Springer Nature will retract an article that reported results of a survey of parents who thought their children’s gender dysphoria resulted from social contagion. The move is “due to concerns about lack of informed consent,” according to tweets by one of the paper’s authors. 

The article, “Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases,” was published in March in the Archives of Sexual Behavior. It has not been cited in the scientific literature, according to Clarivate’s Web of Science, but Altmetric, which tracks the online attention papers receive, ranks the article in the top 1% of all articles of a similar age. 

Rapid Onset Gender Dysphoria (ROGD) is, the article stated, a “controversial theory” that “common cultural beliefs, values, and preoccupations cause some adolescents (especially female adolescents) to attribute their social problems, feelings, and mental health issues to gender dysphoria,” and that “youth with ROGD falsely believe that they are transgender,” in part due to social influences. 

Michael Bailey, a psychology professor at Northwestern University in Evanston, Ill., and the paper’s corresponding author, tweeted:

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

Springer Nature will retract an article that reported results of a survey of parents who thought their children’s gender dysphoria resulted from social contagion. The move is “due to concerns about lack of informed consent,” according to tweets by one of the paper’s authors. 

The article, “Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases,” was published in March in the Archives of Sexual Behavior. It has not been cited in the scientific literature, according to Clarivate’s Web of Science, but Altmetric, which tracks the online attention papers receive, ranks the article in the top 1% of all articles of a similar age. 

Rapid Onset Gender Dysphoria (ROGD) is, the article stated, a “controversial theory” that “common cultural beliefs, values, and preoccupations cause some adolescents (especially female adolescents) to attribute their social problems, feelings, and mental health issues to gender dysphoria,” and that “youth with ROGD falsely believe that they are transgender,” in part due to social influences. 

Michael Bailey, a psychology professor at Northwestern University in Evanston, Ill., and the paper’s corresponding author, tweeted:

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

Springer Nature will retract an article that reported results of a survey of parents who thought their children’s gender dysphoria resulted from social contagion. The move is “due to concerns about lack of informed consent,” according to tweets by one of the paper’s authors. 

The article, “Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases,” was published in March in the Archives of Sexual Behavior. It has not been cited in the scientific literature, according to Clarivate’s Web of Science, but Altmetric, which tracks the online attention papers receive, ranks the article in the top 1% of all articles of a similar age. 

Rapid Onset Gender Dysphoria (ROGD) is, the article stated, a “controversial theory” that “common cultural beliefs, values, and preoccupations cause some adolescents (especially female adolescents) to attribute their social problems, feelings, and mental health issues to gender dysphoria,” and that “youth with ROGD falsely believe that they are transgender,” in part due to social influences. 

Michael Bailey, a psychology professor at Northwestern University in Evanston, Ill., and the paper’s corresponding author, tweeted:

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

Patients with neuromuscular diseases (NMD) face an increased risk of respiratory muscle weakness, which can contribute to various health problems. These include chronic respiratory failure, sleep-related breathing disorders, sialorrhea, and reduced cough effectiveness. In collaboration with AASM, AARC, and ATS, CHEST has developed guidelines to help clinicians manage patients with NMD. Through a systematic review of 128 studies related to this topic, the expert panel developed 15 graded recommendations, a good practice statement, and a consensus-based statement using the population, intervention, comparator, and outcome (PICO) format using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.

A few of the key recommendations are as follows:

1. Addressing the use and timing of pulmonary function tests (PFT), the panel suggests measuring vital capacity (FVC or SVC), MIP/MEP, SNIP, or PCF in patients with NMD every 6 months.

2. For the detection of respiratory failure and sleep-related breathing disorders in symptomatic patients with NMD who have normal PFT and overnight oximetry (ONO), the panel suggested that clinicians consider polysomnography (PSG) to assess whether noninvasive ventilation (NIV) would be beneficial. Adult patients do not have to have PSG to manage NMD if the PFT or ONO criteria support using NIV.

3. The panel recommends the use of NIV for the treatment of respiratory failure. To guide the initiation of NIV, clinicians can use any fall in FVC to < 80% of predicted with symptoms or FVC to < 50% of predicted without symptoms or SNIP/MIP to < –40 cm H₂O or hypercapnia. The panel recommended individualizing treatment.

4. The panel suggested mouth piece ventilation (MPV) for daytime ventilatory support in patients with preserved bulbar function. Its desirable effects include delaying or avoiding tracheostomy and improving speech, cough effectiveness, and coordination of breathing and swallowing.

5. Invasive home mechanical ventilation (MV) by tracheostomy was identified as an acceptable option for patients with progressive respiratory failure, particularly those who were unable to clear secretions. Because of the high costs and caregiver burden, the guideline highlights the need to consider patient preferences, tolerability, the ability to maintain mouthpiece ventilation, and the availability of resources when choosing an appropriate treatment option.

6. The panel suggested practicing clinicians address the management of sialorrhea and airway clearance techniques in patients with NMD, as they face the risk of aspiration and pneumonia. For sialorrhea, the panel suggests starting with a trial of anticholinergic agents, as they are inexpensive and readily available. The panel also provided advice on botulinum toxin therapy and radiation therapy, which have limited data and should be reserved for experienced centers.

7. The panel reviewed data on airway clearance techniques, including glossopharyngeal breathing (GPB), mechanical insufflation-exsufflation (MI-E), also commonly known as cough-assist device, manually assisted cough, lung volume recruitment (LVR) by air stacking, and high-frequency chest wall oscillation (HFCWO). The panel suggested using airway clearance techniques based on local resources, expertise, and shared decision-making with patients.

The panel stressed the importance of respect for patient preferences, treatment goals, and quality of life considerations. The panel emphasized the need to modernize and improve access to ventilatory support for patients with NMD and the role of shared decision-making in improving quality of life and long-term outcomes. The panel also suggests that randomized controlled trials in patients with NMD would help establish a higher grade of evidence.
 

Dr. Hubel and Dr. Khan are from the Division of Pulmonary Allergy and Critical Care Medicine, Oregon Health and Science University, Portland.

Reference

Khan A et al. Respiratory management of patients with neuromuscular weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report [published online ahead of print, 2023 Mar 13]. Chest. 2023;S0012-3692(23)00353-7. doi: 10.1016/j.chest.2023.03.011.

Patients with neuromuscular diseases (NMD) face an increased risk of respiratory muscle weakness, which can contribute to various health problems. These include chronic respiratory failure, sleep-related breathing disorders, sialorrhea, and reduced cough effectiveness. In collaboration with AASM, AARC, and ATS, CHEST has developed guidelines to help clinicians manage patients with NMD. Through a systematic review of 128 studies related to this topic, the expert panel developed 15 graded recommendations, a good practice statement, and a consensus-based statement using the population, intervention, comparator, and outcome (PICO) format using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.

A few of the key recommendations are as follows:

1. Addressing the use and timing of pulmonary function tests (PFT), the panel suggests measuring vital capacity (FVC or SVC), MIP/MEP, SNIP, or PCF in patients with NMD every 6 months.

2. For the detection of respiratory failure and sleep-related breathing disorders in symptomatic patients with NMD who have normal PFT and overnight oximetry (ONO), the panel suggested that clinicians consider polysomnography (PSG) to assess whether noninvasive ventilation (NIV) would be beneficial. Adult patients do not have to have PSG to manage NMD if the PFT or ONO criteria support using NIV.

3. The panel recommends the use of NIV for the treatment of respiratory failure. To guide the initiation of NIV, clinicians can use any fall in FVC to < 80% of predicted with symptoms or FVC to < 50% of predicted without symptoms or SNIP/MIP to < –40 cm H₂O or hypercapnia. The panel recommended individualizing treatment.

4. The panel suggested mouth piece ventilation (MPV) for daytime ventilatory support in patients with preserved bulbar function. Its desirable effects include delaying or avoiding tracheostomy and improving speech, cough effectiveness, and coordination of breathing and swallowing.

5. Invasive home mechanical ventilation (MV) by tracheostomy was identified as an acceptable option for patients with progressive respiratory failure, particularly those who were unable to clear secretions. Because of the high costs and caregiver burden, the guideline highlights the need to consider patient preferences, tolerability, the ability to maintain mouthpiece ventilation, and the availability of resources when choosing an appropriate treatment option.

6. The panel suggested practicing clinicians address the management of sialorrhea and airway clearance techniques in patients with NMD, as they face the risk of aspiration and pneumonia. For sialorrhea, the panel suggests starting with a trial of anticholinergic agents, as they are inexpensive and readily available. The panel also provided advice on botulinum toxin therapy and radiation therapy, which have limited data and should be reserved for experienced centers.

7. The panel reviewed data on airway clearance techniques, including glossopharyngeal breathing (GPB), mechanical insufflation-exsufflation (MI-E), also commonly known as cough-assist device, manually assisted cough, lung volume recruitment (LVR) by air stacking, and high-frequency chest wall oscillation (HFCWO). The panel suggested using airway clearance techniques based on local resources, expertise, and shared decision-making with patients.

The panel stressed the importance of respect for patient preferences, treatment goals, and quality of life considerations. The panel emphasized the need to modernize and improve access to ventilatory support for patients with NMD and the role of shared decision-making in improving quality of life and long-term outcomes. The panel also suggests that randomized controlled trials in patients with NMD would help establish a higher grade of evidence.
 

Dr. Hubel and Dr. Khan are from the Division of Pulmonary Allergy and Critical Care Medicine, Oregon Health and Science University, Portland.

Reference

Khan A et al. Respiratory management of patients with neuromuscular weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report [published online ahead of print, 2023 Mar 13]. Chest. 2023;S0012-3692(23)00353-7. doi: 10.1016/j.chest.2023.03.011.

Patients with neuromuscular diseases (NMD) face an increased risk of respiratory muscle weakness, which can contribute to various health problems. These include chronic respiratory failure, sleep-related breathing disorders, sialorrhea, and reduced cough effectiveness. In collaboration with AASM, AARC, and ATS, CHEST has developed guidelines to help clinicians manage patients with NMD. Through a systematic review of 128 studies related to this topic, the expert panel developed 15 graded recommendations, a good practice statement, and a consensus-based statement using the population, intervention, comparator, and outcome (PICO) format using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.

A few of the key recommendations are as follows:

1. Addressing the use and timing of pulmonary function tests (PFT), the panel suggests measuring vital capacity (FVC or SVC), MIP/MEP, SNIP, or PCF in patients with NMD every 6 months.

