Daniel Devriendt

Irradiation of cochlear structures during vestibular schwannoma radiosurgery and associated hearing outcome

OBJECT The purpose of this study was to measure the dose of radiation delivered to the cochlea during a Gamma knife surgery (GKS) procedure for treatment of patients with vestibular schwannomas (VSs), and to analyze the relationship between cochlear irradiation and the hearing outcome of these patients. METHODS Eighty-two patients with VSs were treated with GKS using a marginal dose of 12 Gy. No patient had neurofibromatosis Type 2 disease, and all had a Gardner-Robertson hearing class of I to IV before treatment, and a radiological and audiological follow-up of at least 1-year after GKS. The dosimetric data of the volume of the cochlea were retrospectively analyzed and were correlated with the auditory outcome of patients. RESULTS The mean radiation dose delivered to the cochlear volume ranged from 1.30 to 10.00 Gy (median 4.15 Gy). The cochlea received significantly higher radiation doses in patients with worsening of hearing after GKS. A highly significant association between the cochlear and the intracanalicular dose of radiation delivered during GKS was found. CONCLUSIONS During GKS for VSs, relatively high doses of radiation can be delivered to the cochlea. Worsening of hearing after GKS can be the consequence of either radiation injury to the cochlea or the irradiation dose delivered into the auditory canal, or both.

Influence of nerve radiation dose in the incidence of trigeminal dysfunction after trigeminal neuralgia radiosurgery

OBJECTIVEThe authors conducted a comparative study to analyze dosimetry and results to understand the significant difference in the rate of trigeminal dysfunction after gamma knife radiosurgery for trigeminal neuralgia between two centers using the same target. METHODSThe data of 358 patients (109 patients from Brussels and 259 patients from Marseilles) were analyzed. Three different dosimetric strategies were found: treatment with less than 90 Gy and no selective beam channel blocking (Group 1; patients from Marseilles only), treatment with 90 Gy and no selective beam channel blocking (Group 2; patients from Brussels and Marseilles), or treatment with 90 Gy and use of selective beam channel blocking (Group 3; patients from Brussels only). RESULTSThe prescription dose and the use of selective beam channel blocking have been significantly associated with a higher energy received by the retrogasserian trigeminal nerve root. The different radiation dose delivered to the nerve root in these three groups of patients was significantly associated with the incidence of mild (15, 21, and 49% for Groups 1, 2, and 3, respectively) and bothersome (1.4, 2.4, and 10% for Groups 1, 2, and 3, respectively) trigeminal dysfunction. The good and excellent rates of pain relief were 81 and 66%, respectively, for Group 1, 85 and 77%, respectively, for Group 2, and 90 and 84%, respectively, for Group 3, and were also related to the amount of energy received by nerve root volume. CONCLUSIONUsing a similar target, the incidence of trigeminal dysfunction and the pain relief rate can vary according to the radiation energy received by the retrogasserian part of the trigeminal nerve root. The prescription dose and the use of beam channel blocking modify the integrated dose delivered to the nerve and may contribute to the different rates of trigeminal numbness and pain outcome. The radiobiological effect of gamma knife radiosurgery may be related to the energy delivered to nerve root volume, rather than to the maximal dose delivered.

Integration of the metabolic data of positron emission tomography in the dosimetry planning of radiosurgery with the gamma knife: early experience with brain tumors. Technical note.

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

11C-methionine PET for the diagnosis and management of recurrent pituitary adenomas

PurposeThe detection of recurrent pituitary adenoma by magnetic resonance imaging (MRI) is rendered uncertain by the tissue remodelling that follows surgery or radiotherapy. We aimed to evaluate the contribution of PET with 11C-methionine (MET-PET) in the detection and management of recurrent pituitary adenoma.MethodsThirty-three patients with pituitary adenoma were evaluated postoperatively by MET-PET, either because of biological evidence of active residual tumour or because of MRI demonstration of non-functional adenoma growth. We studied 24 secreting adenomas and nine non-functional adenomas.ResultsIn 30 patients, MET-PET detected abnormally hypermetabolic tissue. In 14 out of these, MRI did not differentiate between residual tumour and scar formation. In nine of these 14 cases, major therapeutic decisions were undertaken (radiosurgery and surgery). In another group of 16 patients, both MET-PET and MRI detected abnormal tissue. In one case, neither MRI nor MET-PET detected adenomatous tissue. Finally, abnormal tissue was detected in two patients on MRI solely. In these two cases, failure of MET-PET to reveal the adenoma was attributable to concomitant inhibitory therapy. The sensitivity of MET-PET and MRI varied as a function of the tumour type: all non-functional adenomas were localised by both modalities, while MET-PET detected all adrenocorticotropic hormone-secreting adenomas whereas MRI depicted only one of these eight lesions. Fifteen out of 17 patients treated by radiosurgery showed clinical improvement after treatment.ConclusionWe suggest that MET-PET is a sensitive technique complementary to MRI for the detection of residual or recurrent pituitary adenomas. It should gain a place in the efficient management of these tumours.

