Assessing Tumor Volume for Sporadic Vestibular Schwannomas: A Comparison of Methods of Volumetry.

INTRODUCTION: The size of vestibular schwannomas (VS) is a major factor guiding the initial decision of treatment and the definition of tumor control or failure. Accurate measurement and standardized definition are mandatory; yet no standard exist. Various approximation methods using linear measures or segmental volumetry have been reported. We reviewed different methods of volumetry and evaluated their correlation and agreement using our own historical cohort. METHODS: We selected patients treated for sporadic VS by Gammaknife radiosurgery (GKRS) in our department. Using the stereotactic 3D T1 enhancing MRI on the day of GKRS, 4 methods of volumetry using linear measurements (5-axis, 3-axis, 3-axis-averaged, and 1-axis) and segmental volumetry were compared to each other. The degree of correlation was evaluated using an intraclass correlation test (ICC 3,1). The agreement between the different methods was evaluated using Bland-Altman diagrams. RESULTS: A total of 2,188 patients were included. We observed an excellent ICC between 5-axis volumetry (0.98), 3-axis volumetry (0.96), and 3-axis-averaged volumetry (0.96) and segmental volumetry, respectively, irrespective of the Koos grade or Ohata classification. The ICC for 1-axis volumetry was lower (0.72) and varied depending on the Koos and Ohata subgroups. None of these methods were substitutable. CONCLUSION: Although segmental volumetry is deemed the most accurate method, it takes more effort and requires sophisticated computation systems compared to methods of volumetry using linear measurements. 5-axis volumetry affords the best adequacy with segmental volumetry among all methods under assessment, irrespective of the shape of the tumor. 1-axis volumetry should not be used.

Long-Term Hearing Outcome After Radiosurgery for Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Stereotactic radiosurgery (SRS) is one of the main treatment options in the management of small to medium size vestibular schwannomas (VSs), because of high tumor control rate and low cranial nerves morbidity. Series reporting long-term hearing outcome (>3 years) are scarce. OBJECTIVE: To perform a systematic review of the literature and meta-analysis, with the aim of focusing on long-term hearing preservation after SRS. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles published between January 1990 and October 2020 and referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical study or case series of VSs treated with SRS (single dose), reporting hearing outcome after SRS with a median or mean audiometric follow-up of at least 5 years. Hearing preservation, cranial nerves outcomes, and tumor control were evaluated. RESULTS: Twenty-three studies were included. Hearing preservation was found in 59.4% of cases (median follow-up 6.7 years, 1409 patients). Main favorable prognostic factors were young age, good hearing status, early treatment after diagnosis, small tumor volume, low marginal irradiation dose, and maximal dose to the cochlea. Tumor control was achieved in 96.1%. Facial nerve deficit and trigeminal neuropathy were found in 1.3% and 3.2% of patients, respectively, both significantly higher in Linear Accelerator series than Gamma Knife series ( P < .05). CONCLUSION: Long-term hearing preservation remains one of the main issues after SRS, with a major impact on health-related quality of life. Our meta-analysis suggests that hearing preservation can be achieved in almost 60% of patients after a median follow-up of 6.7 years, irrespective of the technique.

Stereotactic radiosurgery for post operative brain metastasic surgical cavities: a single institution experience.

BACKGROUND: The standard therapy for brain metastasis was surgery combined with whole brain radiotherapy (WBRT). The latter is however, associated with important neurocognitive toxicity. To reduce this toxicity, postoperative stereotactic radiosurgery (SRS) is a promising technique. We assessed the efficacy and the tolerance to postoperative Gamma Knife radiosurgery (GK) on the tumor bed after resection of brain metastases. METHODS: Between February 2011 and December 2016, following macroscopic complete surgical resection, 64 patients and 65 surgical cavities were treated by GK in our institution. The indication for adjuvant radiosurgery was a multidisciplinary decision. The main assessment criteria considered in this study were local control, intracranial metastasis-free survival (ICMFS), overall survival and toxicity. RESULTS: Median follow-up: 11.1 months. Median time between surgery and radiosurgery: 35 days. Median dose was 20 Gy prescribed to the 50% isodose line, for a median treated volume of 5.6 cc. Four patients (7%) suffered from local recurrence. Local recurrence-free, intracranial recurrence-free and overall survival at 1 year were 97.5%, 57.6% and 62.4% respectively. In total, 23 patients (41%) suffered from intracranial recurrence outside the tumor bed. In univariate analysis: concomitant GK treatment of multiple lesions and the tumor bed was associated with a decrease in ICMFS (HR = 1.16 [1.005-1.34] p = 0.04). In multivariate analysis: a non-lung primary tumor was significantly associated with a decrease in ICMFS (HR = 8.04 [1.82-35.4] p = 0.006). An increase in performance status (PS) and in the initial number of cerebral metastases significantly reduced overall survival (HR = 5.4 [1.11-26.3] p = 0.037, HR = 2.7 [1.004-7.36] p = 0.049, respectively) and One radiation necrosis histologically proven. CONCLUSION: Our study confirmed that postoperative GK after resection of cerebral metastases is an efficient and well-tolerated technique, to treat volumes of all sizes (0.8 to 40 cc). Iterative SRS or salvage WBRT can be performed in cases of intracranial relapse, postponing WBRT with its potential side effects.

