Boris Hristov and Daniele Rigamonti
What is the cell of origin for vestibular schwannomas and acoustic neuromas (ANs)?
The Schwann cell of the myelin sheath is the cell of origin for ANs.
Which CN do ANs affect?
ANs affect CN VIII. Most affect the vestibular portion of the nerve.
In which anatomic region do ANs arise?
Most ANs are found in a region called the cerebellopontine angle (CPA).
Most people with symptomatic ANs will present between what ages?
Most symptomatic pts are 30–50 yo.
What proportion of ANs are sporadic?
The majority (90%) are sporadic as well as unilat.
What % of ANs are bilat, and with what genetic abnormality are they associated?
10% are bilat and associated with NF-2, the tumor suppressor gene on chromosome 22.
What protein is abnl in NF-2 pts?
Merlin or schwannomin (involved in actin cytoskeleton organization)
What is the name of the anatomic layer of CN VIII that gives rise to most ANs?
The Obersteiner-Redlich zone (the junction between the central and peripheral myelin) gives rise to most ANs.
Subclinical ANs are present in what % of the general population?
Up to 1% (autopsy series) of the general population harbor subclinical ANs.
ANs account for what % of intracranial tumors?
5%–8% of intracranial tumors are ANs.
Apart from NF-2, what are 2 other risk factors that predispose to the development of ANs?
Loud noise exposure (ORR 13) and parathyroid adenoma (ORR 3.4)
What are the Antoni A and Antoni B areas on histopathology?
Antoni A and B are zones of dense and sparse cellularity, respectively.
For what do ANs stain on immunohistochemistry?
Most ANs stain for S100.
How do bilat ANs fare after Tx when compared to unilat ANs?
Bilat ANs have similar failure rates to unilat lesions if treated adequately.
What tests are performed on physical exam for pts with CPA lesions?
Rinne test (mastoid bone, air conduction > bone conduction) and Weber test (occiput, vibratory sound louder on good side) to confirm sensorineural hearing loss; also need to check for other CN deficits (VII, hypesthesia, corneal twitching)
What CN is being tested when a pt is asked to tighten the ant neck muscles?
CN VII (innervates platysma muscle) can often be affected with large AN lesions.
Why are pts with CPA lesions often asked to march in place with their eyes closed on physical exam?
When the vestibular nerve is affected, pts will often veer to the side of the lesion.
What is the best initial screening test for ANs, and what does it usually show?
Audiometry (asymmetric sensorineural loss, more prominent at ↑ frequencies) is the best screening tool for ANs.
What is the avg growth rate per yr for ANs?
~1 mm/yr. Growth rates range from 0.5 mm/yr (slow-growing lesions) to 2 mm/yr (fast-growing lesions).
What % of ANs are stable (shrink/do not grow)?
~20%–40% of ANs are considered stable.
Is the size of the tumor at presentation predictive of the tumor's growth rate?
No. Tumor size is generally not predictive of the tumor's growth rate.
Does AN tumor size correlate with hearing loss?
Usually not. The location of the tumor (i.e., intracanalicular vs. not intracanalicular) is more predictive.
What do brainstem auditory evoked potentials typically show in pts with ANs?
A delay of conduction time on the affected side is seen with auditory evoked potentials.
What imaging study is typically performed for ANs?
Thin-slice (1–1.5 mm) MRI with gadolinium. If NF is suspected, neuraxis MRI is performed.
To what is the “ice cream cone” appearance of ANs on MRI due?
This AN appearance is due to enhancing lesions in the canal (cone) and CPA (ice cream).
What scale is used to grade facial nerve (CN VII) function?
The House-Brackman scale (I [normal] to VI [no movement/spasm/contracture]) is used to assess CN VII function.
Facial nerve Sx are present in what % of AN pts?
~6% of AN pts present with facial nerve Sx.
What options are available for AN pts?
Observation, surgery, or RT
When is observation appropriate for ANs?
1. Observation is appropriate with small tumors ( <2 cm) or no/slow growth without Sx progression.
2. Rosenberg SI, Laryngoscope 2002: >40% no growth. Lesions >2 cm were more likely to grow fast.
What follow-up is required for AN pts opting for observation?
Audiometry and MRI scans q6–12 mos are required for pts opting for observation.
What are the 3 surgical approaches available for ANs, and what are the prominent disadvantages/advantages of each?
