Distinguishing severe asthma from asthma that is difficult to control can present a clinical challenge, especially in primary care settings. Patients with severe asthma often benefit from multidisciplinary assessment and management. 

In this panel ReCAP, experts in allergy, pulmonary disease, and primary care discuss the difference between severe and difficult-to-control asthma and the clinical importance of this distinction. They then outline optimal management of severe asthma using conventional therapies and the six biologics that are now available. 

According to the panelists, patients with asthma that is difficult to control may have comorbidities that have not been addressed and may contribute to their respiratory symptoms. In patients with severe asthma, comorbidities have typically been addressed and patients are adherent to prescribed therapies; their disease worsens if therapy is stepped down. This definition follows the 2022 Global Initiative for Asthma guidelines. 

The experts discuss how tests administered in primary care and specialty settings can distinguish between eosinophilic and non-eosinophilic phenotypes. In patients who continue to have symptoms despite maximized conventional therapies, biologics targeting specific inflammatory pathways may come into play.  

--

Richard Barbers, MD, Professor of Medicine, KECK Medical Center of the University of Southern California, Los Angeles, California 

Richard Barbers, MD, has disclosed no relevant financial relationships. 

Monica Kraft, MD, Murray M. Rosenberg Professor of Medicine, System Chair, Department of Medicine, Icahn School of Medicine at Mount Sinai; System Chair, Department of Medicine, Respiratory Institute at Mount Sinai Hospital, New York, NY 

Monica Kraft, MD, has disclosed the following relevant financial relationships: Serve(d) as a consultant for: Sanofi; Regeneron; AstraZeneca; Chiesi  

Serve(d) as Co-founder for: CMO; RaeSedo, Inc  
Received research grant from: National Institutes of Health; American Lung Association  

Have a 5% or greater equity interest in: RaeSedo, Inc (start-up in preclinical development of therapeutics) 

Received income in an amount equal to or greater than $250 from: UptoDate, section editor; received > $250 and < $5k from consultant activities above 

Louis J. Papa, MD, Professor of Clinical Medicine, Department of Medicine, Primary Care, University of Rochester Medical Center; Director of Professional Licensing and Credentialing Navigation, Olsan Medical Group, Rochester, New York 

Louis J. Papa, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Lifetime Healthcare Cos 

Received income in an amount equal to or greater than $250 from: Lifetime Healthcare Cos 

Distinguishing severe asthma from asthma that is difficult to control can present a clinical challenge, especially in primary care settings. Patients with severe asthma often benefit from multidisciplinary assessment and management. 

In this panel ReCAP, experts in allergy, pulmonary disease, and primary care discuss the difference between severe and difficult-to-control asthma and the clinical importance of this distinction. They then outline optimal management of severe asthma using conventional therapies and the six biologics that are now available. 

According to the panelists, patients with asthma that is difficult to control may have comorbidities that have not been addressed and may contribute to their respiratory symptoms. In patients with severe asthma, comorbidities have typically been addressed and patients are adherent to prescribed therapies; their disease worsens if therapy is stepped down. This definition follows the 2022 Global Initiative for Asthma guidelines. 

The experts discuss how tests administered in primary care and specialty settings can distinguish between eosinophilic and non-eosinophilic phenotypes. In patients who continue to have symptoms despite maximized conventional therapies, biologics targeting specific inflammatory pathways may come into play.  

--

Richard Barbers, MD, Professor of Medicine, KECK Medical Center of the University of Southern California, Los Angeles, California 

Richard Barbers, MD, has disclosed no relevant financial relationships. 

Monica Kraft, MD, Murray M. Rosenberg Professor of Medicine, System Chair, Department of Medicine, Icahn School of Medicine at Mount Sinai; System Chair, Department of Medicine, Respiratory Institute at Mount Sinai Hospital, New York, NY 

Monica Kraft, MD, has disclosed the following relevant financial relationships: Serve(d) as a consultant for: Sanofi; Regeneron; AstraZeneca; Chiesi  

Serve(d) as Co-founder for: CMO; RaeSedo, Inc  
Received research grant from: National Institutes of Health; American Lung Association  

Have a 5% or greater equity interest in: RaeSedo, Inc (start-up in preclinical development of therapeutics) 

Received income in an amount equal to or greater than $250 from: UptoDate, section editor; received > $250 and < $5k from consultant activities above 

Louis J. Papa, MD, Professor of Clinical Medicine, Department of Medicine, Primary Care, University of Rochester Medical Center; Director of Professional Licensing and Credentialing Navigation, Olsan Medical Group, Rochester, New York 

Louis J. Papa, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Lifetime Healthcare Cos 

Received income in an amount equal to or greater than $250 from: Lifetime Healthcare Cos 

Distinguishing severe asthma from asthma that is difficult to control can present a clinical challenge, especially in primary care settings. Patients with severe asthma often benefit from multidisciplinary assessment and management. 

In this panel ReCAP, experts in allergy, pulmonary disease, and primary care discuss the difference between severe and difficult-to-control asthma and the clinical importance of this distinction. They then outline optimal management of severe asthma using conventional therapies and the six biologics that are now available. 

According to the panelists, patients with asthma that is difficult to control may have comorbidities that have not been addressed and may contribute to their respiratory symptoms. In patients with severe asthma, comorbidities have typically been addressed and patients are adherent to prescribed therapies; their disease worsens if therapy is stepped down. This definition follows the 2022 Global Initiative for Asthma guidelines. 

The experts discuss how tests administered in primary care and specialty settings can distinguish between eosinophilic and non-eosinophilic phenotypes. In patients who continue to have symptoms despite maximized conventional therapies, biologics targeting specific inflammatory pathways may come into play.  

--

Richard Barbers, MD, Professor of Medicine, KECK Medical Center of the University of Southern California, Los Angeles, California 

Richard Barbers, MD, has disclosed no relevant financial relationships. 

Monica Kraft, MD, Murray M. Rosenberg Professor of Medicine, System Chair, Department of Medicine, Icahn School of Medicine at Mount Sinai; System Chair, Department of Medicine, Respiratory Institute at Mount Sinai Hospital, New York, NY 

Monica Kraft, MD, has disclosed the following relevant financial relationships: Serve(d) as a consultant for: Sanofi; Regeneron; AstraZeneca; Chiesi  

Serve(d) as Co-founder for: CMO; RaeSedo, Inc  
Received research grant from: National Institutes of Health; American Lung Association  

Have a 5% or greater equity interest in: RaeSedo, Inc (start-up in preclinical development of therapeutics) 

Received income in an amount equal to or greater than $250 from: UptoDate, section editor; received > $250 and < $5k from consultant activities above 

Louis J. Papa, MD, Professor of Clinical Medicine, Department of Medicine, Primary Care, University of Rochester Medical Center; Director of Professional Licensing and Credentialing Navigation, Olsan Medical Group, Rochester, New York 

Louis J. Papa, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Lifetime Healthcare Cos 

Received income in an amount equal to or greater than $250 from: Lifetime Healthcare Cos 

The U.S. Food and Drug Administration has approved an injectable monoclonal antibody to protect newborns and infants against respiratory syncytial virus (RSV).

The monoclonal antibody Beyfortus (nirsevimab-alip), which already is approved for use in Europe and Canada, is indicated for newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who are vulnerable to severe RSV through their second RSV season.

As many as 80,000 children under age 5 years are hospitalized with an RSV infection annually in the United States. Most cases are mild, but infants under 6 months, those born prematurely, and children with weakened immune systems or neuromuscular disorders are at an increased risk for severe illness, according to the Centers for Disease Control and Prevention.

The highly contagious virus is also a concern for immunocompromised adults and older people with underlying health conditions, who are at increased risk for severe disease.

Sanofi and AstraZeneca, which jointly developed the injectable agent, said in a press release that the companies plan to make it available by the fall of 2023. The long-acting antibody is given as a single intramuscular injection.

Beyfortus was approved in part based on data from the phase 3 MELODY trial, which found the shot reduced the incidence of medically attended lower respiratory tract infections associated with RSV by 74.9% versus placebo (95% confidence interval, 50.6-87.3; P < .001).

The phase 2/3 MEDLEY trial, conducted between July 2019 and May 2021, compared Beyfortus with palivizumab, another RSV antibody injection with more limited indications. The trial included more than 900 preterm infants less than 35 weeks’ gestational age and infants with congenital heart disease. Results were similar to the phase 3 MELODY trial, according to the manufacturers.

“Today’s approval marks an unprecedented moment for protecting infant health in the United States, following an RSV season that took a record toll on infants, their families, and the U.S. health care system,” said Thomas Triomphe, executive vice president for vaccines at Sanofi, in a press release about the FDA decision. “Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season.”

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

The U.S. Food and Drug Administration has approved an injectable monoclonal antibody to protect newborns and infants against respiratory syncytial virus (RSV).

The monoclonal antibody Beyfortus (nirsevimab-alip), which already is approved for use in Europe and Canada, is indicated for newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who are vulnerable to severe RSV through their second RSV season.

As many as 80,000 children under age 5 years are hospitalized with an RSV infection annually in the United States. Most cases are mild, but infants under 6 months, those born prematurely, and children with weakened immune systems or neuromuscular disorders are at an increased risk for severe illness, according to the Centers for Disease Control and Prevention.

The highly contagious virus is also a concern for immunocompromised adults and older people with underlying health conditions, who are at increased risk for severe disease.

Sanofi and AstraZeneca, which jointly developed the injectable agent, said in a press release that the companies plan to make it available by the fall of 2023. The long-acting antibody is given as a single intramuscular injection.

Beyfortus was approved in part based on data from the phase 3 MELODY trial, which found the shot reduced the incidence of medically attended lower respiratory tract infections associated with RSV by 74.9% versus placebo (95% confidence interval, 50.6-87.3; P < .001).

The phase 2/3 MEDLEY trial, conducted between July 2019 and May 2021, compared Beyfortus with palivizumab, another RSV antibody injection with more limited indications. The trial included more than 900 preterm infants less than 35 weeks’ gestational age and infants with congenital heart disease. Results were similar to the phase 3 MELODY trial, according to the manufacturers.

“Today’s approval marks an unprecedented moment for protecting infant health in the United States, following an RSV season that took a record toll on infants, their families, and the U.S. health care system,” said Thomas Triomphe, executive vice president for vaccines at Sanofi, in a press release about the FDA decision. “Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season.”

