Reader comment

I am sitting here at my computer crying because I have been so affected by chemo brain and I have not been able to return to work. I live in northern Ontario, in Canada. There seems to be very little info about chemo brain and my employer has so much as said that I am making it up so as not to have to return to work. I work in a fast paced medical laboratory, and multi tasking is a must. I can barely function in my kitchen. I finished chemo for breast cancer in Nov. 2008 and I am 45 years old. My main problem is with very short term memory. I can perform a task and then minutes later not have any recollection of doing it. I grasp for words and have trouble spelling. Many times I know I need to accomplish something, such as putting on my seatbelt but I cannot figure it out immediately. I sit for a minute, and then it is like a slow-moving train coming around the mountain – Oh yeah, I need to do this. I am so frustrated trying to defend the fact that this is real. It was easier when I was bald and looked outwardly sick. At least then I felt I had credibility as to my illness.

Thanks for listening. Debbie Irwin

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Chemobrain vs. smog in LA

A reader writes…
I am always bemused when the medical establishment finally catches up with what everyone has been saying for a long time.  All you have to do to know about chemobrain is go on chemo. I met countless other women on planes, buses, etc. while I was on chemo, who all experienced it.
Somehow we could instantly sense each other. It usually took about 15 seconds after saying hello to a total stranger to find myself deeply immersed in a conversation about how chemo was making it hard to think.  But it is good that now the doctors will believe us.   And it is good to live in L.A. and So. Cal. where everyone is a bit scattered. I have no idea by now what is chemobrain, what is information overload, what is smog, and what is being post menopausal.
Margie W.

NCI to boost Cancer Genome Atlas

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Speaking to an audience of cancer researchers and clinicians at the American Association for Cancer Research, the director of the National Cancer Institute colored in some of the details of how his agency intends to spend its share of the federal stimulus windfall.

After four years of flat-funding, the NCI will pour much of the $1.3 billion into seeding a next generation of cancer research and into expanding the three-year-old Cancer Genome Atlas, according to director John Niederhuber.

The money, part of President Obama’s $787 billion American Recovery and Reinvestment Act, is targeting genetic and cancer research in part because of the efforts of US Senator Arlen Specter, a cancer survivor who is interested in translational biomedical research. In other words, Specter is pushing for the kind of science that can leap from lab bench to bedside.

When it became clear that NCI was due for a significant share of stimulus money over a two-year period (2009 and 2010), Niederhuber and his colleagues took a moment to weigh all the demands — to assess what Americans want in terms of next steps in the so-called war on cancer.

niederhuber1“We came back repeatedly, in these discussions, to the conclusion that they want better ways to prevent cancer; they want the earliest diagnosis; and they want new therapies with fewer side-effects that turn cancer into a condition you can live with and not die from,” he told the conference in his talk on April 20.

Then, he sketched out a broad vision. “Economic stimulus funds give us the chance to be visionary; to make strides today toward realizing the promise of personalized medicine; to enhance the process of drug development from target identification to translation into viable therapies; to move cancer research from the accumulation of scientifically exciting genomic data to a new way of approaching prevention, diagnosis, and therapy and to ensure access to our latest science for all.”

Mindful of Obama’s command to “ignite our imagination,” Niederhuber says the NCI has an eye on the future: fostering a next generation of cancer science and cancer scientists. To that end, the agency plans to award grant money to young investigators who are MD-PhDs, “who are committed to careers in translational cancer research.”

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The money will supply some rocket fuel to The Cancer Genome Atlas (TCGA), launched in 2006 by the NCI and the National Human Genome Research Institute. Since then, Niederhuber says, TCGA has sequenced more than 200 tumors in the brain (glioblastoma), and in lung cancers and ovarian cancer.

“With that foundation of success,” he said, “we plan to move TCGA forward, with a goal of identifying all of the relevant genomic alterations in 20 to 25 major tumor types.” Another NCI program, called TARGET, will get money to expand sequencing to 100 tumor types in childhood cancer. (In the realm of NCI acronyms, TARGET stands for Therapeutically Applicable Research to Generate Effective Treatments.)

Translated into bottom lines and budgets, the stimulus package means money for science: new equipment, and salaries for lab technicians and post-doctoral students who work, like chefs in an exquisite kitchen, with the raw ingredients of life. Mindful that research begun with stimulus funds must be continued beyond the two-year window, the Niederhuber remains an optimist.

Although the TCGA has been criticized by those who believe it is too expensive, inefficient, and likely to lead to descriptive studies rather than real breakthroughs, Niederhuber and his colleagues believe this kind of research is a blueprint for the 21st century. It is, in effect, all about drawing a clear, bright line from discovery to the patient, from the molecular view to the whole of a person.

