Dr. Dietrich on chemobrain, part 2

cnscells

Part two of a Q&A interview with Dr. Jorg Dietrich, a neuro-oncologist at Massachusetts General Hospital. Dr. Dietrich believes that DNA damage to progenitor cells in the brain could play a role in chemobrain. Here, he focuses on the doctor-patient relationship.

Q. How do you approach the discussion when you are talking with a patient?
A. I think one of the main obligations we as oncologists have is to openly discuss the treatment options and all possible associated side effects, even if these are not common. It will have to be accepted that the brain is one of the targeted areas of toxicity and cognitive symptoms may just not be the result of chronic fatigue and depression, as it has been thought initially. We will not be able to avoid chemotherapy and radiation as part of cancer therapy. But I think that it is important to openly discuss all possible side effect profiles to alert patients and their families of potential outcomes of toxicities to the brain and then also to define ways of better monitoring and treating side effects once they occur.

And I think once we define the clinical problem and we know what we are looking for, then it is only a matter of time before we identify the best mechanisms to protect the brain. If no one really looks at the problem, for example to defining the cell populations at risk, then no one will look at protective strategies either because the problems have not been outlined and characterized.

Q. What interested you in this field of medicine?
A. This is a fascinating field to be in. In the past five years, this has really been a hot topic and a problem that affects more people than anticipated. And I think it is really important to further create awareness but also to help patients understand their symptoms because many times they have been without answers. Doctors would say, “Well, you’re just depressed, you’re just fatigued and that’s why you don’t concentrate so well and you’re not attentive as much as you used to be or you were able to multitask and you just can’t do it anymore.”

So there has been all this mystery, coupled with poor explanations, and I think it is our job as physicians to really help patients along and also to support them, as symptoms may come up to deal and to cope with deficits as opposed to just not mentioning or neglecting these. As much as we increase our understanding in this field, it is also important to emphasize that patients should remain encouraged to go on with their treatments. It was never our intention to create contradictions or doubts in a sense that patients would say, “Well, then, we “don’t even want the treatment.” Because I think one has to be careful with creating uncertainty in patients.

Q. Have you encountered that clinically?
A. I think I’ve heard it in comments and in the reviewing process of several scientific articles. Personally, on a patient basis I have never encountered it, because I think the more we are open about alerting patients to potential side effects — to the bone marrow, kidneys and liver — patients usually are accepting of them. And I think if you include just the brain as a potential site of toxicity and say there may be trouble down the road with cognitive issues, you may not be as highly functioning any more in your capacity to do math, calculations, etc., I think if patients know about it they will accept the situation. As opposed to retrospectively to finding out and then to have no answers for what really happened.

Q. So you believe in a degree of openess, but putting it in context.
A. Exactly. I think we treat to the best of our knowledge because survival and quality of life are the highest aims.  We have to really be on the side of the patient to understand what their needs are. I think this is one of our main duties — to balance risks and benefits and to advice patients appropriately when toxicities are unacceptable and life expectancies would be limited anyhow. I think these are the moments when we should use our judgment and advise patients appropriately.

Q. Have you gotten a lot of reaction to this study?
A. Yes, a lot. What has been sometimes saddening to hear is that many patients and their families have now have found answers to unexplained symptoms they encountered for many years.  Nobody knew why they felt that way because the brain was not even targeted. They had received chemotherapy for breast or lung cancer, for example. And then all of a sudden to have clouded memory, fuzziness, not feeling right, and nobody had really been able to pinpoint this… so I think to provide answers is a big relief. The next step is certainly to deal with the symptoms and to help the patients to feel better.

This all remains a delicate issue. I think it is critical for everyone publishing about this topic to keep in mind how important it is to balance provocative thoughts on the one hand, and to be reassuring to patients on the other hand. Our intention is to help and to find means to properly deal with these problems as they occur. As we gain a better understanding of the physiology of nervous system toxicity, we will get closer to counteracting and developing protective measures for the brain. I think it is only a matter of time before we reach this point, as certain agents already exist.

Q. What exists now that can help?
A. I think what is very beneficial in some patients are high-dose antioxidants. These agents generally have a positive effect on brain repair and progenitor cell populations. The downside is that antioxidants may impair the effectiveness of chemotherapeutic agents, when given at the same time. This is part of our current investigations. Physical exercise is extremely important, so I always encourage my patients to break that cycle of fatigue, because the more they become inactive, the more the brain suffers. So we know that just walking or running is one of the strongest stimulating factors for brain plasticity. It is a very provocative thought, and I think this has been very well studied by scientists who extensively looked at the problem of brain repair and the generation of new neurons. And physical exercise is, interestingly, one of the strongest factors in maintaining brain function.

That’s a whole different topic I could talk to you about from the aspect of brain development, brain plasticity and maintenance, even outside of any disease paradigm. For healthy individuals this seems to be extremely beneficial. So a healthy diet, rich in fruits and vegetables, and exercise. These are essential in order to at least give the brain the tools to be able to repair itself. If there are deficient areas to begin with, the patient’s recovery will already not be at the optimal level. There are a number of agents that we are currently studying in experimental paradigms; although these are not ready to be used in clinical practice yet, I think it’s a matter of probably three to five years until we have quite good agents available to treat patients along with their chemotherapy.

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