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 Health El Paso.

Elizabeth: Rick, I think I’d like to start with The BMJ and hopefully one of the last words on the benefits of exercise for people with cancer. I feel that we’ve talked about this quite a few times in the past, and this is a meta-analysis. They included 21 randomized controlled trials in this analysis, looking at, OK, what happens when you exercise if you’re a person who has been treated for cancer?

And what they showed was that, sure enough, there was an improvement in overall survival, a 23% benefit, in the disease-free survival, slightly less, and in all-cause mortality, slightly less benefit. And in reduced cancer-specific mortality, 26% benefit, but not with progression-free survival or pathological complete response. When they took a look at the evidence, they rated it as moderate for overall survival, disease-free survival, and cancer-specific and all-cause mortality. They did see there was a more pronounced benefit among participants who paid more attention to their exercise regimen — so higher adherence — aerobic exercise, and for those with early-stage disease, which is unsurprising.

One of the things about this study that was a little bit of a bias, I think, at least in my mind, was that the majority of the patients in the study were women and had breast cancer. So the question is, what’s going to happen when we extend this to other types of cancers and include a lot more men?

Rick: Yeah. So, Elizabeth, I agree with you. Looking at diverse cancer types and different stages of disease as well, and that will provide additional support. This whole issue, as you said, we’ve been talking about it, but most of the data has come from observational studies. This is a meta-analysis of randomized controlled trials, and the data support the fact that not only does exercise make you feel better, but it also improves your overall survival.

Elizabeth: Yep. They had almost 8,500 participants when they included everybody. There was one piece of data that, I think, it begs the question of whether this ought to be included in all these kinds of trials, and that’s the numeric time since diagnosis. And they said that that was rarely reported across all of these trials, and it seems like that ought to be something that ought to be included.

Rick: Yeah. So additional information could be gleaned. But again, it does appear across the variety of cancers that were examined the results seem pretty consistent. Now, what we need to do is establish what the optimal exercise prescription should be. Individuals that are more adherent to exercise receive the best benefit, so we need to figure out what sort of adherence would we request of the patients.

Elizabeth: And then finally, the authors do speculate on, all right, what might be the mechanisms? And they talked about exercise improving the infiltration of cytotoxic T cells and natural killer cells into the tumor. It improves drug penetration into the tumor via increased circulation, and it also increases glucose uptake and oxidation in skeletal muscles, so it deprives tumors of some of the nutrients they’d like to have.

Rick: And again, no downside.

Elizabeth: On to your first one. Which one are you picking and where is it?

Rick: Elizabeth, since we talked about cancer, let’s talk about colonoscopy interval from when an individual had the initial colonoscopy and a polyp was removed. Those polyps are the precursor to cancer. Now, after removal of polyps at colonoscopy, some patients are considered to be at high risk for new polyps or cancer. Therefore, the current guidelines in the United States recommend frequent colonoscopy surveillance, with the first one conducted at 3 years after polyp removal. That surveillance is now one of the main indications for colonoscopy in many countries and so it consumes a lot of resources.

So these investigators did a study, which was published in the New England Journal of Medicine, that asked a simple question. If we extend that surveillance not to 3 years, but out to 5 years, is there any change in the cumulative incidence of colorectal cancer at 10 years? So this is a study that was conducted in almost 11,000 patients that were randomized to either colonoscopy surveillance at 3 years or 5 years after polyp removal. And the 5-year cumulative incidence of colorectal cancer was 0.8% with less frequent surveillance and 0.8% with more frequent surveillance. This is a non-inferiority study, so it shows that the 5-year surveillance is really non-inferior to the 3-year surveillance.

When they looked at the cancer stage at diagnosis — because you might say, well, the incidence is the same, but if you wait, they’re more likely to be at a later stage at diagnosis — and there was no real difference between the two. This looks like good evidence that you can begin surveillance colonoscopy at 5 years after polyp removal, rather than initiating it at 3 years.

Elizabeth: And this is good news, of course, for patients because that whole preparation for, regardless of whatever method it is that you’re going to be surveyed by, is no fun.

Rick: It is. Here’s the caveat. This is a report of a 10-year study. This is the interim analysis. So at 10 years, we’ll have additional data, but there doesn’t appear to be any difference in 5 years.

Elizabeth: Good news.

Let’s turn to Nature Medicine. This is good news too and, again, a little bit unsurprising, I think, when we take a look at the totality of times we’ve talked about the benefits of vaccination in reducing the risk of all kinds of things, not just the putative infectious disease that we’re trying to prevent.

