Harold Burstein, MD, PhD; Jeffrey A. Meyerhardt, MD, MPH


June 15, 2015

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Harold Burstein, MD, PhD: Hello. I'm Dr Harold Burstein, associate professor of medicine at Harvard Medical School and a medical oncologist at the Breast Cancer Treatment Center at Dana-Farber Cancer Institute in Boston. Welcome to this edition of Medscape Oncology Insights. We're coming to you from the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

Mounting evidence suggests that lifestyle modifications can improve survival for cancer patients and be a very important part of their ongoing care. I wanted to talk today about what those lifestyle modifications are and, in particular, the role of the oncologist in helping patients make those changes.

I'm delighted to welcome my Dana-Farber friend and colleague, Dr Jeffrey Meyerhardt. Jeff is associate professor of medicine at Harvard Medical School and the clinical director of the Center for Gastrointestinal Cancer at the Dana-Farber Cancer Institute in Boston. Thanks, Jeff, for joining us.

Jeffrey A. Meyerhardt, MD, MPH: Thanks, Hal, for having me.

Dr Burstein: You've done a lot of epidemiologic research, you've looked at lifestyle modifications in cooperative group trials, and you have some prospective studies going on. What do we know concretely that patients should absolutely be doing in certain disease contexts, such as colon cancer or breast cancer, to make an impact on outcome?

Dr Meyerhardt: Right now, if we use the word "definitive," there are no randomized trials yet, particularly for exercise. There are ongoing ones. But we have consistent evidence that people who are physically active after being diagnosed with colorectal,[1,2] breast,[3,4] or some other cancer types (prostate cancer[5] and a few others) have a lower risk for recurrence as well as improved survival.

These data have led to various trials. There's a trial in colorectal cancer survivors, for patients with stage 2 and stage 3 colon cancer, where patients are randomly assigned to a supervised physical activity program or a control group; the study is looking specifically at tumor recurrences and survival.[6] That's an ongoing study.

There's a study that's been approved through the National Cancer Institute for breast cancer survivors.[7] It combines exercise and a weight management program to look at how those factors affect women's outcomes after the diagnosis of early-stage breast cancer.

Exercise: Advise Patients to Start Slowly

Dr Burstein: When you talk to patients, what do you actually tell them? What does it mean to engage in a vigorous exercise program? What are we talking about and what kind of guidance do you give them?

Dr Meyerhardt: There's no definitive evidence yet, but there is increasing evidence [that exercise] specifically affects their cancer occurrence. But these patients also have risk for other diseases, so that's why I talk to them about considering increasing their level of physical activity if they're not active now.

Some patients remain active during their treatment. Some were active prior to treatment, and to maintain that is important. For those who were not active, the first advice I give them is, they need to start slowly because you can't suddenly go from not being active to exercising 5 days a week.

Dr Burstein: This is not 0 to 60 in a Porsche.

Dr Meyerhardt: And we don't know the exact level of exercise to recommend. Some studies have shown that maybe there are different levels depending on your cancer type.[8] Probably for all cancer types, the recommendation from various societies of 150 minutes of moderate to rigorous activity weekly is a good guide point.[9] It may take you months to get up to even 100 minutes if you're physically inactive now, but the goal is to get to that level.

Dr Burstein: We're talking about only 20-30 minutes a day.

Dr Meyerhardt: Exactly, and 5 days a week.

Dr Burstein: Five days a week and that's walking, running—that kind of workout.

Dr Meyerhardt: Various activities. "Moderate to rigorous" means walking at least at a fast pace, generally, to where you're a little short of breath. You want to get your heart rate up a little. Stroll-paced walking is fine, but that's probably not a level that will lead to the energy expenditure that might cause some biological changes that help your cancer.

Dr Burstein: It's important, but it's not like you have to join a gym, pump iron, and do the elliptical for an hour a day.

Dr Meyerhardt: Right. I think people can get there different ways. The vast majority of people from these studies are walking as their primary mode of activity. People do racquet sports, people run, people do elliptical training. Other, lower-intensity aerobic activities include yoga and various stretching exercises that can cause some level of shortness of breath.

Dr Burstein: In my clinic, there are two groups of patients. One group is patients who don't exercise a lot. They are having a health awareness moment because they've got a cancer diagnosis. They want to know what they can change to make them feel better and do better.

Then there are the people who come in wearing their workout clothes, and they're already crunching abs 400 times a day. Do the same rules apply to each of those groups? Which one is more likely to actually get benefit from some of these exercises?

Dr Meyerhardt: We don't know what the exact level of exercise should be, so as a guide, 150 minutes [per week] is reasonable. The patient population you talk about that's already in their workout suit is probably doing that.

We also don't know whether increasing that level is even going to further increase their benefits—there's probably some leveling effect—or how that level of activity affects other diseases, such as cardiovascular disease and diabetes. There's probably some threshold.

