Endocrine Cancer

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

A healthier lifestyle mitigated the impact of genetic factors on the risk of thyroid cancer, in a study based on data from more than 260,000 individuals.

Thyroid cancer has increased globally in recent years and ranks 9th among 36 cancers worldwide, at a considerable cost to health care systems, wrote Xiuming Feng of Guangxi Medical University, Nanning, Guangxi, China, and colleagues.

SciePro/Science Source

Both genetic and lifestyle factors are related to thyroid cancer; previous research suggests a heritability of about 50%, but data on the impact of modifiable lifestyle factors on thyroid cancer are limited, the researchers said.

In a prospective cohort study published in JAMA Network Open, the researchers used data from the UK Biobank and recruited adults aged 40-69 years during March 2006–October 2010. The final study population included 264,956 individuals of European descent. The median age of the participants was 57 years, and 52% were women.

Data on lifestyle behaviors were collected using interviews and questionnaires. The researchers constructed a total lifestyle score based on five variables: diet, physical activity, weight, smoking, and alcohol consumption. Each variable was assigned a score of 0 or 1, with 1 being favorable lifestyle behavior. Lifestyle was divided into three categories: unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5).

Each individual’s polygenic risk score (PRS) was categorized as low, intermediate, or high based on a meta–genome-wide association study of three cohorts.

The main outcome was the development of thyroid cancer.

The researchers identified 423 incident thyroid cancer cases over a median follow-up of 11.1 years.

Overall, higher PRSs were significantly associated with thyroid cancer (hazard ratio, 2.25; 95% confidence interval [CI], 1.91-2.64; P < .00001) as was an unfavorable lifestyle score (HR, 1.93; 95% CI, 1.50-2.49; P < .001 for trend).

An unfavorable lifestyle was significantly associated with thyroid cancer in the highest PRS group, and individuals with high PRS and unfavorable lifestyle had a nearly fivefold increased risk of thyroid cancer (HR, 4.89; 95% CI, 3.03-7.91; P < .001). By extension, “Adherence to a healthier lifestyle could decrease the incidence of thyroid cancer in individuals with a higher PRS,” the researchers wrote in their discussion.

The findings were limited by several factors, including the availability of only baseline lifestyle data, and lack of data on iodine intake, radiation exposure, experience, and family history, the researchers noted. Other limitations include the potential lack of generalizability to populations other than the individuals of European descent in the current study, they said.

However, the study is the first known to address the association among lifestyle, genetic factors, and risk of thyroid cancer, and was strengthened by the large study population, and the results suggest that lifestyle interventions may help reduce the risk of thyroid cancer in those with a genetic predisposition, they concluded.

Healthy living can make a difference

The incidence of thyroid cancer has increased annually, and exploring the possible risk factors could prevent the occurrence of thyroid cancer, corresponding author Xiaobo Yang, PhD, said in an interview.

Previous studies have reported that thyroid cancer is related to genetics and lifestyle, said Dr. Yang. “However, whether healthy lifestyle was associated with thyroid cancer risk and could attenuate the impact of genetic variants on thyroid cancer remains equivocal; therefore, it is crucial to determine the associations between genetic and lifestyle with thyroid cancer,” he said.

“To our surprise, we found that adherence to healthier lifestyle also could reduce the risk of thyroid cancer in those with high genetic predispositions,” said Dr. Yang. “The findings highlight the potential role of lifestyle interventions on thyroid cancer, especially in those with high genetic risk, because the heritability of thyroid cancer was very high, approximately 50%,” he said. “More attention should be paid to the role of healthier lifestyle in the prevention of cancer,” he added.

“Adherence to a healthier lifestyle could decrease the risk of thyroid cancer, which is the important message for clinicians,” said Dr. Yang. “It is not too soon to comment on implications for clinical practice, because many studies have maintained the consistent comment that healthier lifestyle could prevent the occurrence of cancer,” he said.

The relationship between sex-specific lifestyle factors such as smoking and alcohol use and thyroid cancer remains uncertain, and more research is needed to validate these associations, Dr. Yang said. More research also is needed to confirm the complex mechanism between lifestyle and genetics in thyroid cancer, he added.

The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

A healthier lifestyle mitigated the impact of genetic factors on the risk of thyroid cancer, in a study based on data from more than 260,000 individuals.

Thyroid cancer has increased globally in recent years and ranks 9th among 36 cancers worldwide, at a considerable cost to health care systems, wrote Xiuming Feng of Guangxi Medical University, Nanning, Guangxi, China, and colleagues.

SciePro/Science Source

Both genetic and lifestyle factors are related to thyroid cancer; previous research suggests a heritability of about 50%, but data on the impact of modifiable lifestyle factors on thyroid cancer are limited, the researchers said.

In a prospective cohort study published in JAMA Network Open, the researchers used data from the UK Biobank and recruited adults aged 40-69 years during March 2006–October 2010. The final study population included 264,956 individuals of European descent. The median age of the participants was 57 years, and 52% were women.

Data on lifestyle behaviors were collected using interviews and questionnaires. The researchers constructed a total lifestyle score based on five variables: diet, physical activity, weight, smoking, and alcohol consumption. Each variable was assigned a score of 0 or 1, with 1 being favorable lifestyle behavior. Lifestyle was divided into three categories: unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5).

Each individual’s polygenic risk score (PRS) was categorized as low, intermediate, or high based on a meta–genome-wide association study of three cohorts.

The main outcome was the development of thyroid cancer.

The researchers identified 423 incident thyroid cancer cases over a median follow-up of 11.1 years.

Overall, higher PRSs were significantly associated with thyroid cancer (hazard ratio, 2.25; 95% confidence interval [CI], 1.91-2.64; P < .00001) as was an unfavorable lifestyle score (HR, 1.93; 95% CI, 1.50-2.49; P < .001 for trend).

An unfavorable lifestyle was significantly associated with thyroid cancer in the highest PRS group, and individuals with high PRS and unfavorable lifestyle had a nearly fivefold increased risk of thyroid cancer (HR, 4.89; 95% CI, 3.03-7.91; P < .001). By extension, “Adherence to a healthier lifestyle could decrease the incidence of thyroid cancer in individuals with a higher PRS,” the researchers wrote in their discussion.

The findings were limited by several factors, including the availability of only baseline lifestyle data, and lack of data on iodine intake, radiation exposure, experience, and family history, the researchers noted. Other limitations include the potential lack of generalizability to populations other than the individuals of European descent in the current study, they said.

However, the study is the first known to address the association among lifestyle, genetic factors, and risk of thyroid cancer, and was strengthened by the large study population, and the results suggest that lifestyle interventions may help reduce the risk of thyroid cancer in those with a genetic predisposition, they concluded.

Healthy living can make a difference

The incidence of thyroid cancer has increased annually, and exploring the possible risk factors could prevent the occurrence of thyroid cancer, corresponding author Xiaobo Yang, PhD, said in an interview.

Previous studies have reported that thyroid cancer is related to genetics and lifestyle, said Dr. Yang. “However, whether healthy lifestyle was associated with thyroid cancer risk and could attenuate the impact of genetic variants on thyroid cancer remains equivocal; therefore, it is crucial to determine the associations between genetic and lifestyle with thyroid cancer,” he said.

“To our surprise, we found that adherence to healthier lifestyle also could reduce the risk of thyroid cancer in those with high genetic predispositions,” said Dr. Yang. “The findings highlight the potential role of lifestyle interventions on thyroid cancer, especially in those with high genetic risk, because the heritability of thyroid cancer was very high, approximately 50%,” he said. “More attention should be paid to the role of healthier lifestyle in the prevention of cancer,” he added.

