Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.

In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”

With all due respect, I can’t do that. I need a desk to function. A REAL one.

I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.

My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.

At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.

But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.

Dr. Allan M. Block

This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.

It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it. I’d much rather have my patients and I talk while sitting across my desk, in comfortable chairs, then in a sterile exam room with them on the exam table and me on a rolling chair trying to balance an iPad on my lap.

Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.

But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.

It’s part of the soul of my practice, and I wouldn’t have it any other way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.

In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”

With all due respect, I can’t do that. I need a desk to function. A REAL one.

I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.

My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.

At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.

But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.

Dr. Allan M. Block

This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.

It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it. I’d much rather have my patients and I talk while sitting across my desk, in comfortable chairs, then in a sterile exam room with them on the exam table and me on a rolling chair trying to balance an iPad on my lap.

Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.

But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.

It’s part of the soul of my practice, and I wouldn’t have it any other way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.

In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”

With all due respect, I can’t do that. I need a desk to function. A REAL one.

I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.

My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.

At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.

But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.

Dr. Allan M. Block

This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.

It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it. I’d much rather have my patients and I talk while sitting across my desk, in comfortable chairs, then in a sterile exam room with them on the exam table and me on a rolling chair trying to balance an iPad on my lap.

Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.

But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.

It’s part of the soul of my practice, and I wouldn’t have it any other way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.

Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.

Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.

After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was  associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.

In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).  

The findings were published online in JAMA Network Open

Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.

“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.

Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.

“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.

New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.

The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.

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

Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.

Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.

Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.

After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was  associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.

In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).  

The findings were published online in JAMA Network Open

Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.

“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.

Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.

“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.

New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.

The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.

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

Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.

Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.

Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.

After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was  associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.

In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).  

The findings were published online in JAMA Network Open

Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.

“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.

Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.

“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.

New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.

The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.

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

Most older adults with low-risk surveillance colonoscopy findings and/or limited life expectancy are advised to undergo a repeat procedure in the future, according to a new study.

Among nearly 10,000 Medicare beneficiaries, the likelihood of finding advanced polyps or colorectal cancer (CRC) on surveillance colonoscopy was low. Yet, among patients for whom any follow-up recommendation – either for or against colonoscopy – was available, the vast majority (87%) were advised to return for the procedure in the future, even if their life expectancy was limited or there were no significant findings on their surveillance colonoscopy.

“These findings suggest that recommending against future surveillance colonoscopy in older adults with low-risk colonoscopy findings and/or limited life expectancy should be considered more frequently than is currently practiced,” say Audrey Calderwood, MD, with Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Because of the lack of clear guidance about when to stop recommending colonoscopies to older patients, it is not surprising that physicians recommend surveillance even for patients with low life expectancy, Ziad Gellad, MD, with Duke University Medical Center, Durham, N.C., said in an interview.

“As someone who performs these procedures, I can tell you that it is not easy to tell patients that they are too old to get preventive care, especially patients in whom your only interaction is the procedure itself,” said Dr. Gellad, who wasn’t involved in the study.

The study was published online in JAMA Internal Medicine.
 

Key findings

For older adults, surveillance after prior findings of colon polyps is the most frequent indication for colonoscopy. Data suggest that an estimated 5.6 million adults older than 75 will undergo follow-up colonoscopy annually by 2024.

For older adults with polyps, current guidelines recommend individualized decision-making about surveillance colonoscopy. That includes weighing the potential benefits (identifying and removing meaningful lesions to prevent CRC) against the burdens and potential harms (such as bleeding or perforation).

While most colon polyps are not harmful, a subset of polyps, if allowed to grow, can develop into cancer over 10-15 years. This long biological time line highlights the importance of considering life expectancy in deciding for whom surveillance colonoscopy should be recommended, Dr. Calderwood and colleagues note.

Using data from the New Hampshire Colonoscopy Registry, which is linked with the Medicare claims database, they evaluated surveillance colonoscopy findings and follow-up advice according to severity of findings and patients’ estimated life expectancy for 9,831 adults (mean age, 73; 54% men).

Life expectancy was 10+ years for 57.5% of patients, 5 to less than 10 years for 35%, and less than 5 years for 7.5%.

Overall, 791 patients (8%) were found to have advanced polyps (7.8%) or CRC (0.2%) on surveillance colonoscopy.

Recommendations to stop or continue future colonoscopy were available for 5,281 patients (53.7%). Among them, 4,588 (86.9%) were recommended to return for future colonoscopy, even when there were no significant colonoscopy findings or the patient’s life expectancy was limited.

Compared with life expectancy of less than 5 years, longer life expectancy was associated with advice to return for future colonoscopy regardless of clinical findings, with adjusted odds ratios of 21.5 and 2.7, respectively, for life expectancy of 10 or more years and of 5 to less than 10 years.

Among patients with no significant findings, 95% of those with life expectancy of 10 or more years were recommended to undergo repeat colonoscopy down the road, compared with 58% of those with estimated life expectancy of less than 5 years.

Among patients expected to live 5 to less than 10 years, future repeat colonoscopy was recommended for 75% who had no significant findings, 82% with one or two small polyps, and 88% with multiple polyps, advanced polyps, or CRC.

The recommended time to repeat colonoscopy was greater than life expectancy for 6.6% of patients with less than 5 years of life expectancy and 6% with 5 to less than 10 years of life expectancy.
 

Nuanced decisions

The findings “may help refine decision-making” about the potential benefits and harms of pursuing or stopping surveillance colonoscopy for older adults who have a history of polyps, Dr. Calderwood and colleagues say.

The risk for a colonoscopy complication has been estimated at 26 per 1,000 people, they note. That’s nearly 10 times greater than the potential benefits seen in their study (that is, identification of CRC in 23 of 9,831 people, or about 2.3 per 1,000).

In the study cohort, 10% of patients had comorbid conditions that have been associated with a higher risk for colonoscopy complications. Those with life expectancy of less than 5 years had higher rates of inadequate bowel preparation, which also is associated with increased risk for colonoscopy complications, including perforation.

Dr. Calderwood and colleagues suggest that clinicians use evidence regarding life expectancy and neoplasia progression to modify their recommendations for surveillance colonoscopy for older adults in the following ways:

• If life expectancy is less than 5 years, recommend against surveillance.
• If life expectancy is 5 to less than 10 years and the patient has only low-risk polyps, recommend against surveillance.
• If the patient is healthy with a life expectancy of 10+ years and has recently been found to have advanced polyps, recommend future surveillance colonoscopy, with a caveat that the ultimate decision is dependent on health and priorities at the time the colonoscopy is due to be performed.
• If future health is unknown or unclear, avoid giving definitive recommendations for future surveillance to allow the flexibility of deciding on the basis of risk and benefit when the time comes.

In comments to this news organization, Dr. Gellad noted that an assessment of patient life expectancy “is not readily accessible at the point of care. These are nuanced decisions that require shared decision-making. Sometimes that is best handled outside the procedure setting.”

Support for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and is a cofounder of Higgs Boson.

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

Most older adults with low-risk surveillance colonoscopy findings and/or limited life expectancy are advised to undergo a repeat procedure in the future, according to a new study.

Among nearly 10,000 Medicare beneficiaries, the likelihood of finding advanced polyps or colorectal cancer (CRC) on surveillance colonoscopy was low. Yet, among patients for whom any follow-up recommendation – either for or against colonoscopy – was available, the vast majority (87%) were advised to return for the procedure in the future, even if their life expectancy was limited or there were no significant findings on their surveillance colonoscopy.

“These findings suggest that recommending against future surveillance colonoscopy in older adults with low-risk colonoscopy findings and/or limited life expectancy should be considered more frequently than is currently practiced,” say Audrey Calderwood, MD, with Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Because of the lack of clear guidance about when to stop recommending colonoscopies to older patients, it is not surprising that physicians recommend surveillance even for patients with low life expectancy, Ziad Gellad, MD, with Duke University Medical Center, Durham, N.C., said in an interview.

“As someone who performs these procedures, I can tell you that it is not easy to tell patients that they are too old to get preventive care, especially patients in whom your only interaction is the procedure itself,” said Dr. Gellad, who wasn’t involved in the study.

The study was published online in JAMA Internal Medicine.
 

Key findings

For older adults, surveillance after prior findings of colon polyps is the most frequent indication for colonoscopy. Data suggest that an estimated 5.6 million adults older than 75 will undergo follow-up colonoscopy annually by 2024.

For older adults with polyps, current guidelines recommend individualized decision-making about surveillance colonoscopy. That includes weighing the potential benefits (identifying and removing meaningful lesions to prevent CRC) against the burdens and potential harms (such as bleeding or perforation).

While most colon polyps are not harmful, a subset of polyps, if allowed to grow, can develop into cancer over 10-15 years. This long biological time line highlights the importance of considering life expectancy in deciding for whom surveillance colonoscopy should be recommended, Dr. Calderwood and colleagues note.

