Radiotherapy/ Radiosurgery

Abstract: 
Background
Management of high-grade gliomas (HGGs) close to motor areas is challenging due to the risk of treatment-related morbidity. Thus, for resection, functional mapping of the corticospinal tract (CST) with navigated transcranial magnetic stimulation (nTMS) combined with diffusion tensor imaging (DTI)-based fiber tracking (nTMS-DTI-FT) is increasingly used. This study investigated the application of nTMS-DTI-FT in adjuvant radiation therapy (RT) planning of HGGs for CST avoidance.
Methods
The preoperative nTMS-DTI-FT based CST of 35 patients harboring HGGs were incorporated into the RT planning system and merged with planning imaging. The CST was delineated as PRV-FTTMS. Intensity-modulated RT (IMRT) plans were optimized to preserve PRV-FTTMS. Segments within the planning target volume (PTV) were not spared (overlap).
Results
With plan optimization, mean dose (Dmean) of PRV-FTTMS can be reduced by 17.1% on average (range 0.1 – 37.9%), thus from 25.5 Gy to 21.2 Gy (p<0.001 For PRV-FTTMS segments beyond the PTV dose, reduction is possible by 26.8% (range 0.1 – 43.9%, Dmean 17.4 Gy vs. 12.5 Gy, p<0.001 Considering only portions within the 50% isodose level, Dmean is decreased by 46.7% from 38.6 Gy to 20.5 Gy (range 19.1 – 62.8%, p<0.001. PTV coverage was not affected: V95% and V90% were 96.4 ± 3.1% and 98.0 ± 3.9% vs. 96.1 ± 3.5% (p=0.34) and 98.3 ± 2.9% (p=0.58). Dose constraints for organs at risk (OARs) were all met.
Conclusion
This study demonstrates that nTMS-DTI-FT can be utilized in the RT planning of HGGs for CST sparing. However, the degree of dose reduction depends on the overlap with the PTV. The functional benefit needs to be investigated in future prospective clinical trials.

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Abstract: Brain metastases can effectively be treated with surgical resection and adjuvant stereotactic radiotherapy (SRT). Navigated transcranial magnetic stimulation (nTMS) has been used to non-invasively map the motor cortex prior to surgery of motor eloquent brain lesions. To date, few studies have reported the integration of such motor maps into radiotherapy planning. The hippocampus has been identified as an additional critical structure of radiation-induced deficits. The aim of this study is to assess the feasibility of selective dose reduction to both the nTMS-based motor cortex and the hippocampi in SRT of motor-eloquent brain metastases. Patients with motor-eloquent brain metastases undergoing surgical resection and adjuvant SRT between 07/2014 and 12/2018 were retrospectively analyzed. The radiotherapy treatment plans were retrieved from the treatment planning system ("original" plan). For each case, two intensity-modulated treatment plans were created: the "motor" plan aimed to reduce the dose to the motor cortex, the "motor & hipp" plan additionally reduce the dose to the hippocampus. The optimized plans were compared with the "original" plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR). 69 plans were analyzed, all of which were clinically acceptable with no significant differences for PTV coverage. All OAR were protected according to standard protocols. Sparing of the nTMS motor map was feasible: mean dose 9.66 ± 5.97 Gy (original) to 6.32 ± 3.60 Gy (motor) and 6.49 ± 3.78 Gy (motor & hipp), p<0.001. In the "motor & hipp" plan, dose to the ipsilateral hippocampi could be significantly reduced (max 1.78 ± 1.44 Gy vs 2.49 ± 1.87 Gy in "original", p = 0.003; mean 1.01 ± 0.92 Gy vs. 1.32 ± 1.07 Gy in "original", p = 0.007). The study confirms the results from previous studies that inclusion of nTMS motor information into radiotherapy treatment planning is possible with a relatively straightforward workflow and can achieve reduced doses to the nTMS-defined motor area without compromising PTV coverage. Furthermore, we demonstrate the feasibility of selective dose reduction to the hippocampus at the same time. The clinical significance of these optimized plans yet remains to be determined. However, with no apparent disadvantages these optimized plans call for further and broader exploration.

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Background:

The aim of the study was to demonstrate the feasibility of integrating navigated transcranial magnetic stimulation (nTMS) in preoperative gamma knife radiosurgery (GKRS) planning of motor eloquent brain tumors.

