Chapter 12: Consolidating the Focus on Mind/Body Research

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Chapter 12: Consolidating the Focus on Mind/Body Research

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Dr. Cohen explains how his focus on mind/body research intensified once he met Dr. Raghuram Nagaranthna from the VYASSA Institute. He talks about the mission of the institute and explains the organization of the pilot study they ran studying the impact of yoga on the quality of life of breast cancer patients undergoing radiation therapy. He talks about the publicity that this study attracted then tells an anecdote to illustrate how a radiologist became convinced of the value of yoga and became a supporter of the study. Next he talks about a study of the treatment of "chemo-brain" with Tibetan sound meditation. He then describes new work on the use of hypnosis in combination with local (as opposed to general) anesthesia for breast cancer procedures. He explains the risks of general anaesthesia.

Identifier

CohenL_03_20160824_C12

Publication Date

7-24-2016

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Understanding Cancer, the History of Science, Cancer Research; Professional Path; Overview; Definitions, Explanations, Translations; Research, Care, and Education; Research; Patients; Patients, Treatment, Survivors; Cancer and Disease; Professional Practice; The Professional at Work; Collaborations

Transcript

Lorenzo Cohen, PhD:

[] So around that same time, but slightly afterward, a very small and intensely, energetically powerful Indian physician comes into my office one day, and in so many words says -- because she'd found out that we were -- you know, that I -- who I was, and that I'd started to do some yoga research -- "You need to do research with us. I was like, "Who are you? You know, she was in a sari, very traditional, and by training a gynecological -- a gynecologist sort of in general, but not necessarily focused in cancer. And she came from this organization in -- outside of Bangalore, India called the Vivekananda Yoga Research Foundation. That's what we called it, but it has this sort of longer name to it, and the acronym is VYASA. I can't remember the exact date that I met her, but it would be great to be able to backtrack at some point. But I think it was before our yoga publication. So VYASA -- I don't know the history of VYASA in Houston, which it would probably be fun to find out... And so I listened to her, and then after she left looked her up, and the organization up, and lo and behold, it turns out they probably are the most well-published yoga research group in the world, with a specific focus in medicine. So their first study they published in 1985 in the British Medical Journal showing that yoga practices, and in particular the Pranayama, the yoga breathing, helped treat patients with chronic asthma. Nineteen eighty-five. That meant that they had to have started the research in 1983 or even 1982, because we all know how long research takes to actually get into a publication from the time you create the first patient, particularly a prestigious journal like the British Medical Journal. So --

T. A. Rosolowski, PhD:

What was her name?

Lorenzo Cohen, PhD:

Dr. Nagarathna. Raghuram Nagarathna. So, you know, after I learned a bit more, and that they, you know, had started this -- you know, that they were founding, or had already founded, a Houston chapter, let's call it -- and, again, I'm not sure what brought VYASA to Houston, but, you know, being the largest medical center in the country, and, you know -- that's a good place to go. VYASA, you know, not only was doing research, but they were training yoga teachers specifically to get engaged in -- within medical centers and hospitals. So their mandate and focus was really in alignment with us, and what we were doing here at MD Anderson, at least as we had started it. So this -- yeah, this dates back to prior, to the publication of the Tibetan yoga study, because I have a document... The first document I have in my records here for the development of the first pilot study with the VYASA group is 2002.

T. A. Rosolowski, PhD:

What was that pilot study?

Lorenzo Cohen, PhD:

So we did a small pilot of 60 patients, incorporating yoga into the radiation treatment plan for women with breast cancer, and they would have yoga two times a week for six weeks of radiation. Then we followed them at the end, I think it was one month and then three months later.

T. A. Rosolowski, PhD:

And this was another sleep study? Or a general quality of life?

Lorenzo Cohen, PhD:

