retrospectively assigning HU/ED conversion table to the available CT study. The comparison was done for different clinical indications. Results: As expected by the inherent approximation of all tissue to water, the TMR algorithm systematically overestimates the actual physical dose delivered compared with CCC method. It was shown that D95 was basically independent, when error bars considered, from the type of the lesion. The CCC/TMR ratios were in the range of 0.92/0.94. It was shown that there were statistically significant correlations for the most of the analyzed dose characteristics. Conclusion: This work indicates the potential for adjusting dose prescriptions with a mathematical factor which could imply a simple transition to use of more advanced and accurate CCC algorithm for calculation of the dose distributions for the Gamma Knife radiosurgery treatments. Elekta Instrument AB have provided means to calculate the data and have been involved in the data analysis.

The microsurgical management of large pituitary adenoma

Objeetive To investigate the microsurgical treatment results of large pituitary adenoma,and discuss the treatment methods and strategies.Methods A retrospective study was performed amongst 56 cases of pituitary adenomas with a diameter of more than 3 cm by analyzing the clinical and imaging data and adjuvant therapy from June 2006 to June 2012; especially the surgical approaches and micromanipulations.Results In the 56 cases of pituitary adenomas,40 cases underwent adenomas resection via the single nostril transsphenoidal approach while 16 cases performed craniotomy.Total removal was achieved in 27 cases,amongst which 2 cases showed relapses in the two years during follow-up.Subtotal removal was achieved in 25 cases,and partial removal in 4 cases,in which 9 cases showed no growth stably and 7 cases underwent general radiotherapy while 13 cases underwent gamma knife radiotherapy,and all 20 cases showed shrinking or no increase of the adenomas.Conclusions Transsphenoidal microsurgery is the first choice for most large pituitary adenomas.Whether a large or giant pituitary adenoma could be completely removed depends on tumor texture and cavernous sinus invasion.For multidirectional invasive giant pituitary adenomas,staging microsurgery accompanyed with medical therapy or radiotherapy may be the better choice. Key words: Large pituitary adenomas ; Microsurgery; Treatment options

Gamma Knife Irradiation of Injured Sciatic Nerve Induces Histological and Behavioral Improvement in the Rat Neuropathic Pain Model

We examined the effects of gamma knife (GK) irradiation on injured nerves using a rat partial sciatic nerve ligation (PSL) model. GK irradiation was performed at one week after ligation and nerve preparations were made three weeks after ligation. GK irradiation is known to induce immune responses such as glial cell activation in the central nervous system. Thus, we determined the effects of GK irradiation on macrophages using immunoblot and histochemical analyses. Expression of Iba-1 protein, a macrophage marker, was further increased in GK-treated injured nerves as compared with non-irradiated injured nerves. Immunohistochemical study of Iba-1 in GK-irradiated injured sciatic nerves demonstrated Iba-1 positive macrophage accumulation to be enhanced in areas distal to the ligation point. In the same area, myelin debris was also more efficiently removed by GK-irradiation. Myelin debris clearance by macrophages is thought to contribute to a permissive environment for axon growth. In the immunoblot study, GK irradiation significantly increased expressions of βIII-tubulin protein and myelin protein zero, which are markers of axon regeneration and re-myelination, respectively. Toluidine blue staining revealed the re-myelinated fiber diameter to be larger at proximal sites and that the re-myelinated fiber number was increased at distal sites in GK-irradiated injured nerves as compared with non-irradiated injured nerves. These results suggest that GK irradiation of injured nerves facilitates regeneration and re-myelination. In a behavior study, early alleviation of allodynia was observed with GK irradiation in PSL rats. When GK-induced alleviation of allodynia was initially detected, the expression of glial cell line-derived neurotrophic factor (GDNF), a potent analgesic factor, was significantly increased by GK irradiation. These results suggested that GK irradiation alleviates allodynia via increased GDNF. This study provides novel evidence that GK irradiation of injured peripheral nerves may have beneficial effects.