2. For the detection of respiratory failure and sleep-related breathing disorders in symptomatic patients with NMD who have normal PFT and overnight oximetry (ONO), the panel suggested that clinicians consider polysomnography (PSG) to assess whether noninvasive ventilation (NIV) would be beneficial. Adult patients do not have to have PSG to manage NMD if the PFT or ONO criteria support using NIV.

3. The panel recommends the use of NIV for the treatment of respiratory failure. To guide the initiation of NIV, clinicians can use any fall in FVC to < 80% of predicted with symptoms or FVC to < 50% of predicted without symptoms or SNIP/MIP to < –40 cm H₂O or hypercapnia. The panel recommended individualizing treatment.

4. The panel suggested mouth piece ventilation (MPV) for daytime ventilatory support in patients with preserved bulbar function. Its desirable effects include delaying or avoiding tracheostomy and improving speech, cough effectiveness, and coordination of breathing and swallowing.

5. Invasive home mechanical ventilation (MV) by tracheostomy was identified as an acceptable option for patients with progressive respiratory failure, particularly those who were unable to clear secretions. Because of the high costs and caregiver burden, the guideline highlights the need to consider patient preferences, tolerability, the ability to maintain mouthpiece ventilation, and the availability of resources when choosing an appropriate treatment option.

6. The panel suggested practicing clinicians address the management of sialorrhea and airway clearance techniques in patients with NMD, as they face the risk of aspiration and pneumonia. For sialorrhea, the panel suggests starting with a trial of anticholinergic agents, as they are inexpensive and readily available. The panel also provided advice on botulinum toxin therapy and radiation therapy, which have limited data and should be reserved for experienced centers.

7. The panel reviewed data on airway clearance techniques, including glossopharyngeal breathing (GPB), mechanical insufflation-exsufflation (MI-E), also commonly known as cough-assist device, manually assisted cough, lung volume recruitment (LVR) by air stacking, and high-frequency chest wall oscillation (HFCWO). The panel suggested using airway clearance techniques based on local resources, expertise, and shared decision-making with patients.

The panel stressed the importance of respect for patient preferences, treatment goals, and quality of life considerations. The panel emphasized the need to modernize and improve access to ventilatory support for patients with NMD and the role of shared decision-making in improving quality of life and long-term outcomes. The panel also suggests that randomized controlled trials in patients with NMD would help establish a higher grade of evidence.
 

Dr. Hubel and Dr. Khan are from the Division of Pulmonary Allergy and Critical Care Medicine, Oregon Health and Science University, Portland.

Reference

Khan A et al. Respiratory management of patients with neuromuscular weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report [published online ahead of print, 2023 Mar 13]. Chest. 2023;S0012-3692(23)00353-7. doi: 10.1016/j.chest.2023.03.011.

Barry Bonds and Roger Clemens are two world-class baseball players who played well enough to earn enduring respect and admiration. However, their reputations have been permanently tainted by their use of performance-enhancing drugs. Although they are both undeniably gifted, we’ll never know where their natural talent ended and their unfair advantage began.

The medical oncology version of this scenario played out in front of our eyes at the ASCO 2023 Plenary Session featuring the ADAURA trial. In this case, the unfair advantage was clear: Nearly two-thirds of patients in the control arm did not cross over to a standard-of-care treatment at relapse.

The ADAURA trial tested the value of the third-generation oral EGFR inhibitor osimertinib vs. placebo for up to 3 years in patients with a resected stage IB-IIIA non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Initially presented in the ASCO 2020 Plenary Session, the preliminary analysis for ADAURA demonstrated a remarkably favorable improvement in disease-free survival (DFS) in the osimertinib arm, which led to its prompt Food and Drug Administration approval in this setting.

At the time, I was among the more vocal critics of the fanfare around this trial. The DFS improvement was impressive but, in this context, represented a low threshold for FDA approval. We already knew that prior trials of other, less effective adjuvant EGFR inhibitors routinely improved DFS but ultimately failed to improve overall survival.

Although in some cases, a DFS benefit can be sufficient to warrant changing practice, I would argue that overall survival is the most critical endpoint in a curative setting by a wide margin. I would also argue that cost should be a consideration for a drug priced at $440,000 over 3 years in the United States. At the very least, we – patients, oncologists, payers – should want to clarify what we get for $440,000 per patient, especially if that money could be better spent on other things.

Of note, we need to know whether the same overall survival may be achieved in this setting by treating only patients whose disease relapses, avoiding both the cost and toxicity of continuous treatment.

The relevance of this question became even more acute when an updated version of the ADAURA trial showed that the DFS benefit from osimertinib began to erode immediately after patients completed active treatment. Although the DFS benefit remained excellent, the findings suggested that ADAURA may echo other adjuvant EGFR inhibitor trials: It may start out from a higher peak, but over time, the benefit of the drug may drop to the disappointing levels seen in other, similar drugs.

The overall survival data – the critical test in my mind – were presented at the ASCO Plenary Session. The results were highly positive, with a hazard ratio for overall survival of 0.49 and a similar benefit observed across all eligible disease stages.

As with the presentation of the DFS data in 2020, these results were accompanied by adulation during the session and fawning in the media. However, a subset of people in the audience, and on Twitter, voiced a major concern: In the control arm, only 38.5% of the patients whose disease had relapsed (79 of 205) ever received osimertinib.

Post-protocol treatment included reassurances that patients in the control arm were offered crossover to osimertinib, but this only occurred starting in April 2020 and only when the treating investigator requested it.

The fact that only a minority of patients in the control arm ever received osimertinib means that ADAURA is not a trial that tests adjuvant osimertinib to osimertinib at relapse, the prevailing standard of care in the United States and the preferred treatment in this setting, based on NCCN guidelines for patients with relapsed/metastatic EGFR mutation–positive NSCLC since the FDA approval in April 2018.

The change in standard of care in the United States and some other countries did not lead to an amendment in the trial, based on the argument that the trial was designed with DFS as the primary endpoint and that patients in the control arm are effectively off trial at relapse. That means patients would receive their country’s standard of care, which may be below, or different from, the standard in the United States or other parts of the world.

While defensible, others considered the low rate of osimertinib delivery in the control arm a serious flaw in the trial design and arguably an ethical problem.

Given this trial design, it’s important to question whether the trial magnified the difference in overall survival between the two arms compared with the standard of care in countries where adjuvant osimertinib will ultimately be marketed. Although I strongly suspect that the overall survival difference would have been significant without the disparity in access to osimertinib in the control arm, we will never know the magnitude of that difference.

With the current design, the trial demonstrates that osimertinib is associated with improved survival in 100% of patients with EGFR mutation–positive NSCLC who receive the agent vs. 38.5% of patients receiving it at some point after relapse.

At the end of the day, ADAURA followed conventional trial rules, which led to a windfall of accolades at the cost of suboptimal care for many of the patients randomly assigned to the control arm.

We need to decide as an oncology community whether we want to accept a system that confers rewards for stakeholders at the expense of patients enrolled in the trial.

We have developed a system that not only permits but depends on global trials enrolling many patients from countries with staging and off-protocol oncology care below standards of care in other parts of the world – effectively condoning and perpetuating disparities in optimal care globally. I am also saddened that some of the most respected leaders in our field have become upset when I question the ethics of accepting this system, one that I believe we have agency to change.

The question here is not whether osimertinib is a good drug; it is remarkably effective for patients with EGFR mutation–positive NSCLC. The question is how to design trials in a fair and balanced way that doesn’t compromise patient care or ethical standards.

If people think my assessment is too harsh, I openly welcome debate.

Bottom line: The ADAURA trial lays bare deeper problems with clinical trial design, and I would challenge readers to reflect on our clinical trial culture in oncology, which offers a system of rules that rewards denying the best identified care for patients on our clinical trials.

At the very least, should we celebrate these wins without fully acknowledging these problems?
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

Barry Bonds and Roger Clemens are two world-class baseball players who played well enough to earn enduring respect and admiration. However, their reputations have been permanently tainted by their use of performance-enhancing drugs. Although they are both undeniably gifted, we’ll never know where their natural talent ended and their unfair advantage began.

The medical oncology version of this scenario played out in front of our eyes at the ASCO 2023 Plenary Session featuring the ADAURA trial. In this case, the unfair advantage was clear: Nearly two-thirds of patients in the control arm did not cross over to a standard-of-care treatment at relapse.

The ADAURA trial tested the value of the third-generation oral EGFR inhibitor osimertinib vs. placebo for up to 3 years in patients with a resected stage IB-IIIA non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Initially presented in the ASCO 2020 Plenary Session, the preliminary analysis for ADAURA demonstrated a remarkably favorable improvement in disease-free survival (DFS) in the osimertinib arm, which led to its prompt Food and Drug Administration approval in this setting.

At the time, I was among the more vocal critics of the fanfare around this trial. The DFS improvement was impressive but, in this context, represented a low threshold for FDA approval. We already knew that prior trials of other, less effective adjuvant EGFR inhibitors routinely improved DFS but ultimately failed to improve overall survival.

Although in some cases, a DFS benefit can be sufficient to warrant changing practice, I would argue that overall survival is the most critical endpoint in a curative setting by a wide margin. I would also argue that cost should be a consideration for a drug priced at $440,000 over 3 years in the United States. At the very least, we – patients, oncologists, payers – should want to clarify what we get for $440,000 per patient, especially if that money could be better spent on other things.

Of note, we need to know whether the same overall survival may be achieved in this setting by treating only patients whose disease relapses, avoiding both the cost and toxicity of continuous treatment.

The relevance of this question became even more acute when an updated version of the ADAURA trial showed that the DFS benefit from osimertinib began to erode immediately after patients completed active treatment. Although the DFS benefit remained excellent, the findings suggested that ADAURA may echo other adjuvant EGFR inhibitor trials: It may start out from a higher peak, but over time, the benefit of the drug may drop to the disappointing levels seen in other, similar drugs.

The overall survival data – the critical test in my mind – were presented at the ASCO Plenary Session. The results were highly positive, with a hazard ratio for overall survival of 0.49 and a similar benefit observed across all eligible disease stages.

As with the presentation of the DFS data in 2020, these results were accompanied by adulation during the session and fawning in the media. However, a subset of people in the audience, and on Twitter, voiced a major concern: In the control arm, only 38.5% of the patients whose disease had relapsed (79 of 205) ever received osimertinib.

Post-protocol treatment included reassurances that patients in the control arm were offered crossover to osimertinib, but this only occurred starting in April 2020 and only when the treating investigator requested it.

