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Cyberknife    has been found to be very useful in treating brain tumors because of the high degree of accuracy and since it can be done frameless (a head frame which is screwed into the skull, as is used for other techniques like gamma knife) the treatments can be fractionated (dose divided into more than one dose or fraction) which should lower the risk of complications.

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CyberKnife stereotactic radiotherapy for patients with malignant glioma.
Yoshikawa K, Saito K, Kajiwara K, Nomura S, Ishihara H, Suzuki M.  Minim Invasive Neurosurg. 2006 Apr;49(2):110-5.

Department of Neurosurgery, Yamaguchi University School of Medicine, Yamaguchi, Japan.

OBJECTIVE: The CyberKnife is a new frameless image-guided radiosurgical modality. The authors report on their experience using the CyberKnife in 25 patients with malignant gliomas. METHODS: Twenty-five patients with histologically proven malignant gliomas (18 glioblastoma: GB, 7 anaplastic astrocytoma: AA) were treated with the CyberKnife at Konan St. Hill Hospital between June 1998 and November 2002. CyberKnife therapy was performed on 44 lesions (31 GB lesions, 13 AA lesions) in the 25 patients. The median target volume was 19.1 mL (range: 0.3 - 90.2). The median prescribed dose was 20.3 Gy (range: 13.9 - 26.4). Patient-, tumor-, and treatment-related variables were analyzed by univariate analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS: In the 18 GB patients, the median survival after diagnosis was 20.7 months (82.6 weeks) with a mean follow-up of 85.7 weeks. Of the 7 AA patients, 6 were alive at the time of analysis with follow-up periods ranging from 11.4 to 52.8 months. Patients younger than 70 years had a median survival after diagnosis of 37.1 months, compared to 12.4 months for older patients (p = 0.003). Similarly, patients with well-controlled lesions had a median survival after diagnosis of 39.8 months compared to 16.0 months for those with uncontrolled lesions (p = 0.031). Late delayed radiation necrosis was seen in 1 GB patient. No other patient suffered acute or delayed neurological morbidity after CyberKnife therapy. CONCLUSION: This is the first report of CyberKnife stereotactic radiotherapy applied to the treatment of malignant gliomas. The frameless and painless CyberKnife stereotactic radiotherapy has the potential to be as useful for treatment of malignant glioma as other radiosurgical modalities.

Radiation necrosis and brain edema association with CyberKnife treatment.

Sato K, Baba Y, Inoue M, Omori R.   Acta Neurochir Suppl. 2003;86:513-7.

Department of Neurosurgery, Okayama Kyokuto Hospital, Okayama, Japan. kengosato@kyokuto.or.jp

The CyberKnife (CK) is a frameless and image guided robotic controlled instrument for stereotactic irradiation. The authors studied CK treatment of glioma and glioblastoma, and analyzed frequency and risk factors of radiation necrosis. Of 61 patients with glioma and glioblastoma treated with CyberKnife, four patients showed symptomatic radiation necrosis. All of these patients were treated with stereotactic radiotherapy, varying from 3 to 6 fractions without previous radiation therapy. Two patients required necrotomy through craniotomy. Two patients were treated conservatively. Our four patients with radiation necrosis were not specific in terms of tumor volume and dose delivery. Glioma cells invade the normal brain tissue and over-radiation to this intermingling area is one of the risk factors for injury to normal endothelial cells. The homogeneity of the maximum dose area is an important factor to reduce over radiation to the normal brain parenchyma. The dose volume effect has been discussed in terms of risk factor; however, the number of fractions and dose per fraction should be considered to avoid radiation necrosis. We consider that conformal treatment with inverse algorism, fractionated stereotactic radiotherapy and precise anatomic targeting reduce the risk of radiation necrosis.

Preliminary report of a phase I study of combined fractionated stereotactic radiosurgery and conventional external beam radiation therapy for unfavorable gliomas.

Regine WF, Patchell RA, Strottmann JM, Meigooni A, Sanders M, Young AB.  Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):421-6.

Department of Radiation Medicine, University of Kentucky, Lexington, KY 40536-0293, USA. wilregi@pop.uky.edu

To determine the tolerance and toxicities of fractionated stereotactic radiosurgery (FSRS) given in combination with conventional external beam radiation therapy (CEBRT).  From March 1995 to September 1998, 14 patients with previously unirradiated and unfavorable glioma (malignant glioma, n = 8; unfavorable low-grade glioma, n = 5; and recurrent glioma, n = 1) were stratified into 3 groups according to tumor volume (TV) to determine the initial FSRS dose schedule: Group A (n = 3): TV </= 5 cc (7 Gy x 2 pre- and post-CEBRT]; Group B (n = 6): 5 cc < TV </= 15 cc [7 Gy x 2 pre- and 7 Gy x 1 post-CEBRT]; and Group C (n = 5): 15 cc < TV </= 30 cc (7 Gy x 1 pre- and post-CEBRT). All patients received CEBRT to 59.4 Gy at 1.8 Gy/fraction. Dose escalation was planned, if toxicity was acceptable. RESULTS: All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity has been limited to patients in groups B (grade 4, n = 2/6) and C (grade 4, n = 2/5). Eight patients required reoperation, with 3 (38%) having necrosis without evidence of tumor. Eleven patients (79%) have had objective partial (>/=50% reduction, n = 2) or minor (>20% reduction, n = 9) imaging response. Follow-up ranged from 9 to 51 months (median 15 months), with 7 patients alive at 22-51 months. CONCLUSIONS: Imaging response and the ability of these patients with unfavorable intracranial gliomas to complete therapy without interruption or experiencing disease progression is very encouraging. Excessive toxicity of combined FSRS and CEBRT as evaluated thus far in this study was seen for patients with group B/C lesions. Evaluation of this novel treatment strategy with dose modification is ongoing.

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma.

Hudes RS, Corn BW, Werner-Wasik M, Andrews D, Rosenstock J, Thoron L, Downes B, Curran WJ Jr.  Int J Radiat Oncol Biol Phys. 1999 Jan 15;43(2):293-8.

Department of Radiation Oncology, Wills Eye Hospital, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.

A phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy. From November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging. RESULTS: No grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fisher's exact test, response of any kind correlated strongly to total dose (p = 0.0056). None of six lesions treated with 21 Gy or 24 Gy responded, whereas there was a 79% response rate among the 19 lesions treated with 30 or 35 Gy. Tumor volumes < or =20 cc were associated with a higher likelihood of response (p = 0.053). CONCLUSIONS: H-SRT used in this cohort of previously irradiated patients with malignant glioma was not associated with the need for reoperation due to toxicity or grade 3 toxicity. This low toxicity profile and encouraging H-SRT dose-related response outcome justifies further evaluation and dose escalation.