Dosimetric Comparison between CyberKnife and HyperArc Treatment Plans for Trigeminal Neuralgia: Cone-Based Robotic System versus High- Definition MLC-Based Linac System

doi:10.21203/rs.3.rs-3197443/v1

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Research Article

Dosimetric Comparison between CyberKnife and HyperArc Treatment Plans for Trigeminal Neuralgia: Cone-Based Robotic System versus High- Definition MLC-Based Linac System

https://doi.org/10.21203/rs.3.rs-3197443/v1

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Background

This study evaluates the feasibility of HyperArc (HA) for trigeminal neuralgia (TN) by comparing dose distribution with CyberKnife (CK).

Methods

Contour sets from twenty patients who had undergone CK for TN were used to generate HA treatment plans for comparison. Two different TN target delineation settings were used: the whole segment of the trigeminal nerve root entry zone (REZ) group and the 5-mm spherical target group. The prescribed dose was 65 Gy in a single fraction, prescribed to the 80% isodose line. The CK and HA treatment plans were compared for target coverage, sparing of organs at risk (OARs), and dose distribution metrics.

Results

In the whole segment of the REZ group, the HA plans showed statistically significant differences with higher target coverage than the CK plans. The mean brain doses for HA and CK were 0.83 Gy and 1.15 Gy, respectively (P < 0.001). The brain V12 was significantly smaller for HA plans (5.9 cm³) than CK plans (6.9 cm³). Significant achievement in the doses of the ipsilateral/contralateral cranial nerve (CN) VII/VIII were observed in the HA plans than the CK plans. The conformity index was significantly greater in the HA plans compared to the CK plans. The dose gradient radius was similar for the CK and HA plans. In the 5mm-spherical target group, both plans showed good target coverage, with the CK plans exhibiting better brain sparing and higher CN VII/VIII dose. The dose distribution metrics were similar for both plans.

Conclusions

The HA technique is a feasible alternative for TN treatment, offering excellent organ-at-risk sparing and favorable dosimetric distribution.

Trigeminal neuralgia

Stereotactic radiosurgery (SRS)

CyberKnife

HyperArc

dosimetric comparison

Trigeminal neuralgia (TN) is a disorder characterized by recurrent unilateral brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve, and triggered by innocuous stimuli[1] that causes a significant impact on quality of life. It remains the most common neuralgia but with a low global incidence of 4–5 cases per 100,000 persons[2]. The leading pathophysiological hypothesis specific to idiopathic TN describes the demyelination of trigeminal sensory fibers within the proximal nerve root[3]. Most patients (80%-90%) present with an overlying blood vessel causing neurovascular compression at the root entry zone (REZ)[4]. This neurovascular conflict may be responsible for demyelination and pain development.

Since the first application of stereotactic radiosurgery (SRS) to treat TN by Dr. Leksell in 1951[5], SRS has been confirmed as an effective and safe treatment option for TN[2, 6]. The primary objective of SRS, irrespective of the SRS techniques employed such as Gamma Knife, linear accelerator (Linac), and CyberKnife (CK), is to precisely target the trigeminal nerve in a single treatment session based on the high-resolution MRI and CT imaging studies. Treatment of TN with Linac is used to be applying arcs with circular-shaped collimators[7]. The previous study[8] reported a Linac-based SRS produced with a fixed tertiary cone collimator equivalent dose fall-off characteristics to Gamma Knife SRS with a large number of arcs. However, studies using multileaf collimator (MLC)-based Linac for TN are limited in the literature[9]. HyperArc (HA, Varian Medical System Inc., Palo Alto, CA, USA) is a novel isocentric-volumetric modulated arc radiotherapy (VMAT) technique explicitly developed for noncoplanar MLC-based stereotactic radiotherapy with automated optimization and delivery[10, 11]. Good dosimetric distribution has made HA an attractive SRS technique for treating benign brain lesions[12]. This study aims to evaluate the feasibility of HA for TN by comparing it with the dose distribution of CyberKnife.

