Tuesday, December 11, 2012

CHEMOBRAIN: THE OFFICIAL PRESENTATION

Since little was offered in the way of solutions, I am going to pick apart the research that was presented in San Antonio regarding chemobrain.  There is so much to share about what I learned in San Antonio but given the origins of my blogging, this seems the most appropriate place to begin.  After, of course, mets which was yesterdays attempt to get the input of the Stage IV patients and where they stand on fresh tissue donation, if given the opportunity.....

I had the good sense to tape the session on my iPhone.  I can access the slides.  I've listened to the presentation no less than three times hoping to tease out ANY information that might lead to us in a NEW direction.  Instead, it would appear that this presentation, at least in my very un-scientific mind, is nothing more than invalidating, insulting, irresponsible and a precisely WHY patients should be involved in steering at least some of the research.

I'm neither a molecular biologist, immunologist, histologist, or oncologist and I do not proclaim to get the gist of any of that stuff.  At best, I listen and learn from the genius-ologists and I listen carefully.  A true mark of brilliance?  Someone who is so ahead of those curves, yet is still able to take the most complex topic and compare it to something in every day life. Dr. Love is a genius at that stuff.  So were every one of the mentors who sat with us from 5:30 until 7:30 each evening to review all of the presentations.  What was alphabet soup with combinations of numbers and letters being bantered about each and every day, came to life thanks to the dedication of the mentors in those sessions.  I can't thank them, or for that matter, The Alamo Breast Cancer Foundation, enough for helping me be a better advocate.

Back to business.  It's being splashed everywhere.  I wrote this as I was waiting for the presentation to begin.  I had a chance to look at the abstract in advance and I had a pretty good idea of what was about to be presented.  I didn't think it was ethical for me to break into the nitty gritty until the researcher did her presentation.  I'm not a "press person" so I don't know what is proper etiquette and what is Bernstein-Woodward-ish.  So I was cryptic.

Now?  Not so much.

Here are just some of the facts regarding the study particulars:

  1. A whopping 97 women were studied in this trial
  2. 28 of them were chemotherapy patients
  3. 37 of them were radiation only patients
  4. 32 of them were healthy
  5. The basis of the study is that worry impaired cognitive function, thus increasing fatigue, thus messing up their brains. It was the worry which was "present before the treatment began."
  6. The "initial evaluation" in the cancer patients was done approximately 24 days AFTER surgery but prior to the commencement of any other treatment
  7. They were all put into an MRI machine and asked to do tasks within that clanking tube
  8. Most of the women were treated with anthracyclines
And here are my questions:


Now to get to the real issue... the reason for the study.  ANXIETY induced fatigue resulting in cognitive issues causes no difference before or after chemotherapy????  Well let's look closer.  Did we examine these cancer patients truly before treatment?  Not really.  Note that the initial evaluations were done almost a month AFTER surgery.  That means, pay attention here folks, this is the important stuff.... these woman already did the runaway train thing.  Bad mammo, call back, biopsy, call back, you have cancer, schedule nine million appointments, decide upon surgery options, stare down the gun of chemo or radiation, learn to live with "I have cancer"  ... and WAIT and WAIT and WAIT some more.

I can still taste the waiting and I can tell you, the waiting was a pretty horrible part of the cancer program.  It's riddled with anxiety.  THEN, for giggles, lets throw ourselves into an MRI tube AND do tasks just because we have nothing else to do..... And, being in an MRI machine isn't stressful all by itself??  And what about the anesthesia.  Are we sure there are no residual effects??  Ditto contrast dye.

Listen, I am all for understanding what is happening.  I'm all for informing patients of the possibility of cognitive issues. I'm all for making sure these patients realize their LIVES are most important and there are work around solutions for many of the problems.  I'm also all for problem solving.  This study didn't add anything to the conversation.  We already accept as a premise that anxiety and depression, fatigue, the cancer diagnosis itself, radiation, chemotherapy, hormone therapy are all part of the chemobrain paradigm.

We didn't really need a study to confirm this.  We needed a study to find ways to prevent it in the future and help those of us whose issues are bad (and somewhat worsening?) ....

THIS folks, is why patients need to be actively involved in what research gets studied.  Did any of us need to see this? Didn't WE all know and accept this already?  Yes, anxiety and fatigue are huge.  All this study did?  Add MORE stress as those headlines continue to pile up and each one of them seems so dismissive.

