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 a way to avoid surgery for some patients with cancer, a new treatment for a form of lung cancer, likely outcomes with cessation of the President’s Emergency Plan for AIDS Relief (PEPFAR), and gun injuries and deer season.
Program notes:
0:47 Gun injuries and deer hunting season
1:47 Other associated injuries
2:47 Coincidence of hunting?
3:48 Restrict hunting guns to that use
4:10 Can we avoid surgery in some with cancer?
5:10 Dostarlimab (Jemperli) treatment
6:10 Can help avoid surgery in few who have this mutation
7:10 Look at specific pathways
8:32 71% responded
9:12 Impact of PEPFAR funding freeze
10:12 Looked at waiver scenarios
11:12 Decreased deaths and infection
12:13 Takes time to resume
13:06 End
Transcript:
Elizabeth: A strategy for avoiding operations in some people with cancer.
Rick: A new therapy for people with lung cancer.
Elizabeth: What’s likely to happen with HIV death and infection with cessation of PEPFAR.
Rick: And firearm incidents and, oh, deer.
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: And Prince of the Pun, so therefore let us turn directly to the British Medical Journal, a look at gun injuries and deer season.
Rick: A number of studies have shown that when firearms and ammunition are more available, the incidents of firearm mishaps increase. By the way, if you restrict guns and ammunition, they seem to go down.
But this is an interesting study as it uses what they call a quasi-randomized trial. Deer season, which normally occurs in the United States from late fall to early winter, is a time where both there’s an increased purchase of firearms, increased use of firearms, and an increased use and advertisement for ammunition as well. So you might suspect that in that situation, that the incidents of firearm-related injuries increases as a result of hunting. Well, what about non-hunting incidents?
So this natural history study allowed these investigators to look at this in 10 different states. They looked at all the firearm incidents during that time and compared it to both before and after, not just hunting incidents, but things like suicide and alcohol, or other substance abuse, domestic violence, home invasions.
At the start of the hunting season, it was associated with a 12.3% relative increase in the rate of firearm incidents overall. Those related to hunting incidents, it increased by about 566%. There were also changes in suicide — about 11% increase, 87% increase in firearm incidents related to alcohol or other substances, domestic violence 27%, home invasion or robbery about 30%. There were no differences observed for incidents involving children or police officers.
What the authors attribute this to — this increased rates of both hunting and non-hunting related firearm incidents — is most plausibly explained because of both the increased availability of firearms and ammunition clearly associated with deer hunting season.
Elizabeth: It’s kind of curious, isn’t it, though, Rick? Because people have these guns at other times of the year and they have ammunition at other times of the year. So what is it about the coincidence of hunting and these things that already exist that accounts for the increase?
Rick: Well, that’s a great question and they don’t dive into that detail. They do highlight that there are about 11.5 million hunters and they spend about 135 million days hunting during the year. So these firearms may be locked up during most of the time and they may not be during hunting season.
They didn’t discern whether these were rifles or handguns, and they also didn’t account for the fact that while people are out hunting, they’re also more likely to be involved in group activities that do involve alcohol or other substances, and there are people purchasing firearms that never had them before when hunting season starts.
Elizabeth: And I guess one other question I would ask is, are these other gun-related incidents relative to the person who owns the gun – the hunter — or other people who are also bystanders?
Rick: Yep, and because they used a database they didn’t have all the details. You’re right. These are details that are missing that would actually inform us a lot about this study.
Elizabeth: And in the short term, if you were going to create a solution for this apparent problem, what would you do?
Rick: One wants to restrict guns, especially hunting guns, to their use and to make sure that they are locked up at all times that they are not being used. Make sure ammunition is [locked] up as well. If we can reduce availability of guns outside of their normal use or hunting use, we can likely decrease the incidence of their use in non-hunting situations.
Elizabeth: Let’s turn to the New England Journal of Medicine. Are there people who have cancer in whom we can avoid surgery?
They were taking a look at patients who have what are called mismatch repair-deficient tumors. That is something that’s discerned by a genetic analysis of cancers to see whether this one particular pathway is deficient or not. And what has been previously shown is that in folks with locally advanced rectal cancer, there’s what’s called a neoadjuvant checkpoint blockade that, in people who have this particular genetic defect, can obviate the need for surgery. What they wanted to see in this study is whether the same approach could be extended to all early-stage mismatch repair-deficient tumors, regardless of the tumor site.
So it’s a phase II trial. They had patients with stage I, II, or III mismatch repair-deficient solid tumors. They would have been amenable to curative-intent surgery and instead they were treated with an agent that’s called dostarlimab, which is a programmed cell death PD-1 blocking agent in a neoadjuvant strategy, for 6 months.
They had two cohorts. The first cohort was patients who had locally advanced rectal cancer and in the second one they had non-rectal solid tumors. In their first cohort, they had 49 patients who completed treatment and had a complete clinical response and had non-operative management. Of those people, 37 patients had a sustained clinical complete response at 12 months. In the second cohort, 35 of 54 patients who completed treatment had a complete clinical response and 33 elected to proceed with this nonoperative management. With both cohorts, 84 had a complete clinical response and 82 did not undergo surgery. Recurrence-free survival at 2 years was 92%.
This is pretty impressive, helping people to avoid surgery, especially what can be quite disfiguring and life-changing. Having said that, I would say that the bad news is that the number of tumors out there that are this type of mismatch repair-deficient tumors is really pretty low.
