Gamma Knife Radiosurgery for Large Vestibular Schwannomas: A Canadian Experience Zeiler FA1, Bigder M1, Kaufmann AM1, McDonald PJ1, Fewer D1, Butler J2, Schroeder G2, West M1 Section of Neurosurgery, Dept of Surgery, University of Manitoba Dept of Radiation Oncology, University of Manitoba

Background Treatment of small to medium sized vestibular schwannomas (VS) with Gamma Knife (GK) stereotactic radiosurgery is a well-documented treatment alternative to surgical resection, with prospective nonrandomized trials demonstrating facial nerve and hearing preservation rates favoring GK over microsurgery1,2.

Background Cont’d Tumor control rates have been described upwards of 94% in recent literature, with acceptable complication rates3 when compared to microsurgery. Long term actuarial resection-free control rates have been documented at 98.3%4-6, emphasizing the lasting effect post-GK.

Background Cont’d Larger VS pose a difficult clinical challenge, with many authors favoring surgical resection due to concerns around radiation dosing and side effects. GK for VS 3-4 cm maximal diameter as an isolated treatment, without surgical resection, has demonstrated an 89% tumor control rate at two years8 in the literature so far. Hearing, facial nerve, and trigeminal nerve preservation rates in these large VS treated with GK have been documented at 58%, 91%, and 86% respectively9.

Objectives To retrospectively review our institutional data for GK in treating VS of 3 – 4cm diameter in order to determine: Tumor control rates Hearing preservation rates Facial nerve preservation rates Complications

Methods Retrospective cohort study of all patients treated for large VS, size 3 to 4 cm in maximal diameter, at our institution up to and including March 2012. A total of 28 patients were identified, from 235 VS treated during that time frame.

Results 28 patients total identified There were 15 male (54%) and 13 female (46%) patients, with an average age of 56 years (range: 26 – 85). Twelve (42.3%) patients had previous resection of their VS remote from their GK treatment, and not as a staged treatment prior to GK. 2 with history of Neurofibromatosis

Results Cont’d 3 patients (10.7%) were lost to follow up. Average follow up = 34.5 months (range: 6 – 99). Fourteen patients had 2 years or greater follow up. Average pre-treatment Gardner-Robertson grade = 3.9 (1-5). Average pre-treatment House-Brackmann grade = 2 (1-6).

Results Cont’d Average tumor maximum diameter was 3.28 cm (range: 3.0-4.0 cm). The anatomical distribution of tumors for the 25 patients were as follows: Cerebellar-pontine angle (CPA) alone (1) CPA with internal acoustic canal (IAC) extension (1) CPA with brainstem compression (4) CPA with IAC extension Brainstem compression (19)

Previous Surgical Resection (n=12) Demographic Category Patients with Follow-Up (n=25) Two Year Follow-up Group (n=14) Previous Surgical Resection (n=12) Age (years) 26-85 (avg: 56) 32-85 (avg: 57) 49-85 (avg: 63) Sex Male 13 (52%) 8 (57.1%) 7 (58.3%) Female 12 (48%) 6 (42.9%) 5 (41.6%) Average AN Diameter (cm) 3.28 3.31 3.21 Average % coverage 97.2% 96.3% 96.7% Average 50% isodose line (Gy) 12.5 Average Time Until VS radiological response (months) 20.4 24.8 19.5 Total Number with Tumor Control 23 (92.0%) 12 (85.7%) 12 (100%) Improved in HB Score 3 (12%) 2 (14%) 2 (16.7%) Worsened HB Score 0 (0%) Improved GR Score Worsened GR Score n = number, Avg = average, cm = centimetre, Gy = gray, VS = vestibular schwannoma, HB = House-Brackmann, GR = Gardner-Robertson

Results Cont’d Average 50% isodose line dose was 12.5 Gy (range: 12 – 13 Gy). The average max dose was 25 Gy (range: 24 – 26 Gy). The average total volume covered (TVC) was 9.71 cm3 (range: 6.9 – 10.6 cm3), with an average coverage of 97.2% (range: 91 - 100%).