“Adherence to a healthier lifestyle could decrease the risk of thyroid cancer, which is the important message for clinicians,” said Dr. Yang. “It is not too soon to comment on implications for clinical practice, because many studies have maintained the consistent comment that healthier lifestyle could prevent the occurrence of cancer,” he said.

The relationship between sex-specific lifestyle factors such as smoking and alcohol use and thyroid cancer remains uncertain, and more research is needed to validate these associations, Dr. Yang said. More research also is needed to confirm the complex mechanism between lifestyle and genetics in thyroid cancer, he added.

The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

A healthier lifestyle mitigated the impact of genetic factors on the risk of thyroid cancer, in a study based on data from more than 260,000 individuals.

Thyroid cancer has increased globally in recent years and ranks 9th among 36 cancers worldwide, at a considerable cost to health care systems, wrote Xiuming Feng of Guangxi Medical University, Nanning, Guangxi, China, and colleagues.

SciePro/Science Source

Both genetic and lifestyle factors are related to thyroid cancer; previous research suggests a heritability of about 50%, but data on the impact of modifiable lifestyle factors on thyroid cancer are limited, the researchers said.

In a prospective cohort study published in JAMA Network Open, the researchers used data from the UK Biobank and recruited adults aged 40-69 years during March 2006–October 2010. The final study population included 264,956 individuals of European descent. The median age of the participants was 57 years, and 52% were women.

Data on lifestyle behaviors were collected using interviews and questionnaires. The researchers constructed a total lifestyle score based on five variables: diet, physical activity, weight, smoking, and alcohol consumption. Each variable was assigned a score of 0 or 1, with 1 being favorable lifestyle behavior. Lifestyle was divided into three categories: unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5).

Each individual’s polygenic risk score (PRS) was categorized as low, intermediate, or high based on a meta–genome-wide association study of three cohorts.

The main outcome was the development of thyroid cancer.

The researchers identified 423 incident thyroid cancer cases over a median follow-up of 11.1 years.

Overall, higher PRSs were significantly associated with thyroid cancer (hazard ratio, 2.25; 95% confidence interval [CI], 1.91-2.64; P < .00001) as was an unfavorable lifestyle score (HR, 1.93; 95% CI, 1.50-2.49; P < .001 for trend).

An unfavorable lifestyle was significantly associated with thyroid cancer in the highest PRS group, and individuals with high PRS and unfavorable lifestyle had a nearly fivefold increased risk of thyroid cancer (HR, 4.89; 95% CI, 3.03-7.91; P < .001). By extension, “Adherence to a healthier lifestyle could decrease the incidence of thyroid cancer in individuals with a higher PRS,” the researchers wrote in their discussion.

The findings were limited by several factors, including the availability of only baseline lifestyle data, and lack of data on iodine intake, radiation exposure, experience, and family history, the researchers noted. Other limitations include the potential lack of generalizability to populations other than the individuals of European descent in the current study, they said.

However, the study is the first known to address the association among lifestyle, genetic factors, and risk of thyroid cancer, and was strengthened by the large study population, and the results suggest that lifestyle interventions may help reduce the risk of thyroid cancer in those with a genetic predisposition, they concluded.

Healthy living can make a difference

The incidence of thyroid cancer has increased annually, and exploring the possible risk factors could prevent the occurrence of thyroid cancer, corresponding author Xiaobo Yang, PhD, said in an interview.

Previous studies have reported that thyroid cancer is related to genetics and lifestyle, said Dr. Yang. “However, whether healthy lifestyle was associated with thyroid cancer risk and could attenuate the impact of genetic variants on thyroid cancer remains equivocal; therefore, it is crucial to determine the associations between genetic and lifestyle with thyroid cancer,” he said.

“To our surprise, we found that adherence to healthier lifestyle also could reduce the risk of thyroid cancer in those with high genetic predispositions,” said Dr. Yang. “The findings highlight the potential role of lifestyle interventions on thyroid cancer, especially in those with high genetic risk, because the heritability of thyroid cancer was very high, approximately 50%,” he said. “More attention should be paid to the role of healthier lifestyle in the prevention of cancer,” he added.

“Adherence to a healthier lifestyle could decrease the risk of thyroid cancer, which is the important message for clinicians,” said Dr. Yang. “It is not too soon to comment on implications for clinical practice, because many studies have maintained the consistent comment that healthier lifestyle could prevent the occurrence of cancer,” he said.

The relationship between sex-specific lifestyle factors such as smoking and alcohol use and thyroid cancer remains uncertain, and more research is needed to validate these associations, Dr. Yang said. More research also is needed to confirm the complex mechanism between lifestyle and genetics in thyroid cancer, he added.

The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Patients with intermediate-risk papillary thyroid cancer and lymph node metastasis show no significant increase in tumor recurrence when undergoing lobectomy compared with a total thyroidectomy, new research shows.

“Results of this cohort study suggest that patients with ipsilateral clinical lateral neck metastasis (cN1b) papillary thyroid cancer who underwent lobectomy exhibited recurrence-free survival rates similar to those who underwent total thyroidectomy after controlling for major prognostic factors,” the authors conclude in the study published online in JAMA Surgery.

“These findings suggest that cN1b alone should not be an absolute indication for total thyroidectomy,” they note.

The study, involving the largest cohort to date to compare patients with intermediate-risk papillary thyroid cancer treated with lobectomy versus total thyroidectomy, “challenged the current guidelines and pushed the boundary of limited surgical treatment even further,” say Michelle B. Mulder, MD, and Quan-Yang Duh, MD, of the department of surgery, University of California, San Francisco, in an accompanying editorial.

“It can be a game changer if confirmed by future prospective and multicenter studies,” they add.
 

Guidelines still recommend total thyroidectomy with subsequent RAI

While lower-intensity treatment options, with a lower risk of complications, have gained favor in the treatment of low-risk papillary thyroid cancer, guidelines still recommend the consideration of total thyroidectomy and subsequent radioactive iodine ablation (RAI) for intermediate-risk cancers because of the higher chance of recurrence, particularly among those with clinically positive nodes.

However, data on the superiority of a total thyroidectomy, with or without RAI, versus lobectomy is inconsistent, prompting first author Siyuan Xu, MD, of the department of head and neck surgical oncology, National Cancer Center, Beijing, and colleagues to compare the risk of recurrence with the two approaches.

For the study, patients with intermediate-risk papillary thyroid cancer treated at the Chinese Academy of Medical Sciences Cancer Hospital in Beijing between January 2000 and December 2017, who had a lobectomy or total thyroidectomy, were paired 1:1 in a propensity score matching analysis.

Other than treatment type, the 265 pairs of patients were matched based on all other potential prognostic factors, including age, sex, primary tumor size, minor extrathyroidal extension, multifocality, number of lymph node metastases, and lymph node ratio.

Participants were a mean age of 37 years and 66% were female.

With a median follow-up of 60 months in the lobectomy group and 58 months in the total thyroidectomy group, structural recurrences occurred in 7.9% (21) and 6.4% (17) of patients, respectively, which was not significantly different.

The primary endpoint, 5-year rate of recurrence-free survival, was also not significantly different between the lobectomy (92.3%) and total thyroidectomy groups (93.7%) (adjusted hazard ratio, 1.10; P = .77).

In a further stratified analysis of patients treated with total thyroidectomy along with RAI (n = 75), the lack of a significant difference in recurrence-free survival versus lobectomy remained (aHR, 0.59; P = .46).

