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Paul M. Arnold

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Juan Pablo Cruz, Arjun Sahgal, Cari Whyne, Michael G. Fehlings and Roger Smith

Balloon kyphoplasty (BKP) has been proven to be safe and effective in the management of pathological vertebral compression fracture (VCF) due to metastatic spinal disease. The most common serious complications related to BKP include cement extravasation and new fractures at adjacent levels. Although the potential for “tumor extravasation” has been discussed as a potential iatrogenic complication, it has yet to be confirmed. The authors report on 2 cases of tumor extravasation following BKP, which they base on an observed unusual rapid tumor spread pattern into the adjacent tissues. They postulate that by increasing the vertebral body internal pressure and disrupting the tissues during balloon inflation and cement application, a soft-tissue tumor can be forced beyond the vertebral bony boundaries through pathological cortical defects. This phenomenon can manifest radiologically as subligamentous spread and/or extension into venous sinusoids, resulting in epidural venous plexus involvement, with subsequent tumor migration into the adjacent vertebral segments. Accordingly, the authors advise caution in using BKP when significant epidural tumor is present. The complication they encountered has caused them to modify their preference such that they now first use radiosurgery and subsequently BKP to ensure the target is appropriately treated, and they are currently developing possible modifications of procedural technique to reduce the risk.

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Arjun Sahgal, Mark Bilsky, Eric L. Chang, Lijun Ma, Yoshiya Yamada, Laurence D. Rhines, Daniel Létourneau, Matthew Foote, Eugene Yu, David A. Larson and Michael G. Fehlings

Stereotactic body radiotherapy (SBRT) for spinal metastases is an emerging therapeutic option aimed at delivering high biologically effective doses to metastases while sparing the adjacent normal tissues. This technique has emerged following advances in radiation delivery that include sophisticated radiation treatment planning software, body immobilization devices, and capabilities of detecting and correcting patient positional deviations with imageguided radiotherapy. There are limited clinical data specifically supporting the role of SBRT as a superior alternative to conventional radiation in the postoperative patient. The focus of this review was to examine the evidence pertaining to spine SBRT in the treatment of spinal metastases and to provide a comprehensive analysis of published patterns of failure, with emphasis on the postoperative patient.

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Ameen Al-Omair, Roger Smith, Tim-Rasmus Kiehl, Louis Lao, Eugene Yu, Eric M. Massicotte, Julia Keith, Michael G. Fehlings and Arjun Sahgal

Spine stereotactic radiosurgery (SRS) is increasingly being used to treat metastatic spinal tumors. As the experience matures, high rates of vertebral compression fracture (VCF) are being observed. What is unknown is the mechanism of action; it has been postulated but not confirmed that radiation itself is a contributing factor. This case report describes 2 patients who were treated with spine SRS who subsequently developed signal changes on MRI consistent with tumor progression and VCF; however, biopsy confirmed a diagnosis of radiation-induced necrosis in 1 patient and fibrosis in the other. Radionecrosis is a rare and serious side effect of high-dose radiation therapy and represents a diagnostic challenge, as the authors have learned from years of experience with brain SRS. These cases highlight the issues in the new era of spine SRS with respect to relying on imaging alone as a means of determining true tumor progression. In those scenarios in which it is unclear based on imaging if true tumor progression has occurred, the authors recommend biopsy to rule out radiation-induced effects within the bone prior to initiating salvage therapies.

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Reirradiation spine stereotactic body radiation therapy for spinal metastases: systematic review

International Stereotactic Radiosurgery Society practice guidelines

Sten Myrehaug, Arjun Sahgal, Motohiro Hayashi, Marc Levivier, Lijun Ma, Roberto Martinez, Ian Paddick, Jean Régis, Samuel Ryu, Ben Slotman and Antonio De Salles

OBJECTIVE

Spinal metastases that recur after conventional palliative radiotherapy have historically been difficult to manage due to concerns of spinal cord toxicity in the retreatment setting. Spine stereotactic body radiation therapy (SBRT), also known as stereotactic radiosurgery, is emerging as an effective and safe means of delivering ablative doses to these recurrent tumors. The authors performed a systematic review of the literature to determine the clinical efficacy and safety of spine SBRT specific to previously irradiated spinal metastases.

