AVAHO

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.

“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.

Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.

So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.

They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.

The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.

“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.

And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.

“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.

In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said

“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.

The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
 

Three subgroups more likely to have deficits

The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits:  those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.

In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.

As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.

A study author explained why the study included mumps, a less threatening infection.

“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.

Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.

The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.

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

Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.

“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.

Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.

So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.

They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.

The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.

“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.

And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.

“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.

In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said

“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.

The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
 

Three subgroups more likely to have deficits

The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits:  those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.

In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.

As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.

A study author explained why the study included mumps, a less threatening infection.

“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.

Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.

The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.

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

Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.

“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.

Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.

So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.

They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.

The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.

“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.

And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.

“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.

In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said

“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.

The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
 

Three subgroups more likely to have deficits

The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits:  those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.

In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.

As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.

A study author explained why the study included mumps, a less threatening infection.

“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.

Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.

The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.

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

Among patients from a single dermatology practice who were diagnosed with two or more melanomas over an 8-year period, 45% lived more than 20 miles away from the practice, and almost 60% were 70 years of age and older, results from single-center study showed.

“Dermatologists have known that many people are underdiagnosed for melanoma, but now our research supports that the problem is especially concentrated among older patients living in remote areas,” corresponding author Rose Parisi, MBA, said in an interview. “With this information, dermatologists should consider identifying and reaching out to their patients in this at-risk subpopulation, increasing the frequency of full-body skin exams, and collaborating with primary care physicians to educate them about melanoma’s dangers.”

In a study published online Aug. 3 in the Journal of the American Academy of Dermatology, Ms. Parisi of Albany Medical College, New York, and colleagues drew from the electronic medical records of a single-specialty private dermatology practice that serves urban, suburban, and rural patient populations to identify 346 melanoma pathology reports from patients cared for between 2012 and 2020. They limited their investigation to those diagnosed with biopsy-confirmed melanoma and analyzed the number of melanomas, Breslow depth, follow-up full-body skin exams, family history of melanoma, gender, insurance, and age (categorized as younger than 70 years and 70 years or older). To determine patient travel distance, they calculated the miles between the ZIP codes of the patient’s residence and the dermatology practice.

Regression analysis revealed that the travel distance of patients and their age were significantly associated with the number of melanomas diagnosed. Specifically, among patients diagnosed with two or more melanomas, 45.0% lived more than 20 miles away and 21.3% lived less than 15 miles away; 59.6% were age 70 and older, while 40.4% were younger than age 70 (P less than .01).

No statistically significant association was observed between travel distance and Breslow depth or follow-up full-body skin exams within 1 year following diagnosis.

In other findings, among patients who lived more than 20 miles from the practice, those aged 70 and older were diagnosed with 0.56 more melanomas than patients between the ages of 58 and 70 (P = .00003), and 0.31 more melanomas than patients who lived 15-20 miles away (P = .014). No statistically significant differences in the number of melanomas diagnosed were observed between patients in either age group who lived fewer than 15 miles from the office.

“We were surprised that the combination of age and patient distance to diagnosing dermatology provider was such a powerful predictor of the number of diagnosed melanomas,” Ms. Parisi said. “It’s probably due to less mobility among older patients living in more remote areas, and it puts them at higher risk of multiple melanomas. This was something we haven’t seen in the dermatology literature.”

She and her coauthors acknowledged that the limited sampling of patients from a single practice “may not generalize across all urban and rural settings, and results must be considered preliminary,” they wrote. However, “our findings reveal an important vulnerability among older patients in nonurban areas, and efforts to improve access to melanoma diagnosis should be concentrated on this geodemographic segment.”

Nikolai Klebanov, MD, of the department of dermatology at Massachusetts General Hospital, Boston, who was asked to comment on the study, described what was addressed in the study as a “timely and an important topic.”

In an interview, he said, “there is less access to dermatologists and other medical specialists outside of large metropolitan and suburban areas,” and there are other health disparities affecting people living in rural or more underserved areas, which, he added, “also became exacerbated by the COVID-19 pandemic.”

For future studies on this topic, Dr. Klebanov said that he would be interested to see diagnoses measured per person-year rather than the total number of melanomas diagnosed. “More elderly patients may also be those who have ‘stuck with the practice’ for longer, and had a longer follow-up that gives more time to catch more melanomas,” he said.

“Adjusting for median income using ZIP codes could also help adjust for socioeconomic status, which would help with external validity of the study. Income relationships to geography are not the same in all cities; some have wealthy suburbs within 20 miles, while some have more underserved and rural areas at that distance.”

Neither the researchers nor Dr. Klebanov reported having financial disclosures.

[email protected]

Among patients from a single dermatology practice who were diagnosed with two or more melanomas over an 8-year period, 45% lived more than 20 miles away from the practice, and almost 60% were 70 years of age and older, results from single-center study showed.

“Dermatologists have known that many people are underdiagnosed for melanoma, but now our research supports that the problem is especially concentrated among older patients living in remote areas,” corresponding author Rose Parisi, MBA, said in an interview. “With this information, dermatologists should consider identifying and reaching out to their patients in this at-risk subpopulation, increasing the frequency of full-body skin exams, and collaborating with primary care physicians to educate them about melanoma’s dangers.”

In a study published online Aug. 3 in the Journal of the American Academy of Dermatology, Ms. Parisi of Albany Medical College, New York, and colleagues drew from the electronic medical records of a single-specialty private dermatology practice that serves urban, suburban, and rural patient populations to identify 346 melanoma pathology reports from patients cared for between 2012 and 2020. They limited their investigation to those diagnosed with biopsy-confirmed melanoma and analyzed the number of melanomas, Breslow depth, follow-up full-body skin exams, family history of melanoma, gender, insurance, and age (categorized as younger than 70 years and 70 years or older). To determine patient travel distance, they calculated the miles between the ZIP codes of the patient’s residence and the dermatology practice.

