Glioma research: Asking right questions

There is an arms race to find the next molecular target. The potential spin-offs are enormous. Royalty payments. Insurance payouts.

Despite insane profits, big pharma has lost its drive to push forward for drug discovery. The easy way is to buy out the biotechnology companies (startups) or chase the clinical conditions which have healthy fat margins (like hypertension). Rare diseases like brain tumours haven’t seen any incremental investments over the past few years because of poor outcomes. Tumour treating field is the only “breakthrough” in recent times for recurrent tumours.

Therefore, the onus lies on informal networks of universities and individual researchers for pushing this narrative forward. Despite the wasted research dollars, there is a lot of promise for translational research.

My proposal has the following (very broad/generic) outline here.

The problem, at the outset, is the cost of sequencing. But it is a necessary evil. Unless we know what type of a tumour we are dealing with or its genetic signature, we cannot hope for proper characterisation. This information needs to be mated to clinical follow up with standard protocols.

Is there any scope for in-vivo monitoring? If yes, what is going to be its timeline? How frequently are we going to see for the mutations? What is the rate of mutations? What is its timescale? When should we intervene?

Another favourite pet theory is the class distinction for stem cells. Do they exist? If yes, why can’t they be reliably identified? What are their niches and what is the best way to target them?

Each sequencing would reveal a wealth of clinical data (both genomics as well as radio-genomics) and spur on more deep dive into the molecular ontology. Yes, that might fulfil the wet dream for molecular targets as well. However, as a radiation oncologist, I am only keen to know whether I can reduce my tumour volumes, how we can reduce the dose to normal structures (brain) and combine efforts with patient-related outcomes.

Bring it on! Let us do it! (Have some laughs!!)

Whole brain radiation dose: think about it.

I have always wondered about the tolerance of brain tissue to radiation. Whole brain radiation can be “safely” given up to 54-60 Gy (in the previous protocols for glioblastoma- NO LONGER used). Brainstem dose, in the current QUANTEC era, is not exceeded to 54Gy as a point dose (disregard the 10cc volume for a minute).

The whole brain mean dose is preferably not exceeded beyond a mean dose of 28Gy which we are propagating in the post-hippocampal era (so as to say).

It brings me back to the original question. Why is a focused radiation dose exceeding 60Gy (for example) more injurious than whole brain dose to the same effect? And why brainstem isn’t affected in that scenario?

Another question. If a phased plan is executed, is it sufficient to only add up the mean doses? This is because both the phases have used different calculation subsets; radiation delivery is also going to be markedly different.

Well, no easy answers!