METHODS

A systematic literature review was conducted, which was specific to SBRT to the spine, using MEDLINE, Embase, Cochrane Evidence-Based Medicine Database, National Guideline Clearinghouse, and CMA Infobase, with further bibliographic review of appropriate articles. Research questions included: 1) Is retreatment spine SBRT efficacious with respect to local control and symptom control? 2) Is retreatment spine SBRT safe?

RESULTS

The initial literature search retrieved 2263 articles. Of these articles, 160 were potentially relevant, 105 were selected for in-depth review, and 9 studies met all inclusion criteria for analysis. All studies were single-institution series, including 4 retrospective, 3 retrospective series of prospective databases, 1 prospective, and 1 Phase I/II prospective study (low- or very low–quality data). The results indicated that spine SBRT is effective, with a median 1-year local control rate of 76% (range 66%–90%). Improvement in patients’ pain scores post-SBRT ranged from 65% to 81%. Treatment delivery was safe, with crude rates of vertebral body fracture of 12% (range 0%–22%) and radiation-induced myelopathy of 1.2%.

CONCLUSIONS

This systematic literature review suggests that SBRT to previously irradiated spinal metastases is safe and effective with respect to both local control and pain relief. Although the evidence is limited to low-quality data, SBRT can be a recommended treatment option for reirradiation.

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Shannon Fogh, Lijun Ma, Nalin Gupta, Arjun Sahgal, Jean L. Nakamura, Igor Barani, Penny K. Sneed, Michael McDermott and David A. Larson

Object

The goal of this study was to develop a technique for performing submillimeter high-precision volume-staged Gamma Knife surgery and investigate its potential benefits in comparison with hypofractionated stereotactic radiotherapy (SRT) for treating large arteriovenous malformations (AVMs).

Methods

The authors analyzed 7 pediatric AVM cases treated with volume-staged stereotactic radiosurgery (SRS) using the Gamma Knife Perfexion at the University of California, San Francisco. The target and normal tissue contours from each case were exported for hypofractionated treatment planning based on the Gamma Knife Extend system or the CyberKnife SRT. Both the Gamma Knife Extend and CyberKnife treatment plans were matched to yield the same level of target coverage (95%–98%) and conformity indices (1.24–1.46). Finally, hypofractionated treatment plans were compared with volume-staged treatment plans for sparing normal brain by using biologically equivalent 12-Gy normal brain volumes.

Results

Hypofractionated Gamma Knife Extend and CyberKnife treatment plans exhibited practically identical sparing of normal brain for the studied cases. However, when matching such values with volume-staged treatments for the biological effective dose, only conservative dose fractionation schemes, such as 27.3 Gy in 5 fractions and 25 Gy in 4 fractions, were found to be comparable to the volume-staged treatments. On average, this represents a mean 18.7% ± 7.3% reduction in the single-fraction biologically equivalent dose for hypofractionated treatments versus the reference volume-staged treatments (p < 0.001).

Conclusions

Volume staging remains advantageous over hypofractionation in delivering a higher dose to the target and for better sparing of normal brain tissue in the treatment of large AVMs. More clinical data are needed, however, to justify the clinical superiority of this increased dose when compared with a hypofractionated treatment regimen.

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Lijun Ma, Arjun Sahgal, Ke Nie, Andrew Hwang, Aliaksandr Karotki, Brian Wang, Dennis C. Shrieve, Penny K. Sneed, Michael McDermott and David A. Larson

Object

Determining accurate target volume is critical for both prescribing and evaluating stereotactic radiosurgery (SRS) treatments. The aim of this study was to determine the reliability of contour-based volume calculations made by current major SRS platforms.

Methods

Spheres ranging in diameter from 6.4 to 38.2 mm were scanned and then delineated on imaging studies. Contour data sets were subsequently exported to 6 SRS treatment-planning platforms for volume calculations and comparisons. This procedure was repeated for the case of a patient with 12 metastatic lesions distributed throughout the brain. Both the phantom and patient datasets were exported to a stand-alone workstation for an independent volume-calculation analysis using a series of 10 algorithms that included approaches such as slice stacking, surface meshing, point-cloud filling, and so forth.

