“ChemoBrain” book excerpt

Chapter 3
My Treatment Is Done: Why Can’t I Think Straight?

After multiple rounds of chemotherapy, radiation, and surgery, Sedra Jayne Varga had a new job with New York City Family Court and an eye on the future. But things were not exactly clicking into place. “I was just not on top of things any more. It could be, oops, I didn’t pay the electric bill. I forgot birthdays, and I had a hard time knowing what task to accomplish first. I sometimes felt I was drowning in day-to-day minutiae.”

It’s not that Varga, a fifty-year-old New Yorker, is prone to complaint. She faced down a daunting regimen of treatments for breast cancer over the last six years with the hope that she would recover her health and her life. First diagnosed with breast cancer in 2000, she had two lumpectomies, chemotherapy, and radiation. Then, in 2001, she received more bad news: she had a recurrence of her cancer, known as a ductal carcinoma in situ, on the same side. She had a mastectomy. In 2006,  the same cancer was found in her remaining breast, and she had a second mastectomy.

Like many cancer survivors, Varga negotiated the changed landscape of her life. She mourned her mother, who had died of metastatic breast cancer. She struggled financially for a time, changed jobs, and watched sorrowfully as  a love affair ended. But her ability to organize her life and stay on top of events—skills that sustained her during her entired adult life —seemed to melt away.
“Chemotherapy has messed up the circuits of my brain in some way,” she says. “I’ve found a very real decrease in linear thinking.” She has a hard time setting priorities or deciding what to do first on her list of myriad everyday tasks. Going through her mail is a scattershot, messy process.

“Here’s the scenario that explains it,” says Varga, a Brooklyn resident who is a clerical worker  in the Family Court system in New York City. “In the old days, let’s say my boss gives me a large multistep project that takes weeks to complete. Not only would I know immediately what steps to take as I walked back to my desk, I would be putting the steps in order in my mind. After chemo, if my boss gave me a project like that, I’d burst into tears.”

A slew of new studies, launched in the past four years, lend credence to complaints like Varga’s. Dr. Stewart Fleishman, director of cancer supportive services at Beth Israel and St. Luke’s–Roosevelt hospitals in New York City, estimates that eighty percent of those who receive chemotherapy for any kind of cancer have some immediate cognitive change. For many, symptoms begin to lift three to four months after the last treatment. But for about twenty to twenty-five percent, he says, symptoms can last five years or more—and sometimes never go away completely.

Dr. Harold J. Burstein, a doctor at the Dana-Farber Cancer Institute in Boston, conducted what he calls “a highly unscientific study of cognitive dysfunction and adjuvant chemotherapy” among twenty-four patients he was treating for breast cancer. Emphasizing that his survey has no scientific significance whatsoever, Burstein says that eighty percent of his patients believe that chemotherapy might have altered their ability to focus and remember. They report the cluster of symptoms that have become the very definition of chemobrain: difficulty concentrating; problems remembering names, words, or numbers; difficulty with following a particular train of thought; a lack of sharpness; a “spaced-out” feeling or a feeling of being easily distracted.

In a long and distinguished career as an activist for women’s rights, Patricia Ireland has fearlessly faced down powerful adversaries. As president of the National Organization for Women from 1991 to 2001, she rallied hundreds of thousands in marches for reproductive rights. She was arrested in front of the White House as she protested the military’s policies on gays and lesbians. She has spoken out for human rights around the world.

But she confronted an unexpected, high-stakes battle in 2007: she was diagnosed with acute myelomonocytic leukemia (AMML).

Ireland had been feeling tired but figured that a vacation in Barcelona with friends would recharge her. “I had been a little tired, but it was the holiday season, and frankly, like most of my friends, I have been a little tired my whole adult life,” she says in a telephone interview from her home outside Miami, where she practices law. “You know, we work too hard. We have too much going on; we are too greedy for our lives in work and family and play and everything. I kept saying to myself, well, I’m going away. I’ll catch up with my rest. I was really looking forward to it.”

