Constantin Tuleasca, Iulia Peciu-Florianu, Henri-Arthur Leroy, Maximilien Vermandel, Mohamed Faouzi, and Nicolas Reyns
Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs.
A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12–154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18–25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7–246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9–138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313–3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4–2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed.
A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (−0.013689 × beam-on time) + (0.021 × age) − 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03).
The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.
Marcos Dellaretti, Nicolas Reyns, Gustavo Touzet, François Dubois, Sebastião Gusmão, Júlio Leonardo Barbosa Pereira, and Serge Blond
Brainstem gliomas were regarded as a single entity prior to the advent of MRI; however, several studies investigating MRI have recognized that these lesions are a heterogeneous group, and certain subgroups have a better prognosis for long-term survival. The aim of this study was to conduct a retrospective analysis of prognostic factors of patients with brainstem gliomas confirmed by histopathological diagnosis, particularly regarding assessment of whether histological grade, age, and MRI findings are prognostic factors for patient survival.
The study evaluated 100 patients diagnosed with brainstem glioma. There were 63 adults (40 men and 23 women; age range 18–75 years, mean 41 years) and 37 children (19 boys and 18 girls; age range 2–12 years, mean 6.9 years).
The mean overall survival of this population, measured from the date of biopsy, was 57 months for diffuse low-grade glioma and 13.8 months for diffuse high-grade glioma (p < 0.001). The mean survival among patients with nonenhancing contrast lesions on MRI was 54.2 months, whereas for patients with enhancing lesions, it was 21.7 months (p < 0.001). Comparisons between the Kaplan-Meier survival curves of adults and children revealed similar median survival periods of 25 and 16 months, respectively (p > 0.05). The multivariate analysis (Cox proportional hazards regression) revealed that only histological grade was a significant prognostic factor (p < 0.001).
The study revealed that histological grade and MRI features were significant prognostic factors for survival in these patients, but in multivariate analysis, only histological grade remained a significant factor.
Rabih Aboukais, Fahed Zairi, Jean-Paul Lejeune, Emile Le Rhun, Maximilien Vermandel, Serge Blond, Patrick Devos, and Nicolas Reyns
World Health Organization Grade 2 meningiomas are aggressive tumors associated with a high recurrence rate leading to repeated surgical procedures, which can seriously worsen a patient's neurological status. Although radiosurgery is an increasingly popular technique, its role in the management of Grade 2 meningiomas has yet to be defined. In this study the authors aimed to evaluate radiosurgery in achieving control of proven tumor progression occurring after resection of Grade 2 meningioma.
This retrospective study included consecutive patients who, between 2000 and 2012, had undergone radiosurgery for radiologically proven progression of a previously surgically treated Grade 2 meningioma.
Twenty-seven patients were eligible for analysis. There were 9 men and 18 women with a mean age of 59 years. The mean radiation dose was 15.2 Gy (range 12–21 Gy), and the mean target volume was 5.4 cm3 (range 0.194–14.2 cm3). Thirty-four radiosurgical procedures were performed in the 27 patients. The mean progression-free survival after radiosurgery was 32.4 months among those with progression in a target irradiated volume and 26.4 months among those with progression in any intracranial meninges. With a mean follow-up of 56.4 months (range 12–108 months), the 12-, 24-, and 36-month actuarial local control rates for all patients were 75%, 52%, and 40%, respectively, and the regional control rates were 75%, 48%, and 33%. A single case of transient hemiparesis completely resolved without sequelae.
Radiosurgery appears to be a safe and effective treatment for the local control of delayed progression after resection of a Grade 2 meningioma. Higher radiation doses similar to those applied for malignant tumors should be recommended when possible.
Christian A. Taschner, Vianney Le Thuc, Nicolas Reyns, Juergen Gieseke, Jean-Yves Gauvrit, Jean-Pierre Pruvo, and Xavier Leclerc
The aim of this study was to develop an algorithm for the integration of time-resolved contrast-enhanced magnetic resonance (MR) angiography into dosimetry planning for Gamma Knife surgery (GKS) of arteriovenous malformations (AVMs) in the brain.
Twelve patients harboring brain AVMs referred for GKS underwent intraarterial digital subtraction (DS) angiography and time-resolved MR angiography while wearing an externally applied cranial stereotactic frame. Time-resolved MR angiography was performed on a 1.5-tesla MR unit (Achieva, Philips Medical Systems) using contrast-enhanced 3D fast field echo sequencing with stochastic central k-space ordering. Postprocessing with interactive data language (Research Systems, Inc.) produced hybrid data sets containing dynamic angiographic information and the MR markers necessary for stereotactic transformation. Image files were sent to the Leksell GammaPlan system (Elekta) for dosimetry planning.
Stereotactic transformation of the hybrid data sets containing the time-resolved MR angiography information with automatic detection of the MR markers was possible in all 12 cases. The stereotactic coordinates of vascular structures predefined from time-resolved MR angiography matched with DS angiography data in all cases. In 10 patients dosimetry planning could be performed based on time-resolved MR angiography data. In two patients, time-resolved MR angiography data alone were considered insufficient. The target volumes showed a notable shift of centers between modalities.
Integration of time-resolved MR angiography data into the Leksell GammaPlan system for patients with brain AVMs is feasible. The proposed algorithm seems concise and sufficiently robust for clinical application. The quality of the time-resolved MR angiography sequencing needs further improvement.
