Surgical treatments for tremors.

Stereotactic surgery is an increasingly popular option for disabling tremors whenever it is insufficiently improved by drug treatment. Surgical approaches are expanding. Thalamic deep brain stimulation is one of the most efficacious treatments. Its recent technological advances with adaptive stimulation and new electrodes configuration will allow a more physiological stimulation. However, a reappraisal of less invasive, new lesioning procedures is underway. Gamma Knife thalamotomy and magnetic resonance-guided focused ultrasounds encounter very few contraindications. Recent studies reported their efficacy on tremor control and safety profile. Besides the ventralis intermedius nucleus of the thalamus, alternative targets are also emerging. The effectiveness of surgical therapies on essential tremor and Parkinson's disease tremor is well established. For more uncommon tremors, preliminary studies are encouraging. All these surgical therapies can be proposed as treatment option for medically refractory tremors.

[Frameless trigeminal neuralgia radiosurgery with a dedicated linear accelerator: From equipment commissioning to initial clinical results]. / Radiochirurgie des névralgies trigéminales avec accélérateur linéaire dédié sans cadre invasif : de la mise en service de l'appareil aux premiers résultats cliniques.

PURPOSE: Radiosurgery for the treatment of trigeminal neuralgia delivers a very high dose in a single fraction, over a few millimeters, at a single isocenter placed along the nerve. We present here the different steps that have been performed to validate small beams by conical collimators, and report the clinical results of the first patients treated on Novalis Tx®, frameless. MATERIAL AND METHODS: First, the geometric accuracy of 4 and 6mm conical collimators was evaluated using Winston-Lutz tests; then dosimetric data acquisition was performed using high spatial resolution detectors (PTW 60019 microdiamond and a PTW 60017 E-diode). The corrective factors of the TRS 483 report were applied to calculate the collimator aperture factors. These dosimetric data were then compared with the data implemented in the iPlan® treatment planning system. Then end-to-end tests were performed to control the entire treatment process using an anthropomorphic phantom "STEEV". Between 2020 and 2022, 18 patients were treated for refractory trigeminal neuralgia on Novalis Tx®, frameless, with Exactrac® repositioning. A total of 17 patients were evaluated (one was lost to follow-up) using the BNI score for pain assessment and MRI with a median follow-up of 12 months. RESULTS: The quality criteria of geometric and dosimetric accuracy were met for the 6-mm cone but not for the 4-mm cone. All patients were treated with a 6-mm cone with a dose of 90Gy prescribed at the isocenter at the root entry zone. Initial pain control was obtained in 70.5% of our patients, and 53% maintained pain control with a median follow-up of 12 months. All recurrences occurred within 3 to 6 months after radiosurgery. No brainstem toxicity was observed. Six patients had non-disabling facial hypoesthesia, half of whom already had pretreatment hypoesthesia. CONCLUSION: The treatment of trigeminal neuralgia on a dedicated linear accelerator is a highly technical treatment whose accuracy and safety are paramount. The physical measurements allowed the commissioning of the technique with a 6mm cone. Our first clinical results are in accordance with the literature.

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases.

PURPOSE: Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery. PATIENTS AND METHODS: From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3. RESULTS: The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05). CONCLUSION: A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.

Third whole-brain radiation therapy for multiple brain metastases. Should it be considered in selected patients?

Whole brain reirradiation for the treatment of multiple brain metastases has shown promising results. However, concerns remain over the possible neurotoxic effects of the cumulative dose as well as the questionable radiosensitivity of recurrent metastases. A second reirradiation of the whole brain is ordinarily performed in our department for palliative purposes in patients presenting with multiple metastatic brain progression. For this study, an investigational third whole brain reirradiation has been administered to highly selected patients to obtain disease control and delay progression. Clinical outcomes and neurological toxicity were also evaluated.

[Stereotactic radiotherapy of non-tumoral brain pathologies: Arteriovenous malformations and trigeminal neuralgias]. / Radiothérapie stéréotaxique des affections cérébrales non tumorales : malformations artérioveineuses et névralgies trigéminales.