1. Retromastoid: may not be able to achieve GTR/good facial nerve preservation
2. Middle fossa: GTR, facial nerve preservation may not be possible/hearing preservation better
3. Translabyrinthine: sacrifices hearing/good facial nerve preservation
When is surgery the preferred Tx option for ANs?
Surgery is preferred for large (>4 cm) symptomatic tumors or recurrence/progression after RT.
What are the recurrence rates after surgery for ANs?
<1% (German data: Samii M et al., J Neurosurg 2001; Johns Hopkins Hospital [JHH] data: Guerin C et al., Ann Acad Med Singapore 1999)
What are the overall facial nerve and hearing preservation rates after surgery for ANs?
After surgery for ANs, there is an 80%–90% facial nerve preservation rate and a 50% hearing preservation rate.
What are the overall facial nerve and hearing preservation rates after RT for ANs?
After RT for ANs, there is ~95% facial nerve preservation rate and ~65% hearing preservation rate (possibly higher with FSR).
What are the long-term LC rates after RT for ANs?
Long-term LC after RT for ANs is 90%–97%. (Lunsford LD et al., J Neurosurg 2005; Combs SE et al., IJROBP 2006)
What are some commonly employed doses when SRS/Gamma Knife (GK) SRS is used for ANs?
12–13 Gy to 50% IDL is a commonly employed SRS regimen for ANs.
What has the dose trend been for the Tx of ANs with SRS?
The dose was lowered from 16 Gy to 12–13 Gy. Pittsburgh and Japanese data showed similar LC rates but less facial weakness and hearing loss with lower doses.
What doses are used with FSR?
1. Combs SE et al., IJROBP 2005: 50–55 Gy (in 25–30 Gy/fx) if larger (>2–3 cm) lesions
2. JHH approach: 25 Gy (500 cGy × 5 fx) with smaller lesions
What are the hearing preservation rates with FSR?
This is controversial, but hearing preservation rates are thought to be better with FSR than with SRS or surgery (94% in Combs SE et al., IJROBP 2005; 81% in Andrews DW et al., IJROBP 2001).
What recent data suggests better hearing preservation and similar LC rates with lower-dose FSR therapy?
Thomas Jefferson data (Andrews DW et al., IJROBP 2009): a lower dose of 46.8 Gy (vs. 50.4 Gy) had 100% LC at 5 yrs with a better hearing preservation rate.
What other RT modalities have been successfully employed in AN?
CyberKnife (Chang SD et al., J Neurosurg 2005) and protons (Weber DC et al., Neurosurg 2003): worse hearing preservation (not used with tumors >2 cm and if pt can hear well)
What important AN studies prospectively compared surgery to SRS? What did they show?
1. Mayo data (Pollock BE et al., J Neurosurg 2006): <3-cm tumors, same tumor control rates but worse pt QOL after surgery.
2. French data (Regis J et al., Neurochirurgie 2002): largest prospective study. GK pts had better function overall.
What AN study prospectively evaluated SRS vs. FSR?
Dutch data (Meijer OW et al., IJROBP 2003): dentate pts rcv FSR (20–25 Gy in 5 fx) and edentate SRS (10–12.5 Gy), with similar LC and functional outcomes.
What agent has recently been shown to be effective in NF-2 pts with refractory ANs?
Bevacizumab (Avastin) was recently shown to be effective in NF-2 pts with refractory ANs. (Plotkin SR et al., NEJM 2009)
The dose fall-off to what structures needs to be carefully evaluated with GK SRS for ANs?
Cochlea and brainstem doses need to be carefully evaluated with GK SRS.
What IDL do we prescribe to in GK? Why? How about for LINAC-based SRS?
1. GK: 50% (sharpest drop-off in dose is at 50% IDL)
2. LINAC: 80%
What is the difference in the onset of side effects after surgery vs. RT for ANs?
Side effects present upfront/immediately after surgery vs. in a delayed/gradual (mos to yrs) fashion after RT.
What is the dose threshold above which hearing preservation rates decrease with RT?
Preservation rates decrease at doses >13 Gy. (Japanese data: Hasegawa T et al., J Neurosurg 2005)
What are some toxicities and rates of toxicities after SRS for ANs?
1. Trigeminal neuropathy/hyperesthesia: 5%–10%
2. Facial nerve neuropathy/palsy: 5%–10%
3. Hearing deficit: useful hearing preserved in 33%–45%
What are the main toxicity differences between RT and surgery?
RT carries a lower risk of facial nerve/trigeminal nerve injury.