1. NF2 and Hearing Preservation After Gamma Knife Treatment Reem Emad, MD Radiation Oncologist National Cancer Institute, Cairo University And Gamma Knife Center, Nasser Institute

2. Principles of Radiosurgery

3. Definitions Stereotaxy: ◦Stereo = 3D ◦Tact = Touch Stereotactic Radiosurgery: ◦Technique of delivering high dose of radiation to a specific target while delivering minimal dose to surrounding tissues.

4. How does it work Tumor reduction rate is equal to the rate of the normal growth of that tumor.

5. Radiosurgery Requirements 1.Precise and accurate target localization 2.Precise and accurate dose delivery (1 mm) 3.Sharp dose fall-off outside target volume 20% Target Volume 20% 20% % Dose fall-off = Distance between target edge and lower isodose surface

6. Equipment Stereotactic Frame system. 1.Rigid immobilization of the head during treatment. 2.Assign a unique coordinate to any point within the brain. Imaging equipment. -MRI -CT -DSA -PET

7. Equipment 3D target localization software. 3D treatment planning software.

8. Radiosurgery Machines  Gamma Knife  LINAC-based systems  Cyber Knife

9. Gamma Knife Radiosurgery For The Management Of Vestibular Shwannomas In Neurofibromatosis Type 2 Patients: Tumor Control And Hearing Preservation K. Abdel Karim 1,2, N. El Mashad 3, W. Reda 1,4, A. El-Shehaby 1,4, and R. Emad 1,5 1 Gamma Knife Centre, Nasser Institute 2 Clinical Oncology Department, Ain Shams University 3 Clinical Oncology Department, Tanta University 4 Neurosurgery Department, Ain Shams University 5 Radiation Oncology Department, NCI

10. NF2  Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic disorder characterized by mutations that affect a tumor suppression gene.  This gene is located on the long arm of chromosome 22.

11. NF2  These patients typically develop multiple CNS tumours, including meningiomas, schwannomas, ependymomas and gliomas.  The hallmark of NF2 is bilateral vestibular schwannomas. Most patients that present with this disorder lose hearing over time, and they may become completely deaf.  Therefore, next to tumour control, hearing preservation is of paramount importance in patients with NF2.

12. Why is NF2 treatment complicated?  Firstly, microsurgical resection of NF 2-associated VS carries a greater risk than sporadic tumors, regarding hearing loss and cranial nerve paresis.  This is because the tumor infiltrates and engulfs the cochlear nerve as well as the surrounding nerves unlike sporadic cases where the nerve is displaced and compressed. Besides, the tumors are commonly more aggressive with greater risk of recurrence.

13. Why is NF2 treatment complicated?  In addition, these tumors commonly occur in the younger age group so they have longer to live and require a treatment that will provide a better quality of life.  Also these patients will commonly harbor many tumors and develop many more during the course of their life span, making repeated surgeries a less practical treatment option.

14. Aim of Study  This study aimed at exploring the effect of GKS on NF2 associated VS in regard to the local control, hearing preservation, factors affecting both and neurological morbidity.

15. Patients  Between February 2002 and December 2010, 79 patients with VS associated with NF2 were treated by GKS at the GKC, Nasser Institute.  Forty patients harboring 69 tumors were available for follow up for a minimum of 2 years after treatment. The follow up duration ranged from 2 to 10.5 years (median 4 years)

16. Patient characteristicsNo. of patients (%) Sex Male18 (45%) Females22 (55%) Age9-56 years (mean 27 years) Previous surgery22 (55%) Previous radiotherapy2 (5%) Shunt8 (20%) Pre ttt Symptoms Hearing loss17 Tinnitus16 Facial palsy18 Ataxia10 Facial pain3 Facial numbness2 Bulbar palsy1

17. Treatment parametersMedian (range) Volume2.6 cc (0.1-27.5 cc) Prescription dose12 Gy (8-13 Gy) Prescription isodose50% (40-70%) Cover94% (77-100%) SI0.7 (0.1-0.9) GI2.9 (1-4.4)

18. Local Control The overall tumor control for this series was 87%. The median time to tumor progression was 39 months. Actuarial tumor control rates were 93%, 84%, and 43.5% at 5, 7 and 10 years, respectively.

19. Local Control Predictors  Predictors of better local control were smaller tumor volume (p 0.012) and older age (p 0.027)  While longer follow up was associated with worse tumor control (p 0.035).

20. The MRI images of a patient treated in 2005 and follow up images in 2008, 2009 and 2014 showing regressive course of the left vestibular schwanoma

21. Hearing Preservation Serviceable hearing preservation was 59.5%. The actuarial hearing preservation rates were 88%, 74.4% and 55.8% at 3, 5 and 7 years, respectively.

22. Hearing Preservation Predictors  Predictors for better hearing preservation were smaller volume (p 0.002), younger age (p 0.004) and pretreatment hearing status (p 0.025)

23. Six Six patients developed temporary adverse effects after GKS  1  1 patient required shunt after treatment. He was not previously shunted. 2  2 patients developed temporary facial palsy. steroids  3  3 patients developed temporary odema and ataxia. Recovery

24. AuthorPatients N.Tumors N.Mean Age Ys Mean V. ccDoseFollow up Ys LC %HP % AbdulKarim et al 2014 4069272.61248760 Massager et al 2013 1825302124.48778 Sun et al 2014 46195305.11298432 Rowe et al 2003 96122246154.15040 Mallory et al 2013 2632372.7147.68425 Hoon et al 2008 3036323.21247037 Mathieu et al 2006 6274365.7144.58342 Sharma et al 2010 3054293.7122.28766

25. VS: NF2 Vs Sporadic  GKS could provide long-term hearing preservation for 25%–67% of NF2 patients, which is less than what is expected for patients with sporadic VS.  This is based on a theoretical consideration that the cochlear nerve is likely to be inseparably entangled within an NF2 tumor, which may also be full of tiny schwannomas along the length of the nerve.

26. VS: NF2 Vs Sporadic  In the current study we found that the cochlear dose did not present a significant factor in hearing preservation when compared to tumor volume. This is in spite of other studies reporting the usefulness of cochlear doses as a predictor of hearing preservation after radiosurgery and radiotherapy.  This also may be due the fact that these studies were reporting on cases of sporadic VS where the cochlear nerve is displaced and not engulfed.

27. Facial and Trigeminal Neuropathy  Studies that used RS to treat NF2-associated VS showed that the risk of facial palsy and trigeminal sensory deficits was related to the quality of the dosimetric plan, accuracy of radiation delivery and radiation doses.  This is consistent with our results where we used low dose (12 Gy) and the absence of any permanent facial or trigeminal neuropathy.

28. Treatment Decisions 1.Size Small ( No ataxia) Large Ataxia 2. Hearing status Deaf Excellent Border line

29. Thank you