When she arrived in Spain, she began to feel worse but chalked it up to a severe case of jet lag. By the end of the first week, she was crashing. She felt so tired and breathless that she could not walk from her bedroom to the kitchen to get a glass of water. She flew back home, where doctors tested her and found she had leukemia. The rapid growth of leukemic white cells had clogged her system and made it difficult to breathe or get enough oxygen to her brain, she says. Summoning her considerable intellect and inner resources, she embarked on a “high-risk, high-reward” course of treatment that involved chemotherapy and a donor stem cell transplant.

“I went over to Barcelona with friends, and I came back literally on death’s door. Of course, as the anniversary [of the trip and diagnosis] came around, I started imagining it was going to happen again. I had to talk myself into the fact that, well, if it did, I’d had a really good year. I’d bought myself some excellent time.”

The first time she heard the term chemobrain was in the hospital when she was undergoing chemotherapy. Talking to a nurse, Ireland suddenly couldn’t find the right words. “She just laughed and said, ‘Oh, chemobrain,’” Ireland says. “And that was literally the first time I heard it. I was quite taken aback by it. I thought, what a terrible thing to hear now. Of course, no one told me about chemo curls, either, but that has a much less disastrous consequence!” Ireland adds, joking, “And in fact I have decided that as long as I have chemo curls, I can claim chemobrain.”

Ireland had a full week of chemotherapy on the first round of treatment then began consolidation therapy, where patients receive a combination of drugs over several days’ time. The goal is to achieve “molecular remission,” according to specialists. Two and a half months after the consolidation therapy, she went in for her transplant. Before she received the donor cells, she had another round of chemo to partially suppress her immune system.

Ireland recovered, chemo curls and all, and returned to work part time in the fall of 2007. But even though she thought she was well on the road to having her brain “back in gear,” problems with short-term memory and her ability to recall words lingered.

One sobering incident occurred when she was driving to a nearby hospital for blood tests. While Ireland concedes that she is not the most attentive driver under the best of circumstances, what happened next left her baffled: She drove to the hospital and got the tests, but when she tried to go home, she drove past her house. “I have no recollection of going past my house, but the next thing I was really aware of, I was several blocks north of where I lived and wasn’t quite sure of where I was. I had to turn around and go back to find my own house. I’ve had that place since 1970, and I was only a couple of blocks north, but I simply couldn’t be sure where I was. And I realized then that my concentration and cognition were both still seriously impaired.”

She didn’t try driving again for a number of weeks. When she got behind the wheel again, she repeated a kind of mantra to herself: Concentrate, stare at the road, you’re driving. Gone were the days when she drove with one hand and rummaged in her purse for directions with the other.
“I have difficulty accepting help under the best of circumstances, and yet I was wholly dependent on other people [for a while] to drive me around. And this was after I was supposed to be out and recovered as far as I was concerned. It made me realize that all of those warnings that they did give in the written materials were right: They said the patient and her family have to maintain a certain degree of patience because you will not be well as quickly as you think you should.”

Not one of the brochures—and Ireland read volumes of information on her treatment—mentioned chemobrain.

Ireland stresses that she is doing fine but acknowledges that her experience with chemobrain has taken an adjustment. She values her intellectual life, her ability to think and reason and live in a rapid-fire world of conversations and debate. “I always say this about beauty queens and football players and basketball players: You’d better have something else to value because your conventional beauty passes quickly, as does your athletic ability. You’ve got the rest of your life to live. I thought, OK, great, I’ve got a brain that’s going to keep going and I’m in a profession where experience is valued. And so a few gray hairs, a few extra wrinkles. . . . People think you’ve really had a lot of experience, you really must know a little bit about what you’re doing.”

It can be hard, at times, so Ireland reminds herself to hold onto her initial emotion, which was a sense of overwhelming gratitude just to be alive—“to have all this beauty around me and to have all these friends, and to say, OK, even if I never get my brain power back any more than it is now, I can still work.”