“This wide-ranging plan will require the contributions of biologists, chemists, informaticians, and clinical scientists who are devoted to a clear path from discovery to patient. that is not only the nature of translation; I believe it will be a model for the study of many diseases and, ultimately, a model of 21st century healthcare, when we are able to match pharmacogenomically characterized patients and molecularly profiled tumor types to highly specific molecularly targeted therapies.”

A pause for inspiration

Michael Paulson, the Pulitzer-prize-winning religion reporter for the Boston Globe, links to some thoughtful and spiritual comments on Susan Boyle, the Scottish singer who stunned the cynical panel of “Britain’s Got Talent.”

When Boyle tottered onto the stage, the audience and the judges were rolling their eyes and stifling laughs. She is (pick one): not blonde, not young, not thin. But her performance put everyone to shame.

As Michael asks, what does it say about our culture?

Here is the link.

Dr. Dietrich on chemobrain, part 2

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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.

Chemobrain: a doctor’s view

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An interview with Dr. Jorg Dietrich of Massachusetts General Hospital

The title of the article is a mouthful: “Clinical Patterns and Biological Correlates of Cognitive Dysfunction Associated with Cancer Therapy.” It made its debut online on Nov. 19, 2008, in the online version of the journal “The Oncologist.” (Many of the most tradition-bound peer-reviewed medical journals now publish shorter, “express” versions of their articles online first. Abstracts – a short summary of the main points – are often available free on PubMed)

But the article, by Dr. Jorg Dietrich at Massachusetts General Hospital in Boston, and colleagues at Stanford University and at the MD Anderson Cancer Center in Houston, contains a thought-provoking theory about what might be causing some symptoms of chemobrain (Dr. Dietrich, a physician who also has a PhD, is a clinical fellow in neuro-oncology at the Stephen E. and Catherine Pappas Center for Neuro-Oncology at Massachusetts General in downtown Boston.)

Let’s be clear: the researchers never actually use the term chemobrain. By most accounts, that is too colloquial and imprecise for scientists. And it is not entirely descriptive, either, because Dr. Dietrich and his team found that people treated with radiation also had problems with memory and thinking. They use terms like neuro-cognitive deficits and cognitive dysfunctions. But the symptoms they are talking about are unmistakably chemobrain: Forgetfulness, difficulty concentrating, trouble staying organized. An overall feeling of “spacing out.” (And, yes, the researchers did use that highly non-technical term!)

The researchers found that adults reported cognitive symptoms soon after they started chemo. “Frequently,” Dr. Dietrich and his colleagues wrote, “these symptoms persist after completion of therapy and are a cause of considerable distress for individuals who are unable to return to their previous academic, occupational, or social activities, or are able to do so only with significant additional mental effort.” These symptoms, they note, can persist, or even emerge later.

So what might be causing this? Tests in the lab and reviews of brain scans found damage to regions in the brain where newborn cells are developing. This view of the brain is relatively new, according to researchers. “We have learned in the past decade that, contrary to our initial belief, the brain has the potential to repair itself.”

But inflammation caused by radiation, and the toxic drugs used in chemotherapy, can strangle these newborn cells in the crib, essentially.
The image I am using here – strangling a newborn – is a bit crude and perhaps sensational, intended to signal the importance of this process of re-creation that is needed to maintain the brain’s structure. Dr. Dietrich, in an interview, uses a more elegant metaphor: a fertile field where crops can thrive. “If you essentially cut off the water source for a cornfield, you will not be able to grow anything in the years to come,” he says from his office at Mass. General. “This is essentially what happens. If you stop the production of newborn cells, you will have to deal with the consequences years down the road. Because you wipe out an essential proliferating pool of cells that is needed. Some are the stem cells to just rebuild what is lost. If you don’t have these tools available, then essentially no more repair mechanisms can take place.

“A simple way to put it is an early aging process that has been triggered. Because that is exactly what happens during aging, you lose some of these potentials to repair, and with these kinds of treatments you actually let the organism prematurely age.”

Here, in Q&A format, is more of my interview with Dr. Dietrich. (And, as an aside, he is an articulate man who seems passionately committed to listening to his patients, and to speaking with them honestly about their illness, the treatments available, and what to expect.)

Q. You found that both chemotherapy and radiation affect these newborn cells, which you call neural progenitor cells, in the brain. What is damaging the cells? And do chemotherapy and radiation cause different sorts of problems?

A. The radiation [studies] are a little older, and I think they have paved the way for allowing the chemotherapy studies on the toxicity on the human brain. The mechanisms of how radiation affects the human brain are somewhat different than toxicity from chemotherapy. We know that patients who are exposed to radiation treatment show signs of inflammation. And inflammation itself in the brain may cause a whole cascade of negative side effects.