Well, general quality of life. We weren't sure exactly, you know, what outcome would end up being the strongest. It turned out that sleep wasn't one of the big ones, and it turned out to be their physical functioning, and then aspects of -- more aspects of spirituality, this measure called benefit finding, and, again, the physical functioning aspects, so quality of life. That led to a... That led to a R21, and for those who don't know what an R21 is, it's small research grants from the NIH, about a quarter of a million dollars, to do smaller pilot studies, and so in the R21 we added that stretching arm, so that you had patients who were doing yoga two times a week -- I think we upped the dose -- three times a week for the six weeks, general stretching exercises, and then we have the control group that got the standard of care, which is nothing. And so -- and we followed them for six months, and replicated those findings, and we also had, importantly, a measure of cortisol, and cortisol's a stress hormone that's high in the morning, so our cortisol's at its highest right now, and it's going to slowly drop throughout the course of the day. There was publications by David Spiegel and JNCI back in early -- the early 2000s, showing that women with breast cancer who had a dysregulation of their cortisol slope, meaning slopes that were less steep or were dysregulated in some fashion, didn't live as long. And so what we found was that by the end of radiation there was actually a blunting of the cortisol slope for everybody, but much less so for the women who were in the yoga group, compared to both the other groups, at the end of radiation as well as one month later. So here, the Tibetan yoga protocol, the first document I have in my records is -- dates back to 2000. So, you know, we started that one first, and then we moved to the -- working with the VYASA group, as well. Oh, here's the manuscript. Yeah, 2004. And I was correct, 39 patients. So that R21 was very successful, tons of publicity, because, again, it was actually the first yoga study to include an active control group. And why that's so important is that you need to -- we couldn't say any -- that it had anything to do with yoga, because maybe it was just stretching. Maybe it was just movement. Maybe it was just attention. Maybe it was just the social support that they're getting. And we know all those what you could call active factors, and then the more inactive, or nonspecific factors, like social support and attention, etc.

T. A. Rosolowski, PhD:

When you say it got a lot of publicity, what do you mean?

Lorenzo Cohen, PhD:

Oh, in newspapers, magazines, you know, that kind of thing.

T. A. Rosolowski, PhD:

OK, so -- yeah.

Lorenzo Cohen, PhD:

News reports, you know, the local... You know, it didn't -- it got a lot of international attention, but it's not like I went on Good Morning, America kind of attention.

T. A. Rosolowski, PhD:

No, I just -- I didn't know kind of what you were referring to, that's all, and --

Lorenzo Cohen, PhD:

Yeah, yeah. So the local Fox News did a story, the Houston Chronical. It was, you know...

T. A. Rosolowski, PhD:

Why do you think there was so much attention?

Lorenzo Cohen, PhD:

Well, one, it's yoga. I mean, you can find more yoga centers than Starbucks in Manhattan now, so, you know, that's one aspect of it. And the other -- you know, the lay press is really interested in this stuff. You know, they're interested in the lifestyle stuff, and things that can help cancer patients. We know that individuals have these chronic illnesses, and, you know, anything that can be shown to help patients tends to get attention in this area.

T. A. Rosolowski, PhD:

What about from the medical community? How was, you know, these sorts of studies that were firsts and were very positive -- what --

Lorenzo Cohen, PhD:

So let me -- so I don't know if I've described this. And I'm sure he'd be fine with me going on record describing this. I can't remember if we'd talked about this. I remember we talked about the story about Pisters, Louis Pisters, and patients, and optimism and pessimism and all that. So when we started the -- this yoga study, we had a very small window of opportunity in which we could recruit the patients and get baseline before they started radiation. So, you know, that -- typically what happens is a patient will finish their chemotherapy, and then they have surgery, or they have had their surgery, then they had their chemotherapy, and then they're about to start radiation. So most of these patients aren't around -- you know, as you might know, two thirds of our patients aren't from the Houston area, so they come in to meet with their radiation oncologist. Maybe, you know, the next week or shortly thereafter they do their radiation simulation so that they can get, you know, all the statistics and everything set up to start their radiation, and then the next week they'll start their radiation. We were collecting sleep measures, so they had to wear these watches, actigraphy watches, for a week before the start of radiation. So we needed at least a week. So ideally we would catch them at the physician consultation before simulation to give us the biggest window of opportunity. So at that time -- gosh, what's his name? The -- he was head of -- so George Perkins was our primary collaborator, who is now head of -- the physician head of our PRS, so breast radiation oncologist. Tom Buchholz, extremely supportive, who's now our physician-in-chief, of bringing this kind of research in. At that point he wasn't department chair; he was a relatively new professor, as I was. We -- I think we both came in 1997. And Eric Strom. [] So Eric Strom was essentially the center medical director for the breast radiation group, and he was very open and willing to have us there, but he said, "You cannot approach patients during the consultation, because I don't want it disrupting our flow. Do anything you want from simulation onward. So don't approach a patient before simulation. So we're like, are you kidding? You know, we're not going to be able to... Because patients could get their -- start radiation the next day, or 48 hours later, and the patients are anxious to kind of get things going. So we're like, OK, you know, you're the boss, and we'll see what we can do. We were really struggling in trying to get patients on the trial in a timely manner, and some patients started radiation, so we had incomplete baseline. And a few months into the study, the research assistant comes to me and says, "You won't believe what happened in clinic today. I was with a patient, and I didn't know that Dr. Strom hadn't seen the patient yet, and she's in the clinic room speaking to the patient. And Dr. Strom opens the door and comes in, you know, kind of -- I don't know if you've met Dr. Strom. He's tall. He's muscular, very athletic, and very well put together kind of guy. And, you know, she panics, and immediately says, you know, "I'll leave, I'll leave, I'll leave you guys. And he's like, "Oh, are you here about the yoga study? And she's like, "Yes, I'm in... And he, "No, take your time, take your time. I'll just be outside. So it turns out that after starting and running the study for a while, patients were going to Dr. Strom and thanking him for allowing them to participate in this study, and having this study as part of the center. And from then on, we could approach the patients whenever we wanted, you know, because he started to see firsthand from the patients how wonderful this program was for them, and how useful they were finding it in their lives. So this was the first study, and then we ran the second study and now we're in the midst of the last year of completing a much larger study where we're trying to get over 400 patients randomized to a similar model of yoga versus stretching, and we've incorporated some relaxation exercises versus usual care.