Results Cont’d Fifteen patients recorded a brainstem dose on average 12.3 Gy (range: 10.7 – 14.6 Gy).

Results Cont’d Tumor control was defined as stability or decrease in size as of last follow-up imaging. Twenty-three of 25 patients (92.0%) displayed tumor control. Tumor size decreased in 14 of 25 (56.0%) and remained stable in 9 of 25 (36.0%). Permanent complications following GK occurred in one patient displaying worsened hemifacial spasm. No patients demonstrated deterioration in pre-GK facial nerve function, with the exception of the patient with worsened hemifacial spasm. No appreciable change, improvement or deterioration, was noted in GR score for any patient’s post-GK.

Discussion Our tumor control rate of 85.7% at 2 years is well within that described in the limited literature for large VS to date8,9. Facial nerve preservation rate is likely related to strict adherence to marginal dosing of 13 Gy or less, average age of 57 (less than 60), in addition to the majority of our patients (84%) having a HB grade of I, II, or III pre-GK. Sixteen of 25 (64%) patients had a GR grade of V prior to GK, indicating complete hearing loss and not amenable to deterioration post-treatment. However, the good rates of hearing preservation in the remainder of the population treated, we believe are related strict marginal dose adherence. We displayed a low rate of permanent complications, with only one patient having worsening hemifacial spasm.

Conclusions Gamma Knife of VS 3 – 4 cm diameter is feasible with good local control, low CN VII and VIII deterioration, and low complications. We believe these results stem from specific literature supporting: marginal tumor dose at 13 Gy or less maintenance of defined marginal doses and good pre-GK HB scores provided the opportunity for the facial nerve preservation reducing the trigeminal nerve dose where possible to a goal of less than 13 Gy, affords a low rate of temporary and permanent radiation induced trigmeninal neuropathy

Conclusions strive to reduce the cochlear dose where possible in order to prevent post-GK hearing deterioration vigilance at maintaining tight treatment conformality we believe affords a high rate of tumor control and low permanent complication rate

References 1. Pollock BE, Driscoll CL, Foote RL, et al. Patient outcomes after vestibular schwannoma management: a prospective comparison of microsurgical resection and stereotacic radiosurgery. Neurosurgery. 2006; 59:77-85. 2. Myrseth E, Moller P, Pedersen P, Lund-Johansen M. Vestibular schwannoma: surgery or Gamma Knife radiosurgery, A prospective, nonrandomized study. Neurosurgery. 2009; 64(4):654-63. 3. Timmer FCA, Hanssens PEJ, van Haren AE, et al. Follow-up after Gamma Knife radiosurgery for vestibular schwannomas: volumetric and axial control rates. Laryngoscope. 2011; 121:1359-66. 4. Chopra R, Kondziolka D, Nironjan A, Lunsford LD, Flickinger JC. Long-term follow-up of acoustic schwannoma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int J Radiation Oncology Biol Phys. 2007; 68(3):845-51. 5. Murphy ES, Barnett GH, Vogelbaum MA, et al. Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas. J Neurosurg. 2011; 114:432-40. 6. Roos DE, Potter AE, Brophy BP. Stereotactic radiosurgery for acoustic neuromas: what happens long term. Int J Radiation Oncology Biol Phys. 2012; 82(4):1352-55.

References 7. Yang H, Kano H, Awan NR, et al. Gamma Knife radiosurgery for larger-volume vestibular schwannomas. J Neurosurg. 2011; 114:801-7. 8. Van de Langenberg R, Hanssens PEJ, Verheul JB, et al. Management of large vestibular schwannoma. part II. primary Gamma Knife surgery: radiological and clinical aspects. J Neurosurg. 2011; 115:885-93.