Regression analysis revealed that the travel distance of patients and their age were significantly associated with the number of melanomas diagnosed. Specifically, among patients diagnosed with two or more melanomas, 45.0% lived more than 20 miles away and 21.3% lived less than 15 miles away; 59.6% were age 70 and older, while 40.4% were younger than age 70 (P less than .01).

No statistically significant association was observed between travel distance and Breslow depth or follow-up full-body skin exams within 1 year following diagnosis.

In other findings, among patients who lived more than 20 miles from the practice, those aged 70 and older were diagnosed with 0.56 more melanomas than patients between the ages of 58 and 70 (P = .00003), and 0.31 more melanomas than patients who lived 15-20 miles away (P = .014). No statistically significant differences in the number of melanomas diagnosed were observed between patients in either age group who lived fewer than 15 miles from the office.

“We were surprised that the combination of age and patient distance to diagnosing dermatology provider was such a powerful predictor of the number of diagnosed melanomas,” Ms. Parisi said. “It’s probably due to less mobility among older patients living in more remote areas, and it puts them at higher risk of multiple melanomas. This was something we haven’t seen in the dermatology literature.”

She and her coauthors acknowledged that the limited sampling of patients from a single practice “may not generalize across all urban and rural settings, and results must be considered preliminary,” they wrote. However, “our findings reveal an important vulnerability among older patients in nonurban areas, and efforts to improve access to melanoma diagnosis should be concentrated on this geodemographic segment.”

Nikolai Klebanov, MD, of the department of dermatology at Massachusetts General Hospital, Boston, who was asked to comment on the study, described what was addressed in the study as a “timely and an important topic.”

In an interview, he said, “there is less access to dermatologists and other medical specialists outside of large metropolitan and suburban areas,” and there are other health disparities affecting people living in rural or more underserved areas, which, he added, “also became exacerbated by the COVID-19 pandemic.”

For future studies on this topic, Dr. Klebanov said that he would be interested to see diagnoses measured per person-year rather than the total number of melanomas diagnosed. “More elderly patients may also be those who have ‘stuck with the practice’ for longer, and had a longer follow-up that gives more time to catch more melanomas,” he said.

“Adjusting for median income using ZIP codes could also help adjust for socioeconomic status, which would help with external validity of the study. Income relationships to geography are not the same in all cities; some have wealthy suburbs within 20 miles, while some have more underserved and rural areas at that distance.”

Neither the researchers nor Dr. Klebanov reported having financial disclosures.

[email protected]

Among patients from a single dermatology practice who were diagnosed with two or more melanomas over an 8-year period, 45% lived more than 20 miles away from the practice, and almost 60% were 70 years of age and older, results from single-center study showed.

“Dermatologists have known that many people are underdiagnosed for melanoma, but now our research supports that the problem is especially concentrated among older patients living in remote areas,” corresponding author Rose Parisi, MBA, said in an interview. “With this information, dermatologists should consider identifying and reaching out to their patients in this at-risk subpopulation, increasing the frequency of full-body skin exams, and collaborating with primary care physicians to educate them about melanoma’s dangers.”

In a study published online Aug. 3 in the Journal of the American Academy of Dermatology, Ms. Parisi of Albany Medical College, New York, and colleagues drew from the electronic medical records of a single-specialty private dermatology practice that serves urban, suburban, and rural patient populations to identify 346 melanoma pathology reports from patients cared for between 2012 and 2020. They limited their investigation to those diagnosed with biopsy-confirmed melanoma and analyzed the number of melanomas, Breslow depth, follow-up full-body skin exams, family history of melanoma, gender, insurance, and age (categorized as younger than 70 years and 70 years or older). To determine patient travel distance, they calculated the miles between the ZIP codes of the patient’s residence and the dermatology practice.

Regression analysis revealed that the travel distance of patients and their age were significantly associated with the number of melanomas diagnosed. Specifically, among patients diagnosed with two or more melanomas, 45.0% lived more than 20 miles away and 21.3% lived less than 15 miles away; 59.6% were age 70 and older, while 40.4% were younger than age 70 (P less than .01).

No statistically significant association was observed between travel distance and Breslow depth or follow-up full-body skin exams within 1 year following diagnosis.

In other findings, among patients who lived more than 20 miles from the practice, those aged 70 and older were diagnosed with 0.56 more melanomas than patients between the ages of 58 and 70 (P = .00003), and 0.31 more melanomas than patients who lived 15-20 miles away (P = .014). No statistically significant differences in the number of melanomas diagnosed were observed between patients in either age group who lived fewer than 15 miles from the office.

“We were surprised that the combination of age and patient distance to diagnosing dermatology provider was such a powerful predictor of the number of diagnosed melanomas,” Ms. Parisi said. “It’s probably due to less mobility among older patients living in more remote areas, and it puts them at higher risk of multiple melanomas. This was something we haven’t seen in the dermatology literature.”

She and her coauthors acknowledged that the limited sampling of patients from a single practice “may not generalize across all urban and rural settings, and results must be considered preliminary,” they wrote. However, “our findings reveal an important vulnerability among older patients in nonurban areas, and efforts to improve access to melanoma diagnosis should be concentrated on this geodemographic segment.”

Nikolai Klebanov, MD, of the department of dermatology at Massachusetts General Hospital, Boston, who was asked to comment on the study, described what was addressed in the study as a “timely and an important topic.”

In an interview, he said, “there is less access to dermatologists and other medical specialists outside of large metropolitan and suburban areas,” and there are other health disparities affecting people living in rural or more underserved areas, which, he added, “also became exacerbated by the COVID-19 pandemic.”

