GBM misdiagnosed

Were you doing the standard 200mg/m2, 5 days every 28, for all those years? Or were you doing a lower dose?

It is said that TMZ only works if you are (significantly) methylated, and has no effect otherwise. Did you ever do a methylation test? It is usually written in the biopsy report but you can ask for it if they have not done it.

An oligo has a specific mutation, 1p19q, and it is a standard test they do during biopsy. I am surprised they missed it.

Another prognostic and therapeutic factor is IDH1/2 mutation, for which there are now a couple of targeted medicines. Again, that should be in the biopsy.

Did you just have another surgery? There will be a new biopsy now, and you could again ask to have all these (routine) tests done. Do not forget the methylation status.

Have you been looking at your MRIs? Have you had a persistent (but stable) flair signal all those years? What's changed now, is it enhancing?

Which oncologist prescribed TMZ all these years? It is not common, not in the UK.

Have you had radiotherapy? It is possible the tumour has mutated now or be a completely different makeup, I am guessing of course.

Thank you for your reply,

The answer to the first question is no, I didn’t have 200mg 5/23 for all those years; I did, in fact, have 300mg 5/23 for all those years. 

My original oncologist was, I think, stuck between a rock and a hard place; she prescribed me TMZ for so long as, when I first was in hospital, I was so ill, I was treated as a palliative case with very little chance of surviving more than a couple of months; in fact, I was so ill that my body wasn’t strong enough to take radiotherapy. 

The standard of care in these situations, I believe, is to continue soc until, basically, you die. The fact that I’m still here is testament to the care I received both in hospital and at hone by my wife and her family. 

My scans up till a few months ago showed no growth whatsoever. It was only after they had removed TMZ from my treatment regime that this area of concern was shown up. On the initial scan from November last year, everything was still stable but in March 2021, it showed an area of interest that, after a couple of weeks only, had grown considerably in size. 

My methylation status is somewhere around 58% positive, so has responded well to treatment. 

However, what neither my medical team nor ourselves know is whether the TMZ had been doing me any good all this time or not, and whether it was just mere coincidence none of us will never know, seeing as TMZ is not necessarily soc for AOs. 

So far I have only had that one operation.

Hope this makes some sort of sense. 

Stu

Hello Stu,

If you had 300mg it means you are 1.5m2 - which is your BSA height and your weight in combination, look here for example: https://patient.info/doctor/body-surface-area-calculator-mosteller

1.5m2 is little for men, I am over 2 and am not tall at all (1.73m, 88kg), so my usual dose is 200 x 2 = 400mg/day

Maybe you were on a reduced dose or maybe you are really thin :-)

There are two main parts to the MRI, in very layman's terms, flair and enhancement. Flair will pick up almost anything, any abnormality, it is very sensitive and typically shows you the extends of the cancer. On lower grade gliomas (grade 2) the flair signal increases, say, 3-5mm per year, unless you are unlucky like me and your grade 2 increases much faster.

A grade 3 goes faster, mine moves at 15mm over 3 months. And a grade 4 really gallops, it doubles in volume every two weeks! But if you have oligo it will not become grade 4.

Enhancement is the other bit you're looking out for on the MRI, and it is usually bad news. Enhancement almost always means grade 3 or 4.

The cancer is not uniform, it has areas that can be grade2 and areas that can be grade 3. Or more typically, the cancer is mostly grade 2, and then, years later, some part of it transforms and becomes grade 3 and that area starts enhancing and growing quicker.

I have seen it many times in the past, in the US, patients stop a long term TMZ after doctor's advice and within weeks the cancer starts to grow! I say in the US, because there they are happy prescribing TMZ for years, whereas in the UK they stick to the standard is 6 months.

I asked if you were having surgery because you said that professor was arranging another surgery for you.

As you have not had radiotherapy I suppose they will now push you for it? What is your take on it?

If you go down the chemo route, please read up on the ceteg trial, it combines CCNU and TMZ, and if you are methylated you are a good match (we know you have 1p/19q and methylated, may be even IDH1). Of course you will have to persuade an oncologist. Basically ceteq is PCV without the P and without the V. Many doctors believe that the V is useless and that TMZ is much better than P, so they combined CCNU + TMZ and got good results for those with 1p/19q and methylated.

Oh I forgot to say, during the pandemic, hospitals and doctors dropped the P and V, no questions asked. The Royal Marsden dropped the V and St Barts dropped both P and V. That could be an argument for any sceptical oncologist.

Wow, akist , that is a lot of information to take in. 
I will read it over and over again until it sticks!

The Professor and the clinical nurse specialist both said about PCV instead of TMZ (as that’s the first port of call in Oligos - as well you know). 

Radiation? I’m easy with it; my surgery is scheduled for Monday next week, so we will have to wait until all that is done and dusted before, I assume, any further treatment is discussed but, quite simply, anything that keeps me here for longer is a bonus. 

One thing my stepdaughter said yesterday, when we told her was “to be fair, 2012 wasn’t the dark ages; pathology had seen plenty of GBMs in the past. Why didn’t they pick up on this particular tumour and say ‘this doesn’t look like a GBM at all’?”

Which sort of mirrors what you said in your first reply. 

Anyway, time will tell. Surgery is scheduled for next Monday morning, so we will have to see from there. 

Thank you again for your reply,

Stu. 

Oh, and about TMZ and weight, I am about 14st 10lb so make of that what you will!