- Norton Healthcare, Norton Neuroscience Institute, Louisville, Kentucky, United States.
- Norton Neuroscience Institute, Norton Healthcare, Norton Cancer Institute, Louisville, Kentucky, United States.
- Department of Bioinformatics and Biostatistics, University of Louisville, School of Public Health and Information Sciences, Louisville, Kentucky, United States.
Correspondence Address:
Aaron C. Spalding, M.D., Ph.D. The Norton Cancer Institute Radiation Center, Norton Healthcare, 676 S. Floyd Street, Suite 100, Louisville, KY 40202 U.S.A.
DOI:10.25259/SNI_101_2024
Copyright: © 2024 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.How to cite this article: Lisa B. E. Shields1, Azzam Malkawi2, Michael W. Daniels3, Abigail J. Rao1, Brian M. Plato1, Tom L. Yao1, Jonathan N. Howe2, Aaron C. Spalding2. Frameless image-guided linear accelerator (LINAC) stereotactic radiosurgery for medically refractory trigeminal neuralgia: Clinical outcomes in 116 patients. 31-May-2024;15:181
How to cite this URL: Lisa B. E. Shields1, Azzam Malkawi2, Michael W. Daniels3, Abigail J. Rao1, Brian M. Plato1, Tom L. Yao1, Jonathan N. Howe2, Aaron C. Spalding2. Frameless image-guided linear accelerator (LINAC) stereotactic radiosurgery for medically refractory trigeminal neuralgia: Clinical outcomes in 116 patients. 31-May-2024;15:181. Available from: https://surgicalneurologyint.com/surgicalint-articles/12918/
Abstract
Background: Frameless image-guided radiosurgery (IGRS) is an effective and non-invasive method of treating patients who are unresponsive to medical management for trigeminal neuralgia (TN). This study evaluated the use of frameless IGRS to treat patients with medically refractory TN.
Methods: We performed a retrospective review of records of 116 patients diagnosed with TN who underwent frameless IGRS using a linear accelerator (LINAC) over 10 years (March 2012-February 2023). All patients had failed medical management for TN. Facial pain was graded using the Barrow Neurological Institute (BNI) scoring system. Each patient received a BNI score before frameless IGRS and following treatment. Failure was defined as a BNI score IV-V at the last follow-up and/or undergoing a salvage procedure following IGRS.
Results: All patients had a BNI score of either IV or V before the frameless IGRS. The mean follow-up duration for all 116 patients following IGRS was 44.1 months. Most patients (81 [69.8%]) had not undergone surgery (microvascular decompression [MVD] or rhizotomy) or stereotactic radiosurgery (SRS) for TN before frameless IGRS. A total of 41 (35.3%) patients underwent a salvage procedure (MVD, rhizotomy, or an additional IGRS) following frameless IGRS. The mean duration between the initial frameless IGRS and salvage procedure was 20.1 months. At the last follow-up, a total of 110 (94.8%) patients had a BNI score of I-III. No complications were reported after the frameless IGRS. The BNI score at the last follow-up was lower compared to the initial BNI for patients regardless of prior intervention (P P = 0.05). Patients with pain relief had a shorter follow-up compared to those with pain refractory to SRS (38.0 vs. 55.1, P = 0.005).
Conclusion: In this large cohort of patients with medically refractory TN, frameless IGRS resulted in durable pain control in the majority of patients without any toxicity.
Keywords: Linear accelerator, Neurology, Radiation Oncology, Stereotactic radiation, Trigeminal neuralgia
INTRODUCTION
According to the Beta version of the 3rd edition of the International Classification of Headache Disorders 3 Beta, trigeminal neuralgia (TN) is a debilitating condition marked by recurrent unilateral brief electric shock-like pain paroxysms that are abrupt in onset and termination.[
TN is classified into primary TN, which includes typical type 1 TN (predominantly paroxysmal pain) and atypical type 2 TN (predominantly constant pain), as well as secondary TN.[
Patients with TN are initially medically managed with sodium channel blockers (carbamazepine and oxcarbazepine); other medications (lamotrigine, baclofen, pregabalin, and gabapentin) may be subsequently added to the regimen.[
The Barrow Neurological Institute (BNI) scoring system classifies TN based on levels of pain and medication requirements (I: No pain, no medication; II: Occasional pain, not requiring medication; III: Some pain, adequately controlled with medication; IV: Some pain, not adequately controlled with medication; and V: Severe pain/no pain relief).[
In our previous study of 20 patients who underwent frameless image-guided radiosurgery (IGRS) for refractory TN,[
Herein, we expand on our previous study by greatly increasing the number of patients with medically refractory TN who were treated with frameless IGRS and following their post-IGRS course over a longer duration of time. The benefits and limitations of various modalities of SRS, as well as percutaneous procedures for TN before frameless IGRS, are discussed. We have also compared the clinical characteristics and treatment outcomes between patients diagnosed with type 1 and type 2 TN. The challenges of treating patients with concurrent multiple sclerosis and TN are also highlighted.