The results were similar in unadjusted as well as adjusted analyses, and a power analysis indicated that the study had a 90% power to detect a more than 4.9% difference in recurrence-free survival.

“Given the lower complication rate of lobectomy, a maximal 4.9% recurrence-free survival difference is acceptable, which enhances the reliability of the study results,” the authors say.

They conclude that “our findings call into question whether cN1b alone [ipsilateral clinical lateral neck metastasis papillary thyroid cancer] should be an absolute determinant for deciding the optimal extent of thyroid surgery for papillary thyroid cancer.”
 

With total thyroidectomy, RAI can be given

An important argument in favor of total thyroidectomy is that with the complete resection of thyroid tissue, RAI ablation can then be used for postoperative detection of residual or metastatic disease, as well as for treatment, the authors note.

Indeed, a study using the Surveillance, Epidemiology, and End Results (SEER) database showed RAI ablation is associated with a 29% reduction in the risk of death in patients with intermediate-risk papillary thyroid cancer, with a hazard risk of 0.71.

However, conflicting data from Memorial Sloan-Kettering Cancer Center, New York, suggests no significant benefit with total thyroidectomy and RAI ablation.

The current study’s analysis of patients treated with RAI, though limited in size, supports the latter study’s findings, the authors note.

“When we performed further stratified analyses in patients treated with total thyroidectomy plus RAI ablation and their counterparts, no significant difference was found, which conformed with [the] result from the whole cohort.”

“Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection [and] further study is needed on this topic,” they write.
 

Some limitations warrant cautious interpretation

In their editorial, Dr. Mulder and Dr. Duh note that while some previous studies have shown similar outcomes relating to tumor size, thyroid hormone suppression therapy, and multifocality, “few have addressed lateral neck involvement.”

They suggest cautious interpretation, however, due to limitations, acknowledged by the authors, including the single-center nature of the study.

“Appropriate propensity matching may mitigate selection bias but cannot eliminate it entirely and their findings may not be replicated in other institutions by other surgeons,” they note.

Other limitations include that changes in clinical practice and patient selection were likely over the course of the study because of significant changes in American Thyroid Association (ATA) guidelines between 2009 and 2017, and characteristics including molecular genetic testing, which could have influenced final results, were not taken into consideration.

Furthermore, for patients with intermediate-risk cancer, modifications in postoperative follow-up are necessary following lobectomy versus total thyroidectomy; “the role of radioiodine is limited and the levels of thyroglobulin more complicated to interpret,” they note.

The study and editorial authors had no disclosures to report.

A version of this article first appeared on Medscape.com.

Patients with intermediate-risk papillary thyroid cancer and lymph node metastasis show no significant increase in tumor recurrence when undergoing lobectomy compared with a total thyroidectomy, new research shows.

“Results of this cohort study suggest that patients with ipsilateral clinical lateral neck metastasis (cN1b) papillary thyroid cancer who underwent lobectomy exhibited recurrence-free survival rates similar to those who underwent total thyroidectomy after controlling for major prognostic factors,” the authors conclude in the study published online in JAMA Surgery.

“These findings suggest that cN1b alone should not be an absolute indication for total thyroidectomy,” they note.

The study, involving the largest cohort to date to compare patients with intermediate-risk papillary thyroid cancer treated with lobectomy versus total thyroidectomy, “challenged the current guidelines and pushed the boundary of limited surgical treatment even further,” say Michelle B. Mulder, MD, and Quan-Yang Duh, MD, of the department of surgery, University of California, San Francisco, in an accompanying editorial.

“It can be a game changer if confirmed by future prospective and multicenter studies,” they add.
 

Guidelines still recommend total thyroidectomy with subsequent RAI

While lower-intensity treatment options, with a lower risk of complications, have gained favor in the treatment of low-risk papillary thyroid cancer, guidelines still recommend the consideration of total thyroidectomy and subsequent radioactive iodine ablation (RAI) for intermediate-risk cancers because of the higher chance of recurrence, particularly among those with clinically positive nodes.

However, data on the superiority of a total thyroidectomy, with or without RAI, versus lobectomy is inconsistent, prompting first author Siyuan Xu, MD, of the department of head and neck surgical oncology, National Cancer Center, Beijing, and colleagues to compare the risk of recurrence with the two approaches.

For the study, patients with intermediate-risk papillary thyroid cancer treated at the Chinese Academy of Medical Sciences Cancer Hospital in Beijing between January 2000 and December 2017, who had a lobectomy or total thyroidectomy, were paired 1:1 in a propensity score matching analysis.

Other than treatment type, the 265 pairs of patients were matched based on all other potential prognostic factors, including age, sex, primary tumor size, minor extrathyroidal extension, multifocality, number of lymph node metastases, and lymph node ratio.

Participants were a mean age of 37 years and 66% were female.

With a median follow-up of 60 months in the lobectomy group and 58 months in the total thyroidectomy group, structural recurrences occurred in 7.9% (21) and 6.4% (17) of patients, respectively, which was not significantly different.

The primary endpoint, 5-year rate of recurrence-free survival, was also not significantly different between the lobectomy (92.3%) and total thyroidectomy groups (93.7%) (adjusted hazard ratio, 1.10; P = .77).

In a further stratified analysis of patients treated with total thyroidectomy along with RAI (n = 75), the lack of a significant difference in recurrence-free survival versus lobectomy remained (aHR, 0.59; P = .46).

The results were similar in unadjusted as well as adjusted analyses, and a power analysis indicated that the study had a 90% power to detect a more than 4.9% difference in recurrence-free survival.

“Given the lower complication rate of lobectomy, a maximal 4.9% recurrence-free survival difference is acceptable, which enhances the reliability of the study results,” the authors say.

They conclude that “our findings call into question whether cN1b alone [ipsilateral clinical lateral neck metastasis papillary thyroid cancer] should be an absolute determinant for deciding the optimal extent of thyroid surgery for papillary thyroid cancer.”
 

With total thyroidectomy, RAI can be given

An important argument in favor of total thyroidectomy is that with the complete resection of thyroid tissue, RAI ablation can then be used for postoperative detection of residual or metastatic disease, as well as for treatment, the authors note.

Indeed, a study using the Surveillance, Epidemiology, and End Results (SEER) database showed RAI ablation is associated with a 29% reduction in the risk of death in patients with intermediate-risk papillary thyroid cancer, with a hazard risk of 0.71.

However, conflicting data from Memorial Sloan-Kettering Cancer Center, New York, suggests no significant benefit with total thyroidectomy and RAI ablation.

The current study’s analysis of patients treated with RAI, though limited in size, supports the latter study’s findings, the authors note.

“When we performed further stratified analyses in patients treated with total thyroidectomy plus RAI ablation and their counterparts, no significant difference was found, which conformed with [the] result from the whole cohort.”

“Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection [and] further study is needed on this topic,” they write.
 

Some limitations warrant cautious interpretation

In their editorial, Dr. Mulder and Dr. Duh note that while some previous studies have shown similar outcomes relating to tumor size, thyroid hormone suppression therapy, and multifocality, “few have addressed lateral neck involvement.”

They suggest cautious interpretation, however, due to limitations, acknowledged by the authors, including the single-center nature of the study.

“Appropriate propensity matching may mitigate selection bias but cannot eliminate it entirely and their findings may not be replicated in other institutions by other surgeons,” they note.

Other limitations include that changes in clinical practice and patient selection were likely over the course of the study because of significant changes in American Thyroid Association (ATA) guidelines between 2009 and 2017, and characteristics including molecular genetic testing, which could have influenced final results, were not taken into consideration.