For future studies on this topic, Dr. Klebanov said that he would be interested to see diagnoses measured per person-year rather than the total number of melanomas diagnosed. “More elderly patients may also be those who have ‘stuck with the practice’ for longer, and had a longer follow-up that gives more time to catch more melanomas,” he said.

“Adjusting for median income using ZIP codes could also help adjust for socioeconomic status, which would help with external validity of the study. Income relationships to geography are not the same in all cities; some have wealthy suburbs within 20 miles, while some have more underserved and rural areas at that distance.”

Neither the researchers nor Dr. Klebanov reported having financial disclosures.

[email protected]

There will be “routine application” and “broader acceptance” of minimally invasive focal therapies for early-stage prostate cancer within the next 5 years in the United States, predict a trio of clinicians in a new essay published online July 28 in JAMA Surgery.

They maintain that focal therapy (FT) offers a “middle ground” between two extremes: Treating the whole gland with radical prostatectomy or radiotherapy and not treating immediately via active surveillance or watchful waiting.

Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.

The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.

“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.

But payees are already making changes, even without such data, they add.

For example, in January the American Medical Association announced a new code for high-intensity focal ultrasound (HIFU): This approach now has a Current Procedural Terminology (CPT) code from the U.S. Centers for Medicare & Medicaid Services

This news organization reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California, San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.

“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Dr. Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”

The challenge with focal therapy – regardless of energy modality – remains patient selection and accurate ablation zone definition, he added.

Notably, UCSF has launched a new HIFU program – and Dr. Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
 

While waiting for CHRONOS, select wisely

The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minn., in an explanatory article. “This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.”

However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.

Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Dr. Lebastchi and colleagues write in their essay.  

They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”

Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
 

What is that evidence?

In the essay, Dr. Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: This compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease and uniformly showed better post-treatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).

However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.

Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinders acceptance [of focal therapy] in the urology community,” the essay authors comment.

Meanwhile, careful patient selection is very important, they say.

The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.

A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.

UCSF’s Dr. Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas, but we’re not there yet,” he says.

To date, some patients have been managed poorly, Dr. Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”

Some of those unfortunate results may have arisen from the U.S. Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car, but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.

Dr. Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech, and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech. Dr. Cooperberg is a consultant for Alessa Therapeutics.

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

There will be “routine application” and “broader acceptance” of minimally invasive focal therapies for early-stage prostate cancer within the next 5 years in the United States, predict a trio of clinicians in a new essay published online July 28 in JAMA Surgery.

They maintain that focal therapy (FT) offers a “middle ground” between two extremes: Treating the whole gland with radical prostatectomy or radiotherapy and not treating immediately via active surveillance or watchful waiting.

Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.

The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.

“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.

But payees are already making changes, even without such data, they add.

For example, in January the American Medical Association announced a new code for high-intensity focal ultrasound (HIFU): This approach now has a Current Procedural Terminology (CPT) code from the U.S. Centers for Medicare & Medicaid Services

This news organization reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California, San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.

“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Dr. Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”

The challenge with focal therapy – regardless of energy modality – remains patient selection and accurate ablation zone definition, he added.

Notably, UCSF has launched a new HIFU program – and Dr. Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
 

While waiting for CHRONOS, select wisely

The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minn., in an explanatory article. “This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.”

However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.

Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Dr. Lebastchi and colleagues write in their essay.  

They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”

Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
 

What is that evidence?

In the essay, Dr. Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: This compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease and uniformly showed better post-treatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).

However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.

Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinders acceptance [of focal therapy] in the urology community,” the essay authors comment.

Meanwhile, careful patient selection is very important, they say.

The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.

A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.

UCSF’s Dr. Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas, but we’re not there yet,” he says.

To date, some patients have been managed poorly, Dr. Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”

Some of those unfortunate results may have arisen from the U.S. Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car, but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.

Dr. Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech, and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech. Dr. Cooperberg is a consultant for Alessa Therapeutics.

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

There will be “routine application” and “broader acceptance” of minimally invasive focal therapies for early-stage prostate cancer within the next 5 years in the United States, predict a trio of clinicians in a new essay published online July 28 in JAMA Surgery.

They maintain that focal therapy (FT) offers a “middle ground” between two extremes: Treating the whole gland with radical prostatectomy or radiotherapy and not treating immediately via active surveillance or watchful waiting.

Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.

The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.

“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.

But payees are already making changes, even without such data, they add.

For example, in January the American Medical Association announced a new code for high-intensity focal ultrasound (HIFU): This approach now has a Current Procedural Terminology (CPT) code from the U.S. Centers for Medicare & Medicaid Services

This news organization reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California, San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.

“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Dr. Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”

The challenge with focal therapy – regardless of energy modality – remains patient selection and accurate ablation zone definition, he added.

Notably, UCSF has launched a new HIFU program – and Dr. Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
 

While waiting for CHRONOS, select wisely

The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minn., in an explanatory article. “This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.”

However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.

Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Dr. Lebastchi and colleagues write in their essay.  

They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”

Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
 

What is that evidence?

In the essay, Dr. Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: This compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease and uniformly showed better post-treatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).

However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.

Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinders acceptance [of focal therapy] in the urology community,” the essay authors comment.

Meanwhile, careful patient selection is very important, they say.

The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.

A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.

UCSF’s Dr. Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas, but we’re not there yet,” he says.

To date, some patients have been managed poorly, Dr. Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”

Some of those unfortunate results may have arisen from the U.S. Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car, but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.

Dr. Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech, and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech. Dr. Cooperberg is a consultant for Alessa Therapeutics.