Case Description:

The first case was a 53-year-old female patient with metastatic breast cancer who developed focal epileptic seizures and weakness of the left hand. The magnetic resonance imaging (MRI) scan demonstrated a 30 mm metastasis neighboring the right precentral gyrus and central sulcus. The lesion was treated with adaptive hypofractionated GKRS following preoperative nTMS-based motor mapping. Subsequent follow-up imaging (up to 12 months) revealed next to complete tumor ablation without toxicity. The second case involved a previously healthy 73-year-old male who similarly developed new left-handed weakness. A subsequent MRI demonstrated a 26 mm metastatic lesion, located in the right postcentral gyrus and 5 mm from the hand motor area. The extracranial screening revealed a likely primary lung adenocarcinoma. The patient underwent preoperative nTMS motor mapping prior to treatment. Perilesional edema was noted 6 months postradiosurgery; nevertheless, long- term tumor control was demonstrated. Both patients experienced motor function normalization shortly after treatment, continuing to final follow-up.

Conclusion:

Integrating preoperative nTMS motor mapping in treatment planning allowed us to reduce dose distributions to perilesional motor fibers while achieving salvage of motor function, lasting seizure freedom, and tumor control. These initial data along with our review of the available literature suggest that nTMS can be of significant assistance in brain radiosurgery. Prospective studies including larger number of patients are still warranted.

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Purpose: Navigated transcranial magnetic stimulation (nTMS) provides noninvasive visualization of eloquent brain areas. The nTMS is usually applied in presurgical planning to minimize the risk of surgery-related neurological deterioration. The aim of this study was to evaluate the usefulness of nTMS data for GammaKnife treatment planning for patients suffering from brain metastases. Methods: Motor cortex mapping with nTMS was performed in eight patients with brain metastases within or adjacent to the precentral gyrus. The nTMS data set was imported into the planning software and fused with anatomical MRI. Then contouring of the target and critical structures was performed. Treatment plans with and without visualization of the functional structures by nTMS were analyzed and compared by neurosurgeon and medical physicist.

Results: The primary motor cortex was successfully delineated even in all cases despite significant peritumoral edema. Beam shaping and combined isocenters were used for conformal dose distribution and steeper dose fall-off near the identified eloquent zone. Compared with plans without nTMS data, treatment plans with integration of cortical nTMS mapping data showed a 2% to 78% (mean, 35.2% ± 22.7%) lower 12-Gy volume within the motor cortex without reduction of the dose applied to the tumor.

Conclusions: The presented approach allows the easy and reliable integration of neurophysiological mapping data into GammaKnife treatment plans by the standard GammaPlan software. Diminishing the dose to critical structures might help to minimize side effects and therefore improve quality of life for brain metastasis patients.

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BACKGROUND:

Navigated transcranial magnetic stimulation (nTMS) is applied in neurosurgical routine to detect motor-eloquent brain areas for safe resection of high-grade gliomas (HGGs). However, in radiation therapy (RT) planning, the primary motor cortex is not respected yet in target volume delineation. This study evaluates the implementation of nTMS motor mapping in RT planning in patients harboring motor-eloquent HGGs with the aim of reducing dose applications to the motor cortex.

METHODS:

nTMS motor maps of 30 patients diagnosed with motor-eloquent HGGs were fused with RT planning imaging and volumetric modulated RT plans were optimized using nTMS motor maps as an organ at risk (OAR). Doses to nTMS motor maps were evaluated using dose-volume histogram (DVH) parameters.
RESULTS:

Mean dose (Dmean) to the nTMS motor maps was 42.3 Gy (3.7-61.1 Gy) and was significantly reduced by 14.3% to 37.0 Gy (3.6-55.8 Gy, p < 0.05) when constraining the dose to nTMS motor areas to 45 Gy. Areas within the planning target volume (PTV) were not spared (overlap). Yet, the dose to PTV was not compromised. Even with an additional dose escalation (70 Gy) to the tumor area, nTMS motor maps can be spared by 4.6 ± 3.5 Gy (12.8%, p < 0.05).

CONCLUSIONS:

nTMS motor maps can be easily implemented in standard RT planning and applied for target contouring in RT of HGGs. Doses to motor-eloquent areas can be significantly reduced when considering nTMS motor maps without affecting treatment doses to the PTV. Thus, nTMS could be used as a valuable tool in RT planning.

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(Level of Evidence III)

Purpose: In radiotherapy (RT) of brain tumors, the primary motor cortex is not regularly considered in target volume delineation, although decline in motor function is possible due to radiation. Non-invasive identification of motor-eloquent brain areas is currently mostly restricted to functional magnetic resonance imaging (fMRI), which has shown to lack precision for this purpose.