Furthermore, for patients with intermediate-risk cancer, modifications in postoperative follow-up are necessary following lobectomy versus total thyroidectomy; “the role of radioiodine is limited and the levels of thyroglobulin more complicated to interpret,” they note.

The study and editorial authors had no disclosures to report.

A version of this article first appeared on Medscape.com.

Patients with intermediate-risk papillary thyroid cancer and lymph node metastasis show no significant increase in tumor recurrence when undergoing lobectomy compared with a total thyroidectomy, new research shows.

“Results of this cohort study suggest that patients with ipsilateral clinical lateral neck metastasis (cN1b) papillary thyroid cancer who underwent lobectomy exhibited recurrence-free survival rates similar to those who underwent total thyroidectomy after controlling for major prognostic factors,” the authors conclude in the study published online in JAMA Surgery.

“These findings suggest that cN1b alone should not be an absolute indication for total thyroidectomy,” they note.

The study, involving the largest cohort to date to compare patients with intermediate-risk papillary thyroid cancer treated with lobectomy versus total thyroidectomy, “challenged the current guidelines and pushed the boundary of limited surgical treatment even further,” say Michelle B. Mulder, MD, and Quan-Yang Duh, MD, of the department of surgery, University of California, San Francisco, in an accompanying editorial.

“It can be a game changer if confirmed by future prospective and multicenter studies,” they add.
 

Guidelines still recommend total thyroidectomy with subsequent RAI

While lower-intensity treatment options, with a lower risk of complications, have gained favor in the treatment of low-risk papillary thyroid cancer, guidelines still recommend the consideration of total thyroidectomy and subsequent radioactive iodine ablation (RAI) for intermediate-risk cancers because of the higher chance of recurrence, particularly among those with clinically positive nodes.

However, data on the superiority of a total thyroidectomy, with or without RAI, versus lobectomy is inconsistent, prompting first author Siyuan Xu, MD, of the department of head and neck surgical oncology, National Cancer Center, Beijing, and colleagues to compare the risk of recurrence with the two approaches.

For the study, patients with intermediate-risk papillary thyroid cancer treated at the Chinese Academy of Medical Sciences Cancer Hospital in Beijing between January 2000 and December 2017, who had a lobectomy or total thyroidectomy, were paired 1:1 in a propensity score matching analysis.

Other than treatment type, the 265 pairs of patients were matched based on all other potential prognostic factors, including age, sex, primary tumor size, minor extrathyroidal extension, multifocality, number of lymph node metastases, and lymph node ratio.

Participants were a mean age of 37 years and 66% were female.

With a median follow-up of 60 months in the lobectomy group and 58 months in the total thyroidectomy group, structural recurrences occurred in 7.9% (21) and 6.4% (17) of patients, respectively, which was not significantly different.

The primary endpoint, 5-year rate of recurrence-free survival, was also not significantly different between the lobectomy (92.3%) and total thyroidectomy groups (93.7%) (adjusted hazard ratio, 1.10; P = .77).

In a further stratified analysis of patients treated with total thyroidectomy along with RAI (n = 75), the lack of a significant difference in recurrence-free survival versus lobectomy remained (aHR, 0.59; P = .46).

The results were similar in unadjusted as well as adjusted analyses, and a power analysis indicated that the study had a 90% power to detect a more than 4.9% difference in recurrence-free survival.

“Given the lower complication rate of lobectomy, a maximal 4.9% recurrence-free survival difference is acceptable, which enhances the reliability of the study results,” the authors say.

They conclude that “our findings call into question whether cN1b alone [ipsilateral clinical lateral neck metastasis papillary thyroid cancer] should be an absolute determinant for deciding the optimal extent of thyroid surgery for papillary thyroid cancer.”
 

With total thyroidectomy, RAI can be given

An important argument in favor of total thyroidectomy is that with the complete resection of thyroid tissue, RAI ablation can then be used for postoperative detection of residual or metastatic disease, as well as for treatment, the authors note.

Indeed, a study using the Surveillance, Epidemiology, and End Results (SEER) database showed RAI ablation is associated with a 29% reduction in the risk of death in patients with intermediate-risk papillary thyroid cancer, with a hazard risk of 0.71.

However, conflicting data from Memorial Sloan-Kettering Cancer Center, New York, suggests no significant benefit with total thyroidectomy and RAI ablation.

The current study’s analysis of patients treated with RAI, though limited in size, supports the latter study’s findings, the authors note.

“When we performed further stratified analyses in patients treated with total thyroidectomy plus RAI ablation and their counterparts, no significant difference was found, which conformed with [the] result from the whole cohort.”

“Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection [and] further study is needed on this topic,” they write.
 

Some limitations warrant cautious interpretation

In their editorial, Dr. Mulder and Dr. Duh note that while some previous studies have shown similar outcomes relating to tumor size, thyroid hormone suppression therapy, and multifocality, “few have addressed lateral neck involvement.”

They suggest cautious interpretation, however, due to limitations, acknowledged by the authors, including the single-center nature of the study.

“Appropriate propensity matching may mitigate selection bias but cannot eliminate it entirely and their findings may not be replicated in other institutions by other surgeons,” they note.

Other limitations include that changes in clinical practice and patient selection were likely over the course of the study because of significant changes in American Thyroid Association (ATA) guidelines between 2009 and 2017, and characteristics including molecular genetic testing, which could have influenced final results, were not taken into consideration.

Furthermore, for patients with intermediate-risk cancer, modifications in postoperative follow-up are necessary following lobectomy versus total thyroidectomy; “the role of radioiodine is limited and the levels of thyroglobulin more complicated to interpret,” they note.

The study and editorial authors had no disclosures to report.

A version of this article first appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be at a higher risk of developing pancreatic cancer, say researchers reporting a single-center case-control study.

A diagnosis of PCOS was associated with a 1.9-fold higher risk of pancreatic cancer after adjusting for age, race, ethnicity, estrogen level, and diabetes.

This is the second study to find such an association.

“Our study findings combined with those from the 2019 Swedish Registry study offer compelling evidence that PCOS may be a novel risk factor for pancreatic cancer,” said corresponding author Mengmeng Du, ScD, department of epidemiology and biostatistics, Memorial Sloan Kettering Cancer Center.

“These data suggest some individuals may have unknown metabolic derangements that may underlie the development of both conditions,” the team concluded.

The findings were published in JAMA Oncology.

Approached for comment, Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research medicine, Cedars-Sinai, suggested that the findings may pave the way for a better understanding of the two diseases, but he emphasized that more research is needed.

“I think there’s more research to be done because now we’re seeing more younger women get pancreatic cancer,” Dr. Gaddam said. “So that makes it interesting whether PCOS itself contributes to pancreatic cancer. I still think the jury is out there.”

Dr. Gaddam drew attention to the confidence interval for the finding – the adjusted odds ratio was 1.88 (95% confidence interval, 1.02-3.46). “Because their odds ratio includes 1, I’m left with the question as to whether or not this is truly associated. I’m not certain that we can draw any conclusions based on this,” he commented.

The investigators acknowledge that they did “not observe statistically significant interactions” and comment that “prospective studies are needed to examine underlying biologic mechanisms and confirm our findings.”

For the study, the team used data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. They identified patients with pancreatic cancer who also self-reported a diagnosis of PCOS.

The investigators compared data from 446 women with pathologically or cytologically confirmed pancreatic adenocarcinoma with 209 women who had no history of cancer. The mean age at cancer diagnosis or enrollment was 63.8 years among patients with pancreatic cancer and 57.7 years in the control group.