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

Acquired von Willebrand disease (aVWD) is a rare and serious condition associated with lymphoproliferative disorders, malignancy, autoimmune disorders, and cardiovascular disease. It is most commonly caused by monoclonal gammopathy of undetermined significance (MGUS), which acts to clear von Willebrand factor from the patient’s bloodstream. However, a continuous-infusion of plasma-derived von Willebrand factor (VWF) concentrate provided adequate hemostasis in aVWD resulting from MGUS, according to Kathryn E. Dane, PharmD, of Johns Hopkins University, Baltimore, and colleagues.

The infusion rapidly achieved target ristocetin cofactor activity with or without intravenous immunoglobulin in three patients, as detailed in the report published online in Blood Advances.

The three consecutive patients with aVWD were treated with plasma-derived VWF concentrate administered for periprocedural optimization (patient 1, an 85-year old woman) or to treat bleeding episodes (patient 2, an 88-year-old man; and patient 3, a 53-year-old woman). Factor VIII activity was measured via a 1-stage clotting test and von Willebrand factor activity was measured with a ristocetin cofactor assay.
 

Promising results

All three patients demonstrated increased VWF ristocetin cofactor and factor VIII activities within hours of initiation of the continuous infusion concentrate, according to the report.

“We hypothesize that the efficacy of CI VWF concentrate in aVWD may be related to continuous provision of VWF, allowing binding and neutralization of anti-VWF IgG antibodies, and providing adequate circulating unbound VWF for appropriate hemostatic efficacy,” the researchers concluded.

The authors reported that they had no competing financial interests.

[email protected]

Acquired von Willebrand disease (aVWD) is a rare and serious condition associated with lymphoproliferative disorders, malignancy, autoimmune disorders, and cardiovascular disease. It is most commonly caused by monoclonal gammopathy of undetermined significance (MGUS), which acts to clear von Willebrand factor from the patient’s bloodstream. However, a continuous-infusion of plasma-derived von Willebrand factor (VWF) concentrate provided adequate hemostasis in aVWD resulting from MGUS, according to Kathryn E. Dane, PharmD, of Johns Hopkins University, Baltimore, and colleagues.

The infusion rapidly achieved target ristocetin cofactor activity with or without intravenous immunoglobulin in three patients, as detailed in the report published online in Blood Advances.

The three consecutive patients with aVWD were treated with plasma-derived VWF concentrate administered for periprocedural optimization (patient 1, an 85-year old woman) or to treat bleeding episodes (patient 2, an 88-year-old man; and patient 3, a 53-year-old woman). Factor VIII activity was measured via a 1-stage clotting test and von Willebrand factor activity was measured with a ristocetin cofactor assay.
 

Promising results

All three patients demonstrated increased VWF ristocetin cofactor and factor VIII activities within hours of initiation of the continuous infusion concentrate, according to the report.

“We hypothesize that the efficacy of CI VWF concentrate in aVWD may be related to continuous provision of VWF, allowing binding and neutralization of anti-VWF IgG antibodies, and providing adequate circulating unbound VWF for appropriate hemostatic efficacy,” the researchers concluded.

The authors reported that they had no competing financial interests.

[email protected]

Acquired von Willebrand disease (aVWD) is a rare and serious condition associated with lymphoproliferative disorders, malignancy, autoimmune disorders, and cardiovascular disease. It is most commonly caused by monoclonal gammopathy of undetermined significance (MGUS), which acts to clear von Willebrand factor from the patient’s bloodstream. However, a continuous-infusion of plasma-derived von Willebrand factor (VWF) concentrate provided adequate hemostasis in aVWD resulting from MGUS, according to Kathryn E. Dane, PharmD, of Johns Hopkins University, Baltimore, and colleagues.

The infusion rapidly achieved target ristocetin cofactor activity with or without intravenous immunoglobulin in three patients, as detailed in the report published online in Blood Advances.

The three consecutive patients with aVWD were treated with plasma-derived VWF concentrate administered for periprocedural optimization (patient 1, an 85-year old woman) or to treat bleeding episodes (patient 2, an 88-year-old man; and patient 3, a 53-year-old woman). Factor VIII activity was measured via a 1-stage clotting test and von Willebrand factor activity was measured with a ristocetin cofactor assay.
 

Promising results

All three patients demonstrated increased VWF ristocetin cofactor and factor VIII activities within hours of initiation of the continuous infusion concentrate, according to the report.

“We hypothesize that the efficacy of CI VWF concentrate in aVWD may be related to continuous provision of VWF, allowing binding and neutralization of anti-VWF IgG antibodies, and providing adequate circulating unbound VWF for appropriate hemostatic efficacy,” the researchers concluded.

The authors reported that they had no competing financial interests.

[email protected]

Ultrasonography screening intervals of less than 6-12 months were associated with early detection of hepatocellular carcinoma, as well as increased life expectancy and quality of life, according to data from a nationwide comparative effectiveness study of nearly 60,000 patients in Taiwan.

Many international societies, including the American Association for the Study of Liver Diseases, the Asian Pacific Association for the Study of the Liver, and the European Association for the Study of the Liver, recommend abdominal ultrasonography screening for hepatocellular carcinoma (HCC) with or without alpha-fetoprotein every 6 months for patients at increased risk for HCC, wrote Shih-Chiang Kuo, MD, of National Cheng Kung University, Tainan, Taiwan, and colleagues.

However, some studies do not support this recommendation, and data suggest that “adherence to regular screenings by high-risk patients has been inadequate, leading to reduced overall benefits of ultrasonography screening in real-world practice,” and the impact of screening schedules on quality of life has not been assessed, they said.

In a study published in JAMA Network Open, the researchers identified adults with newly diagnosed HCC from 2002 through 2015 using data from the Taiwan National Cancer Registry. Barcelona Clinic Liver Cancer (BCLC) staging information was available for 42,081 men and 17,113 women; the average age was 62 years for men and 69 years for women. The patients were divided into five cohorts based on the time between their last ultrasonography screening and an index date of 90 days before their HCC diagnosis. These groups were 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months.