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

The U.S. Food and Drug Administration has approved an injectable monoclonal antibody to protect newborns and infants against respiratory syncytial virus (RSV).

The monoclonal antibody Beyfortus (nirsevimab-alip), which already is approved for use in Europe and Canada, is indicated for newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who are vulnerable to severe RSV through their second RSV season.

As many as 80,000 children under age 5 years are hospitalized with an RSV infection annually in the United States. Most cases are mild, but infants under 6 months, those born prematurely, and children with weakened immune systems or neuromuscular disorders are at an increased risk for severe illness, according to the Centers for Disease Control and Prevention.

The highly contagious virus is also a concern for immunocompromised adults and older people with underlying health conditions, who are at increased risk for severe disease.

Sanofi and AstraZeneca, which jointly developed the injectable agent, said in a press release that the companies plan to make it available by the fall of 2023. The long-acting antibody is given as a single intramuscular injection.

Beyfortus was approved in part based on data from the phase 3 MELODY trial, which found the shot reduced the incidence of medically attended lower respiratory tract infections associated with RSV by 74.9% versus placebo (95% confidence interval, 50.6-87.3; P < .001).

The phase 2/3 MEDLEY trial, conducted between July 2019 and May 2021, compared Beyfortus with palivizumab, another RSV antibody injection with more limited indications. The trial included more than 900 preterm infants less than 35 weeks’ gestational age and infants with congenital heart disease. Results were similar to the phase 3 MELODY trial, according to the manufacturers.

“Today’s approval marks an unprecedented moment for protecting infant health in the United States, following an RSV season that took a record toll on infants, their families, and the U.S. health care system,” said Thomas Triomphe, executive vice president for vaccines at Sanofi, in a press release about the FDA decision. “Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season.”

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

Implementing stewardship strategies for immune checkpoint inhibitor (ICI) therapy, including personalized weight-based dosing, dose rounding, and pharmacy-level vial sharing, could generate savings of as much as $74 million each year for the Veterans Health Administration (VHA), a new analysis suggests.

That $74 million in savings would translate to nearly 14% less spent on ICI therapy annually.

“Our work suggests that implementing these strategies across the VHA could lead to tens of millions of dollars in annual savings – and that’s just for immunotherapy – without sacrificing outcomes,” first author Alex Bryant, MD, University of Michigan, Ann Arbor, said in an interview.

The study was published in Health Affairs.

ICI therapy is used in about 40 unique cancer indications and, in 2020, accounted for more than $6 billion in Medicare Part B spending.

Two of the most prescribed ICIs – pembrolizumab and nivolumab – initially received their U.S. approval at personalized weight-based doses. But at the request of the manufacturers, the Food and Drug Administration approved “one-size-fits-all” flat doses, despite a lack of data to support this strategy compared with weight-based dosing.

With a fixed dose strategy, “patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel,  told this news organization last year. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”

To compare the cost of a weight-based vs. fixed-dose strategy, Dr. Bryant and colleagues conducted a simulation analysis under four stewardship scenarios, using data from the VHA and Medicare drug prices. Strategy one looked at weight-based dosing; strategy two combined weight-based dosing and dose rounding but not single-use vial sharing; strategy three used weight-based dosing and single-use vial sharing but not dose rounding; and strategy four, the most aggressive, combined all three.

ICIs in the VHA national formulary included pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab-rwlc.

Using an algorithm to extract data, the team identified 49,851 administration events in 8,276 unique patients in 2021 – just over half were pembrolizumab, nearly 23% were nivolumab, and the remaining 26% largely included atezolizumab (12.1%) and durvalumab (11.9%).

The team found that the VHA spends roughly $537 million annually on ICIs. But implementing the stewardship measures that combined weight-based dosing, dose rounding, and vial sharing could save the VHA $74 million, or about 14%, annually on ICIs.

Most of the savings came from dosing changes to pembrolizumab and nivolumab, with greater savings achieved by combining more stewardship strategies. For instance, using strategy one (weight-based dosing alone) could lead to annual pembrolizumab savings of $14 million. Adding dose rounding (strategy two) could reduce pembrolizumab spending by $24 million. And using strategy four, with an unlimited window for vial sharing, could mean annual savings of nearly $60 million.

“Our results should prompt cost-conscious systems and payers to ask whether the amounts of drugs they’re providing to patients and how they go about making those doses are the most cost-effective approaches,” said corresponding author Garth W. Strohbehn, MD, of the University of Michigan and the VA Ann Arbor Healthcare System.

Dr. Strohbehn said the prospect of adopting these strategies hinges on several factors, with financial incentives at the prescriber and medical center level likely being the most influential.

“In fee-for-service systems, reimbursement scales with the amount of drug administered, so there can be a financial disincentive to decreasing overall drug usage,” Dr. Strohbehn explained.

“Conversely, integrated systems such as Kaiser Permanente or the VHA and large self-insured employers are incentivized to contain costs and take great care of patients, so they may be more inclined to promote these strategies,” he added.

However, Adam C. Powell, PhD, president, Payer+Provider Syndicate, who wasn’t involved in the analysis, cautioned that such a shift may come with unintended consequences.

The Infrastructure, Investment, and Jobs Act of 2021 let the Centers for Medicare and Medicaid Services seek reimbursement for discarded drugs – in effect, changing the reimbursement model for medications. That led pharmaceutical manufacturers to respond in kind by changing the dosing model, Dr. Powell said. 

“Drugs that previously had personalized weight-based dosing were moved to uniform flat dosing, eliminating the potential for the manufacturer to have to issue a reimbursement if the patient’s personalized dose fell short of the amount in the single-use vial,” Dr. Powell added.  

If there is a substantial migration to weight-based dosing, “it is possible that pharmaceutical manufacturers will rethink their dosing and pricing models, just as happened previously,” he cautioned.

However, these strategies could also provide relief for another escalating issue: drug shortages. Especially in the current moment, having a stewardship mindset, “might be helpful in navigating drug shortages,” Dr. Strohbehn said.

This research had no commercial funding. Dr. Bryant, Dr. Strohbehn, and Dr. Powell report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Implementing stewardship strategies for immune checkpoint inhibitor (ICI) therapy, including personalized weight-based dosing, dose rounding, and pharmacy-level vial sharing, could generate savings of as much as $74 million each year for the Veterans Health Administration (VHA), a new analysis suggests.

That $74 million in savings would translate to nearly 14% less spent on ICI therapy annually.

“Our work suggests that implementing these strategies across the VHA could lead to tens of millions of dollars in annual savings – and that’s just for immunotherapy – without sacrificing outcomes,” first author Alex Bryant, MD, University of Michigan, Ann Arbor, said in an interview.

The study was published in Health Affairs.

ICI therapy is used in about 40 unique cancer indications and, in 2020, accounted for more than $6 billion in Medicare Part B spending.

Two of the most prescribed ICIs – pembrolizumab and nivolumab – initially received their U.S. approval at personalized weight-based doses. But at the request of the manufacturers, the Food and Drug Administration approved “one-size-fits-all” flat doses, despite a lack of data to support this strategy compared with weight-based dosing.

With a fixed dose strategy, “patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel,  told this news organization last year. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”

To compare the cost of a weight-based vs. fixed-dose strategy, Dr. Bryant and colleagues conducted a simulation analysis under four stewardship scenarios, using data from the VHA and Medicare drug prices. Strategy one looked at weight-based dosing; strategy two combined weight-based dosing and dose rounding but not single-use vial sharing; strategy three used weight-based dosing and single-use vial sharing but not dose rounding; and strategy four, the most aggressive, combined all three.

ICIs in the VHA national formulary included pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab-rwlc.

Using an algorithm to extract data, the team identified 49,851 administration events in 8,276 unique patients in 2021 – just over half were pembrolizumab, nearly 23% were nivolumab, and the remaining 26% largely included atezolizumab (12.1%) and durvalumab (11.9%).

The team found that the VHA spends roughly $537 million annually on ICIs. But implementing the stewardship measures that combined weight-based dosing, dose rounding, and vial sharing could save the VHA $74 million, or about 14%, annually on ICIs.

Most of the savings came from dosing changes to pembrolizumab and nivolumab, with greater savings achieved by combining more stewardship strategies. For instance, using strategy one (weight-based dosing alone) could lead to annual pembrolizumab savings of $14 million. Adding dose rounding (strategy two) could reduce pembrolizumab spending by $24 million. And using strategy four, with an unlimited window for vial sharing, could mean annual savings of nearly $60 million.

“Our results should prompt cost-conscious systems and payers to ask whether the amounts of drugs they’re providing to patients and how they go about making those doses are the most cost-effective approaches,” said corresponding author Garth W. Strohbehn, MD, of the University of Michigan and the VA Ann Arbor Healthcare System.

Dr. Strohbehn said the prospect of adopting these strategies hinges on several factors, with financial incentives at the prescriber and medical center level likely being the most influential.

“In fee-for-service systems, reimbursement scales with the amount of drug administered, so there can be a financial disincentive to decreasing overall drug usage,” Dr. Strohbehn explained.

“Conversely, integrated systems such as Kaiser Permanente or the VHA and large self-insured employers are incentivized to contain costs and take great care of patients, so they may be more inclined to promote these strategies,” he added.

However, Adam C. Powell, PhD, president, Payer+Provider Syndicate, who wasn’t involved in the analysis, cautioned that such a shift may come with unintended consequences.

The Infrastructure, Investment, and Jobs Act of 2021 let the Centers for Medicare and Medicaid Services seek reimbursement for discarded drugs – in effect, changing the reimbursement model for medications. That led pharmaceutical manufacturers to respond in kind by changing the dosing model, Dr. Powell said. 

“Drugs that previously had personalized weight-based dosing were moved to uniform flat dosing, eliminating the potential for the manufacturer to have to issue a reimbursement if the patient’s personalized dose fell short of the amount in the single-use vial,” Dr. Powell added.  

If there is a substantial migration to weight-based dosing, “it is possible that pharmaceutical manufacturers will rethink their dosing and pricing models, just as happened previously,” he cautioned.

However, these strategies could also provide relief for another escalating issue: drug shortages. Especially in the current moment, having a stewardship mindset, “might be helpful in navigating drug shortages,” Dr. Strohbehn said.