Marcos Dellaretti, Gustavo Touzet, Nicolas Reyns, François Dubois, Sebastião Gusmão, Júlio Leonardo Barbosa Pereira, and Serge Blond
The aim of this study was to compare MR imaging characteristics with histopathological findings of intrinsic brainstem lesions and also to show the prognostic factors in patients with diffuse brainstem glioma.
Between February 1988 and August 2007, 44 brainstem biopsies were performed at the Roger Salengro Hospital in Lille, France, in children with intrinsic brainstem lesions not amenable to excision. Twenty-six were female and 18 male, and the mean age was 6 years.
Histological evaluation revealed diffuse brainstem glioma in all patients with diffuse nonenhancing brainstem lesions. Diffuse brainstem glioma was found in 18 patients (90%) with diffuse enhancing brainstem lesions. Pathological entities different from diffuse glioma were verified in 2 patients (10%)—1 with ependymoma and 1 with ganglioglioma.
In 4 of 5 patients with a focal nonenhancing brainstem lesion, the histopathological diagnosis was diffuse low-grade glioma. In 6 of 10 patients with focal enhancing brainstem lesion, the diagnosis was diffuse brainstem glioma, and pathological entities different from diffuse brainstem glioma were verified in 2 (20%), both with pilocytic astrocytoma.
The mean 1-year actuarial survival rates for patients classified with low-grade and high-grade glioma were 80.4% ± 0.08% and 48.6% ± 0.14%, respectively.
The impact of stereotactic biopsy on intrinsic brainstem lesions was greater in patients with MR imaging–documented enhancing lesions in whom the diagnosis of diffuse glioma was less frequent. Patients with low-grade glioma seem to have longer survival than those with high-grade glioma.
Marcos Dellaretti, Nicolas Reyns, Gustavo Touzet, Thierry Sarrazin, François Dubois, Eric Lartigau, and Serge Blond
Stereotactic radiosurgery is an increasingly used, and the least invasive, surgical option for patients with trigeminal neuralgia (TN). In this study, the authors performed a retrospective evaluation of the safety and efficacy of this method for idiopathic TN.
The authors reviewed data from 76 patients with idiopathic TN who underwent Gamma Knife surgery (GKS). The mean age of the patients was 64 years (range 27–83 years). All patients had typical features of TN. Thirty patients (39.5%) had previously undergone surgery. The intervention consisted of GKS on the retrogasserian cisternal portion of the fifth cranial nerve. The mean maximum GKS dose used was 85.1 Gy (range 75–90 Gy).
Patients were followed-up from 6 to 42 months (mean 20.3 months) after GKS. Complete pain relief was achieved in 83.1% of the patients within 1 year, 70.9% within 2 years, and 62.5% within 3 years. Patients who underwent previous surgery demonstrated a lower rate of pain relief (p < 0.05). Twenty patients (26.3%) reported pain recurrence between 6 and 42 months after treatment. New or worsened persistent trigeminal dysfunction developed after GKS in 16 patients (21%); 8 of these patients described some facial numbness/not bothersome, and 8 reported some facial numbness/somewhat bothersome. None of the patients developed troublesome dysesthesia or anesthesia dolorosa.
Gamma Knife surgery for idiopathic TN proved to be safe and effective and was associated with a particularly low rate of complications.
Phillip A. Bonney and Michael E. Sughrue
Benjamin Pommier, Gustavo Touzet, Christian Lucas, Maximilien Vermandel, Serge Blond, and Nicolas Reyns
Glossopharyngeal neuralgia (GPN) is a rare and disabling condition. Just as for trigeminal neuralgia, Gamma Knife radiosurgery (GKRS) is increasingly proposed as a therapeutic option for GPN. The purpose of this study was to assess long-term safety and efficacy of GKRS for this indication.
From 2007 to 2015, 9 patients (4 male and 5 female) underwent a total of 10 GKRS procedures. All of the patients presented with GPN that was refractory to all medical treatment, and all had a long history of pain. One patient had previously undergone surgical microvascular decompression. In 5 cases, a neurovascular conflict had been identified on MRI. For the GKRS procedure, the glossopharyngeal nerve was localized on MRI and CT under stereotactic conditions. The target was located at the glossopharyngeal meatus of the jugular foramen. The dose administered to the nerve was 80 Gy in 3 procedures and 90 Gy in the others. Follow-up was planned for 3, 6, and 12 months after the procedure and annually thereafter.
Eight patients experienced an improvement in their pain. The median length of time from GKRS to symptom improvement in this group was 7 weeks (range 2–12 months). At the first follow-up, 6 patients were pain-free (pain intensity scores of I–III, based on an adaptation of the Barrow Neurological Institute scoring system for trigeminal neuralgia), including 4 patients who were also medication-free (I). One patient had partial improvement (IV) and 2 patients had no change. The mean duration of follow-up was 46 months (range 10–90 months). At the last follow-up 6 patients remained pain-free (pain scores of I–III), including 4 patients who were pain free with no medication (I). No side effect was observed.
Because of its safety and efficacy, GKRS appears to be a useful tool for treatment of GPN, including first-line treatment.
Iulia Peciu-Florianu, Maximilien Vermandel, Nicolas Reyns, and Constantin Tuleasca
John W. Hopewell, Ian Paddick, Bleddyn Jones, and Thomas Klinge