Stereotactic radiotherapy and radiosurgery allow delivery of high irradiation doses in a limited volume. These techniques are specially adapted to brain and nervous pathologies. Indication are not only cancers and tumors but also non tumor tissues such as arteriovenous malformations. In some case purpose of stereotactic radiotherapy is solely functional, for example for trigeminal neuralgia. We detail the questions that raise treatment of these non-tumor pathologies. These pathologies imply a multidisciplinary approach that associate radiation oncologists, neuro-radiologist and neurosurgeons.

[Trigeminal Neuralgia - What Do We Know about the Causes, Diagnosis and Treatment?] / Trigeminusneuralgie ­ was wissen wir über die Ursachen, Diagnostik und Therapie?

Trigeminal Neuralgia - What Do We Know about the Causes, Diagnosis and Treatment? Abstract. Classical trigeminal neuralgia is typically characterized by a stimulus-evoked, recurrent and intense short-lasting stabbing pain in the innervation area of the trigeminal nerve. Its intensity is among the most severe pain imaginable in humans, and yet it is often misdiagnosed and undertreated. Triggers are common activities of daily life like talking or eating. The classical trigeminal neuralgia is due to a neurovascular compression at the nerve root entry zone. The secondary form is related to an underlying neurological disease (caused for example by multiple sclerosis or compression by a brain tumor); the etiology of the idiopathic trigeminal neuralgia is unknown. Treatment options include both medication (mostly antiepileptic drugs) and escalated interventional approaches (microvascular decompression, neurolesional percutaneous procedures, neuromodulative therapeutic options and radiosurgery).

[Role of tractography in stereotactic radiosurgery and brain stereotactic radiotherapy]. / Intérêt de la tractographie pour la radiochirurgie et la radiothérapie stéréotaxique cérébrale.

Hypofractionated stereotactic radiotherapy and stereotactic radiosurgery are major therapeutic weapons in the brain, whether for tumor, vascular or functional treatments. They tend increasingly to democratize and to become standard treatments. However, human brain anatomy is very complex and not limited to the currently described organs at risk. Diffusion tensor imaging (DTI) tractography is a simple tool that enables to identify reproducibly big white matter fiber tracts. Not only does tractography allow a redefinition of organs at risk in the brain, but it would also allow the identification of new targets, such as the ventral intermediate nucleus (Vim) within the thalamus for treatment of movement disorders. We present here a review of the role of tractography and the anatomy, function and currently described dose-effect relationships of white matter fiber tracts with a major functional impact: the pyramidal tract for motor ability, the optic radiation for vision and the arcuate fasciculus for language.

Ablative radiosurgery for cardiac arrhythmias - A systematic review.

Stereotactic body radiotherapy (SBRT) is a high precision technique that is commonly used for malignant lesions in lung, liver, pancreas and spine. Recent reports suggest promise in use of SBRT as a tool in atrial and ventricular cardiac arrhythmias. The present systematic review deals with the use of SBRT technology for this novel indication. A PubMed search was done for articles published between 1990 and 2020. All original articles, case reports, case series of treated patients were included in the analyses. Out of the 55 articles in PubMed search, our search found 1 phase I/II clinical case series, 3 clinical case reports, 3 animal studies and 4 dosimetric studies related to cardiac SBRT for arrythmias. All studies used a uniform cardiac dose of 25Gy. The available preclinical, dosimetric and clinical studies have suggested that SBRT for cardiac arrhythmias could become a potential alternative in suitable patients. Cardiac and radiation oncology community await further data and experience in this modality, including safety and outcomes.

Efficacy and safety of hypofractionated stereotactic radiotherapy for brain metastases using three fractions: A single-centre retrospective study.