But the vast majority of our patients are limited in their level of activity. They may have been more active prior to their diagnosis, but because of surgery or the treatments they're having after surgery—whether chemotherapy or radiation—their level of activity has gone down. They may have some side effects from their therapy—in particular, neuropathy—that may affect their ability to do certain exercises. That's why rebuilding at a slow but steady level is going to be important to discuss with patients.

Dr Burstein: That makes a lot of sense. Certainly after abdominal surgery or radiotherapy to the chest, you're not feeling as good as you were beforehand.

Diet Advice: Lower the Intake of Red Meat, Refined Grains, Sugar

Dr Burstein: What in the way of dietary interventions is also important? Do you give specific diets—such as, patients should be on an Atkins diet, a low-carb diet, or the Paleo diet—or is it more general health awareness?

Dr Meyerhardt: That probably depends on the cancer type. As you know, there were two large randomized studies in breast cancer that both had, as part of the intervention, to lower intake of total fats. One of them also included increasing the intake of fruits and vegetables. The one with fruits and vegetables and the goal of lowering fat didn't show a difference [in breast cancer events or mortality] compared with the control group.[10]

The one that wanted patients to decrease their total fat intake did seem to show a difference, but [the intervention group] also had some weight loss associated.[11] For breast cancer, I'm not sure we know exactly what the right intervention is, whether it's the diet alone or a diet combined with some level of physical activity that leads to weight control or loss.

For colorectal cancer, there hasn't been a randomized study yet. We've done some studies where we've looked at what people eat and then we've followed them over time to look at recurrences and survival.[12,13] The factors that seem to have had associations have been a Western-pattern diet (in other words, high levels of red meat, sugary desserts, refined grains) as well as a high glycemic load, which is an indicator of the body's insulin response. What the exact right diet is, I don't think we know yet. Going back to the Western-pattern diet, the people who did best were the people who had no more than two servings of red meat per week, a decreased amount of refined grains (substituting with whole grains instead), and no more than two or three sugary desserts per week. That was the group that did best in that study.[14] We need to validate it in other studies.

Nuts are interesting because there have been studies showing that eating more nuts, particularly nuts other than peanuts, is associated with a lower risk of developing diabetes and certain cardiovascular diseases.[15] We are actually looking at how nuts affect colorectal cancer survivors.

Dr Burstein: I think many patients might be generally aware that, yes, probably less red meat, less in the way of refined carbs, more fruits and vegetables. That makes sense. How do you actually get people to do that? A lot of us know what we need to do, but it's hard to actually do it.

Working It Out

Dr Meyerhardt: For both diet and exercise—to get people to change their behavior and, importantly, sustain that level of change—that's a challenge for a lot of patients. The challenge for oncology clinics as well as other providers who care for these patients is having the right resources. A lot of oncology clinics have nutritionists associated with them and some access to nutritional support. I think having their involvement helps.

For physical activity, increasingly, people have access to various ways to help increase their level of physical activity, whether through the partnership between Livestrong and the YMCA[16] or the use of physical therapists. More physical therapists are focusing on cancer patients. Certain centers, particularly large centers, will have specific programs to help patients understand what level of exercise would be helpful and how to get there. It's still a challenge for a lot of patients.

Dr Burstein: When you meet with patients, what concrete things do you do? Do you have a brochure that you give them? Do you refer them to a website? Do you arrange a nutrition consultation? Do you tell them about a good book to read? How do you operationalize those pieces of advice?

Find out what's been a barrier and what they would be willing to do.

Dr Meyerhardt: The first thing you want to do is see what they're doing now. If they haven't been physically active or maybe never were physically active, ask what has been a barrier for them to do that. At Dana-Farber we have programs, both through clinical trials as well as non-trial access, to an exercise physiologist who will do consultations with patients to talk about ways to be able to increase their level of physical activity. We have some group classes. In our area, there are YMCAs that have partnered with oncology programs and support groups to be able to increase the access to patients.

I start there; I find out what's been a barrier and what they would be willing to do. Not everyone wants to walk. Not everyone wants to join a gym. I discuss it frequently. I don't think it's a single-visit discussion.

Aspirin: May Lower Cancer Risk but Adds Risk of Its Own

Dr Burstein: Reinforcement is important, isn't it? Let's shift gears and talk about some supplements, like vitamin D and aspirin[17,18] —an emerging literature on several products that may be important. I think we're finally going to have a trial in breast cancer looking prospectively at the role of aspirin. There have been a lot of indirect data about nonsteroidal anti-inflammatory drugs (NSAIDs) and colon cancer and polyp formation. What do you tell patients they should be doing?

Dr Meyerhardt: I agree that there are a lot of data already, and there's a mix of data on efficacy and issues of safety. In colorectal cancer there are large randomized trials [suggesting] that patients who take aspirin or a type of NSAID called COX-2 inhibitors can lower their risk of developing further polyps.[19,20,21]

We currently have a large adjuvant trial looking at celecoxib specifically in addition to chemotherapy for patients with stage 3 colon cancer.[22] But [use of aspirin and COX-2 inhibitors] has to be weighed against risk because gastrointestinal bleeding can occur in patients. Ulcers can occur. So you have to make sure it's a safe intervention for patients. We don't know exactly what the right dose is.

