Stereotactic radiosurgery for trigeminal neuralgia: a systematic review

International Stereotactic Radiosurgery Society practice guidelines

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OBJECTIVES

The aims of this systematic review are to provide an objective summary of the published literature specific to the treatment of classical trigeminal neuralgia with stereotactic radiosurgery (RS) and to develop consensus guideline recommendations for the use of RS, as endorsed by the International Society of Stereotactic Radiosurgery (ISRS).

METHODS

The authors performed a systematic review of the English-language literature from 1951 up to December 2015 using the Embase, PubMed, and MEDLINE databases. The following MeSH terms were used in a title and abstract screening: “radiosurgery” AND “trigeminal.” Of the 585 initial results obtained, the authors performed a full text screening of 185 studies and ultimately found 65 eligible studies. Guideline recommendations were based on level of evidence and level of consensus, the latter predefined as at least 85% agreement among the ISRS guideline committee members.

RESULTS

The results for 65 studies (6461 patients) are reported: 45 Gamma Knife RS (GKS) studies (5687 patients [88%]), 11 linear accelerator (LINAC) RS studies (511 patients [8%]), and 9 CyberKnife RS (CKR) studies (263 patients [4%]). With the exception of one prospective study, all studies were retrospective.

The mean maximal doses were 71.1–90.1 Gy (prescribed at the 100% isodose line) for GKS, 83.3 Gy for LINAC, and 64.3–80.5 Gy for CKR (the latter two prescribed at the 80% or 90% isodose lines, respectively). The ranges of maximal doses were as follows: 60–97 Gy for GKS, 50–90 Gy for LINAC, and 66–90 Gy for CKR.

Actuarial initial freedom from pain (FFP) without medication ranged from 28.6% to 100% (mean 53.1%, median 52.1%) for GKS, from 17.3% to 76% (mean 49.3%, median 43.2%) for LINAC, and from 40% to 72% (mean 56.3%, median 58%) for CKR. Specific to hypesthesia, the crude rates (all Barrow Neurological Institute Pain Intensity Scale scores included) ranged from 0% to 68.8% (mean 21.7%, median 19%) for GKS, from 11.4% to 49.7% (mean 27.6%, median 28.5%) for LINAC, and from 11.8% to 51.2% (mean 29.1%, median 18.7%) for CKR. Other complications included dysesthesias, paresthesias, dry eye, deafferentation pain, and keratitis. Hypesthesia and paresthesia occurred as complications only when the anterior retrogasserian portion of the trigeminal nerve was targeted, whereas the other listed complications occurred when the root entry zone was targeted. Recurrence rates ranged from 0% to 52.2% (mean 24.6%, median 23%) for GKS, from 19% to 63% (mean 32.2%, median 29%) for LINAC, and from 15.8% to 33% (mean 25.8%, median 27.2%) for CKR. Two GKS series reported 30% and 45.3% of patients who were pain free without medication at 10 years.

CONCLUSIONS

The literature is limited in its level of evidence, with only one comparative randomized trial (1 vs 2 isocenters) reported to date. At present, one can conclude that RS is a safe and effective therapy for drug-resistant trigeminal neuralgia. A number of consensus statements have been made and endorsed by the ISRS.

ABBREVIATIONS BMC = balloon microcompression; BNI = Barrow Neurological Institute; CKR = CyberKnife radiosurgery; DVH = dose-volume histogram; FFP = freedom from pain; GKS = Gamma Knife surgery; HSRT = hypofractionated stereotactic radiotherapy; ISRS = International Society of Stereotactic Radiosurgery; LINAC = linear accelerator; MVD = microvascular decompression; QOL = quality of life; RCT = randomized controlled trial; REZ = root entry zone; RFT = radiofrequency thermocoagulation; RS = radiosurgery; SCA = superior cerebellar artery; TN = trigeminal neuralgia; TTPR = time to pain relief.

Article Information

Correspondence Constantin Tuleasca: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. email: constantin.tuleasca@gmail.com.

INCLUDE WHEN CITING Published online April 27, 2018; DOI: 10.3171/2017.9.JNS17545.

C.T. and J.R. contributed equally to this study.

Disclosures Mr. Paddick has been a consultant for Elekta AB. Dr. Régis has been a consultant for Medtronic and has received support from Elekta for non–study-related clinical or research effort. Dr. Sahgal has received honoraria for past educational seminars from Medtronic, Elekta AB, Accuray Inc., and Varian Medical Systems and research grants from Elekta AB and belongs to the Elekta MR LINAC Research Consortium.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Flow chart to final number of eligible studies.

  • View in gallery

    Examples of different types of targeting (simulation), including the plexus triangularis (A), retrogasserian portion (far anterior cisternal, B), REZ with 30% isodose line overlapping the brainstem (C), and the use of 2 isocenters (D). Purple line indicates the brainstem area (for further DVH measurements; light blue line, the trigeminal nerve; green line, the 50% isodose line; and dark blue area, approximate middle point of trigeminal nerve, in the retrogasserian area. Figure is available in color online only.

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    When initial efficacy was pooled (A), there was no statistically significant difference between the retrogasserian and the REZ target, with an HR = 1.44 (95% CI 0.78, 2.68), p = 0.25. For toxicity (B), there was a statistically significant increase in the REZ group, with an HR = 1.78 (95% CI 1.04, 3.05), p = 0.03. For the maintenance of pain relief (C), there was no statistically significant difference between the two targets, with an HR = 1.69 (95% CI 0.78, 3.65), p = 0.18. Figure is available in color online only.

  • View in gallery

    When initial efficacy was pooled (A), there was no statistically significant difference between 1 and 2 isocenters, with an HR = 1.21 (95% CI 0.40, 3.68), p = 0.74. For toxicity (B), there was no statistically significant difference in the number of isocenters used, with an HR = 0.82 (95% CI 0.41, 1.65), p = 0.58; however, the study by Flickinger et al.32 clearly shows a major increase in toxicity with 2-isocenter use. Figure is available in color online only.

  • View in gallery

    When initial efficacy was pooled (A), there was a statistically significant difference between cases with prior MVD and those without, with an HR = 7.08 (95% CI 3.76, 13.34), p < 0.00001. For the maintenance of pain relief on a long-term basis (B), there was no statistically significant difference, with an HR = 1.20 (95% CI 0.65, 2.24), p = 0.56. Figure is available in color online only.

  • View in gallery

    When the maintenance of pain relief on a long-term basis was compared between MVD and GKS, there was a statistically significant difference, with an HR = −0.29 (95% CI −0.49, −0.10), p = 0.003. Figure is available in color online only.

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