Participant Selection

This dosimetric comparison study included the data sets of the CT, target/normal organ contours, treatment plan metrics of twenty patients who underwent CK treatment for TN between 2018 and 2021. Two different target delineation settings were employed: the first setting involved delineating the whole segment of the trigeminal nerve REZ with a 2-mm distance from the brainstem[13], which was the primary TN delineation used at our institution for CK treatment. The second delineation setting was the 5mm-spherical target[2, 8, 13], which employed a 5-mm brush contouring tool to delineate the TN passing through the prepontine cistern, while maintaining a 2-mm distance from the brainstem[2].

Treatment Plans for the Whole Segment of the Trigeminal Nerve REZ Group

CyberKnife Treatment Plans

For this group, the treatment targeted the whole segment of the trigeminal nerve REZ with a 2-mm sparing from the brainstem[13]. The prescription dose was 65Gy delivered in a single fraction, prescribed to the 80% isodose line with a maximum dose of 81.25Gy in the REZ[13]. The brainstem surface received a maximum dose constraint of 40Gy[14]. All patients were positioned in a supine position and immobilized using a Pre-Molded U-Frame mask. Contrast-enhanced CT cisternography was performed, and high-resolution CT simulation with 0.5-mm contiguous slices was utilized to visualize the segment of the trigeminal nerve in the prepontine cistern. The CK treatment plans were generated using the MultiPlan software (version 2.2.0, Accuray Inc., Sunnyvale, CA, USA) in non-isocentric conformal mode with 6 MV flattening filter-free photon beams. The plans included a balance of homogeneity and conformality using an iterative optimizer. The trigeminal path set with a special source-to-axis distance of 65 cm and the smallest fixed cone size of either 5mm or 7.5 mm diameter were applied to the CK treatment plans[13]. The optimization algorithm used was the Simplex optimization algorithm, and the calculation algorithm utilized the Ray-Tracing algorithm.

HyperArc Treatment Plans

The CT data sets and target/normal organ contours from the twenty enrolled patients were transferred to the Varian Eclipse treatment planning system (Eclipse, version 15.5, Varian Medical System Inc., Palo Alto, CA, USA). A virtual Encompass mask (QFix, Avondale, PA, USA) was added to all HA plans. The treatment plan goal for the HA plans was the same as that for the CK plans, with a prescription dose of 65 Gy covering the whole REZ and a maximal dose of 81.25 Gy. The main constraint was to ensure that the maximum brainstem dose was less than 40 Gy. The HA plans were designed using 6 MV flattening filter-free photon beams and a dose rate of 1400 MU/min from a Varian TrueBeam (Varian Medical System Inc., Palo Alto, CA, USA) equipped with a 120-leaf high-definition multileaf collimator (HD-MLC) with a dynamic beam aperture and a spatial resolution of 2.5 mm at the isocenter. The details of the HA treatment planning were similar to the description provided previously. Four arc fields, three of which were noncoplanar, were automatically arranged: one full or half coplanar arc with a couch rotation of 0° and partial noncoplanar arcs with couch rotations of 315°, 45°, and 90° (or 270°)[15, 16]. The calculation algorithm used was Acuros XB (Varian Medical System Inc., version 15.5.11) with a 1.25 mm dose grid, and the optimization algorithm employed was SRS NTO.

Treatment Plans for the 5mm-Spherical Target Group

Five cases were selected from the twenty enrolled patients; the treatment plans were re-contoured and re-generated using the 5mm-spherical target in both CK and HA treatment plan system to compare the differences in dose distribution. In this group, the prescription dose of 65 Gy in one fraction was prescribed to the 80% isodose line, with the center of the target receiving 125% of the prescription dose (81.25 Gy), while maintaining the brainstem surface dose below 40 Gy. The CK plans utilized the virtual cone for the five 5mm-Spherical Target treatment plans. For the HA plans, a 5mm-spherical dose distribution was used one coplanar arc and three noncoplanar arcs through the HD-MLC. The treatment planning methods for CK and HA were similar to the description provided above.

Plan Evaluation Statistics

The treatment plans for TN in both groups were evaluated by comparing the dosimetric parameters derived from the dose-volume histograms (DVHs) for target coverage and sparing of organs at risk (OARs), as well as the dosimetric parameters recommended by the report of AAPM Task Group 101[17]. The calculation of the conformity index (CI), as previously described by Paddick[18], involved the formula:

$$CI=\frac{{TV}_{{PIV}^{2}}}{TV \times PIV}$$

In the equation, TV_PIV denotes the volume of the target covered by the prescription isodose volume, TV represents the target volume, and PIV corresponds to the prescription isodose volume. A higher CI value indicates a greater level of conformity in the treatment plan, with a CI value of 1 indicating ideal conformity.