The fact that only a minority of patients in the control arm ever received osimertinib means that ADAURA is not a trial that tests adjuvant osimertinib to osimertinib at relapse, the prevailing standard of care in the United States and the preferred treatment in this setting, based on NCCN guidelines for patients with relapsed/metastatic EGFR mutation–positive NSCLC since the FDA approval in April 2018.

The change in standard of care in the United States and some other countries did not lead to an amendment in the trial, based on the argument that the trial was designed with DFS as the primary endpoint and that patients in the control arm are effectively off trial at relapse. That means patients would receive their country’s standard of care, which may be below, or different from, the standard in the United States or other parts of the world.

While defensible, others considered the low rate of osimertinib delivery in the control arm a serious flaw in the trial design and arguably an ethical problem.

Given this trial design, it’s important to question whether the trial magnified the difference in overall survival between the two arms compared with the standard of care in countries where adjuvant osimertinib will ultimately be marketed. Although I strongly suspect that the overall survival difference would have been significant without the disparity in access to osimertinib in the control arm, we will never know the magnitude of that difference.

With the current design, the trial demonstrates that osimertinib is associated with improved survival in 100% of patients with EGFR mutation–positive NSCLC who receive the agent vs. 38.5% of patients receiving it at some point after relapse.

At the end of the day, ADAURA followed conventional trial rules, which led to a windfall of accolades at the cost of suboptimal care for many of the patients randomly assigned to the control arm.

We need to decide as an oncology community whether we want to accept a system that confers rewards for stakeholders at the expense of patients enrolled in the trial.

We have developed a system that not only permits but depends on global trials enrolling many patients from countries with staging and off-protocol oncology care below standards of care in other parts of the world – effectively condoning and perpetuating disparities in optimal care globally. I am also saddened that some of the most respected leaders in our field have become upset when I question the ethics of accepting this system, one that I believe we have agency to change.

The question here is not whether osimertinib is a good drug; it is remarkably effective for patients with EGFR mutation–positive NSCLC. The question is how to design trials in a fair and balanced way that doesn’t compromise patient care or ethical standards.

If people think my assessment is too harsh, I openly welcome debate.

Bottom line: The ADAURA trial lays bare deeper problems with clinical trial design, and I would challenge readers to reflect on our clinical trial culture in oncology, which offers a system of rules that rewards denying the best identified care for patients on our clinical trials.

At the very least, should we celebrate these wins without fully acknowledging these problems?
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

Barry Bonds and Roger Clemens are two world-class baseball players who played well enough to earn enduring respect and admiration. However, their reputations have been permanently tainted by their use of performance-enhancing drugs. Although they are both undeniably gifted, we’ll never know where their natural talent ended and their unfair advantage began.

The medical oncology version of this scenario played out in front of our eyes at the ASCO 2023 Plenary Session featuring the ADAURA trial. In this case, the unfair advantage was clear: Nearly two-thirds of patients in the control arm did not cross over to a standard-of-care treatment at relapse.

The ADAURA trial tested the value of the third-generation oral EGFR inhibitor osimertinib vs. placebo for up to 3 years in patients with a resected stage IB-IIIA non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Initially presented in the ASCO 2020 Plenary Session, the preliminary analysis for ADAURA demonstrated a remarkably favorable improvement in disease-free survival (DFS) in the osimertinib arm, which led to its prompt Food and Drug Administration approval in this setting.

At the time, I was among the more vocal critics of the fanfare around this trial. The DFS improvement was impressive but, in this context, represented a low threshold for FDA approval. We already knew that prior trials of other, less effective adjuvant EGFR inhibitors routinely improved DFS but ultimately failed to improve overall survival.

Although in some cases, a DFS benefit can be sufficient to warrant changing practice, I would argue that overall survival is the most critical endpoint in a curative setting by a wide margin. I would also argue that cost should be a consideration for a drug priced at $440,000 over 3 years in the United States. At the very least, we – patients, oncologists, payers – should want to clarify what we get for $440,000 per patient, especially if that money could be better spent on other things.

Of note, we need to know whether the same overall survival may be achieved in this setting by treating only patients whose disease relapses, avoiding both the cost and toxicity of continuous treatment.

The relevance of this question became even more acute when an updated version of the ADAURA trial showed that the DFS benefit from osimertinib began to erode immediately after patients completed active treatment. Although the DFS benefit remained excellent, the findings suggested that ADAURA may echo other adjuvant EGFR inhibitor trials: It may start out from a higher peak, but over time, the benefit of the drug may drop to the disappointing levels seen in other, similar drugs.

The overall survival data – the critical test in my mind – were presented at the ASCO Plenary Session. The results were highly positive, with a hazard ratio for overall survival of 0.49 and a similar benefit observed across all eligible disease stages.

As with the presentation of the DFS data in 2020, these results were accompanied by adulation during the session and fawning in the media. However, a subset of people in the audience, and on Twitter, voiced a major concern: In the control arm, only 38.5% of the patients whose disease had relapsed (79 of 205) ever received osimertinib.

Post-protocol treatment included reassurances that patients in the control arm were offered crossover to osimertinib, but this only occurred starting in April 2020 and only when the treating investigator requested it.

The fact that only a minority of patients in the control arm ever received osimertinib means that ADAURA is not a trial that tests adjuvant osimertinib to osimertinib at relapse, the prevailing standard of care in the United States and the preferred treatment in this setting, based on NCCN guidelines for patients with relapsed/metastatic EGFR mutation–positive NSCLC since the FDA approval in April 2018.

The change in standard of care in the United States and some other countries did not lead to an amendment in the trial, based on the argument that the trial was designed with DFS as the primary endpoint and that patients in the control arm are effectively off trial at relapse. That means patients would receive their country’s standard of care, which may be below, or different from, the standard in the United States or other parts of the world.

While defensible, others considered the low rate of osimertinib delivery in the control arm a serious flaw in the trial design and arguably an ethical problem.

Given this trial design, it’s important to question whether the trial magnified the difference in overall survival between the two arms compared with the standard of care in countries where adjuvant osimertinib will ultimately be marketed. Although I strongly suspect that the overall survival difference would have been significant without the disparity in access to osimertinib in the control arm, we will never know the magnitude of that difference.

With the current design, the trial demonstrates that osimertinib is associated with improved survival in 100% of patients with EGFR mutation–positive NSCLC who receive the agent vs. 38.5% of patients receiving it at some point after relapse.

At the end of the day, ADAURA followed conventional trial rules, which led to a windfall of accolades at the cost of suboptimal care for many of the patients randomly assigned to the control arm.

We need to decide as an oncology community whether we want to accept a system that confers rewards for stakeholders at the expense of patients enrolled in the trial.

We have developed a system that not only permits but depends on global trials enrolling many patients from countries with staging and off-protocol oncology care below standards of care in other parts of the world – effectively condoning and perpetuating disparities in optimal care globally. I am also saddened that some of the most respected leaders in our field have become upset when I question the ethics of accepting this system, one that I believe we have agency to change.

The question here is not whether osimertinib is a good drug; it is remarkably effective for patients with EGFR mutation–positive NSCLC. The question is how to design trials in a fair and balanced way that doesn’t compromise patient care or ethical standards.

If people think my assessment is too harsh, I openly welcome debate.

Bottom line: The ADAURA trial lays bare deeper problems with clinical trial design, and I would challenge readers to reflect on our clinical trial culture in oncology, which offers a system of rules that rewards denying the best identified care for patients on our clinical trials.

At the very least, should we celebrate these wins without fully acknowledging these problems?
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

While millions of Americans in the Midwest and on the Eastern Seaboard got some relief from the wildfire smoke from Canada, with more relief expected over the weekend, health experts warned that for at-risk people, some hazardous health effects may persist. 

People with moderate to severe asthma, chronic obstructive pulmonary disease, and other risk factors are used to checking air quality warnings before heading outside. But this situation is anything but typical.

Even people not normally at risk can have burning eyes, a runny nose, and a hard time breathing. These are among the symptoms to watch for as health effects of wildfire smoke. Special considerations should be made for people with heart disease, lung disease, and other conditions that put them at increased risk. Those affected can also have trouble sleeping, anxiety, and ongoing mental health issues.

The smoke will stick around the next few days, possibly clearing out early next week when the winds change direction, Weather Channel meteorologist Ari Sarsalari predicted June 8. But that doesn’t mean any physical or mental health effects will clear up as quickly.

“We are seeing dramatic increases in air pollution, and we are seeing increases in patients coming to the ED and the hospital. We expect that this will increase in the days ahead,” said Meredith McCormack, MD, MHS, a volunteer medical spokesperson for the American Lung Association.

“The air quality in our area – Baltimore – and other surrounding areas is not healthy for anyone,” said Dr. McCormack, who specializes in pulmonary and critical care medicine at Johns Hopkins University, Baltimore.
 

How serious are the health warnings?

Residents of California might be more familiar with the hazards of wildfire smoke, but this is a novel experience for many people along the East Coast. Air quality advisories are popping up on cellphones for people living in Boston, New York, and as far south as Northern Virginia. What should the estimated 75 million to 128 million affected Americans do? 

We asked experts to weigh in on when it’s safe or not safe to spend time outside, when to seek medical help, and the best ways for people to protect themselves.

“It’s important to stay indoors and close all windows to reduce exposure to smoke from wildfires. It’s also essential to stay away from any windows that may not have a good seal, in order to minimize any potential exposure to smoke,” said Robert Glatter, MD, editor at large for Medscape Emergency Medicine and an emergency medicine doctor at Lenox Hill Hospital/Northwell Health in New York.

Dr. Glatter noted that placing moist towels under doors and sealing leaking windows can help. 

Monitor your symptoms, and contact your doctor or go to urgent care, Dr. McCormack advised, if you see any increase in concerning symptoms. These include shortness of breath, coughing, chest tightness, or wheezing. Also make sure you take recommended medications and have enough on hand, she said.
 

Fine particles, big concerns

The weather is warming in many parts of the country, and that can mean air conditioning. Adding a MERV 13 filter to a central air conditioning system could reduce exposure to wildfire smoke. Using a portable indoor air purifier with a HEPA filter also can help people without central air conditioning. The filter can help remove small particles in the air but must be replaced regularly.

Smoke from wildfires contains multiple toxins, including heavy metals, carcinogens, and fine particulate matter (PM) under 2.5 microns. Dr. Glatter explained that these particles are about 100 times thinner than a human hair. Because of their size, they can embed deeper into the airways in the lungs and trigger chronic inflammation.