T. A. Rosolowski, PhD:

So what were the benefits that the patients were seeing that made them so enthusiastic about it?

Lorenzo Cohen, PhD:

Well, actually, the patients -- and we report this in the first paper -- again, in the first paper it was mainly the area of physical functioning and benefit finding, which we replicated in the second study, but when we asked the patients to, you know, to write -- to tell us, you know, what benefits do you see, they talked about actually sleeping better, having more range of motion, and we measured range of motion, but it wasn't a sensitive enough measure to actually detect that there was a difference. But they felt and reported that they were sleeping better, that they were able to move better, that their mood was better, that they were more relaxed, you know, all these benefits that they were detecting, many of which we weren't able to see between the two groups, because, again, a lot of our subjective measures are very clinically laden. All these women had very good mental health, so they weren't in the depression range. They actually were better for a generic measure of mental health than women in the general population.

T. A. Rosolowski, PhD:

Wow! (laughter)

Lorenzo Cohen, PhD:

So you can't improve somebody's mental health beyond perfect kind of thing. But they reported being more relaxed after they did it and, you know, all these types of things. So those were probably the kind of anecdotes that they were feeding to Dr. Strom for him to be able to, you know, open the door. And the radiation oncologists, you know, loved this study, and it continues today. And, as I mentioned, the first draft of the first protocol we wrote in 2002, and we're now almost in 2017, and we've continuously recruited patients on this kind of research in the breast radiation group. So that's the -- that's kind of the yoga study in that line, and, again, it continues today with -- as I kind of mentioned, in the area of trying to treat peripheral neuropathy with a number of different integrated medicine interventions. We've started to get, for some of the studies, a little more symptom-specific, so we conducted a small study of Tibetan sound meditation to treat chemo brain, which is one of the other symptoms I forgot to mention to you, which is cognitive dysfunction that's induced by the chemotherapy, which is for many people permanent, and extremely debilitating, and for some they cannot continue with the original occupations that they had. Chemotherapy is a neurotoxic agent, as well as generally toxic, and it's been documented through brain scans and everything that for many people these changes are permanent. And we found that through this form of meditation that you could actually improve cognitive functioning. So we did a small pilot study, published that, and then I have subsequently done a larger study with the neuroimaging and with collaborations in Brazil, part of our sister institution network, and we're actually meeting with them in the next couple weeks to see where things are, and so that kind of continues.

T. A. Rosolowski, PhD:

Have I told you about that book Meditation Is Medicine? I think I told you about that a couple years ago. But anyway, I remember it was about sound, so it would be interesting, you know, extra supplement to --

Lorenzo Cohen, PhD:

Definitely.

T. A. Rosolowski, PhD:

-- let people know about, yeah. So how exactly did you use sound in that study to treat this --

Lorenzo Cohen, PhD:

Well, this comes from the Tibetan Bön tradition, and Alejandro helped to design that, and did... It's a combination of sounds, so these ancient syllables from -- both used in Sanskrit and the Yogic tradition, as well as Tibetan tradition: the sound of "ah,the sound of "om,and the sound, in this case, of "hung. And in combination with emitting the sounds, you have a particular color, a particular spot in the body, and a particular cognitive task that you're doing. So it's relatively complex, which is theoretically good, to kind of engage this complex network in the brain, versus this kind of just seated meditation of, you know, empty your mind, or transcendental meditation, which is a focused meditation, focusing to say this mantra over and over and over and over. So anyway, we tried to continue the work, struggled to get it funded by the NIH, but hopefully this follow-up study will be compelling.