Mask-Based versus Frame-Based Gamma Knife ICON Radiosurgery in Brain Metastases: A Prospective Randomized Trial.

BACKGROUND: Radiosurgery is performed with a diversity of instruments relying usually either on a stereotactic frame or a mask for patient head fixation. Comfort and safety efficacy of the 2 systems have never been rigorously evaluated and compared. MATERIAL AND METHOD: Between February 2016 and January 2017, 58 patients presenting with nonsmall cell lung cancer brain metastases have been treated by Gamma Knife radiosurgery (GKS) with random use of a frame or a mask for fixation were included patients older than 18, with <5 brain metastases (at the exclusion of brainstem and optic pathway's locations) and no earlier history of radiotherapy. The primary outcome measure was the pain scale assessment (PSA) at the beginning of the GKS procedure. RESULTS: The PSA at the beginning of the GKS procedure was not different between the 2 groups. The PSA at the day before GKS, before magnetic resonance imaging, just after frame application, and the day after radiosurgery (departure) has shown no difference between the 2 groups. At the end of the radiosurgery itself (just after frame or mask removal) and 1 h after, the mean pain scale was higher in patients treated with the frame (p < 0.05 and p < 0.001, respectively) but 2 patients were not able to tolerate the mask discomfort and had to be treated with frame. Tumor control and morbidity probability were demonstrated to be no difference between the 2 groups in this population of patients with BM not in highly functional area. The median of the extra dose to the body due to the cone-beam computed tomography was 7.5 mGy with a maximum of 35 mGy in patients treated with a mask fixation (null in the others treated with frame). Mask fixation was associated to longer treatment time although the beam on time was not different between the 2 groups. CONCLUSION: In selected patients, with brain oligo-metastases out of critical location, single-dose mask-based GKS can be done with a comfort and a safety efficacy comparable to frame-based GKS. There seems to be no clear patient data that confirm the value of the mask system with regards to comfort.

Radiosurgery for vestibular schwannomas.

This article investigates the role of radiosurgery and stereotactic radiotherapy in the management of vestibular schwannomas (VS), reviewing the authors' own prospective cohort and the current literature. For patients with large Stage IV VS (according to the Koos classification), a combined approach with deliberate partial microsurgical removal followed by radiosurgery to the residual tumor is proposed. The authors' cohort is unique with respect to the size of the population and the length of the follow-up, and demonstrates the efficacy and safety of VS radiosurgery, with particular regard to its high rate of hearing preservation.

Wait-and-see strategy compared with proactive Gamma Knife surgery in patients with intracanalicular vestibular schwannomas.

