Advances in radiotherapy

Optic Nerve-sheath Meningioma: Advances in radiotherapy
Presenter: James Acheson

The Schick classification of perioptic meningiomas does have limitations because it’s trying to split an already very small group of patients into a number of even smaller groups (J.Neurosurgery 2004). But it does help the conversation in one important way, which is it shows us that the term optic nerve sheath meningioma (ONSM) needs to be used slightly advisedly. Type 1 tumours, which are entirely in the orbit should be discussed separately from those growing through the superior orbital fissure or optic canal into the middle cranial fossa (Types 2 and 3) as the natural history and outcomes from treatment as different.

Schick types 1a and b typically are offered primary radiotherapy when vision drops. 1c (with significant exophytic growth) may in addition have surgery if the eye is blind and painful but not otherwise.  Patients with Type 2 disease involving the optic canal or superior orbital fissure and extension into the middle cranial fossa may benefit from a neurosurgery approach, with radiotherapy reserved for disease recurrence or an unsatisfactory surgical result.

An important consideration is that best practice in perioptic meningioma leads to radiotherapy without the advantage of a biopsy, because biopsy is typically thought to be too destructive and may create a problem with recurrent local disease.

A further area of difficult is the diversity of radiotherapy delivery techniques and systems: this is important when reviewing the literature because case series utilising fractionated stereotactic methods are readily not comparable to other series using conventional external beam or non-fractionated  Gamma Knife or Cyber Knife machines.

I have picked out some landmark papers from the published literature on radiotherapy for perioptic meningioma to illustrate these points. The starting point is a review paper with metanalysis of all previous material by Dutton and colleagues from Duke University, North Carolina, published in 1992. Patients treated by observation only all got worse or sometimes remained stable.  Those undergoing surgery group they also all got worse with the added complication that 25% had the problem of recurrent disease, and personally I recall from when I  was a trainee in the late 1980’s how big a problem that was.  However, the cohort of patients who had primary radiotherapy showed favourable outcomes: 73% of patients improved, 9% have made the same and 18% got worse.  This is a game-changing summary of a retrospective review of multiple case reports.

In the following ten or fifteen years two papers should be highlighted:  Turbin (2002) which is a large multidisciplinary group from the East Coast the United States and Landau (2005) from Switzerland. ‘s group in Zurich in 2005. These studies are led by ophthalmologists who were able to document important details on visual function, and not just on the scan appearances.

In the Turbin series, there is long follow-up of patients mostly treated with fractionated conformal, systems.  They had an observation group, surgery only, radiotherapy only, some had a combination of both radiotherapy and surgery. Only the radiotherapy group remains stable and all the other patient got worse.  However, in that era radiation to damage to the lens and ocular surface, retinal vasculopathy and optic neuropathy, plus injury to the temporal lobe in the brain from non-stereotactic systems remained a problem.

The Landau series reports quite small numbers of patients, carefully observed and treated with  with intensity-modulated 3-dimensional systems with a very low morbidity rate but not very long follow-up. Stereotactic 3-dimensional systems can be expected to reduce injury to adjacent structures, but the technical challenge remains to deliver an effective dose to the tumour which surrounds a radiosensitive optic nerve.  In other words how to avoid damaging the structure you’re trying to save.

There is a further review paper of radiotherapy outcomes by Saeed (2009), with stabilisation in at least half the patients and improvement in 41% which I think is a realistic conclusion to draw on averaged visual outcomes.

Outstanding issues and controversies in radiotherapy for perioptic meningioma include the diversity of delivery systems already mentioned, and also the lack of agreed treatment thresholds or outcome parameters.  For example we do have some patients whose visual acuity or visual field  is only mildly subnormal but there is quite a substantial tumour with proptosis  on imaging and there is a question about the threshold which you should go in to treat. Delayed treatment may reduce the chances of visual recovery as irreversible axonal loss replaces axonal swelling. Unnecessarily early treatment creates an avoidable risk of radiotherapy complications.