Using data from the New Hampshire Colonoscopy Registry, which is linked with the Medicare claims database, they evaluated surveillance colonoscopy findings and follow-up advice according to severity of findings and patients’ estimated life expectancy for 9,831 adults (mean age, 73; 54% men).

Life expectancy was 10+ years for 57.5% of patients, 5 to less than 10 years for 35%, and less than 5 years for 7.5%.

Overall, 791 patients (8%) were found to have advanced polyps (7.8%) or CRC (0.2%) on surveillance colonoscopy.

Recommendations to stop or continue future colonoscopy were available for 5,281 patients (53.7%). Among them, 4,588 (86.9%) were recommended to return for future colonoscopy, even when there were no significant colonoscopy findings or the patient’s life expectancy was limited.

Compared with life expectancy of less than 5 years, longer life expectancy was associated with advice to return for future colonoscopy regardless of clinical findings, with adjusted odds ratios of 21.5 and 2.7, respectively, for life expectancy of 10 or more years and of 5 to less than 10 years.

Among patients with no significant findings, 95% of those with life expectancy of 10 or more years were recommended to undergo repeat colonoscopy down the road, compared with 58% of those with estimated life expectancy of less than 5 years.

Among patients expected to live 5 to less than 10 years, future repeat colonoscopy was recommended for 75% who had no significant findings, 82% with one or two small polyps, and 88% with multiple polyps, advanced polyps, or CRC.

The recommended time to repeat colonoscopy was greater than life expectancy for 6.6% of patients with less than 5 years of life expectancy and 6% with 5 to less than 10 years of life expectancy.
 

Nuanced decisions

The findings “may help refine decision-making” about the potential benefits and harms of pursuing or stopping surveillance colonoscopy for older adults who have a history of polyps, Dr. Calderwood and colleagues say.

The risk for a colonoscopy complication has been estimated at 26 per 1,000 people, they note. That’s nearly 10 times greater than the potential benefits seen in their study (that is, identification of CRC in 23 of 9,831 people, or about 2.3 per 1,000).

In the study cohort, 10% of patients had comorbid conditions that have been associated with a higher risk for colonoscopy complications. Those with life expectancy of less than 5 years had higher rates of inadequate bowel preparation, which also is associated with increased risk for colonoscopy complications, including perforation.

Dr. Calderwood and colleagues suggest that clinicians use evidence regarding life expectancy and neoplasia progression to modify their recommendations for surveillance colonoscopy for older adults in the following ways:

• If life expectancy is less than 5 years, recommend against surveillance.
• If life expectancy is 5 to less than 10 years and the patient has only low-risk polyps, recommend against surveillance.
• If the patient is healthy with a life expectancy of 10+ years and has recently been found to have advanced polyps, recommend future surveillance colonoscopy, with a caveat that the ultimate decision is dependent on health and priorities at the time the colonoscopy is due to be performed.
• If future health is unknown or unclear, avoid giving definitive recommendations for future surveillance to allow the flexibility of deciding on the basis of risk and benefit when the time comes.

In comments to this news organization, Dr. Gellad noted that an assessment of patient life expectancy “is not readily accessible at the point of care. These are nuanced decisions that require shared decision-making. Sometimes that is best handled outside the procedure setting.”

Support for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and is a cofounder of Higgs Boson.

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

Most older adults with low-risk surveillance colonoscopy findings and/or limited life expectancy are advised to undergo a repeat procedure in the future, according to a new study.

Among nearly 10,000 Medicare beneficiaries, the likelihood of finding advanced polyps or colorectal cancer (CRC) on surveillance colonoscopy was low. Yet, among patients for whom any follow-up recommendation – either for or against colonoscopy – was available, the vast majority (87%) were advised to return for the procedure in the future, even if their life expectancy was limited or there were no significant findings on their surveillance colonoscopy.

“These findings suggest that recommending against future surveillance colonoscopy in older adults with low-risk colonoscopy findings and/or limited life expectancy should be considered more frequently than is currently practiced,” say Audrey Calderwood, MD, with Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Because of the lack of clear guidance about when to stop recommending colonoscopies to older patients, it is not surprising that physicians recommend surveillance even for patients with low life expectancy, Ziad Gellad, MD, with Duke University Medical Center, Durham, N.C., said in an interview.

“As someone who performs these procedures, I can tell you that it is not easy to tell patients that they are too old to get preventive care, especially patients in whom your only interaction is the procedure itself,” said Dr. Gellad, who wasn’t involved in the study.

The study was published online in JAMA Internal Medicine.
 

Key findings

For older adults, surveillance after prior findings of colon polyps is the most frequent indication for colonoscopy. Data suggest that an estimated 5.6 million adults older than 75 will undergo follow-up colonoscopy annually by 2024.

For older adults with polyps, current guidelines recommend individualized decision-making about surveillance colonoscopy. That includes weighing the potential benefits (identifying and removing meaningful lesions to prevent CRC) against the burdens and potential harms (such as bleeding or perforation).

While most colon polyps are not harmful, a subset of polyps, if allowed to grow, can develop into cancer over 10-15 years. This long biological time line highlights the importance of considering life expectancy in deciding for whom surveillance colonoscopy should be recommended, Dr. Calderwood and colleagues note.

Using data from the New Hampshire Colonoscopy Registry, which is linked with the Medicare claims database, they evaluated surveillance colonoscopy findings and follow-up advice according to severity of findings and patients’ estimated life expectancy for 9,831 adults (mean age, 73; 54% men).

Life expectancy was 10+ years for 57.5% of patients, 5 to less than 10 years for 35%, and less than 5 years for 7.5%.

Overall, 791 patients (8%) were found to have advanced polyps (7.8%) or CRC (0.2%) on surveillance colonoscopy.

Recommendations to stop or continue future colonoscopy were available for 5,281 patients (53.7%). Among them, 4,588 (86.9%) were recommended to return for future colonoscopy, even when there were no significant colonoscopy findings or the patient’s life expectancy was limited.

Compared with life expectancy of less than 5 years, longer life expectancy was associated with advice to return for future colonoscopy regardless of clinical findings, with adjusted odds ratios of 21.5 and 2.7, respectively, for life expectancy of 10 or more years and of 5 to less than 10 years.

Among patients with no significant findings, 95% of those with life expectancy of 10 or more years were recommended to undergo repeat colonoscopy down the road, compared with 58% of those with estimated life expectancy of less than 5 years.

Among patients expected to live 5 to less than 10 years, future repeat colonoscopy was recommended for 75% who had no significant findings, 82% with one or two small polyps, and 88% with multiple polyps, advanced polyps, or CRC.

The recommended time to repeat colonoscopy was greater than life expectancy for 6.6% of patients with less than 5 years of life expectancy and 6% with 5 to less than 10 years of life expectancy.
 

Nuanced decisions

The findings “may help refine decision-making” about the potential benefits and harms of pursuing or stopping surveillance colonoscopy for older adults who have a history of polyps, Dr. Calderwood and colleagues say.

The risk for a colonoscopy complication has been estimated at 26 per 1,000 people, they note. That’s nearly 10 times greater than the potential benefits seen in their study (that is, identification of CRC in 23 of 9,831 people, or about 2.3 per 1,000).

In the study cohort, 10% of patients had comorbid conditions that have been associated with a higher risk for colonoscopy complications. Those with life expectancy of less than 5 years had higher rates of inadequate bowel preparation, which also is associated with increased risk for colonoscopy complications, including perforation.

Dr. Calderwood and colleagues suggest that clinicians use evidence regarding life expectancy and neoplasia progression to modify their recommendations for surveillance colonoscopy for older adults in the following ways:

• If life expectancy is less than 5 years, recommend against surveillance.
• If life expectancy is 5 to less than 10 years and the patient has only low-risk polyps, recommend against surveillance.
• If the patient is healthy with a life expectancy of 10+ years and has recently been found to have advanced polyps, recommend future surveillance colonoscopy, with a caveat that the ultimate decision is dependent on health and priorities at the time the colonoscopy is due to be performed.
• If future health is unknown or unclear, avoid giving definitive recommendations for future surveillance to allow the flexibility of deciding on the basis of risk and benefit when the time comes.

In comments to this news organization, Dr. Gellad noted that an assessment of patient life expectancy “is not readily accessible at the point of care. These are nuanced decisions that require shared decision-making. Sometimes that is best handled outside the procedure setting.”

Support for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and is a cofounder of Higgs Boson.

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

CASE Patient inquires about new technology to detect cancer

A 51-year-old woman (para 2) presents to your clinic for a routine gynecology exam. She is up to date on her screening mammogram and Pap testing. She has her first colonoscopy scheduled for next month. She has a 10-year remote smoking history, but she stopped smoking in her late twenties. Her cousin was recently diagnosed with skin cancer, her father had prostate cancer and is now in remission, and her paternal grandmother died of ovarian cancer. She knows ovarian cancer does not have an effective screening test, and she recently heard on the news about a new blood test that can detect cancer before symptoms start. She would like to know more about this test. Could it replace her next Pap, mammogram, and future colonoscopies? She also wants to know—How can a simple blood test detect cancer?