The study found that having PCOS nearly doubled a person’s risk of developing pancreatic cancer.

When adjusted for type 2 diabetes diagnosis, the odds ratio fell slightly to 1.78 (95% CI, 0.95-3.34).

Dr. Du, along with lead author Noah Peeri, PhD, were surprised that even after adjusting for body mass index and the presence of type 2 diabetes, PCOS remained strongly associated with pancreatic cancer risk.

“We originally thought type 2 diabetes may drive this association, given more than half of those with PCOS develop type 2 diabetes by age 40, according to the CDC, and type 2 diabetes has also been linked with increased pancreatic cancer risk,” said Dr. Du.

“While the association was slightly weaker and no longer statistically significant after we controlled for type 2 diabetes, the magnitude of the association remained largely unchanged,” he said.

Dr. Peeri believes that some of the factors that have been causally related to PCOS may increase an individual’s pancreatic cancer risk.

“PCOS itself does not likely cause pancreatic cancer, but metabolic problems (for example, improper breakdown of insulin) and chronic inflammation can contribute to both PCOS and pancreatic cancer risk,” Dr. Peeri said.

He concluded that the study results “suggest other underlying metabolic dysfunction may increase an individual’s pancreatic cancer risk.”

An important limitation of this study was that women in the study self-reported PCOS and may have incorrectly recalled their diagnosis. However, the authors believe it is unlikely that that had a bearing on the study findings.

The study was supported by National Cancer Institute grants, the Geoffrey Beene Foundation, and the Arnold and Arlene Goldstein Family Foundation.

A version of this article first appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be at a higher risk of developing pancreatic cancer, say researchers reporting a single-center case-control study.

A diagnosis of PCOS was associated with a 1.9-fold higher risk of pancreatic cancer after adjusting for age, race, ethnicity, estrogen level, and diabetes.

This is the second study to find such an association.

“Our study findings combined with those from the 2019 Swedish Registry study offer compelling evidence that PCOS may be a novel risk factor for pancreatic cancer,” said corresponding author Mengmeng Du, ScD, department of epidemiology and biostatistics, Memorial Sloan Kettering Cancer Center.

“These data suggest some individuals may have unknown metabolic derangements that may underlie the development of both conditions,” the team concluded.

The findings were published in JAMA Oncology.

Approached for comment, Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research medicine, Cedars-Sinai, suggested that the findings may pave the way for a better understanding of the two diseases, but he emphasized that more research is needed.

“I think there’s more research to be done because now we’re seeing more younger women get pancreatic cancer,” Dr. Gaddam said. “So that makes it interesting whether PCOS itself contributes to pancreatic cancer. I still think the jury is out there.”

Dr. Gaddam drew attention to the confidence interval for the finding – the adjusted odds ratio was 1.88 (95% confidence interval, 1.02-3.46). “Because their odds ratio includes 1, I’m left with the question as to whether or not this is truly associated. I’m not certain that we can draw any conclusions based on this,” he commented.

The investigators acknowledge that they did “not observe statistically significant interactions” and comment that “prospective studies are needed to examine underlying biologic mechanisms and confirm our findings.”

For the study, the team used data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. They identified patients with pancreatic cancer who also self-reported a diagnosis of PCOS.

The investigators compared data from 446 women with pathologically or cytologically confirmed pancreatic adenocarcinoma with 209 women who had no history of cancer. The mean age at cancer diagnosis or enrollment was 63.8 years among patients with pancreatic cancer and 57.7 years in the control group.

The study found that having PCOS nearly doubled a person’s risk of developing pancreatic cancer.

When adjusted for type 2 diabetes diagnosis, the odds ratio fell slightly to 1.78 (95% CI, 0.95-3.34).

Dr. Du, along with lead author Noah Peeri, PhD, were surprised that even after adjusting for body mass index and the presence of type 2 diabetes, PCOS remained strongly associated with pancreatic cancer risk.

“We originally thought type 2 diabetes may drive this association, given more than half of those with PCOS develop type 2 diabetes by age 40, according to the CDC, and type 2 diabetes has also been linked with increased pancreatic cancer risk,” said Dr. Du.

“While the association was slightly weaker and no longer statistically significant after we controlled for type 2 diabetes, the magnitude of the association remained largely unchanged,” he said.

Dr. Peeri believes that some of the factors that have been causally related to PCOS may increase an individual’s pancreatic cancer risk.

“PCOS itself does not likely cause pancreatic cancer, but metabolic problems (for example, improper breakdown of insulin) and chronic inflammation can contribute to both PCOS and pancreatic cancer risk,” Dr. Peeri said.

He concluded that the study results “suggest other underlying metabolic dysfunction may increase an individual’s pancreatic cancer risk.”

An important limitation of this study was that women in the study self-reported PCOS and may have incorrectly recalled their diagnosis. However, the authors believe it is unlikely that that had a bearing on the study findings.

The study was supported by National Cancer Institute grants, the Geoffrey Beene Foundation, and the Arnold and Arlene Goldstein Family Foundation.

A version of this article first appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be at a higher risk of developing pancreatic cancer, say researchers reporting a single-center case-control study.

A diagnosis of PCOS was associated with a 1.9-fold higher risk of pancreatic cancer after adjusting for age, race, ethnicity, estrogen level, and diabetes.

This is the second study to find such an association.

“Our study findings combined with those from the 2019 Swedish Registry study offer compelling evidence that PCOS may be a novel risk factor for pancreatic cancer,” said corresponding author Mengmeng Du, ScD, department of epidemiology and biostatistics, Memorial Sloan Kettering Cancer Center.

“These data suggest some individuals may have unknown metabolic derangements that may underlie the development of both conditions,” the team concluded.

The findings were published in JAMA Oncology.

Approached for comment, Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research medicine, Cedars-Sinai, suggested that the findings may pave the way for a better understanding of the two diseases, but he emphasized that more research is needed.

“I think there’s more research to be done because now we’re seeing more younger women get pancreatic cancer,” Dr. Gaddam said. “So that makes it interesting whether PCOS itself contributes to pancreatic cancer. I still think the jury is out there.”

Dr. Gaddam drew attention to the confidence interval for the finding – the adjusted odds ratio was 1.88 (95% confidence interval, 1.02-3.46). “Because their odds ratio includes 1, I’m left with the question as to whether or not this is truly associated. I’m not certain that we can draw any conclusions based on this,” he commented.

The investigators acknowledge that they did “not observe statistically significant interactions” and comment that “prospective studies are needed to examine underlying biologic mechanisms and confirm our findings.”

For the study, the team used data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. They identified patients with pancreatic cancer who also self-reported a diagnosis of PCOS.

The investigators compared data from 446 women with pathologically or cytologically confirmed pancreatic adenocarcinoma with 209 women who had no history of cancer. The mean age at cancer diagnosis or enrollment was 63.8 years among patients with pancreatic cancer and 57.7 years in the control group.

The study found that having PCOS nearly doubled a person’s risk of developing pancreatic cancer.

When adjusted for type 2 diabetes diagnosis, the odds ratio fell slightly to 1.78 (95% CI, 0.95-3.34).

Dr. Du, along with lead author Noah Peeri, PhD, were surprised that even after adjusting for body mass index and the presence of type 2 diabetes, PCOS remained strongly associated with pancreatic cancer risk.

