Symposium for Patients & Caregivers

Andrew G. Shetter M.D.

Barrow Neurological Institute

Phoenix, AZ

GAMMA KNIFE RADIOSURGERY FOR HYPOTHALAMIC HAMARTOMA

“ The delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the intact skull ”.

L. LEKSELLL 1949 :Lars Leksell

Definition of Radiosurgery

A single dose of ionizing radiation given with millimeter accuracy to a small volume of tissue

GK RADIOSURGERY

Devices for Radiosurgery

- Gamma Knife

- CyberKnife

- Infini

- Varian Trilogy system

- X Knife

- Novalis Brain Lab system

GK Procedure

Stereotactic frame applied using pin fixation

Anesthesia: Age <6 yrs - generalAge >12yrs - local + sedationAge 6-12yrs - either, depending on child

GK Procedure

- Hi Res MR scan obtained with frame in place

- Images transferred to treatment planning computer for planning process that may take several hours

- HH is outline and viewed in different projections or 3D

GK Procedure

- Oval spheres or “shots” of radiation are placed within the HH to conform the radiation dose to the size and shape of the lesion

- Deliver a minimum dose of 18-20Gy to margins of the HH, while keeping dose to the nearby optic chiasm and optic tracts below 8-10Gy

GK Procedure

- After planning completed, pt brought to treatment area, placed on mobile couch, and stereotactic frame attached to GK

- HH automatically positioned in center of 192 convergent radiation beams using varying predetermined target points and treatment times

GK Procedure

- Total treatment time 30-90min

- Frame removed post treatment, pt discharged same day

- No convalescent interval

GK Results

Regis et al, 2006- 54 pts treated from 1999-2005, 27 pts followed >3 yrs and available for analysis

- Median maximal diameter 9.5mm (range 5-26mm)

- Median marginal radiation dose 17Gy

GK Results

Regis et al, 2006- 37% seizure free, 22% >90% reduction

- No instances of memory loss, paralysis, endocrine dysfunction, wt gain, visual impairment

- Most pts experienced improvements in behavior, school performance, and quality of life based on subjective observations by family and physicians

GK Results

BNI Experience, Abla et al, 2010

- From 2003-2008, 19 pts treated with GK and prospectively followed

- 111 pts treated with open surgery over same interval

- 10 pts with >18mo follow up available for analysis

- 30 pts treated with GK to date, repeat analysis in progress

Mean / Median Range

Age at treatment 15.1 (mean)16.2 ( median)

5.7 – 29.3

Age at onset 6 in 1st year of life3 between ages 6 to 8

1 month – 14 years

Male Sex 8 of 10

Size 695 mm3 (mean)265 mm3 (median)

169 – 3000

Average Daily seizures 3.6 (mean)2.5 (median)

0.1 – 6.5

Max Daily Seizures 15.9 (mean)5 (median)

1 – 100

Prior treatments 3 with prior resection2 others: cyst resection / lobectomy

Anesthesia type – local with iv sedation 7 of 10

Followup 43 months (mean)30.5 months (median)

18 – 81 months

Isocenters / shots needed 7.4 (mean)5.5 (median)

3 – 16

Marginal dose (Gy) 18 (mean & median) 16 – 20 Gy

Maximum point dose to optic apparatus 7.5 (mean)8.3 (median)

5 – 10 Gy

All 3 patients with baseline STM loss experienced resolution

Improved quality of life :

9 of 10

Cognitive/STM Deficits Behavioral

Abnormalities

p = 0.5

Prior Surgeries and Outcome

Complications

• All Transient • Poikilothermia (n=1)• Weight Gain / Appetite Increase (n=2)• Fear of the Dark (n=1)• Increased Depression, now improving (n=1)

• No instances of:• DI• visual field deficits • cranial nerve deficits • vascular injuries • new short term memory loss

GK for HH

Advantages

- 60% seizure free or nearly seizure free, comparable or sl. inferior to endoscopic resection

- Minimal or no risk of memory dysfunction, stroke, endocrine abnormalities, or wt gain compared to open surgery

- Radiation dose can be shaped very precisely to maximize dose to HH and minimize dose to surrounding normal structures

GK for HH

Advantages- No risk of hemorrhage

- Outpatient procedure, local anesthesia with sedation in most instances

- Open surgery or laser thermoablation not precluded at a later date if GK unsuccessful

GK for HH

Disadvantages

- Limited to relatively small lesions

- Latency interval of 1-3 yrs until full effect is seen, so not a good option for pts with very frequent seizures or those who are experiencing cognitive or behavioral decline

- Theoretic risk of radiation producing secondary tumors many years after treatment

Best Candidates for GK

- Small HH (<2.5cm) with >2mm clearance between lesion and optic apparatus

- Pts with intact cognitive and memory function, particularly older pts who are high functioning

- Pts with relatively stable seizure frequency who are not experiencing cognitive or behavioral decline and can afford to wait 1-3 yrs to see full effect of radiosurgery

- Pts with residual HH after open surgical resection who are not seizure free

vs Endoscopic resection vs Laser thermoablation

Efficacy

GK - 37% seizure free, 21% with >90% reduction, ≥ 3 yr follow up (Regis et al)

Endo - 49% seizure free, 21% with >90% reduction, ≥ 1 yr follow up (Ng et al) - 36% seizure free, ≥ 1 yr follow up (Drees et al)

Laser - Good initial success rate in small number of pts, no long term results available

GK

vs Endoscopic resection vs Laser thermoablation

RisksGK - No permanent neurologic deficits, rare transient poikilothermia (Regis et al, BNI)

Endo - Permanent short term memory loss 8%, transient hemiparesis 11% (Ng et al) - Persistent deficits = stroke 5%, hormonal disturbance 24%, wt gain 59%, 1 death (Drees et al)

Laser - No permanent neurologic deficits reported, but number of pts treated is small. Similar stereotactic procedures have 2-3% incidence of intracranial hemorrhage

GK

vs Endoscopic Resection vs Laser Thermoablation

Latency

GK - Requires 1-3 yrs to see full effect. Some pts may experience temporary increase in seizures 6-12mo. post GK

Endo - Immediate effect if successful, but some pts may experience recurrent seizures after being seizure free for 6-24mo. post op

Laser - Immediate effect if successful. No data regarding long- term recurrence rate

GK

GK - How Does it Work?Kerrigan et al, 2012

- HH tissue obtained at the time of surgical resection was examined in 10 pts who had undergone prior GK treatment, and compared to 19 pts who had received no prior irradiation

- Total cell density was significantly decreased in the GK treated group, with a tendency to be more pronounced in pts who received a higher radiation dose

- Cell loss resulting from GK may contribute to decreased excitation in the neural networks responsible for generating seizures in HH tissue

- GK is the least invasive and lowest risk surgical procedure for treating medically intractable epilepsy due to a small-medium size HH

- Approx. 60% of pts will become seizure free or nearly seizure free post treatment

- Full effect of GK treatment is not seen for 1-3 yrs

- Our knowledge regarding the best surgical option for any given HH is still incomplete. Treatment decisions must be individualized and tailored to the expectations and comfort level of each patient and their family.

GK for HH - CONCLUSIONS

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Thank You Thank You

A Special Thanks to our Sponsors• Aesculap

• Barrow Neurological Institute @ St. Joseph’s Hospital

• Barrow Neurological Institute @ Phoenix Children’s Hospital

• Great Council for the Improved

• Hope for Hypothalamic Hamartoma Foundation

• KARL STORZ Endoskope