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Lawrence S. Chin, Lijun Ma and Steven DiBiase

Object. Radiation necrosis is the only significant complication of gamma knife surgery (GKS). The authors studied treatment plan parameters in patients who had radiation necrosis to determine if risk factors for necrosis could be identified.

Methods. Between September 1994 and December 1998, 286 patients were treated with GKS by the senior author. Of the 243 patients who were suitable for analysis, 17 developed radiation necrosis and were prospectively followed. Concurrently, 17 patients without necrosis were randomly selected as case controls on the basis of histological findings in their lesions. Integral dose—volume histograms (DVHs) were calculated and dose—volume treatment parameters were determined. A comparison was made with both the established Kjellberg and Flickinger isonecrosis risk lines. Clinical outcome was assessed according to time to resolution of symptoms and return to normal radiographic appearance.

Conclusions. Treatment plan variables associated with the risk of necrosis were increased tumor volume (TV) integral dose, increased TV, and increased 10-Gy volume. Other risk factors included repeated radiosurgery to the same lesion and glioma histological findings. The Kjellberg 1% risk line predicted a 5% risk of radiation necrosis and the Flickinger 3% risk line predicted a 3% risk. The median time to development of necrosis was 4 months, and symptomatic and radiographic recovery times were 7.5 and 10.5 months, respectively. The median survival time in patients with necrosis was 30 months. The authors recommend prospective TV determination and DVH calculation for all radiosurgical treatments and the avoidance of repeated radiosurgical treatments to the same lesion when possible.

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Lijun Ma, Lynn Verhey, Cynthia Chuang, Martina Descovich, Vernon Smith, Kim Huang, Michael McDermott and Penny Sneed

Object

The new capability of composite sector collimation in Gamma Knife Perfexion produces complex, nonspherical, and nonelliptical dose distributions. In this study, the authors investigated the effect of composite sector collimation on average dose fall-off compared with the previous Gamma Knife model.

Methods

A general formalism was derived to describe the peripheral dose distribution of all Gamma Knife models in the form of (V/V0) = (D/D0)γ, where V is the volume of the peripheral isodose line with the value of D, V0 is the reference prescription isodose volume, D0 is the prescription dose, and γ is the fitting parameter that determines how fast the dose falls off near the target. Based on this formula, the authors compared 40 cases involving patients treated with Gamma Knife Perfexion with 40 similar cases involving patients treated with Gamma Knife model 4C. The cases were grouped based on the use of the sector collimators in the treatment planning process. For each group as well as all cases combined, the mean γ values were compared by means of the Student t-test for varying ranges of the peripheral dose distribution—from 100% of the prescription dose to 75, 50, and 25% of the prescription dose.

Results

The fit of general formula to the data was excellent for both Gamma Knife Perfexion and Gamma Knife 4C with R2> 0.99 for all the cases. The overall γ values (mean ± 2 standard deviations) were as follows: γ = −1.74 ± 0.47 (Model 4C) versus −1.77 ± 0.40 (Perfexion) within 100–75% of the prescription dose; γ = −1.57 ± 0.26 (Model 4C) versus −1.58 ± 0.25 (Perfexion) within 100–50% of the prescription dose; γ = −1.47 ± 0.18 (Model 4C) versus −1.50 ± 0.16 (Perfexion) within 100–25% of the prescription dose. No statistical significance between the mean differences for Gamma Knife Perfexion and Model 4C was found within these ranges. The probability values were 0.65, 0.84, and 0.22, respectively.

Conclusions

The use of composite sector collimators in Gamma Knife Perfexion demonstrated no statistically significant effects on the volume-averaged dose fall-off near a target periphery for typical treatment cases.

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Joshua Chiu, Steve Braunstein, Jean Nakamura, Philip Theodosopoulos, Penny Sneed, Michael McDermott and Lijun Ma

OBJECTIVE

Interfractional residual patient shifts are often observed during the delivery of hypofractionated brain radiosurgery. In this study, the authors developed a robustness treatment planning check procedure to assess the dosimetric effects of residual target shifts on hypofractionated Gamma Knife radiosurgery (GKRS).

METHODS

The residual patient shifts were determined during the simulation process immediately after patient immobilization. To mimic incorporation of residual target shifts during treatment delivery, a quality assurance procedure was developed to sample and shift individual shots according to the residual uncertainties in the prescribed treatment plan. This procedure was tested and demonstrated for 10 hypofractionated GKRS cases.

RESULTS

The maximum residual target shifts were less than 1 mm for the studied cases. When incorporating such shifts, the target coverage varied by 1.9% ± 2.2% (range 0.0%–7.1%) and selectivity varied by 3.6% ± 2.5% (range 1.1%–9.3%). Furthermore, when incorporating extra random shifts on the order of 0.5 mm, the target coverage decreased by as much as 7%, and nonisocentric variation in the dose distributions was noted for the studied cases.