She wishes she had been forewarned about chemobrain—she would have considered its effects and known what to expect as she evaluated the consequences of the treatment that saved her life. Yet she accepts the tradeoffs.

“I do wish somebody had told me. Of all the things that I expected, this. . . .” She pauses. “I just like to know what’s coming. It’s like any of the treatments that they gave me that were painful, and I certainly did redefine pain along the way. If I knew that it was coming, I was better off.”

She hopes that future research focuses on causes and advances in treatment. “In that sense, if there are research dollars to be spent, while I would like to have some way to figure out how to not have chemobrain or get rid of it quicker or get rid of it more thoroughly, I’d still rather have them focus on what are the causes  of cancer, and [the question of ] how we prevent this?”

Writer Susan Sontag, the novelist and social critic who died in 2004 after her third encounter with cancer, found that she was somewhat cognitively impaired after chemotherapy. “I think my mother found, and I found being around her, that chemotherapy itself short-circuits a lot of cognitive ability,” says her son, journalist David Rieff, who in 2008 completed a memoir/investigation of her illness called Swimming in a Sea of Death. Sontag underwent chemotherapy treatment and an unsuccessful bone marrow transplant after her diagnosis of myelodysplastic syndrome, or MDS, in March 2004. She died in December. Sontag was treated for advanced breast cancer in 1975 and went on to write a probing book about her confrontation with her own body and with society’s fraught view of cancer, Illness as Metaphor. A second cancer, a uterine sarcoma, appeared in 1998 and necessitated further aggressive treatment.

“I think what my mother discovered, not just after the cancer that took her life, but even after the other two, was that the sense of being somewhat cognitively impaired after chemo is bigger than people thought or that doctors said,” Rieff says. “Obviously, doctors lowball things, once they’re committed to a procedure or a course of action. Good doctors give patients and family members some sense of what the price is for treatment. But once that is decided, a kind of tropism toward understating sets in, in my experience. This is not a scientific conclusion, obviously. [Doctors] want to get on with things—maybe they themselves don’t want to be touched by it all.”

Rieff says his mother used to compare her sense of “fuzziness” to what her friends had described to her after having a small stroke. “She would talk about something missing, a slowness, a tendency to be more confused than she was before. There was a certain unsureness in all cognitive senses, a little fuzziness of expression, of understanding, a hesitancy,” he says. “I’m speaking just in terms of her experience of it, and I don’t know what the biochemical process is, nor have I ever looked into why people think this is so. But it just seems obvious that if you get chemotherapy, you may not function at the same level as you were before.”

Rieff reflects on the intensity inherent in the relationship between doctor and patient: when Sontag used the term chemobrain, he says, her doctors took her seriously. “I do feel that doctors, whether sincerely or not, aren’t as prone to contradict their patients as they used to be.”

Although the cause—or causes—of chemobrain remain elusive, one likely culprit is brain damage.
Two separate studies conducted in fall 2006 provide a tantalizing look inside the brains of patients receiving chemotherapy. One study, done in Japan, showed in vivid high-resolution MRI scans that parts of the brain that control visual memory and concentration actually shrank after chemotherapy. The study’s author, Dr. Masatoshi Inagaki, suggests that neural damage plays a part in chemobrain, and notes that doctors have found that the toxic chemicals used to kill cancer cells elsewhere in the body can penetrate the blood-brain barrier and show up in cerebrospinal fluid and brain tissue. Inagaki says he launched the study, done at the National Cancer Center Hospital East in Chiba, Japan, to delve into the cause of “distressing symptoms which cancer patients feel, especially treatment-resistant psycho-neurological symptoms.”

In the study, he says, “we had an impression that many cancer patients complain of their subjective loss of cognitive function.” His hope, he says, is that the study will lead to development of an “effective intervention” for cognitive problems.

