ASTRO 2015

Radiological management of intermediate-risk meningioma

Dr Leland Rogers - Virginia Commonwealth University, Richmond, USA

Meningiomas are the most common intercranial tumour by quite a bit; they’re about 8-10% more likely than the second most common. So we have known about them for a long time and they’ve developed treatment paradigms over many decades but they differ quite widely from institution to institution. Even the paradigms that have developed don’t necessarily address all the problems that we see with this tumour. These are usually benign tumours but they come in three grades, the highest grade, fortunately the least common one, is malignant and is a very aggressive tumour.

How are meningiomas currently treated and what did you do in the study?

The main treatment for the majority of patients with meningioma is and remains surgery. Surgery can address the symptoms quickly that patients present with and surgery is also valuable in telling us the grade of the meningioma. With data from this study and other recent studies I think we’re learning quickly that grade matters a lot and we need to know what the grade is and surgery performs that function as well.

Now, the broad study here had three groups, we called them group 1, 2 and 3 and split that up by progression risk, we called it low risk, intermediate risk, high risk, that corresponds precisely with grade 1, 2 or 3. The low risk patients were treated with surgery alone and observed; the intermediate risk group patients, which is what my talk at ASTRO this year is about, were recurrent low grade meningiomas or new intermediate grade or grade 2 meningiomas. They were treated with surgery followed by radiation therapy. There was also a high risk group that we’re not ready to present yet that were also all given surgery and radiation therapy. So that’s how treatment proceeded on the study. This was the first study to be completed in a co-operative group on meningioma; several others have been tried but had failed, this was the first one to be completed.

Why did you look at the intermediate-risk group of patients?

They’re kind of the most interesting. They are the ones about which there’s the greatest disagreement. Many well thought of institutions, good places, would provide surgery alone for this group and many others would provide surgery and radiation therapy and arguments can be vehement, at least there are strong proponents for either of those approaches. I favour the latter but in order to go down that road and try to really address the question scientifically we needed a co-operative group study.

What were the study findings?

Our primary endpoint was three year progression free survival and three year progression free survival was 96%. In essence the local control was a little better; progression free survival takes into account both a death from any cause or a recurrence. Only one patient recurred so the local control rate was 98% in that group with radiation. Typically if you look at the literature at large, at the retrospective literature at large, we would have expected something like 70%, 60-70%, with surgery alone. So that’s a very encouraging finding.

How do you intend to build on these phase II study data?

We have put the phase III together and we’re meeting with CTEP at NIH soon, next month, to iron out the final details. That study will be a randomised trial of newly diagnosed grade 2 meningiomas. They’ll have surgery, they’ll be randomised between observation and radiation therapy. So that study will really answer the question about how to approach gross totally resected intermediate risk meningioma patients. I think that will be the final answer.

What do the study findings mean for clinical practice?

For now we’ve learned a couple of important things and will learn more from this study. We’ve learned that the local control with radiation therapy after surgery is excellent. Again, only one patient out of 56 had progression at our three year endpoint. We’ve also learned that the side effects are very low. Side effects are commonly split up into grade 1, 2, 3, 4, 5 and we had no grade 3 or higher complications in the radiation therapy arm showing that this can be done safely and effectively. We’ve already published outcomes related to pathology concordance. I may be getting a little esoteric here but the concept is ten years ago grade 2 meningiomas were diagnosed in about 5% of meningioma patients; nowadays it’s changed dramatically, it’s about 25%. So there has been a five-fold change in about ten years and we didn’t know whether one pathologist would agree with another on what a grade 2 was. So we published that data first and we showed that in academic centres, at least, in the centres that participated in this co-operative group trial, those were largely academic centres, they agreed on meningioma grading. We found some elements where there was disagreement and we’re going to use those findings to address how to describe grading in the future, so it will have that impact in the future but the concordance is pretty good. We’ll also learn from blood tests, urine tests and pathology samples more about what predicts recurrence. So by studying who recurred and who didn’t recur in the future we’ll be able to perhaps provide clinicians with tools to make that assessment themselves.

What is the take home message from the study?

The main value of our trial was to prove that you can put meningioma patients on study. This was a very difficult ten year process to try to get this open in the first place because many trials had failed. We’ve now proven that you can do it, it takes work but it’s possible, and we accrued patients more rapidly than we anticipated. So I think the real importance of this study is that we’ve proven that you can do this and that we can now answer more detailed questions inside co-operative groups that will be practice-changing.