[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.

Hypofractionated stereotactic radiotherapy for large brain metastases: Optimizing the dosimetric parameters.

PURPOSE: Stereotactic radiotherapy plays a major role in the treatment of brain metastases (BM). We aimed to compare the dosimetric results of four plans for hypofractionated stereotactic radiotherapy (HFSRT) for large brain metastases. MATERIAL AND METHODS: Ten patients treated with upfront NovalisTx® non-coplanar multiple dynamic conformal arcs (DCA) HFSRT for≥25mm diameter single BM were included. Three other volumetric modulated arc therapy (VMAT) treatment plans were evaluated: with coplanar arcs (Eclipse®, Varian, VMATcEclipse®), with coplanar and non-coplanar arcs (VMATncEclipse®), and with non-coplanar arcs (Elements Cranial SRS®, Brainlab, VMATncElements®). The marginal dose prescribed for the PTV was 23.1Gy (isodose 70%) in three fractions. The mean GTV was 27mm3. RESULTS: Better conformity indices were found with all VMAT techniques compared to DCA (1.05 vs 1.28, P<0.05). Better gradient indices were found with VMATncElements® and DCA (2.43 vs 3.02, P<0.001). High-dose delivery in healthy brain was lower with all VMAT techniques compared to DCA (5.6 to 6.3 cc vs 9.4 cc, P<0.001). Low-dose delivery (V5Gy) was lower with VMATncEclipse® or VMATncElements® than with DCA (81 or 94 cc vs 110 cc, P=0.02). CONCLUSIONS: NovalisTx® VMAT HFSRT for≥25mm diameter brain metastases provides the best dosimetric compromise in terms of target coverage, sparing of healthy brain tissue and low-dose delivery compared to DCA.

Long-Term Outcomes After Linac Radiosurgery for Benign Meningiomas.

AIMS: Although several studies on outcomes following stereotactic radiosurgery (SRS) for benign meningiomas have been reported, Linac-based SRS outcomes have not been as widely evaluated. The aim of this retrospective institutional single-centre study was to determine long-term outcomes of Linac-based SRS for benign intracranial meningiomas. MATERIALS AND METHODS: From July 1996 to May 2011, 60 patients with 69 benign meningiomas were included. All patients were treated with single-fraction Linac-based SRS with four to five non-coplanar arcs, dynamic or not. The marginal dose prescribed for the periphery was 16 Gy. Prognostic factors associated with local control, progression-free survival (PFS) and overall survival were tested. RESULTS: The median follow-up was 128 months. No patient was lost to follow-up. The values observed at 1, 5 and 10 years were, respectively, 100%, 98.4% and 92.6% for local control, 94.9%, 93.2% and 78% for PFS and 100%, 94.7% and 92.7% for overall survival. In univariate analysis, local control after SRS was significantly higher for skull base and parasagittal meningiomas compared with convexity meningiomas (P = 0.031). Multivariate analyses showed significantly longer PFS when the minimum dose delivered to the tumour was greater than 10 Gy (P = 0.0082). No grade 5 toxicity was reported. CONCLUSION: Our long-term results from a large sample size of benign meningiomas treated with Linac-based SRS confirmed excellent local control (>90%) and good safety, which is in line with published studies on Gamma Knife surgery. Above all, we showed significantly poorer PFS if the minimum dose to the tumour was under 10 Gy.

[Stereotactic lung radiotherapy: Technical setting up on Novalis Tx® and single centre prospective study of the 100 first malignant pulmonary nodules treated at centre Jean-Perrin]. / Radiothérapie en conditions stéréotaxiques pulmonaire : mise en place de la technique sur accélérateur linéaire d'électrons Novalis Tx® et évaluation prospective monocentrique des 100 premiers nodules pulmonaires traités au centre Jean-Perrin.