This research had no commercial funding. Dr. Bryant, Dr. Strohbehn, and Dr. Powell report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Implementing stewardship strategies for immune checkpoint inhibitor (ICI) therapy, including personalized weight-based dosing, dose rounding, and pharmacy-level vial sharing, could generate savings of as much as $74 million each year for the Veterans Health Administration (VHA), a new analysis suggests.

That $74 million in savings would translate to nearly 14% less spent on ICI therapy annually.

“Our work suggests that implementing these strategies across the VHA could lead to tens of millions of dollars in annual savings – and that’s just for immunotherapy – without sacrificing outcomes,” first author Alex Bryant, MD, University of Michigan, Ann Arbor, said in an interview.

The study was published in Health Affairs.

ICI therapy is used in about 40 unique cancer indications and, in 2020, accounted for more than $6 billion in Medicare Part B spending.

Two of the most prescribed ICIs – pembrolizumab and nivolumab – initially received their U.S. approval at personalized weight-based doses. But at the request of the manufacturers, the Food and Drug Administration approved “one-size-fits-all” flat doses, despite a lack of data to support this strategy compared with weight-based dosing.

With a fixed dose strategy, “patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel,  told this news organization last year. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”

To compare the cost of a weight-based vs. fixed-dose strategy, Dr. Bryant and colleagues conducted a simulation analysis under four stewardship scenarios, using data from the VHA and Medicare drug prices. Strategy one looked at weight-based dosing; strategy two combined weight-based dosing and dose rounding but not single-use vial sharing; strategy three used weight-based dosing and single-use vial sharing but not dose rounding; and strategy four, the most aggressive, combined all three.

ICIs in the VHA national formulary included pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab-rwlc.

Using an algorithm to extract data, the team identified 49,851 administration events in 8,276 unique patients in 2021 – just over half were pembrolizumab, nearly 23% were nivolumab, and the remaining 26% largely included atezolizumab (12.1%) and durvalumab (11.9%).

The team found that the VHA spends roughly $537 million annually on ICIs. But implementing the stewardship measures that combined weight-based dosing, dose rounding, and vial sharing could save the VHA $74 million, or about 14%, annually on ICIs.

Most of the savings came from dosing changes to pembrolizumab and nivolumab, with greater savings achieved by combining more stewardship strategies. For instance, using strategy one (weight-based dosing alone) could lead to annual pembrolizumab savings of $14 million. Adding dose rounding (strategy two) could reduce pembrolizumab spending by $24 million. And using strategy four, with an unlimited window for vial sharing, could mean annual savings of nearly $60 million.

“Our results should prompt cost-conscious systems and payers to ask whether the amounts of drugs they’re providing to patients and how they go about making those doses are the most cost-effective approaches,” said corresponding author Garth W. Strohbehn, MD, of the University of Michigan and the VA Ann Arbor Healthcare System.

Dr. Strohbehn said the prospect of adopting these strategies hinges on several factors, with financial incentives at the prescriber and medical center level likely being the most influential.

“In fee-for-service systems, reimbursement scales with the amount of drug administered, so there can be a financial disincentive to decreasing overall drug usage,” Dr. Strohbehn explained.

“Conversely, integrated systems such as Kaiser Permanente or the VHA and large self-insured employers are incentivized to contain costs and take great care of patients, so they may be more inclined to promote these strategies,” he added.

However, Adam C. Powell, PhD, president, Payer+Provider Syndicate, who wasn’t involved in the analysis, cautioned that such a shift may come with unintended consequences.

The Infrastructure, Investment, and Jobs Act of 2021 let the Centers for Medicare and Medicaid Services seek reimbursement for discarded drugs – in effect, changing the reimbursement model for medications. That led pharmaceutical manufacturers to respond in kind by changing the dosing model, Dr. Powell said. 

“Drugs that previously had personalized weight-based dosing were moved to uniform flat dosing, eliminating the potential for the manufacturer to have to issue a reimbursement if the patient’s personalized dose fell short of the amount in the single-use vial,” Dr. Powell added.  

If there is a substantial migration to weight-based dosing, “it is possible that pharmaceutical manufacturers will rethink their dosing and pricing models, just as happened previously,” he cautioned.

However, these strategies could also provide relief for another escalating issue: drug shortages. Especially in the current moment, having a stewardship mindset, “might be helpful in navigating drug shortages,” Dr. Strohbehn said.

This research had no commercial funding. Dr. Bryant, Dr. Strohbehn, and Dr. Powell report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Medical student loans top hundreds of thousands of dollars, so it’s understandable that physicians may want to select a specialty that pays well.

But overwhelmingly, the physicians this news organization spoke to said they chose a specialty they were passionate about rather than focusing on going where more money was. Moreover, most advised young doctors to follow their hearts rather than their wallets.

“There is no question that many young kids immediately think about money when deciding to pursue medicine, but the thought of a big paycheck will never sustain someone long enough to get them here,” says Sergio Alvarez, MD, a board-certified plastic surgeon based in Miami, Fla., and the CEO and medical director of Mia Aesthetics, which has several national locations.

“Getting into medicine is a long game, and there are many hurdles along the way that only the dedicated overcome,” says Dr. Alvarez.

Unfortunately, he says it may be late in that long game before some realize that the pay rate for certain specialties isn’t commensurate with the immense workload and responsibility they require.

“The short of it is that to become a happy doctor, medicine really needs to be a calling: a passion! There are far easier things to do to make money.”

Here is what physicians said about choosing between love or money.
 

The lowest-paying subspecialty in a low-paying specialty

Sophia Yen, MD, MPH, cofounder and CEO of Pandia Health, a women-founded, doctor-led birth control delivery service in Sunnyvale, Calif., and clinical associate professor at Stanford (Calif.) University, says you should pursue a specialty because you love the work.

“I chose the lowest-paying subspecialty (adolescent medicine) of a low-paying specialty (pediatrics), but I’d do it all again because I love the patient population – I love what I do.”

Dr. Yen says she chose adolescent medicine because she loves doing “outpatient gynecology” without going through the surgical training of a full ob.gyn. “I love the target population of young adults because you can talk to the patient versus in pediatrics, where you often talk to the parent. With young adults you can catch things – for example, teach a young person about consent, alcohol, marijuana’s effects on the growing brain, prevent unplanned pregnancies and sexually transmitted infections, instill healthy eating, and more.

“Do I wish that I got paid as much as a surgeon?” Dr. Yen says yes. “I hope that someday society will realize the time spent preventing future disease is worth it and pay us accordingly.”

Unfortunately, she says, since the health care system makes more money if you get pregnant, need a cardiac bypass, or need gastric surgery, those who deliver babies or do surgery get paid more than someone who prevents the need for those services.
 

Money doesn’t buy happiness

Stella Bard, MD, a rheumatologist in McKinney, Tex., says she eats, lives, and breathes rheumatology. “I never regret the decision of choosing this specialty for a single second,” says Dr. Bard. “I feel like it’s a rewarding experience with every single patient encounter.” Dr. Bard notes that money is no guarantee of happiness and that she feels blessed to wake up every morning doing what she loves.

Career or calling?

For Dr. Alvarez, inspiration came when watching his father help change people’s lives. “I saw how impactful a doctor is during a person’s most desperate moments, and that was enough to make medicine my life’s passion at the age of 10.”

He says once you’re in medical school, choosing a specialty is far easier than you think. “Each specialty requires a certain personality or specific characteristics, and some will call to you while others simply won’t.”

“For me, plastics was about finesse, art, and life-changing surgeries that affected people from kids to adults and involved every aspect of the human body. Changing someone’s outward appearance has a profoundly positive impact on their confidence and self-esteem, making plastic surgery a genuinely transformative experience.”

Patricia Celan, MD, a postgraduate psychiatry resident in Canada, also chose psychiatry for the love of the field. “I enjoy helping vulnerable people and exploring what makes a person tick, the source of their difficulties, and how to help people counteract and overcome the difficult cards they’ve been dealt in life.”

She says it’s incredibly rewarding to watch someone turn their life around from severe mental illness, especially those who have been victimized and traumatized, and learn to trust people again.

“I could have made more money in a higher-paying specialty, yes, but I’m not sure I would have felt as fulfilled as psychiatry can make me feel.”

Dr. Celan says everyone has their calling, and some lucky people find their deepest passion in higher-paying specialties. “My calling is psychiatry, and I am at peace with this no matter the money.”
 

For the love of surgery

“In my experience, most people don’t choose their specialty based on money,” says Nicole Aaronson, MD, MBA, an otolaryngologist and board-certified in the subspecialty of pediatric otolaryngology, an attending surgeon at Nemours Children’s Health of Delaware and clinical associate professor of otolaryngology and pediatrics at Sidney Kimmel Medical College, Philadelphia.

“The first decision point in medical school is usually figuring out if you are a surgery person or a medicine person. I knew very early that I wanted to be a surgeon and wanted to spend time in the OR fixing problems with my hands.”

Part of what attracted Dr. Aaronson to otolaryngology was the variety of conditions managed within the specialty, from head and neck cancer to voice problems to sleep disorders to sinus disease. “I chose my subspecialty because I enjoy working with children and making an impact that will help them live their best possible lives.”

She says a relatively simple surgery like placing ear tubes may help a child’s hearing and allow them to be more successful in school, opening up a new world of opportunities for the child’s future.

“While I don’t think most people choose their specialty based on prospective compensation, I do think all physicians want to be compensated fairly for their time, effort, and level of training,” says Dr. Aaronson.
 

Choosing a specialty for the money can lead to burnout and dissatisfaction

“For me, the decision to pursue gastroenterology went beyond financial considerations,” says Saurabh Sethi, MD, MPH, a gastroenterologist specializing in hepatology and interventional endoscopy. “While financial stability is undoubtedly important, no doctor enters this field solely for the love of money. The primary driving force for most medical professionals, myself included, is the passion to help people and make a positive difference in their lives.”

Dr. Sethi says the gratification that comes from providing quality care and witnessing patients’ improved well-being is priceless. Moreover, he believes that selecting a specialty based solely on financial gain is likely to lead to burnout and greater dissatisfaction over time.