MATERIALS AND METHODS
Under an Institutional Review Board-approved protocol and according to the Declaration of Helsinki, we performed a 10-year (March 01, 2012–February 28, 2023) retrospective review of consecutively treated patients with TN who underwent frameless IGRS using the LINAC. All patients had failed medical management for TN. All patients were evaluated by a neurosurgeon, neurologist, and radiation oncologist. Each patient received a BNI score before the frameless IGRS and following treatment.
Frameless IGRS failure was defined as receiving a BNI score of IV or V at the last follow-up and/or undergoing a salvage procedure for TN (MVD, rhizotomy, or additional frameless IGRS) after the initial frameless IGRS. Good-to-excellent results were defined as a BNI score of I-III.
Simulation and treatment delivery
The immobilization, simulation, treatment planning, and SRS delivery methodology were previously published.[
After each patient signed informed consent, a bivalve-style thermoplastic mask was fabricated to immobilize the head. All patients were simulated and treated supine and head-first. Next, a stereotactic localizer frame was attached to the imaging frame, and then, patients underwent a 0.6 mm axial slice CT scan using a 40-slice Siemens Sensation Open (Siemens, Munich, Germany) from the vertex to the third cervical vertebra. We obtained a 0.5 mm CISS T2 MRI sequence using a three Tesla magnet with zero gantry tilt and registered the CT and MRI datasets using BrainLAB iPlan RT Image software.
Treatment planning
The affected side trigeminal nerve and organs at risk were contoured by the neurosurgeon and radiation oncologist on the fused data set. There was a 0 mm expansion from the prescription point to the planning target volume. The trigeminal nerve and brainstem were contoured on a T2 CISS sequence with 0.6 mm slice spacing. The use of real time orthogonal imaging allows for no expansion to minimize dose to the brainstem. The isocenter was placed along the trigeminal nerve, proximal to any vascular abnormality or nerve compression. The SRS plan was prescribed at the isocenter, and all plans used between seven and nine non-coplanar arcs with fixed diameter cones ranging from 4.0 to 7.5 mm aperture, with total scatter factors of 0.669 and 0.815, respectively [
Figure 1:
(a) Stereotactic radiosurgery plan with dorsal root entry zone for a patient with right-sided trigeminal neuralgia utilizing nine non-coplanar arcs with the patient position shown in the lower left corner green anthropomorphic figure. The resulting delivered dose is displayed in the (b) axial, (c) coronal, and (d) sagittal planes, with the trigeminal nerve contoured in yellow. The 40 Gy line is light blue, the 80 Gy line is dark blue, the 85% Gy line is green, and the isocenter location is red.
Evaluation after the IGRS
Patients were seen 1 month after the frameless IGRS and every 2–3 months afterward. Patients continued to follow up until they were pain-free and all TN medications were discontinued. Facial sensation was assessed, and a BNI score was determined.
Statistical analysis
We employed descriptive statistics for data summarization. Continuous measures were presented as mean ± standard deviation or median with interquartile range, while categorical data were expressed in frequencies and percentages. The relationship between categorical variables was assessed using Chi-square or Fisher’s exact tests, and continuous variables were compared using t-tests or Mann– Whitney U-tests, as dictated by the data distribution. Survival outcomes were estimated with the Kaplan–Meier method, with the Log-Rank test assessing group differences. A Cox proportional hazards model was used to evaluate the impact of type 1 versus type 2 classification on the probability of success over time, controlling for age as a confounder. Statistical significance was predetermined at P < 0.05. Analyses were conducted using R software (version 4.3.1).[
RESULTS
Clinical characteristics
A total of 116 patients were identified with medically intractable TN who underwent frameless IGRS. The median age was 65.3 years, and the majority (68.1%) of patients were female. The clinical characteristics of patients with TN are presented in
Surgical/SRS intervention for TN before frameless IGRS
A total of 35 (30.2%) patients underwent a prior intervention for TN before the frameless IGRS [
Initial frameless IGRS
All 116 patients underwent frameless IGRS, with a mean radiation dose to the target of 85.6 Gy [
Salvage procedure following initial frameless IGRS
Of the total 116 patients who underwent initial frameless IGRS, 44 (37.9%) patients failed this procedure (BNI 4–5 at last follow-up and/or undergoing a salvage procedure). A total of 41 (35.3%) patients underwent a salvage procedure following the frameless IGRS. Twenty-two (19.0%) patients underwent surgical intervention, 13 (11.2%) had a second frameless IGRS, and 6 (5.2%) had both surgery and a second frameless IGRS. Salvage surgical procedures included an MVD in 15 patients and a rhizotomy in 15 patients. A cranial nerve stimulator for the 2nd and 3rd divisions of the trigeminal nerve was placed in one patient. A total of 18 patients had a salvage frameless IGRS. The duration between the initial frameless IGRS and salvage procedure was 20.1 months. Of the 19 patients who had salvage frameless IGRS, 12 (70.6%) had their radiation targeted to Meckel’s cave. One patient underwent two salvage IGRS procedures.