T. A. Rosolowski, PhD:

Has there -- are there studies underway to examine why this works? You know, like, what's the explanation for...?

Lorenzo Cohen, PhD:

Yeah. So not... Well...

T. A. Rosolowski, PhD:

I mean, I realize so much of this falls outside the domain --

Lorenzo Cohen, PhD:

It's pretty hard. I mean, why... You could ask why from a physical perspective. So is -- my mood is improving because my amygdala is shrinking, and my prefrontal cortex and my hippocampus are growing. There's decreased reactivity, let's say, between the amygdala and the prefrontal cortex. That's not explaining why. That's explaining -- that's sort of the physiological mediator of why somebody who does meditation is less reactive, quote-unquote happier, but it doesn't explain how meditation makes you happier.

T. A. Rosolowski, PhD:

Right, the difference between brain and mind, or brain and consciousness, or brain and spirit. Yeah.

Lorenzo Cohen, PhD:

Yeah. So, I mean, we've measured those kinds of things, and haven't delved deeply into it yet, and will now, so things like social support, social connection, measures of mindfulness. I'm just more mindful of my environment, just to -- you know, 30 questions that tap into how mindful are you. Are you mindful about yourself? About others? About your environment? So, you know, it's probably something along those lines in terms of the first person subjective narrative of what's changing in that human being. Again, how that happens, it's -- you know, the neuroscientists could do the brain scans and say, "Oh, well, because, you know, this is less active, and that is more active, that explains, you know, biologically why...

T. A. Rosolowski, PhD:

I guess the -- part of the reason I ask is -- you know, one part is curiosity, but I guess the other part is if there's still a need to convince people who are more firmly rooted in the, you know, "I want biological evidence,they might be open to information of that sort as a convincer.

Lorenzo Cohen, PhD:

Oh yeah, so that... Yeah, that data's there now, and it's pretty overwhelming, you know, what's changing in the brain, and Anil Sood's research, and our research, showing that, you know, chronic stress causes progression of disease, and Anil Sood, who's a gynecological medical oncologist here, and head of the ovarian and breast cancer Moon Shot, co-head, has definitely documented the mechanisms whereby stress leads to the progression of disease, and we've shown in a large kidney cancer population all the stage fours, so very heterogeneous, as well as more homogeneous bladder population, that depression at the time of diagnosis is a predictor of survival. And we looked at some of the mechanisms, the biological mechanisms, both telomeres as well as gene expression profiles that explained why the depressed die sooner. So there's no question from the meditation perspective also that meditation changes our brain, both its function as well as literally neuroanatomy. So you go to the gym, and you do bench presses, and the pectoral muscles get larger. You do cardiovascular, you do aerobic exercise, your heart gets stronger, healthier. Exact same, you know, analogy fits for meditation: your brain gets healthier, in the colloquial term, and we know the exact parts of the brain that are being enervated. Different kind of meditations will enervate different brain areas, but in general we're seeing -- if you're looking at, from the EEG perspective, decrease in beta activity, which is sort of that high alert associated with anxiety, and more alpha activity, which, you know, we associate more with relaxation and calm and bliss, and then in high states of meditation you get into gamma and theta and things like that. So, you know, we've continued that line of research, you know, looking at I guess you could call them these mind/body practices, and currently... We actually have a study -- I don't know where it is now, but I think it was resubmitted -- that a graduate student of mine did where we incorporated brief meditation into stereotactic breast biopsies, so during the biopsy the women were engaging in a brief meditation, and we measured EEG and, you know, all that kind of stuff. And actually expanding that now to do some work with hypnosis during invasive medical procedures, so we've been doing it clinically for PICC and PORT placement and removal, where patients will have a local, and then we'll put them in a deep, hypnotic state to help them relax during the procedure, and it's been quite profound. [] But the most exciting avenue in this area, before shifting to a different area, has been collaboration with breast surgeons, who have allowed us into the surgical suite, to offer to the patients the opportunity to not have to have general anesthesia for major breast surgery, and instead we give them local and hypnosis. And we've now run almost a dozen patients through this program, and it's just been incredible. Not only did the patients go through the procedures smoother, we're able to avoid giving general anesthesia, which, unbeknownst to many people, except the anesthesiologist, is really bad for you. And, in fact, there's data showing that women who have their breast surgery with general anesthesia, compared to ones who use an alternate procedure, such as the paravertebral block, they actually have better clinical outcomes, lower probability of recurrence of disease. So general anesthesia we've known for decades, if not half a century, is immunosuppressive, and it results in cognitive dysfunctioning that is even there six months later, and there's FMRI data showing these cognitive dysfunctions. And the list of, you know, side effects goes on and on from general anesthesia. I sat with the division head of Anesthesia here, as well as the chair of the Department of Anesthesia, and they say "˜if there is anything that allows us to not have to give anesthesia, we are on board.' I mean, they do not want to give anesthesia, because they know how harmful it is to the body. And, in fact, the mantra that they also say, which is always shocking to me, is, "And we don't even know why it works. It's like, oh. And you call that evidence-based medicine? (laughter) You know, they just don't understand these concepts of consciousness and unconsciousness and, you know, why does this drug make this person go into this state. And they continue to do it because there's really no alternatives. Now, some alternatives have been developed, like Propofol, but Propofol is not strong enough and deep enough to be able to do some of the surgeries around here. So that's been -- that's just been phenomenal. And we've done that small study in now our... (phone buzzing)