“For both sexes, the proportions of patients with HCC classified as being in earlier stages (stage 0 and A) were higher in subcohorts with shorter screening intervals since the most recent ultrasonography,” the researchers wrote.

The researchers also assessed quality of life measures using the European Quality of Life Five-Dimensions in 807 men (3,370 repeated assessments) and 252 women (1,044 repeated assessments). Among men, the loss of quality of life expectancy in terms of quality of life years (QALYs) was 10.0, 11.1, 12.1, 13.1, and 14.6 for screening intervals of 6 months, 12 months, 24 months, 36 months, and beyond 36 months, respectively. The corresponding QALYs for women at the same screening intervals were 9.0, 9.7, 10.3, 10.7, and 11.4, respectively.

In a subgroup analysis according to underlying liver disease, patients with underlying hepatitis B virus infection or cirrhosis showed the greatest benefits from shorter screening intervals. For those with hepatitis B virus infection, abdominal ultrasonography screening 6 months or less prior to diagnosis of HCC was associated with an additional 4.8 QALYs for men and 2.8 QALYs for women, compared with screening longer than 36 months prior to diagnosis. The corresponding savings in QALY for men and women with underlying cirrhosis was 4.8 QALYs and 2.4 QALYs. Patients with no underlying liver disease also benefited from shorter intervals, with potential savings of 3.2 QALYs for men and 1.6 QALYs for women in the 6-month screening groups, compared with the longer than 36 months groups.

However, less than half of the men overall underwent screening withing 6 months or 12 months before diagnosis (31.4% and 39.3%, respectively); for women, 42.2% received screening within 6 months of diagnosis and 51.9% received screening within 12 months.

The study findings were limited by several factors including the use of only the last screening before diagnosis, which allows the possibility that patients in the 6- or 12-month groups did not have regular screening, the researchers noted. In addition, the lack of data on quality of life for women with BCLC stage D might have caused an underestimation of quality of life loss, they said. However, the results were strengthened by the use of a national database and long follow-up period, they said.

The results support intervals of 6-12 months or less for regular ultrasonography screening as a way to improve early detection of HCC, “and may save lives and improve utility for patients with HCC from a lifetime perspective,” the researchers emphasized. “Because people with underlying risk factors (including hepatitis B virus or hepatitis C virus infection, cirrhosis, and alcoholic liver disease) showed only slightly more frequent ultrasonography screening than those without underlying risk factors, we recommend improving this clinical practice,” they concluded.
 

Impact of identifying risk

“This study is important because HCC remains the third leading cause of cancer deaths, and the 5-year survival rate is low,” said Atsushi Sakuraba, MD, of the University of Chicago, in an interview.

Dr. Sakuraba said that he was not surprised by any of the study findings. “Earlier diagnosis of cancer is often associated with improved outcome in many cancers,” he noted.

However, “Overutilization of resources may lead to increased health care costs, so correct identification of high-risk populations is needed,” Dr. Sakuraba said.

Additional research is warranted in several areas in order to make an impact on clinical practice, Dr. Sakuraba said, notably, “confirmation in other countries and ethnicities where the incidence of viral hepatitis varies.” Comparison to other tests, such as tumor markers, CT, and MRI, is needed as well, he concluded.

The study was supported by the Taiwan Ministry of Science and Technology. The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Ultrasonography screening intervals of less than 6-12 months were associated with early detection of hepatocellular carcinoma, as well as increased life expectancy and quality of life, according to data from a nationwide comparative effectiveness study of nearly 60,000 patients in Taiwan.

Many international societies, including the American Association for the Study of Liver Diseases, the Asian Pacific Association for the Study of the Liver, and the European Association for the Study of the Liver, recommend abdominal ultrasonography screening for hepatocellular carcinoma (HCC) with or without alpha-fetoprotein every 6 months for patients at increased risk for HCC, wrote Shih-Chiang Kuo, MD, of National Cheng Kung University, Tainan, Taiwan, and colleagues.

However, some studies do not support this recommendation, and data suggest that “adherence to regular screenings by high-risk patients has been inadequate, leading to reduced overall benefits of ultrasonography screening in real-world practice,” and the impact of screening schedules on quality of life has not been assessed, they said.

In a study published in JAMA Network Open, the researchers identified adults with newly diagnosed HCC from 2002 through 2015 using data from the Taiwan National Cancer Registry. Barcelona Clinic Liver Cancer (BCLC) staging information was available for 42,081 men and 17,113 women; the average age was 62 years for men and 69 years for women. The patients were divided into five cohorts based on the time between their last ultrasonography screening and an index date of 90 days before their HCC diagnosis. These groups were 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months.

“For both sexes, the proportions of patients with HCC classified as being in earlier stages (stage 0 and A) were higher in subcohorts with shorter screening intervals since the most recent ultrasonography,” the researchers wrote.

The researchers also assessed quality of life measures using the European Quality of Life Five-Dimensions in 807 men (3,370 repeated assessments) and 252 women (1,044 repeated assessments). Among men, the loss of quality of life expectancy in terms of quality of life years (QALYs) was 10.0, 11.1, 12.1, 13.1, and 14.6 for screening intervals of 6 months, 12 months, 24 months, 36 months, and beyond 36 months, respectively. The corresponding QALYs for women at the same screening intervals were 9.0, 9.7, 10.3, 10.7, and 11.4, respectively.