“By following my love for gut health and prioritizing patient care, I have found a sense of fulfillment and purpose in my career. It has been a rewarding journey, and I’m grateful for the opportunity to contribute to the well-being of my patients through my expertise in gastroenterology.”
 

Key takeaways: Love or money?

Multiple factors influence doctors’ specialty choices, including genuine love for the work and the future of the specialty. Others include job prospects, hands-on experience they receive, mentors, childhood dreams, parental expectations, complexity of cases, the lifestyle of each specialty, including office hours worked, on-call requirements, and autonomy.

Physicians also mentioned other factors they considered when choosing their specialty:

• Personal interest.
• Intellectual stimulation.
• Work-life balance.
• Patient populations.
• Future opportunities.
• Desire to make a difference.
• Passion.
• Financial stability.
• Being personally fulfilled.

Overwhelmingly, doctors say to pick a specialty you can envision yourself loving 40 years from now and you won’t go wrong.

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

Medical student loans top hundreds of thousands of dollars, so it’s understandable that physicians may want to select a specialty that pays well.

But overwhelmingly, the physicians this news organization spoke to said they chose a specialty they were passionate about rather than focusing on going where more money was. Moreover, most advised young doctors to follow their hearts rather than their wallets.

“There is no question that many young kids immediately think about money when deciding to pursue medicine, but the thought of a big paycheck will never sustain someone long enough to get them here,” says Sergio Alvarez, MD, a board-certified plastic surgeon based in Miami, Fla., and the CEO and medical director of Mia Aesthetics, which has several national locations.

“Getting into medicine is a long game, and there are many hurdles along the way that only the dedicated overcome,” says Dr. Alvarez.

Unfortunately, he says it may be late in that long game before some realize that the pay rate for certain specialties isn’t commensurate with the immense workload and responsibility they require.

“The short of it is that to become a happy doctor, medicine really needs to be a calling: a passion! There are far easier things to do to make money.”

Here is what physicians said about choosing between love or money.
 

The lowest-paying subspecialty in a low-paying specialty

Sophia Yen, MD, MPH, cofounder and CEO of Pandia Health, a women-founded, doctor-led birth control delivery service in Sunnyvale, Calif., and clinical associate professor at Stanford (Calif.) University, says you should pursue a specialty because you love the work.

“I chose the lowest-paying subspecialty (adolescent medicine) of a low-paying specialty (pediatrics), but I’d do it all again because I love the patient population – I love what I do.”

Dr. Yen says she chose adolescent medicine because she loves doing “outpatient gynecology” without going through the surgical training of a full ob.gyn. “I love the target population of young adults because you can talk to the patient versus in pediatrics, where you often talk to the parent. With young adults you can catch things – for example, teach a young person about consent, alcohol, marijuana’s effects on the growing brain, prevent unplanned pregnancies and sexually transmitted infections, instill healthy eating, and more.

“Do I wish that I got paid as much as a surgeon?” Dr. Yen says yes. “I hope that someday society will realize the time spent preventing future disease is worth it and pay us accordingly.”

Unfortunately, she says, since the health care system makes more money if you get pregnant, need a cardiac bypass, or need gastric surgery, those who deliver babies or do surgery get paid more than someone who prevents the need for those services.
 

Money doesn’t buy happiness

Stella Bard, MD, a rheumatologist in McKinney, Tex., says she eats, lives, and breathes rheumatology. “I never regret the decision of choosing this specialty for a single second,” says Dr. Bard. “I feel like it’s a rewarding experience with every single patient encounter.” Dr. Bard notes that money is no guarantee of happiness and that she feels blessed to wake up every morning doing what she loves.

Career or calling?

For Dr. Alvarez, inspiration came when watching his father help change people’s lives. “I saw how impactful a doctor is during a person’s most desperate moments, and that was enough to make medicine my life’s passion at the age of 10.”

He says once you’re in medical school, choosing a specialty is far easier than you think. “Each specialty requires a certain personality or specific characteristics, and some will call to you while others simply won’t.”

“For me, plastics was about finesse, art, and life-changing surgeries that affected people from kids to adults and involved every aspect of the human body. Changing someone’s outward appearance has a profoundly positive impact on their confidence and self-esteem, making plastic surgery a genuinely transformative experience.”

Patricia Celan, MD, a postgraduate psychiatry resident in Canada, also chose psychiatry for the love of the field. “I enjoy helping vulnerable people and exploring what makes a person tick, the source of their difficulties, and how to help people counteract and overcome the difficult cards they’ve been dealt in life.”

She says it’s incredibly rewarding to watch someone turn their life around from severe mental illness, especially those who have been victimized and traumatized, and learn to trust people again.

“I could have made more money in a higher-paying specialty, yes, but I’m not sure I would have felt as fulfilled as psychiatry can make me feel.”

Dr. Celan says everyone has their calling, and some lucky people find their deepest passion in higher-paying specialties. “My calling is psychiatry, and I am at peace with this no matter the money.”
 

For the love of surgery

“In my experience, most people don’t choose their specialty based on money,” says Nicole Aaronson, MD, MBA, an otolaryngologist and board-certified in the subspecialty of pediatric otolaryngology, an attending surgeon at Nemours Children’s Health of Delaware and clinical associate professor of otolaryngology and pediatrics at Sidney Kimmel Medical College, Philadelphia.

“The first decision point in medical school is usually figuring out if you are a surgery person or a medicine person. I knew very early that I wanted to be a surgeon and wanted to spend time in the OR fixing problems with my hands.”

Part of what attracted Dr. Aaronson to otolaryngology was the variety of conditions managed within the specialty, from head and neck cancer to voice problems to sleep disorders to sinus disease. “I chose my subspecialty because I enjoy working with children and making an impact that will help them live their best possible lives.”

She says a relatively simple surgery like placing ear tubes may help a child’s hearing and allow them to be more successful in school, opening up a new world of opportunities for the child’s future.

“While I don’t think most people choose their specialty based on prospective compensation, I do think all physicians want to be compensated fairly for their time, effort, and level of training,” says Dr. Aaronson.
 

Choosing a specialty for the money can lead to burnout and dissatisfaction

“For me, the decision to pursue gastroenterology went beyond financial considerations,” says Saurabh Sethi, MD, MPH, a gastroenterologist specializing in hepatology and interventional endoscopy. “While financial stability is undoubtedly important, no doctor enters this field solely for the love of money. The primary driving force for most medical professionals, myself included, is the passion to help people and make a positive difference in their lives.”

Dr. Sethi says the gratification that comes from providing quality care and witnessing patients’ improved well-being is priceless. Moreover, he believes that selecting a specialty based solely on financial gain is likely to lead to burnout and greater dissatisfaction over time.

“By following my love for gut health and prioritizing patient care, I have found a sense of fulfillment and purpose in my career. It has been a rewarding journey, and I’m grateful for the opportunity to contribute to the well-being of my patients through my expertise in gastroenterology.”
 

Key takeaways: Love or money?

Multiple factors influence doctors’ specialty choices, including genuine love for the work and the future of the specialty. Others include job prospects, hands-on experience they receive, mentors, childhood dreams, parental expectations, complexity of cases, the lifestyle of each specialty, including office hours worked, on-call requirements, and autonomy.

Physicians also mentioned other factors they considered when choosing their specialty:

• Personal interest.
• Intellectual stimulation.
• Work-life balance.
• Patient populations.
• Future opportunities.
• Desire to make a difference.
• Passion.
• Financial stability.
• Being personally fulfilled.

Overwhelmingly, doctors say to pick a specialty you can envision yourself loving 40 years from now and you won’t go wrong.

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

Medical student loans top hundreds of thousands of dollars, so it’s understandable that physicians may want to select a specialty that pays well.

But overwhelmingly, the physicians this news organization spoke to said they chose a specialty they were passionate about rather than focusing on going where more money was. Moreover, most advised young doctors to follow their hearts rather than their wallets.

“There is no question that many young kids immediately think about money when deciding to pursue medicine, but the thought of a big paycheck will never sustain someone long enough to get them here,” says Sergio Alvarez, MD, a board-certified plastic surgeon based in Miami, Fla., and the CEO and medical director of Mia Aesthetics, which has several national locations.

“Getting into medicine is a long game, and there are many hurdles along the way that only the dedicated overcome,” says Dr. Alvarez.

Unfortunately, he says it may be late in that long game before some realize that the pay rate for certain specialties isn’t commensurate with the immense workload and responsibility they require.

“The short of it is that to become a happy doctor, medicine really needs to be a calling: a passion! There are far easier things to do to make money.”

Here is what physicians said about choosing between love or money.
 

The lowest-paying subspecialty in a low-paying specialty

Sophia Yen, MD, MPH, cofounder and CEO of Pandia Health, a women-founded, doctor-led birth control delivery service in Sunnyvale, Calif., and clinical associate professor at Stanford (Calif.) University, says you should pursue a specialty because you love the work.

“I chose the lowest-paying subspecialty (adolescent medicine) of a low-paying specialty (pediatrics), but I’d do it all again because I love the patient population – I love what I do.”

Dr. Yen says she chose adolescent medicine because she loves doing “outpatient gynecology” without going through the surgical training of a full ob.gyn. “I love the target population of young adults because you can talk to the patient versus in pediatrics, where you often talk to the parent. With young adults you can catch things – for example, teach a young person about consent, alcohol, marijuana’s effects on the growing brain, prevent unplanned pregnancies and sexually transmitted infections, instill healthy eating, and more.

“Do I wish that I got paid as much as a surgeon?” Dr. Yen says yes. “I hope that someday society will realize the time spent preventing future disease is worth it and pay us accordingly.”

Unfortunately, she says, since the health care system makes more money if you get pregnant, need a cardiac bypass, or need gastric surgery, those who deliver babies or do surgery get paid more than someone who prevents the need for those services.
 

Money doesn’t buy happiness

Stella Bard, MD, a rheumatologist in McKinney, Tex., says she eats, lives, and breathes rheumatology. “I never regret the decision of choosing this specialty for a single second,” says Dr. Bard. “I feel like it’s a rewarding experience with every single patient encounter.” Dr. Bard notes that money is no guarantee of happiness and that she feels blessed to wake up every morning doing what she loves.

Career or calling?

For Dr. Alvarez, inspiration came when watching his father help change people’s lives. “I saw how impactful a doctor is during a person’s most desperate moments, and that was enough to make medicine my life’s passion at the age of 10.”