One of the most important side effects that we see, in terms of symptoms, is cognitive impairment that may propagate even years after radiation treatment has been finished. Radiation may impact the rejuvenation of brain cells and mainly has negative effects on the newborn neurons. We have learned in the past decade that the brain is actually able to repair itself to some degree, contrary to what was originally thought.

This alone was a revolutionary finding — to see that there are certain areas in the brain called germinal zones that are on a daily basis engaged in providing a source for newborn cells of all lineages. These newborn cells become neurons, which are key for the neuronal network. They also become the support cells, called astrocytes and oligodendrocytes. They are suffering, and may not allow the neurons even to work properly.

Q. So for people who get radiation therapy, it is inflammation that causes serious problems?

A. Inflammation is one of the consequences of radiation to the brain. And it is probably one of the key reasons why cells in the germinal zones of the brain stop dividing and why the generation of new neurons is impaired.

Q. And that can affect memory?

A. Yes. One of the target areas that suffers most under radiation treatment is the hippocampus formation, which is critically important for storing and retrieval of memory.

Q. How is chemotherapy different?

A. With chemotherapy, it looks like some of the mechanisms are very different because inflammation may not play an important role at all.
Unlike with radiation, chemotherapy appears to compromise the generation of newborn neurons and glia cells throughout the brain, although these effects are most notably in the germinal zones and so called white matter tracts – bundles of cells and fiber tracts that connect different areas of the brain. In this regard, chemotherapy is probably more broadly targeting all [cell] lineages at the earliest stages. And with that, the network system, the overall brain function, and just the ability of the brain to do its job cannot be fully maintained. I think this is one of the key differences between both treatments.

Q. What about patients who receive a combination of radiation and chemotherapy?

A. Some patients only receive one type of treatment and others receive a combination, so the ones who are essentially exposed to both kinds are the ones who are considered to be  at highest risk to develop side effects.
Q. What was the biggest surprise in your research?

A. In terms of the chemotherapy treatment, one of the most surprising outcomes I must say is that patients who don’t even have a brain disease, who are treated, let’s say, for breast cancer or for lung cancer, may develop toxicity to the brain over the long term, over the years to come.
Unfortunately, right now, we have no good means of following this, or identifying the patients who are at highest risk, or even to define means of protecting the brain.

Q. Protecting the brain seems so important – are you optimistic that some way can be found to accomplish this?

A. In chemotherapy, there is a good analogy that has been well studied and accepted in the cancer / oncology community, and that is toxicity in the bone marrow.

Bone marrow typically suffers with many forms of chemotherapy treatment. And this is why we closely observe patients on a regular basis to see how the bone marrow behaves. And when the bone marrow suffers and certain lineages like the platelets or the white counts drop significantly, and there is an increased risk of bleeding or infection, then chemotherapy will be put on hold until the bone marrow recovers. This is the standard.

In the bone marrow again, to compare this organ system with the brain, we have ways to protect the bone marrow. We can give support agents to help the bone marrow to repopulate again — growth factors are given subcutaneously [under the skin] by injection or intravenously [into a vein]. And with this the bone marrow is able to get some mileage and rebuild cells quicker and patients are functionally maintained so they can receive further treatment.

Q. That’s a good analogy, one that everyone has heard of or read about. How does this relate to the brain?

A. We feel that similar mechanisms exist in the nervous system. But we currently have no means of thoroughly monitoring damage to the brain in order to say, “Well this patient has now developed a very notable drop in his brain repair capacity. And we need to put chemotherapy for at least a month or so on hold to let the brain recover.”

Q. What does this mean for the whole field of chemotherapy as a cancer treatment?

A. Chemotherapy is one of the hallmarks and cornerstones of cancer therapy and will be in the foreseeable future. But we need to define ways of monitoring patients better, either with imaging or with certain cognitive assessments in order to identify the ones most at risk and then to choose treatments appropriately. In addition, there is a strong need to develop strategies to more effectively protect the brain, especially in patients treated for cancer outside the nervous system.

Q. That’s a goal of your research?

A. Yes, I think that is the main goal, this is the direction we want to try to move the field.

Q. So you are in essence calling for more research to develop better ways to monitor patients treated for cancer in regard to their brain function and to identify both protective and brain repair strategies to be used in affected individuals.

A. Correct, I think there are three big areas where one has to move forward in the future.

One is to define ways to better monitor patients who are at risk and who are developing side effects — dementia, cognitive issues, trouble with concentration and attention, fatigue, all of these are part of a syndrome complex that is explained by the damage to these germinal zones and connecting fiber tracts.

