Fractionated stereotactic radiosurgery for malignant gliomas: comparison with single session stereotactic radiosurgery

Journal of Neuro-Oncology - Stereotactic radiosurgery (SRS) is feasible for malignant glioma; however, delivering the optimal radiation dose with sufficient large-volume coverage is a major...     

CyberKnife stereotactic ablative radiotherapy for lung tumors

Stereotactic ablative radiotherapy (SABR) has emerged as a promising treatment for early stage non-small cell lung cancer, particularly for patients unable to tolerate surgical resection. High rates of local tumor control have been demonstrated with acceptable toxicity and the practical advantage of a short course of treatment. The CyberKnife image-guided robotic radiosurgery system has unique technical characteristics that make it well suited for SABR of tumors that move with breathing, including lung tumors. We review the qualities of the CyberKnife platform for lung tumor SABR, and provide a summary of clinical data using this system specifically.     

Gamma Knife stereotactic radiosurgery for intracranial hemangiopericytomas

The purpose of this study is to determine the efficacy of Gamma Knife stereotactic radiosurgery (GK SRS) for intracranial hemangiopericytomas, and to investigate the optimal dose for successful tumor control without adverse effects. We evaluated 17 hemangiopericytomas of nine patients treated with GK SRS between 1999 and 2008. The mean tumor volume was 2.2 cm³ (range 0.2–9.9 cm³), and the mean and median marginal doses were 18.1 and 20 Gy (range 11–22 Gy), respectively, at the 50% isodose line. Mean clinical and radiological follow-up periods were 49 and 34 months, respectively. Successful tumor control was achieved in 14 of 17 lesions (82.4%) at time of last follow-up after GK SRS. Actuarial local tumor control rates at 1, 2, and 5 years after GK SRS were 100%, 84.6%, and 67.7%, respectively. No adverse effects, such as radiation necrosis or marked peritumoral edema, were observed in any patient. Marginal dose (≥17 Gy) was the only statistically significant factor for local tumor control on univariate analysis. Extended analysis using lesion data available from previous studies revealed that higher marginal dose (≥17 Gy) was also significant (P = 0.028). GK SRS provides an effective and safe adjuvant management option for patients with recurrent or residual hemangiopericytomas. Our results suggest that doses higher than previously used (around 15 Gy) are desirable to achieve better local tumor control of hemangiopericytomas. Close radiological follow-up is also necessary for early detection of small recurrent lesions.     

Stereotactic radiosurgery for hypervascular intracranial tumors

Purpose

MicroRNAs (miRNAs) have been shown to be involved in the initiation and progression of glioma. However, the underlying molecular mechanisms are still unclear.

Methods

We performed microarray analysis to evaluate miRNA expression levels in 158 glioma tissue samples, and examined miR-1231 levels in glioma samples and healthy brain tissues using qRT-PCR. In vitro analyses were performed using miR-1231 mimics, inhibitors, and siRNA targeting EGFR. We used flow cytometry, CCK-8 assays, and colony formation assays to examine glioma proliferation and cell cycle analysis. A dual luciferase reporter assay was performed to examine miR-1231 regulation of EGFR, and the effect of upregulated miR-1231 was investigated in a subcutaneous GBM model.

Results

We found that miR-1231 expression was decreased in human glioma tissues and negatively correlated with EGFR levels. Moreover, the downregulation of miR-1231 negatively correlated with the clinical stage of human glioma patients. miR-1231 overexpression dramatically downregulated glioma cell proliferation, and suppressed tumor growth in a nude mouse model. Bioinformatics prediction and a luciferase assay confirmed EGFR as a direct target of miR-1231. EGFR overexpression abrogated the suppressive effect of miR-1231 on the PI3K/AKT pathway and G1 arrest.

Conclusions

Taken together, these results demonstrated that EGFR is a direct target of miR-1231. Our findings suggest that the miR-1231/EGFR axis may be a helpful future diagnostic target for malignant glioma.

     

Radiological response and histological changes in malignant astrocytic tumors after stereotactic radiosurgery