“We originally thought type 2 diabetes may drive this association, given more than half of those with PCOS develop type 2 diabetes by age 40, according to the CDC, and type 2 diabetes has also been linked with increased pancreatic cancer risk,” said Dr. Du.

“While the association was slightly weaker and no longer statistically significant after we controlled for type 2 diabetes, the magnitude of the association remained largely unchanged,” he said.

Dr. Peeri believes that some of the factors that have been causally related to PCOS may increase an individual’s pancreatic cancer risk.

“PCOS itself does not likely cause pancreatic cancer, but metabolic problems (for example, improper breakdown of insulin) and chronic inflammation can contribute to both PCOS and pancreatic cancer risk,” Dr. Peeri said.

He concluded that the study results “suggest other underlying metabolic dysfunction may increase an individual’s pancreatic cancer risk.”

An important limitation of this study was that women in the study self-reported PCOS and may have incorrectly recalled their diagnosis. However, the authors believe it is unlikely that that had a bearing on the study findings.

The study was supported by National Cancer Institute grants, the Geoffrey Beene Foundation, and the Arnold and Arlene Goldstein Family Foundation.

A version of this article first appeared on Medscape.com.

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

The global burden of thyroid cancer is substantial, and incidence rates are increasing in many developed countries, including the Unites States, concluded a new analysis based on 30 years of observational data.

“We report overall increases in the burden of thyroid cancer across the majority of EU15+ countries between 1990 and 2019, evidenced by plateaus in incidence rates and reductions in mortality and DALY [disability-adjusted life-years] rates,” the authors reported.

“However, in a number of countries, including the U.S., there are unfavorable increasing mortality and DALY trends over this time period ... [and] a better understanding of the trends in the disease burden of thyroid cancer may help to inform future health system planning,” they added.

The study was published online March 10, 2022, in JAMA Otolaryngology–Head & Neck Surgery.
 

Trends in thyroid cancer

For the analysis, James Schuster-Bruce, MBChB, from St. George’s University Hospital NHS Foundation Trust, London, and colleagues compared trends in thyroid cancer across 30 years of follow-up among 15 countries of the (pre-2004) European Union as well as those in the United States, Australia, Canada, and Norway (EU15+).

Data from the Global Burden of Disease study database were used to track these trends. “We extracted age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for thyroid cancer from EU15+ countries between 1990 and 2019 using the dedicated GBD study results tool,” the investigators explained.

In 2019, ASIRs were highest in Italy at 6.36 per 100,000 population, followed by the United States at a rate of 5.59 per 100,000 population – although incidence rates of thyroid cancer have actually recently decreased in U.S. women, they noted.

“Thirteen of 19 countries showed an average annual percentage increase in ASIR across the study period,” the investigators added. Out of all the EU15+ countries, the average annual percentage change (AAPC) was the highest in Australia at 2.5 per 100,000 population and the United States at 1.2 per 100,000.

On the other hand, a largely plateauing trend in incidence rates across the majority of EU15+ nations has been observed since 1990, as reflected by incidence rates ranging from –0.8 to 0.8 per 100,000 in the most recent period, the researchers added. ASMRs ranged from a 0.40 per 100,000 in Greece to 0.57 per 100,000 in Luxembourg.

In the United States, the ASMR in 2019 was 0.43 per 100,000 population while the ASMR was the lowest in the United Kingdom in the same year at 0.38 per 100,000 population.

Australia, Denmark, and the United States were the only countries showing positive AAPC changes, the team observed. For example, in the most recent period to 2019, Denmark and Australia had reductions in ASMR trends, whereas in the United States, the trend was toward increasing ASMRs 

In 2019, the DALYs of the EU15+ nations ranged from 9.63 per 100,000 in the United Kingdom to 14.46 per 100,000 in Luxembourg. In the most recent period, a downward trend in DALYs was observed in Australia and Denmark while it plateaued in the United States.

“Overall, we identified improvements in thyroid cancer mortality and DALYs, but overall increases in thyroid cancer incidence in EU15+ countries over the past 3 decades,” the investigators commented.

It has been widely suggested that improvements in diagnostic techniques have contributed significantly to increasing incidence rates of thyroid cancer, but there is concern about overdiagnosis.  Newer diagnostic techniques detect significant numbers of slow-growing, subclinical papillary thyroid cancers that make up at least one quarter of all thyroid cancer subtypes, the authors pointed out.

“It has therefore been suggested that an increase in subclinical disease has inflated the data to look more substantial than the clinical reality,” the authors wrote. However, they insisted that overdiagnosis alone is unlikely to account entirely for increasing incidence trends in the current analysis.

Rather, their concern for countries with high incidence rates of thyroid cancer is the surveillance burden of disease that does not affect mortality. “Close observation of future time trends in thyroid cancer disease burden should be performed in the context of recent changes in international clinical practice guidelines, which have suggested more conservative diagnostic and management strategies,” the authors suggested.

“In the context of the more conservative treatment guidelines and reported increase in true disease, it is important to closely observe mortality and DALYs over the coming years to ensure optimum thyroid cancer management in these nations,” they added.

The study had no specific funding. Dr. Schuster-Bruce disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The global burden of thyroid cancer is substantial, and incidence rates are increasing in many developed countries, including the Unites States, concluded a new analysis based on 30 years of observational data.

“We report overall increases in the burden of thyroid cancer across the majority of EU15+ countries between 1990 and 2019, evidenced by plateaus in incidence rates and reductions in mortality and DALY [disability-adjusted life-years] rates,” the authors reported.

“However, in a number of countries, including the U.S., there are unfavorable increasing mortality and DALY trends over this time period ... [and] a better understanding of the trends in the disease burden of thyroid cancer may help to inform future health system planning,” they added.

The study was published online March 10, 2022, in JAMA Otolaryngology–Head & Neck Surgery.
 

Trends in thyroid cancer

For the analysis, James Schuster-Bruce, MBChB, from St. George’s University Hospital NHS Foundation Trust, London, and colleagues compared trends in thyroid cancer across 30 years of follow-up among 15 countries of the (pre-2004) European Union as well as those in the United States, Australia, Canada, and Norway (EU15+).

Data from the Global Burden of Disease study database were used to track these trends. “We extracted age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for thyroid cancer from EU15+ countries between 1990 and 2019 using the dedicated GBD study results tool,” the investigators explained.

In 2019, ASIRs were highest in Italy at 6.36 per 100,000 population, followed by the United States at a rate of 5.59 per 100,000 population – although incidence rates of thyroid cancer have actually recently decreased in U.S. women, they noted.

“Thirteen of 19 countries showed an average annual percentage increase in ASIR across the study period,” the investigators added. Out of all the EU15+ countries, the average annual percentage change (AAPC) was the highest in Australia at 2.5 per 100,000 population and the United States at 1.2 per 100,000.

On the other hand, a largely plateauing trend in incidence rates across the majority of EU15+ nations has been observed since 1990, as reflected by incidence rates ranging from –0.8 to 0.8 per 100,000 in the most recent period, the researchers added. ASMRs ranged from a 0.40 per 100,000 in Greece to 0.57 per 100,000 in Luxembourg.

In the United States, the ASMR in 2019 was 0.43 per 100,000 population while the ASMR was the lowest in the United Kingdom in the same year at 0.38 per 100,000 population.

Australia, Denmark, and the United States were the only countries showing positive AAPC changes, the team observed. For example, in the most recent period to 2019, Denmark and Australia had reductions in ASMR trends, whereas in the United States, the trend was toward increasing ASMRs 

In 2019, the DALYs of the EU15+ nations ranged from 9.63 per 100,000 in the United Kingdom to 14.46 per 100,000 in Luxembourg. In the most recent period, a downward trend in DALYs was observed in Australia and Denmark while it plateaued in the United States.