Brain metastases in HER2-positive breast cancer: The evolving role of lapatinib

Due to improvements in diagnosis and systemic therapy, brain metastases are an increasingly common cause of morbidity and mortality for patients with advanced breast cancer. The incidence of symptomatic brain metastases among women with metastatic breast cancer ranges from 10% to 16%. The HER2 receptor, which is overexpressed in approximately 25% of all breast cancers, is an important risk factor for the development of central nervous system metastases. Surgery and radiation therapy are the primary approaches to the treatment of brain metastases but new chemotherapy and biological agents promise to play an important role in the future management of central nervous system disease. This article reviews the epidemiology, current treatment options and recent advances in the field, with a focus on HER2-positive disease and the emerging role of lapatinib for the treatment and prevention of brain metastases.

Neurovascular compression anatomy and pain outcome in patients with classic trigeminal neuralgia treated by radiosurgery.

OBJECTIVE To study the influence of the anatomy of neurovascular compression (NVC) on pain outcome in patients with classic trigeminal neuralgia treated by radiosurgery. METHODS Analysis of the anatomy of the trigeminal nerve, brainstem, and vessels was performed in 89 consecutive patients treated by Leksell gamma knife (Elekta Instruments, Stockholm, Sweden) for classic trigeminal neuralgia. One-millimeter axial magnetic resonance imaging slices (T1-weighted, T1-weighted enhanced, and T2-weighted selected partial inversion recovery) with coronal, sagittal, and three-dimensional reconstructions were viewed. The end point for outcome was total pain remission and no medication. The follow-up period ranged between 6 and 42 months. RESULTS In 82 patients (92%), a vascular structure in contact with the nerve was observed. In four patients, the NVC was produced by a large vessel (basilar or vertebral artery) and in 78 by a smaller vessel. The superior cerebellar artery was the cause of the NVC in 64 patients (78%). The NVC was proximal (<3 mm to the brainstem) in 34 patients (41%) and distal in 43 patients (52%). Nerve dislocation was present in 29 patients (33%), and nerve atrophy was present in 21 (24%) patients. Visualization of NVC on magnetic resonance imaging scans was not associated with outcome. The two variables associated with poor outcome were a large vessel contacting the nerve with brainstem deformation and proximal NVC. Nerve atrophy and nerve dislocation were not associated with outcome. CONCLUSION The visualization of NVC, nerve atrophy, and nerve dislocation on magnetic resonance imaging scans was not associated with pain outcome. A large vessel compressing the nerve and deforming the brainstem and proximal NVC were associated with a lesser pain control.

Radiosurgery for trigeminal neuralgia.

Radiosurgery has recently emerged as a suitable treatment of pharmacologically resistant idiopathic trigeminal neuralgia. Results and complications of this treatment are related to parameters of the dosimetry, i.e. the dose and the target. We found that the irradiation dose delivered to the brainstem, the distance between the target and the brainstem, and the occurrence of facial numbness after radiosurgery are related to a better pain outcome.

Internal Carotid Occlusion following Gamma Knife Radiosurgery for Cavernous Sinus Meningioma

Gamma knife radiosurgery is a safe and effective treatment for cavernous sinus meningioma, associated with a very low morbidity. However, a high dose of radiation could lead to modifications of the vascular wall such as in radiosurgical treatment of arteriovenous malformations. We present a patient treated by gamma knife radiosurgery for a left cavernous sinus meningioma using a margin dose of 13 Gy at the 50% isodose. A complete occlusion of the intracavernous segment of the ICA occurred during the follow-up, in combination with a regression of the meningioma volume. The patient sustained no neurological deficit. We found that a hot spot of dose was administered to the intracavernous segment of the internal carotid artery, with a maximum dose of 22.3 Gy. Dose heterogeneity inside the target volume can produce hot spots of dose inside the internal carotid artery that can lead to a vascular occlusion. Therefore, we recommend shifting the hot spot during the dosimetry planning in order to reduce the incidence of such vascular injury.

Integration of functional imaging in radiosurgery: the example of PET scan.

Radiosurgery relies critically on the imaging modalities that are used for targeting. Leksell Gamma Knife (LGK) radiosurgery presents the highest requirements in terms of imaging accuracy as the treatment is applied in a single high-dose session with no other spatial control than medical imaging. The advent of functional imaging modalities opens new challenges for LGK planning strategies. The integration of stereotactic PET in LGK represents an example of such application of modern multimodality imaging in radiosurgery. Our experience consists of 130 patients treated with the combination of MR/CT and PET guidance. In order to analyze the specific contribution of PET, we developed a classification reflecting the strategy used to define the target volume. When combining PET and MR information, 149 target volumes were defined, because some patients presented with multiple lesions or multifocal tumor areas. Abnormal PET uptake was found in 88% of the lesions; using the classification, we found that the information provided by PET altered significantly the MR-based definition of the tumor in 73%. In conclusion, integration of PET in radiosurgery provides additional functional information opening new perspectives for the treatment of brain tumors. The use of a standardized classification allows to assess the relative role of PET. A similar approach could be useful and may serve as a template for the evaluation of the integration of other new imaging modalities in radiosurgery.

Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial

BACKGROUND Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. METHODS Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. RESULTS The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. CONCLUSIONS The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.