Another small but provocative study found that patients who were given a memory task showed increased activity in parts of the brain that control memory, learning, and integration of sensory perception, indicating that the brain had to work harder. In 2006, Dr. Daniel Silverman at UCLA gave PET scans to twenty-one breast cancer survivors. The scans compared blood flow in the brain of women who had received chemo, women who had been treated with surgery, and women who had never had breast cancer. Another scan was done while their brain was at rest. In the group that received chemo, Silverman found “altered frontocortical, cerebellar and basal ganglia activity” in survivors five to ten years after chemo. “The same area of the brain that was most different when performing the tasks was the area that had the most decrease in metabolism in the women who had the most severe symptoms,” Silverman writes.

Small studies provide a window into the problem, but not a definitive answer. The next step: measuring the brains of cancer patients before and after chemo.

A third researcher found a gene linked to Alzheimer’s disease in survivors of breast cancer and lymphoma who had cognitive problems. That study, done by Dr. Tim Ahles, then at the Dartmouth-Hitchcock Medical Center in New Hampshire, reported that patients with the gene, known as APOE, were at risk for long-term chemotherapy-induced cognitive decline—even though they were treated with standard doses of the most common drug cocktails. (Study participants were given some of the classic combinations of chemotherapy drugs, such as cyclophosphamide, methotrexate, vinblastine, vincristine, and doxorubicin, among others.)

Ahles and his colleagues found evidence for their theory that standard drug combinations given to cancer patients—in regular doses as well as high doses—affected their ability to reason and remember as clearly as they could before receiving treatment. Ahles’s study drew a conclusion that neatly sums up the worries of many cancer survivors: that “these cognitive changes can affect attainment of educational and vocational goals and have a negative impact on the quality of life.”

“Increasing evidence supports the hypothesis that high- and standard-dose chemotherapy can have a negative effect on the cognitive functioning of cancer survivors,” Ahles and his colleagues write. “. . . These cognitive changes can affect attainment of educational and vocational goals and have a negative impact on the quality of life of cancer survivors. The potential cognitive effects of chemotherapy have become an increasing concern among cancer survivors and health-care teams that care for them.”

Eighty cancer survivors who had been treated for breast cancer or lymphoma were given a battery of standard neuropsychological tests. Their blood was drawn and tested for the presence of the APOE gene. The study found differences in test results between those who tested positive for the gene and those who tested negative—particularly in visual memory and spatial ability. “The results of this study provide preliminary support for the hypothesis that APOE is a genetic marker for increased vulnerability to chemotherapy-induced cognitive decline,” Ahles writes.

More research is needed, he insists, noting that he and his team are looking at the relationship between the APOE gene and cognitive functioning in a larger, prospective longitudinal study of breast cancer and lymphoma patients.

In another study that found that systemic chemotherapy had a negative impact on cognitive functioning among survivors of breast cancer and lymphoma, Ahles calls for longitudinal studies to get to the bottom of things. Like many researchers, he believes that a critical step in designing future studies involves evaluating patients before treatment begins and following them after treatment concludes.

In fact, Ahles, considered one of the nation’s top specialists in this area, joined two researchers at the City of Hope National Medical Center in Duarte, California, in proposing a new name for chemobrain: “cancer- or cancer-therapy-associated cognitive change.” They discuss its complexity and express a worry that fear of cognitive side effects will play too large a factor in patient decisions on therapy. Other factors that might affect cognitive function include the impact of surgery, anesthesia, menopause, depression, anxiety, and even other underlying diseases. Beyond a new name, they write, “large, multicenter studies are needed to begin to understand the magnitude and mechanism of cognitive changes in cancer survivors and to assess the impact of cognitive changes in the patient’s daily lives.” But the term chemobrain, immortalized on T-shirts and news articles, is likely to stick.

Ahles and others have suggested that other factors associated with invasive cancer, such as DNA damage or elevated levels of cytokines (tiny proteins or peptides involved in immune response) could be involved in chemobrain.