“Overall, we identified improvements in thyroid cancer mortality and DALYs, but overall increases in thyroid cancer incidence in EU15+ countries over the past 3 decades,” the investigators commented.

It has been widely suggested that improvements in diagnostic techniques have contributed significantly to increasing incidence rates of thyroid cancer, but there is concern about overdiagnosis.  Newer diagnostic techniques detect significant numbers of slow-growing, subclinical papillary thyroid cancers that make up at least one quarter of all thyroid cancer subtypes, the authors pointed out.

“It has therefore been suggested that an increase in subclinical disease has inflated the data to look more substantial than the clinical reality,” the authors wrote. However, they insisted that overdiagnosis alone is unlikely to account entirely for increasing incidence trends in the current analysis.

Rather, their concern for countries with high incidence rates of thyroid cancer is the surveillance burden of disease that does not affect mortality. “Close observation of future time trends in thyroid cancer disease burden should be performed in the context of recent changes in international clinical practice guidelines, which have suggested more conservative diagnostic and management strategies,” the authors suggested.

“In the context of the more conservative treatment guidelines and reported increase in true disease, it is important to closely observe mortality and DALYs over the coming years to ensure optimum thyroid cancer management in these nations,” they added.

The study had no specific funding. Dr. Schuster-Bruce disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The global burden of thyroid cancer is substantial, and incidence rates are increasing in many developed countries, including the Unites States, concluded a new analysis based on 30 years of observational data.

“We report overall increases in the burden of thyroid cancer across the majority of EU15+ countries between 1990 and 2019, evidenced by plateaus in incidence rates and reductions in mortality and DALY [disability-adjusted life-years] rates,” the authors reported.

“However, in a number of countries, including the U.S., there are unfavorable increasing mortality and DALY trends over this time period ... [and] a better understanding of the trends in the disease burden of thyroid cancer may help to inform future health system planning,” they added.

The study was published online March 10, 2022, in JAMA Otolaryngology–Head & Neck Surgery.
 

Trends in thyroid cancer

For the analysis, James Schuster-Bruce, MBChB, from St. George’s University Hospital NHS Foundation Trust, London, and colleagues compared trends in thyroid cancer across 30 years of follow-up among 15 countries of the (pre-2004) European Union as well as those in the United States, Australia, Canada, and Norway (EU15+).

Data from the Global Burden of Disease study database were used to track these trends. “We extracted age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for thyroid cancer from EU15+ countries between 1990 and 2019 using the dedicated GBD study results tool,” the investigators explained.

In 2019, ASIRs were highest in Italy at 6.36 per 100,000 population, followed by the United States at a rate of 5.59 per 100,000 population – although incidence rates of thyroid cancer have actually recently decreased in U.S. women, they noted.

“Thirteen of 19 countries showed an average annual percentage increase in ASIR across the study period,” the investigators added. Out of all the EU15+ countries, the average annual percentage change (AAPC) was the highest in Australia at 2.5 per 100,000 population and the United States at 1.2 per 100,000.

On the other hand, a largely plateauing trend in incidence rates across the majority of EU15+ nations has been observed since 1990, as reflected by incidence rates ranging from –0.8 to 0.8 per 100,000 in the most recent period, the researchers added. ASMRs ranged from a 0.40 per 100,000 in Greece to 0.57 per 100,000 in Luxembourg.

In the United States, the ASMR in 2019 was 0.43 per 100,000 population while the ASMR was the lowest in the United Kingdom in the same year at 0.38 per 100,000 population.

Australia, Denmark, and the United States were the only countries showing positive AAPC changes, the team observed. For example, in the most recent period to 2019, Denmark and Australia had reductions in ASMR trends, whereas in the United States, the trend was toward increasing ASMRs 

In 2019, the DALYs of the EU15+ nations ranged from 9.63 per 100,000 in the United Kingdom to 14.46 per 100,000 in Luxembourg. In the most recent period, a downward trend in DALYs was observed in Australia and Denmark while it plateaued in the United States.

“Overall, we identified improvements in thyroid cancer mortality and DALYs, but overall increases in thyroid cancer incidence in EU15+ countries over the past 3 decades,” the investigators commented.

It has been widely suggested that improvements in diagnostic techniques have contributed significantly to increasing incidence rates of thyroid cancer, but there is concern about overdiagnosis.  Newer diagnostic techniques detect significant numbers of slow-growing, subclinical papillary thyroid cancers that make up at least one quarter of all thyroid cancer subtypes, the authors pointed out.

“It has therefore been suggested that an increase in subclinical disease has inflated the data to look more substantial than the clinical reality,” the authors wrote. However, they insisted that overdiagnosis alone is unlikely to account entirely for increasing incidence trends in the current analysis.

Rather, their concern for countries with high incidence rates of thyroid cancer is the surveillance burden of disease that does not affect mortality. “Close observation of future time trends in thyroid cancer disease burden should be performed in the context of recent changes in international clinical practice guidelines, which have suggested more conservative diagnostic and management strategies,” the authors suggested.

“In the context of the more conservative treatment guidelines and reported increase in true disease, it is important to closely observe mortality and DALYs over the coming years to ensure optimum thyroid cancer management in these nations,” they added.

The study had no specific funding. Dr. Schuster-Bruce disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.¹ To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.

Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.¹ Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.

Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.¹

Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.¹

When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.

The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.

If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.

If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.²

Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.

Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at obnews@mdedge.com.
 

References

1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.

2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.

A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.¹ To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.

Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.¹ Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.

Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.¹

Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.¹

When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.

The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.

If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.

If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.²

Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.

Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at obnews@mdedge.com.
 

References

1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.

2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.

A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.¹ To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.

Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.¹ Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.

Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.¹

Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.¹

When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.

The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.

If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.

If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.²

Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.

Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at obnews@mdedge.com.
 

References

1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.

2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.

The federal government is stepping up actions to protect Americans from per- and polyfluoroalkyl substances that continue to threaten health through pollution in the air, water, and foods, according to a statement from the White House on Oct. 18.

tupungato/Thinkstock

The comprehensive plan includes efforts to prevent per- and polyfluoroalkyl substances (PFAS) from being released into the air, drinking and ground water, and the food supply chain, according to the statement. Other efforts will expand cleanup and remediation of the impact of PFAS already present in the environment.

PFAS are a category of endocrine-disrupting chemicals (EDCs) that have been used for decades in a range of consumer products including cookware, stain-resistant clothes, fast food wrappers, treatments for carpets and furniture, and firefighting foams. PFAS can be released into the air, and also into surface water, drinking water, and ground water, because of how they are disposed, according to a 2020 report from the Endocrine Society and the International Pollutants Elimination Network. The report suggested that creation of more plastic products will likely increase exposure to PFAS and other EDCs.

The Environmental Protection Agency will take the lead on the Biden administration’s PFAS reduction efforts. The agency announced a PFAS Roadmap, which outlines actions to control PFAS over the next 3 years. The Roadmap’s goals include keeping PFAS out of the environment, holding polluters accountable for their actions, investing in scientific research to learn more about the impact of PFAS on human health, and prioritizing protection for disadvantaged communities. The EPA described its approach to PFAS as three pronged (Research, Restrict, Remediate). Planned actions noted on the EPA website include publication of a national PFAS testing strategy, establishing an improved review process for new PFAS, reviewing existing PFAS, and enhancing reporting to track sources and quantities of PFAS.