OBJECT: The roles of the wait-and-see strategy and proactive Gamma Knife surgery (GKS) in the treatment paradigm for small intracanalicular vestibular schwannomas (VSs) is still a matter of debate, especially when patients present with functional hearing. The authors compare these 2 methods. METHODS: Forty-seven patients (22 men and 25 women) harboring an intracanalicular VS were followed prospectively. The mean age of the patients at the time of inclusion was 54.4 years (range 20-71 years). The mean follow-up period was 43.8 ± 40 months (range 9-222 months). Failure was defined as significant tumor growth and/or hearing deterioration that required microsurgical or radiosurgical treatment. This population was compared with a control group of 34 patients harboring a unilateral intracanalicular VS who were consecutively treated by GKS and had functional hearing at the time of radiosurgery. RESULTS: Of the 47 patients in the wait-and-see group, treatment failure (tumor growth requiring treatment) was observed in 35 patients (74%), although conservative treatment is still ongoing for 12 patients. Treatment failure in the control (GKS) group occurred in only 1 (3%) of 34 patients. In the wait-and-see group, there was no change in tumor size in 10 patients (21%), tumor growth in 36 patients (77%), and a mild decrease in tumor size in 1 patient (2%). Forty patients in the wait-and-see group were available for a hearing level study, which demonstrated no change in Gardner-Robertson hearing class for 24 patients (60%). Fifteen patients (38%) experienced more than 10 db of hearing loss and 2 of them became deaf. At 3, 4, and 5 years, the useful hearing preservation rates were 75%, 52%, and 41% in the wait-and-see group and 77%, 70%, and 64% in the control group, respectively. Thus, the chances of maintaining functional hearing and avoiding further intervention were much higher in cases treated by GKS (79% and 60% at 2 and 5 years, respectively) than in cases managed by the wait-and-see strategy (43% and 14% at 2 and 5 years, respectively). CONCLUSIONS: These data indicate that the wait-and-see policy exposes the patient to elevated risks of tumor growth and degradation of hearing. Both events may occur independently in the mid-term period. This information must be presented to the patient. A careful sequential follow-up may be adopted when the wait-and-see strategy is chosen, but proactive GKS is recommended when hearing is still useful at the time of diagnosis. This recommendation may be a main paradigm shift in the practice of treating intracanalicular VSs.

Repeat gamma knife surgery for regrowth of vestibular schwannomas.

OBJECTIVE: Gamma knife surgery (GKS) has become established as a minimally invasive treatment modality for patients with vestibular schwannomas. Treatment failure and/or tumor regrowth, however, is occasionally encountered, and microsurgical resection is usually warranted in such cases. The role of repeat GKS in these situations is still unclear. The goal of this study was to investigate whether repeat GKS is an effective treatment for recurrent vestibular schwannomas and to assess the conservation of residual neurological function. METHODS: Between July 1992 and December 2007, 1951 patients harboring a unilateral vestibular schwannoma were treated with GKS. Of these, 48 patients (2.5%) had to undergo a subsequent intervention because of progression or regrowth of the tumor. Repeat GKS was performed in a total of 15 patients, 8 of whom had more than 2 years of follow-up and were eligible to be enrolled in the present study. The median follow-up period after repeat GKS was 64 months, and the median interval between these interventions was 46 months. The median tumor volume was 0.51 and 1.28 mL at the initial and second GKS treatments, respectively. Patients received a median prescription dose of 12.0 Gy at both interventions. RESULTS: We report no cases of failure. Six patients demonstrated a significant reduction in tumor volume. In 1 patient, the final tumor volume was less than the initial volume. The other 2 patients showed stabilization of tumor growth. Useful hearing ability was preserved in only 1 of the 3 patients who had serviceable hearing ability at the time of the second GKS. Neither aggravation of facial nerve dysfunction nor other neurological deficits secondary to GKS were observed. CONCLUSION: This is the first report to address repeat GKS for vestibular schwannomas. After long-term follow-up, repeat GKS with a low marginal dose seems to be a safe and effective treatment in selected patients harboring regrowth of small vestibular schwannomas that have previously been treated with GKS.

Morphological changes of vestibular schwannomas after radiosurgical treatment: pitfalls and diagnosis of failure.

RATIONALE: Evaluate the morphological changes following radiosurgery in order to better define failure parameters. METHODS: 332 non-neurofibromatosis type 2 vestibular schwannomas not previously treated surgically or radiosurgically were subjected to Gamma Knife radiosurgery between 1992 and 2004 at the Gamma Knife Center in Marseille with at least three sequential MRI scans after radiosurgery. Five length measurements were systematically obtained. RESULTS: Mean follow-up was 4.6 years. Transient loss of contrast enhancement appeared in 213 patients (68%). Significant increase was present at 6 months in 178 patients. In 74 patients, the volume at 3 years was still higher than on the day of radiosurgery but remained stable. Failure occurred in 16 patients. Most showed progressive growth at all MRI controls after radiosurgery but late failure after initial response was possible. CONCLUSIONS: Sequential MRI scans after radiosurgery are necessary. A progressive and continuous growth at 3 years is essential to make diagnosis of failure.

Hearing preservation in patients with unilateral vestibular schwannoma after gamma knife surgery.