He says once you’re in medical school, choosing a specialty is far easier than you think. “Each specialty requires a certain personality or specific characteristics, and some will call to you while others simply won’t.”

“For me, plastics was about finesse, art, and life-changing surgeries that affected people from kids to adults and involved every aspect of the human body. Changing someone’s outward appearance has a profoundly positive impact on their confidence and self-esteem, making plastic surgery a genuinely transformative experience.”

Patricia Celan, MD, a postgraduate psychiatry resident in Canada, also chose psychiatry for the love of the field. “I enjoy helping vulnerable people and exploring what makes a person tick, the source of their difficulties, and how to help people counteract and overcome the difficult cards they’ve been dealt in life.”

She says it’s incredibly rewarding to watch someone turn their life around from severe mental illness, especially those who have been victimized and traumatized, and learn to trust people again.

“I could have made more money in a higher-paying specialty, yes, but I’m not sure I would have felt as fulfilled as psychiatry can make me feel.”

Dr. Celan says everyone has their calling, and some lucky people find their deepest passion in higher-paying specialties. “My calling is psychiatry, and I am at peace with this no matter the money.”
 

For the love of surgery

“In my experience, most people don’t choose their specialty based on money,” says Nicole Aaronson, MD, MBA, an otolaryngologist and board-certified in the subspecialty of pediatric otolaryngology, an attending surgeon at Nemours Children’s Health of Delaware and clinical associate professor of otolaryngology and pediatrics at Sidney Kimmel Medical College, Philadelphia.

“The first decision point in medical school is usually figuring out if you are a surgery person or a medicine person. I knew very early that I wanted to be a surgeon and wanted to spend time in the OR fixing problems with my hands.”

Part of what attracted Dr. Aaronson to otolaryngology was the variety of conditions managed within the specialty, from head and neck cancer to voice problems to sleep disorders to sinus disease. “I chose my subspecialty because I enjoy working with children and making an impact that will help them live their best possible lives.”

She says a relatively simple surgery like placing ear tubes may help a child’s hearing and allow them to be more successful in school, opening up a new world of opportunities for the child’s future.

“While I don’t think most people choose their specialty based on prospective compensation, I do think all physicians want to be compensated fairly for their time, effort, and level of training,” says Dr. Aaronson.
 

Choosing a specialty for the money can lead to burnout and dissatisfaction

“For me, the decision to pursue gastroenterology went beyond financial considerations,” says Saurabh Sethi, MD, MPH, a gastroenterologist specializing in hepatology and interventional endoscopy. “While financial stability is undoubtedly important, no doctor enters this field solely for the love of money. The primary driving force for most medical professionals, myself included, is the passion to help people and make a positive difference in their lives.”

Dr. Sethi says the gratification that comes from providing quality care and witnessing patients’ improved well-being is priceless. Moreover, he believes that selecting a specialty based solely on financial gain is likely to lead to burnout and greater dissatisfaction over time.

“By following my love for gut health and prioritizing patient care, I have found a sense of fulfillment and purpose in my career. It has been a rewarding journey, and I’m grateful for the opportunity to contribute to the well-being of my patients through my expertise in gastroenterology.”
 

Key takeaways: Love or money?

Multiple factors influence doctors’ specialty choices, including genuine love for the work and the future of the specialty. Others include job prospects, hands-on experience they receive, mentors, childhood dreams, parental expectations, complexity of cases, the lifestyle of each specialty, including office hours worked, on-call requirements, and autonomy.

Physicians also mentioned other factors they considered when choosing their specialty:

• Personal interest.
• Intellectual stimulation.
• Work-life balance.
• Patient populations.
• Future opportunities.
• Desire to make a difference.
• Passion.
• Financial stability.
• Being personally fulfilled.

Overwhelmingly, doctors say to pick a specialty you can envision yourself loving 40 years from now and you won’t go wrong.

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

Topline

Even 2 days off from radiotherapy for triple-negative breast cancer (TNBC) may affect overall survival.

Methodology

• Clinicians sometimes give women with TNBC a break between radiation sessions so that their skin can heal.
• To gauge the impact, investigators reviewed data from the National Cancer Database on 35,845 patients with TNBC who were treated between 2010 and 2014.
• The researchers determined the number of interrupted radiation treatment days as the difference between the number of days women received radiotherapy versus the number of expected treatment days.
• The team then correlated treatment interruptions with overall survival.

Takeaway

• Longer duration of treatment was associated with worse overall survival (hazard ratio, 1.023).
• Compared with no days or just 1 day off, 2-5 interrupted days (HR, 1.069), 6-10 interrupted days (HR, 1.239), and 11-15 interrupted days (HR, 1.265) increased the likelihood of death in a stepwise fashion.
• More days between diagnosis and first cancer treatment of any kind (HR, 1.001) were associated with worse overall survival.
• Older age (HR, 1.014), Black race (HR, 1.278), race than other Black or White (HR, 1.337), grade II or III/IV tumors (HR, 1.471 and 1.743, respectively), and clinical N1-N3 stage (HR, 2.534, 3.729, 4.992, respectively) were also associated with worse overall survival.

In practice

“All reasonable efforts should be made to prevent any treatment interruptions,” including “prophylactic measures to reduce the severity of radiation dermatitis,” and consideration should be given to the use of hypofractionated regimens to shorten radiation schedules.

Source

The study was led by Ronald Chow, MS, of the Memorial Sloan Kettering Cancer Center, New York, and was published  in the Journal of the National Cancer Institute.

Limitations

• The findings may not be applicable to less aggressive forms of breast cancer.
• Treatment interruptions may have been caused by poor performance status and other confounders that shorten survival.

Disclosures

The study was funded by the National Cancer Institute. The investigators had no disclosures.

A version of this article appeared on Medscape.com.

Topline

Even 2 days off from radiotherapy for triple-negative breast cancer (TNBC) may affect overall survival.

Methodology

• Clinicians sometimes give women with TNBC a break between radiation sessions so that their skin can heal.
• To gauge the impact, investigators reviewed data from the National Cancer Database on 35,845 patients with TNBC who were treated between 2010 and 2014.
• The researchers determined the number of interrupted radiation treatment days as the difference between the number of days women received radiotherapy versus the number of expected treatment days.
• The team then correlated treatment interruptions with overall survival.

Takeaway

• Longer duration of treatment was associated with worse overall survival (hazard ratio, 1.023).
• Compared with no days or just 1 day off, 2-5 interrupted days (HR, 1.069), 6-10 interrupted days (HR, 1.239), and 11-15 interrupted days (HR, 1.265) increased the likelihood of death in a stepwise fashion.
• More days between diagnosis and first cancer treatment of any kind (HR, 1.001) were associated with worse overall survival.
• Older age (HR, 1.014), Black race (HR, 1.278), race than other Black or White (HR, 1.337), grade II or III/IV tumors (HR, 1.471 and 1.743, respectively), and clinical N1-N3 stage (HR, 2.534, 3.729, 4.992, respectively) were also associated with worse overall survival.

In practice

“All reasonable efforts should be made to prevent any treatment interruptions,” including “prophylactic measures to reduce the severity of radiation dermatitis,” and consideration should be given to the use of hypofractionated regimens to shorten radiation schedules.

Source

The study was led by Ronald Chow, MS, of the Memorial Sloan Kettering Cancer Center, New York, and was published  in the Journal of the National Cancer Institute.

Limitations

• The findings may not be applicable to less aggressive forms of breast cancer.
• Treatment interruptions may have been caused by poor performance status and other confounders that shorten survival.

Disclosures

The study was funded by the National Cancer Institute. The investigators had no disclosures.

A version of this article appeared on Medscape.com.

Topline

Even 2 days off from radiotherapy for triple-negative breast cancer (TNBC) may affect overall survival.

Methodology

• Clinicians sometimes give women with TNBC a break between radiation sessions so that their skin can heal.
• To gauge the impact, investigators reviewed data from the National Cancer Database on 35,845 patients with TNBC who were treated between 2010 and 2014.
• The researchers determined the number of interrupted radiation treatment days as the difference between the number of days women received radiotherapy versus the number of expected treatment days.
• The team then correlated treatment interruptions with overall survival.

Takeaway

• Longer duration of treatment was associated with worse overall survival (hazard ratio, 1.023).
• Compared with no days or just 1 day off, 2-5 interrupted days (HR, 1.069), 6-10 interrupted days (HR, 1.239), and 11-15 interrupted days (HR, 1.265) increased the likelihood of death in a stepwise fashion.
• More days between diagnosis and first cancer treatment of any kind (HR, 1.001) were associated with worse overall survival.
• Older age (HR, 1.014), Black race (HR, 1.278), race than other Black or White (HR, 1.337), grade II or III/IV tumors (HR, 1.471 and 1.743, respectively), and clinical N1-N3 stage (HR, 2.534, 3.729, 4.992, respectively) were also associated with worse overall survival.

In practice

“All reasonable efforts should be made to prevent any treatment interruptions,” including “prophylactic measures to reduce the severity of radiation dermatitis,” and consideration should be given to the use of hypofractionated regimens to shorten radiation schedules.

Source

The study was led by Ronald Chow, MS, of the Memorial Sloan Kettering Cancer Center, New York, and was published  in the Journal of the National Cancer Institute.

Limitations

• The findings may not be applicable to less aggressive forms of breast cancer.
• Treatment interruptions may have been caused by poor performance status and other confounders that shorten survival.

Disclosures

The study was funded by the National Cancer Institute. The investigators had no disclosures.

A version of this article appeared on Medscape.com.

Topline

Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.

Methodology

• Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
• Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
• Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
• General fatigue trajectories were classified as low, moderate, high, or decreasing.

Takeaways

• In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
• About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
• Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
• Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.

In practice

“Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered,” the authors concluded.
 

Source

The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
 

Limitations

About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
 

Disclosures

The study had no commercial funding. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Topline

Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.

Methodology

• Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
• Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
• Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
• General fatigue trajectories were classified as low, moderate, high, or decreasing.

Takeaways

• In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
• About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
• Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
• Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.

In practice

“Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered,” the authors concluded.
 

Source

The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
 

Limitations

About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
 

Disclosures

The study had no commercial funding. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Topline

Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.

Methodology

• Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
• Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
• Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
• General fatigue trajectories were classified as low, moderate, high, or decreasing.

