Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas

Abstract

OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients experienced worsening of trigeminal nerve function. Facial nerve function worsened in 1 patient (2.5%). No significant differences in tumor control, hearing preservation, or complications were found in comparing the results of GKRS for NF2-related VS versus GKRS for sporadic VS. CONCLUSIONS With modern GKRS, the use of low margin doses for treating growing VSs in patients with NF2 demonstrates good long-term tumor control rates. Feiling-Gardner phenotype and tumor volume smaller than 6 cm seem to be independently associated with prolonged progression-free survival, highlighting the clinical importance of phenotype assessment before GKRS treatment. In addition, no significant differences in tumor control rates or complications were found in the matched-control cohort analysis comparing GKRS for VS in patients with NF2 and GKRS for sporadic VS. These results show that GKRS is a valid treatment option for NF2-related VS, in addition to being a good option for sporadic VS, particularly in patients with the Feiling-Gardner phenotype and/or tumors that are small to ...

Clinical Results After Single-fraction Radiosurgery for 1,002 Vestibular Schwannomas

“…Contrary to most research on SRS for VS, NF2 was not associated with reduced local control. Given the limited number of NF2-associated tumors (n = 31) in this study (but also in many other publications), drawing definite conclusions from this finding is difficult [16][17][18]. However, the median tumor volume for NF2-associated tumors was 0.82 ccm, which is considerably smaller than in many existing publications [18].…”

“…One could, therefore, hypothesize that the effect of reduced local control associated with NF2 loses predictive significance once the tumors are irradiated while at a sufficiently small volume. As many studies on NF2-associated schwannomas already report tumor volume as a predictor of local control, subgroup analyses of these collectives could answer the question, whether treatment of small NF2-associated tumors may result in equally good local control rates as treatment of sporadic VS [16][17].…”

Long-Term Outcomes of Stereotactic Radiosurgery for Vestibular Schwannoma Associated with Neurofibromatosis Type 2 in Comparison to Sporadic Schwannoma

“…In particular, stereotactic radiosurgery (SRS) is a main therapeutic modality for small to medium-large sporadic VS, offering advantages such as excellent tumor control, low toxicity for the facial nerve, and minimal invasiveness [11,12,13,14,15,16]. Nevertheless, robust evidence regarding the use of SRS for NF2-associated VSs is lacking, and long-term outcomes have not been fully elucidated [17,18,19,20,21,22,23,24,25,26,27]. To address these deficiencies, we conducted the present retrospective study to investigate radiosurgical outcomes for NF2-associated VSs and to compare the results with those for sporadic VS using matched cohort analysis.…”

Outcomes and prognostic stratification of patients with recurrent glioblastoma treated with salvage stereotactic radiosurgery

“…chemotherapeutic agents, 9,13,35,59,[65][66][67] targeted therapies, 2,7,13,23,38 immunotherapeutic options, 15,37,41 and tumor treating fields 53,55,56 have all been utilized with varied success. Salvage radiation with SRS is a well-established treatment modality for a variety of benign 17,19,24,64 and malignant brain tumors. 11,16,21,34,39,50,62,68 There is, however, insufficient evidence to either support or refute the use of radiosurgery in patients with recurrent or progressive malignant glioma; 63 various salvage SRS series have reported a median overall survival (OS) ranging between 5.3 and 24 months in patients with rGBM.…”