Leksell Gamma Knife® Icon™ Clinical Experience [Document reference number: 4513 371 1489]

Overview of treatment patterns to date Survey of current clinical experience Overview based on survey of 11 operational sites Directional information only To protect the integrity of the reporting centers, no center-specific data is published Data was reported from July 2015 through July 2016 Regional distribution of reporting centers

Global case mix

Immobilization: distribution of methods utilized

Immobilization: distribution of methods utilized July 21, 2018 Immobilization: distribution of methods utilized Per highest volume indications Choice of fixations used, example: Adapted from: Transforming brain radiosurgery: Clinical application of a novel tool. Webinar by D Prasad, MD. https://www.brighttalk.com/webcast/8013/218733

Immobilization: distribution of methods utilized Per number of metastases

Fractionation: Distribution of number of fractions

Icon increases patient volume Incremental volumes reported of up to 25% with LGK Icon compared to Perfexion. Increased volume includes cases not possible to treat with Perfexion: Fractionation preferred because of: Target volume Abutting critical structures Avoid repeat fixed frame fit Patient refuses frame

Icon opens up new types of treatments New treatment paradigms with an adaptive, mask-based approach range from single session treatments and hypo-fractionation to full fraction schemes Case report* Adaptive fractionated stereotactic Gamma Knife radiotherapy of meningioma using integrated stereotactic cone-beam-CT and adaptive re-planning (a-gkFSRT) Examples of treatment regimens as reported Pituitary 1.80Gy @80% in 25# (fractions) Vestibular Schwannoma 50Gy in 25# Meningioma (contacting optic nerve/chiasm) 25Gy @50% in 5# Meningioma 31 cc 25Gy @45% in 5# Metastasis 16 cc 30Gy @51% in 5# Metastasis 14 cc 27Gy @63/50/52% in 3# Metastasis (contact with optics) 30Gy @50% and 24Gy @50% in 5# 76 yr old female Benign meningioma, WHO grade I, located at left petrous bone. Volume 5.88 cm3 Hypofractionated mask-based treatment. 5x 5 Gy to GTV, to preserve the acoustic and facial nerve. Adaptive daily re-plan Outcome: Adaptive daily re-planning was accurate and yielded quality measures, e. g., coverage, selectivity, and gradient for the delivered dose identical to the initial values Treatment well tolerated (slight headache after 1st treatment resolved with dexamethasone) Follow-up at 6 weeks and 4 months: no neurological symptoms * Stieler F, Wenz F, Abo-Madyan et al. Strahlenther Onkol July 2016.

Over 1,000,000 patients treated with LGK Over 1,000 Icon treatments have been reported through July, 2016. Source: Leksell Gamma Knife Society, Annual Treatment Statistics 2015

17 LGK Icon sites in clinical use July 21, 2018 17 LGK Icon sites in clinical use Status: September 2016