In a subgroup analysis according to underlying liver disease, patients with underlying hepatitis B virus infection or cirrhosis showed the greatest benefits from shorter screening intervals. For those with hepatitis B virus infection, abdominal ultrasonography screening 6 months or less prior to diagnosis of HCC was associated with an additional 4.8 QALYs for men and 2.8 QALYs for women, compared with screening longer than 36 months prior to diagnosis. The corresponding savings in QALY for men and women with underlying cirrhosis was 4.8 QALYs and 2.4 QALYs. Patients with no underlying liver disease also benefited from shorter intervals, with potential savings of 3.2 QALYs for men and 1.6 QALYs for women in the 6-month screening groups, compared with the longer than 36 months groups.

However, less than half of the men overall underwent screening withing 6 months or 12 months before diagnosis (31.4% and 39.3%, respectively); for women, 42.2% received screening within 6 months of diagnosis and 51.9% received screening within 12 months.

The study findings were limited by several factors including the use of only the last screening before diagnosis, which allows the possibility that patients in the 6- or 12-month groups did not have regular screening, the researchers noted. In addition, the lack of data on quality of life for women with BCLC stage D might have caused an underestimation of quality of life loss, they said. However, the results were strengthened by the use of a national database and long follow-up period, they said.

The results support intervals of 6-12 months or less for regular ultrasonography screening as a way to improve early detection of HCC, “and may save lives and improve utility for patients with HCC from a lifetime perspective,” the researchers emphasized. “Because people with underlying risk factors (including hepatitis B virus or hepatitis C virus infection, cirrhosis, and alcoholic liver disease) showed only slightly more frequent ultrasonography screening than those without underlying risk factors, we recommend improving this clinical practice,” they concluded.
 

Impact of identifying risk

“This study is important because HCC remains the third leading cause of cancer deaths, and the 5-year survival rate is low,” said Atsushi Sakuraba, MD, of the University of Chicago, in an interview.

Dr. Sakuraba said that he was not surprised by any of the study findings. “Earlier diagnosis of cancer is often associated with improved outcome in many cancers,” he noted.

However, “Overutilization of resources may lead to increased health care costs, so correct identification of high-risk populations is needed,” Dr. Sakuraba said.

Additional research is warranted in several areas in order to make an impact on clinical practice, Dr. Sakuraba said, notably, “confirmation in other countries and ethnicities where the incidence of viral hepatitis varies.” Comparison to other tests, such as tumor markers, CT, and MRI, is needed as well, he concluded.

The study was supported by the Taiwan Ministry of Science and Technology. The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Ultrasonography screening intervals of less than 6-12 months were associated with early detection of hepatocellular carcinoma, as well as increased life expectancy and quality of life, according to data from a nationwide comparative effectiveness study of nearly 60,000 patients in Taiwan.

Many international societies, including the American Association for the Study of Liver Diseases, the Asian Pacific Association for the Study of the Liver, and the European Association for the Study of the Liver, recommend abdominal ultrasonography screening for hepatocellular carcinoma (HCC) with or without alpha-fetoprotein every 6 months for patients at increased risk for HCC, wrote Shih-Chiang Kuo, MD, of National Cheng Kung University, Tainan, Taiwan, and colleagues.

However, some studies do not support this recommendation, and data suggest that “adherence to regular screenings by high-risk patients has been inadequate, leading to reduced overall benefits of ultrasonography screening in real-world practice,” and the impact of screening schedules on quality of life has not been assessed, they said.

In a study published in JAMA Network Open, the researchers identified adults with newly diagnosed HCC from 2002 through 2015 using data from the Taiwan National Cancer Registry. Barcelona Clinic Liver Cancer (BCLC) staging information was available for 42,081 men and 17,113 women; the average age was 62 years for men and 69 years for women. The patients were divided into five cohorts based on the time between their last ultrasonography screening and an index date of 90 days before their HCC diagnosis. These groups were 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months.

“For both sexes, the proportions of patients with HCC classified as being in earlier stages (stage 0 and A) were higher in subcohorts with shorter screening intervals since the most recent ultrasonography,” the researchers wrote.

The researchers also assessed quality of life measures using the European Quality of Life Five-Dimensions in 807 men (3,370 repeated assessments) and 252 women (1,044 repeated assessments). Among men, the loss of quality of life expectancy in terms of quality of life years (QALYs) was 10.0, 11.1, 12.1, 13.1, and 14.6 for screening intervals of 6 months, 12 months, 24 months, 36 months, and beyond 36 months, respectively. The corresponding QALYs for women at the same screening intervals were 9.0, 9.7, 10.3, 10.7, and 11.4, respectively.

In a subgroup analysis according to underlying liver disease, patients with underlying hepatitis B virus infection or cirrhosis showed the greatest benefits from shorter screening intervals. For those with hepatitis B virus infection, abdominal ultrasonography screening 6 months or less prior to diagnosis of HCC was associated with an additional 4.8 QALYs for men and 2.8 QALYs for women, compared with screening longer than 36 months prior to diagnosis. The corresponding savings in QALY for men and women with underlying cirrhosis was 4.8 QALYs and 2.4 QALYs. Patients with no underlying liver disease also benefited from shorter intervals, with potential savings of 3.2 QALYs for men and 1.6 QALYs for women in the 6-month screening groups, compared with the longer than 36 months groups.

However, less than half of the men overall underwent screening withing 6 months or 12 months before diagnosis (31.4% and 39.3%, respectively); for women, 42.2% received screening within 6 months of diagnosis and 51.9% received screening within 12 months.

The study findings were limited by several factors including the use of only the last screening before diagnosis, which allows the possibility that patients in the 6- or 12-month groups did not have regular screening, the researchers noted. In addition, the lack of data on quality of life for women with BCLC stage D might have caused an underestimation of quality of life loss, they said. However, the results were strengthened by the use of a national database and long follow-up period, they said.