The power of genomics in cancer care

Since the first human genome was sequenced in 2000, the power of genomics has been evident across many aspects of medicine, including cancer care.¹ Whereas the first human genome to be sequenced took more than 10 years to sequence and cost over  $1 billion, sequencing of your entire genome can now be obtained for less than $400—with results in a week.²

Genomics is now an integral part of cancer care, with results having implications for both cancer risk and prevention as well as more individualized treatment. For example, a healthy 42-year-old patient with a strong family history of breast cancer may undergo genetic testing and discover she has a mutation in the tumor suppression gene BRCA1, which carries a 39% to 58% lifetime risk of ovarian cancer.³ By undergoing a risk-reducing bilateral salpingooophorectomy she will lower her ovarian cancer risk by up to 96%.^4,5 A 67-year-old with a new diagnosis of stage III ovarian cancer and a BRCA2 mutation may be in remission for 5+ years due to her BRCA2 mutation, which makes her eligible for the use of the poly(ADPribose) polymerase (PARP) inhibitor olaparib.⁶ Genetic testing as illustrated above has led to decreased cancer-related mortality and prolonged survival.⁷ However, many women with such germline mutations are faced with difficult choices about surgical risk reduction, with the potential harms of early menopause and quality of life concerns. Having a test that does not just predict cancer risk but in fact quantifies that risk for the individual would greatly help in these decisions. Furthermore, more than 75% of ovarian cancers occur without a germline mutation. 

Advances in genetic testing technology also have led to the ability to obtain genetic information from a simple blood test. For example, cell-free DNA (cfDNA), which is DNA fragments that are normally found to be circulating in the bloodstream, is routinely used as a screening tool for prenatal genetic testing to detect chromosomal abnormalities in the fetus.⁸ This technology relies on analyzing fetal free (non-cellular) DNA that is naturally found circulating in maternal blood. More recently, similar technology using cfDNA has been applied for the screening and characterization of certain cancers.⁹ This powerful technology can detect cancer before symptoms begin—all from a simple blood test, often referred to as a “liquid biopsy.” However, understanding the utility, supporting data, and target population for these tests is important before employing them as part of routine clinical practice. 

Continue to: Current methods of cancer screening are limited...

Current methods of cancer screening are limited 

Cancer is a leading cause of death worldwide, with nearly 10 million cancer-related deaths annually, and it may surpass cardiovascular disease as the leading cause over the course of the century.^10,11 Many cancer deaths are in part due to late-stage diagnosis, when the cancer has already metastasized.¹² Early detection of cancer improves outcomes and survival rates, but it is often difficult to detect early due to the lack of early symptoms with many cancers, which can limit cancer screening and issues with access to care.¹³

 Currently, there are only 5 cancers: cervical, prostate, breast, colon, and lung (for high-risk adults) that are screened for in the general population (see "Cancer screening has helped save countless lives" at the end of this article).¹⁴ The Pap test to screen for cervical cancer, developed in the 1940s, has saved millions of women’s lives and reduced the mortality of cervical cancer by 70%.¹⁵ Coupled with the availability and implementation of the human papillomavirus (HPV) vaccine, cervical cancer rates are decreasing at substantial rates.¹⁶ However, there are no validated screening tests for uterine cancer, the most common gynecologic malignancy in the United States, or ovarian cancer, the most lethal. 

Screening tests for cervical, prostate, breast, colon, and lung cancer have helped save millions of lives; however, these tests also come with high false-positive rates and the potential for overdiagnosis and overtreatment. For example, half of women undergoing mammograms will receive a false-positive result over a 10-year time period,¹⁷ and up to 50% of men undergoing prostate cancer screening have a positive prostate-specific antigen (PSA) test result when they do not actually have prostate cancer.¹⁸ Additionally, the positive predictive value of the current standard-of-care screening tests can be as low as <5%. Most diagnoses of cancer are made from a surgical biopsy, but these types of procedures can be difficult depending on the location or size of the tumor.¹⁹ 

The liquid biopsy. Given the limitations of current cancer screening and diagnostic tests, there is a great need for a more sensitive test that also can detect cancer from multiple organ sites. Liquid biopsy-based biomarkers can include circulating tumor cells, exosomes, microRNAs, and circulating tumor DNA (ctDNA). With advances in next-generation sequencing, ctDNA techniques remain the most promising.²⁰ 

Methylation-based MCED testing: A new way of  cancer screening 

Multi-cancer early detection (MCED) technology was developed to address the need for better cancer screening and has the potential to detect up to 50 cancers with a simple blood test. This new technology opens the possibility for early detection of multiple cancers before symptoms even begin. MCED testing is sometimes referred to as “GRAIL” testing, after the American biotechnology company that developed the first commercially available MCED test, called the Galleri test (Galleri, Menlo Park, California). Although other biotechnology companies are developing similar technology (Exact Sciences, Madison, Wisconsin, and Freenome, South San Francisco, California, for example), this is the first test of its kind available to the public.²¹

The MCED test works by detecting the cfDNA fragments that are released into the blood passively by necrotic or apoptotic cells or secreted actively from tumor cells. The DNA from tumor cells is also known as circulating tumor DNA (ctDNA). CtDNA is found in much lower quantities in the blood stream compared with cfDNA from cells, making it difficult to distinguish a cancer versus a noncancer cell and to determine the tumor site of origin.²²

Through innovation, the first example of detecting cancer through this method in fact came as a surprise result from an abnormal cfDNA test. A pregnant 37-yearold woman had a cfDNA result suggestive of aneuploidy for chromosomes 18 and 13; however, she gave birth to a normal male fetus. Shortly thereafter, a vaginal biopsy confirmed small-cell carcinoma with alterations in chromosomes 18 and 13.²³ GRAIL testing for this patient was subsequently able to optimize their methods of detecting both the presence of cancer cells and the tumor site of origin by utilizing next-generation genomic sequencing and methylation. Their development of a methylation-based assay combined with 46 machine-learning allowed the test to determine, first, if there is cancer present or not, and second, the tissue of origin prediction. It is important to note that these tests are meant to be used in addition to standard-of-care screening tests, not as an alternative, and this is emphasized throughout the company’s website and the medical literature.²⁴ 

Continue to: The process to develop and validate GRAIL’s blood-based cancer screening test...

The process to develop and validate GRAIL’s blood-based cancer screening test includes 4 large clinical trials of more than 180,000 participants, including those with cancer and those without. The Circulating Cell-Free Genome Atlas (CCGA) Study, was a prospective, case-controlled, observational study enrolling approximately 15,000 participants with 3 prespecified sub-studies. The first sub-study developed the machine-learning classifier for both early detection and tumor of origin detection.^25,26 

The highest performing assay from the first sub-study then went on to be further validated in the 2nd and 3rd sub-studies. The 3rd sub-study, published in the Annals of Oncology in 2021 looked at a cohort of 4,077 participants with and without cancer, and found the specificity of cancer signal detection to be 99.5% and the overall sensitivity to be 51.5%, with increasing sensitivity by cancer stage (stage I - 17%, stage II - 40%, stage III - 77%, and stage IV - 90.1%).²⁴ The false-positive rate was low, at 0.7%, and the true positive rate was 88.7%. Notably, the test was able to correctly identify the tumor of origin for 93% of samples.²⁴ The study overall demonstrated high specificity and accuracy of tumor site of origin and supported the use of this blood-based MCED assay. 

The PATHFINDER study was another prospective, multicenter clinical trial that enrolled more than 6,000 participants in the United States. The participants were aged >50 years with or without additional cancer risk factors. The goal of this study was to determine the extent of testing required to achieve diagnosis after a “cancer signal detected” result. The study results found that, when MCED testing was added to the standard-of-care screening, the number of cancers detected doubled when compared with standard cancer screening alone.^27,28 Of the 92 participants with positive cancer signals, 35 were diagnosed with cancer, and 71% of these cancer types did not have standard-ofcare screening. The tumor site of origin was correctly detected in 97% of cases, and there were less than 1% of false positives. Overall, the test led to diagnostic evaluation of 1.4% of patients and a cancer diagnosis in 0.5%. 

Currently, there are 2 ongoing clinical trials to further evaluate the Galleri MCED test. The STRIVE trial that aims to prospectively validate the MCED test in a population of nearly 100,000 women undergoing mammography,²⁹ and the SUMMIT trial,³⁰ which is similarly aiming to validate the test in a group of individuals, half of whom have a significantly elevated risk of lung cancer. 