PURPOSE: Description of the treatment technique of stereotactic lung radiotherapy on Novalis Tx® and prospective study of the first 100 pulmonary nodules treated at centre Jean-Perrin (France). MATERIAL AND METHODS: From October 2012 to December 2015, 100 inoperable pulmonary nodules (62 stage I non-small-cell lung cancer and 38 metastases) of 90 patients with a mean age of 68.2 years (range: 46-89 years) were prospectively treated with dynamic arctherapy on Novalis Tx®. Mean gross tumour and planning target volumes were respectively 6.9 cm3 (range: 0.2-31.4 cm3) and 38.7 cm3 (range: 1.7-131 cm3), which correspond to diameters equal to 2.3cm and 4.2cm. Prescribed doses to the 80% isodose line were 54Gy in three fractions for peripheral non-small-cell lung cancer, 50Gy in five fractions for central non-small-cell lung cancer and 45Gy in three fractions for lung metastases. Clinical and radiological follow-up was done every three months with RECIST criteria for efficacy and NCI-CTCAE v4 scale for toxicity. Median follow-up was 12.5 months. RESULTS: Complete response was observed in 23.8% of cases. Local control rates were 100% and 90.7% respectively at 12 and 24 months, with 96% at 24 months for stage I non-small-cell lung cancer. Overall survival rates of patients with stage I non-small-cell lung cancer were 77.4% and 73.5% at 12 and 24 months (median overall survival was 32 months). Diffusing capacity of the lungs for carbon monoxide corrected for alveolar volume below 40% was significantly associated to a poor prognostic factor on univariate analysis (P=0.00013). At least three deaths were due to an acute respiratory failure, which correspond to about 4.8% of grade 5 radiation pneumonitis. Overall survival rate for metastatic patients were 95.2% and 59.5% respectively at 12 and 24 months (median overall survival was 25 months); 23.3% of grade 2 or less radiation pneumonitis, 7.8% of grade 2 or less radiation dermatitis, 2.2% of asymptomatic ribs fracture and 3.3% of chest pains were observed. CONCLUSION: Stereotactic lung radiotherapy is an effective treatment for inoperable stage I non-small-cell lung cancer and lung oligometastases of well informed and selected patients. Initial respiratory state, and especially the diffusing capacity of the lungs for carbon monoxide corrected for alveolar volume, seems to be important for tolerance.

[Equipment and positioning technologies in stereotactic body radiation therapy]. / Appareillage et technologies de repositionnement en radiothérapie stéréotaxique extracrânienne.

Strereotactic body radiation therapy needs adapted or dedicated equipment to allow fulfilling the particular conditions of the stereotactic treatments: submillimetric accuracy during the treatment delivery, high doses for a reduced number of sessions. This kind of treatment can be either performed using delivery equipment conceived and dedicated to the technique, or performed on conventional machines adapted to meet the criteria. Contrary to intracranial treatments, the positioning of the target volume raises new difficulties, mainly due to the diversity of localization to treat and also due to inter- and intrafraction movements that can occur. To reduce these effects that could affect the irradiation accuracy, positioning or movement compensation, mostly due to respiration, tools have been developed.

Measurements of extracellular volume fraction and capillary permeability in tissues using dynamic spin-lattice relaxometry: studies in rabbit muscles.

Dynamic MR longitudinal R(1) relaxometry after administration of a gadolinium contrast bolus (Gd-DTPA) has been used for in vivo measurements of the extracellular volume fraction (v) and the capillary permeability (k min(-1)) in rabbit muscles to distinguish between red slow- and white fast-twitch muscle fiber types. For this purpose a protocol imaging sequence has been used which allows fast R(1) measurements during the contrast agent uptake. Physiological tissue parameters, k and v, were obtained by computing procedures assuming a simplified monoexponential plasma model. These were shown to be about twice as large in the slow-twitch semimembranosous proprius muscle (SP), containing 100% oxidative type-I fiber, that in the fast-twitch rectus femorus muscle (RF), containing only 6% type-I fiber type. The capillary permeability has been found to be 0.25 +/- 0.02 min(-1) for the (SP) and 0.10 +/- 0.01 min(-1) for the (RF). Similarly, the extracellular volume fractions were 0.189 +/- 0.015 and 0.082 +/- 0.006 respectively, in close agreement with literature data and experimental results obtained by invasive radionuclide measurements. For the pool of the 10 studied animals, no significant variation among animals was observed in the extracellular volume fraction and the capillary permeability for the different muscle fiber types. The dynamic relaxometry method used is easy to implement on conventional MR imagers and has potential applications in muscle diseases. The method has also potential applications for tissue characterization based on extracellular volume and capillary permeability quantification. In particular, the method can be used for the evaluation of tumors and their responses to therapies.