INTRODUCTION: The majority of patients still lose the functionality of their hearing in spite of the technical advances in microsurgery. Our aim was to evaluate the hearing preservation potential of Gamma Knife Surgery. We have reviewed our experience and the literature in order to evaluate the probability to obtain such functional preservation and the factors influencing it. METHODS: Since July 1992, 2,053 patients have been operated on by Gamma Knife Radiosurgery in Timone University Hospital. This population included 184 unilateral schwannoma patients with functional preoperative hearing (Gardner-Robertson 1 or 2) treated by first intention radiosurgery with a marginal dose lower than 13 Gy. The population included 74 patients with subnormal hearing (class 1). All have been studied with a follow-up longer than 3 years. Univariate and multivariate analyses have been carried out. RESULTS: Numerous parameters greatly influence the probability of functional hearing preservation at 3 years, which is globally 60%. The main preoperative parameters of predictability are limited hearing loss that is Gardner-Robertson stage 1 (vs. 2), presence of tinnitus, young age of the patient and small size of the lesion. The functional hearing preservation at 3 years is 77.8% when the patient is initially in stage 1, 80% in patients with tinnitus as a first symptom and 95% when the patient has both. In these patients, the probability of functional preservation at 5 years is 84%. Comparison of these results with the main series of the literature confirms the reproducibility of our results. Additionally, we have demonstrated a higher chance of hearing preservation when the dose to the cochlea is lower than 4 Gy. CONCLUSION: We report a large population of patients treated by radiosurgery with functional preoperative hearing. These results demonstrate the possibility to preserve functional hearing in a high percentage of selected patients. Radiosurgery offers them a higher chance of functional hearing preservation than microsurgery or simple follow-up.

Surgical removal of vestibular schwannoma after failed gamma knife radiosurgery.

One of the main criticisms of vestibular schwannoma (VS) radiosurgery is that the risk of surgical morbidity is increased for patients whose tumor progresses in cases of failed procedures. The authors reviewed the French neurosurgical experience of operated patients after failed Gamma Knife radiosurgery (GKR). From July 1992 to December 2000, 23 unilateral VS out of the 1,000 treated patients have undergone a microsurgical procedure after failed GKR. In order to analyze the difficulties observed during the surgery, a questionnaire was completed by the surgeons. The mean interval between radiosurgery and removal was 39 months (range: 10-92 months). The mean increasing volume was 389% (range: 37-1,600) and the median was 150%. Seven patients have been operated on for radiological tumor growth and 13 for clinicoradiological evolution. In 10 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 15 cases, near total in 4 cases and subtotal in 4 cases. One case of venous infarction was noticed on the 2nd day following surgery and was responsible for hemiparesis and aphasia that gradually recovered. At the last follow-up examination, facial nerve was normal or near normal (House-Brackmann grades 1 and 2) in 12 cases (52%) while it was grade 3 in 9 cases and grades 4 and 5 in 2 cases. Our results show that the quality of removal and of facial nerve preservation might be impaired after GKR in half of cases. However, these results do not support a change in our policy of first intention radiosurgical treatment of small- to medium-sized VSs.

Modern management of vestibular schwannomas.

Within the last 3 decades, microsurgery and stereotactic radiosurgery (SRS) have become well-established management options for vestibular schwannomas (VSs). Advancement in the management of VSs can be separated into three periods: the microsurgical pioneer period, the demonstration of SRS as a first-line therapy for small and medium-sized VSs, and currently, a period of SRS maturity based on a large worldwide patient accrual. The Marseille SRS experience includes 1,500 patients, with 1,000 patients having follow-up longer than 3 years. A long-term tumor control rate of 97%, transient facial palsy lower than 1%, and a probability of functional hearing preservation between 50 and 95% was achieved in this large series of patients treated with state-of-the-art SRS.

Brainstem metastases: management using gamma knife radiosurgery.