What was NOT dismissive?  Dr. Patricia Ganz walking up to the microphone to pepper the researcher with questions about the validity of the points in the presentation.  And the researcher acknowledging her own trepidation as she watched "Patti Ganz" (as she called herself) approach the microphone.  Coincidentally, Dr. Ganz presented on Monday in an educational session and she told the whole story and included all factors....

Basically, it's complicated.  And more basically, it's irresponsible journalism.  Major props to Medscape for finally printing THIS which hit my feed yesterday as I was outlining this post.  They tell the whole story.  In case you don't have your own login... it's printed below.  They have peer comments.  I underlined them... Judge for yourselves.  Just note, NO one in this study was given "MF"  and that, quite frankly is all I have to say about THAT.

I've got plenty more to say about the rest, but this rant is over.  I'm feeling a bit like Michael Corleone at the end of the Godfather, don't tell me about my cognitive issues because:

"It insults my intelligence and it makes me very angry."

Before I turn the page over to You Tube and Medscape, one final note:  I'll accept the whole "Cancer Brain" thing as a name changer, game changer, too. Except, there are "levels" to everything in life.  Knowing that the damn M-F (er) wreaked havoc on things inside my skull.....Me?  I'll stick with ChemoBrain... because I WAS fine for a while... and then, I wasn't. And no, I'm NOT tired, my anxiety is well controlled.......EXCEPT when I'm angered by skewed numbers and misleading stories.

Time to turn this over to some third party people.....

Medscape, the only RESPONSIBLE piece of journalism about this study, is below the embedded video.  This would be a good place to share my conversation with Dr. Jay Harness of Breast Cancer Answers while in San Antonio.  We talk about chemobrain and The Jody Study (the one that actually hit the national nightly news.... and JODY is the hero of the piece for truth telling!)

Here's the You Tube link in case the embedded thing doesn't work.  My interview is at the 25 minute mark:

http://www.youtube.com/watch?feature=player_embedded&v=pdDo4tExHkA









And now, with my own skewing of the story... vis-a-vis: the underlined sections, Here's MEDSCAPE:

SAN ANTONIO, Texas — New brain imaging research suggests that "chemo brain" is an inappropriate label for the neurocognitive deficits often reported by cancer patients. That's because reduced brain function caused by fatigue and worry is often present even before chemotherapy begins, according to a new study. However, the research, presented here at the 35th Annual San Antonio Breast Cancer Symposium, was greeted with plenty of criticism.

The lead researcher did not dismiss the concept of chemo brain. "Cognitive changes do occur in women treated with chemotherapy," acknowledged Bernadine Cimprich, PhD, RN, associate professor emeritus at the University of Michigan School of Nursing in Ann Arbor. "But pretreatment-altered neural activation and fatigue can also contribute to cognitive problems," she said during a meeting press conference. "This is a strong argument, in our estimation, for early intervention.... Existing interventions to reduce stress and fatigue may alleviate neurocognitive problems over the course of breast cancer treatment," Dr. Cimprich explained.

The research involved functional magnetic resonance imaging (fMRI) in breast cancer patients performed 24 to 34 days after surgery and before chemotherapy (n = 29) or radiotherapy (n = 37). The control group consisted of 32 age-matched healthy subjects. The prechemotherapy group reported more severe fatigue before treatment than the control and preradiotherapy groups ( P < 0.01); this increased after chemotherapy, but remained stable in the other groups. Dr. Cimprich said the study shows a "moderately strong" correlation between fatigue and cognition in all study participants at baseline and at 5 months ( P < .001). "The lower the level of activation, the greater the increase in fatigue over time....

This was an interesting finding for us; you rarely see a correlation between level of activation and any kind of affective or experiential measure," she noted. Women awaiting chemotherapy are more vulnerable to cognitive problems related to worry and fatigue, and these problems can begin before any adjuvant treatment, she said.

Critics Weigh In Audience member Patricia Ganz, MD, professor of health services and medicine at the University of California, Los Angeles, questioned the study's conclusions. The chemotherapy patients had larger tumors at baseline and had undergone more extensive surgery — both of which can influence cognitive function, said Dr. Ganz. "We know that surgery itself can lead to an increase in proinflammatory cytokines," she explained. "It may be that proinflammatory cytokines, which...are associated with fatigue and cognitive dysfunction, are influencing the underlying biology," she noted. "The chemo patients likely had reconstruction with mastectomy, which causes much more tissue trauma," she told Medscape Medical News. "I am not sure [the researchers] used covariates in the analysis, which could have explained differences in fatigue, and they did not always show P values when they compared groups,” Dr. Ganz added.