Results

Contour data–rendered volumes exhibited large variations across the current SRS platforms investigated for both the phantom (−3.6% to 22%) and patient case (1.0%–10.2%). The majority of the clinical SRS systems and algorithms overestimated the volumes of the spheres, compared with their known physical volumes. An independent algorithm analysis found a similar trend in variability, and large variations were typically associated with small objects whose volumes were < 0.4 cm3 and with those objects located near the end-slice of the scan limits.

Conclusions

Significant variations in volume calculation were observed based on data obtained from the SRS systems that were investigated. This observation highlights the need for strict quality assurance and benchmarking efforts when commissioning SRS systems for clinical use and, moreover, when conducting multiinstitutional cross-SRS platform clinical studies.

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Lijun Ma, Paula Petti, Brian Wang, Martina Descovich, Cynthia Chuang, Igor J. Barani, Sandeep Kunwar, Dennis C. Shrieve, Arjun Sahgal and David A. Larson

Object

Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent.

Methods

The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator–based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain.

Results

Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted.

Conclusions

The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.

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Michael W. Chan, Isabelle Thibault, Eshetu G. Atenafu, Eugene Yu, B. C. John Cho, Daniel Letourneau, Young Lee, Albert Yee, Michael G. Fehlings and Arjun Sahgal

OBJECT

The authors performed a pattern-of-failure analysis, with a focus on epidural disease progression, in patients treated with postoperative spine stereotactic body radiotherapy (SBRT).

METHODS

Of the 70 patients with 75 spinal metastases (cases) treated with postoperative spine SBRT, there were 26 cases of local disease recurrence and 25 cases with a component of epidural disease progression. Twenty-four of the 25 cases had preoperative epidural disease with subsequent epidural disease progression, and this cohort was the focus of this epidural-specific pattern-of-failure investigation. Preoperative, postoperative, and follow-up MRI scans were reviewed, and epidural disease was characterized based on location according to a system in which the vertebral anatomy is divided into 6 sectors, with the anterior compartment comprising Sectors 1, 2, and 6, and the posterior compartment comprising Sectors 3, 4, and 5.

RESULTS

Patterns of epidural progression are reported specifically for the 24 cases with preoperative epidural disease and subsequent epidural progression. Epidural disease progression within the posterior compartment was observed to be significantly lower in those with preoperative epidural disease confined to the anterior compartment than in those with preoperative epidural disease involving both anterior and posterior compartments (56% vs 93%, respectively; p = 0.047). In a high proportion of patients with epidural disease progression, treatment failure was found in the anterior compartment, including both those with preoperative epidural disease confined to the anterior compartment and those with preoperative epidural disease involving both anterior and posterior compartments (100% vs. 73%, respectively). When epidural disease was confined to the anterior compartment on the preoperative and postoperative MRIs, no epidural disease progression was observed in Sector 4, which is the most posterior sector. Postoperative epidural disease characteristics alone were not predictive of the pattern of epidural treatment failure.

CONCLUSIONS

Reviewing the extent of epidural disease on preoperative MRI is imperative when planning postoperative SBRT. When epidural disease is confined to the anterior epidural sectors pre- and postoperatively, covering the entire epidural space circumferentially with a prophylactic “donut” distribution may not be needed.

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Veronica L. Chiang, Samuel T. Chao, Constantin Tuleasca, Matthew C. Foote, Cheng-chia Lee, David Mathieu, Hany Soliman and Arjun Sahgal

In order to determine what areas of research are a clinical priority, a small group of young Gamma Knife investigators was invited to attend a workshop discussion at the 19th International Leksell Gamma Knife Society Meeting. Two areas of interest and the need for future radiosurgical research involving multiple institutions were identified by the young investigators working group: 1) the development of additional imaging sequences to guide the understanding, treatment, and outcome tracking of diseases such as tremor, radiation necrosis, and AVM; and 2) trials to clarify the role of hypofractionation versus single-fraction radiosurgery in the treatment of large lesions such as brain metastases, postoperative cavities, and meningiomas.