“This has also been linked to increased rates of lung cancer and brain tumors,” he said, based on a 2022 study in Canada.

The effects of smoke from wildfires can continue for many years. After the 2014 Hazelwood coal mine fire, emergency department visits for respiratory conditions and cardiovascular complaints remained higher for up to 2-5 years later, Dr. Glatter said. Again, large quantities of fine particulate matter in the smoke, less than 2.5 microns (PM 2.5), was to blame.

Exposure to smoke from wildfires during pregnancy has also been linked to abnormal fetal growth, preterm birth, as well as low birth weight, a January 2023 preprint on MedRxiv suggested.
 

Time to wear a mask again?

A properly fitted N95 mask will be the best approach to lessen exposure to smoke from wildfires, “but by itself cannot eliminate all of the risk,” Dr. Glatter said. Surgical masks can add minimal protection, and cloth masks will not provide any significant protection against the damaging effects of smoke from wildfires.

KN95 masks tend to be more comfortable to wear than N95s. But leakage often occurs that can make this type of protection less effective, Dr. Glatter said.

“Masks are important if you need to go outdoors,” Dr. McCormack said. Also, if you’re traveling by car, set the air conditioning system to recirculate to filter the air inside the vehicle, she recommended.
 

What does that number mean?

The federal government monitors air quality nationwide. In case you’re unfamiliar, the U.S. Air Quality Index includes a color-coded scale for ozone levels and particle pollution, the main concern from wildfire smoke. The lowest risk is the Green or satisfactory air quality category, where air pollution poses little or no risk, with an Index number from 0 to 50.

The index gets progressively more serious, from Yellow for moderate risk (51-100) up to a Maroon category, a hazardous range of 300 or higher on the index. When a Maroon advisory is issued, it means an emergency health warning where “everyone is more likely to be affected.”

How do you know if your outside air is polluted? Your local Air Quality Index (AQI) from the EPA can help. It’s a scale of 0 to 500, and the greater the number, the more harmful pollution in the air. It has six levels: good, moderate, unhealthy for sensitive groups, unhealthy, very unhealthy, and hazardous. You can find it at AirNow.gov.

New York is under an air quality alert until midnight Friday with a current “unhealthy” Index report of 200. The city recorded its worst-ever air quality on Wednesday. The New York State Department of Environmental Conservation warns that fine particulate levels – small particles that can enter a person’s lungs – are the biggest concern.

AirNow.gov warns that western New England down to Washington has air quality in the three worst categories – ranging from unhealthy to very unhealthy and hazardous. The ten worst locations on the U.S. Air Quality Index as of 10 a.m. ET on June 8 include the Wilmington, Del., area with an Index of 241, or “very unhealthy.”

• 244: Suburban Washington/Maryland.
• 252: Southern coastal New Jersey.
• 252: Kent County, Del.
• 270: Philadelphia.
• 291: Greater New Castle County, Del.
• 293: Northern Virginia.
• 293: Metropolitan Washington.

These two locations are in the “hazardous” or health emergency warning category:

• 309: Lehigh Valley, Pa.
• 399: Susquehanna Valley, Pa.

To check an air quality advisory in your area, enter your ZIP code at AirNow.gov.

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

While millions of Americans in the Midwest and on the Eastern Seaboard got some relief from the wildfire smoke from Canada, with more relief expected over the weekend, health experts warned that for at-risk people, some hazardous health effects may persist. 

People with moderate to severe asthma, chronic obstructive pulmonary disease, and other risk factors are used to checking air quality warnings before heading outside. But this situation is anything but typical.

Even people not normally at risk can have burning eyes, a runny nose, and a hard time breathing. These are among the symptoms to watch for as health effects of wildfire smoke. Special considerations should be made for people with heart disease, lung disease, and other conditions that put them at increased risk. Those affected can also have trouble sleeping, anxiety, and ongoing mental health issues.

The smoke will stick around the next few days, possibly clearing out early next week when the winds change direction, Weather Channel meteorologist Ari Sarsalari predicted June 8. But that doesn’t mean any physical or mental health effects will clear up as quickly.

“We are seeing dramatic increases in air pollution, and we are seeing increases in patients coming to the ED and the hospital. We expect that this will increase in the days ahead,” said Meredith McCormack, MD, MHS, a volunteer medical spokesperson for the American Lung Association.

“The air quality in our area – Baltimore – and other surrounding areas is not healthy for anyone,” said Dr. McCormack, who specializes in pulmonary and critical care medicine at Johns Hopkins University, Baltimore.
 

How serious are the health warnings?

Residents of California might be more familiar with the hazards of wildfire smoke, but this is a novel experience for many people along the East Coast. Air quality advisories are popping up on cellphones for people living in Boston, New York, and as far south as Northern Virginia. What should the estimated 75 million to 128 million affected Americans do? 

We asked experts to weigh in on when it’s safe or not safe to spend time outside, when to seek medical help, and the best ways for people to protect themselves.

“It’s important to stay indoors and close all windows to reduce exposure to smoke from wildfires. It’s also essential to stay away from any windows that may not have a good seal, in order to minimize any potential exposure to smoke,” said Robert Glatter, MD, editor at large for Medscape Emergency Medicine and an emergency medicine doctor at Lenox Hill Hospital/Northwell Health in New York.

Dr. Glatter noted that placing moist towels under doors and sealing leaking windows can help. 

Monitor your symptoms, and contact your doctor or go to urgent care, Dr. McCormack advised, if you see any increase in concerning symptoms. These include shortness of breath, coughing, chest tightness, or wheezing. Also make sure you take recommended medications and have enough on hand, she said.
 

Fine particles, big concerns

The weather is warming in many parts of the country, and that can mean air conditioning. Adding a MERV 13 filter to a central air conditioning system could reduce exposure to wildfire smoke. Using a portable indoor air purifier with a HEPA filter also can help people without central air conditioning. The filter can help remove small particles in the air but must be replaced regularly.

Smoke from wildfires contains multiple toxins, including heavy metals, carcinogens, and fine particulate matter (PM) under 2.5 microns. Dr. Glatter explained that these particles are about 100 times thinner than a human hair. Because of their size, they can embed deeper into the airways in the lungs and trigger chronic inflammation.

“This has also been linked to increased rates of lung cancer and brain tumors,” he said, based on a 2022 study in Canada.

The effects of smoke from wildfires can continue for many years. After the 2014 Hazelwood coal mine fire, emergency department visits for respiratory conditions and cardiovascular complaints remained higher for up to 2-5 years later, Dr. Glatter said. Again, large quantities of fine particulate matter in the smoke, less than 2.5 microns (PM 2.5), was to blame.

Exposure to smoke from wildfires during pregnancy has also been linked to abnormal fetal growth, preterm birth, as well as low birth weight, a January 2023 preprint on MedRxiv suggested.
 

Time to wear a mask again?

A properly fitted N95 mask will be the best approach to lessen exposure to smoke from wildfires, “but by itself cannot eliminate all of the risk,” Dr. Glatter said. Surgical masks can add minimal protection, and cloth masks will not provide any significant protection against the damaging effects of smoke from wildfires.

KN95 masks tend to be more comfortable to wear than N95s. But leakage often occurs that can make this type of protection less effective, Dr. Glatter said.

“Masks are important if you need to go outdoors,” Dr. McCormack said. Also, if you’re traveling by car, set the air conditioning system to recirculate to filter the air inside the vehicle, she recommended.
 

What does that number mean?

The federal government monitors air quality nationwide. In case you’re unfamiliar, the U.S. Air Quality Index includes a color-coded scale for ozone levels and particle pollution, the main concern from wildfire smoke. The lowest risk is the Green or satisfactory air quality category, where air pollution poses little or no risk, with an Index number from 0 to 50.

The index gets progressively more serious, from Yellow for moderate risk (51-100) up to a Maroon category, a hazardous range of 300 or higher on the index. When a Maroon advisory is issued, it means an emergency health warning where “everyone is more likely to be affected.”

How do you know if your outside air is polluted? Your local Air Quality Index (AQI) from the EPA can help. It’s a scale of 0 to 500, and the greater the number, the more harmful pollution in the air. It has six levels: good, moderate, unhealthy for sensitive groups, unhealthy, very unhealthy, and hazardous. You can find it at AirNow.gov.

New York is under an air quality alert until midnight Friday with a current “unhealthy” Index report of 200. The city recorded its worst-ever air quality on Wednesday. The New York State Department of Environmental Conservation warns that fine particulate levels – small particles that can enter a person’s lungs – are the biggest concern.

AirNow.gov warns that western New England down to Washington has air quality in the three worst categories – ranging from unhealthy to very unhealthy and hazardous. The ten worst locations on the U.S. Air Quality Index as of 10 a.m. ET on June 8 include the Wilmington, Del., area with an Index of 241, or “very unhealthy.”

• 244: Suburban Washington/Maryland.
• 252: Southern coastal New Jersey.
• 252: Kent County, Del.
• 270: Philadelphia.
• 291: Greater New Castle County, Del.
• 293: Northern Virginia.
• 293: Metropolitan Washington.

These two locations are in the “hazardous” or health emergency warning category:

• 309: Lehigh Valley, Pa.
• 399: Susquehanna Valley, Pa.

To check an air quality advisory in your area, enter your ZIP code at AirNow.gov.

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

While millions of Americans in the Midwest and on the Eastern Seaboard got some relief from the wildfire smoke from Canada, with more relief expected over the weekend, health experts warned that for at-risk people, some hazardous health effects may persist. 

People with moderate to severe asthma, chronic obstructive pulmonary disease, and other risk factors are used to checking air quality warnings before heading outside. But this situation is anything but typical.

Even people not normally at risk can have burning eyes, a runny nose, and a hard time breathing. These are among the symptoms to watch for as health effects of wildfire smoke. Special considerations should be made for people with heart disease, lung disease, and other conditions that put them at increased risk. Those affected can also have trouble sleeping, anxiety, and ongoing mental health issues.

The smoke will stick around the next few days, possibly clearing out early next week when the winds change direction, Weather Channel meteorologist Ari Sarsalari predicted June 8. But that doesn’t mean any physical or mental health effects will clear up as quickly.

“We are seeing dramatic increases in air pollution, and we are seeing increases in patients coming to the ED and the hospital. We expect that this will increase in the days ahead,” said Meredith McCormack, MD, MHS, a volunteer medical spokesperson for the American Lung Association.

