Long-term results of Gamma-knife stereotactic radiosurgery for vestibular schwannomas in patients with type 2 neurofibromatosis.

INTRODUCTION: The aim of this study was to analyze the long-term results of Gamma-knife radiosurgery treatment of vestibular schwannomas in type 2 neurofibromatosis patients. MATERIALS AND METHODS: A cohort of 129 treatments for vestibular schwannomas in 103 patients was selected from a prospectively-maintained clinical database. Tumor control was assessed by volumetric analysis of the tumor at the last follow-up. Any need of a further procedure such as microsurgical removal or second treatment was regarded as a failure of tumor control. Hearing function was assessed based on Gardner-Robertson classification. Progression-free survival and functional hearing preservation rates were estimated using the Kaplan-Meier method. RESULTS: The median age at treatment was 34 years with no gender predominance. The median tumor volume was 1.5cm3. At a median clinical follow-up of 5.9 years, five patients had died, four underwent a second radiosurgical procedure and eight underwent microsurgical resection. Progression-free survival was 88 and 75% respectively at 5 and 10 years. Hearing was considered serviceable in 70 ears and remained functional in 28 ears. Kaplan-Meier estimates for 5 and 10 years functional hearing was 47 and 34%, respectively. Three patients developed new facial nerve palsy after radiosurgery at 15 days, 6 and 19 months respectively and only one partially recovered. Five patients complained of a subjective instability worsening. Four cases developed trigeminal neuropathy. No predictive factors were found to be statistically correlated with a better hearing outcome or an improved tumor growth control. CONCLUSION: Results prove less satisfying than in sporadic unilateral schwannomas. However, the lower rate of mortality and morbidity compared with microsurgical resection may support a proactive role of Gamma-knife in this pathology.

On demand Gamma-Knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases.

BACKGROUND: Both Gamma-Knife radiosurgery (GKRS) and BRAF inhibitors (BRAF-I) have been shown to be useful in melanoma patients with brain metastases (BMs), thus suggesting that it could be interesting to combine their respective advantages. However, cases of radiosensitization following conventional radiation therapy in BRAF-I treated patients have raised serious concerns about the real feasibility and risk/benefit ratio of this combination. PATIENTS AND METHODS: Review by two independent observers of brain magnetic resonance imaging (MRI) follow-up pictures, and volume and edema quantifications, and survival assessment in all patients who had been treated by GKRS and BRAF-I at a single institution. RESULTS: Among 53 GKRS carried out in 30 patients who ever received BRAF-I and GKRS, 33 GKRS were carried out in 24 patients while under BRAF-I treatment, from which only 4 with an interruption of BRAF-I. The 20 other GKRS were carried out in 15 patients (including 9 of the 24) before initiation of BRAF-I treatment. No case of radiation-induced necrosis and no scalp radiation dermatitis occurred. A >20% increase in volume was observed in 35 of the 263 BM treated by GKRS (13.3%), but only 3 clear-cut edemas and 3 hemorrhages were detected within 2 months after GKRS, and 4 edemas and 7 hemorrhages later. Neither the MRI features nor the incidence of the volume changes, hemorrhage and edema were deemed unexpected for melanoma BM treated by GKRS. Median survival from first GKRS under BRAF-I and first dose of BRAF-I were 24.8 and 48.8 weeks, respectively. CONCLUSION: This series does not show immediate radiotoxicity nor radiation recall, in melanoma patients with BRAF-I whose BMs are treated by GKRS. Interrupting BRAF-I for stereotactic radiosurgery (SRS) of BM seems useless, although it is still advised for other radiation therapies. The potential benefit of combining SRS and BRAF-I can be safely tested.

[Functional outcomes of radiosurgical treatment of vestibular schwannomas: 1000 successive cases and review of the literature]. / Résultats fonctionnels de la radiochirurgie des schwannomes vestibulaires. A propos de 1,000 cas successifs et revue de la littérature.