T. A. Rosolowski, PhD:

You need to take that?

Lorenzo Cohen, PhD:

No. Doing a... I just submitted, and hopefully we'll have approved soon, to the IRB here to do a randomized trial of this, and have a grant under review at the NIH to try and get some big funding to have it done.

T. A. Rosolowski, PhD:

That's amazing.

Lorenzo Cohen, PhD:

So that's been very exciting, very rewarding, because it's really been pushed by the anesthesiologists and the surgeons to do this, because, again, you know, if they can avoid it... They've documented -- the anesthesiologists have documented the immunosuppressive effects of anesthesia in breast cancer cohort, so, you know, if they can avoid having to give general anesthesia...

T. A. Rosolowski, PhD:

What's the reaction of the patients to being able to do that? I mean, that to --

Lorenzo Cohen, PhD:

Well, some are, like, so on board. They love it, you know. And one patient actually had to have a re-excision, and they said, "Well, I want to do it with hypnosis,same...

T. A. Rosolowski, PhD:

Well, I mean, not only is it amazing because you avoid all these risks and side effects, but also, I mean, to allow a patient to have an element of control of that type during a procedure, I mean, how empowering is that?

Lorenzo Cohen, PhD:

And they're part of the process. You know, they're awake during the whole procedure. They're conscious. They hear. You know, so it's not for all surgeons. You know, there's the stereotypical surgeon who, you know, is having conversations, you know, during surgery, and jamming on the heavy metal music, and, you know, those days, I think, are, you know, past to some degree. But, you know, there's still those surgeons who don't want the patient awake, for multiple reasons. The surgery, I don't believe -- we don't really have a great comparison, but it certainly doesn't take longer, but everyone has to be quiet. Everyone has to speak in hushed tones, and they have to be polite to each other, and they -- the patient's awake. (laughter) You know, they're right there, talking, as appropriately, with the hypnotherapist. So...

T. A. Rosolowski, PhD:

Yeah, changing the culture of the surgical suite. (laughter)

Lorenzo Cohen, PhD:

Totally changing the culture. And it's a great change. And, not surprisingly, the -- actually, the primary surgeon and anesthesiologist are women who are pushing this.

T. A. Rosolowski, PhD:

Oh, interesting, yeah. Huh.

Lorenzo Cohen, PhD:

I'm guessing not a coincidence. There are some women surgeons who are not excited to be involved, either, so it's not a purely gender thing. And the two anesthesiologists who are not part of the breast group who have really started this whole area from the anesthesias end are men: Ian Lipski, who's a brain surgery anesthesiologist; and Kenneth Safire. And Ian's actually been doing this with the open craniotomy patients for years and years, just kind of -- it's his standard of care, because those patients, you know, get knocked out to cut the skull open, and then they have to wake them up, and they're awake during the whole surgery. They're on, you know, all kinds of things, but they have to be conscious, they have to be able to speak, and so Ian keeps them relaxed with this form of --

T. A. Rosolowski, PhD:

Interesting, yeah. Well, so it makes sense that he would be on board. I mean, he's already seen that it's possible, and --

Lorenzo Cohen, PhD:

That's right.

T. A. Rosolowski, PhD:

-- you know, the culture of the surgical suite doesn't -- isn't destroyed. (laughter) You can actually function.

Lorenzo Cohen, PhD:

And that he kind of needs it. And they're different patients -- again, because, you know, they're awake, and the surgeon needs them awake to be able to know that they're not damaging things.

T. A. Rosolowski, PhD:

Right, right, interesting. Wow, that is incredibly exciting.

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Chapter 12: Consolidating the Focus on Mind/Body Research

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