Rapid relaxation times measurements by MRI: an in vivo application to contrast agent modeling for muscle fiber types characterization.

This paper is a description of a simulation method to evaluate the contrast in NMR imaging and its aim is to help to optimize the use of contrast media in clinical imaging. Indeed, there is a need to define objective criteria in order to choose among several contrast media the ones that are the most effective and to define their optimal conditions of use, such as: the dose to be injected, the required time after injection to obtain the best enhancement and the optimal imaging sequence parameter values. The method is based on NMR signal simulation in the presence of contrast media and requires the fast measurement of the T1 and T2 relaxation times to obtain the dynamic relaxometry variation of tissues after contrast injection. In this work the fast imaging techniques that are to be described enable the measurement of T1 and T2 with a 30sec temporal resolution on 128*256 matrix images. The accuracy of the method was assessed in rabbit muscles after the injection of two gadolinium chelates (Gd-DTPA and Gd-DOTA) with the aim of improving the in vivo characterization of fast-twitch and slow-twitch muscle fiber types. The simulation results were in close agreement with contrast image analysis and showed, for relevant clinical doses, a small efficacy for both chelates. The interest of the proposed simulation method lies in the fact that it enables to objectively compare the efficacy of different contrast agents, to forecast the efficacy of a given contrast reagent and to define the optimal dose and the optimal imaging sequence parameters that give the best contrast. This simulation method obviates numerous prior experiments to evaluate the benefit expected from different contrast media. The method, which has been evaluated here for muscle investigations is applicable to any tissue analysis and can help to guide the best condition of use of contrast agents in MR imaging.

In vivo tissue extracellular volume fraction measurement by dynamic spin-lattice MRI relaxometry: application to the characterization of muscle fiber types.

RATIONALE AND OBJECTIVES: The extracellular volume fraction (v) was estimated in leg rabbit muscles by MRI dynamic longitudinal relaxation rate (R1) relaxometry to distinguish between slow- and fast-twitch muscle fiber types. METHOD: The extracellular volume fraction was calculated from the dynamic increase of the longitudinal relaxation rate after intravenous administration of a gadolinium (Gd-DTPA) contrast bolus, assuming a biexponential plasma concentration model. RESULTS: It has been shown that the extracellular volume fraction increases with the slow fiber content (oxidative type I); the maximal value (v = 0.186+/-0,018) was obtained in pure slow-twitch muscle fiber (100% type I). CONCLUSION: NMR extracellular volume estimates closely agree with those obtained using the more classic invasive isotopic method (99mTc-DTPA) carried out on the same rabbit strain and with data reported in the literature. The method has potential applications to characterize the pathophysiologic status of tissues. It is also applicable to a wide range of tissues and pathologies, in particular for the characterization of malignant tissues and their response to therapies.

Characterization in vivo of muscle fiber types by magnetic resonance imaging.

Magnetic resonance imaging has been used to characterize muscle fiber types. Here, T1 and T2 values were determined in pure slow-twitch and fast-twitch rabbit muscles and in rabbit muscles with mixed fiber types. The muscles with high proportions of oxidative slow-twitch fibers had higher T2 values than the others. Echo time, orientation of muscle fibers in B0, and moving spins had no effect on relaxation parameters. The results are discussed in terms of slow myosin isoform content and oxidative metabolism.