Takeaways

• In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
• About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
• Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
• Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.

In practice

“Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered,” the authors concluded.
 

Source

The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
 

Limitations

About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
 

Disclosures

The study had no commercial funding. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The history and findings in this case are suggestive of combined small cell lung cancer (SCLC).

Globally, lung cancer is the leading cause of cancer incidence and mortality, accounting for an estimated 2 million new diagnoses and 1.76 million deaths per year. It consists of two major subtypes: non-small cell lung cancer (NSCLC) and SCLC. SCLC is unique in its presentation, imaging appearances, treatment, and prognosis. SCLC accounts for approximately 15% of all lung cancers and is associated with an exceptionally high proliferative rate, strong predilection for early metastasis, and poor prognosis.

There are two subtypes of SCLC: oat cell carcinoma and combined SCLC. Combined SCLC is defined as SCLC with non-small cell components, such as squamous cell or adenocarcinoma. Men are affected more frequently than are women. Most presenting patients are older than 70 years and are either a current or former smoker. Patients frequently have multiple cardiovascular or pulmonary comorbidities.

In most cases, patients experience rapid onset of symptoms, normally beginning 8-12 weeks before presentation. Signs and symptoms vary depending on the location and bulk of the primary tumor, but may include cough, wheezing, and hemoptysis as well as weight loss, debility, and other signs of metastatic disease. Local intrathoracic tumor growth can affect the superior vena cava (leading to superior vena cava syndrome), chest wall, or esophagus. Neurologic problems, recurrent nerve pain, fatigue, and anorexia may result from extrapulmonary metastasis. Nearly 60% of patients present with metastatic disease, most commonly in the brain, liver, adrenal glands, bone, and bone marrow. If left untreated, SCLC tumors progress rapidly, with a median survival of 2-4 months.

All patients with SCLC require a thorough staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. The initial imaging workup includes plain film radiography and contrast-enhanced CT of the chest and upper abdomen, brain MRI, and PET-CT. Laboratory studies to evaluate for the presence of neoplastic syndromes include complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase, total bilirubin, and creatinine. Biopsy is usually obtained via CT-guided biopsy or transbronchial biopsy, though this can vary depending on the location of the tumor.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), most patients with limited-stage SCLC are not eligible for surgery or stereotactic ablative radiotherapy (SABR). Surgery is only recommended for select patients with stage I–IIA SCLC (about 5% of patients). Concurrent chemoradiation or SABR is recommended for patients with limited stage I-IIA (T1-2,N0) SCLC who are ineligible for or do not want to pursue surgical resection. The majority of patients with SCLC have extensive-stage disease, and treatment with systemic therapy alone (with or without palliative radiotherapy) is recommended. Preferred cytotoxic and immunotherapeutic agents can be found in the NCCN guidelines. 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of combined small cell lung cancer (SCLC).

Globally, lung cancer is the leading cause of cancer incidence and mortality, accounting for an estimated 2 million new diagnoses and 1.76 million deaths per year. It consists of two major subtypes: non-small cell lung cancer (NSCLC) and SCLC. SCLC is unique in its presentation, imaging appearances, treatment, and prognosis. SCLC accounts for approximately 15% of all lung cancers and is associated with an exceptionally high proliferative rate, strong predilection for early metastasis, and poor prognosis.

There are two subtypes of SCLC: oat cell carcinoma and combined SCLC. Combined SCLC is defined as SCLC with non-small cell components, such as squamous cell or adenocarcinoma. Men are affected more frequently than are women. Most presenting patients are older than 70 years and are either a current or former smoker. Patients frequently have multiple cardiovascular or pulmonary comorbidities.

In most cases, patients experience rapid onset of symptoms, normally beginning 8-12 weeks before presentation. Signs and symptoms vary depending on the location and bulk of the primary tumor, but may include cough, wheezing, and hemoptysis as well as weight loss, debility, and other signs of metastatic disease. Local intrathoracic tumor growth can affect the superior vena cava (leading to superior vena cava syndrome), chest wall, or esophagus. Neurologic problems, recurrent nerve pain, fatigue, and anorexia may result from extrapulmonary metastasis. Nearly 60% of patients present with metastatic disease, most commonly in the brain, liver, adrenal glands, bone, and bone marrow. If left untreated, SCLC tumors progress rapidly, with a median survival of 2-4 months.

All patients with SCLC require a thorough staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. The initial imaging workup includes plain film radiography and contrast-enhanced CT of the chest and upper abdomen, brain MRI, and PET-CT. Laboratory studies to evaluate for the presence of neoplastic syndromes include complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase, total bilirubin, and creatinine. Biopsy is usually obtained via CT-guided biopsy or transbronchial biopsy, though this can vary depending on the location of the tumor.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), most patients with limited-stage SCLC are not eligible for surgery or stereotactic ablative radiotherapy (SABR). Surgery is only recommended for select patients with stage I–IIA SCLC (about 5% of patients). Concurrent chemoradiation or SABR is recommended for patients with limited stage I-IIA (T1-2,N0) SCLC who are ineligible for or do not want to pursue surgical resection. The majority of patients with SCLC have extensive-stage disease, and treatment with systemic therapy alone (with or without palliative radiotherapy) is recommended. Preferred cytotoxic and immunotherapeutic agents can be found in the NCCN guidelines. 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of combined small cell lung cancer (SCLC).

Globally, lung cancer is the leading cause of cancer incidence and mortality, accounting for an estimated 2 million new diagnoses and 1.76 million deaths per year. It consists of two major subtypes: non-small cell lung cancer (NSCLC) and SCLC. SCLC is unique in its presentation, imaging appearances, treatment, and prognosis. SCLC accounts for approximately 15% of all lung cancers and is associated with an exceptionally high proliferative rate, strong predilection for early metastasis, and poor prognosis.

There are two subtypes of SCLC: oat cell carcinoma and combined SCLC. Combined SCLC is defined as SCLC with non-small cell components, such as squamous cell or adenocarcinoma. Men are affected more frequently than are women. Most presenting patients are older than 70 years and are either a current or former smoker. Patients frequently have multiple cardiovascular or pulmonary comorbidities.

In most cases, patients experience rapid onset of symptoms, normally beginning 8-12 weeks before presentation. Signs and symptoms vary depending on the location and bulk of the primary tumor, but may include cough, wheezing, and hemoptysis as well as weight loss, debility, and other signs of metastatic disease. Local intrathoracic tumor growth can affect the superior vena cava (leading to superior vena cava syndrome), chest wall, or esophagus. Neurologic problems, recurrent nerve pain, fatigue, and anorexia may result from extrapulmonary metastasis. Nearly 60% of patients present with metastatic disease, most commonly in the brain, liver, adrenal glands, bone, and bone marrow. If left untreated, SCLC tumors progress rapidly, with a median survival of 2-4 months.

All patients with SCLC require a thorough staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. The initial imaging workup includes plain film radiography and contrast-enhanced CT of the chest and upper abdomen, brain MRI, and PET-CT. Laboratory studies to evaluate for the presence of neoplastic syndromes include complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase, total bilirubin, and creatinine. Biopsy is usually obtained via CT-guided biopsy or transbronchial biopsy, though this can vary depending on the location of the tumor.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), most patients with limited-stage SCLC are not eligible for surgery or stereotactic ablative radiotherapy (SABR). Surgery is only recommended for select patients with stage I–IIA SCLC (about 5% of patients). Concurrent chemoradiation or SABR is recommended for patients with limited stage I-IIA (T1-2,N0) SCLC who are ineligible for or do not want to pursue surgical resection. The majority of patients with SCLC have extensive-stage disease, and treatment with systemic therapy alone (with or without palliative radiotherapy) is recommended. Preferred cytotoxic and immunotherapeutic agents can be found in the NCCN guidelines. 

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

Anxiety symptoms in children are common, ranging from a toddler’s fear of the dark to an adolescent worrying about a major exam. Anxiety disorders, symptoms that are persistent and impact functioning, are the most common psychiatric illnesses of childhood. The good news is that, if they are detected early and treated appropriately, they are curable. Unfortunately, they are often silent, or present with misleading symptoms. Screening for anxiety disorders, especially in the presence of the most common presenting concerns, can illuminate the true nature of a child’s challenge and point the way forward. In this month’s article, we will provide details on the prevalence of anxiety disorders in children, how they typically present, and how best to screen for them. We will offer some strategies for speaking about them with your patients and their parents, as well as introduce some of the strategies that can improve mild to moderate anxiety disorders. We will follow up with another piece on the evidence-based treatments for these common disorders, how to find appropriate referrals, and what you can do in your office to get treatment started.

Anxiety disorders: Common and treatable

Anxiety disorders – including separation anxiety disorder, social phobia, simple phobias, generalized anxiety disorder, panic disorder, and PTSD – affect between 15% and 20% of children before the age of 18, with some recent estimates as high as 31.9% of youth being affected. Indeed, the mean age of onset for most anxiety disorders (excluding panic disorder and PTSD) is between 5 and 9 years of age. Despite being so common, many anxiety disorders in childhood are never properly diagnosed, and most (as many as 80%) do not receive treatment from a mental health professional. With early diagnosis and evidence-based treatment, most anxiety disorders can be “cured” and no longer impair functioning. Untreated, anxiety disorders usually have a chronic course, causing significant behavioral problems and disruption of a child’s critical social, emotional, and identity development and their academic function. Untreated, they are frequently complicated in adolescence by mood, substance use, and eating disorders. With the passage of time, developmental consequences and comorbid illnesses, a curable childhood anxiety disorder can become a complex and entrenched psychiatric syndrome in young adulthood.

One of the reasons these illnesses frequently go unrecognized is that states of fearful distress, such as separation anxiety or social anxiety, are developmentally normal at different stages of childhood, and it can be difficult to discriminate between normal and pathological anxiety. Anxiety itself is an “internalizing” symptom, and is invisible except for the behaviors that can accompany it. Some behaviors suggest anxiety, such as fearful expressions, clinginess, excessive need for reassurance, or avoidance. But anxiety can also lead to obstinate refusal to do certain things. It might lead to explosive tantrums when a child is pushed to do something that makes them intensely anxious. It can lead to irritability and moody tantrums for a child exhausted after a long school day spent managing high levels of anxiety by themselves. Anxious children often appear inattentive in school. Anxiety disorders frequently disrupt restful sleep, leading to children who are irritable and moody as well as inattentive. These children may present to the pediatrician with frustrated parents concerned that they are oppositional or explosive, or because their teachers are concerned about ADHD, when the culprit is actually anxiety.