The gradient radius, is determined by the disparity between the equivalent sphere radii of the volume enclosing 50% of the prescription isodose curve and the prescription isodose volume.[19] A low gradient radius indicates a limited dose spread outside the lesion and a sharp dose fall-off. The gradient radius was calculated using the formula:

$$Gradient Radius=\sqrt[3]{\frac{3{V}_{50\%}}{4\pi }}-\sqrt[3]{\frac{3{V}_{100\%}}{4\pi }}$$

Statistical Analysis

The dosimetric endpoints of the target volumes, OARs, CIs, gradient radius, and monitor units (MUs) were analyzed using the Wilcoxon signed-rank test (SPSS Statistics, Version 19, IBM, NY, USA). Statistical analyses were conducted as two-tailed tests, and a significance level of P < 0.05 was employed to determine statistical significance.

Patient and Treatment Characteristics

In the whole segment of the REZ group, the mean target volume was 0.19 cm³. The segment of the nerve encompassed by the 80% isodose line had a mean length of 7.2 mm (range 5–12 mm). In the 5 mm-spherical target group, the mean target volume and length were 0.02 cm³ and 5 mm, respectively. Table 1 provides an overview of the geometric characteristics of the patients included in this study cohort.

Table 1

Characteristics of the treatment groups
Objectives	Parameters
The whole segment of the REZ group (n = 20)
Target volume (CTV, mean)	0.19 cm³
Range	0.12–0.3 cm³
Length (mean)	7.2 mm
Range	5–12 mm
Prescription dose (Gy)	65
CyberKnife beam angles (mean)	220
Range	89–344
HyperArc arc numbers	1 coplanar and 3 noncoplanar
The 5mm-spherical target group (n = 5)
Target volume (CTV, mean)	0.02 cm³
Length (mean)	5 mm
Prescription dose (Gy)	65
CyberKnife beam angles (mean)	86
Range	84–92
HyperArc arc numbers	1 coplanar and 3 noncoplanar
Abbreviations: CTV, clinical target volume; REZ, root entry zone

The Whole Segment of the Trigeminal Nerve REZ Group

Target Coverage

The HA plans demonstrated higher target coverage compared to the CK plans, with statistically significant differences (HA plans vs. CK plans, 96.9% vs. 92.2%, P < 0.001).

Sparing of Organs at Risk

We analyzed the volume-dose parameters for OAR sparing. The HA plans consistently achieved better sparing of all other OARs compared to the CK plans, as shown in Table 2. The mean brain doses were 83 cGy for HA plans and 115 cGy for CK plans (P < 0.001). The brain V12 was significantly smaller in the HA plans compared to the CK plans (5.9 cm³ in HA vs. 6.9 cm³ in CK, P = 0.019). Significant differences in the maximal and mean doses of the ipsi-/contralateral cranial nerve (CN) VII/VIII were observed between the HA and CK plans (Table 2). Figure 1 illustrates that the 100% and 50% prescription isodose lines (prescription dose: 65 Gy) were more compact to the target in the HA plan compared to the CK plan.