Stereotactic radiosurgery is an encouraging approach to deliver higher doses of radiation boost for malignant gliomas safely and precisely. The purpose of this study was to investigate the radiation response and histological changes of malignant astrocytic tumors after stereotactic linac radiosurgery (SLRS). We studied an autopsy case of recurrent glioblastoma multiforme (GBM) and two surgical cases with gross total removal of recurrent GBM and anaplastic astrocytoma transformed from fibrillary astrocytoma treated with SLRS. Destructive changes, such as the disappearance of viable cells, coagulation necrosis, and fibrinoid degeneration of vascular walls, were observed in the center of the target of SLRS, which showed histologically similar radiobiological reactions to well-known delayed central nervous system radiation necrosis caused by conventional radiotherapy. The region showing such radiation necrosis was within the area irradiated with approximately 15–20Gy or more by SLRS; however, dense viable tumor cells remained in the periphery that was irradiated with less than 15 Gy. In a comparative immunohistochemical study of the tumors before and after SLRS, neither MIB-1 and p53 labeling indices nor immunoreactivity for GFAP represented any persistent tendencies. There were very few TUNEL-positive cells in either tumor before and after SLRS. These results showed that radiosurgery for malignant gliomas leads to earlier radiation necrosis than conventional radiation and that it is useful in eradicating tumor cells in the center of the target. However, some viable tumor cells may remain in the periphery irradiated with an insufficient dose for cell death and may be partly transformed in character by DNA damage due to radiation. Proton magnetic resonance spectroscopy (MRS) was suggested to characterize the radiation response in radiosurgery tumor targets for correlation with histological findings.     

The accuracy of frameless stereotactic intracranial radiosurgery

Purpose

To determine the accuracy of frameless stereotactic radiosurgery using the BrainLAB ExacTrac system and robotic couch by measuring the individual contributions such as the accuracy of the imaging and couch correction system, the linkage between this system and the linac isocenter and the possible intrafraction motion of the patient in the frameless mask.

Materials and methods

An Alderson head phantom with hidden marker was randomly positioned 31 times. Automated 6D couch shifts were performed according to ExacTrac and the deviation with respect to the linac isocenter was measured using the hidden marker. ExacTrac-based set-up was performed for 46 patients undergoing hypofractionated stereotactic radiotherapy for 135 fractions, followed by verification X-rays. Forty-three of these patients received post-treatment X-ray verification for 79 fractions to determine the intrafraction motion.

Results

The hidden target test revealed a systematic error of 1.5 mm in one direction, which was corrected after replacement of the system calibration phantom. The accuracy of the ExacTrac positioning is approximately 0.3 mm in each direction, 1 standard deviation. The intrafraction motion was 0.35 ± 0.21 mm, maximum 1.15 mm.

Conclusion

Intrafraction motion in the BrainLAB frameless mask is very small. Users are strongly advised to perform an independent verification of the ExacTrac isocenter in order to avoid systematic deviations.     

Megavoltage CT-assisted stereotactic radiosurgery for thoracic tumors: original research in the treatment of thoracic neoplasms

PURPOSE: The aim of the study was to evaluate the efficacy of stereotactic radiosurgery (SRS) for thoracic tumors with megavoltage computed tomography (MVCT) from the point of view of symptom palliation as well as local control. METHODS AND MATERIALS: MVCT-assisted positioning verification and real-time monitoring for a multileaf collimator (MLC) were used to enhance the accuracy of the thoracic SRS. Twenty-two thoracic tumors in 15 patients underwent the present treatment. All but 1 tumor were metastases from various primary malignancies. Eleven patients were symptomatic. The treatment site was the chest wall/pleura in 10 tumors, and the lung in 12 tumors. The median volume of the clinical target was 4.5 cc and the median peripheral dose was 20 Gy, for the lung tumors. For the chest wall/pleura tumors, the median volume of the clinical target was 40 cc and the median peripheral dose was 20 Gy. Conventional fractionated conformal radiation therapy (CRT) followed SRS in 10 tumors. RESULTS: Of 21 tumors eligible for evaluation, there were 13 with complete responses, 6 with partial responses, and 2 without response. Duration of local control ranged from 0.6 to 82 months with a median of 8 months, with only one local recurrence seen. Immediate palliation was obtained in most symptomatic patients. Interstitial changes in the lung were limited. Autopsy performed for a patient revealed remarkable histologic effects with minimal injuries to the lung. CONCLUSION: The geometric accuracy of MVCT-assisted SRS appeared to enhance the clinical efficacy and safety of treatment to thoracic malignancies.     

Stereotactic irradiation for intracranial arteriovenous malformation using stereotactic radiosurgery or hypofractionated stereotactic radiotherapy