“The air quality in our area – Baltimore – and other surrounding areas is not healthy for anyone,” said Dr. McCormack, who specializes in pulmonary and critical care medicine at Johns Hopkins University, Baltimore.
 

How serious are the health warnings?

Residents of California might be more familiar with the hazards of wildfire smoke, but this is a novel experience for many people along the East Coast. Air quality advisories are popping up on cellphones for people living in Boston, New York, and as far south as Northern Virginia. What should the estimated 75 million to 128 million affected Americans do? 

We asked experts to weigh in on when it’s safe or not safe to spend time outside, when to seek medical help, and the best ways for people to protect themselves.

“It’s important to stay indoors and close all windows to reduce exposure to smoke from wildfires. It’s also essential to stay away from any windows that may not have a good seal, in order to minimize any potential exposure to smoke,” said Robert Glatter, MD, editor at large for Medscape Emergency Medicine and an emergency medicine doctor at Lenox Hill Hospital/Northwell Health in New York.

Dr. Glatter noted that placing moist towels under doors and sealing leaking windows can help. 

Monitor your symptoms, and contact your doctor or go to urgent care, Dr. McCormack advised, if you see any increase in concerning symptoms. These include shortness of breath, coughing, chest tightness, or wheezing. Also make sure you take recommended medications and have enough on hand, she said.
 

Fine particles, big concerns

The weather is warming in many parts of the country, and that can mean air conditioning. Adding a MERV 13 filter to a central air conditioning system could reduce exposure to wildfire smoke. Using a portable indoor air purifier with a HEPA filter also can help people without central air conditioning. The filter can help remove small particles in the air but must be replaced regularly.

Smoke from wildfires contains multiple toxins, including heavy metals, carcinogens, and fine particulate matter (PM) under 2.5 microns. Dr. Glatter explained that these particles are about 100 times thinner than a human hair. Because of their size, they can embed deeper into the airways in the lungs and trigger chronic inflammation.

“This has also been linked to increased rates of lung cancer and brain tumors,” he said, based on a 2022 study in Canada.

The effects of smoke from wildfires can continue for many years. After the 2014 Hazelwood coal mine fire, emergency department visits for respiratory conditions and cardiovascular complaints remained higher for up to 2-5 years later, Dr. Glatter said. Again, large quantities of fine particulate matter in the smoke, less than 2.5 microns (PM 2.5), was to blame.

Exposure to smoke from wildfires during pregnancy has also been linked to abnormal fetal growth, preterm birth, as well as low birth weight, a January 2023 preprint on MedRxiv suggested.
 

Time to wear a mask again?

A properly fitted N95 mask will be the best approach to lessen exposure to smoke from wildfires, “but by itself cannot eliminate all of the risk,” Dr. Glatter said. Surgical masks can add minimal protection, and cloth masks will not provide any significant protection against the damaging effects of smoke from wildfires.

KN95 masks tend to be more comfortable to wear than N95s. But leakage often occurs that can make this type of protection less effective, Dr. Glatter said.

“Masks are important if you need to go outdoors,” Dr. McCormack said. Also, if you’re traveling by car, set the air conditioning system to recirculate to filter the air inside the vehicle, she recommended.
 

What does that number mean?

The federal government monitors air quality nationwide. In case you’re unfamiliar, the U.S. Air Quality Index includes a color-coded scale for ozone levels and particle pollution, the main concern from wildfire smoke. The lowest risk is the Green or satisfactory air quality category, where air pollution poses little or no risk, with an Index number from 0 to 50.

The index gets progressively more serious, from Yellow for moderate risk (51-100) up to a Maroon category, a hazardous range of 300 or higher on the index. When a Maroon advisory is issued, it means an emergency health warning where “everyone is more likely to be affected.”

How do you know if your outside air is polluted? Your local Air Quality Index (AQI) from the EPA can help. It’s a scale of 0 to 500, and the greater the number, the more harmful pollution in the air. It has six levels: good, moderate, unhealthy for sensitive groups, unhealthy, very unhealthy, and hazardous. You can find it at AirNow.gov.

New York is under an air quality alert until midnight Friday with a current “unhealthy” Index report of 200. The city recorded its worst-ever air quality on Wednesday. The New York State Department of Environmental Conservation warns that fine particulate levels – small particles that can enter a person’s lungs – are the biggest concern.

AirNow.gov warns that western New England down to Washington has air quality in the three worst categories – ranging from unhealthy to very unhealthy and hazardous. The ten worst locations on the U.S. Air Quality Index as of 10 a.m. ET on June 8 include the Wilmington, Del., area with an Index of 241, or “very unhealthy.”

• 244: Suburban Washington/Maryland.
• 252: Southern coastal New Jersey.
• 252: Kent County, Del.
• 270: Philadelphia.
• 291: Greater New Castle County, Del.
• 293: Northern Virginia.
• 293: Metropolitan Washington.

These two locations are in the “hazardous” or health emergency warning category:

• 309: Lehigh Valley, Pa.
• 399: Susquehanna Valley, Pa.

To check an air quality advisory in your area, enter your ZIP code at AirNow.gov.

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

CHICAGO – Before determining the best treatment for post-inflammatory hyperpigmentation (PIH), it’s important to understand the pathogenesis, according to Seemal Desai, MD.

Dr. Desai, clinical assistant professor in the department of dermatology at the University of Texas Southwestern Medical Center, Dallas, spoke at the Pigmentary Disorders Exchange Symposium, provided by MedscapeLive!

MedscapeLive!

Like all dermatologists, he said at the meeting, he sees lots of acne cases. However, PIH is often the presenting reason for the visit in his practice, which focuses predominantly on skin of color.

“Most of my patients come in not even worried about the acne,” he said. “They come in wanting me to fix the dark spots.”
 

Inflammation persists

Dermatologists, Dr. Desai said, should educate patients with active PIH resulting from acne or other diseases that even though the condition has been labeled post- inflammatory hyperpigmentation, the inflammation continues to be a problem.

He said, while patients may think PIH is “just scars,” the inflammation is still active and the condition needs to be treated from a skin-lightening perspective but, more importantly, with a focus on halting the inflammation. “If you were to biopsy the areas of hyperpigmentation, you would find a high density of active inflammatory behaviors still present in the skin,” he said.

When treating patients, it’s critical to first treat the underlying skin condition aggressively, he said. “Things like topical retinoids and azelaic acid mechanistically actually make a lot more sense for PIH than even hydroquinone, in some cases, because these therapies are actually anti-inflammatory for many of the diseases we treat.”

Dr. Desai noted that, in patients with darker skin tones, even diseases like seborrheic dermatitis and plaque psoriasis can result in PIH, while in patients with lighter skin tones, the same diseases may leave some residual postinflammatory erythema.

“I think it’s very important, particularly when you’re treating a darker skin–toned patient, to arrest the erythema early on to prevent that further worsening of hyperpigmentation,” he said.
 

Biopsies important

In cases of PIH, determining the best treatment requires finding out where the pigment is and how deep it is, Dr. Desai said.

He noted dermatologists are often worried about doing biopsies, particularly in patients with darker skin, because of the risk of scarring and keloid formation for those more prone to keloids. The preference is also for a therapeutic effect without using invasive procedures.

“But particularly with PIH, in patients who have been therapeutically challenging, I don’t hesitate to do very small biopsies – 2- and 3-mm punch biopsies – particularly if they are from the head and neck area.”

He suggests doing biopsies on part of the ear, lower jaw line, or the neck area, as these areas tend to heal nicely. “You don’t have to be so concerned about the scarring if you counsel appropriately,” he said.

The biopsy can be valuable in determining whether a very expensive treatment will reach the intended target.

Topical retinoids play an important role as anti-inflammatories for PIH, Dr. Desai said.

He gave an example of a patient with Fitzpatrick skin type IV or V with chronic acne and extensive PIH. “Are you going to effectively tell that patient to apply 4% hydroquinone triple-combination compound across 30 different areas of PIH on their face? The answer is that’s really not very efficient or effective.”

That’s why therapies, such as retinoids, that target the pathogenesis of PIH, particularly the inflammatory component, are important, he added.


 

Psychological burden

PIH comes with significant stigma and loss of quality of life loss that can last many years.

During another presentation at the meeting, Susan C. Taylor, MD, professor and vice chair of diversity, equity and inclusion in the department of dermatology, at the University of Pennsylvania, Philadelphia, pointed out that in a 2016 study of 324 patients in seven Asian countries, acne-related PIH lasted longer than 1 year in 65.2% of patients and 5 years or longer in 22.3%, significantly affecting their quality of life.

Dr. Desai added that, in a paper recently published in the British Journal of Dermatology, on the impact of postacne hyperpigmentation in patients, the authors pointed out that the reported prevalence of PIH in patients with acne ranges between 45.5% and 87.2%, depending on skin phototype, and that in most cases, PIH takes more than a year to fade.

“Studies have demonstrated that patients with acne and resulting scarring often face stigmatization, leading to quality of life impairment, social withdrawal and body image disorders, which can further contribute to higher risk for depression and social anxiety,” the paper’s authors wrote.

Dr. Desai reported no financial disclosures relevant to his talk.

CHICAGO – Before determining the best treatment for post-inflammatory hyperpigmentation (PIH), it’s important to understand the pathogenesis, according to Seemal Desai, MD.

Dr. Desai, clinical assistant professor in the department of dermatology at the University of Texas Southwestern Medical Center, Dallas, spoke at the Pigmentary Disorders Exchange Symposium, provided by MedscapeLive!

MedscapeLive!

Like all dermatologists, he said at the meeting, he sees lots of acne cases. However, PIH is often the presenting reason for the visit in his practice, which focuses predominantly on skin of color.

“Most of my patients come in not even worried about the acne,” he said. “They come in wanting me to fix the dark spots.”
 

Inflammation persists

Dermatologists, Dr. Desai said, should educate patients with active PIH resulting from acne or other diseases that even though the condition has been labeled post- inflammatory hyperpigmentation, the inflammation continues to be a problem.

He said, while patients may think PIH is “just scars,” the inflammation is still active and the condition needs to be treated from a skin-lightening perspective but, more importantly, with a focus on halting the inflammation. “If you were to biopsy the areas of hyperpigmentation, you would find a high density of active inflammatory behaviors still present in the skin,” he said.

When treating patients, it’s critical to first treat the underlying skin condition aggressively, he said. “Things like topical retinoids and azelaic acid mechanistically actually make a lot more sense for PIH than even hydroquinone, in some cases, because these therapies are actually anti-inflammatory for many of the diseases we treat.”