RATIONALE: To evaluate the functional results of Gamma Knife surgery of vestibular schwannomas relying on a large and prospective series of consecutive cases. MATERIAL AND METHOD: The first 1000 patients with cerebello-pontine angle schwannomas were consecutively treated by Gamma Knife in Marseille Timone University Hospital between July 1992 and March 2001. Patients without NF2 and or clinico-radiological arguments in favor of a facial origin accounted for a population of 927 patients (414 males, for 513 females) including 843 treated in first intention. In this series the Koos classification was: stage I 77 patients, stage II 520 patients, stage III 287 patients and stage IV 42 patients. The average Volume was 12.7mm3. Haring was usefull (Gardner and Robertson) before radiosurgery in 47% of the patients (subnormal in 20.3%). RESULTS: Tumor control at last follow-up was 97%. Globally, a clinical trigeminal injury was observed in 0.6% of the patients and a facial palsy in 1.3%. There was clearly a decrease of the incidence of neuropathies with time; no facial palsy being reported among the last 258 patients. The rate of functional hearing preservation (Gardner) for patients initially in class I was 77.8% (47.6% for class II) at 3 Years. This rate of functional preservation reached 95% among patients with tinnitus as a first symptom. CONCLUSION: Today, strong evidence surports the superiority of Gamma Knife surgery in term of functional perservation and equal efficacy compared with microsurgical removal. Consequently, radiosurgery must be preferred as a first intention choice for young patients with few symptoms presenting with a small to middle size vestibular schwannomas (Koos I-III).

[Changing radiological results, pitfalls and criteria of failure]. / Dynamique des résultats radiologiques, pièges et critères d'échec.

RATIONALE: To evaluate the morphological changes occurring during the Years following radiosurgery in order to better define the cure-failure parameters. MATERIAL AND METHODS: Between July 1992 and January 2002 the otoneurosurgical group of the Timone Hospital in Marseille have operated 1000 vestibular schwannomas. The MR imaging performed before (at diagnosis) during and after radiosurgery (6 months, 1 year, 2 years, 3 years, 5 years, 7 years and 10 years) was carefully studied. Systematically six lenghts measurements were obtained for each lesion. RESULTS: Preoperatively 129 patients were had progressive tumors. At time of radiosurgery, median tumor Volume was 732mm3 (mean: 1346, range: 20-14405). According to the Koos topographical classification, lesions were stage I in 80 patients, stage II in 538 patients, stage III in 322 patients and stage IV in 56 patients. A clear loss of the central enhancement was visible on the postoperative MR control at 6 months and/or 1 Year in 45.5% of patients. In 64% of these patients, this loss of the central contrast enhancement have disappeared. A significant increase of the tumor size was recorded in 15% of the patients. The median increase was 62% (mean: 78%, range: 30-350%). Progression led to salvage surgery (either resection or radiosurgery), in only 3% of the patients. CONCLUSION: The specificity of the morphological changes after radiosurgery, when ignored, can lead to misinterpretation and eventually to inappropriate decisions, dangerous for the patient. The analysis of our results had led us to consider continuous progression after 3 Years as mandatory to retain the diagnosis of failure.

[Preserving hearing function after Gamma Knife radiosurgery for unilateral vestibular schwannoma]. / Préservation de l'audition dans le traitement par radiochirurgie Gamma Knife des schwannomes vestibulaires unilatéraux.

