Protons 101: An Example of a CNS Tumor Proton Therapy Plan

Today we’ll look at a place where there actually are not large studies showing significant benefits to proton therapy. So if you don’t think protons are better, you could easily use this disease site to state that there is very little evidence of improvement in outcomes with the use of proton therapy.

I will point out a bit of data later, but in simple terms, this area would be considered a “theoretical” improvement area. It’s not a typical proton tumor. It’s not recommended in many cases by “experts”. Along those lines, this is place where often, there is not good cooperation from private insurance for people between the ages of 18 and 65.

(From my standpoint, I’d also point out that there also isn’t much good data showing that IMRT is better than 3D treatment and no data other than clinic observational data that 3D is better than simple 2D. But similar to many other treatment sites, an arbitrary bar has been set higher for proton therapy than for any other modality in the history of radiation oncology – but that is probably a different post for a different day).

So just to be clear – ASTRO (American Society of Therapeutic Radiation Oncology) – the “advocacy” group for radiation oncology in general – have a model policy that groups proton beam patients into different tiers based on the level of evidence – level 1 is the highest / strongest group. Level 2 is the next tier where, in some cases, proton therapy should be considered. Gliomas or brain tumors are NOT included in either group 1 or group 2. So essentially, it really isn’t considered for use by experts based on outcome data.

So we’ve set the stage – insurance, experts, and even the radiation oncology advocacy group doesn’t come out in support of proton therapy for routine brain cases. The treatment isn’t supported by guidelines, there isn’t much data. Ironically, I think it is great example case of just how broken decisions are regarding proton therapy.

My job is to convince you they are wrong and that, even without data, it would seem very reasonable and appropriate to use protons to decrease the radiation to normal functioning brain tissue.

Why Proton Therapy is the Better Choice for Treating CNS Cancer

Generally, the day job of the radiation oncologist is to “pick the plan that treats the cancer and minimizes normal tissue radiation” – this is our job whether we are looking at protons or photons or whatever – we try to pick the best plan.

So below are images. The left side shows representative CT slices from an IMRT plan and the right side shows representative slices through a Proton Therapy plan. Red is the highest dose of radiation. From there, the yellow, green, and blue represent lower and lower doses respectively – the levels between the two sides are identical – so blue dose on the left is equal to blue dose on the right. The blue is still a lot of radiation to those tissues. Only in radiation oncology is the blue dose considered “low dose”. If the blue dose were delivered to the whole body, we would see some significant percentage of patients die from radiation toxicity.

So the question below is – which is the better plan? The x-ray IMRT plan on the left or the proton therapy plan on the right?

CNS compare protons101 oklahoma CNS compare protons101 oklahoma CNS compare protons101 oklahoma CNS compare protons101 oklahoma

So again, I’ll repeat: There is very little outcome data showing benefits that we can measure between the two plans – but I think it pretty clear that the proton therapy plan treats less normal brain and should be the preferred choice from a medical standpoint.

If it were me or my family, I would seek to avoid treatment to regions of the brain that are not at risk.

I mean really…. It is just your normal brain tissue receiving needless radiation. (Please read sarcastically.)

The Harm of Excessive Radiation to the Brain

The short term complications from the difference may very well be hard to sort out, but long term there have (my emphasis because it opinion) to be differences. Radiation simply isn’t good for normal brain tissue – it can’t be. Seems crazy to me that somehow, I even have to argue that.

Now, if you are in the business of managing healthcare costs then I guess you can argue value, but as a physician who takes care of cancer patients, I’m thrilled to be aligned with what, I believe, will result in better outcomes long-term. The radiation dose above is not a theoretical difference – it is our best estimate of exactly how much dose this particular patient will receive if treated with photons vs. protons. You can ague (if you want) that it hasn’t been proven to make a difference, and while that may be true on some level, I can point to example after example of common sense historical changes in radiation treatment that show; very simply, that less radiation and more targeted treatments result in better outcomes.

If proton facilities did not exist, or you are in the evaluation phase of a potential future project, then the cost / benefit discussion is real. But once the resources are in place, it is a poor time to push that argument. Rather, we should be supportive of progress in the management of cancer. And:

Less radiation to normal healthy brain tissue seems like progress.

Data Suporting Proton Therapy Treatment for CNS

So now, lets look at some data and trials – there isn’t much and it isn’t large studies because ASTRO, experts, the proton industry and insurance haven’t supported using it for a number of complex issues that would take me much longer to walk through.

A few articles:

Proton hippocampaldosimetry

So this study showed that kids who had the hippocampus treated to 20 Gy or more showed short and long term verbal and visual memory issues at just 3 years of follow-up. In our adult example, that region in the opposite uninvolved area receives about 10 Gy. We know dose does damage according to the study above. The question becomes; in an adult is the effect less (which is likely) and how much less at half the dose and then trying to translate that into a dollar figure. Let’s say the patient in our example is around 50 – what will the effect be on a that patient at age 70? What is the dollar figure that is worth? (I don’t believe that is my role and not sure you can ever really answer that)

Proton Low Grade Gliomas

Here is a study that simply shows that there is work and progress being made with proton therapy in the treatment of CNS tumors. Small study – showing some patients, even with protons can have neuroendocrine deficiencies from radiation. So even with the most targeted approaches, we can still see side effects from the radiation from treatment of normal, not at risk areas of the brain.

wholebrain hippocampalsparing protons101

This final one is very interesting. It looks at whole brain treatment (Not what is shown above) using x-rays and whether or not you can show that sparing the hippocampus (memory part of the brain) can improve patient outcomes. This study shows that 1) everyone understands radiation does damage, 2) there are critical areas to try and avoid dose delivery, 3) and that memory and outcome can be improved with better technology that is often more complicated and more expensive. So the results:

Big surprise here – IT WORKS! Less radiation on the photon x-ray side improves outcomes! Based on this study, they quickly recommend that IMRT with hippocampal sparing should be considered standard of care.

Conclusion

Again, it is a great study – I agree with the results. I just wish we had this type of enthusiasm when it came to cases like the one I presented here today.

I think this post highlights some of the current difficulty in getting a consistent answer / opinion on the topic of protons. From my standpoint, I really believe that less radiation to normal tissues is better and I’m glad to be on the side of the argument. I believe we’ll have places where it is more beneficial and less beneficial and so properly utilizing the scarce number of facilities we have is important, but it is also true that we wouldn’t have to work so hard to promote potential benefits if the resource that is proton therapy was utilized more willingly by the medical system at large. Unfortunately today, it is often a fight and requires patients to be their own advocates.

Dr Mark Storey MD

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