CONCLUSIONS

A pretreatment robustness check procedure was developed and demonstrated for hypofractionated GKRS. Further studies are underway to implement this procedure to assess maximum tolerance levels for individual patient cases.

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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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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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Martina Descovich, Penny K. Sneed, Nicholas M. Barbaro, Michael W. McDermott, Cynthia F. Chuang, Igor J. Barani, Jean L. Nakamura and Lijun Ma

Object

The Leksell Gamma Knife and the Accuray CyberKnife systems have been used in the radiosurgical treatment of trigeminal neuralgia. The 2 techniques use different delivery methods and different treatment parameters. In the past, CyberKnife treatments have been associated with an increased incidence of treatment-related complications, such as facial numbness. The goal of this study was to develop a method for planning a CyberKnife treatment for trigeminal neuralgia that would reproduce the dosimetric characteristics of a Gamma Knife plan. A comparison between Gamma Knife and CyberKnife treatment plans obtained with this method is presented.

Methods

Five patients treated using the Gamma Knife Perfexion Unit were selected for this study. All patients underwent CT cisternography to accurately identify the position of the trigeminal nerve. The Gamma Knife plans used either one 4-mm-diameter collimator or two coincident 4-mm collimators (one open and one with sector blocking) placed at identical isocenter coordinates. A maximum local dose of 80 Gy was prescribed. Critical structures and representative isodose lines were outlined in GammaPlan and exported to the CyberKnife treatment planning platform. CyberKnife treatments were developed using the 5-mm-diameter cone and the trigeminal node set, which provides an effective collimation diameter of 4 mm at the isocenter. The 60-Gy isodose volume imported from GammaPlan was used as the target in the CyberKnife plans. The CyberKnife treatments were optimized to achieve target dose and critical structure sparing similar to the Gamma Knife plans. Isocentric and nonisocentric delivery techniques were investigated. Treatment plans were compared in terms of dosimetric characteristics, delivery, and planning efficiency.

Results

CyberKnife treatments using the 5-mm cone and the trigeminal node set can closely reproduce the dose distribution of Gamma Knife plans. CyberKnife isocentric and nonisocentric plans provide comparable results. The average length of the trigeminal nerve receiving a dose of 60 Gy was 4.5, 4.5, and 4.4 mm for Gamma Knife, nonisocentric CyberKnife, and isocentric CyberKnife, respectively. However, minimizing the dose to the critical structures was more difficult with the CyberKnife and required the use of tuning structures. In addition, the dose falloff away from the target was steeper in Gamma Knife plans, probably due to the larger number of beams (192 beams for Perfexion vs ~ 100 beams for CyberKnife). While the treatment time with the CyberKnife is generally shorter, the planning time is significantly longer.

Conclusions

CyberKnife radiosurgical parameters can be optimized to mimic the dose distribution of Gamma Knife plans. However, Gamma Knife plans result in superior sparing of critical structures (brainstem, temporal lobe, and cranial nerves VII and VIII) and in steeper dose falloff away from the target. The clinical significance of these effects is unknown.

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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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Stereotactic body radiotherapy for de novo spinal metastases: systematic review

International Stereotactic Radiosurgery Society practice guidelines

Zain A. Husain, Arjun Sahgal, Antonio De Salles, Melissa Funaro, Janis Glover, Motohiro Hayashi, Masahiro Hiraoka, Marc Levivier, Lijun Ma, Roberto Martínez-Alvarez, J. Ian Paddick, Jean Régis, Ben J. Slotman and Samuel Ryu

OBJECTIVE

The aim of this systematic review was to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously untreated spinal metastases.

METHODS

The authors performed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of the literature found in a search of Medline, PubMed, Embase, and the Cochrane Library up to March 2015. The search strategy was limited to publications in the English language.

RESULTS

A total of 14 full-text articles were included in the analysis. All studies were retrospective except for 2 studies, which were prospective. A total of 1024 treated spinal lesions were analyzed. The median follow-up time ranged from 9 to 49 months. A range of dose-fractionation schemes was used, the most common of which were 16–24 Gy/1 fraction (fx), 24 Gy/2 fx, 24–27 Gy/3 fx, and 30–35 Gy/5 fx. In studies that reported crude results regarding in-field local tumor control, 346 (85%) of 407 lesions remained controlled. For studies that reported actuarial values, the weighted average revealed a 90% 1-year local control rate. Only 3 studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases; 2 cases (0.2%) of neurologic injury were reported.

CONCLUSION

There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review found that SBRT is associated with favorable rates of local control (approximately 90% at 1 year) and complete pain response (approximately 50%), and low rates of serious adverse events were found. Practice guidelines are summarized based on these data and International Stereotactic Radiosurgery Society consensus.