A further point of controversy is the approach to optic nerve sheath meningiomas with canalicular involvement but no significant middle cranial fossa extension.  Here there is an argument in favour of limited neurosurgery to decompress the canal, and subsequent radiotherapy if indicated by recurrence: canal decompression alone may bring improved visual function.

To conclude: radiotherapy for perioptic meningioma is here to stay. 1980’s external beam non- stereotactic systems have been superseded by much safer modern techniques especially stereotactic 3-dimensional fractionated systems.  Surgery does have a role in selected cases only. Finally we don’t have any consensus about what the treatment threshold should be, but it is clearly important not to treat unless the vision is shown to be progressively failing.

Q & As section

Comment 1
Gillian, about the point you made about delivering radiation to an object which will try to preserve the vision, it must give us some clue about the tolerance the optic nerve, which would appear to be much higher in this group than it is intracranially.

Answer (Dr. Gillian Whitfield)
You’re giving a fractionated treatment for an uninjured optic nerve, we know pretty much what the tolerances are and we know that an already slightly compromised nerve might have slightly lower tolerance. I mean we would treat to 50Gy/30 fractions which is smaller than typical fractions 1.67 Gy per fraction, and that should even in an injured optic nerve, be incredibly safe. The risk of that causing visual loss is very low. In terms of a threshold when to treat, I wouldn’t put an absolute number on it, it depends on the rate of change and it tends to depend on what the patient has to lose from treatment, often they are younger patients, obviously you are a bit concerned about late radiotherapy effects albeit small. For me, it depends on the rate of change, because we can salvage damage to an extent but if the worse the damage, the less likely you are to salvage it.

Question 2
What about those tumours which will right up against the back of the globe and they’re higher risk of retinopathy?

Answer (Dr. Gillian Whitfield)
Even if they are maybe three or four millimetres from the back of the globe, we would allow a margin along the optic nerve for microscopic spread. In practice often the volume you treat does come to the back of the globe and then we try very hard to keep dose off the lens to avoid cataract (although that’s treatable), off the cornea to avoid corneal problems, off the lacrimal gland and as much as possible off the retina, but you can’t avoid some retinal dose. But again sort of a dose of 50 Gy in 30 fractions does carry some risk of retinopathy but it’s pretty low for most people, unless there’s other factors like diabetes, etc. I think if you do it in small doses per fraction to a modest dose, I notice in those series somewhat a higher dose like 54 Gy, then I think you’re more likely to get retinopathy.

Question 3
Question of intracannalicular involvement of the ONSM meningioma radiotherapy; Is it fair to say Gillian, will induce some degree of inflammation in the tissues? If you’ve got an enclosed optic nerve within the bony optic canal would it not be potentially beneficial to do a cautious canal decompression before treating with radiotherapy?

Answer (Dr. Gillian Whitfield)
I don’t think we’re entirely sure. Radiotherapy can cause a bit of oedema and if you’ve got severe compression of the optic canal, it could make things a bit worse. When we treat a variety of meningiomas -not just optic nerve ones- with disease in the canal, we’re always prepared if vision deteriorates to give a small dose of steroid. It’s rarely necessary, it may depend on the amount of compression the patient has in the optic canal, whether they’ll tolerate a little bit more oedema with radiotherapy or not, but it would be lovely perhaps to see some kind of randomised comparison. I’m not really convinced it’s necessary but there might be selected patients for whom it might help.

Question 4
Regarding the more advanced imaging, Is the uptake on the Dotatate scan the same in all of these? is it quantifiable? Would that be a sign of whom to treat or not rather than just look at the uptake? Is it just yes or no?

Answer (Dr. Geoffrey Rose)
It’s largely yes or no. It’s very useful, it’s positive in about 95% if I remember rightly of optic nerve sheath meningiomas, but presumably it’ll be a bit patchy depending on whether they express somatostatin receptors.