Another expert admired the study but also has reservations. "Our field is in need of prospective studies like this, and prospective fMRI studies are especially sparse," Sanne Schagen, PhD, director of psychosocial research and epidemiology at the Netherlands Cancer Institute in Amsterdam, told Medscape Medical News. However, other studies that have reported prechemotherapy cognitive impairment have failed to find a link with fatigue or anxiety, she said, warning against drawing strong conclusions from this study. The researchers conclude that pretreatment cognitive compromise and fatigue are key contributors to the cognitive impact often solely attributed to chemotherapy. However, Dr. Schagen explained that "it is important to realize that the correlations on which these conclusions are based are very weak." "Fatigue may be contributory factor, but to conclude that it is a key contributor is, based on the current data, in my opinion, too strong," she added.

Another breast cancer clinician described the issue as a "multifactorial problem." It's "very interesting" that we see fatigue and cognitive dysfunction in breast cancer patients even before treatment, said Kent Osborne, MD, director of the Dan L. Duncan Cancer Center and the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, Texas. "I've often wondered whether some of these cognitive dysfunctions that have been reported with all kinds of different medicines for cancer are as much related to this problem of worry, anxiety, and fatigue as they are to the treatment," he added.

Study Details All of the study participants had noninvasive breast cancer, but more patients in the prechemotherapy group had a higher stage of disease, which is what "you would expect with standard treatment approaches," said Dr. Cimprich. Specifically, stage II and IIIa disease was more common in the prechemotherapy group than in the preradiotherapy group (82% vs 16%); earlier stages were more common in the preradiotherapy group (18% vs 84%). In addition, more women had undergone mastectomy in the prechemotherapy group than in the preradiotherapy group (46% vs 5%), whereas more women had undergone breast-conservation surgery in the preradiotherapy group (54% vs 95%). In the prechemotherapy group, 79% of women received a regimen of doxorubicin and cyclophosphamide followed by docetaxel (AC-T); 18% received a regimen of cyclophosphamide and docetaxel (CT), and 3% received a regimen of doxorubicin and cyclophosphamide (AC).

Brain function was tested while subjects performed a 30-minute verbal working memory task (VWMT) in the scanner. Immediately after that, they were asked to self-report cognitive function (using the Attentional Function Index) and fatigue (using the Functional Assessment of Cancer Therapy-Fatigue). Subjects were tested again 5 months from baseline (about 1 month after the end of chemotherapy). The median age of the patients was 50 to 53 years, and 79% of them were white. Before treatment, all patients were less able than the control subjects to activate the left inferior frontal gyrus — the brain region critical for working memory ( P < .05). "The prechemotherapy group had the lowest level of activation compared to the controls; the preradiotherapy group fell in between," Dr. Cimprich reported.

Before treatment, the patients performed worse than control subjects on the VWMT (error rate, 10.0% vs 6.5%; P < .05). After treatment, cognition improved to the level of the control group in the preradiotherapy group, but the error rate worsened to about 12% in the prechemotherapy group. "Women who were less able to perform this working memory task suffered greater fatigue over time, regardless of treatment," she said. "So this low function before treatment predicted severity of fatigue later on," Dr. Cimprich noted.

The study was funded by the National Institutes of Health and the National Institute of Nursing Research. Dr. Cimprich, Dr. Schagen, and Dr. Ganz have disclosed no relevant financial relationships. Dr. Osborne reports being a consultant/advisor for Genentech, Novartis, and AstraZeneca. 35th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S6-3. Presented December 7, 2012.

12 comments:

  1. Thanks for sharing all of this, Anne Marie. Wish I'd been there, Elaine

    ReplyDelete
  2. I'm going to have to read this a few more times, but want to say now thanks so much for being in SA and thanks for sharing all of this.

    ReplyDelete
  3. Just wanted to note for the record that Dr. Cimprich didn't answer the questions Dr. Ganz put to her. IMO, her evasions were not elegant.

    That aside, I'm reluctant to give her the time of day. To any thinking person, it is blatantly obvious that the study was poorly framed. Dr. Cimprich and her muddy thought processes are not worthy of our attention. We have better and brighter voices telling the true story from day to day.

    ReplyDelete
  4. Brava, my friend. So proud of you.

