TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week's topics include the impact of genetics on healthy life years, multivitamins and Alzheimer's disease, predicting who will respond to CAR T-cell therapy, and active surveillance for prostate cancer and outcomes.
Program notes:
0:38 Alzheimer's and multivitamins
1:36 Multivitamins slowed rate of progression
2:36 Slight benefit
3:36 Uniform benefit
3:40 CAR-T therapy and relapse
4:40 Blood factors to predict
5:26 Genetic risk factors and healthy years
6:26 Maybe see genes and disease in the future
7:26 Is it genes or environment?
8:03 Active surveillance for prostate cancer and outcomes
9:02 Most with prostate cancer in active surveillance
10:02 The younger you are with cancer
11:01 Does it apply to Black men?
12:00 End
Transcript:
Elizabeth: Is there a benefit to taking a multivitamin to stave off Alzheimer's disease?
Rick: Predicting who will respond to immunotherapy for cancer.
Elizabeth: What is the impact of genetic risk factors on healthy life years?
Rick: And what is the long-term outcome for men who undergo active surveillance for prostate cancer?
Elizabeth: That's what we're talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso where I'm also dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, if it's okay with you, we'll start with Alzheimer's & Dementia. This is the journal of the Alzheimer's Association. This has been getting just an enormous amount of press.
This was a study -- a large randomized 2 × 2 factorial 3-year trial -- that was taking a look ostensibly at the beginning of cocoa extract and whether or not it could have any impact on someone's subsequent development of dementia and Alzheimer's disease.
They have this cocoa extract and then since it's this 2 × 2 factorial design they also use the multivitamin supplement. They looked at a number of assessments of somebody's cognition -- including executive function and memory composite scores -- and they also subdivided this into different subgroups who are at higher risk for cognitive decline.
What they discerned in this study was that while the cocoa extract had no benefit whatsoever, the multivitamin group did seem to slow the rate of progression. That's kind of an interesting finding. In light of the many, many times we have talked about supplementation, once again this throws some muddiness into the waters.
Rick: This is a relatively short-term study. As you mentioned, they gave people either a multivitamin or cocoa, or neither, or both, for a period of about 2½ years, and every year tested cognitive function. However, we have a prior large study. It was a physician health study and they had a 6,000-person sub-study in there in which they used multivitamins as well and looked at cognitive function over a 12-year period. In that study, done in men over the age of 65, a highly educated group, multivitamins did not alter cognitive function compared to placebo. So why do you think that this particular study -- the one you're reporting on -- is at odds with the other one?
Elizabeth: Well, I can't explain that. I think it's just tantalizing this notion that when you compare it that you actually see a slight benefit and it still is admittedly a slight benefit. It delays this onset of dementia just a little bit.
Rick: One possible explanation is maybe it helps in the very early part, the first 2½ years. These patients were a little bit different. The group I mentioned was all men. Your study had both men and women, both in the older age group. The multivitamins could have been a little bit different -- and they were.
I think what it goes to show is this study report doesn't really settle the issue. In fact, they make the comment, "Gosh, we need follow-up studies to confirm this." Would you agree?
Elizabeth: I do agree with that. The other thing that they note in here is that, based on the self-report of TIAs, congestive heart failure, CABG, angioplasty, or stent, those folks appeared to have a slightly greater benefit. I guess that's also something that I'd like to see substantiated further.
Rick: You're right. You'd like to see it be available and efficacious or effective in every group or not, which again says we just need confirmation before we take this as gospel truth.
Elizabeth: Yes, indeed.
Rick: So Elizabeth, let's talk about immunotherapy for cancer. Is that okay?
Elizabeth: Sure. That sounds great. That's in Nature Medicine.
Rick: We're going to talk about what's called CAR T-cell therapy. CAR stands for chimeric antigen receptor T-cell therapy. What a mouthful.
Here is what happens for particular types of cancer and particularly what's known as lymphoma. The T-cells can actually kill the tumor. Unfortunately, we just don't have enough of those T-cells around. This CAR-T therapy is if you have cancer I'll take your blood and I'll isolate the T-cells. I'll expose them to the cancer antigen. I'll grow millions of those T-cells over the course of several weeks and then I'll infuse them back into you to treat the cancer.
Despite that, there is a large number of individuals, as many as 60% of individuals, that even after this still have progression of disease. What you would like to know is, "Can we predict who those individuals may or may not be?"
In a relatively small study of 32 patients, they provide a CAR T-cell therapy and they analyzed the blood in those individuals to see if they can identify factors that predicted who didn't respond or else had a toxicity, in this particular case a neurotoxicity.
They could actually identify another group of T-cells, not the ones you infuse, but another group, that if they increased it actually predicted progression and less neurotoxicity. They are what's called regulatory T-cells. These people made T-cells of their own that counteracted the T-cells that were meant to fight the cancer.
Elizabeth: Since it's such an incredibly promising therapy and has been expanded, and increasingly being modified, I think figuring out who is likely to respond and who isn't is really an important issue.
Rick: It is. Now, unfortunately this particular thing that they were measuring is done after the fact. It's after you've given the CAR T-cell therapy. You'd like to know before you gave it.