Short‐term Histopathology Effects of Gamma Knife Radiosurgery on a Vestibular Schwannoma

Radiosurgery is a popular management strategy for vestibular schwannoma (VS), with approximately one-third of patients being treated with this modality today. The goal in radiosurgery is to halt tumor growth. Tumor growth control rates range from 70% to 97%.1 The direct effect of radiation on tumor cells is DNA damage, triggering apoptosis. Immediate or delayed cell death may occur, depending on whether the cell is actively dividing. Because of the benign and slow-growing nature of VS, this effect may not account for the cumulative effect of radiation. Radiation also induces vascular damage, leading to ischemia and cell death. In a series of 5 patients who had microsurgical resection after stereotactic radiation, immunohistochemistry using antibodies directed against the vascular endothelial markers, factor VIII and CD34, demonstrated decreased staining with increasing isodoses and no staining at the tumor center.1 Damage to the vascular endothelial cells occurs 2 to 4 months after radiation. Here, we show results of a histological/immunohistochemical investigation of a VS tumor 5 months following treatment with radiosurgery. While prior studies have shown long-term radiation effects, this case represents a unique view into the short-term biological effects of schwannoma gamma knife irradiation, which may provide clues to radiation failure, tumor regrowth, and potential strategies for tumor control.

Influence of single-fraction Gamma-Knife radiosurgery on ocular surface and tear function in choroidal melanoma patients

AimTo evaluate ocular surface and tear function in patients with choroidal melanoma treated with single-fraction radiosurgery.Methods36 patients (median age 62 years; range 26–84 years) were enrolled between 2001 and 2006...

The Maximum Tolerated Dose of Gamma Radiation to the Optic Nerve during Gamma Knife Radiosurgery in an Animal Study

Background: The safety of gamma knife radiosurgery should be considered when treating pituitary adenomas. Objectives: To determine the maximum tolerated dose of radiation delivered by gamma knife radiosurgery to optic nerves. Methods: An animal model designed to establish prolonged balloon compression of the optic chiasm and parasellar region was developed to mimic the optic nerve compression caused by pituitary adenomas. Twenty cats underwent surgery to place a balloon for compression effect and 20 cats in a sham operation group received microsurgery without any treatment. The effects of gamma knife irradiation at 10–13 Gy on normal (sham operation group) and compressed (optic nerve compression group) optic nerves were investigated by pattern visual evoked potential examination and histopathology. Results: Gamma knife radiosurgery at 10 Gy had almost no effect. At 11 Gy, P100 latency was significantly prolonged and P100 amplitude was significantly decreased in compressed optic nerves, but there was little change in the normal optic nerves. Doses of 11 Gy and higher induced significant electrophysiological variations and degeneration of the myelin sheath and axons in both normal and compressed optic nerves. Conclusions: Compressed optic nerves are more sensitive to gamma knife radiosurgery than normal optic nerves. The minimum dose of gamma knife radiosurgery that causes radiation injury in normal optic nerves is 12 Gy; however, the minimum dose is 11 Gy in compressed optic nerves.

Peripheral doses in children undergoing Gamma Knife radiosurgery and second cancer risk

Abstract Gamma Knife radiosurgery stereotactically delivers a high single dose of external radiation to a small well-defined intracranial lesions. Due to a large amount of dose delivered in a single fraction (10–30 Gy), dose outside the treatment volume is an important issue. The aim of the study was to measure the out-of-field doses during the Leksell Gamma Knife Model C radiosurgery for children. The children population was chosen due to their higher susceptibility to radiation. Also, due to smaller size of their bodies, the larger doses are expected to all out-of-field tissues and organs than for adults for the same irradiation conditions. The purpose was to identify doses delivered to the eye lens, thyroid glands, breasts, sternum, upper abdomen and gonads from the doses measured with dosimeters placed on the some positions on the surface of the patients. There were 5 patients between 4 and 14 years old. The relation of the organ doses and doses on the surface was determined by measurements using the anthropomorphic phantom (CIRS, ten-year old child). For dosimetry measurements two types of thermoluminescent dosimeters were used, LiF:Mg,Ti and LiF:Mg,Cu,P and radiophotoluminescent glass dosimeters type GD-352M. The agreement between three types of dosimeters was on average within 4%. Doses on the patients have shown large dissipation for the same positions above specified organs. This is due to different influential parameters (position and volume of the target, height and weight of patient, irradiation dose). For example, doses to the eyes and gonads varied from 0.7% to 2.55% and from 0.05% to 0.22% of the mean target dose, respectively. Results of organ dose measurements in the phantom and on the surface of the phantom show differences between 5 and 25% for different organs. Lifetime attributable risks of cancer incidence associated with a chosen Gamma Knife radiation treatment were calculated for selected radiosensitive organs.