With the promising results described above, the Galleri test became the first MCED test available for commercial use starting in 2022. It is only available for use in people who are aged 50 and older, have a family history of cancer, or are at an increased risk for cancer (although GRAIL does not elaborate on what constitutes increased risk). However, the Galleri test is only available through prescription—therefore, if interested, patients must ask their health care provider to register with GRAIL and order the test (https://www .galleri.com/hcp/the-galleri-test/ordering). Additionally, the test will cost the patient $949 and is not yet covered by insurances. Currently, several large health care groups such as the United States Department of Veterans Affairs, Cleveland Clinic, and Mercy hospitals have partnered with GRAIL to offer their test to certain patients for use as part of clinical trials. Currently, no MCED test, including the Galleri, is approved by the US Food and  Drug Administration. 

Incorporating MCED testing into clinical practice

The Galleri MCED test has promising potential to make multi-cancer screening feasible and obtainable, which could ultimately reduce late-stage cancer diagnosis and decrease mortality from all cancers. The compelling data from large cohorts and numerous clinical trials demonstrate its accuracy, reliability, reproducibility, and specificity. It can detect up to 50 different types of cancers, including cancers that affect our gynecologic patients, including breast, cervical, ovarian, and uterine. Additionally, its novel methylation-based assay accurately identifies the tumor site of origin in 97% of cases.²⁸ Ongoing and future clinical trials will continue to validate and refine these methods and improve the sensitivity and positive-predictive value of this assay. As mentioned, although it has been incorporated into various large health care systems, it is not FDA approved and has not been validated in the general population. Additionally, it should not be used as a replacement for recommended screening. 

CASE Resolved

The patient is eligible for the Galleri MCED test if ordered by her physician. However, she will need to pay for the test out-of-pocket. Due to her family history, she should consider germline genetic testing (either for herself, or if possible, for her father, who should meet criteria based on his prostate cancer).³ Panel testing for germline mutations has become much more accessible, and until MCED testing is ready for prime time, it remains one of the best ways to predict and prevent cancers. Additionally, she should continue to undergo routine screening for cervical, breast, and colon cancer as indicated. ●

CASE Patient inquires about new technology to detect cancer

A 51-year-old woman (para 2) presents to your clinic for a routine gynecology exam. She is up to date on her screening mammogram and Pap testing. She has her first colonoscopy scheduled for next month. She has a 10-year remote smoking history, but she stopped smoking in her late twenties. Her cousin was recently diagnosed with skin cancer, her father had prostate cancer and is now in remission, and her paternal grandmother died of ovarian cancer. She knows ovarian cancer does not have an effective screening test, and she recently heard on the news about a new blood test that can detect cancer before symptoms start. She would like to know more about this test. Could it replace her next Pap, mammogram, and future colonoscopies? She also wants to know—How can a simple blood test detect cancer?

The power of genomics in cancer care

Since the first human genome was sequenced in 2000, the power of genomics has been evident across many aspects of medicine, including cancer care.¹ Whereas the first human genome to be sequenced took more than 10 years to sequence and cost over  $1 billion, sequencing of your entire genome can now be obtained for less than $400—with results in a week.²

Genomics is now an integral part of cancer care, with results having implications for both cancer risk and prevention as well as more individualized treatment. For example, a healthy 42-year-old patient with a strong family history of breast cancer may undergo genetic testing and discover she has a mutation in the tumor suppression gene BRCA1, which carries a 39% to 58% lifetime risk of ovarian cancer.³ By undergoing a risk-reducing bilateral salpingooophorectomy she will lower her ovarian cancer risk by up to 96%.^4,5 A 67-year-old with a new diagnosis of stage III ovarian cancer and a BRCA2 mutation may be in remission for 5+ years due to her BRCA2 mutation, which makes her eligible for the use of the poly(ADPribose) polymerase (PARP) inhibitor olaparib.⁶ Genetic testing as illustrated above has led to decreased cancer-related mortality and prolonged survival.⁷ However, many women with such germline mutations are faced with difficult choices about surgical risk reduction, with the potential harms of early menopause and quality of life concerns. Having a test that does not just predict cancer risk but in fact quantifies that risk for the individual would greatly help in these decisions. Furthermore, more than 75% of ovarian cancers occur without a germline mutation. 

Advances in genetic testing technology also have led to the ability to obtain genetic information from a simple blood test. For example, cell-free DNA (cfDNA), which is DNA fragments that are normally found to be circulating in the bloodstream, is routinely used as a screening tool for prenatal genetic testing to detect chromosomal abnormalities in the fetus.⁸ This technology relies on analyzing fetal free (non-cellular) DNA that is naturally found circulating in maternal blood. More recently, similar technology using cfDNA has been applied for the screening and characterization of certain cancers.⁹ This powerful technology can detect cancer before symptoms begin—all from a simple blood test, often referred to as a “liquid biopsy.” However, understanding the utility, supporting data, and target population for these tests is important before employing them as part of routine clinical practice. 

Continue to: Current methods of cancer screening are limited...

Current methods of cancer screening are limited 

Cancer is a leading cause of death worldwide, with nearly 10 million cancer-related deaths annually, and it may surpass cardiovascular disease as the leading cause over the course of the century.^10,11 Many cancer deaths are in part due to late-stage diagnosis, when the cancer has already metastasized.¹² Early detection of cancer improves outcomes and survival rates, but it is often difficult to detect early due to the lack of early symptoms with many cancers, which can limit cancer screening and issues with access to care.¹³

 Currently, there are only 5 cancers: cervical, prostate, breast, colon, and lung (for high-risk adults) that are screened for in the general population (see "Cancer screening has helped save countless lives" at the end of this article).¹⁴ The Pap test to screen for cervical cancer, developed in the 1940s, has saved millions of women’s lives and reduced the mortality of cervical cancer by 70%.¹⁵ Coupled with the availability and implementation of the human papillomavirus (HPV) vaccine, cervical cancer rates are decreasing at substantial rates.¹⁶ However, there are no validated screening tests for uterine cancer, the most common gynecologic malignancy in the United States, or ovarian cancer, the most lethal. 

Screening tests for cervical, prostate, breast, colon, and lung cancer have helped save millions of lives; however, these tests also come with high false-positive rates and the potential for overdiagnosis and overtreatment. For example, half of women undergoing mammograms will receive a false-positive result over a 10-year time period,¹⁷ and up to 50% of men undergoing prostate cancer screening have a positive prostate-specific antigen (PSA) test result when they do not actually have prostate cancer.¹⁸ Additionally, the positive predictive value of the current standard-of-care screening tests can be as low as <5%. Most diagnoses of cancer are made from a surgical biopsy, but these types of procedures can be difficult depending on the location or size of the tumor.¹⁹ 

The liquid biopsy. Given the limitations of current cancer screening and diagnostic tests, there is a great need for a more sensitive test that also can detect cancer from multiple organ sites. Liquid biopsy-based biomarkers can include circulating tumor cells, exosomes, microRNAs, and circulating tumor DNA (ctDNA). With advances in next-generation sequencing, ctDNA techniques remain the most promising.²⁰ 

Methylation-based MCED testing: A new way of  cancer screening 

Multi-cancer early detection (MCED) technology was developed to address the need for better cancer screening and has the potential to detect up to 50 cancers with a simple blood test. This new technology opens the possibility for early detection of multiple cancers before symptoms even begin. MCED testing is sometimes referred to as “GRAIL” testing, after the American biotechnology company that developed the first commercially available MCED test, called the Galleri test (Galleri, Menlo Park, California). Although other biotechnology companies are developing similar technology (Exact Sciences, Madison, Wisconsin, and Freenome, South San Francisco, California, for example), this is the first test of its kind available to the public.²¹

The MCED test works by detecting the cfDNA fragments that are released into the blood passively by necrotic or apoptotic cells or secreted actively from tumor cells. The DNA from tumor cells is also known as circulating tumor DNA (ctDNA). CtDNA is found in much lower quantities in the blood stream compared with cfDNA from cells, making it difficult to distinguish a cancer versus a noncancer cell and to determine the tumor site of origin.²²

Through innovation, the first example of detecting cancer through this method in fact came as a surprise result from an abnormal cfDNA test. A pregnant 37-yearold woman had a cfDNA result suggestive of aneuploidy for chromosomes 18 and 13; however, she gave birth to a normal male fetus. Shortly thereafter, a vaginal biopsy confirmed small-cell carcinoma with alterations in chromosomes 18 and 13.²³ GRAIL testing for this patient was subsequently able to optimize their methods of detecting both the presence of cancer cells and the tumor site of origin by utilizing next-generation genomic sequencing and methylation. Their development of a methylation-based assay combined with 46 machine-learning allowed the test to determine, first, if there is cancer present or not, and second, the tissue of origin prediction. It is important to note that these tests are meant to be used in addition to standard-of-care screening tests, not as an alternative, and this is emphasized throughout the company’s website and the medical literature.²⁴ 

Continue to: The process to develop and validate GRAIL’s blood-based cancer screening test...