While anxiety is uncomfortable, these children are unlikely to experience their anxiety as unusual and foreign, like a sudden toothache. Instead, it feels to them like they are fearful for good reason, responding appropriately to something real. These children are more likely to respond to a novel or uncertain situation with worry rather than curiosity, and to a new challenge as a threat. For children who are managing their anxiety more internally, their parents are often unaware of their degree of distress. Indeed, these children are often careful, thoughtful, and attentive to detail. Parents and teachers may think they are doing wonderfully. They are typically very sensitive to physical discomforts, which are heightened by an anxious state. These are likely to present to the pediatrician’s office with parents very worried about a cluster of vague physical complaints (stomach ache, headache, “just not feeling good”), which coincides with a change, challenge, or anxious stimulus. In this situation, the parents may dismiss the possibility of anxiety, and the child may not even be aware of it. But it will get worse if they are pushed to bear the source of anxiety (going to school, sports practice, etc.).
 

Anxiety screening and treatment

When a child presents for a sick visit with vague symptoms, or a negative workup for specific ones, you should screen them for an anxiety disorder. When they present with concerns about inattention, insomnia, moodiness, obstinacy, and even explosive behaviors, you should screen them for an anxiety disorder. This is especially true if they are prepubertal, when anxiety disorders are far more common than mood disorders. But you should consider anxiety disorders alongside mood disorders in adolescents presenting with these complaints. While parents may be unaware of the presence of anxiety in their child, explain to them that anxiety disorders are very common and treatable in childhood to help them understand the value of screening. Asking children directly about their internal experience can also be helpful. Avoid asking about “anxiety,” instead asking if they ever worry about specific things, such as “talking to kids you don’t know at recess,” “being alone at home,” “getting robbed or kidnapped,” or “something bad happening to your parents.” Just asking helps children pay attention to their thoughts and feelings, and is a powerful screening instrument.

There are also real screening instruments that you might use routinely for sick visits in prepubertal children or when anxiety should be in the differential. These instruments can be prone to recall bias, but generally make it easier for (anxious) children to accurately describe their internal experience. An instrument like the GAD7 is brief, free, and sensitive, but not very specific. If it is positive, you can then offer a longer screen such as the SCARED, also free, which indicates likely diagnoses such as generalized anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. There is a parent version and a self-report, and it is validated for youths 8-18 years old and takes approximately 20 minutes to complete and score.

A positive screen should lead to a more nuanced conversation with your patient and their parents about their anxiety symptoms. You may feel comfortable doing a more extensive interview to make the likely diagnosis or may prefer to refer to a psychiatrist or psychologist to assist with diagnosis and treatment recommendations. In either case, you can offer your patient and their parents meaningful reassurance that the intense discomfort of their anxiety will get better with effective treatment. In this visit, you can get treatment started by identifying what parents and their children can do right away to begin addressing anxiety symptoms. Offer strategies to protect and promote restful sleep and daily vigorous exercise, both of which can directly improve mild to moderate anxiety symptoms. Suggest to parents that they should help their children to notice what they are feeling, rather than rushing in to remove a source of anxiety. These measures can help their child to identify what is a thought, a feeling, a physical sensation, or a fact. They can offer support and validation around how uncomfortable these feelings are, but just being curious will reassure their child that they will be able to manage and master this feeling. This “practice” is akin to what their child will do in most effective treatments, and will have the added benefit of helping them to build skills that all children need to manage the challenges and worries that are a normal, but difficult part of growing up and of adult life. Finally, you can tell them that anxious temperaments come with advantages also, such as great powers of observation, attention to detail, and thoroughness, high levels of empathy, drive, and tenacity. By learning to manage anxiety early, these children can grow up to be engaged, resilient, successful, and satisfied adults.

Once identified, the range of effective treatments available include cognitive-behavioral therapy, graduated exposure, mindfulness/relaxation techniques, and medication, and we will discuss these in our next article.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Reference

Beesdo K et al. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. doi: 10.1016/j.psc.2009.06.002.

Anxiety symptoms in children are common, ranging from a toddler’s fear of the dark to an adolescent worrying about a major exam. Anxiety disorders, symptoms that are persistent and impact functioning, are the most common psychiatric illnesses of childhood. The good news is that, if they are detected early and treated appropriately, they are curable. Unfortunately, they are often silent, or present with misleading symptoms. Screening for anxiety disorders, especially in the presence of the most common presenting concerns, can illuminate the true nature of a child’s challenge and point the way forward. In this month’s article, we will provide details on the prevalence of anxiety disorders in children, how they typically present, and how best to screen for them. We will offer some strategies for speaking about them with your patients and their parents, as well as introduce some of the strategies that can improve mild to moderate anxiety disorders. We will follow up with another piece on the evidence-based treatments for these common disorders, how to find appropriate referrals, and what you can do in your office to get treatment started.

Anxiety disorders: Common and treatable

Anxiety disorders – including separation anxiety disorder, social phobia, simple phobias, generalized anxiety disorder, panic disorder, and PTSD – affect between 15% and 20% of children before the age of 18, with some recent estimates as high as 31.9% of youth being affected. Indeed, the mean age of onset for most anxiety disorders (excluding panic disorder and PTSD) is between 5 and 9 years of age. Despite being so common, many anxiety disorders in childhood are never properly diagnosed, and most (as many as 80%) do not receive treatment from a mental health professional. With early diagnosis and evidence-based treatment, most anxiety disorders can be “cured” and no longer impair functioning. Untreated, anxiety disorders usually have a chronic course, causing significant behavioral problems and disruption of a child’s critical social, emotional, and identity development and their academic function. Untreated, they are frequently complicated in adolescence by mood, substance use, and eating disorders. With the passage of time, developmental consequences and comorbid illnesses, a curable childhood anxiety disorder can become a complex and entrenched psychiatric syndrome in young adulthood.

One of the reasons these illnesses frequently go unrecognized is that states of fearful distress, such as separation anxiety or social anxiety, are developmentally normal at different stages of childhood, and it can be difficult to discriminate between normal and pathological anxiety. Anxiety itself is an “internalizing” symptom, and is invisible except for the behaviors that can accompany it. Some behaviors suggest anxiety, such as fearful expressions, clinginess, excessive need for reassurance, or avoidance. But anxiety can also lead to obstinate refusal to do certain things. It might lead to explosive tantrums when a child is pushed to do something that makes them intensely anxious. It can lead to irritability and moody tantrums for a child exhausted after a long school day spent managing high levels of anxiety by themselves. Anxious children often appear inattentive in school. Anxiety disorders frequently disrupt restful sleep, leading to children who are irritable and moody as well as inattentive. These children may present to the pediatrician with frustrated parents concerned that they are oppositional or explosive, or because their teachers are concerned about ADHD, when the culprit is actually anxiety.

While anxiety is uncomfortable, these children are unlikely to experience their anxiety as unusual and foreign, like a sudden toothache. Instead, it feels to them like they are fearful for good reason, responding appropriately to something real. These children are more likely to respond to a novel or uncertain situation with worry rather than curiosity, and to a new challenge as a threat. For children who are managing their anxiety more internally, their parents are often unaware of their degree of distress. Indeed, these children are often careful, thoughtful, and attentive to detail. Parents and teachers may think they are doing wonderfully. They are typically very sensitive to physical discomforts, which are heightened by an anxious state. These are likely to present to the pediatrician’s office with parents very worried about a cluster of vague physical complaints (stomach ache, headache, “just not feeling good”), which coincides with a change, challenge, or anxious stimulus. In this situation, the parents may dismiss the possibility of anxiety, and the child may not even be aware of it. But it will get worse if they are pushed to bear the source of anxiety (going to school, sports practice, etc.).
 

Anxiety screening and treatment

When a child presents for a sick visit with vague symptoms, or a negative workup for specific ones, you should screen them for an anxiety disorder. When they present with concerns about inattention, insomnia, moodiness, obstinacy, and even explosive behaviors, you should screen them for an anxiety disorder. This is especially true if they are prepubertal, when anxiety disorders are far more common than mood disorders. But you should consider anxiety disorders alongside mood disorders in adolescents presenting with these complaints. While parents may be unaware of the presence of anxiety in their child, explain to them that anxiety disorders are very common and treatable in childhood to help them understand the value of screening. Asking children directly about their internal experience can also be helpful. Avoid asking about “anxiety,” instead asking if they ever worry about specific things, such as “talking to kids you don’t know at recess,” “being alone at home,” “getting robbed or kidnapped,” or “something bad happening to your parents.” Just asking helps children pay attention to their thoughts and feelings, and is a powerful screening instrument.

There are also real screening instruments that you might use routinely for sick visits in prepubertal children or when anxiety should be in the differential. These instruments can be prone to recall bias, but generally make it easier for (anxious) children to accurately describe their internal experience. An instrument like the GAD7 is brief, free, and sensitive, but not very specific. If it is positive, you can then offer a longer screen such as the SCARED, also free, which indicates likely diagnoses such as generalized anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. There is a parent version and a self-report, and it is validated for youths 8-18 years old and takes approximately 20 minutes to complete and score.

A positive screen should lead to a more nuanced conversation with your patient and their parents about their anxiety symptoms. You may feel comfortable doing a more extensive interview to make the likely diagnosis or may prefer to refer to a psychiatrist or psychologist to assist with diagnosis and treatment recommendations. In either case, you can offer your patient and their parents meaningful reassurance that the intense discomfort of their anxiety will get better with effective treatment. In this visit, you can get treatment started by identifying what parents and their children can do right away to begin addressing anxiety symptoms. Offer strategies to protect and promote restful sleep and daily vigorous exercise, both of which can directly improve mild to moderate anxiety symptoms. Suggest to parents that they should help their children to notice what they are feeling, rather than rushing in to remove a source of anxiety. These measures can help their child to identify what is a thought, a feeling, a physical sensation, or a fact. They can offer support and validation around how uncomfortable these feelings are, but just being curious will reassure their child that they will be able to manage and master this feeling. This “practice” is akin to what their child will do in most effective treatments, and will have the added benefit of helping them to build skills that all children need to manage the challenges and worries that are a normal, but difficult part of growing up and of adult life. Finally, you can tell them that anxious temperaments come with advantages also, such as great powers of observation, attention to detail, and thoroughness, high levels of empathy, drive, and tenacity. By learning to manage anxiety early, these children can grow up to be engaged, resilient, successful, and satisfied adults.