OBJECTIVE: Brainstem metastasis is an uncommon complication of systemic cancer, generally considered to have a highly unfavorable prognosis. Surgical risks are high and standard radiation or chemotherapy have little effect. The purpose of this study is to evaluate our experience using Gamma Knife radiosurgery (GKRS) for the management of brainstem metastasis. METHODS: Between July 1992 and March 2001, we treated 28 patients with brainstem metastasis using GKRS. Lesions were located in the pons in 17 patients, midbrain in nine, and medulla oblongata in two. At time of the radiosurgery, eight patients presented with another supratentorial metastasis. The most frequent primary tumor site was the lung (13 cases) followed by the melanoma in four cases, the kidney in two, and other locations in six. Only six patients underwent fractionated whole-brain radiation therapy. Mean marginal radiation dose for GKRS was 19.6 Gy (range, 11-30). Mean maximum diameter was 17.2 mm (range, 10-30). RESULTS: No GKRS-related morbidity was observed. Local tumor control was achieved in 92% of patients. Twenty-six patients have died. Death was related to the progression of the brainstem lesion in two cases. Mean and median survival after GKRS were 10.2 and 12 months, respectively. Follow-up periods in the two surviving patients were 12 and 13 months. CONCLUSION: The results of this small series demonstrate that GKRS can be a valuable modality for safe and effective management of brain stem metastasis. Owing to the high risk of surgical resection and low efficacy of medical treatment, radiosurgery can be proposed upfront.

Functional outcome after gamma knife surgery or microsurgery for vestibular schwannomas.

OBJECT: Microsurgical excision is an established treatment for vestibular schwannoma (VS). In 1992 the authors used a patient questionnaire to evaluate the functional outcome and quality of life in a series of 224 consecutive patients. In addition, starting with gamma knife surgery (GKS) in 1992, the authors decided to use the same methodology to evaluate prospectively the results of this modality to compare the two alternatives. METHODS: Among the 500 patients who were included prospectively, the authors only evaluated patients in whom GKS was the primary treatment for unilateral VS. Four years of follow up was available for the first 104 consecutive patients. Statistical analysis of the GKS and microsurgery populations has shown that only a comparison of Stage II and III (according to the Koos classification) was meaningful in terms of group size and preoperative risk factor distribution. Objective results and questionnaire answers from the first 97 consecutive patients were compared with the 110 patients in the microsurgery group who fulfilled the inclusion criteria. Questionnaire answers indicated that 100% of patients who underwent GKS compared with 63% of patients who underwent microsurgery had no new facial motor disturbance. Forty-nine percent of patients who underwent GKS (17% in the microsurgery study) had no ocular symptoms, and 91% of patients treated with GKS (61% in the microsurgery study) had no functional deterioration after treatment. The mean hospitalization stay was 3 days after GKS and 23 days after microsurgery. All the patients who underwent GKS who had been employed, except one, had kept the same professional activity (56% in the microsurgery study). The mean time away from work was 7 days for GKS (130 days in the microsurgery study). Among patients whose preoperative hearing level was Class 1 according to the Gardner and Robertson scale, 70% preserved functional hearing after GKS (Class 1 or 2) compared with only 37.5% in the microsurgery group. CONCLUSIONS: Functional side effects happen during the first 2 years after radiosurgery. Findings after 4 years of follow up indicated that GKS provided better functional outcomes than microsurgery in this patient series.

Impact of the model C and Automatic Positioning System on gamma knife radiosurgery: an evaluation in vestibular schwannomas.

OBJECT: The technical advances associated with the model C gamma knife include a robotized system enabling automatic positioning of the stereotactic coordinates. The purpose of this study was to analyze the clinical impact of this technical modification. METHODS: The authors studied a sample of patients with vestibular schwannoma (VS). This sample included three groups treated using gamma knife radiosurgery. Group I comprised 21 patients with VS treated just before the installation of the Automatic Positioning System (APS). Group II included patients in Group I with new dose plans created using the APS (in other words, simulated dose plans). Group III consisted of a control group of 20 patients matched for tumor grade with the previous group and treated recently with the APS. Treatment times were calculated after correcting the time for each shot according to the age of the sources after reloading. The treatment times, including total time, irradiation time, and duration of the neurosurgical procedure, were analyzed. In addition, dose planning including number of isocenters, number of different collimators, malfunctions, and the conformity and selectivity indices were recorded. The trend was to reduce the mean number of collimator runs from 7.9 to 1.2 and to increase the mean number of shots from 7.9 to 15.6, mostly by using the 4-mm collimator exclusively. The APS-related conformity and selectivity were improved from 95 to 97% and from 78 to 84%, respectively. The total treatment time was reduced by 53%, and time required to interact with the patient in the room was considerably reduced (75%), giving the neurosurgeon greater freedom to perform other tasks during the treatment period. The reduction of the time spent by the neurosurgeon at work in the room was 84%. The total radiation time was increased by 54%. CONCLUSIONS: The preliminary results of this study indicate that the robotization of the gamma knife is likely a major advance in radiosurgery.