If you're talking specifically about aspirin, a low dose is 81 mg and a full dose is 325 mg. Some patients will be taking it for cardiovascular disease already. For a lot of patients I will recommend that they consider aspirin use unless they've had a history of gastric ulcers or gastrointestinal bleeding. In patients who have already had one of those risk factors, it's hard to know how much that benefit will outweigh the risk.

Dr Burstein: Let's say you have a 57-year-old man who's got stage 2 colon cancer, so he's not going to be eligible for the adjuvant trial. He says, "I've been reading about this and I'm willing to try it." What do you tell him? Take 325 mg of aspirin a day?

Dr Meyerhardt: I tell him to take an enteric-coated aspirin because it's relatively gastroprotective, and always take it with some food. Take it on a daily basis, but watch for bleeding. If the patient is having increased bruising or bleeding, then he needs to notify me.

Alcohol: How Prescriptive Should Doctors Be?

Dr Burstein: What about alcohol? Large epidemiologic studies certainly say that excessive alcohol consumption has its own issues,[23] but how prescriptive are you in terms of telling patients how much to drink?

Dr Meyerhardt: I think there are two times to have that discussion: while they're getting treatment and after they complete treatment. During treatment, a lot of the drugs we use in oncology have some level of metabolism through the liver. I discourage patients from drinking at all a day before treatment, during treatment, and a few days after treatment. Outside of that, an occasional drink, not anywhere to excess, is probably okay, although we don't know that for sure.

We don't know definitively how alcohol affects survivors long-term.

In terms of survivors—particularly in terms of colorectal cancer, which is what I know best—there really aren't data either way. Does it affect efficacy? Does it help patients? There are also some data in women with breast cancer [suggesting] that it may be beneficial, at least in terms of the risk for cardiovascular disease.[24]

We don't know definitively how alcohol affects survivors long-term, but while they're on chemotherapy in particular, they should discuss alcohol consumption with their physician. Different oncologists believe different things about what level of drinking is appropriate during treatment. That's an important discussion.

Dr Burstein: I tell my patients a very important rule: No cheap wine. It's got to be good stuff. That controls absolute level of consumption, too.

Oncologists, PCPs: Tag-Team in a Teachable Moment

Dr Burstein: These lifestyle factors are important and of interest to patients. They're questions that oncologists historically have not devoted a lot of time and effort to answering. How much do you expect that this is part of an oncologist's job to manage on a day-to-day basis, versus either someone within the cancer center (the nutritionist or the nurse) or the primary care team?

Do you say, "Look, we know that diet and exercise are really important and that cancer is a piece of that. Go talk to your primary care team." Or do you really feel that this is something you need to own as part of the care of the patient?

Dr Meyerhardt: Most survivors we follow for several years at least after their diagnosis, and we think these factors may affect their risk for recurrence, which for most cancers is highest in the first several years. For breast cancer, survival can be 15-20 years, but the highest risk is in the first several years. Certainly for colorectal cancer, most of the risk is in the first 5 years. We're the ones primarily following them related to their cancer. It has to be part of the discussion, because if you think that these factors may affect the micrometastases that cause a recurrence, you need to intervene while that's the worry.

I think the primary care doctors should be involved as well. I encourage my patients, after they've completed therapy, to have a joint relationship with me and primary care. The primary care doctor is involved in their other care, whether it be their cardiovascular disease or checking their blood pressure or checking for diabetes. So they need to be involved as well, and if both groups are delivering the message, then that's also very helpful.

Dr Burstein: I think that's a good point, because a lot of people know that this is part of the dialogue for general health maintenance. But somehow, knowing that this might be critical for their cancer outcomes provides that extra layer of motivation that often kicks it up a notch in terms of their interest and commitment to the activity.

Dr Meyerhardt: Having a diagnosis of cancer is a teachable moment. This is an opportunity to be able to look at some factors and be able to potentially affect their cancer outcomes. These are risk factors for cardiovascular disease and diabetes. For certain cancers, some risk factors for cardiovascular disease and diabetes are the same, and so affecting those hopefully will affect those comorbidities later in life.

Dr Burstein: One trick I've tried is to engage the family. They're sitting there saying, "What can I do to help my mom who had breast cancer?" I say, "Here's something you can do: You can help the whole family think about nutrition, levels of activity, alcohol consumption" if that's an issue within the family.

I think it's a nice way of broadening the base of interest and making it more successful, but I don't have proof of that.

Dr Meyerhardt: Absolutely. I agree. It will probably help the family members too if they do it together. Sometimes you look at the room and you realize that none of the people in the room are exercising. You want to try to have an impact on the family members' health as well as the patient's.

Dr Burstein: Fantastic. We are here at the ASCO meeting in 2015 in Chicago. I'm Harold Burstein from Dana-Farber. I've been talking to my colleague at Dana-Farber, Jeff Meyerhardt, about a variety of lifestyle and health modifications that are important for cancer survivors, and also thinking through who is responsible for these aspects of care. Thank you very much for joining us today.


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