The second point is having protective agents at hand to be used in patients who are receiving chemotherapy drugs that may damage the brain. There is already an array of different agents available and being currently tested in laboratories.

The third point is to routinely employ certain drug screening assays [tests] to identify agents that may potentially be harmful to certain brain cells, even before these agents are used in patients. The scientific knowledge in this area has steadily increased over the past few years and we have learned that potential harmful effects on brain cells may not be identified if less sensitive drug screening assays are used in pre-clinical testing. In other words, as much as novel drugs are rigorously tested for bone marrow or other potential organ toxicity before these drugs are released and approved by the FDA, more sophisticated screening tests will need to be used to identify potential nervous system toxicity.

Q.  Some doctors I talked to said chemotherapy does not cross the blood-brain-barrier, and that you’re on the wrong track if you believe it does.

A. Yes, I think this is a misbelief. While certain drugs certainly may cross the blood-brain-barrier easier than others, current research has put this question on a more scientific footing. Our increasing scientific understanding in this area still has to translate into clinical practice and it will have to be accepted in the oncology community that chemotherapy can be a major cause of toxicity to the brain. The good news is that the brain actually has recovery potential. Even if toxicity to the brain develops, this does not mean that this is irreversible damage. As in any other organ system in the human body, the brain has a tolerance level, and the more the brain is exposed to drugs over years, the more irreversible the damage may be.

Q. So what is a patient to do? Patients are willing to do anything to return to their lives, to live. But the implication of a group of long-term survivors who are impaired is quite significant.

A. Yes, this appears to be a problem especially in the children’s population. We have high cure rates in some forms of leukemia – over 70 percent, 80 percent. I think it is important for oncologists and parents who guide the treatments of their loved ones to discuss that certain drugs come with brain toxicities and that these could be expected down the road so there is no surprise.

There has been an increasing awareness about long-term toxicities as a result of numerous clinical reports documenting persistent side effects in children who were treated many years earlier with chemotherapy. In the late 90ies there were a number of papers suggesting that this may also be a problem in adults, especially with prolonged survival. Now, in the past four or five years, the first scientific papers have been published to explain why this damage occurs.

Coming tomorrow: What patients want.

Journalist Susan Tifft’s “Chemo Blues”

 

Susan Tifft, the Eugene C. Patterson Professor of the Practice of Journalism and Public Policy Studies at Duke University, is stepping down this year. After taking a year-long academic leave to research and write a book, she had to abandon plans to return to Duke this fall when she was diagnosed with stage 4 uterine cancer. (Former Washington Post managing editor Phil Bennett will move to Duke in the fall to take over as Patterson professor of the practice.) Tifft, a longtime writer for Time magazine, is the co-author, with Alex Jones, of The Trust: The Private and Powerful Family Behind The New York Times (Little Brown, 1999), which was not only a delicious read but a finalist for the National Book Critics Circle Award in biography. Her first biography, also co-authored with Jones, was The Patriarch: The Rise and Fall of the Bingham Dynasty, a biography of the family behind the Louisville newspapers (Summit Books, 1991).

Susan Tifft and Alex Jones

Susan Tifft and Alex Jones

Duke reports that Tifft has undergone chemotherapy treatments to arrest the cancer, which had spread to her lungs. On her journal for CaringBridge.org, she documents her treatments, her emotions, her celebrations. She also rewrites a Dylan tune to describe her reaction to chemo. Here it is: 

“The Day Before Chemo Blues”

IF BOB DYLAN HAD CANCER, or ‘The Day Before Chemo Blues” (with apologies to Bob)

I feel good, I feel fine.

I’ve even had a little wine!

But them salad days are over and done.

Mass General Hospital again has won.

I got the knock-me-down, throw-me-up, I’m fixin’ to heave, day-before-chemo blues.

No more yoga, no more fun.

For the next few days it’s walk don’t run.

Phooey on rest, phooey on quiet.

I’d much prefer to stage a riot.

I got the knock-me-down, throw-me-up, I’m fixin’ to heave, day-before-chemo blues.

Food ain’t tasty, drink ain’t cool.

I stare at the wall, I start to drool.

My mind’s a fog, my brain’s a mess.

I even forget to brush with Crest.

I got the knock-me-down, throw-me-up, I’m fixin’to heave, day-before-chemo blues.

This isn’t such a woeful plight.

It’s just a week or so out of sight.

I’ll think of you, my dearest friends,

And be back to you when chemo ends.

I got the knock-me-down, throw-me-up, I’m fixin’ to heave, day-before-chemo blues. (see you soon! xo Susan)