OBJECTIVE: The majority of the patients still lose hearing function in spite of the technical advances in microsurgery. We wanted to evaluate preservation of hearing function potential after Gamma Knife Surgery. MATERIAL AND METHOD: In Marseille, we performed 1000 Gamma-Knife procedures for vestibular schwannomas between July 1992 and January 2002. This population included 175 patients undergoing first intention surgery for a unilateral schwannoma with functional preoperative hearing (Gardner and Robertson 1 or 2) who were studied with a follow-up longer than 3 Years. Univariate and multivariate analysis was performed. RESULTS: Numerous parameters significantly influenced the probability of functional hearing preservation at 3 years. The overall rate of preservation was 60%. The main parameters of predictability were limited hearing loss (Gardner and Robertson stage 1 versus 2) before radiosurgery, presence of tinnitus as the initial symptom, young age and the small tumor size. Preservation of functional hearing at 3 years was 77.8% when the patient was initially in stage I, 80% when the patient's first symptom was tinnitus, and 95% when the patient had both. In these patients, the probability of functional preservation at 5 years was 84%. CONCLUSION: We report a large population of patients treated by radiosurgery with initial functional hearing. These results demonstrate that a large percentage of selected patients can preserve functional hearing after Gamma Knife Surgery, their chances of functional preservation being greater than after microsurgery or simple surveillance.

[Surgical removal of unilateral vestibular schwannomas after failed Gamma Knife radiosurgery]. / Exérèse microchirurgicale des schwannomes vestibulaires unilatéraux préalablement traites par radiochirurgie Gamma Knife.

One of the primary criticismes of vestibular schwannoma (VS) radiosurgery is that the risk of surgical morbidity is increased for patients whose tumor progresses after the procedures. We reviewed the French experience of operated patients after failed Gamma Knife radiosurgery. From July 1992 to January 2002, 25 out of the 1000 treated patients underwent another treatment procedure for a gamma knife failure. Excluding the NF2 patients, 21 patients have been operated and the present study shows the data collected for 20 of them. In order to analyze the difficulties observed during the surgery, a questionnaire was filled by the surgeons. The mean interval between radiosurgery and removal was 36 Months, from 10 to 83 Months. The mean increase in Volume was 559% (37 to 3036%, median 160%). Evolution of the Koos grading was found from 8 grade II, 10 grade III et 2 grade IV to 10 grade III and 10 grade IV. Patients have been operated for radiological tumor growth in 7 cases and for clinico-radiological evolution in 13 cases. In 9 cases, the surgeon considered that he had to face unusual difficulties mainly because of adhesion of the tumor to neurovascular structures. Tumor removal was total in 14 cases, near total in 4 cases and subtotal in 2 cases. One case of venous infarction was noticed at the second day following surgery responsible of hemiparesis and aphasia that gradually recovered. At last follow-up examination, facial nerve was normal (House and Brackmann grade I and II) in 10 cases while it was a grade III in 7 cases and grade IV and V in 3 cases. We recommend that the decision for surgical removal of growing vestibular schwannoma after Gamma Knife treatment should be done after a sufficiently long follow-up period. Our results show that the quality of removal and of facial nerve preservation might be impaired by radiosurgery in half of cases. However these results do not support a change in our policy of radiosurgical treatment of small to medium size vestibular schwannoma.

[Radiosurgery of vestibular schwannomas after microsurgery and combined radio-microsurgery]. / Radiochirurgie Gamma Knife après microchirurgie des schwannomes vestibulaires et stratégie combinée radio-microchirurgicale.

Significant morbidity is expected after microsurgery for recurrent or growing residual vestibular schwannoma (VS). In order to avoid this procedure, radiosurgery appeared as an interesting alternative. The purpose of this study is to analyze the results of Gamma Knife radiosurgery in this indication. Between July 1992 and January 2002, 60 patients (including 12 NF2 patients) underwent radiosurgical treatment after one or more attempts of surgical resection (including 27 growing remnant VS and 19 recurrent VS) and could be followed with enough informations, out of 103 patients (10% of the VS population treated during the same period). Mean interval between surgical removal and radiosurgery was 71.5 Months (1.8-127.8 Months). Technical difficulties during the procedure were observed in the 12 cases, mainly due to problems in identifying the target. Median follow-up was 51.6 Months. Four out of 58 patients (7%, confidence interval: 1.9-16.7) were diagnosed as failure. Statistical study failed to find significant parameters influencing failure. Facial and trigeminal nerves were not impaired while one case of severe bulbopontine radio-induced injury leading to a lower cranial nerve deficit was observed. These results show that, in spite of additional difficulties to treat these patients with radiosurgery, this treatment is efficient with acceptable morbidity and can avoid another microsurgical procedure. The strategy of planned combined micro-and radiosurgical treatment of large VS deserves additional investigations to be validated.