Elizabeth: Yeah. Staying in Nature Medicine, let's turn to this study taking a look at genetic risk factors and their impact on healthy life years. What's in your genes, what's in the environment and other exposures that you might have, and how does that really impact your ability to live a healthy life. I think there has been a lot of debate about that over the years. Would you agree?
Rick: I totally agree.
Elizabeth: This study takes a look at the effect of genetic risk factors on disability adjusted life years, or DALYs. They got genetic information from over 735,000 people and they looked at 80 diseases. They also looked at polygenic scores for multisite chronic pain and for other things. In fact, in this multisite chronic pain, it really impacted on the DALYs in those folks.
This is a paper that's just full of all kinds of really intense analyses. I think at the end of the day what I came out with was this is great and maybe we're going to be taking a look at peoples' genes and seeing whether or not they have these particular variants that they have associated with different things.
Interestingly, a lot of these variants were associated with cardiovascular disease. Maybe that's going to help us tailor things so that we can help people to avoid the development of them. I do not think it answers anything about the environmental factors and lifestyle factors that people choose, and what that interaction is.
Rick: I think your point is well taken. In fact, for those individuals that aren't familiar with DALYs, these are lost healthy life years. Elizabeth, you're right. You can identify these genetic things, but right now these genetic risk factors are really not yet modifiable in practice.
What it might do is say, "If you've got this genetic predisposition, maybe you ought to have a healthy lifestyle." But you and I would say, "Well, that shouldn't determine it. You ought to have a healthy lifestyle no matter what." These are just what we have identified. There are other things we haven't even identified.
When people debate is it genes or is it environment, the answer is, "Yes, it's both." There are interactions. The genetic component is important, but it doesn't negate the environment and things that we need to do in terms of preventive medicine. But it does show that some of the more common genetic abnormalities we see -- they were spread out across the population and they put people at increased risk -- do substantially impact our healthy life years.
Elizabeth: At some point, I think in the probably not too distant future we're going to be integrating this with personalized medicine and helping people to avoid what they might be at risk to develop.
Rick: These genetic things just put you at risk. It doesn't mean you're going to have a particular condition or disease.
Elizabeth: Finally, let's turn to JAMA Network Open. Let's look at prostate cancer and active surveillance.
Rick: This active surveillance is really the management strategy for men that have low-risk prostate cancer. When you say active surveillance, that means you do regular testing to see if there is progression of the disease. If there is, then you would treat it and you don't treat it initially at the beginning. Because those treatments -- whether it's some type of chemotherapy, radiation therapy, or radical prostatectomy -- they all carry some side effects. Do I treat it now? Or can I just kind of wait and then treat it if I need to?
That's what this study did. They assessed the long-term outcomes of men with prostate cancer, who had low-risk prostate cancer and they were managed with active surveillance. This is a 30-year follow-up.
They got the data from a database in Sweden. These are people that weren't referred to a center. This is 98% of all the men in Sweden. Like if you got prostate cancer, we know about it. These men, most of them that had low-risk cancer, were a part of an active surveillance program. They said, "Okay, how does that work out for them?" Here is what they found out.
If you were a man over the age of 65 and you are enrolled in an active surveillance program, your risk of dying from prostate cancer over that 30 years or until age 85 was usually less than 5%. What was the likelihood that you would need therapy? Somewhere between 30% or 35%. If you're already 65, then active surveillance is a really good treatment strategy. However, if you're younger, if you're under the age of 60, then they actually had a high risk of prostate cancer death and little benefit in terms of time without active treatment by doing active surveillance. Those are the individuals under the age 60 that probably shouldn't be subjected to active surveillance. Conversely, over the age of 65 active surveillance ends up being the preferred management strategy.
Elizabeth: I find this pretty interesting because I think that cancer is a different disease at different points in the lifespan. It's been my observation that the younger you are when you get cancer in general, the more aggressive the disease is. I'm wondering about that relationship with regard to this observation about men younger than 60 who present with prostate cancer.
Rick: That's an interesting thought. However, all of these men, at least by our traditional risk factor algorithms, all had low-risk cancer. So their risk -- based upon the type of cancer and where it was located -- was supposed to be the same.
One of the differences, if you have it at age 50, as opposed to age 75, you got longer years to either die or develop progression. Your other point may be right, is that maybe these cancers, as they are exposed to more testosterone or other things, that they are more likely to progress as well. Your point is well taken, but all men in this particular study had low-risk cancer by typical pathologic definitions.
Elizabeth: I'm also wondering about the implications for groups of other ethnicities. I'm specifically thinking about Black men in whom prostate cancer is more of an issue and does progress more quickly than it does in other ethnicities.
Rick: Yeah. Elizabeth, even though this is the first study to compare these benefits over a long period of time, as you noted this is a very unique group of people. They are Swedish men. You're right. Does this apply to other groups, Black men, Hispanic, Asians? Unfortunately, this study doesn't tell us, but it should spur us to do those studies in those populations.
Now, active surveillance hasn't been around for a long period of time. It was routinely recommended in 2005, so in most populations we have a shorter time period.
Elizabeth: More to come no doubt. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.