Navigated transcranial magnetic stimulation (nTMS) is a novel tool to identify motor-eloquent brain areas. This study aims to integrate nTMS motor maps in RT planning and evaluates the influence on dosage modulations in patients harboring brain metastases. Materials and Methods: Preoperative nTMS motor maps of 30 patients diagnosed with motor-eloquent brain metastases were fused with conventional planning imaging and transferred to the RT planning software. RT plans of eleven patients were optimized by contouring nTMS motor maps as organs at risk (OARs). Dose modulation analyses were performed using dose-volume histogram (DVH) parameters. Results: By constraining the dose applied to the nTMS motor maps outside the planning target volume (PTV) to 15 Gy, the mean dose (Dmean) to the nTMS motor maps was significantly reduced by 18.1% from 23.0 Gy (16.9-30.4 Gy) to 18.9 Gy (13.5-28.8 Gy, p < 0.05). The Dmean of the PTV increased by 0.6 ± 0.3 Gy (1.7%).

Conclusion: Implementing nTMS motor maps in standard RT planning is feasible in patients suffering from intracranial metastases. A significant reduction of the dose applied to the nTMS motor maps can be achieved without impairing treatment doses to the PTV. Thus, nTMS might provide a valuable tool for safer application of RT in patients harboring motor-eloquent brain metastases.

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BACKGROUND:

Radiosurgical treatment of brain lesions near motor or language eloquent areas requires careful planning to achieve the optimal balance between effective dose prescription and preservation of function. Navigated brain stimulation (NBS) is the only non-invasive modality that allows the identification of functionally essential areas by electrical stimulation or inhibition of cortical neurons analogous to the gold-standard of intraoperative electrical mapping.

OBJECTIVE:

To evaluate the feasibility of NBS data integration into the radiosurgical environment, and to analyze the influence of NBS data on the radiosurgical treatment planning for lesions near or within motor or language eloquent areas of the brain.

METHODS:

Eleven consecutive patients with brain lesions in presumed motor or language eloquent locations eligible for radiosurgical treatment were mapped with NBS. The radiosurgical team prospectively analyzed the data transfer and classified the influence of the functional NBS information on the radiosurgical treatment planning using a standardized questionnaire.

RESULTS:

The semi-automatized data transfer to the radiosurgical planning workstation was flawless in all cases. The NBS data influenced the radiosurgical treatment planning procedure as follows: improved risk-benefit balancing in all cases, target contouring in 0 %, dose plan modification in 81.9 %, reduction of radiation dosage in 72.7 % and treatment indication in 63.7 % of the cases.

CONCLUSIONS:

NBS data integration into radiosurgical treatment planning is feasible. By mapping the spatial relationship between the lesion and functionally essential areas, NBS has the potential to improve radiosurgical planning safety for eloquently located lesions.

(Level of Evidence IIa)

OBJECT:

The integration of state-of-the-art neuroimaging into treatment planning may increase the therapeutic potential of stereotactic radiosurgery. Functional neuroimaging, including functional MRI, navigated brain stimulation, and diffusion tensor imaging-based tractography, may guide the orientation of radiation beams to decrease the dose to critical cortical and subcortical areas. The authors describe their method of integrating functional neuroimaging technology into radiosurgical treatment planning using the CyberKnife radiosurgery system.

METHODS:

The records of all patients who had undergone radiosurgery for brain lesions at the CyberKnife Center of the University of Messina, Italy, between July 2010 and July 2012 were analyzed. Among patients with brain lesions in critical areas, treatment planning with the integration of functional neuroimaging was performed in 25 patients. Morphological and functional imaging data sets were coregistered using the Multiplan dedicated treatment planning system. Treatment planning was initially based on morphological data; radiation dose distribution was then corrected in relation to the functionally relevant cortical and subcortical areas. The change in radiation dose distribution was then calculated.

RESULTS:

The data sets could be easily and reliably integrated into the Cyberknife treatment planning. Using an inverse planning algorithm, the authors achieved an average 17% reduction in the radiation dose to functional areas. Further gain in terms of dose sparing compromised other important treatment parameters, including target coverage, conformality index, and number of monitor units. No neurological deficit due to radiation was recorded at the short-term follow-up.

CONCLUSIONS:

Radiosurgery treatments rely on the quality of neuroimaging. The integration of functional data allows a reduction in radiation doses to functional organs at risk, including critical cortical areas, subcortical tracts, and vascular structures. The relative simplicity of integrating functional neuroimaging into radiosurgery warrants further research to implement, standardize, and identify the limits of this procedure.