Table 2

Comparison of dosimetric parameters for CyberKnife and HyperArc for trigeminal neuralgia patients.
Parameters	CyberKnife Mean (SEM)	HyperArc Mean (SEM)	p value
The whole segment of the REZ group
Target coverage (%)	92.2 (1.85)	96.9 (1.04)	< 0.001*
Organs at risk
Brainstem (cGy, Dmax)	3883 (52)	3212 (94)	< 0.001*
Brainstem (cGy, mean)	265 (14)	160 (8)	< 0.001*
Ipsilateral CN VII/VIII (cGy, Dmax)	3791 (409)	2831 (336)	< 0.001*
Ipsilateral CN VII/VIII (cGy, mean)	1603 (179)	1266 (145)	0.005*
Contralateral CN VII/VIII (cGy, Dmax)	235 (33)	44 (5)	< 0.001*
Contralateral CN VII/VIII (cGy, mean)	120 (14)	33 (3)	< 0.001*
Brain (cGy, mean)	115 (8)	83 (4)	< 0.001*
Brain V12 (cm³)	6.9 (0.6)	5.9 (0.5)	0.019*
Dose distribution metrics
Gradient radius (cm)	0.28 (0.01)	0.29 (0.01)	0.984
Conformity index	1.79 (0.29)	1.59 (0.24)	0.004*
Monitor units	43999 (2920)	23204 (671)	0.003
The 5mm-spherical target group
Target coverage (%)	97.9 (0.43)	97.5 (0.68)	0.686
Organs at risk
Brainstem (cGy, Dmax)	1788 (129)	1809 (123)	0.225
Brainstem (cGy, mean)	105 (5)	158 (27)	0.043*
Ipsilateral CN VII/VIII (cGy, Dmax)	1402 (333)	1011(264)	0.043*
Ipsilateral CN VII/VIII (cGy, mean)	498 (99)	516 (97)	0.893
Contralateral CN VII/VIII (cGy, Dmax)	110 (20)	45 (18)	0.043*
Contralateral CN VII/VIII (cGy, mean)	54 (13)	29 (11)	0.043*
Brain (cGy, mean)	42 (1)	42 (3)	0.893
Brain V12 (cm³)	1.0 (0.1)	1.8 (0.2)	0.043*
Dose distribution metrics
Gradient radius (cm)	0.20 (0.01)	0.21 (0.01)	0.276
Conformity index	1.04 (0.01)	1.05 (0.01)	0.588
Monitor units	15950 (224)	16248 (353)	0.063
Abbreviations: REZ, root entry zone; CN, cranial nerve; SEM, standard error of the mean; V12, the volume of brain that receiving more than 12Gy; *, statistically significant, p < 0.05.

Dosimetric Parameters

The HA plans, utilizing the new optimization algorithm (SRS-NTO) to improve dose gradients, resulted in significantly greater CI than the CK plans (HA plans vs. CK plans, 1.59 vs. 1.71, P = 0.004). Furthermore, the HA plans required 47% fewer MUs than the CK plans (HA: 23,204 MU; CK: 43,999 MU).

The 5mm-Spherical Target Group

Target Coverage

The 5 mm trigeminal nerve target was effectively covered by the prescription dose (65 Gy) with the thin deep-blue isodose line (Fig. 2). Both the HA plans and CK plans exhibited good target coverage without statistically significant differences (HA plans vs. CK plans, 97.5% vs. 97.9%, P = 0.686).

Sparing of Organs at Risk

The OAR constraints were met in both the HA and CK treatment plans for the 5 mm-spherical target group. The brainstem doses achieved by the 5 mm-spherical target group plans were consistently lower than those in the whole segment of the REZ group plans, as shown in Table 2. The maximal doses to the brainstem were similar between the CK and HA plans in the 5mm-spherical target group. The mean brain doses generated by the CK plans were significantly lower than those generated by the HA plans (105 cGy in CK vs. 158 cGy in HA, P = 0.043). The brain V12 was significantly smaller in the CK plans compared to the HA plans (1.0 cm³ in CK vs. 1.8 cm³ in HA, P = 0.043). There were no differences in the mean brain dose between the CK and HA plans. The maximal and mean doses for the contralateral CN VII/VIII were significantly lower in the HA plans compared to the CK plans. For the ipsilateral CN VII/VIII, the HA plans had a significantly lower maximal dose than the CK plans (Dmax: 1011 cGy in HA vs. 1402 cGy in CK, P = 0.043). Figure 2 illustrates that the 100% and 50% prescription isodose lines (prescription dose: 81.25 Gy) were more closely aligned with the target in the CK plan, especially in the axial and coronal views.

Dosimetric Parameters

The HA plans exhibited similar CI compared to the CK plans (HA vs. CK, 1.05 vs. 1.04, P = 0.588). The HA plans resulted in a similar dose gradient radius as the CK plans (HA: 0.21 vs. CK: 0.20, P = 0.276) (Fig. 2 and Table 2). Moreover, the HA plans and CK plans had similar numbers of MUs (HA: 16,249 MU; CK: 15,950 MU).