Dr. Desai noted that, in patients with darker skin tones, even diseases like seborrheic dermatitis and plaque psoriasis can result in PIH, while in patients with lighter skin tones, the same diseases may leave some residual postinflammatory erythema.

“I think it’s very important, particularly when you’re treating a darker skin–toned patient, to arrest the erythema early on to prevent that further worsening of hyperpigmentation,” he said.
 

Biopsies important

In cases of PIH, determining the best treatment requires finding out where the pigment is and how deep it is, Dr. Desai said.

He noted dermatologists are often worried about doing biopsies, particularly in patients with darker skin, because of the risk of scarring and keloid formation for those more prone to keloids. The preference is also for a therapeutic effect without using invasive procedures.

“But particularly with PIH, in patients who have been therapeutically challenging, I don’t hesitate to do very small biopsies – 2- and 3-mm punch biopsies – particularly if they are from the head and neck area.”

He suggests doing biopsies on part of the ear, lower jaw line, or the neck area, as these areas tend to heal nicely. “You don’t have to be so concerned about the scarring if you counsel appropriately,” he said.

The biopsy can be valuable in determining whether a very expensive treatment will reach the intended target.

Topical retinoids play an important role as anti-inflammatories for PIH, Dr. Desai said.

He gave an example of a patient with Fitzpatrick skin type IV or V with chronic acne and extensive PIH. “Are you going to effectively tell that patient to apply 4% hydroquinone triple-combination compound across 30 different areas of PIH on their face? The answer is that’s really not very efficient or effective.”

That’s why therapies, such as retinoids, that target the pathogenesis of PIH, particularly the inflammatory component, are important, he added.


 

Psychological burden

PIH comes with significant stigma and loss of quality of life loss that can last many years.

During another presentation at the meeting, Susan C. Taylor, MD, professor and vice chair of diversity, equity and inclusion in the department of dermatology, at the University of Pennsylvania, Philadelphia, pointed out that in a 2016 study of 324 patients in seven Asian countries, acne-related PIH lasted longer than 1 year in 65.2% of patients and 5 years or longer in 22.3%, significantly affecting their quality of life.

Dr. Desai added that, in a paper recently published in the British Journal of Dermatology, on the impact of postacne hyperpigmentation in patients, the authors pointed out that the reported prevalence of PIH in patients with acne ranges between 45.5% and 87.2%, depending on skin phototype, and that in most cases, PIH takes more than a year to fade.

“Studies have demonstrated that patients with acne and resulting scarring often face stigmatization, leading to quality of life impairment, social withdrawal and body image disorders, which can further contribute to higher risk for depression and social anxiety,” the paper’s authors wrote.

Dr. Desai reported no financial disclosures relevant to his talk.

CHICAGO – Before determining the best treatment for post-inflammatory hyperpigmentation (PIH), it’s important to understand the pathogenesis, according to Seemal Desai, MD.

Dr. Desai, clinical assistant professor in the department of dermatology at the University of Texas Southwestern Medical Center, Dallas, spoke at the Pigmentary Disorders Exchange Symposium, provided by MedscapeLive!

MedscapeLive!

Like all dermatologists, he said at the meeting, he sees lots of acne cases. However, PIH is often the presenting reason for the visit in his practice, which focuses predominantly on skin of color.

“Most of my patients come in not even worried about the acne,” he said. “They come in wanting me to fix the dark spots.”
 

Inflammation persists

Dermatologists, Dr. Desai said, should educate patients with active PIH resulting from acne or other diseases that even though the condition has been labeled post- inflammatory hyperpigmentation, the inflammation continues to be a problem.

He said, while patients may think PIH is “just scars,” the inflammation is still active and the condition needs to be treated from a skin-lightening perspective but, more importantly, with a focus on halting the inflammation. “If you were to biopsy the areas of hyperpigmentation, you would find a high density of active inflammatory behaviors still present in the skin,” he said.

When treating patients, it’s critical to first treat the underlying skin condition aggressively, he said. “Things like topical retinoids and azelaic acid mechanistically actually make a lot more sense for PIH than even hydroquinone, in some cases, because these therapies are actually anti-inflammatory for many of the diseases we treat.”

Dr. Desai noted that, in patients with darker skin tones, even diseases like seborrheic dermatitis and plaque psoriasis can result in PIH, while in patients with lighter skin tones, the same diseases may leave some residual postinflammatory erythema.

“I think it’s very important, particularly when you’re treating a darker skin–toned patient, to arrest the erythema early on to prevent that further worsening of hyperpigmentation,” he said.
 

Biopsies important

In cases of PIH, determining the best treatment requires finding out where the pigment is and how deep it is, Dr. Desai said.

He noted dermatologists are often worried about doing biopsies, particularly in patients with darker skin, because of the risk of scarring and keloid formation for those more prone to keloids. The preference is also for a therapeutic effect without using invasive procedures.

“But particularly with PIH, in patients who have been therapeutically challenging, I don’t hesitate to do very small biopsies – 2- and 3-mm punch biopsies – particularly if they are from the head and neck area.”

He suggests doing biopsies on part of the ear, lower jaw line, or the neck area, as these areas tend to heal nicely. “You don’t have to be so concerned about the scarring if you counsel appropriately,” he said.

The biopsy can be valuable in determining whether a very expensive treatment will reach the intended target.

Topical retinoids play an important role as anti-inflammatories for PIH, Dr. Desai said.

He gave an example of a patient with Fitzpatrick skin type IV or V with chronic acne and extensive PIH. “Are you going to effectively tell that patient to apply 4% hydroquinone triple-combination compound across 30 different areas of PIH on their face? The answer is that’s really not very efficient or effective.”

That’s why therapies, such as retinoids, that target the pathogenesis of PIH, particularly the inflammatory component, are important, he added.


 

Psychological burden

PIH comes with significant stigma and loss of quality of life loss that can last many years.

During another presentation at the meeting, Susan C. Taylor, MD, professor and vice chair of diversity, equity and inclusion in the department of dermatology, at the University of Pennsylvania, Philadelphia, pointed out that in a 2016 study of 324 patients in seven Asian countries, acne-related PIH lasted longer than 1 year in 65.2% of patients and 5 years or longer in 22.3%, significantly affecting their quality of life.

Dr. Desai added that, in a paper recently published in the British Journal of Dermatology, on the impact of postacne hyperpigmentation in patients, the authors pointed out that the reported prevalence of PIH in patients with acne ranges between 45.5% and 87.2%, depending on skin phototype, and that in most cases, PIH takes more than a year to fade.

“Studies have demonstrated that patients with acne and resulting scarring often face stigmatization, leading to quality of life impairment, social withdrawal and body image disorders, which can further contribute to higher risk for depression and social anxiety,” the paper’s authors wrote.

Dr. Desai reported no financial disclosures relevant to his talk.

DENVER – Patients with multiple sclerosis (MS) who switched from anti-CD20 monoclonal antibody therapy to fumarates showed no significant differences in relapse rates or total health care encounters, compared with those who remained on anti-CD20 mAbs, according to a retrospective study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Those who switched did, however, experience a lower rate of inpatient infection-related health care visits per year than those who continued anti-CD20 mAbs.

“As MS is a chronic disease requiring long-term treatment, switching between disease-modifying therapies [DMTs] is a common clinical strategy to optimize individual patient outcomes,” lead author Aliza Ben-Zacharia, PhD, DNP, RN, an assistant professor at the Phillips School of Nursing at Mount Sinai and Hunter College, both in New York, and colleagues reported. They noted that anti-CD20 mAbs are considered high-efficacy DMTs while fumarates are considered moderate-efficacy DMTs.

The researchers used data from the Komodo Health Sentinel Claims Database to track and compare 108 patients who were clinically stable on anti-CD20 mAbs and then switched to fumarates with 540 patients who remained on anti-CD20 mAbs for a follow-up period of approximately 1 year.

The study included adults with a diagnosis of MS between January 2015 and August 2022, and only those with a gap of no more than 9 months between anti-CD20 mAbs and fumarates were included as switchers. The researchers also required that switchers had not had any relapses in the previous year on anti-CD20 mAbs before switching, and had to have been on fumarates for at least 3 months after switching.

Women made up 70% of both groups, and both had an average age of 49 years. The racial/ethnic demographics were similar in both groups, and the average MS severity score was 5.5 in the switching group and 5.6 in the staying group. Most patients had been taking or remained on ocrelizumab (93.5%) with a smaller proportion on rituximab (5.6%). Just over a third of those who switched therapy took diroximel fumarate while 64% took dimethyl fumarate.

The researchers noted that patients who stayed on anti-CD20 mAbs had “slightly higher use of other mAbs prior to anti-CD20 mAbs.” Further, “a higher proportion of patients were DMT naive prior to anti-CD20 mAb initiation, compared with those in the switchers group.”

Patients who switched had been on anti-CD20 mAbs an average 730 days before switching to fumarates, and the average time between their last anti-CD20 mAbs dose and starting fumarates was 274 days. Average exposure to fumarates was 341 days.

The 10.2% of patients who relapsed during follow-up after switching to fumarates was not significantly statistically different than the 6.7% of patients who relapsed while remaining on anti-CD20 mAbs (P = .17). A relapse was considered “an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and a prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid 7 days or sooner after the outpatient visit,” the researchers explained. The researchers could not track mild relapses that didn’t involve a health care interaction.

There was also no significant difference in overall average health care encounters between those who switched (7.85 encounters) and those who stayed (8.08; P = .57). Further, average health care costs were statistically similar between those who switched ($22,512) and those who stayed ($20,634; P = 0.59).

The likelihood of having more than one infection-related health care encounter was greater for those who remained on anti-CD20 mAbs, but the difference was not statistically significant. The annual rate of infection-related health care encounters was also not statistically different for outpatient and ED visits, but those who switched did have a statistically lower rate of annual infection-related inpatient visits (P = .03).

Among those who switched, 2.8% were hospitalized for infections, compared with 6.5% who stayed on anti-CD20 mAbs. Urinary tract infections, sepsis, and Escherichia coli were the most common infections among those who switched to fumarates, compared with COVID-19, sepsis, and pneumonia, among those who stayed on anti-CD20 mAbs.

The research was sponsored by and funded by Biogen. Six of the authors are Biogen employees who hold stock options in the company. The other three authors reported combined consulting fees from Biogen, EMD Serono, Greenwich Biosciences, TG Therapeutics, Bristol-Myers Squibb, Horizon, and Novartis; research funding from Genentech and Novartis; and stock options in Pfizer.