The results support intervals of 6-12 months or less for regular ultrasonography screening as a way to improve early detection of HCC, “and may save lives and improve utility for patients with HCC from a lifetime perspective,” the researchers emphasized. “Because people with underlying risk factors (including hepatitis B virus or hepatitis C virus infection, cirrhosis, and alcoholic liver disease) showed only slightly more frequent ultrasonography screening than those without underlying risk factors, we recommend improving this clinical practice,” they concluded.
 

Impact of identifying risk

“This study is important because HCC remains the third leading cause of cancer deaths, and the 5-year survival rate is low,” said Atsushi Sakuraba, MD, of the University of Chicago, in an interview.

Dr. Sakuraba said that he was not surprised by any of the study findings. “Earlier diagnosis of cancer is often associated with improved outcome in many cancers,” he noted.

However, “Overutilization of resources may lead to increased health care costs, so correct identification of high-risk populations is needed,” Dr. Sakuraba said.

Additional research is warranted in several areas in order to make an impact on clinical practice, Dr. Sakuraba said, notably, “confirmation in other countries and ethnicities where the incidence of viral hepatitis varies.” Comparison to other tests, such as tumor markers, CT, and MRI, is needed as well, he concluded.

The study was supported by the Taiwan Ministry of Science and Technology. The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

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

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

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

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

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

There may be a notable survival benefit for men with advanced prostate cancer and bone metastases when they are prescribed bone-protecting drugs after progressing to “castrate-resistant” status (no longer responsive to androgen deprivation therapy) and move onto first-line therapy with abiraterone acetate (Zytiga).

Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.

The findings were published online July 22, 2021, in JAMA Network Open.

All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.

While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.

So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.

Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).

There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.

Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).

Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).

Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.” 
 

Importance of bone-targeted drugs

“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.

Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.

So, why aren’t more men receiving BRIs?

“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.

“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.

As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).

“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.

“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
 

Costly vs. inexpensive BRI

The study found no difference in the OS benefit between the different BRIs used, that is, between that seen with zoledronic acid versus denosumab.

The editorialists suggested that this finding is important, even though it “must be considered preliminary given the limitations of a retrospective study.” These results add “to data suggesting that these agents are comparably beneficial; thus, decisions between them should focus on clinical factors, such as kidney function, patient preference, and cost.”

The two agents differ mechanistically, they added, with zoledronic acid preferentially inhibiting osteoclast proliferation and denosumab inhibiting an important factor in osteoclast maturation.

In terms of having differentiating characteristics, the editorialists say that zoledronic acid is “more often associated with acute phase reactions and required monitoring of kidney function” while “denosumab conferred a higher risk of hypocalcemia.” Rates of osteonecrosis of the jaw are comparable.

International guidelines endorse the use of either agent for the treatment of men with mCRPC. But “some argue that the marginal benefit of denosumab must be weighed against its dramatically higher cost (the annual cost of zoledronic acid is approximately $140 vs. $29,000 for denosumab),” the editorialists said.

The dramatically higher cost of denosumab versus zoledronic acid has also been noted by other oncologists treating patients with other cancers, including multiple myeloma.

In addition to drug costs, there is another issue at stake: the prescribing oncologist is reimbursed by Medicare Part D at 6% for whichever drug is chosen, which represents a “financial conflict” for oncologists, said Vincent Rajkumar, MD, professor of medicine and a hematologist/oncologist at the Mayo Clinic, Rochester, Minn.

There is also a difference in how the drugs are administered, which may influence patient preference, the myeloma experts noted. Zoledronic acid is given intravenously every 3 months and requires a 15-minute infusion at a center, while denosumab needs to be given more frequently (every month) but is administered by subcutaneous injection.

Dr. Francini reported receiving grants from Roche Italia and personal fees for research travel from Janssen-Cilag outside the submitted work. A number of other authors disclosed financial ties to Janssen or Amgen, makers of abiraterone and denosumab, respectively. The editorialists reported no relevant financial relationships.

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

There may be a notable survival benefit for men with advanced prostate cancer and bone metastases when they are prescribed bone-protecting drugs after progressing to “castrate-resistant” status (no longer responsive to androgen deprivation therapy) and move onto first-line therapy with abiraterone acetate (Zytiga).

Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.

The findings were published online July 22, 2021, in JAMA Network Open.

All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.

While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.

So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.

Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).

There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.

Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).

Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).

Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.” 
 

Importance of bone-targeted drugs

“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.

Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.

So, why aren’t more men receiving BRIs?

“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.

“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.

As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).

“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.

“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
 

Costly vs. inexpensive BRI

The study found no difference in the OS benefit between the different BRIs used, that is, between that seen with zoledronic acid versus denosumab.

The editorialists suggested that this finding is important, even though it “must be considered preliminary given the limitations of a retrospective study.” These results add “to data suggesting that these agents are comparably beneficial; thus, decisions between them should focus on clinical factors, such as kidney function, patient preference, and cost.”

The two agents differ mechanistically, they added, with zoledronic acid preferentially inhibiting osteoclast proliferation and denosumab inhibiting an important factor in osteoclast maturation.

In terms of having differentiating characteristics, the editorialists say that zoledronic acid is “more often associated with acute phase reactions and required monitoring of kidney function” while “denosumab conferred a higher risk of hypocalcemia.” Rates of osteonecrosis of the jaw are comparable.

International guidelines endorse the use of either agent for the treatment of men with mCRPC. But “some argue that the marginal benefit of denosumab must be weighed against its dramatically higher cost (the annual cost of zoledronic acid is approximately $140 vs. $29,000 for denosumab),” the editorialists said.

The dramatically higher cost of denosumab versus zoledronic acid has also been noted by other oncologists treating patients with other cancers, including multiple myeloma.