PURPOSE: To investigate the appropriateness of the treatment policy of stereotactic irradiation using both hypofractionated stereotactic radiotherapy (HSRT) and stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) located in an eloquent region or for large AVMs and using SRS alone for the other AVMs. METHODS AND MATERIALS: Included in this study were 75 AVMs in 72 patients, with a mean follow-up of 52 months. Of the 75 AVMs, 33 were located in eloquent regions or were >2.5 cm in maximal diameter and were given 25-35 Gy (mean, 32.4 Gy) in four daily fractions at a single isocenter if the patient agreed to prolonged wearing of the stereotactic frame for 5 days. The other 42 AVMs were treated with SRS at a dose of 15-25 Gy (mean, 24.1 Gy) at the isocenter. The 75 AVMs were classified according to the Spetzler-Martin grading system; 21, 23, 28, 2, and 1 AVM were Grade I, II, III, IV, V, and VI, respectively. RESULTS: The overall actuarial rate of obliteration was 43% (95% confidence interval [CI], 30-56%) at 3 years, 72% (95% CI, 58-86%) at 5 years, and 78% (95% CI, 63-93%) at 6 years. The actuarial obliteration rate at 5 years was 79% for the 42 AVMs <2.0 cm and 66% for the 33 AVMs >2 cm. The 5- and 6-year actuarial obliteration rate was 61% (95% CI, 39-83%) and 71% (95% CI, 47-95%), respectively, after HSRT and 81% (95% CI, 66-96%) and 81% (95% CI, 66-96%), respectively, after SRS; the difference was not statistically significant. Radiation-induced necrosis was observed in 4 subjects in the SRS group and 1 subject in the HSRT group. Cyst formation occurred in 3 patients in the SRS group and no patient in the HSRT group. A permanent symptomatic complication was observed in 3 cases (4.2%), and 1 of the 3 was fatal. All 3 patients were in the SRS group. The annual intracranial hemorrhage rate was 5.5-5.6% for all patients. CONCLUSION: Our treatment policy using SRS and HSRT was as effective as the policy involving SRS alone. The HSRT schedule was suggested to have a lower frequency of radiation necrosis and cyst formation than the high-dose SRS schedule. The benefit of HSRT compared with lower dose SRS has not yet been determined.     

X-刀立体放射治疗脑部恶性肿瘤的临床分析—附21例报告

目的　探讨X 刀立体放射治疗脑部恶性肿瘤的效果、剂量、CT改变。方法　对 2 1例脑部恶性肿瘤进行X 刀立体放射治疗并随访。结果　 2 1例病人中随访 1～ 17个月原发肿瘤中位生存期为 10个月 ,转移瘤的中位生存期为9个月 ,脑部原发恶性肿瘤及转移瘤外照剂量 ( 3 4～ 40Gy) X 刀立体放射剂量 ( 2 5～ 3 0Gy) ,可以较好地控制肿瘤 ,2～ 4个月内CT可以显示肿瘤是否控制。结论　X 刀立体放射治疗脑部恶性肿瘤可以较好地控制病变 ,提高病人生存期。CT可以较好评价X 刀治疗效果。     

Fractionated stereotactic radiation therapy for intracranial tumors

In stereotactic radio surgery, a single, large dose of radiation is delivered to a small, well-defined, stereotactically localized intracranial lesion. In contrast to conventional radiation therapy, in radio surgery no attempt is made to spare normal cells within the target volume by fractionating the tumor dose. In 1987, the authors began a program of fractionated stereotactic radiation therapy for selected tumors involving sensitive brain structures. Their objective was to improve the therapeutic index and study the feasibility of the fractionated technique. Fifteen patients were treated with a multifraction regimen typically consisting of six fractions of 700 cGy each, given on alternate days for 2 weeks (total tumor dose, 4200 cGy). All patients were treated with the dynamic stereotactic radio surgical technique. A head ring ("halo frame") was used for immobilization and setup during radiation treatments. At a median follow-up time of 27 months, the symptoms of the majority of the patients improved clinically; this improvement usually occurred within a few weeks after completion of the treatment. The radiologic response was much slower. Currently, only two patients have had complete radiologic disappearance of their lesions; the majority of the patients have only had a decrease in tumor size. The treatments were well tolerated by the patients and no acute complications were observed. One patient who had a vasogenic edema 11 months after treatment fully recovered after steroid therapy. Fractionated stereotactic radiation therapy is a feasible treatment technique and may prove to be useful for selected patients with intracranial tumors. Although the preliminary data are encouraging, this technique should still be considered experimental. A larger number of patients and a longer follow-up time are necessary to determine whether the results of this technique are actually better than those of conventional radiation therapy.     

Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas

BACKGROUND: The objective of this prospective cohort study was to determine the efficacy of stereotactic radiosurgery (SRS) as a salvage treatment in patients with recurrent malignant gliomas. METHODS: Between January 2000 and December 2006, 114 consecutive patients were treated with SRS as a salvage treatment for recurrent malignant gliomas at a single institution. Clinical outcome and its prognostic factors were analyzed and compared with the historical control group who were treated at the same institution between 1995 and 1999. RESULTS: The median overall survival from the time of diagnosis was 37.5 months (95% confidence interval [95% CI], 11.7-63.2 months) for patients with grade 3 gliomas (according to World Health Organization criteria) and was 23 months (95% CI, 16.2-29.3 months) for patients with glioblastomas. The median progression-free survival after SRS was 8.6 months (95% CI, 1.1-16.2 months) for patients with grade 3 gliomas and 4.6 months for patients with glioblastomas (95% CI, 4.0-5.2 months). With regard to treatment-related complications, radiation-induced necrosis was observed in 22 of 114 patients (24.4%). Compared with this historic control group, SRS significantly prolonged survival as a salvage treatment in patients with recurrent glioblastomas (23 months vs 12 months; P < .0001), but it was not found to provide a significant surgical benefit in patients with recurrent grade 3 gliomas (37.5 months vs 26 months; P = .789). On univariate analysis of prognostic factors, tumor volume (<10 mL) and low histologic grade were found to significantly influence better survival (P = .009 and P = .041, respectively). CONCLUSIONS: SRS is a safe and effective modality in selected patients with recurrent small-sized glioblastomas. However, the efficacy of SRS for recurrent grade 3 gliomas needs to be further evaluated in well-designed clinical studies.     

Stereotactic radiosurgery of benign intracranial tumors

Stereotactic radiosurgery is a frequently performed procedure for patients with benign intracranial tumors. Benign tumors are good candidates for radiosurgery because they are generally non-invasive, are well visualized by magnetic resonance imaging, and their slow rate of proliferation makes conventional radiation dose fractionation unnecessary. Stereotactic radiosurgery is now an important part of both neurosurgical and radiation oncology training. This chapter will review the indications and results of radiosurgery for patients with intracranial meningiomas, vestibular schwannomas, and pituitary adenomas having single-fraction radiosurgery at the Mayo Clinic since 1990.     

CyberKnife robotic radiosurgery system for tumor treatment

Defined by its high level of accuracy and rapid radiation dose fall-off, radiosurgery has emerged as an effective radiation technique over the past few decades. Although it was once limited to conditions of the brain, head and neck regions, technological advances in computing and imaging have allowed the application of radiosurgery to conditions throughout the entire body. Using advanced imaging and robotics, the CyberKnife (Accuray, Inc., Sunnyvale, CA, USA) is one of few systems capable of delivering radiosurgery with exquisite accuracy to tumors, cancers and other conditions throughout the body. This review focuses on the development, technology, clinical efficacy and future directions of the CyberKnife.     

Single and hypofractionated stereotactic radiotherapy with CyberKnife for craniopharyngioma

Craniopharyngiomas are slow-growing tumors found in the suprasellar region, with especially high incidence in Japanese children. Due to the location, proximity and adhesiveness of the tumor to adjacent critical structures, these tumors remain a significant clinical challenge. The purpose of this study was to evaluate the clinical outcome of single and hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for craniopharyngioma. Forty-three patients (21 men and 22 women; median age 44 years; range 3–85 years) were treated at two institutions. Three cases were treated in a single fraction to a marginal dose of 13–16 Gy. The other 40 cases were treated in 2–5 fractions to a marginal dose of 13–25 Gy. Tumor volumes ranged from 0.09 to 20.8 cm³ (median 2.0 cm³). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period was 40 months (range 12–92 months). The 3-year overall survival and local control rates were 100 and 85%, respectively. In-field cyst enlargement was observed in 9 patients. These tumors had significantly larger volumes (mean 6.9 cm³; 95% confidence interval, CI, 2.8–10.9 cm³) than the 34 controlled tumors (2.9 cm³; CI 1.5–4.3 cm³) (P = 0.02). Out-field tumor regrowth was observed in 4 patients. No radiation-induced symptomatic visual disorder or brain necrosis was observed. Hypopituitarism was observed in only 1 patient. Single and hypofractionated SRT using CyberKnife produced high tumor control rates with minimal complications. Hypofractionated SRT may be useful for protecting the visual nerve and neuroendocrine function, especially for tumors located near the optic pathways and for large tumors.     

A system for stereotactic radiosurgery with a linear accelerator

A small field irradiation technique to deliver high doses of single fraction photon radiation to small, precisely located volumes (0.5 to 8 cm3) within the brain has been developed. Our method uses a modified Brown-Roberts-Wells (BRS), CT-guided, stereotactic system and a 6 MV linear accelerator equipped with a special collimator (diameters of 12.5 mm to 30.0 mm projected to isocenter) located 23 cm from isocenter. Target localization via planar angiography has been added. Treatment consists of a series of arcing beams using both gantry and couch rotations. During treatment, the patient's head is immobilized independently of the radiotherapy couch and is precisely positioned without reference to room lasers or light field. A precise verification of alignment precedes each treatment. Extensive performance tests have shown that a target, localized by CT, can be irradiated with a positional accuracy of 2.4 mm in any direction with 95% confidence. If angiography is used for localization, the results are better. The dose 1.0 cm outside the target volume is less than 20% of the prescribed dose for a medium sized collimator.