[Cystic vestibular schwannomas]. / Schwannomes vestibulaires kystiques.

RATIONALE: Patients with cystic vestibular schwannomas (VS) are a radiologically well-defined subgroup of patients who classically have poor outcome after microsurgical resection. Since Pendl's report of a high rate of failures, they are also considered as poor candidates for radiosurgery. MATERIAL AND METHOD: Among the 1000 consecutive patients who underwent Gamma Knife surgery in Marseilles, France between July 1992 and January 2002, we have collected and studied 54 patients with cystic VS at the time of treatment. RESULTS: The median follow-up of this group was 26 Months (mean: 33, range: 6-90). Failure (6.4%) led to microsurgical removal in 2 patients and a radiosurgery in 1 patient with a delay of 2 Years for 2 of them and 3 Years for the third. No facial palsy has been reported. Two patients developed transient hypesthesia. Among the 32 patients with functional hearing at the time of treatment, 53% preserved their hearing function at 3 Years. CONCLUSIONS: We found an increased risk of failure in this group compared to patients with no cyst at time of radiosurgery (93.6% instead of 98%). But this is also a group were we observe most dramatic shrinkage. Prudent radiosurgical treatment of cystic vestibular schwannomas remains mandatory: strict follow-up is specially important.

Relative indications for radiosurgery and microsurgery for acoustic schwannoma.

The physical and biological principles underlying the use of radiosurgery for the treatment of vestibular schwannomas of up to 2.5 cm in diameter are reviewed together with the historical controversies that have surrounded its introduction. The results in terms of mortality, quality of life, preservation of facial movement and hearing, incidence of shunt-dependent hydrocephalus, cancer neogenesis and brain stem damage are compared in the Marseilles series of 600 microsurgical procedures and 830 Gamma knife procedures and with the peer-reviewed literature. The key principles of a steep profile to radiation exposure at the tumour margin, careful topographical planning of the radiation against the tumour shape to minimise the radiation dose to the cranial nerves and brain stem, early tumour swelling, tumour texture and national history of the tumour are analysed. Protocols for the management of unilateral schwannoma, Type II neurofibromatosis (both the Wishart and the Gardner types) and residual/recurrent tumours are presented. In summary, the growth of nearly 97% of vestibular schwannomas (up to 2.5 cm) is arrested by the Gamma knife, the facial nerve is preserved in almost all cases and hearing may be preserved at its pre-operative level in nearly 70% of cases without the complications of microsurgery.

Gamma knife radiosurgery in the management of cavernous sinus meningiomas.

OBJECT: The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). METHODS: Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6-71 years). The mean tumor volume was 5.8 cm3 (range 0.9-18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12-50 Gy), delivered with an average of eight isocenters (range two-18). The median peripheral isodose was 50% (range 30-70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12-79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. CONCLUSIONS: Gamma knife radiosurgery was found to be an effective low morbidity-related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.

Preservation of hearing in acoustic neuromas treated by gamma knife surgery.

138 acoustic schwannomas were treated by Gamma Knife surgery from July 1992 to May 1994. Cases with neurofibromatosis were excluded because of differences in the patterns of growth and development of tumors in these cases. Hearing was evaluated by tonal and vocal audiometry and classified using the Gardner and Robertson score. 104 patients were observed at 3 years after treatment. Hearing studies, the relation of tumor volume to hearing, central and marginal dose, number of shots and preoperative brain-stem-evoked responses (BER) were all recorded. 70% of patients with normal hearing maintained a useful hearing, and 50% of patients with useful hearing maintained serviceable hearing. No correlation was found between hearing preservation and tumor volume, central and marginal dose and number of shots. Gamma Knife surgery seems to be superior to microsurgery with regard to preservation of useful hearing.