In addition to drug costs, there is another issue at stake: the prescribing oncologist is reimbursed by Medicare Part D at 6% for whichever drug is chosen, which represents a “financial conflict” for oncologists, said Vincent Rajkumar, MD, professor of medicine and a hematologist/oncologist at the Mayo Clinic, Rochester, Minn.

There is also a difference in how the drugs are administered, which may influence patient preference, the myeloma experts noted. Zoledronic acid is given intravenously every 3 months and requires a 15-minute infusion at a center, while denosumab needs to be given more frequently (every month) but is administered by subcutaneous injection.

Dr. Francini reported receiving grants from Roche Italia and personal fees for research travel from Janssen-Cilag outside the submitted work. A number of other authors disclosed financial ties to Janssen or Amgen, makers of abiraterone and denosumab, respectively. The editorialists reported no relevant financial relationships.

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

There may be a notable survival benefit for men with advanced prostate cancer and bone metastases when they are prescribed bone-protecting drugs after progressing to “castrate-resistant” status (no longer responsive to androgen deprivation therapy) and move onto first-line therapy with abiraterone acetate (Zytiga).

Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.

The findings were published online July 22, 2021, in JAMA Network Open.

All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.

While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.

So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.

Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).

There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.

Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).

Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).

Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.” 
 

Importance of bone-targeted drugs

“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.

Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.

So, why aren’t more men receiving BRIs?

“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.

“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.

As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).

“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.

“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
 

Costly vs. inexpensive BRI

The study found no difference in the OS benefit between the different BRIs used, that is, between that seen with zoledronic acid versus denosumab.

The editorialists suggested that this finding is important, even though it “must be considered preliminary given the limitations of a retrospective study.” These results add “to data suggesting that these agents are comparably beneficial; thus, decisions between them should focus on clinical factors, such as kidney function, patient preference, and cost.”

The two agents differ mechanistically, they added, with zoledronic acid preferentially inhibiting osteoclast proliferation and denosumab inhibiting an important factor in osteoclast maturation.

In terms of having differentiating characteristics, the editorialists say that zoledronic acid is “more often associated with acute phase reactions and required monitoring of kidney function” while “denosumab conferred a higher risk of hypocalcemia.” Rates of osteonecrosis of the jaw are comparable.

International guidelines endorse the use of either agent for the treatment of men with mCRPC. But “some argue that the marginal benefit of denosumab must be weighed against its dramatically higher cost (the annual cost of zoledronic acid is approximately $140 vs. $29,000 for denosumab),” the editorialists said.

The dramatically higher cost of denosumab versus zoledronic acid has also been noted by other oncologists treating patients with other cancers, including multiple myeloma.

In addition to drug costs, there is another issue at stake: the prescribing oncologist is reimbursed by Medicare Part D at 6% for whichever drug is chosen, which represents a “financial conflict” for oncologists, said Vincent Rajkumar, MD, professor of medicine and a hematologist/oncologist at the Mayo Clinic, Rochester, Minn.

There is also a difference in how the drugs are administered, which may influence patient preference, the myeloma experts noted. Zoledronic acid is given intravenously every 3 months and requires a 15-minute infusion at a center, while denosumab needs to be given more frequently (every month) but is administered by subcutaneous injection.

Dr. Francini reported receiving grants from Roche Italia and personal fees for research travel from Janssen-Cilag outside the submitted work. A number of other authors disclosed financial ties to Janssen or Amgen, makers of abiraterone and denosumab, respectively. The editorialists reported no relevant financial relationships.

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

The Centers for Disease Control and Prevention is expected to announce in early August that new data shows people vaccinated against COVID-19 who become infected with the Delta variant can spread it and infect others, the New York Times reported on July 29.

The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.

The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the New York Times said. The bottom line is that the CDC data shows people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.

ABC News reported earlier on Jul 29 that the CDC’s updated mask guidance followed an outbreak on Cape Cod, where crowds gathered for the Fourth of July.

As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.

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

The Centers for Disease Control and Prevention is expected to announce in early August that new data shows people vaccinated against COVID-19 who become infected with the Delta variant can spread it and infect others, the New York Times reported on July 29.

The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.

The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the New York Times said. The bottom line is that the CDC data shows people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.

ABC News reported earlier on Jul 29 that the CDC’s updated mask guidance followed an outbreak on Cape Cod, where crowds gathered for the Fourth of July.

As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.

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

The Centers for Disease Control and Prevention is expected to announce in early August that new data shows people vaccinated against COVID-19 who become infected with the Delta variant can spread it and infect others, the New York Times reported on July 29.

The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.

The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the New York Times said. The bottom line is that the CDC data shows people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.

ABC News reported earlier on Jul 29 that the CDC’s updated mask guidance followed an outbreak on Cape Cod, where crowds gathered for the Fourth of July.

As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.

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

Sleep patterns may influence risk of dementia, even decades before the onset of symptoms, according to a new analysis of data from the Whitehall II cohort study.

Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.

“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.

Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.

The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
 

Multifactorial risk

Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.

Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.

Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
 

Decades of data

During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.

A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.

The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.

Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.

Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.

Dr. Sabia and Dr. Sexton have no relevant financial disclosures.

Sleep patterns may influence risk of dementia, even decades before the onset of symptoms, according to a new analysis of data from the Whitehall II cohort study.

Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.

“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.

Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.

The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
 

Multifactorial risk

Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.

Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.

Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
 

Decades of data

During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.

A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.

The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.

Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.

Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.

Dr. Sabia and Dr. Sexton have no relevant financial disclosures.

Sleep patterns may influence risk of dementia, even decades before the onset of symptoms, according to a new analysis of data from the Whitehall II cohort study.

Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.

“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.

Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.

The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
 

Multifactorial risk

Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.

Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.

Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
 

Decades of data

During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.

A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.

The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.

Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.

Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.

Dr. Sabia and Dr. Sexton have no relevant financial disclosures.