PURPOSE: Hypofractionated stereotactic radiotherapy (HFSRT) has become a standard of care for patients with a limited number of brain metastases (BM). An increasing number of linear accelerators (LA) are able to accurately perform HFSRT including VersaHD® (Elekta®) LA. The main aim of this study was to report clinical outcomes of BM treated by HFSRT using 3×7.7Gy on 70% isodose line in terms of local control (LC). PATIENTS AND METHODS: Between November 2016 and October 2018, all patients suffering from histologically-proven primary with one or several newly diagnosed BM treated by HFSRT were retrospectively included and evaluated. Patients who had received prior treatment by neurosurgery or cerebral radiotherapy were excluded. RESULTS: Among 44 patients, 61 BM were treated. With a median follow-up of 31.9 months, LC rates at 6 and 12 months were 93.2% and 90.9, respectively. Single-BM was independently predictive of LC (P=0.025) and overall survival (P=0.013). Acute toxicity rates were acceptable: 65.9% of patients had grade 1 and 2 and no acute grade 3 toxicity according to the NCI-CTCAE (version 5.0). Regarding delayed toxicity, one case (2.3%) of radionecrosis was confirmed by magnetic resonance spectroscopy. CONCLUSION: In our single-centre retrospective analysis, BM treatment by HFSRT delivered in three fractions showed a 12-month LC rate of 90.9% without major toxicities, which suggests safety and efficiency of this technique. However, longer-term follow-up and prospective studies are still needed to confirm these results.

Radiosurgery and stereotactic irradiation of multiple and contiguous brain metastases: A practical proposal of dose prescription methods and a literature review.

PURPOSE: In literature, there are no guidelines on how to prescribe dose in the case of radiosurgery (SRS) or stereotactic irradiation of multiple and adjacent BM. Aim of this work is to furnish practical proposals of dosimetric methods for multiple neighboring BM, and to make a literature review about the SRS treatment of multiple BM, comparing radiotherapy techniques on the basis of different dosimetric parameters. MATERIALS AND METHODS: A theoretical proposal of dosimetric approaches to prescribe dose in case of multiple contiguous BM is done. A literature review between 2010 and 2020 was performed on MEDLINE and Cochrane databases according to the PRISMA methodology, with the following keywords dose prescription, radiosurgery, multiple BM. Papers not reporting dosimetric solutions to irradiate multiple BM were excluded. RESULTS: Only one article in the literature reports a practical modality of dose prescription for multiple adjacent BM. Thus, we proposed other five practical solutions to prescribe radiation dose in case of two or more neighboring BM, describing advantages and drawbacks of each method in terms of different dosimetric parameters. The literature review about dosimetric solutions to irradiate multiple BM led to 56 titles; 14 articles met the chosen criteria and we reported their results in terms of dosimetric indexes and low doses to the normal brain tissue. CONCLUSIONS: The six dosimetric approaches here described can be used by physicians for multiple contiguous BM, depending on the clinical situation. These methods may be applied in clinical studies to better evaluate their usefulness in practice.

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases.

PURPOSE: The objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Seventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0. RESULTS: The median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47-62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06-3.01; P=0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77-15.27; P<0.001) tumour volume (>12cc vs. ≤12cc; HR, 1.84; 95% CI, 1.10-3.11; P=0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19-0.70; P=0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients. CONCLUSION: With acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.

Collision prediction for intracranial stereotactic radiosurgery planning: An easy-to-implement analytical solution.

PURPOSE: Gantry collision is a concern in linac-based stereotactic radiosurgery (SRS). Without collision screening, the planner may compromise optimal planning, unnecessary re-planning delays can occur, and incomplete treatments may be delivered. To address these concerns, we developed a software for collision prediction based on simple machine measurements. MATERIALS AND METHODS: Three types of collision were identified; gantry-couch mount, gantry-couch and gantry-patient. Trigonometric formulas to calculate the distance from each potential point of collision to the gantry rotation axis were generated. For each point, collision occurs when that distance is greater than the gantry head to gantry rotational axis distance. The colliding arc for each point is calculated. A computer code incorporating these formulas was generated. The inputs required are the couch coordinates relative to the isocenter, the patient dimensions, and the presence or absence of a circular SRS collimator. The software outputs the collision-free gantry angles, and for each point, the shortest distance to the gantry or the colliding sector when collision is identified. The software was tested for accuracy on a TrueBEAM® machine equipped with BrainLab® accessories for 80 virtual isocenter-couch angle configurations with and without a circular collimator and a parallelepiped phantom. RESULTS: The software predicted the absence of collision for 19 configurations. The mean absolute error between the measured and predicted gantry angle of collision for the remaining 61 cases was 0.86 (0.01-2.49). CONCLUSION: This tool accurately predicted collisions for linac-based intracranial SRS and is easy to implement in any radiotherapy facility.