Treatment of brain glioblastoma multiforme with pcDNA3.1-Egr. 1p-p16 combined with gamma knife radiation: An experimental study on nude mice

High post-operative recurrence and poor prognosis are likely to be related to the infiltrative growth of the glioblastoma multiforme (GBM). The primary objective of this study is to investigate the possible synergistic effect of the combined treatment of gamma knife radio-surgery (GKRS) and gene therapy for GBM and secondary objective is to explore the role of GKRS for the temporal and spatial regulation of the gene expression. The study performed on 70 nude mice and randomly divided into seven groups. Subcutaneous injection of human GBM tumor cells (T98G) was carried out to establish the animal models. Various doses of liposome-mediated pcDNA3.1-Egr. 1p-p16 recombinant plasmid were transfected through intra-tumor injection. GKRS was scheduled following the plasmid transfection. Tumor volumes were measured every 4 days after the treatment. Subcutaneous tumor nodule specimens were collected to analyze the cell apoptosis and p16 gene expression using terminal-deoxynucleoitidyl transferase mediated nick end labeling staining and reverse transcription-polymerase chain reaction. Tumor volumes, levels of cell apoptosis and p16 gene expression were compared between groups. Rates of tumor growth were significantly lower in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS groups than that in the remaining groups 28 days following the GKRS management. The p16mRNA expression was noted in both of the pcDNA3.1-Egr. 1p-p16 plasmid group and the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with marginal-dose of 20 Gy group. The level of messenger ribonucleic acid expression was higher in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with the marginal-dose of 20 Gy group, with a markedly increased apoptotic and necrotic cells, than that in the pcDNA3.1-Egr. 1p-p16 plasmid group. In animal studies, pcDNA3.1-Egr. 1p-p16 in combination with GKRS is a preferable management option for the GBM to the sole use of GKRS or gene therapy. It may be a novel approach for the treatment of human patient with GBM.

Aggressive and malignant prolactin pituitary tumors: pathological diagnosis and patient management

According to the World Health Organization classification of pituitary tumors, only tumors with systemic metastasis must be considered as carcinomas. Invasive tumors with multiple recurrences are only classified as aggressive tumors or "atypical adenomas". To illustrate the problems encountered in the pathological diagnosis of pituitary carcinoma and in patient management, we present two male patients operated on for an aggressive prolactin pituitary adenoma with and without metastasis. In case 1, 5 surgeries, 3 irradiations, increased doses of dopamine agonists, and trials of temozolomide and carboplatine-VP16 failed to control tumor progression and the appearance of metastases which lead to death 16 years after onset. In case 2, based on the initial diagnosis of an aggressive-invasive adenoma that was resistant to dopamine agonists, gamma-Knife irradiation was initially performed on the intra-cavernous remnant. Eight years after onset, the remnant remained stabilized and the plasma PRL normalized under dopamine agonist. From these 2 cases alongside other cases found in the literature, we propose that the association of certain clinical signs (male sex, dopamine-resistant hyperprolactinemia), radiological signs (invasive macro or giant tumor on MRI) and histological signs (angiogenesis, Ki-67 > 3%, p53 positive, mitoses >2 per high power field, vascular invasion, up-regulation of genes related to invasion and proliferation, and allelic loss of chromosome 11) might suggest aggressiveness and be suspicious of malignancy before the appearance of metastasis. The early detection of an aggressive phenotype of a prolactin pituitary tumor should permit the earlier establishment of the optimum therapeutic strategy associating surgery and radiotherapy to delay or inhibit metastasis.

Visual acuity after Gamma-Knife radiosurgery of choroidal melanomas

Background/aimsTo report on conservation of visual acuity after Gamma-Knife radiosurgery of choroidal melanoma.MethodsA total of 189 patients with choroidal melanoma were treated with Gamma-Knife stereotactic single-fraction radiosurgery at a single...

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

Regression curves of brain metastases after gamma knife irradiation: Difference by tumor and patient characteristics

Regression curves and local control rates of brain metastases after gamma knife treatment were evaluated to investigate differences in tumor response to radiation. A total of 203 metastases were serially evaluated using contrast-enhanced MRI (or computed tomography) at 1, 2, 3, 4.5 and 6months after a 20-Gy dose. Differences were evaluated in regression curves and control rates between tumors ≥10mm and tumors <10mm in mean diameter, among three major histological subtypes of lung cancer, among adenocarcinomas of the lung, breast and colorectum, and between tumors in patients with above and below median hemoglobin levels. Smaller tumors shrank faster and yielded better control rates than larger tumors. Metastases from small cell and squamous cell carcinomas of the lung shrank faster than those from lung adenocarcinoma, but 6-month control rates were not different. Breast adenocarcinomas tended to shrink faster than lung adenocarcinomas, but the control rates were not different among adenocarcinomas of the lung, breast and colorectum. Tumors in patients with higher hemoglobin levels tended to shrink faster but the control rates were not different. Small cell and squamous cell carcinomas of the lung regress more rapidly than adenocarcinomas, although local control rates might not differ significantly.