The process to develop and validate GRAIL’s blood-based cancer screening test includes 4 large clinical trials of more than 180,000 participants, including those with cancer and those without. The Circulating Cell-Free Genome Atlas (CCGA) Study, was a prospective, case-controlled, observational study enrolling approximately 15,000 participants with 3 prespecified sub-studies. The first sub-study developed the machine-learning classifier for both early detection and tumor of origin detection.^25,26 

The highest performing assay from the first sub-study then went on to be further validated in the 2nd and 3rd sub-studies. The 3rd sub-study, published in the Annals of Oncology in 2021 looked at a cohort of 4,077 participants with and without cancer, and found the specificity of cancer signal detection to be 99.5% and the overall sensitivity to be 51.5%, with increasing sensitivity by cancer stage (stage I - 17%, stage II - 40%, stage III - 77%, and stage IV - 90.1%).²⁴ The false-positive rate was low, at 0.7%, and the true positive rate was 88.7%. Notably, the test was able to correctly identify the tumor of origin for 93% of samples.²⁴ The study overall demonstrated high specificity and accuracy of tumor site of origin and supported the use of this blood-based MCED assay. 

The PATHFINDER study was another prospective, multicenter clinical trial that enrolled more than 6,000 participants in the United States. The participants were aged >50 years with or without additional cancer risk factors. The goal of this study was to determine the extent of testing required to achieve diagnosis after a “cancer signal detected” result. The study results found that, when MCED testing was added to the standard-of-care screening, the number of cancers detected doubled when compared with standard cancer screening alone.^27,28 Of the 92 participants with positive cancer signals, 35 were diagnosed with cancer, and 71% of these cancer types did not have standard-ofcare screening. The tumor site of origin was correctly detected in 97% of cases, and there were less than 1% of false positives. Overall, the test led to diagnostic evaluation of 1.4% of patients and a cancer diagnosis in 0.5%. 

Currently, there are 2 ongoing clinical trials to further evaluate the Galleri MCED test. The STRIVE trial that aims to prospectively validate the MCED test in a population of nearly 100,000 women undergoing mammography,²⁹ and the SUMMIT trial,³⁰ which is similarly aiming to validate the test in a group of individuals, half of whom have a significantly elevated risk of lung cancer. 

With the promising results described above, the Galleri test became the first MCED test available for commercial use starting in 2022. It is only available for use in people who are aged 50 and older, have a family history of cancer, or are at an increased risk for cancer (although GRAIL does not elaborate on what constitutes increased risk). However, the Galleri test is only available through prescription—therefore, if interested, patients must ask their health care provider to register with GRAIL and order the test (https://www .galleri.com/hcp/the-galleri-test/ordering). Additionally, the test will cost the patient $949 and is not yet covered by insurances. Currently, several large health care groups such as the United States Department of Veterans Affairs, Cleveland Clinic, and Mercy hospitals have partnered with GRAIL to offer their test to certain patients for use as part of clinical trials. Currently, no MCED test, including the Galleri, is approved by the US Food and  Drug Administration. 

Incorporating MCED testing into clinical practice

The Galleri MCED test has promising potential to make multi-cancer screening feasible and obtainable, which could ultimately reduce late-stage cancer diagnosis and decrease mortality from all cancers. The compelling data from large cohorts and numerous clinical trials demonstrate its accuracy, reliability, reproducibility, and specificity. It can detect up to 50 different types of cancers, including cancers that affect our gynecologic patients, including breast, cervical, ovarian, and uterine. Additionally, its novel methylation-based assay accurately identifies the tumor site of origin in 97% of cases.²⁸ Ongoing and future clinical trials will continue to validate and refine these methods and improve the sensitivity and positive-predictive value of this assay. As mentioned, although it has been incorporated into various large health care systems, it is not FDA approved and has not been validated in the general population. Additionally, it should not be used as a replacement for recommended screening. 

CASE Resolved

The patient is eligible for the Galleri MCED test if ordered by her physician. However, she will need to pay for the test out-of-pocket. Due to her family history, she should consider germline genetic testing (either for herself, or if possible, for her father, who should meet criteria based on his prostate cancer).³ Panel testing for germline mutations has become much more accessible, and until MCED testing is ready for prime time, it remains one of the best ways to predict and prevent cancers. Additionally, she should continue to undergo routine screening for cervical, breast, and colon cancer as indicated. ●

CASE Patient inquires about new technology to detect cancer

A 51-year-old woman (para 2) presents to your clinic for a routine gynecology exam. She is up to date on her screening mammogram and Pap testing. She has her first colonoscopy scheduled for next month. She has a 10-year remote smoking history, but she stopped smoking in her late twenties. Her cousin was recently diagnosed with skin cancer, her father had prostate cancer and is now in remission, and her paternal grandmother died of ovarian cancer. She knows ovarian cancer does not have an effective screening test, and she recently heard on the news about a new blood test that can detect cancer before symptoms start. She would like to know more about this test. Could it replace her next Pap, mammogram, and future colonoscopies? She also wants to know—How can a simple blood test detect cancer?

The power of genomics in cancer care

Since the first human genome was sequenced in 2000, the power of genomics has been evident across many aspects of medicine, including cancer care.¹ Whereas the first human genome to be sequenced took more than 10 years to sequence and cost over  $1 billion, sequencing of your entire genome can now be obtained for less than $400—with results in a week.²

Genomics is now an integral part of cancer care, with results having implications for both cancer risk and prevention as well as more individualized treatment. For example, a healthy 42-year-old patient with a strong family history of breast cancer may undergo genetic testing and discover she has a mutation in the tumor suppression gene BRCA1, which carries a 39% to 58% lifetime risk of ovarian cancer.³ By undergoing a risk-reducing bilateral salpingooophorectomy she will lower her ovarian cancer risk by up to 96%.^4,5 A 67-year-old with a new diagnosis of stage III ovarian cancer and a BRCA2 mutation may be in remission for 5+ years due to her BRCA2 mutation, which makes her eligible for the use of the poly(ADPribose) polymerase (PARP) inhibitor olaparib.⁶ Genetic testing as illustrated above has led to decreased cancer-related mortality and prolonged survival.⁷ However, many women with such germline mutations are faced with difficult choices about surgical risk reduction, with the potential harms of early menopause and quality of life concerns. Having a test that does not just predict cancer risk but in fact quantifies that risk for the individual would greatly help in these decisions. Furthermore, more than 75% of ovarian cancers occur without a germline mutation. 

Advances in genetic testing technology also have led to the ability to obtain genetic information from a simple blood test. For example, cell-free DNA (cfDNA), which is DNA fragments that are normally found to be circulating in the bloodstream, is routinely used as a screening tool for prenatal genetic testing to detect chromosomal abnormalities in the fetus.⁸ This technology relies on analyzing fetal free (non-cellular) DNA that is naturally found circulating in maternal blood. More recently, similar technology using cfDNA has been applied for the screening and characterization of certain cancers.⁹ This powerful technology can detect cancer before symptoms begin—all from a simple blood test, often referred to as a “liquid biopsy.” However, understanding the utility, supporting data, and target population for these tests is important before employing them as part of routine clinical practice. 

Continue to: Current methods of cancer screening are limited...

Current methods of cancer screening are limited 

Cancer is a leading cause of death worldwide, with nearly 10 million cancer-related deaths annually, and it may surpass cardiovascular disease as the leading cause over the course of the century.^10,11 Many cancer deaths are in part due to late-stage diagnosis, when the cancer has already metastasized.¹² Early detection of cancer improves outcomes and survival rates, but it is often difficult to detect early due to the lack of early symptoms with many cancers, which can limit cancer screening and issues with access to care.¹³

 Currently, there are only 5 cancers: cervical, prostate, breast, colon, and lung (for high-risk adults) that are screened for in the general population (see "Cancer screening has helped save countless lives" at the end of this article).¹⁴ The Pap test to screen for cervical cancer, developed in the 1940s, has saved millions of women’s lives and reduced the mortality of cervical cancer by 70%.¹⁵ Coupled with the availability and implementation of the human papillomavirus (HPV) vaccine, cervical cancer rates are decreasing at substantial rates.¹⁶ However, there are no validated screening tests for uterine cancer, the most common gynecologic malignancy in the United States, or ovarian cancer, the most lethal. 