TN presents significant challenges for neurosurgeons and radiation oncologists when determining the optimal treatment approach. Traditional SRS involves directing a focused beam to the trigeminal nerve at the REZ near the brainstem, as initially proposed by Leksell[5]. However, treatment strategies have evolved over time, leading to the identification of more optimal approaches.

Recent studies have suggested that targeting the intracisternal portion of the trigeminal nerve can achieve lower complication rates while maintaining efficacy[2]. The choice between an anterior or posterior target has been explored, revealing similar initial efficacy but lower complication rates with an anterior target. Complications such as dry eye syndrome, bothersome hypesthesias, and numbness are less prevalent with an anterior target[2, 20, 21]. Moreover, an anterior target provides higher rates of pain relief and fewer instances of hypesthesia during long-term follow-up[2, 20, 21]. It is important to note that increasing the treatment volume or length for TN SRS does not significantly enhance pain relief but may increase complications[22].

Based on current evidence, it is recommended to limit the treatment to a 6-mm length of the trigeminal nerve[13]. The minimum effective dose for SRS should be at least 70 Gy, with a maximally effective dose of 90 Gy. Doses above 90 Gy show similar efficacy rates but are associated with a higher frequency of complications[23]. To minimize the risk of complications, critical organ sparing is typically achieved by ensuring that an isodose line between 20% and 50% of the prescription touches the brainstem[14].

Several treatment techniques are available for TN SRS. For instance, GammaKnife utilizes stereotactic head frame immobilization and delivers radiation from various angles using stationary radioactive Cobalt-60 gamma-emitting sources[24, 25]. On the other hand, CK treatment involves immobilization with a facial mask and delivers radiation using a 6-MV beam from a Linac mounted on a robotic arm[13]. Linac-based SRS can be delivered using cone-based and MLC-based platforms, with target localization achieved through the fusion of MR and CT images[8, 26–31].

However, few studies have been reported using high-definition MLC-based Linacs for TN treatment. The advancement in software and hardware of the MLC-based SRS system has made this alternative approach possible[32]. The combination of the VMAT technique and the new generation of high-definition MLCs (2.5-mm leaf width) fulfills the demands of SRS dose delivery for small targets within the brain[16]. In this study, we elucidated the dosimetric distribution of the novel SRS technique, HA, for TN. The results demonstrated that HA plans showed significantly better sparing of OARs and CI compared to cone-based CK plans in the whole segment of the REZ treatment. In the 5-mm spherical treatment group, cone-based CK showed slightly better mean brainstem dose and Brain V12 compared to HA, but the differences were minor. Moreover, both HA and CK showed significantly reduced doses to the brainstem and other OARs when using the 5-mm spherical target. Overall, HA demonstrated efficient delivery, rapid dose falloff, and high-quality treatment plans with coplanar and up to 3 noncoplanar arcs. Additionally, the automated HA treatment plan delivery in the SRS workflow increased physicians' confidence in managing small target lesions[12].

It is essential to acknowledge the limitations of this study, which focused on comparing two specific treatment techniques: HA and cone-based CK. The findings may not be directly generalizable to all available treatment options, highlighting the need to consider other treatment modalities and evaluate their comparative effectiveness and potential benefits. Future research should encompass a broader range of SRS techniques to provide a more comprehensive understanding of their relative merits.

Another important limitation of this study is the lack of assessment of delivery accuracy for the SRS techniques. Accurate and precise delivery of radiation is crucial for achieving optimal treatment outcomes while minimizing complications. Factors such as immobilization devices, imaging techniques for target localization, and overall treatment workflow can influence delivery accuracy. Therefore, assessing and comparing delivery accuracy among different SRS techniques would provide valuable insights into their clinical efficacy.