DENVER – Patients with multiple sclerosis (MS) who switched from anti-CD20 monoclonal antibody therapy to fumarates showed no significant differences in relapse rates or total health care encounters, compared with those who remained on anti-CD20 mAbs, according to a retrospective study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Those who switched did, however, experience a lower rate of inpatient infection-related health care visits per year than those who continued anti-CD20 mAbs.

“As MS is a chronic disease requiring long-term treatment, switching between disease-modifying therapies [DMTs] is a common clinical strategy to optimize individual patient outcomes,” lead author Aliza Ben-Zacharia, PhD, DNP, RN, an assistant professor at the Phillips School of Nursing at Mount Sinai and Hunter College, both in New York, and colleagues reported. They noted that anti-CD20 mAbs are considered high-efficacy DMTs while fumarates are considered moderate-efficacy DMTs.

The researchers used data from the Komodo Health Sentinel Claims Database to track and compare 108 patients who were clinically stable on anti-CD20 mAbs and then switched to fumarates with 540 patients who remained on anti-CD20 mAbs for a follow-up period of approximately 1 year.

The study included adults with a diagnosis of MS between January 2015 and August 2022, and only those with a gap of no more than 9 months between anti-CD20 mAbs and fumarates were included as switchers. The researchers also required that switchers had not had any relapses in the previous year on anti-CD20 mAbs before switching, and had to have been on fumarates for at least 3 months after switching.

Women made up 70% of both groups, and both had an average age of 49 years. The racial/ethnic demographics were similar in both groups, and the average MS severity score was 5.5 in the switching group and 5.6 in the staying group. Most patients had been taking or remained on ocrelizumab (93.5%) with a smaller proportion on rituximab (5.6%). Just over a third of those who switched therapy took diroximel fumarate while 64% took dimethyl fumarate.

The researchers noted that patients who stayed on anti-CD20 mAbs had “slightly higher use of other mAbs prior to anti-CD20 mAbs.” Further, “a higher proportion of patients were DMT naive prior to anti-CD20 mAb initiation, compared with those in the switchers group.”

Patients who switched had been on anti-CD20 mAbs an average 730 days before switching to fumarates, and the average time between their last anti-CD20 mAbs dose and starting fumarates was 274 days. Average exposure to fumarates was 341 days.

The 10.2% of patients who relapsed during follow-up after switching to fumarates was not significantly statistically different than the 6.7% of patients who relapsed while remaining on anti-CD20 mAbs (P = .17). A relapse was considered “an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and a prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid 7 days or sooner after the outpatient visit,” the researchers explained. The researchers could not track mild relapses that didn’t involve a health care interaction.

There was also no significant difference in overall average health care encounters between those who switched (7.85 encounters) and those who stayed (8.08; P = .57). Further, average health care costs were statistically similar between those who switched ($22,512) and those who stayed ($20,634; P = 0.59).

The likelihood of having more than one infection-related health care encounter was greater for those who remained on anti-CD20 mAbs, but the difference was not statistically significant. The annual rate of infection-related health care encounters was also not statistically different for outpatient and ED visits, but those who switched did have a statistically lower rate of annual infection-related inpatient visits (P = .03).

Among those who switched, 2.8% were hospitalized for infections, compared with 6.5% who stayed on anti-CD20 mAbs. Urinary tract infections, sepsis, and Escherichia coli were the most common infections among those who switched to fumarates, compared with COVID-19, sepsis, and pneumonia, among those who stayed on anti-CD20 mAbs.

The research was sponsored by and funded by Biogen. Six of the authors are Biogen employees who hold stock options in the company. The other three authors reported combined consulting fees from Biogen, EMD Serono, Greenwich Biosciences, TG Therapeutics, Bristol-Myers Squibb, Horizon, and Novartis; research funding from Genentech and Novartis; and stock options in Pfizer.

DENVER – Patients with multiple sclerosis (MS) who switched from anti-CD20 monoclonal antibody therapy to fumarates showed no significant differences in relapse rates or total health care encounters, compared with those who remained on anti-CD20 mAbs, according to a retrospective study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Those who switched did, however, experience a lower rate of inpatient infection-related health care visits per year than those who continued anti-CD20 mAbs.

“As MS is a chronic disease requiring long-term treatment, switching between disease-modifying therapies [DMTs] is a common clinical strategy to optimize individual patient outcomes,” lead author Aliza Ben-Zacharia, PhD, DNP, RN, an assistant professor at the Phillips School of Nursing at Mount Sinai and Hunter College, both in New York, and colleagues reported. They noted that anti-CD20 mAbs are considered high-efficacy DMTs while fumarates are considered moderate-efficacy DMTs.

The researchers used data from the Komodo Health Sentinel Claims Database to track and compare 108 patients who were clinically stable on anti-CD20 mAbs and then switched to fumarates with 540 patients who remained on anti-CD20 mAbs for a follow-up period of approximately 1 year.

The study included adults with a diagnosis of MS between January 2015 and August 2022, and only those with a gap of no more than 9 months between anti-CD20 mAbs and fumarates were included as switchers. The researchers also required that switchers had not had any relapses in the previous year on anti-CD20 mAbs before switching, and had to have been on fumarates for at least 3 months after switching.

Women made up 70% of both groups, and both had an average age of 49 years. The racial/ethnic demographics were similar in both groups, and the average MS severity score was 5.5 in the switching group and 5.6 in the staying group. Most patients had been taking or remained on ocrelizumab (93.5%) with a smaller proportion on rituximab (5.6%). Just over a third of those who switched therapy took diroximel fumarate while 64% took dimethyl fumarate.

The researchers noted that patients who stayed on anti-CD20 mAbs had “slightly higher use of other mAbs prior to anti-CD20 mAbs.” Further, “a higher proportion of patients were DMT naive prior to anti-CD20 mAb initiation, compared with those in the switchers group.”

Patients who switched had been on anti-CD20 mAbs an average 730 days before switching to fumarates, and the average time between their last anti-CD20 mAbs dose and starting fumarates was 274 days. Average exposure to fumarates was 341 days.

The 10.2% of patients who relapsed during follow-up after switching to fumarates was not significantly statistically different than the 6.7% of patients who relapsed while remaining on anti-CD20 mAbs (P = .17). A relapse was considered “an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and a prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid 7 days or sooner after the outpatient visit,” the researchers explained. The researchers could not track mild relapses that didn’t involve a health care interaction.

There was also no significant difference in overall average health care encounters between those who switched (7.85 encounters) and those who stayed (8.08; P = .57). Further, average health care costs were statistically similar between those who switched ($22,512) and those who stayed ($20,634; P = 0.59).

The likelihood of having more than one infection-related health care encounter was greater for those who remained on anti-CD20 mAbs, but the difference was not statistically significant. The annual rate of infection-related health care encounters was also not statistically different for outpatient and ED visits, but those who switched did have a statistically lower rate of annual infection-related inpatient visits (P = .03).

Among those who switched, 2.8% were hospitalized for infections, compared with 6.5% who stayed on anti-CD20 mAbs. Urinary tract infections, sepsis, and Escherichia coli were the most common infections among those who switched to fumarates, compared with COVID-19, sepsis, and pneumonia, among those who stayed on anti-CD20 mAbs.

The research was sponsored by and funded by Biogen. Six of the authors are Biogen employees who hold stock options in the company. The other three authors reported combined consulting fees from Biogen, EMD Serono, Greenwich Biosciences, TG Therapeutics, Bristol-Myers Squibb, Horizon, and Novartis; research funding from Genentech and Novartis; and stock options in Pfizer.

MANNHEIM, GERMANY – Patients with high lipoprotein(a) (Lp[a]) levels not only have an almost twofold higher coronary plaque burden than those with low levels but also a faster rate of plaque progression, an observational imaging study shows.

This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.

The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.

At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.

Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.

Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.

He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.

He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”

Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”

However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.

“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
 

Plaque burden

Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.

Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.

“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.

But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.

Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”

It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”

Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.

These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”

Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”

For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”

Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”

What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.

To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.

In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.

After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.

The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).

The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).

Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.

Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).

High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)

Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).

No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.

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

MANNHEIM, GERMANY – Patients with high lipoprotein(a) (Lp[a]) levels not only have an almost twofold higher coronary plaque burden than those with low levels but also a faster rate of plaque progression, an observational imaging study shows.

This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.

The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.

At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.

Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.

Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.

He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.

He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”

Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”

However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.

“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
 

Plaque burden

Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.

Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.

“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.

But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.

Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”

It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”

Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.

These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”

Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”

For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”

Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”

What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.

To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.

In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.

After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.

The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).

The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).

Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.

Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).

High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)

Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).

No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.

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

MANNHEIM, GERMANY – Patients with high lipoprotein(a) (Lp[a]) levels not only have an almost twofold higher coronary plaque burden than those with low levels but also a faster rate of plaque progression, an observational imaging study shows.

This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.

The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.

At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.

Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.

Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.

He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.

He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”

Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”

However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.

“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
 

Plaque burden

Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.

Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.

“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.

But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.

Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”

It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”

Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.

These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”

Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”

For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”

Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”

What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.

To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.

In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.

After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.

The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).

The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).

Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.

Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).

High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)

Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).

No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.

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

Adult survivors of childhood cancer have an elevated risk of developing cognitive impairment years after their cancer diagnosis and treatment, new research shows.

Among more than 2,300 adult survivors of childhood cancer and their siblings, who served as controls, new-onset memory impairment emerged more often in survivors decades later.

The increased risk was associated with the cancer treatment that was provided as well as modifiable health behaviors and chronic health conditions.

Even 35 years after being diagnosed, cancer survivors who never received chemotherapies or radiation therapies known to damage the brain reported far greater memory impairment than did their siblings, first author Nicholas Phillips, MD, told this news organization.

What the findings suggest is that “we need to educate oncologists and primary care providers on the risks our survivors face long after completion of therapy,” said Dr. Phillips, of the epidemiology and cancer control department at St. Jude Children’s Research Hospital, Memphis, Tenn.

The study was published online in JAMA Network Open.

Cancer survivors face an elevated risk for severe neurocognitive effects that can emerge 5-10 years following their diagnosis and treatment. However, it’s unclear whether new-onset neurocognitive problems can still develop a decade or more following diagnosis.

Over a long-term follow-up, Dr. Phillips and colleagues explored this question in 2,375 adult survivors of childhood cancer from the Childhood Cancer Survivor Study and 232 of their siblings.

