Yong-Seok Im

Gamma knife surgery for brain metastases in patients harboring four or more lesions: survival and prognostic factors.

OBJECT This study was performed to evaluate the role of gamma knife surgery (GKS) in patients with a large number (four or more) of metastatic brain lesions. METHODS The authors retrospectively reviewed the outcome in 130 patients who underwent GKS for metastatic lesions. Eighty-four patients presented with one to three lesions (Group A) and 46 presented with four or more lesions (Group B). The overall median survival time after GKS was 35 weeks. The median survival time in Group A (48 weeks) was significantly longer (p = 0.005) than the survival time in Group B (26 weeks). The recursive partitioning analysis (RPA) class was the only significant prognostic factor identified in multivariate analysis. The median survival for patients in RPA Classes I, II, and III was 72, 48, and 19 weeks, respectively, in Group A and 36 and 13 weeks for Classes II and III in Group B. The number of lesions, tumor volume, whole brain radiotherapy, primary tumor site, age, and sex did not affect survival significantly. CONCLUSIONS It is suggested that GKS provides an increase in survival time even in patients with a large number (four or more) of metastatic lesions. Concerning the selection of patients for GKS, RPA class should be considered as the most important factor and multiplicity of the lesions alone should not be a reason for withholding GKS.

Gamma Knife Radiosurgery for Ten or More Brain Metastases

OBJECTIVE This study was performed to assess the efficacy of GKS in patients with ten or more brain metastases. METHODS From Aug 2002 to Dec 2007, twenty-six patients (13 men and 13 women) with ten or more cerebral metastatic lesions underwent GKS. The mean age was 55 years (32-80). All patients had Karnofsky performance status (KPS) score of 70 or better. According to recursive partitioning analysis (RPA) classification, 3 patients belonged to class I and 23 to class II. The location of primary tumor was lung (21), breast (3) and unknown (2). The mean number of the lesions per patient was 16.6 (10-37). The mean cumulated volume was 10.9 cc (1.0-42.2). The median marginal dose was 15 Gy (9-23). Overall survival and the prognostic factors for the survival were retrospectively analyzed by using Kaplan Meier method and univariate analysis. RESULTS Overall median survival from GKS was 34 weeks (8-199). Local control was possible for 79.5% of the lesions and control of all the lesions was possible in at least 14 patients (53.8%) until 6 months after GKS. New lesions appeared in 7 (26.9%) patients during the same period. At the last follow-up, 18 patients died; 6 (33.3%) from systemic causes, 10 (55.6%) from neurological causes, and 2 (11.1%) from unknown causes. Synchronous onset in non-small cell lung cancer (p=0.007), high KPS score (>/=80, p=0.029), and controlled primary disease (p=0.020) were favorable prognostic factors in univariate analysis. CONCLUSION In carefully selected patients, GKS may be a treatment option for ten or more brain metastases.

Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

Preliminary report of multisession gamma knife radiosurgery for benign perioptic lesions: visual outcome in 22 patients.

OBJECTIVE Radiosurgery may be contraindicated for lesions adjacent to the optic pathways because of the substantial risk of visual complication. Multisession radiosurgery has been tried as a compromise between single session radiosurgery and fractionated radiotherapy. The purpose of this study is to evaluate the outcomes of multisession gamma knife radiosurgery (GKRS) in 22 patients with perioptic lesions of benign pathology. METHODS In all 22 cases, the lesions were within 1 mm of the optic apparatus and were therefore not considered suitable for single session radiosurgery. Radiation was delivered in 3 to 4 fractions with a median cumulated marginal dose of 20 Gy (range, 15-20 Gy). RESULTS During a mean follow-up of 29 months (range, 14-44 months), tumor control was achieved in 21 patients. Visual function improved in 7 patients, remained unchanged in 14 patients, and deteriorated in 1 patient with tumor progression. No other complication was observed. CONCLUSION This preliminary result supports the idea that multisession GKRS may be an effective and safe alternative for treatment in perioptic lesions that are unsuitable for single session radiosurgery.

Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

PURPOSE The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. METHODS AND MATERIALS Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables were performed using the Cox proportional hazards model. RESULTS Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. CONCLUSIONS These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.

Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute

Background This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions. Methods Thirty-eight patients with perioptic tumors were treated at our institute from May 2004 to December 2008. All patients had a lesion in close contact with the optic apparatus. Twenty-four of these patients had undergone surgical resection before fractionated GKRS. Radiation was delivered in four sessions with 12 hours intervals between sessions. The mean target volume was 3,851 mm3 and the median cumulative marginal dose was 20 Gy. The median follow-up was 38.2 months. Visual acuity and visual fields were analyzed according to visual impairment score using the German Ophthalmological Society guidelines. Results Tumor control was achieved in 35 (94.6%) of the 37 patients with available follow-up images. Progressive tumor growth was observed in two craniopharyngioma patients (5.4%). Favorable visual outcomes in the postoperative period were achieved in 94.7% of cases (36/38). Sixteen patients showed visual function after fractionated GKRS, twenty cases were stationary, and two patients showed visual function deterioration after GKRS. Conclusion GKRS is a safe and effective alternative to either surgery or fractionated radiotherapy for selected benign lesions that are adjacent to the optic apparatus.

Stereotactic Device for Gamma Knife Radiosurgery in Experimental Animals: Technical Note

Objective: Radiosurgery has become a well-established treatment modality for many intracranial lesions and the information obtained from animal experiments is crucial in devising new strategies with improved efficacy and less risk. We constructed a stereotactic device for rats which can be used for both usual laboratory work and radiosurgery using a Gamma Knife. Materials and Methods: The stereotactic device was made by modifying the basic design of the ordinary stereotactic frames used for usual laboratory work. It was developed for both Gamma Knife model B and C. An auxiliary tool was also devised which facilitates the placement of the target point at the radiation isocenter. Results: The reliability of the device was verified by checking the radiation profile and absorbed dose. The results of the experimental irradiation in normal and tumor-cell-inoculated rats demonstrated the usefulness of the device. Conclusions: The modified animal stereotactic frame described herein can be used for both the production of experimental animal models and for performing radiosurgery with a common apparatus.

Multisession Gamma Knife Radiosurgery for Orbital Apex Tumors

OBJECTIVE This study was performed to analyze the outcome of multisession gamma knife radiosurgery (GKS) in benign tumors located at the orbital apex. METHODS Medical records of 23 patients who underwent multisession GKS for benign orbital apex tumors were reviewed retrospectively. Three patients were diagnosed by histology, and the other 20 patients were given the diagnoses on the basis of clinical and radiological findings. Diagnoses included cavernous hemangioma (8 cases), meningioma (8 cases), and schwannoma (7 cases). All patients were treated with 4 sessions of GKS with 12 hours of interval. Median marginal dose in each session was 5 Gy (range, 4.5-5.5 Gy) at the 50% isodose line (range, 50%-55%). RESULTS Mean clinical and imaging follow-up duration after treatment were 52.1 and 34.2 months, respectively. Tumor control was achieved in 22 patients (95.7%). Significant tumor shrinkage was observed in 17 patients (73.9%), and mean tumor volume reduction rate was 53.9%. Visual function was improved in 16 patients (69.6%) and stable in 4 patients (17.4%). Deterioration of visual acuity was reported by 3 patients (13.0%). Clinical and radiological response to multisession GKS was most excellent in cavernous hemangiomas with tumor control in all patients, and the mean tumor volume reduction rate was 68.3%. CONCLUSIONS Multisession GKS proved to be an effective and safe management strategy for benign orbital apex tumors. Response to treatment was different according to the pathology, and multisession GKS may be considered as the initial treatment of choice for specific pathology such as cavernous hemangioma.

Effectiveness of Postoperative Gamma Knife Radiosurgery to the Tumor Bed After Resection of Brain Metastases

OBJECTIVE The role of Gamma knife radiosurgery (GKS) after the resection of brain metastases remains undefined. We evaluated the outcomes of postoperative GKS to the tumor bed after the resection of brain metastasis compared with GKS alone without resection in the same patients. METHODS We performed a retrospective review of 24 patients who underwent GKS to the tumor bed after the resection of brain metastases. In this cohort, 25 metastatic lesions were treated with postoperative GKS, and 37 brain metastatic lesions were simultaneously managed with GKS alone without resection. RESULTS The median target volume and marginal dose of GKS to the surgical bed were 10.5 cm(3) and 15.0 Gy, respectively. The median target volume and marginal dose of GKS alone for the metastatic lesions were 0.5 cm(3) and 21.0 Gy, respectively. The actuarial 1-year and 2-year overall survival of the patients were 43.1% and 28.7%, respectively. The median overall survival of all patients was 11 months. The actuarial 6-month and 12-month local progression-free survival of GKS alone for metastatic lesions without resection were 92.6% and 84.9%; however, the actuarial 6-month and 12-month local progression-free survival of GKS to the surgical bed were 82% and 71%, respectively. CONCLUSIONS For patients with brain metastases treated with surgical resection, postoperative GKS to the resection area is an effective and safe treatment option. Particularly, concurrent postoperative GKS to the surgical cavity with GKS alone for multiple small metastatic lesions is a feasible treatment strategy for multiple brain metastases.