Ensuring delivery accuracy at Linac may necessitate the adjustment of the planning target volume (PTV) margin to accommodate potential errors during delivery and patient setup. Notably, the HA plans in this study did not modify the contours of the targets and OARs. The cone-based CK G4 system currently achieves submillimeter accuracy and precision, with an accuracy of less than 1 mm[33]. The total uncertainty of the Gamma Knife Icon workflow has been reported to be 1.3 mm[25]. Modern Linacs, such as the TrueBeam system, have improved technology and can achieve an overall couch/gantry/collimator isocentric accuracy within the range of 0.6–0.75 mm[9, 34]. Additionally, cone-beam CT guidance can further enhance accuracy for small intracranial targets[35]. Given the similar submillimeter accuracy of TrueBeam and CK, the corresponding PTV margin does not appear to be a major concern in terms of delivery accuracy or dose distribution. These findings suggest the importance of avoiding enlarged treatment areas, whether intentionally introduced or resulting from delivery errors. Maintaining a high degree of accuracy is crucial when delivering SRS treatments for TN using any treatment modality[8]. Furthermore, achieving the treatment criteria established by current guidelines may lead to similar clinical outcomes regardless of the specific SRS technique used.

Moreover, it is important to acknowledge that this study solely focused on the dosimetric aspects of the treatment techniques and did not evaluate clinical outcomes or the overall quality of life experienced by patients. To gain a comprehensive understanding of the efficacy and potential side effects of different SRS techniques for TN, future research should include larger sample sizes, longer follow-up periods, and assessments of patient-reported outcomes and quality of life measures.

This dosimetric comparison study provides valuable insights into the potential benefits of HA as a promising SRS technique for treating TN. HA demonstrated excellent sparing of OARs, good dosimetric distribution, and efficient delivery. However, it is crucial to acknowledge the limitations of this study, including its focus on specific treatment techniques, small sample size, and the absence of clinical outcomes assessment. Future research should expand the scope of investigation, consider larger sample sizes, evaluate clinical outcomes, and address delivery accuracy to provide a more comprehensive understanding of the comparative effectiveness of different SRS techniques for TN.

HyperArc, HA

Trigeminal neuralgia, TN

CyberKnife, CK

Root entry zone, REZ

Organs at risk, OARs

Cranial nerve, CN

Stereotactic radiosurgery, SRS

Linear accelerator, Linac

Multileaf collimator, MLC

Volumetric modulated arc radiotherapy, VMAT

High-definition multileaf collimator, HD-MLC

Dose volume histogram, DVH

Conformity index, CI

Monitor units, MUs

Planning target volume, PTV

Ethics Approval and Consent to participate

This study was approved by the Institutional Review Board at Chi Mei Medical Center (No.11105-013). The institutional review board waived the need for written informed consent from the participants because this was a retrospective electric treatment plan-review study.

Consent for publication

All authors have carefully reviewed and approved the final version of the manuscript.

Availability of data and material

Not applicable.

Competing interests

None of the authors of this manuscript have conflicts of interest, except the corresponding author (YW Lin) has received Speaker honorarium from Varian Medical Systems, and the first co-author (CC Yang) who is the principal investigator for a clinical HyperArc study for recurrent nasopharyngeal cancer, granted by Varian Medical System.

Funding

No funding was received for this study.

Authors' contributions

Study concepts/design: CC Yang, HW Ho, YW Lin

Data acquisition: HW Ho, HM Lin, HY Chen, WC Ting, YW Lin

Quality control of data and algorithms: HM Lin, HY Chen, CC Yang, SC Wang

Data analysis and interpretation: HW Ho, HM Lin, WC Ting, HY Chen, YW Lin

Statistical analysis: HM Lin, SC Wang

Manuscript preparation: HM Lin, CC Yang, WC Ting, SC Wang

Manuscript editing/review: CC Yang, HW Ho, YW Lin

Acknowledgments

Part of this manuscript was presented at the 64th Annual Meeting of the American Society for Radiation Oncology, San Antonio, October 2022.

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No competing interests reported.

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Dosimetric Comparison between CyberKnife and HyperArc Treatment Plans for Trigeminal Neuralgia: Cone-Based Robotic System versus High- Definition MLC-Based Linac System

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Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Participant Selection

Treatment Plans for the Whole Segment of the Trigeminal Nerve REZ Group

CyberKnife Treatment Plans

HyperArc Treatment Plans

Treatment Plans for the 5mm-Spherical Target Group

Plan Evaluation Statistics

Statistical Analysis

Results

Patient and Treatment Characteristics

The Whole Segment of the Trigeminal Nerve REZ Group

Target Coverage

Sparing of Organs at Risk

Dosimetric Parameters

The 5mm-Spherical Target Group

Target Coverage

Sparing of Organs at Risk

Dosimetric Parameters

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

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