Rick: Okay. So, Elizabeth, this is a little bit of a paradigm shift for 2 reasons. One is, we used to attribute cancers to where they were located. So you would treat colorectal cancer different than you would treat liver cancer or gynecologic cancer or GU cancer. In these particular patient populations, they did a genetic analysis of the cancer regardless of where it was. So in the 2% or 3% of cancers, no matter where they occur in the body that have this, you could apply this particular therapy. The other paradigm shift, as you said, is that we usually try to remove those cancers. But now they can respond to this particular agent, which is incredibly effective.
Elizabeth: And it will be great to discern other types of genetic defects that would be amenable to some strategy like this.
Rick: Yep. So what’s the genetic abnormality that caused that particular cancer and how can we affect those specific pathways to cure it?
Elizabeth: They did drill down a little bit and they were able to discern that the majority of patients in whom it didn’t really work out also had a high degree of what’s called microsatellite instability at baseline. So yet another assessment that might predict that it would be better to go ahead and have surgery versus elect a strategy like this.
Rick: Since we’re talking about cancer, let’s move on to the New England Journal of Medicine. We’re going to talk about another cancer, lung cancer with specific genetic abnormalities.
Lung cancers are generally divided into two large categories, either small cell or non-small cell cancers in the lung, and like your previous report, about 2% to 4% of these have a particular mutation called a HER2 mutation.
HER2, it’s a receptor responsible for regulating cell growth. And if it’s abnormal or there’s too many, there’s a mutation that can actually result in cancerous growths. We now have a way of giving particular antibodies that are directed towards that receptor to treat these individuals.
What these investigators did was they found a new agent, this is called zongertinib. It’s an oral therapy that can be given once a day and it targets specifically only that HER2 receptor. They tested it in 75 patients that had already been previously treated. They evaluated whether this particular drug could be affected, because they all had recurrence of cancer, and what they discovered was that about 71% of these individuals had a response to this agent after the other agents have already failed, and that duration of response was about 14 months. Serious side effects occurred infrequently.
Elizabeth: Good news, of course, for this subset of people who have this particular subset of non-small cell lung cancer.
Rick: Right. And, again, this goes to the point of we’re drilling down into the specific mutations that caused it and targeting specific pathways.
Elizabeth: And as we’ve talked about before, I think this points clearly, both this study and the other study, to the notion that one needs to have one’s cancer genotyped pretty carefully in order to determine what’s the best strategy for treatment.
Finally, let’s turn to The Lancet. This is a look at the impact of PEPFAR funding freeze on HIV deaths and infections in a study of seven countries in sub-Saharan Africa.
So we know that the current administration imposed this 90-day funding freeze on PEPFAR, and PEPFAR has been an initiative that has resulted in lots and lots of folks, especially in sub-Saharan Africa, receiving treatment for HIV and also preventive strategies for HIV for many years.
And so this study took a look at what will happen with this funding freeze in terms of both HIV death and infection. They created 4 different models where they had a hypothesis driven — what will happen with this executive order, another executive order-realistic model, and then assuming near total system collapse due to program dependencies. They did also look at waiver scenarios where treatment was resumed after 4 or 8 weeks.
What they’ve concluded is that a 90-day funding freeze would result in 60,000 excess HIV deaths for this executive order-proportional scenario, 74,000 if there’s a realistic scenario, and then additional deaths for these other complete cessations and collapses of the programs, noting that this only represents about half of all the folks on the continent who are likely to be infected.
Rick: PEPFAR stands for the President’s Emergency Plan For AIDS Relief. It’s been going on for about 20 years now and there are about 21 million people that are receiving HIV treatment as a result. And so what’s happened is before it started in sub-Saharan Africa, there were about 2.2 million deaths. That’s decreased to about 390,000 recently. And new HIV infections decreased from 3.2 million in 2003 to about 640,000 in 2023 and [it] directly supports 342,000 health workers.
To me, this is disturbing. Stopping just for 90 days increases excess HIV deaths to 74,000 and the people that are most likely to die are those that were recently started on [treatment] or people that have very low CD4 counts.
Elizabeth: They also note that there are other services that were provided under PEPFAR and those include HIV pre-exposure prophylaxis [PrEP], which we know is incredibly effective in preventing transmission, voluntary medical male circumcision, condom distribution, targeted combination prevention programs for key populations, and programs for preventing mother-to-child transmission of HIV.
Rick: And, Elizabeth, it isn’t like turning the water spigot off and on, where you can turn it off and immediately turn it on and things are back to normal. Because over those 90 days, a lot of the processes we have, a lot of the people we have that are distributing this medication will be gone or severely reduced. It’s going to take a while to get those back up, so the excess deaths that you mentioned only account for those in the first 90 days. It doesn’t occur with what’s going to happen until we get these processes and people to return to normal.
Elizabeth: I guess I would finally note that we can’t pretend that we’re in isolation. If we learned anything from COVID, it’s that viruses know no boundaries and that allowing HIV to once again become a good deal more prominent in Africa is going to spill over into other parts of the world, including domestically.
Rick: Globally, what this means is we shouldn’t come to rely on one particular country for providing this. I mean, there needs to be a global strategy.
Elizabeth: 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.
Please enable JavaScript to view the