    As far as this study goes, let me tell you something: I felt JUST FINE after my surgery. It was no picnic losing half a breast and being swollen, but I was fine. My body could cope with recovery from surgery. But I remember vividly the day that my brain and body were slammed by fog and fatigue, and it was almost 2 months after surgery, when I returned home from my seventh radiation treatment. I pulled into my driveway, opened my car door, and collapsed in the driveway. I haven't been the same since. Then, a few weeks after I finished radiation, I started tamoxifen. After being told I just needed 'a little extra sleep for few months,' I kept waiting and waiting and waiting to feel better, and instead I felt worse and worse, until I could no longer work full-time anymore. I got no help from my docs until I found myself a research study on cancer-related fatigue in which I could participate. After I finished with the study, one of the physician researchers sat me down, worked out a treatment plan with me, contacted my primary care physician about how to carry it out, gave me his phone number and email address, and invited me to contact him anytime, forever, for free.

    Fog or not, I still have a grad degree in science, and I did clinical research myself in grad school. And though it may have only been 'prospective,' this study was wrong-headed going in, in my opinion. What may have improved it is input from patients, before it was undertaken. With all the other valid research that has been done on cognitive dysfunction and fatigue related to cancer treatment -- like Dr. Ganz's, for example -- which has found biomarkers and radiologic evidence of physicological changes related to treatment, I do not understand why this study received more than passing media attention. What kind of brain fog was surrounding the reporters, I wonder? At least WE have a good excuse.

    xoxo, Kathi

    ReplyDelete
  5. Thanks for all your taping and note-taking, AnneMarie. I need to read it again when I don't have a bazillion interruptions to comprehend it all. I did pick up on one item - they only studied 97 women? And we're supposed to think it's significant? Geez. (Even an OPEN MRI machine makes me anxious!!)

    By the way, I also took CMF - went through the 6-cycle regimen twice. Think I've mentioned it before, but I believe it had to have crossed the brain/blood barrier. I had the most intense, vivid, technicolor dreams while I was on chemo - both times. I didn't have anything like that before treatment, not have I had anything like that post-treatment. Now I'm certain I have ADD or something like it.

    Keep feeding us all this info, girl. Just make sure you take some time for yourself to enjoy the holidays. Love you! xoxo

    ReplyDelete
  6. Wow, AnneMarie, your report on the conference and specifically on the study is an amazing piece of scholarship. I am so impressed by you. I also watched your entire interview with Dr. Harness and you were sensational. I felt like you were talking for me as well.

    About the material in this blog post, there's so much here that I'm not even sure where to start commenting.

    First, just thank you for being at the conference and sharing insights that are beyond valuable.

    Second, regarding Dr. Cimprich's study, I suspect it got as much attention as it did because her findings are brand new, so new in fact that (I believe) they have yet to be published in a peer-reviewed journal. That happens all the time with new studies. There's a lot of excitement, write-ups in the press, presentations at conferences, and then, unless they add significantly to the literature, no one hardly remembers them the following year.

    I've seen this over and over. We've had our major studies, the ones you and I have talked about regarding CMF; the historic studies reported in 2006: 1) Japanese researchers (Masatoshi Inagaki) found that regions of the brain involved in learning, reasoning, and intuition, had shrunk significantly in women who had chemotherapy; 2) Researchers at UCLA discovered that these effects remained in some women even 5 to 10 years later(and worse in combination with tamoxifen); and of course, all the studies out of University of Rochester that showed the destruction of animal and human brain cells as a result of 5-FU and other agents. And there have been others by Wefel, and Ganz and Saykin and Schagen and Ahles... These are the studies that set the gold standard for research. Many, many others that have come since have moved the research forward, but only barely. Until the leaders in the field come up with some real science showing how to prevent or reverse chemo brain, it's like we're all just chewing the same gum, trying to get a few more drops of flavor out of it.

    In fairness to Dr. Cimprich, she's been studying chemo brain for some time (I interviewed her for our book)and she has done some fabulous research on the positive effects of being out in nature and how the experience helps breast cancer patients renew attention. As far as this current study is concerned, I’m sure she would have rather tested for cognitive dysfunction at the time of diagnosis, prior to ANY type of treatment (including surgery and anesthesia). It would have made it a cleaner study. But it was interesting (although not at all surprising) that cognitive dysfunction got even worse AFTER the participants finished chemotherapy.

    Anyway, that’s my two cents on this. Let’s hope for more significant studies that help us get our minds back.

    xoxox

    ReplyDelete
  7. AnneMarie I am glad that you are showing people how important it is to look at these presentations and what went in to the trial to see if it is significant or not. There have been so many better studies that did the MRI's while people were actively going through chemo and after chemo demonstrating that chemobrain is real. Just even seeing the headline when I gathered articles from San Antonio I knew this one was a ridiculous premise. It is obvious one month after surgery knowing that someone is facing chemo...their mind is all over the place. These are the kind of studies that leave me so frustrated because we have to get funding for studies with metastatic breast cancer. Anyone that has done chemo, knows chemobrain is real. I can't wait till Dr. Susan Love is back on and on the panel of Doctors with Alamo going over the information. Great job AnneMarie! Thank you!