Screening tests for cervical, prostate, breast, colon, and lung cancer have helped save millions of lives; however, these tests also come with high false-positive rates and the potential for overdiagnosis and overtreatment. For example, half of women undergoing mammograms will receive a false-positive result over a 10-year time period,¹⁷ and up to 50% of men undergoing prostate cancer screening have a positive prostate-specific antigen (PSA) test result when they do not actually have prostate cancer.¹⁸ Additionally, the positive predictive value of the current standard-of-care screening tests can be as low as <5%. Most diagnoses of cancer are made from a surgical biopsy, but these types of procedures can be difficult depending on the location or size of the tumor.¹⁹ 

The liquid biopsy. Given the limitations of current cancer screening and diagnostic tests, there is a great need for a more sensitive test that also can detect cancer from multiple organ sites. Liquid biopsy-based biomarkers can include circulating tumor cells, exosomes, microRNAs, and circulating tumor DNA (ctDNA). With advances in next-generation sequencing, ctDNA techniques remain the most promising.²⁰ 

Methylation-based MCED testing: A new way of  cancer screening 

Multi-cancer early detection (MCED) technology was developed to address the need for better cancer screening and has the potential to detect up to 50 cancers with a simple blood test. This new technology opens the possibility for early detection of multiple cancers before symptoms even begin. MCED testing is sometimes referred to as “GRAIL” testing, after the American biotechnology company that developed the first commercially available MCED test, called the Galleri test (Galleri, Menlo Park, California). Although other biotechnology companies are developing similar technology (Exact Sciences, Madison, Wisconsin, and Freenome, South San Francisco, California, for example), this is the first test of its kind available to the public.²¹

The MCED test works by detecting the cfDNA fragments that are released into the blood passively by necrotic or apoptotic cells or secreted actively from tumor cells. The DNA from tumor cells is also known as circulating tumor DNA (ctDNA). CtDNA is found in much lower quantities in the blood stream compared with cfDNA from cells, making it difficult to distinguish a cancer versus a noncancer cell and to determine the tumor site of origin.²²

Through innovation, the first example of detecting cancer through this method in fact came as a surprise result from an abnormal cfDNA test. A pregnant 37-yearold woman had a cfDNA result suggestive of aneuploidy for chromosomes 18 and 13; however, she gave birth to a normal male fetus. Shortly thereafter, a vaginal biopsy confirmed small-cell carcinoma with alterations in chromosomes 18 and 13.²³ GRAIL testing for this patient was subsequently able to optimize their methods of detecting both the presence of cancer cells and the tumor site of origin by utilizing next-generation genomic sequencing and methylation. Their development of a methylation-based assay combined with 46 machine-learning allowed the test to determine, first, if there is cancer present or not, and second, the tissue of origin prediction. It is important to note that these tests are meant to be used in addition to standard-of-care screening tests, not as an alternative, and this is emphasized throughout the company’s website and the medical literature.²⁴ 

Continue to: The process to develop and validate GRAIL’s blood-based cancer screening test...

The process to develop and validate GRAIL’s blood-based cancer screening test includes 4 large clinical trials of more than 180,000 participants, including those with cancer and those without. The Circulating Cell-Free Genome Atlas (CCGA) Study, was a prospective, case-controlled, observational study enrolling approximately 15,000 participants with 3 prespecified sub-studies. The first sub-study developed the machine-learning classifier for both early detection and tumor of origin detection.^25,26 

The highest performing assay from the first sub-study then went on to be further validated in the 2nd and 3rd sub-studies. The 3rd sub-study, published in the Annals of Oncology in 2021 looked at a cohort of 4,077 participants with and without cancer, and found the specificity of cancer signal detection to be 99.5% and the overall sensitivity to be 51.5%, with increasing sensitivity by cancer stage (stage I - 17%, stage II - 40%, stage III - 77%, and stage IV - 90.1%).²⁴ The false-positive rate was low, at 0.7%, and the true positive rate was 88.7%. Notably, the test was able to correctly identify the tumor of origin for 93% of samples.²⁴ The study overall demonstrated high specificity and accuracy of tumor site of origin and supported the use of this blood-based MCED assay. 

The PATHFINDER study was another prospective, multicenter clinical trial that enrolled more than 6,000 participants in the United States. The participants were aged >50 years with or without additional cancer risk factors. The goal of this study was to determine the extent of testing required to achieve diagnosis after a “cancer signal detected” result. The study results found that, when MCED testing was added to the standard-of-care screening, the number of cancers detected doubled when compared with standard cancer screening alone.^27,28 Of the 92 participants with positive cancer signals, 35 were diagnosed with cancer, and 71% of these cancer types did not have standard-ofcare screening. The tumor site of origin was correctly detected in 97% of cases, and there were less than 1% of false positives. Overall, the test led to diagnostic evaluation of 1.4% of patients and a cancer diagnosis in 0.5%. 

Currently, there are 2 ongoing clinical trials to further evaluate the Galleri MCED test. The STRIVE trial that aims to prospectively validate the MCED test in a population of nearly 100,000 women undergoing mammography,²⁹ and the SUMMIT trial,³⁰ which is similarly aiming to validate the test in a group of individuals, half of whom have a significantly elevated risk of lung cancer. 

With the promising results described above, the Galleri test became the first MCED test available for commercial use starting in 2022. It is only available for use in people who are aged 50 and older, have a family history of cancer, or are at an increased risk for cancer (although GRAIL does not elaborate on what constitutes increased risk). However, the Galleri test is only available through prescription—therefore, if interested, patients must ask their health care provider to register with GRAIL and order the test (https://www .galleri.com/hcp/the-galleri-test/ordering). Additionally, the test will cost the patient $949 and is not yet covered by insurances. Currently, several large health care groups such as the United States Department of Veterans Affairs, Cleveland Clinic, and Mercy hospitals have partnered with GRAIL to offer their test to certain patients for use as part of clinical trials. Currently, no MCED test, including the Galleri, is approved by the US Food and  Drug Administration. 

Incorporating MCED testing into clinical practice

The Galleri MCED test has promising potential to make multi-cancer screening feasible and obtainable, which could ultimately reduce late-stage cancer diagnosis and decrease mortality from all cancers. The compelling data from large cohorts and numerous clinical trials demonstrate its accuracy, reliability, reproducibility, and specificity. It can detect up to 50 different types of cancers, including cancers that affect our gynecologic patients, including breast, cervical, ovarian, and uterine. Additionally, its novel methylation-based assay accurately identifies the tumor site of origin in 97% of cases.²⁸ Ongoing and future clinical trials will continue to validate and refine these methods and improve the sensitivity and positive-predictive value of this assay. As mentioned, although it has been incorporated into various large health care systems, it is not FDA approved and has not been validated in the general population. Additionally, it should not be used as a replacement for recommended screening. 

CASE Resolved

The patient is eligible for the Galleri MCED test if ordered by her physician. However, she will need to pay for the test out-of-pocket. Due to her family history, she should consider germline genetic testing (either for herself, or if possible, for her father, who should meet criteria based on his prostate cancer).³ Panel testing for germline mutations has become much more accessible, and until MCED testing is ready for prime time, it remains one of the best ways to predict and prevent cancers. Additionally, she should continue to undergo routine screening for cervical, breast, and colon cancer as indicated. ●

REVIEW

FEMCERV^®: Well-designed technology that can minimize patient discomfort

The FemCerv^® Endocervical Sampler, developed by Femasys, Inc (Suwanee, Georgia) expands options for colposcopy biopsy.


Background. In the United States, approximately 3 million women per year undergo colposcopic evaluation to work-up abnormal screening cytology. While some controversy exists regarding the exact role of endocervical curettage (ECC) within each age group and clinical situation, it is nonetheless an important component of the colposcopy-biopsy examination in many cases. For over a century, the 3 mm metal endocervical curette has been the primary tool employed to obtain the tissue sample from the endocervical canal. Unfortunately, sharp curettage with a metal curette can have inadequate sampling rates as high as 14%,¹ it runs the risk of ectocervical contamination, and it is painful, with almost half the participants in one study rating the procedural pain 3 ̶ 5 out of 8 on a VAS scale.² So, maybe there is a better way.


Design/Functionality. According to Femasys, the FemCerv^® Endocervical Sampler was designed to be the better way of performing an endocervical curettage. FemCerv is a single-use sterile device that comes in a standard 13 F size as well as an 11 F size for the narrower/stenotic os. In truth, at first glance it looks pretty complicated compared with a Kevorkian curette or an endocervical brush. The user end has a handle with a rotatable knob that transitions to a shaft with a flange at the end right before the sampling mechanism. To use the device, the sampling end is inserted into the endocervical canal up to the flange. The knob on the handle is then turned clockwise to open the sheath, thereby exposing sharp rigid plastic edges. The device is then rotated 360° clockwise and then 360° counterclockwise to “curette” the endocervical canal. Finally, the knob on the handle is turned counterclockwise to close the sheath and the device is removed. The specimen is then transferred to a standard vial for processing.

In my experience with its use, it actually exceeded my expectations. The device was easy to use, and the specimens were more than adequate. Truth be told, I came into the trial with a negative mindset having already convinced myself that this device was a waste of money given that doing an ECC with traditional methods is so straightforward. What I had not anticipated was the complete lack of patient discomfort when I used the FemCerv compared with a Kevorkian device.