None of the clinical characteristics were statistically significant between the patients who failed the initial frameless IGRS and those who did not [
BNI score at last follow-up
The mean duration between the initial frameless IGRS and the last follow-up for all 116 patients was 44.1 months. The mean BNI score at the last follow-up for all patients was 2.6. At the last follow-up, a total of 110 (94.8%) patients had a BNI score of I-III, specifically, 29 (26.4%) with an excellent response (BNI I [
The BNI score at last follow-up was lower than the BNI score before the initial frameless IGRS for patients who had a surgical/SRS intervention before the initial frameless SRS (before the initial frameless IGRS: 4.3, last follow-up: 2.8, P < 0.001) as well as for patients who did not have a surgical/SRS intervention before the initial frameless SRS (before the initial frameless IGRS: 4.3, last follow-up: 2.5, P < 0.001). The time to treatment failure was marginally (P = 0.06) shorter for the patients who did not have a prior intervention [
Figure 2:
Kaplan–Meier plot depicting that the time to treatment failure (Barrow Neurological Institute score IV-V at last follow-up or salvage procedure) following frameless image-guided radiosurgery (IGRS) was marginally (P = 0.06) shorter for the patients who did not have an intervention (microvascular decompression, rhizotomy, and/or stereotactic radiosurgery) before the frameless IGRS.
Clinical characteristics and treatment outcomes between patients with type 1 and type 2 TN
Of the total 116 patients with TN, 79 (68%) were diagnosed with type 1 and 37 (32%) with type 2 [
Kaplan–Meier survival estimates depicted the temporal probability of treatment success for both TN subtypes [
Figure 3:
Kaplan–Meier survival curves comparing treatment success in type 1 and type 2 trigeminal neuralgia. This figure illustrates the estimated survival functions for both patient groups over 120 months, with the solid line depicting type 1 and the dashed line depicting type 2. A marginally significant P = 0.065 from the log-rank test suggests a trend toward improved survival for type 1.
DISCUSSION
SRS is a viable option for patients who do not attain durable pain relief from medications or who do not want or are not candidates for invasive surgery.[
Several studies have reported their experience with frameless SRS using a LINAC for the treatment of TN [
Our study concurs with the extant literature with respect to the female predominance, older age of patients, more right laterality of symptoms, and the highest percentage of patients with symptoms in the 2nd distribution of the trigeminal nerve followed by the 3rd distribution. Compared to the works of Rashid et al.[
Our study also coincides with the literature with respect to better outcomes for patients with type 1 TN.[
TN affects approximately 7% of patients with multiple sclerosis and is often challenging to treat with pharmacology and surgery.[
Three primary percutaneous procedures are currently utilized to treat TN, including percutaneous balloon compression, glycerol rhizotomy, and radiofrequency lesioning.[
Strengths and limitations of the present study
The strength of the present study is the largest group of patients, to our knowledge, with medically refractory TN who underwent frameless IGRS using the LINAC over a 10-year duration. Our study also features a long mean duration of follow-up of 44.1 months from the initial frameless IGRS (mean 55.1 months for patients who failed SRS and mean 38.0 months for those who did not). This difference likely reflects that patients who attained pain relief stopped seeking care while those with pain persistently sought help to find relief. This lengthy monitoring period permitted us to evaluate the patient’s response to the frameless IGRS and offer additional surgical or SRS options if the patients did not adequately benefit from the initial treatment. Our study also shows that the time to treatment failure was marginally shorter for the patients who did not have a prior intervention. This finding is consistent with naive nerve tissue having a higher radioresistance than previously manipulated nerve. Our study adds to the flourishing literature about the importance of frameless IGRS using the LINAC for patients with medically resistant TN and highlights the need for prospective studies that assess this modality of treatment. The limitation of the present study is its retrospective nature.
CONCLUSION
Our study reported 116 patients diagnosed with medically refractory TN who underwent frameless IGRS using a LINAC over 10 years. The benefits and limitations of various modalities of SRS, as well as percutaneous procedures for TN before frameless IGRS, were presented. The challenges of treating patients with concurrent multiple sclerosis and TN, as well as the importance of distinguishing between type 1 and type 2 TN, were also discussed. In this large cohort of patients with medically refractory TN, frameless IGRS resulted in durable pain control in the majority of patients without any toxicity. While frameless IGRS delivers precise radiation therapy in a fast and effective approach and is valuable for patients who are not appropriate surgical candidates, it is also associated with high recurrence rates.
Ethical approval
The research/study was approved by the University of Louisville Institutional Review Board, number 07.0070, dated January 09, 2021.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Disclaimer
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
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