[Biologic effects of high doses per fraction]. / Effets biologiques des hautes doses par fraction.

The radiobiological concepts described for conventional doses per fraction (1.8 to 2Gy) seem difficult to translate to high doses per fraction radiobiology. In fact, specific mechanisms are involved during high dose per fraction irradiation, involving vascular microenvironment damage and anti tumor immune response. The "5R's" of "classical" radiobiology (factors influencing the response of healthy or cancer cells to irradiation) seem to play a less important role in case of high doses per fraction. In addition, applicability of the linear quadratic model in this context is debated. It is therefore difficult to obtain reliable equivalent doses, hence the importance of including our patients in clinical trials, especially in case of concomitant systemic treatments. In addition to stereotactic radiotherapy, flash irradiations defined by a dose rate approximately 2000 times faster than "conventional" irradiation can also deliver high doses per fraction, with a much better tolerance for normal tissue without loss of anti tumor efficacy. Finally, availability of robust prospective data is a prerequisite to answer the question of short and long-term risk/benefit ratio of these different irradiation techniques.

[Functional stereotactic radiosurgery: Indications and perspectives]. / Radiochirurgie fonctionnelle : indications et perspectives.

Stereotactic radiosurgery (SRS) is a non-invasive technique that enables to create brain focal lesions with a high precision and localization. Thus, functional brain disorders can be treated by SRS in case of pharmacoresistance or inoperability. To date, treatment of trigeminal neuralgia is the most described and known indication. Other indications will be developed in the future like movement disorders, refractory epilepsy, obsessive compulsive disorder and severe depression. We present here a review of actual and future indications of functional brain SRS with their level of evidence. All these SRS treatments have to be strictly conducted by trained teams with an excellent collaboration between radiation physicists, medical physicists, neurosurgeons, neurologists, psychiatrists and probably neuroradiologists.

Role of radiation therapy in brain metastases management.

The challenge of the management of brain metastases has not finished yet. Although new diagnosis-specific prognostic assessment classifications and guidelines for patients with brain metastases help to guide treatment more appropriately, and even if the development of modern technologies in imaging and radiation treatment, as well as improved new systemic therapies, allow to reduce cognitive side effects and make retreatment or multiple and combined treatment possible, several questions remain unanswered. However, tailoring the treatment to the patient and his expectations is still essential; in other words, patients with a poor prognosis should not be over-treated, and those with a favorable prognosis may not be subtracted to the best treatment option. Some ongoing trials with appropriate endpoints could better inform our choices. Finally, a case-by-case inter-disciplinary discussion remains essential.

Radiological assessment after stereotactic body radiation of lung tumours.

The increasing use of stereotactic body radiation therapy for lung tumours comes along with new post-therapeutic imaging findings that should be known by physicians involved in patient follow-up. Radiation-induced lung injury is much more frequent than after conventional radiation therapy, it can also be delayed and has a different radiological presentation. Radiation-induced lung injury after stereotactic body radiation therapy involves the lung parenchyma surrounding the target tumour and appears as a dynamic process continuing for years after completion of the treatment. Thus, the radiological pattern and the severity of radiation-induced lung injury are prone to changes during follow-up, which can make it difficult to differentiate from local recurrence. Contrary to radiation-induced lung injury, local recurrence after stereotactic body radiation therapy is rare. Other complications mainly depend on tumour location and include airway complications, rib fractures and organizing pneumonia. The aim of this article is to provide a wide overview of radiological changes occurring after SBRT for lung tumours. Awareness of changes following stereotactic body radiation therapy should help avoiding unnecessary interventions for pseudo tumoral presentations.

Hypofractionated stereotactic radiotherapy for challenging brain metastases using 36 Gy in six fractions.

PURPOSE: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. MATERIAL AND METHODS: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. RESULTS: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. CONCLUSION: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.

Dose fall-off patterns with volumetric modulated arc therapy and three-dimensional conformal radiotherapy including the "organ at risk" effect. Experience of linear accelerator-based frameless radiosurgery from a single institution.

