scholarly journals Establishment of a Therapeutic Ratio for Gamma Knife Radiosurgery of Trigeminal Neuralgia: The Critical Importance of Biologically Effective Dose Versus Physical Dose

2020 ◽  
Vol 134 ◽  
pp. e204-e213 ◽  
Author(s):  
Constantin Tuleasca ◽  
Ian Paddick ◽  
John W. Hopewell ◽  
Bleddyn Jones ◽  
William T. Millar ◽  
...  
2016 ◽  
Vol 125 (Supplement_1) ◽  
pp. 154-159 ◽  
Author(s):  
Benjamin H. Kann ◽  
James B. Yu ◽  
John M. Stahl ◽  
James E. Bond ◽  
Christopher Loiselle ◽  
...  

OBJECTIVEFunctional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder. Although its rates of toxicity are low, GKRS has been associated with some, if low, risks for serious sequelae, including hemiparesis and even death. Anecdotal reports have suggested that even with a standardized prescription dose, rates of functional GKRS toxicity increase after replacement of an old cobalt-60 source with a new source. Dose rate changes over the course of the useful lifespan of cobalt-60 are not routinely considered in the study of patients treated with functional GKRS, but these changes may be associated with significant variation in the biologically effective dose (BED) delivered to neural tissue.METHODSThe authors constructed a linear-quadratic model of BED in functional GKRS with a dose-protraction factor to correct for intrafraction DNA-damage repair and used standard single-fraction doses for trigeminal nerve ablation for TN (85 Gy), thalamotomy for tremor (130 Gy), and capsulotomy for obsessive-compulsive disorder (180 Gy). Dose rate and treatment time for functional GKRS involving 4-mm collimators were derived from calibrations in the authors' department and from the cobalt-60 decay rate. Biologically plausible values for the ratio for radiosensitivity to fraction size (α/β) and double-strand break (DSB) DNA repair halftimes (τ) were estimated from published experimental data. The biphasic characteristics of DSB repair in normal tissue were accounted for in deriving an effective τ1 halftime (fast repair) and τ2 halftime (slow repair). A sensitivity analysis was performed with a range of plausible parameter values.RESULTSAfter replacement of the cobalt-60 source, the functional GKRS dose rate rose from 1.48 to 2.99 Gy/min, treatment time fell, and estimated BED increased. Assuming the most biologically plausible parameters, source replacement resulted in an immediate relative BED increase of 11.7% for GKRS-based TN management with 85 Gy, 15.6% for thalamotomy with 130 Gy, and 18.6% for capsulotomy with 180 Gy. Over the course of the 63-month lifespan of the cobalt-60 source, BED decreased annually by 2.2% for TN management, 3.0% for thalamotomy, and 3.5% for capsulotomy.CONCLUSIONSUse of a new cobalt-60 source after replacement of an old source substantially increases the predicted BED for functional GKRS treatments for the same physical dose prescription. Source age, dose rate, and treatment time should be considered in the study of outcomes after high-dose functional GKRS treatments. Animal and clinical studies are needed to determine how this potential change in BED contributes to GKRS toxicity and whether technical adjustments should be made to reduce dose rates or prescription doses with newer cobalt-60 sources.


2020 ◽  
pp. 1-11 ◽  
Author(s):  
Constantin Tuleasca ◽  
Iulia Peciu-Florianu ◽  
Henri-Arthur Leroy ◽  
Maximilien Vermandel ◽  
Mohamed Faouzi ◽  
...  

OBJECTIVEArteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs.METHODSA total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12–154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18–25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7–246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9–138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313–3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4–2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed.RESULTSA total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (−0.013689 × beam-on time) + (0.021 × age) − 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03).CONCLUSIONSThe BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.


2020 ◽  
Vol 133 (3) ◽  
pp. 727-735
Author(s):  
Peter Shih-Ping Hung ◽  
Sarasa Tohyama ◽  
Jia Y. Zhang ◽  
Mojgan Hodaie

OBJECTIVEGamma Knife radiosurgery (GKRS) is a noninvasive surgical treatment option for patients with medically refractive classic trigeminal neuralgia (TN). The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear. To better understand this topic, the authors used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.METHODSNinety-two sets of 3-T anatomical and diffusion-weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief.RESULTSGKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point.CONCLUSIONSUltimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN.


2002 ◽  
Vol 97 ◽  
pp. 533-535 ◽  
Author(s):  
Jin Woo Chang ◽  
Jae Young Choi ◽  
Young Sul Yoon ◽  
Yong Gou Park ◽  
Sang Sup Chung

✓ The purpose of this paper was to present two cases of secondary trigeminal neuralgia (TN) with an unusual origin and lesion location. In two cases TN was caused by lesions along the course of the trigeminal nerve within the pons and adjacent to the fourth ventricle. Both cases presented with typical TN. Brain magnetic resonance imaging revealed linear or wedge-shaped lesions adjacent to the fourth ventricle, extending anterolaterally and lying along the pathway of the intraaxial trigeminal fibers. The involvement of the nucleus of the spinal trigeminal tract and of the principal sensory trigeminal nucleus with segmental demyelination are suggested as possible causes for trigeminal pain in these cases. It is postulated that these lesions are the result of an old viral neuritis. The patients underwent gamma knife radiosurgery and their clinical responses have been encouraging to date.


Neurosurgery ◽  
2010 ◽  
Vol 67 (6) ◽  
pp. 1637-1645 ◽  
Author(s):  
Hideyuki Kano ◽  
Douglas Kondziolka ◽  
Huai-Che Yang ◽  
Oscar Zorro ◽  
Javier Lobato-Polo ◽  
...  

Abstract BACKGROUND: Trigeminal neuralgia (TN) that recurs after surgery can be difficult to manage. OBJECTIVE: To define management outcomes in patients who underwent gamma knife stereotactic radiosurgery (GKSR) after failing 1 or more previous surgical procedures. METHODS: We retrospectively reviewed outcomes after GKSR in 193 patients with TN after failed surgery. The median patient age was 70 years (range, 26-93 years). Seventy-five patients had a single operation (microvascular decompression, n = 40; glycerol rhizotomy, n = 24; radiofrequency rhizotomy, n = 11). One hundred eighteen patients underwent multiple operations before GKSR. Patients were evaluated up to 14 years after GKSR. RESULTS: After GKSR, 85% of patients achieved pain relief or improvement (Barrow Neurological Institute grade I-IIIb). Pain recurrence was observed in 73 of 168 patients 6 to 144 months after GKSR (median, 6 years). Factors associated with better long-term pain relief included no relief from the surgical procedure preceding GKSR, pain in a single branch, typical TN, and a single previous failed surgical procedure. Eighteen patients (9.3%) developed new or increased trigeminal sensory dysfunction, and 1 developed deafferentation pain. Patients who developed sensory loss after GKSR had better long-term pain control (Barrow Neurological Institute grade I-IIIb: 86% at 5 years). CONCLUSION: GKSR proved to be safe and moderately effective in the management of TN that recurs after surgery. Development of sensory loss may predict better long-term pain control. The best candidates for GKSR were patients with recurrence after a single failed previous operation and those with typical TN in a single trigeminal nerve distribution.


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