Optimizing Adjuvant Stereotactic Radiotherapy of Motor-Eloquent Brain Metastases: Sparing the nTMS-Defined Motor Cortex and the Hippocampus

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.

Automatic Radiotherapy Planning for Glioblastoma Radiotherapy With Sparing of the Hippocampus and nTMS-Defined Motor Cortex

“…Focusing on the nTMS-defined motor cortex, Tokarev et al (25) could reduce the maximum dose by up to 17% (average 6%) and the >12 Gy-volume by 2-78% (average 35.2%) in eight patients planned using GammaKnife. For linearaccelerator-based treatment of brain metastases, Schwendner et al (22) reported a mean dose reduction to the nTMS-based motor cortex of 18% for a collective of 30 patients planned with VMAT, which corresponded to our own results for patients with metastases treated with IMRT, non-coplanar arcs, or static beams [sparing of about 30% in mean dose, but depending on planning technique and distance between the lesion and the motor cortex, (26)].…”

“…Beyond sparing the nTMS-defined motor cortex, we emphasize the importance of maintaining hippocampus sparing. In a previous study for brain metastases, we could show that the inclusion of motor cortex objectives in treatment planning without additional hippocampus objectives may even increase hippocampus dose (26). Hence, we here assess the possibility of the combined motor cortex and hippocampus optimization in radiotherapy treatment of glioblastoma (GBM).…”

“…Consequently, a number of studies have included the motor cortex as a radiosensitive organ in radiotherapy treatment planning (20)(21)(22)(23)(24)(25)(26). All these studies have employed navigated transcranial magnetic stimulation (nTMS) as a reliable technique to non-invasively define the motor cortex, which has proven useful in pre-surgical mapping (27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Stereotactic body radiation therapy in brain metastases in the elderly population

“…Many sites require dose control during irradiation. The brainstem, hippocampus, temporal lobe, optic nerve and auditory nerve are common sites where long-term clinical damage can occur due to radiation therapy [24]. Physician-controlled doses to organs in the brain are generally as low as possible.…”

Measuring out-of-field dose to the hippocampus in common radiotherapy indications

“…Repeated exposures with doses of 100 mGy (0.1 Gy) have been shown to compromise the structural and functional integrity of hippocampal neurogenesis which has been associated with neurocognitive dysfunctions that affect learning and memory [4][5][6][7]. Numerous clinical studies have aimed to reduce the hippocampus dose in brain radiotherapy by hippocampus-avoiding dose distributions [8][9][10][11][12].…”