This is looking at COVID-19 vaccination around immune checkpoint inhibitor start and survival in a national cohort of patients with cancer. And this is in France, where they identified 95,000-plus adults who were initiating immune checkpoint inhibitor therapy over a 3-year period. They assessed mRNA vaccination within 100 days before their immune checkpoint inhibitor initiation and within 100 days after that initiation among previously unvaccinated patients. And their primary outcome was all-cause mortality, and the secondary outcomes were cancer-specific and non-COVID-19 mortality.

What they basically showed was that this pre-ICI — or immune checkpoint inhibitor — vaccination was associated with lower early all-cause mortality. It’s modest, 10% at 1 to 3 months, and then declining until there was no significant association after 12 months. In their post-ICI mRNA vaccination, they showed pretty similar, a 16% benefit at 3 months and then 14% at 6 months. Also, no significant association after 12 months.

Basically, what they conclude is that there’s a modest, transient association that might be due to healthy-recipient-of-the-vaccine effects rather than a specific mRNA COVID-19 vaccine effect. I interpret this, within the context of all of this data we’ve discussed so many times, relative to, as I suggested, the benefits of vaccination — for example, in reducing [myocardial infarctions] in people over the winter — an off-target effect, but still one that turns out to be pretty significant.

Rick: Yeah. If you’re a cancer patient or an oncologist and you’re treating patients with immune checkpoint therapy, and you’ve heard that there are case reports somehow providing that vaccination could interfere with your therapy, or in some cases, concerns that it actually could exacerbate immune-related, life-threatening toxicities, then people are reluctant to give either COVID vaccination or either other vaccination related to flu or [respiratory syncytial virus]. And so what this study establishes is these patients do well. The vaccinations, regardless of whether it’s COVID or non-COVID vaccinations, does not decrease the efficacy of the immune checkpoint therapy, nor does it exacerbate any immune-related complications.

Elizabeth: And I’m also just really interested in potential benefits of other immunizations that might take place around the initiation of ICI therapy because, as I suggested, we have seen, for example, another one, the shingles vaccine and reduction in risk of dementia. So if we’re looking at an anti-inflammatory or even a directional push for the immune system that might result in benefit, maybe other vaccinations would be more beneficial at this time.

Rick: Right. And Elizabeth, this is especially important because, as we discussed last week in our podcast, there’s a lot of misinformation and disinformation regarding the safety and efficacy of vaccines. This particular study really builds upon what we reported last week, that is the importance of vaccines in a number of different diseases, as you mentioned. Everything from preventing infectious disease to influencing dementia and Alzheimer’s, and here, not interfering with cancer therapy.

Elizabeth: And finally, we’re going to turn to…

Rick: Do critically ill adults with metabolic acidosis and shock benefit from sodium bicarbonate? Many of our listeners say, well, why does this matter to me? I’m not actually prescribing it. But many of the physicians that care for individuals in the ICU [intensive care unit] do. What’s apparent is that when individuals develop shock, they develop metabolic acidosis. And if they’re on medicines to try to maintain their blood pressure — vasopressors — in that setting, the vasopressors are less effective.

When I trained, you could definitely see a benefit when someone had metabolic acidosis and you gave them sodium bicarbonate to raise their pH to help resolve this, the vasopressors were more effective. Well, that’s great, but the real question is, does it improve overall outcome? Does it reduce death or the use of renal replacement therapy or reduce the risk of persistent renal dysfunction in individuals with shock and metabolic acidosis?

So this was a very pragmatic study. The results are published in the New England Journal of Medicine, where they took 500 patients in 55 ICUs across seven different countries. These are individuals that had shock, that had a metabolic acidosis, a pH less than 7.3. They were all receiving vasopressors in the intensive care unit, and they were randomized to receive either placebo or sodium bicarbonate infused for up to 5 hours. And then they examined the risk of death, renal replacement therapy, or persistent renal dysfunction at 30 days. And what they discovered was that there was no difference. This primary outcome occurred in 40% of individuals who received sodium bicarb and 39% in the placebo group.

Elizabeth: So yet one more intervention that we can give a miss because it doesn’t really result in any significant benefit. I find this, again, one of those things that when we fit it into the constellation of things we know about people who are critically ill — for example, their glucose levels in their blood and our attempts to bring those down, and the impact on long-term outcomes and survival — once again, we found that that’s largely futile. And it sounds like this administration of sodium bicarb falls into that exact same category.

Rick: It did. Again, in fairness, there have been previous trials and observational studies that suggested that sodium bicarb may not change mortality, but it can prevent long-term kidney injury in survivors. But this study really closes that door. It’s disappointing that the therapy doesn’t benefit patients. On the other hand, it informs us not to administer something that’s not going to be helpful.

Elizabeth: We like those messages too.

And on that note, 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.

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Exercise and Cancer Survival; COVID Vaccine and Immune Checkpoint Inhibitors

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