Effects of titanium mesh implant on dosimetry during Gamma Knife radiosurgery.

Calvarial reconstruction following resection of tumors involving the skull is often followed by stereotactic radiosurgery. Prior studies have addressed the effects of various cranioplasty materials on dose distributions in linac‐based radiosurgery. We aim to determine the effects of titanium mesh implants on Gamma Knife dose. Radiation backscatter and transmission were measured for eight types of titanium mesh using film, ion chamber, and Theratron Co‐60 teletherapy device. A single mesh was selected for Gamma Knife irradiation using a CaSO4 skull filled with ballistics gel. Dose profiles for reconstructed and intact skulls were compared with the planning system prediction at 2.5 and 5.5 cm depth. Titanium contact backscatter and transmission dose perturbations ranged from ‐18% to 23%. Radiation dose measured at 1.5 cm below the calvarial implant increased by 0.5% to 3.3% relative to bone. Measured Gamma Knife dose profile diameters agreed with expected profiles. Maximum dose within the intact phantom was 3% less than planned due to skull attenuation. Maximum dose within the reconstructed phantom was between the intact phantom and planned doses. Titanium mesh implants and hydroxyapatite cranioplasty result in minimal alteration (<3%) in the delivered Gamma Knife dose.PACS number: 87.00

Endovascular treatment of aneurysms arising from basilar artery trunk and branches

Objective To study the therapeutic characteristics and experience about the endovascular treatment of basilar artery (BA) trunk and branch aneurysms.Methods Subjects included 14 patients with BA trunk and branch aneurysms,including 7 patients with associated other diseases.12 berry aneurysms were given endovascular coil embolization,together with stent or balloon assistance when necessary,meanwhile 2 dissecting and fusiform aneurysms were given parent artery occlusion.Associated diseases were managed intraoperatively,or in the second stage,or treated with gamma knife radiotherapy,or followed up.Results The follow-up period was from 1 to 2 years.Two patients with unsuccessful embolization died of re-rupture at the follow-up.The remaining 12 patients reported good outcomes and experienced no re-rupture of both the aneurysm or associated disease.Angiographic follow-ups were conducted for the 12 patients.Digital subtraction angiography ( DSA ) examination at the last follow-up showed no recurrence of the BA trunk and branch aneurysms.Conclusions BA trunk and branch aneurysms should be actively managed via endovascular techniques to prevent serious consequences due to aneurysm rupture and bleeding.Favorable outcomes can be obtained by the proper selection of endovascular treatment regimens. Key words: Basilar artery trunk; Aneurysm; Branch; Endovaseular treatment

Abstract 1456: Sulfasalazine sensitizes glioblastoma cells to radiation treatment

Abstract Glioblastoma (GBM) is a lethal cancer with a limited response to ionizing radiation. Recent studies suggest that Sulfasalazine (SAS), a drug used to treat inflammatory bowel disease, inhibits the Xc- antiporter system in glioma cells, thereby blocking their uptake of cystein. Since the availability of cystein is a rate limiting step in intracellular antioxidant production, we wanted to investigate whether sulfasalazine sensitizes glioma cells to radiation. Expression of xCT, the catalytic subunit of system Xc-, was found in 30 patient GBM biopsies. SAS effect on glioma cell growth was investigated using an electric cell substrate impedance sensing (ECIS) instrument. All glioma cell lines showed altered growth curves in response to SAS treatment. To assess the effect of blocking the antiporter, intracellular levels of the antioxidant glutathione were measured. With increasing doses of SAS, glutathione levels decreased in a dose response manner. In addition, cysteine was added to the medium to see if the cells could survive high doses of SAS. U251 glioma cells were treated with escalating doses of SAS, alone or in combination with radiation (8 Gy). Nuclear integrity was evaluated to estimate cell death following treatment, as well as the presence of double stranded breaks. In addition, cell death and viability were investigated using live/dead staining and the MTS assay. All treatment groups exhibited increased rates of cell death compared to untreated controls. A combination of SAS and radiation resulted in higher levels of cell death, than radiation or SAS administered alone. In order to assess whether this can be exploited therapeutically, we are preparing to treat nude rats harbouring glioblastoma biopsy xenografts with SAS, alone or in combination with gamma knife radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1456. doi:1538-7445.AM2012-1456