Innovation. From an innovation standpoint, FemCerv is not super-disruptive technology, but it is well designed and pretty clever in that the opening and closing sheath prevents ectocervical cellular contamination, and the rotational sampling, rather than in-and-out sampling, does dramatically reduce the patient discomfort.


Summary. As I previously noted, before trying it, I did not anticipate liking FemCerv as much as I did. Does it add some non-reimbursable cost to a relatively low-reimbursing procedure? Absolutely. But it is not too expensive and, for me, making a painful procedure relatively painless is good value every time. I think all our patients would agree.

For more information, visit https://femasys.com/.

UPDATE

Hologic, Inc. announces that they received the following 2022 IMV ServiceTrak^TM Awards for Mammography: Best Service, Best Customer Satisfaction, and Best System Performance. In addition, Hologic announces that their Affirm Contrast Biopsy software is commercially available in the United States. Tissue samples may be targeted and acquired using the Affirm Contrast Biopsy software from lesions identified using Hologic’s I-View Contrast Enhanced Mammography software. The latter software allows health care facilities an alternative to breast magnetic resonance imaging, which is used as supplemental imaging to mammography and/or ultrasonography.

For more information, visit https://www.hologic.com/

REVIEW

FEMCERV^®: Well-designed technology that can minimize patient discomfort

The FemCerv^® Endocervical Sampler, developed by Femasys, Inc (Suwanee, Georgia) expands options for colposcopy biopsy.


Background. In the United States, approximately 3 million women per year undergo colposcopic evaluation to work-up abnormal screening cytology. While some controversy exists regarding the exact role of endocervical curettage (ECC) within each age group and clinical situation, it is nonetheless an important component of the colposcopy-biopsy examination in many cases. For over a century, the 3 mm metal endocervical curette has been the primary tool employed to obtain the tissue sample from the endocervical canal. Unfortunately, sharp curettage with a metal curette can have inadequate sampling rates as high as 14%,¹ it runs the risk of ectocervical contamination, and it is painful, with almost half the participants in one study rating the procedural pain 3 ̶ 5 out of 8 on a VAS scale.² So, maybe there is a better way.


Design/Functionality. According to Femasys, the FemCerv^® Endocervical Sampler was designed to be the better way of performing an endocervical curettage. FemCerv is a single-use sterile device that comes in a standard 13 F size as well as an 11 F size for the narrower/stenotic os. In truth, at first glance it looks pretty complicated compared with a Kevorkian curette or an endocervical brush. The user end has a handle with a rotatable knob that transitions to a shaft with a flange at the end right before the sampling mechanism. To use the device, the sampling end is inserted into the endocervical canal up to the flange. The knob on the handle is then turned clockwise to open the sheath, thereby exposing sharp rigid plastic edges. The device is then rotated 360° clockwise and then 360° counterclockwise to “curette” the endocervical canal. Finally, the knob on the handle is turned counterclockwise to close the sheath and the device is removed. The specimen is then transferred to a standard vial for processing.

In my experience with its use, it actually exceeded my expectations. The device was easy to use, and the specimens were more than adequate. Truth be told, I came into the trial with a negative mindset having already convinced myself that this device was a waste of money given that doing an ECC with traditional methods is so straightforward. What I had not anticipated was the complete lack of patient discomfort when I used the FemCerv compared with a Kevorkian device.

Innovation. From an innovation standpoint, FemCerv is not super-disruptive technology, but it is well designed and pretty clever in that the opening and closing sheath prevents ectocervical cellular contamination, and the rotational sampling, rather than in-and-out sampling, does dramatically reduce the patient discomfort.


Summary. As I previously noted, before trying it, I did not anticipate liking FemCerv as much as I did. Does it add some non-reimbursable cost to a relatively low-reimbursing procedure? Absolutely. But it is not too expensive and, for me, making a painful procedure relatively painless is good value every time. I think all our patients would agree.

For more information, visit https://femasys.com/.

UPDATE

Hologic, Inc. announces that they received the following 2022 IMV ServiceTrak^TM Awards for Mammography: Best Service, Best Customer Satisfaction, and Best System Performance. In addition, Hologic announces that their Affirm Contrast Biopsy software is commercially available in the United States. Tissue samples may be targeted and acquired using the Affirm Contrast Biopsy software from lesions identified using Hologic’s I-View Contrast Enhanced Mammography software. The latter software allows health care facilities an alternative to breast magnetic resonance imaging, which is used as supplemental imaging to mammography and/or ultrasonography.

For more information, visit https://www.hologic.com/

REVIEW

FEMCERV^®: Well-designed technology that can minimize patient discomfort

The FemCerv^® Endocervical Sampler, developed by Femasys, Inc (Suwanee, Georgia) expands options for colposcopy biopsy.


Background. In the United States, approximately 3 million women per year undergo colposcopic evaluation to work-up abnormal screening cytology. While some controversy exists regarding the exact role of endocervical curettage (ECC) within each age group and clinical situation, it is nonetheless an important component of the colposcopy-biopsy examination in many cases. For over a century, the 3 mm metal endocervical curette has been the primary tool employed to obtain the tissue sample from the endocervical canal. Unfortunately, sharp curettage with a metal curette can have inadequate sampling rates as high as 14%,¹ it runs the risk of ectocervical contamination, and it is painful, with almost half the participants in one study rating the procedural pain 3 ̶ 5 out of 8 on a VAS scale.² So, maybe there is a better way.


Design/Functionality. According to Femasys, the FemCerv^® Endocervical Sampler was designed to be the better way of performing an endocervical curettage. FemCerv is a single-use sterile device that comes in a standard 13 F size as well as an 11 F size for the narrower/stenotic os. In truth, at first glance it looks pretty complicated compared with a Kevorkian curette or an endocervical brush. The user end has a handle with a rotatable knob that transitions to a shaft with a flange at the end right before the sampling mechanism. To use the device, the sampling end is inserted into the endocervical canal up to the flange. The knob on the handle is then turned clockwise to open the sheath, thereby exposing sharp rigid plastic edges. The device is then rotated 360° clockwise and then 360° counterclockwise to “curette” the endocervical canal. Finally, the knob on the handle is turned counterclockwise to close the sheath and the device is removed. The specimen is then transferred to a standard vial for processing.

In my experience with its use, it actually exceeded my expectations. The device was easy to use, and the specimens were more than adequate. Truth be told, I came into the trial with a negative mindset having already convinced myself that this device was a waste of money given that doing an ECC with traditional methods is so straightforward. What I had not anticipated was the complete lack of patient discomfort when I used the FemCerv compared with a Kevorkian device.

Innovation. From an innovation standpoint, FemCerv is not super-disruptive technology, but it is well designed and pretty clever in that the opening and closing sheath prevents ectocervical cellular contamination, and the rotational sampling, rather than in-and-out sampling, does dramatically reduce the patient discomfort.


Summary. As I previously noted, before trying it, I did not anticipate liking FemCerv as much as I did. Does it add some non-reimbursable cost to a relatively low-reimbursing procedure? Absolutely. But it is not too expensive and, for me, making a painful procedure relatively painless is good value every time. I think all our patients would agree.

For more information, visit https://femasys.com/.

UPDATE

Hologic, Inc. announces that they received the following 2022 IMV ServiceTrak^TM Awards for Mammography: Best Service, Best Customer Satisfaction, and Best System Performance. In addition, Hologic announces that their Affirm Contrast Biopsy software is commercially available in the United States. Tissue samples may be targeted and acquired using the Affirm Contrast Biopsy software from lesions identified using Hologic’s I-View Contrast Enhanced Mammography software. The latter software allows health care facilities an alternative to breast magnetic resonance imaging, which is used as supplemental imaging to mammography and/or ultrasonography.

For more information, visit https://www.hologic.com/

In June 2022, the US Supreme Court’s decision in Dobbs v Jackson Women’s Health Organization removed federal protections for abortion that previously had been codified in Roe v Wade. Since this removal, most abortions have been banned in at least 13 states, and about half of states are expected to attempt to ban or heavily restrict abortion.^1,2 These laws banning abortion are having effects on patient care far beyond abortion, leading to uncertainty and fear among providers and denied or delayed care for patients.^3,4 It is critical that research documents the harmful effects of this policy change.

Patients that are pregnant with fetuses with severe malformations have had to travel long distances to other states to obtain care.⁵ Others have faced delays in obtaining treatment for ectopic pregnancy, miscarriage, and even for other conditions that use medications that could potentially cause an abortion.^6,7 These cases have the potential to result in serious harm or death of the patient with altered care. There is a published report from Texas showing how the change in practice due to the 6-week abortion ban imposed in 2021 was associated with a doubling of severe morbidity for patients presenting with preterm premature rupture of membranes and other complications before 22 weeks’ gestation.⁸

While these cases have been highlighted in the media, there has not been a resource that comprehensively documents the changes in care that clinicians have been forced to make because of abortion bans as well as the consequences for their patients’ health. The media also may not be the most desirable platform for sharing cases of substandard care if providers feel their confidentiality may be breached as they are told by their employers to avoid speaking with reporters.⁹ Bearing this in mind, our team of researchers at Advancing New Standards in Reproductive Health at the University of California San Francisco and the Texas Policy Evaluation Project at the University of Texas at Austin has launched a project aiming to collect stories of poor quality care post-Roe from health care professionals across the United States. The aim of the study is to document examples of the challenges in patient care that have arisen since the Dobbs decision.