White House statement noted that other agencies committed to controlling PFAS include the Department of Defense, which will conduct cleanups and assessments at DOD and National Guard locations; the Food and Drug Administration, which will to expand its food supply testing to estimate dietary exposure to PFAS; and the Department of Agriculture, which is investigating causes and impacts of PFAS in the food system, and supporting research on environmental contaminants including PFAS.

The Department of Homeland Security has conducted an inventory of PFAS use, notably the use of PFAS in firefighting foams, and established an Emerging Contaminants Working Group to remediate PFAS and other contaminants. In addition, the Department of Health & Human Services monitors the evolving science on human health and PFAS and anticipates a report by the Centers for Disease Control and Prevention on the health effects of PFAS exposure, with data from eight states.

The American Chemistry Council (ACC), a trade association for American chemistry companies, issued a statement in response to the EPA’s PFAS Strategic Roadmap in which they supported the value of science-based regulation, but emphasized that PFAS are distinct from one another, and should not be grouped together for regulation purposes.

“According to EPA, approximately 600 PFAS substances are manufactured or in use today, each with its own unique properties and uses, from cellphones to solar panels, for which alternatives are not always available,” according to the ACC statement. “EPA’s Roadmap reinforces the differences between these chemistries and that they should not all be grouped together.” The newly formed Interagency Policy Committee on PFAS will coordinate PFAS response efforts across agencies and “help develop new policy strategies to support research, remediation, and removal of PFAS in communities across the country,” according to the White House statement.

The federal government is stepping up actions to protect Americans from per- and polyfluoroalkyl substances that continue to threaten health through pollution in the air, water, and foods, according to a statement from the White House on Oct. 18.

tupungato/Thinkstock

The comprehensive plan includes efforts to prevent per- and polyfluoroalkyl substances (PFAS) from being released into the air, drinking and ground water, and the food supply chain, according to the statement. Other efforts will expand cleanup and remediation of the impact of PFAS already present in the environment.

PFAS are a category of endocrine-disrupting chemicals (EDCs) that have been used for decades in a range of consumer products including cookware, stain-resistant clothes, fast food wrappers, treatments for carpets and furniture, and firefighting foams. PFAS can be released into the air, and also into surface water, drinking water, and ground water, because of how they are disposed, according to a 2020 report from the Endocrine Society and the International Pollutants Elimination Network. The report suggested that creation of more plastic products will likely increase exposure to PFAS and other EDCs.

The Environmental Protection Agency will take the lead on the Biden administration’s PFAS reduction efforts. The agency announced a PFAS Roadmap, which outlines actions to control PFAS over the next 3 years. The Roadmap’s goals include keeping PFAS out of the environment, holding polluters accountable for their actions, investing in scientific research to learn more about the impact of PFAS on human health, and prioritizing protection for disadvantaged communities. The EPA described its approach to PFAS as three pronged (Research, Restrict, Remediate). Planned actions noted on the EPA website include publication of a national PFAS testing strategy, establishing an improved review process for new PFAS, reviewing existing PFAS, and enhancing reporting to track sources and quantities of PFAS.

White House statement noted that other agencies committed to controlling PFAS include the Department of Defense, which will conduct cleanups and assessments at DOD and National Guard locations; the Food and Drug Administration, which will to expand its food supply testing to estimate dietary exposure to PFAS; and the Department of Agriculture, which is investigating causes and impacts of PFAS in the food system, and supporting research on environmental contaminants including PFAS.

The Department of Homeland Security has conducted an inventory of PFAS use, notably the use of PFAS in firefighting foams, and established an Emerging Contaminants Working Group to remediate PFAS and other contaminants. In addition, the Department of Health & Human Services monitors the evolving science on human health and PFAS and anticipates a report by the Centers for Disease Control and Prevention on the health effects of PFAS exposure, with data from eight states.

The American Chemistry Council (ACC), a trade association for American chemistry companies, issued a statement in response to the EPA’s PFAS Strategic Roadmap in which they supported the value of science-based regulation, but emphasized that PFAS are distinct from one another, and should not be grouped together for regulation purposes.

“According to EPA, approximately 600 PFAS substances are manufactured or in use today, each with its own unique properties and uses, from cellphones to solar panels, for which alternatives are not always available,” according to the ACC statement. “EPA’s Roadmap reinforces the differences between these chemistries and that they should not all be grouped together.” The newly formed Interagency Policy Committee on PFAS will coordinate PFAS response efforts across agencies and “help develop new policy strategies to support research, remediation, and removal of PFAS in communities across the country,” according to the White House statement.

The federal government is stepping up actions to protect Americans from per- and polyfluoroalkyl substances that continue to threaten health through pollution in the air, water, and foods, according to a statement from the White House on Oct. 18.

tupungato/Thinkstock

The comprehensive plan includes efforts to prevent per- and polyfluoroalkyl substances (PFAS) from being released into the air, drinking and ground water, and the food supply chain, according to the statement. Other efforts will expand cleanup and remediation of the impact of PFAS already present in the environment.

PFAS are a category of endocrine-disrupting chemicals (EDCs) that have been used for decades in a range of consumer products including cookware, stain-resistant clothes, fast food wrappers, treatments for carpets and furniture, and firefighting foams. PFAS can be released into the air, and also into surface water, drinking water, and ground water, because of how they are disposed, according to a 2020 report from the Endocrine Society and the International Pollutants Elimination Network. The report suggested that creation of more plastic products will likely increase exposure to PFAS and other EDCs.

The Environmental Protection Agency will take the lead on the Biden administration’s PFAS reduction efforts. The agency announced a PFAS Roadmap, which outlines actions to control PFAS over the next 3 years. The Roadmap’s goals include keeping PFAS out of the environment, holding polluters accountable for their actions, investing in scientific research to learn more about the impact of PFAS on human health, and prioritizing protection for disadvantaged communities. The EPA described its approach to PFAS as three pronged (Research, Restrict, Remediate). Planned actions noted on the EPA website include publication of a national PFAS testing strategy, establishing an improved review process for new PFAS, reviewing existing PFAS, and enhancing reporting to track sources and quantities of PFAS.

White House statement noted that other agencies committed to controlling PFAS include the Department of Defense, which will conduct cleanups and assessments at DOD and National Guard locations; the Food and Drug Administration, which will to expand its food supply testing to estimate dietary exposure to PFAS; and the Department of Agriculture, which is investigating causes and impacts of PFAS in the food system, and supporting research on environmental contaminants including PFAS.

The Department of Homeland Security has conducted an inventory of PFAS use, notably the use of PFAS in firefighting foams, and established an Emerging Contaminants Working Group to remediate PFAS and other contaminants. In addition, the Department of Health & Human Services monitors the evolving science on human health and PFAS and anticipates a report by the Centers for Disease Control and Prevention on the health effects of PFAS exposure, with data from eight states.

The American Chemistry Council (ACC), a trade association for American chemistry companies, issued a statement in response to the EPA’s PFAS Strategic Roadmap in which they supported the value of science-based regulation, but emphasized that PFAS are distinct from one another, and should not be grouped together for regulation purposes.

“According to EPA, approximately 600 PFAS substances are manufactured or in use today, each with its own unique properties and uses, from cellphones to solar panels, for which alternatives are not always available,” according to the ACC statement. “EPA’s Roadmap reinforces the differences between these chemistries and that they should not all be grouped together.” The newly formed Interagency Policy Committee on PFAS will coordinate PFAS response efforts across agencies and “help develop new policy strategies to support research, remediation, and removal of PFAS in communities across the country,” according to the White House statement.