Once identified, the range of effective treatments available include cognitive-behavioral therapy, graduated exposure, mindfulness/relaxation techniques, and medication, and we will discuss these in our next article.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Reference

Beesdo K et al. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. doi: 10.1016/j.psc.2009.06.002.

Anxiety symptoms in children are common, ranging from a toddler’s fear of the dark to an adolescent worrying about a major exam. Anxiety disorders, symptoms that are persistent and impact functioning, are the most common psychiatric illnesses of childhood. The good news is that, if they are detected early and treated appropriately, they are curable. Unfortunately, they are often silent, or present with misleading symptoms. Screening for anxiety disorders, especially in the presence of the most common presenting concerns, can illuminate the true nature of a child’s challenge and point the way forward. In this month’s article, we will provide details on the prevalence of anxiety disorders in children, how they typically present, and how best to screen for them. We will offer some strategies for speaking about them with your patients and their parents, as well as introduce some of the strategies that can improve mild to moderate anxiety disorders. We will follow up with another piece on the evidence-based treatments for these common disorders, how to find appropriate referrals, and what you can do in your office to get treatment started.

Anxiety disorders: Common and treatable

Anxiety disorders – including separation anxiety disorder, social phobia, simple phobias, generalized anxiety disorder, panic disorder, and PTSD – affect between 15% and 20% of children before the age of 18, with some recent estimates as high as 31.9% of youth being affected. Indeed, the mean age of onset for most anxiety disorders (excluding panic disorder and PTSD) is between 5 and 9 years of age. Despite being so common, many anxiety disorders in childhood are never properly diagnosed, and most (as many as 80%) do not receive treatment from a mental health professional. With early diagnosis and evidence-based treatment, most anxiety disorders can be “cured” and no longer impair functioning. Untreated, anxiety disorders usually have a chronic course, causing significant behavioral problems and disruption of a child’s critical social, emotional, and identity development and their academic function. Untreated, they are frequently complicated in adolescence by mood, substance use, and eating disorders. With the passage of time, developmental consequences and comorbid illnesses, a curable childhood anxiety disorder can become a complex and entrenched psychiatric syndrome in young adulthood.

One of the reasons these illnesses frequently go unrecognized is that states of fearful distress, such as separation anxiety or social anxiety, are developmentally normal at different stages of childhood, and it can be difficult to discriminate between normal and pathological anxiety. Anxiety itself is an “internalizing” symptom, and is invisible except for the behaviors that can accompany it. Some behaviors suggest anxiety, such as fearful expressions, clinginess, excessive need for reassurance, or avoidance. But anxiety can also lead to obstinate refusal to do certain things. It might lead to explosive tantrums when a child is pushed to do something that makes them intensely anxious. It can lead to irritability and moody tantrums for a child exhausted after a long school day spent managing high levels of anxiety by themselves. Anxious children often appear inattentive in school. Anxiety disorders frequently disrupt restful sleep, leading to children who are irritable and moody as well as inattentive. These children may present to the pediatrician with frustrated parents concerned that they are oppositional or explosive, or because their teachers are concerned about ADHD, when the culprit is actually anxiety.

While anxiety is uncomfortable, these children are unlikely to experience their anxiety as unusual and foreign, like a sudden toothache. Instead, it feels to them like they are fearful for good reason, responding appropriately to something real. These children are more likely to respond to a novel or uncertain situation with worry rather than curiosity, and to a new challenge as a threat. For children who are managing their anxiety more internally, their parents are often unaware of their degree of distress. Indeed, these children are often careful, thoughtful, and attentive to detail. Parents and teachers may think they are doing wonderfully. They are typically very sensitive to physical discomforts, which are heightened by an anxious state. These are likely to present to the pediatrician’s office with parents very worried about a cluster of vague physical complaints (stomach ache, headache, “just not feeling good”), which coincides with a change, challenge, or anxious stimulus. In this situation, the parents may dismiss the possibility of anxiety, and the child may not even be aware of it. But it will get worse if they are pushed to bear the source of anxiety (going to school, sports practice, etc.).
 

Anxiety screening and treatment

When a child presents for a sick visit with vague symptoms, or a negative workup for specific ones, you should screen them for an anxiety disorder. When they present with concerns about inattention, insomnia, moodiness, obstinacy, and even explosive behaviors, you should screen them for an anxiety disorder. This is especially true if they are prepubertal, when anxiety disorders are far more common than mood disorders. But you should consider anxiety disorders alongside mood disorders in adolescents presenting with these complaints. While parents may be unaware of the presence of anxiety in their child, explain to them that anxiety disorders are very common and treatable in childhood to help them understand the value of screening. Asking children directly about their internal experience can also be helpful. Avoid asking about “anxiety,” instead asking if they ever worry about specific things, such as “talking to kids you don’t know at recess,” “being alone at home,” “getting robbed or kidnapped,” or “something bad happening to your parents.” Just asking helps children pay attention to their thoughts and feelings, and is a powerful screening instrument.

There are also real screening instruments that you might use routinely for sick visits in prepubertal children or when anxiety should be in the differential. These instruments can be prone to recall bias, but generally make it easier for (anxious) children to accurately describe their internal experience. An instrument like the GAD7 is brief, free, and sensitive, but not very specific. If it is positive, you can then offer a longer screen such as the SCARED, also free, which indicates likely diagnoses such as generalized anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. There is a parent version and a self-report, and it is validated for youths 8-18 years old and takes approximately 20 minutes to complete and score.

A positive screen should lead to a more nuanced conversation with your patient and their parents about their anxiety symptoms. You may feel comfortable doing a more extensive interview to make the likely diagnosis or may prefer to refer to a psychiatrist or psychologist to assist with diagnosis and treatment recommendations. In either case, you can offer your patient and their parents meaningful reassurance that the intense discomfort of their anxiety will get better with effective treatment. In this visit, you can get treatment started by identifying what parents and their children can do right away to begin addressing anxiety symptoms. Offer strategies to protect and promote restful sleep and daily vigorous exercise, both of which can directly improve mild to moderate anxiety symptoms. Suggest to parents that they should help their children to notice what they are feeling, rather than rushing in to remove a source of anxiety. These measures can help their child to identify what is a thought, a feeling, a physical sensation, or a fact. They can offer support and validation around how uncomfortable these feelings are, but just being curious will reassure their child that they will be able to manage and master this feeling. This “practice” is akin to what their child will do in most effective treatments, and will have the added benefit of helping them to build skills that all children need to manage the challenges and worries that are a normal, but difficult part of growing up and of adult life. Finally, you can tell them that anxious temperaments come with advantages also, such as great powers of observation, attention to detail, and thoroughness, high levels of empathy, drive, and tenacity. By learning to manage anxiety early, these children can grow up to be engaged, resilient, successful, and satisfied adults.

Once identified, the range of effective treatments available include cognitive-behavioral therapy, graduated exposure, mindfulness/relaxation techniques, and medication, and we will discuss these in our next article.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Reference

Beesdo K et al. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. doi: 10.1016/j.psc.2009.06.002.

TOPLINE:

Adults with high-risk serrated polyps (with or without high-risk adenomas) have a high risk for metachronous colorectal cancer (CRC) within a median of 3 years after the baseline colonoscopy for a positive fecal immunochemical test (FIT) screen, a study suggests.

,

METHODOLOGY:

• Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
• A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
• Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
• High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.

TAKEAWAY:

• Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
• Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
• The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
• Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).

IN PRACTICE:

“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.

SOURCE:

The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.

LIMITATIONS:

The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.

DISCLOSURES:

Dr. van Toledo declared no relevant financial relationships.

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

TOPLINE:

Adults with high-risk serrated polyps (with or without high-risk adenomas) have a high risk for metachronous colorectal cancer (CRC) within a median of 3 years after the baseline colonoscopy for a positive fecal immunochemical test (FIT) screen, a study suggests.

,

METHODOLOGY:

• Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
• A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
• Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
• High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.

TAKEAWAY:

• Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
• Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
• The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
• Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).

IN PRACTICE:

“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.

SOURCE:

The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.

LIMITATIONS:

The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.

DISCLOSURES:

Dr. van Toledo declared no relevant financial relationships.

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

TOPLINE:

Adults with high-risk serrated polyps (with or without high-risk adenomas) have a high risk for metachronous colorectal cancer (CRC) within a median of 3 years after the baseline colonoscopy for a positive fecal immunochemical test (FIT) screen, a study suggests.

,

METHODOLOGY:

• Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
• A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
• Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
• High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.

TAKEAWAY:

• Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
• Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
• The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
• Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).

IN PRACTICE:

“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.

SOURCE:

The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.

LIMITATIONS:

The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.

DISCLOSURES:

Dr. van Toledo declared no relevant financial relationships.

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

New research supports the use of liquid biopsy as an adjunct biomarker for the diagnosis and surveillance of human papillomavirus (HPV)–associated oropharyngeal cancer.

In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.

“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.

“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.

The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
 

‘Remarkable promise’

The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.

The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.

In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.

The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).

In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.

The median lead time from positive test to pathologic confirmation was 47 days.

“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.

“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.

In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.

“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.

Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”

The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.

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

New research supports the use of liquid biopsy as an adjunct biomarker for the diagnosis and surveillance of human papillomavirus (HPV)–associated oropharyngeal cancer.

In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.

“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.

“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.

The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
 

‘Remarkable promise’

The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.

The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.

In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.

The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).

In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.

The median lead time from positive test to pathologic confirmation was 47 days.

“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.

“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.

In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.

“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.

Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”

The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.

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

New research supports the use of liquid biopsy as an adjunct biomarker for the diagnosis and surveillance of human papillomavirus (HPV)–associated oropharyngeal cancer.

In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.

“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.

“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.

The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
 

‘Remarkable promise’

The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.

The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.

In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.

The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).

In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.

The median lead time from positive test to pathologic confirmation was 47 days.

“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.

“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.

In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.

“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.

Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”

The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.

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