The study website CarePostRoe.com was launched in October 2022 to collect narratives from health care providers who participated in the care of a patient whose management was different from the usual standard due to a need to comply with new restrictions on abortion since the Dobbs decision. These providers can include physicians, nurses, nurse practitioners, midwives, physician assistants, social workers, pharmacists, psychologists, or other allied health professionals. Clinicians can share information about a case through a brief survey linked on the website that will allow them to either submit a written narrative or a voice memo. The submissions are anonymous, and providers are not asked to submit any protected health information. If the submitter would like to share more information about the case via telephone interview, they will be taken to a separate survey which is not linked to the narrative submission to give contact information to participate in an interview.

Since October, more than 40 cases have been submitted that document patient cases from over half of the states with abortion bans. Clinicians describe pregnant patients with severe fetal malformations who have had to overcome financial and logistical barriers to travel to access abortion care. Several cases of patients with cesarean scar ectopic pregnancies have been submitted, including cases that are being followed expectantly, which is inconsistent with the standard of care.¹⁰ We also have received several submissions about cases of preterm premature rupture of membranes in the second trimester where the patient was sent home and presented several days later with a severe infection requiring management in the intensive care unit. Cases of early pregnancy loss that could have been treated safely and routinely also were delayed, increasing the risk to patients who, in addition to receiving substandard medical care, had the trauma of fearing they could be prosecuted for receiving treatment.

We hope these data will be useful to document the impact of the Court’s decision and to improve patient care as health care institutions work to update their policies and protocols to reduce delays in care in the face of legal ambiguities. If you have been involved in such a case since June 2022, including caring for a patient who traveled from another state, please consider submitting it at CarePostRoe.com, and please spread the word through your networks. ●

In June 2022, the US Supreme Court’s decision in Dobbs v Jackson Women’s Health Organization removed federal protections for abortion that previously had been codified in Roe v Wade. Since this removal, most abortions have been banned in at least 13 states, and about half of states are expected to attempt to ban or heavily restrict abortion.^1,2 These laws banning abortion are having effects on patient care far beyond abortion, leading to uncertainty and fear among providers and denied or delayed care for patients.^3,4 It is critical that research documents the harmful effects of this policy change.

Patients that are pregnant with fetuses with severe malformations have had to travel long distances to other states to obtain care.⁵ Others have faced delays in obtaining treatment for ectopic pregnancy, miscarriage, and even for other conditions that use medications that could potentially cause an abortion.^6,7 These cases have the potential to result in serious harm or death of the patient with altered care. There is a published report from Texas showing how the change in practice due to the 6-week abortion ban imposed in 2021 was associated with a doubling of severe morbidity for patients presenting with preterm premature rupture of membranes and other complications before 22 weeks’ gestation.⁸

While these cases have been highlighted in the media, there has not been a resource that comprehensively documents the changes in care that clinicians have been forced to make because of abortion bans as well as the consequences for their patients’ health. The media also may not be the most desirable platform for sharing cases of substandard care if providers feel their confidentiality may be breached as they are told by their employers to avoid speaking with reporters.⁹ Bearing this in mind, our team of researchers at Advancing New Standards in Reproductive Health at the University of California San Francisco and the Texas Policy Evaluation Project at the University of Texas at Austin has launched a project aiming to collect stories of poor quality care post-Roe from health care professionals across the United States. The aim of the study is to document examples of the challenges in patient care that have arisen since the Dobbs decision.

The study website CarePostRoe.com was launched in October 2022 to collect narratives from health care providers who participated in the care of a patient whose management was different from the usual standard due to a need to comply with new restrictions on abortion since the Dobbs decision. These providers can include physicians, nurses, nurse practitioners, midwives, physician assistants, social workers, pharmacists, psychologists, or other allied health professionals. Clinicians can share information about a case through a brief survey linked on the website that will allow them to either submit a written narrative or a voice memo. The submissions are anonymous, and providers are not asked to submit any protected health information. If the submitter would like to share more information about the case via telephone interview, they will be taken to a separate survey which is not linked to the narrative submission to give contact information to participate in an interview.

Since October, more than 40 cases have been submitted that document patient cases from over half of the states with abortion bans. Clinicians describe pregnant patients with severe fetal malformations who have had to overcome financial and logistical barriers to travel to access abortion care. Several cases of patients with cesarean scar ectopic pregnancies have been submitted, including cases that are being followed expectantly, which is inconsistent with the standard of care.¹⁰ We also have received several submissions about cases of preterm premature rupture of membranes in the second trimester where the patient was sent home and presented several days later with a severe infection requiring management in the intensive care unit. Cases of early pregnancy loss that could have been treated safely and routinely also were delayed, increasing the risk to patients who, in addition to receiving substandard medical care, had the trauma of fearing they could be prosecuted for receiving treatment.

We hope these data will be useful to document the impact of the Court’s decision and to improve patient care as health care institutions work to update their policies and protocols to reduce delays in care in the face of legal ambiguities. If you have been involved in such a case since June 2022, including caring for a patient who traveled from another state, please consider submitting it at CarePostRoe.com, and please spread the word through your networks. ●

In June 2022, the US Supreme Court’s decision in Dobbs v Jackson Women’s Health Organization removed federal protections for abortion that previously had been codified in Roe v Wade. Since this removal, most abortions have been banned in at least 13 states, and about half of states are expected to attempt to ban or heavily restrict abortion.^1,2 These laws banning abortion are having effects on patient care far beyond abortion, leading to uncertainty and fear among providers and denied or delayed care for patients.^3,4 It is critical that research documents the harmful effects of this policy change.

Patients that are pregnant with fetuses with severe malformations have had to travel long distances to other states to obtain care.⁵ Others have faced delays in obtaining treatment for ectopic pregnancy, miscarriage, and even for other conditions that use medications that could potentially cause an abortion.^6,7 These cases have the potential to result in serious harm or death of the patient with altered care. There is a published report from Texas showing how the change in practice due to the 6-week abortion ban imposed in 2021 was associated with a doubling of severe morbidity for patients presenting with preterm premature rupture of membranes and other complications before 22 weeks’ gestation.⁸

While these cases have been highlighted in the media, there has not been a resource that comprehensively documents the changes in care that clinicians have been forced to make because of abortion bans as well as the consequences for their patients’ health. The media also may not be the most desirable platform for sharing cases of substandard care if providers feel their confidentiality may be breached as they are told by their employers to avoid speaking with reporters.⁹ Bearing this in mind, our team of researchers at Advancing New Standards in Reproductive Health at the University of California San Francisco and the Texas Policy Evaluation Project at the University of Texas at Austin has launched a project aiming to collect stories of poor quality care post-Roe from health care professionals across the United States. The aim of the study is to document examples of the challenges in patient care that have arisen since the Dobbs decision.

The study website CarePostRoe.com was launched in October 2022 to collect narratives from health care providers who participated in the care of a patient whose management was different from the usual standard due to a need to comply with new restrictions on abortion since the Dobbs decision. These providers can include physicians, nurses, nurse practitioners, midwives, physician assistants, social workers, pharmacists, psychologists, or other allied health professionals. Clinicians can share information about a case through a brief survey linked on the website that will allow them to either submit a written narrative or a voice memo. The submissions are anonymous, and providers are not asked to submit any protected health information. If the submitter would like to share more information about the case via telephone interview, they will be taken to a separate survey which is not linked to the narrative submission to give contact information to participate in an interview.

Since October, more than 40 cases have been submitted that document patient cases from over half of the states with abortion bans. Clinicians describe pregnant patients with severe fetal malformations who have had to overcome financial and logistical barriers to travel to access abortion care. Several cases of patients with cesarean scar ectopic pregnancies have been submitted, including cases that are being followed expectantly, which is inconsistent with the standard of care.¹⁰ We also have received several submissions about cases of preterm premature rupture of membranes in the second trimester where the patient was sent home and presented several days later with a severe infection requiring management in the intensive care unit. Cases of early pregnancy loss that could have been treated safely and routinely also were delayed, increasing the risk to patients who, in addition to receiving substandard medical care, had the trauma of fearing they could be prosecuted for receiving treatment.

We hope these data will be useful to document the impact of the Court’s decision and to improve patient care as health care institutions work to update their policies and protocols to reduce delays in care in the face of legal ambiguities. If you have been involved in such a case since June 2022, including caring for a patient who traveled from another state, please consider submitting it at CarePostRoe.com, and please spread the word through your networks. ●

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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