PURPOSE: This study aimed to evaluate characteristics of dose fall-off pattern for linear accelerator based frameless stereotactic radiotherapy and radiosurgery using two different techniques, three-dimensional conformal radiotherapy and volumetric modulated arc therapy. MATERIALS AND METHODS: The data from thirty patients who underwent frameless stereotactic radiotherapy/radiosurgery were considered for this analysis. These included 11 patients treated using three-dimensional conformal radiation and 19 patients treated with volumetric modulated arc therapy. Dose fall-offs in six predetermined directions from the edge of planning target volume and in direction of organs at risk were evaluated. These included determining dose fall-off (distance range) of 100%-80%, 100%-50%, 100%-20% from the treatment planning system. The first derivative (percentage of dose fall-off per millimetre) and second derivative (percentage of dose per square millimetre) of the dose fall-off was calculated. RESULTS: The dose fall-off is sharpest in the organ at risk direction if the organ at risk is hugging the planning target volume. However, for organs at risk separated from the planning target volume sharpest dose fall-off could be in either planning target volume superior or inferior direction. Three-dimensional conformal radiotherapy plans had a mean±SD of 14±2 beams (range: 11-17). Volumetric modulated arc therapy planning comprised of arc angles with sum±SD of 953±172.5° (range: 610°-1170°). Mean±SD for the single sharpest dose fall-off for all patients receiving three-dimensional conformal radiotherapy was 11.3±4.7%·mm-1, 7.8±4.8%·mm-1 and 7.1±5.6%·mm-1 for 100%-80%, 100%-50% and 100%-20% fall-off ranges respectively. For volumetric modulated arc therapy, the mean±SD of the single sharpest fall-off was 10.4±4.6%·mm-1, 7.8±3.0%·mm-1 and 7.3±5.0%·mm-1 for 100%-80%, 100%-50% and 100%-20% range. All organs at risk doses received doses within limits prescribed by AAPM-TG report 21. Mean dose to monitor units (MU) modulation factor MF=totalMUdeliveredprescriptiondoseincGy for three-dimensional conformal radiotherapy and volumetric modulated arc therapy were 1.97±1.0 MU·cGy-1 and 2.5±0.75 MU·cGy-1 respectively. CONCLUSION: Our study presents the dose fall-off patterns in context of frameless stereotactic radiation therapy. We have presented the dose fall-off data in the framework of three-dimensional conformal radiotherapy and volumetric modulated arc therapy in brain lesions.

[Stereotactic ablative body radiotherapy: Which machine for which therapeutic indication? A focus on prostate cancer]. / Radiothérapie stéréotaxique extracrânienne : quelle machine pour quelle indication ? Stéréotaxie prostatique.

For the last decade, stereotactic body radiotherapy has become a leading treatment for localized prostate cancer. It can be delivered using a wide array of radiotherapy machines. However, although numerous clinical studies, both prospective and retrospective, have been published, the different techniques have never been properly compared. This article aims at giving an overview of the published trials, and at pointing out the major differences between the machines, from a clinical (efficacy end toxicity), technical and radiobiological point of view.

Fractionated radiotherapy and radiosurgery of intracranial meningiomas.

This review focuses on the role of radiosurgery and fractionated radiotherapy in the management of intracranial meningiomas, which are the most common benign intracranial tumors. Whenever feasible, surgery remains a cornerstone of treatment in effective health care treatment where modern radiotherapy plays an important role. Irradiation can be proposed as first-line treatment, as adjuvant treatment, or as a second-line treatment after recurrence. Stereotactic radiosurgery consists of delivering, a high-dose of radiation with high precision, to the tumor in a single-fraction with a minimal exposure of surrounding healthy tissue. Stereotactic radiosurgery, especially with the gamma knife technique, has reached a high level of success for the treatment of intracranial meningiomas with excellent local control and low morbidity. However, stereotactic radiosurgery is limited by tumor size,<3-4cm, and location, i.e. reasonable distance from the organs at risk. Fractionated radiation therapy is an interesting alternative (5 to 6weeks treatment time) for large inoperable tumors. The results of fractionated radiation therapy seem encouraging as regards both local control and morbidity although long-term prospective studies are still needed.