GRACE :: Radiation Oncology
Dr West

Can a drug reduce risk of cognitive side effects from whole brain radiation therapy?

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Last week, I wrote a post highlighting a relatively new blog and a review article about whole brain radiation therapy (WBRT) by my friend, Moffitt Cancer Center-based radiation oncologist Dr. Jacob Scott.   I found the review article to be among the very best I’ve ever encountered on this very important subject, but it only made passing reference to an important trial called RTOG (for Radiation Therapy Oncology Group) 0614, which randomized patients to WBRT with or without the agent memantine (Namenda), a medication for Alzheimer’s disease.  Memantine works by blocking glutamate receptors in the brain, which can excite brain cells, but at high levels of transmission, the effect can be harmful on memory formation and brain function.  Radiation oncologists developed the study to ask whether the this agent that can have a (modestly) beneficial effect on cognitive function on Alzheimer’s disease might also be beneficial in reducing cognitive deficits in patients who undergo WBRT.

I asked Dr. Scott for his thoughts on the recently reported preliminary results of the RTOG 0614 trial, which was among the most important results presented at the big radiation oncology conference in October of last year, called ASTRO (American Society for Radiation Oncology — I think the T is sometimes said to abbreviate “Therapeutic”, sometimes acknowledged as gratuitous to make an elegant abbreviation).  As described in a very nice follow-up post by Dr. Scott, the results suggested a borderline statistically significant result, with a p value just above our magic threshold of 0.05 that makes us more convinced that it should change our practice patterns.  

Dr. Scott offered his personal commentary on what this should mean.  I’ve had my own discussions with radiation oncologists and found, as he did, that there isn’t any clear consensus on whether these results should establish a new standard of care.  But like Dr. Scott, I think it’s a mistake to over-interpret a statistical result, whether it does or doesn’t meet a threshold of 0.05, as having some magical significance.  Particularly in trials that have smaller patient numbers (as occurred here because, unfortunately, many patients died without being able to be followed longitudinally), potentially very clinically significant results may be dismissed because insufficient numbers leave a difference with a p value that falls a little short of a line we’ve drawn as being critically important.  I’ve touched on this important issue of clinical vs. statistical significance myself and have even written a post about it, nearly 5 years ago, that comes to the same conclusion Dr. Scott reached: we shouldn’t let a p value threshold come between us and the logical acceptance of a compelling result.

Accordingly, I’m increasingly inclined to favor inclusion of memantine for my patients who undergo WBRT, and several of the radiation oncologists with whom I work share this strategy.  The challenge we then face is whether insurers are swayed enough by the results to cover memantine for patients who don’t have Alzheimer’s disease.  I haven’t had enough patients to say what to expect in this regard, but I expect that they will if this agent becomes a more universally accepted standard of care paired with WBRT.


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