    ReplyDelete
  8. AnneMarie,

    Thank you for sharing all of this. Your interview was amazing. It infuriates me that so many researchers and doctors deny chemobrain exists. Like you, I had CMF. Before treatment, my mind was all over the place with the diagnosis. I was reeling. But my mind was sharp as a tack...until chemo. Now, 11 years later, I still struggle with chemobrain. My cognitive dysfunction also includes ADD, fog, the inability to grasp things, and so much more.

    Thank you for validating us and being a voice for so many of us. It really made me feel empowered to hear you speak out, and your blog is also validation that this is so real.

    ReplyDelete
  9. Thanks to all for sharing your thoughts. I was out all day yesterday and was joking with a few people that I "set a fire and walked away!" The thing is, I KNEW I was preaching to the choir. I KNOW everyone who reads this "gets it." Interestingly, when I sat down with Dr. Harness, I didn't KNOW this study was being presented. It was a bit of serendipity that he asked about the challenges we deal with on a fairly regular basis. Gave this blog piece some additional professional input!!

    ReplyDelete
  10. dear annemarie,

    honestly? i can't yet process all that you've so painstakingly and cogently and caringly laid out. though i am exceedingly interested, and WANT to be able to join in the conversation, the degree of chemo brain that i am experiencing is a real handicap, and that really, really devastates me. i've spent years combing through scientific research and scholarly articles on multiple myeloma because my husband was diagnosed with it in 2009, and i needed to be an informed advocate for him. i was very proud of being able to sift through it all and cull off what was needed to assure we found the very best care for him and could navigate through 2 stem cell transplants, make the right decisions about indiviualized treatment options (so many! and changing so rapidly!) post transplant. as a hospice nurse for 30 years, never dreaming both hugh and i would have cancer at the same time, i was so grateful for having a background that helped me be able to be on top all the latest information that was meaningful to his case. luckily, when i was diagnosed with st IV met BC nearly a year ago, i still had my groove on to research for myself.

    but now? if N.E.D., that fickle fellow, decides to hit the road will i ever again be able to do that same sort of research, attack a scientific paper or article that i need to understand and discuss with my doctors? and believe me - i dodged so many potential bullets - like the "standard of care" with radiation that would have left me with cardiac, respiratory, and esophageal long-term damage by taking my case to a tumor board, winning them over, and then saying, "in this case, the patient was the voice of reason"! it's scary, and maddening, and distressing to think that i might not have the wherewithall (is that all one word?) to be the staunch advocate i once was - for both hugh, and for me. multiple myeloma is not curable, either, so the concerns i have sometimes haunt me when i feel vulnerable and the "what ifs" punch me in the solar plexus.

    so my dear annemarie, please know that, though i can't quite get my pudding brain wrapped around all that you have reported, it's a work in progress i will continue to revisit. all i know for sure is that chemo brain is real, and that we need you to peel off the layers of faulty studies and the media hype that ensues. your zeal, tenacity, and courage to challenge what could affect legions of BC patients and expose the flaws and wrong-headed approaches of those studies is so greatly admired and appreciated.

    now, i hope you are taking good care of yourself, getting some rest, and feeling well and happy with the incredible body of work you have done. and please know i will keep your mom close to my heart sending powerful vibes of hope that all will be well.

    love, XOXO,

    karen, TC








    ReplyDelete
    Replies
    1. One of the best lines in every word of this entire BLOG: "In this case, the patient was the voice of reason" and THAT,my dearest karen, tells the whole story.

      I do feel for you.... the concerns about being able to continue being the voice of reason for both you and hugh. In almost every conversation in San Antonio, good patient/doctor communication was brought up..... Doctors should have the information so we can make informed choices. If this, then that... and we choose.

      Thank you for your thoughts about my mom. Keep them coming... a bone biopsy is now being scheduled. Just found out a few hours ago.

      xoxoxo

      Delete
  11. dear annemarie,

    thank you so much for you generous and kind feedback, and for the empathy you express. it means the world to me that you took the time to validate my concerns.

    about your mom - i'm on it, honey girl, i'm on it.

    love you, XOXO

    ReplyDelete