Among the cancer cohort, 1,316 patients were survivors of acute lymphoblastic leukemia (ALL), 488 were survivors of central nervous system (CNS) tumors, and 571 had survived Hodgkin lymphoma.

The researchers determined the prevalence of new-onset neurocognitive impairment between baseline (23 years after diagnosis) and follow-up (35 years after diagnosis). New-onset neurocognitive impairment – present at follow-up but not at baseline – was defined as having a score in the worst 10% of the sibling cohort.

A higher proportion of survivors had new-onset memory impairment at follow-up compared with siblings. Specifically, about 8% of siblings had new-onset memory trouble, compared with 14% of ALL survivors treated with chemotherapy only, 26% of ALL survivors treated with cranial radiation, 35% of CNS tumor survivors, and 17% of Hodgkin lymphoma survivors.

New-onset memory impairment was associated with cranial radiation among CNS tumor survivors (relative risk [RR], 1.97) and alkylator chemotherapy at or above 8,000 mg/m² among survivors of ALL who were treated without cranial radiation (RR, 2.80). The authors also found that smoking, low educational attainment, and low physical activity were associated with an elevated risk for new-onset memory impairment.

Dr. Phillips noted that current guidelines emphasize the importance of short-term monitoring of a survivor’s neurocognitive status on the basis of that person’s chemotherapy and radiation exposures.

However, “our study suggests that all survivors, regardless of their therapy, should be screened regularly for new-onset neurocognitive problems. And this screening should be done regularly for decades after diagnosis,” he said in an interview.

Dr. Phillips also noted the importance of communicating lifestyle modifications, such as not smoking and maintaining an active lifestyle.

“We need to start early and use the power of repetition when communicating with our survivors and their families,” Dr. Phillips said. “When our families and survivors hear the word ‘exercise,’ they think of gym memberships, lifting weights, and running on treadmills. But what we really want our survivors to do is stay active.”

What this means is engaging for about 2.5 hours a week in a range of activities, such as ballet, basketball, volleyball, bicycling, or swimming.

“And if our kids want to quit after 3 months, let them know that this is okay. They just need to replace that activity with another activity,” said Dr. Phillips. “We want them to find a fun hobby that they will enjoy that will keep them active.”

The study was supported by the National Cancer Institute. Dr. Phillips has disclosed no relevant financial relationships.

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

Adult survivors of childhood cancer have an elevated risk of developing cognitive impairment years after their cancer diagnosis and treatment, new research shows.

Among more than 2,300 adult survivors of childhood cancer and their siblings, who served as controls, new-onset memory impairment emerged more often in survivors decades later.

The increased risk was associated with the cancer treatment that was provided as well as modifiable health behaviors and chronic health conditions.

Even 35 years after being diagnosed, cancer survivors who never received chemotherapies or radiation therapies known to damage the brain reported far greater memory impairment than did their siblings, first author Nicholas Phillips, MD, told this news organization.

What the findings suggest is that “we need to educate oncologists and primary care providers on the risks our survivors face long after completion of therapy,” said Dr. Phillips, of the epidemiology and cancer control department at St. Jude Children’s Research Hospital, Memphis, Tenn.

The study was published online in JAMA Network Open.

Cancer survivors face an elevated risk for severe neurocognitive effects that can emerge 5-10 years following their diagnosis and treatment. However, it’s unclear whether new-onset neurocognitive problems can still develop a decade or more following diagnosis.

Over a long-term follow-up, Dr. Phillips and colleagues explored this question in 2,375 adult survivors of childhood cancer from the Childhood Cancer Survivor Study and 232 of their siblings.

Among the cancer cohort, 1,316 patients were survivors of acute lymphoblastic leukemia (ALL), 488 were survivors of central nervous system (CNS) tumors, and 571 had survived Hodgkin lymphoma.

The researchers determined the prevalence of new-onset neurocognitive impairment between baseline (23 years after diagnosis) and follow-up (35 years after diagnosis). New-onset neurocognitive impairment – present at follow-up but not at baseline – was defined as having a score in the worst 10% of the sibling cohort.

A higher proportion of survivors had new-onset memory impairment at follow-up compared with siblings. Specifically, about 8% of siblings had new-onset memory trouble, compared with 14% of ALL survivors treated with chemotherapy only, 26% of ALL survivors treated with cranial radiation, 35% of CNS tumor survivors, and 17% of Hodgkin lymphoma survivors.

New-onset memory impairment was associated with cranial radiation among CNS tumor survivors (relative risk [RR], 1.97) and alkylator chemotherapy at or above 8,000 mg/m² among survivors of ALL who were treated without cranial radiation (RR, 2.80). The authors also found that smoking, low educational attainment, and low physical activity were associated with an elevated risk for new-onset memory impairment.

Dr. Phillips noted that current guidelines emphasize the importance of short-term monitoring of a survivor’s neurocognitive status on the basis of that person’s chemotherapy and radiation exposures.

However, “our study suggests that all survivors, regardless of their therapy, should be screened regularly for new-onset neurocognitive problems. And this screening should be done regularly for decades after diagnosis,” he said in an interview.

Dr. Phillips also noted the importance of communicating lifestyle modifications, such as not smoking and maintaining an active lifestyle.

“We need to start early and use the power of repetition when communicating with our survivors and their families,” Dr. Phillips said. “When our families and survivors hear the word ‘exercise,’ they think of gym memberships, lifting weights, and running on treadmills. But what we really want our survivors to do is stay active.”

What this means is engaging for about 2.5 hours a week in a range of activities, such as ballet, basketball, volleyball, bicycling, or swimming.

“And if our kids want to quit after 3 months, let them know that this is okay. They just need to replace that activity with another activity,” said Dr. Phillips. “We want them to find a fun hobby that they will enjoy that will keep them active.”

The study was supported by the National Cancer Institute. Dr. Phillips has disclosed no relevant financial relationships.

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

Adult survivors of childhood cancer have an elevated risk of developing cognitive impairment years after their cancer diagnosis and treatment, new research shows.

Among more than 2,300 adult survivors of childhood cancer and their siblings, who served as controls, new-onset memory impairment emerged more often in survivors decades later.

The increased risk was associated with the cancer treatment that was provided as well as modifiable health behaviors and chronic health conditions.

Even 35 years after being diagnosed, cancer survivors who never received chemotherapies or radiation therapies known to damage the brain reported far greater memory impairment than did their siblings, first author Nicholas Phillips, MD, told this news organization.

What the findings suggest is that “we need to educate oncologists and primary care providers on the risks our survivors face long after completion of therapy,” said Dr. Phillips, of the epidemiology and cancer control department at St. Jude Children’s Research Hospital, Memphis, Tenn.

The study was published online in JAMA Network Open.

Cancer survivors face an elevated risk for severe neurocognitive effects that can emerge 5-10 years following their diagnosis and treatment. However, it’s unclear whether new-onset neurocognitive problems can still develop a decade or more following diagnosis.

Over a long-term follow-up, Dr. Phillips and colleagues explored this question in 2,375 adult survivors of childhood cancer from the Childhood Cancer Survivor Study and 232 of their siblings.

Among the cancer cohort, 1,316 patients were survivors of acute lymphoblastic leukemia (ALL), 488 were survivors of central nervous system (CNS) tumors, and 571 had survived Hodgkin lymphoma.

The researchers determined the prevalence of new-onset neurocognitive impairment between baseline (23 years after diagnosis) and follow-up (35 years after diagnosis). New-onset neurocognitive impairment – present at follow-up but not at baseline – was defined as having a score in the worst 10% of the sibling cohort.

A higher proportion of survivors had new-onset memory impairment at follow-up compared with siblings. Specifically, about 8% of siblings had new-onset memory trouble, compared with 14% of ALL survivors treated with chemotherapy only, 26% of ALL survivors treated with cranial radiation, 35% of CNS tumor survivors, and 17% of Hodgkin lymphoma survivors.

New-onset memory impairment was associated with cranial radiation among CNS tumor survivors (relative risk [RR], 1.97) and alkylator chemotherapy at or above 8,000 mg/m² among survivors of ALL who were treated without cranial radiation (RR, 2.80). The authors also found that smoking, low educational attainment, and low physical activity were associated with an elevated risk for new-onset memory impairment.

Dr. Phillips noted that current guidelines emphasize the importance of short-term monitoring of a survivor’s neurocognitive status on the basis of that person’s chemotherapy and radiation exposures.

However, “our study suggests that all survivors, regardless of their therapy, should be screened regularly for new-onset neurocognitive problems. And this screening should be done regularly for decades after diagnosis,” he said in an interview.

Dr. Phillips also noted the importance of communicating lifestyle modifications, such as not smoking and maintaining an active lifestyle.

“We need to start early and use the power of repetition when communicating with our survivors and their families,” Dr. Phillips said. “When our families and survivors hear the word ‘exercise,’ they think of gym memberships, lifting weights, and running on treadmills. But what we really want our survivors to do is stay active.”

What this means is engaging for about 2.5 hours a week in a range of activities, such as ballet, basketball, volleyball, bicycling, or swimming.

“And if our kids want to quit after 3 months, let them know that this is okay. They just need to replace that activity with another activity,” said Dr. Phillips. “We want them to find a fun hobby that they will enjoy that will keep them active.”

The study was supported by the National Cancer Institute. Dr. Phillips has disclosed no relevant financial relationships.

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

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and much more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora. It is also not totally clear how information is stored and processed in these kinds of tools, and who has access to that information, he noted.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said. “I don’t think there’s a way out of that at this point.”
 

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

“We think that’s not appropriate, because coauthorship means that you are taking responsibility for the analysis and the generation of data that are included in a manuscript. A machine that is dictated by AI can’t take responsibility,” said Daniel Solomon, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, and the editor in chief of the ACR journal Arthritis & Rheumatology.
 

Issues with AI

One of the big concerns around using AI in writing is that it can generate text that seems plausible but is untrue or not supported by data. For example, Dr. Greene and colleague Milton Pividori, PhD, also of the University of Colorado, were writing a journal article about new software they developed that uses a large language model to revise scientific manuscripts.

“We used the same software to revise that article and at one point, it added a line that noted that the large language model had been fine-tuned on a data set of manuscripts from within the same field. This makes a lot of sense, and is absolutely something you could do, but was not something that we did,” Dr. Greene said. “Without a really careful review of the content, it becomes possible to invent things that were not actually done.”

In another case, ChatGPT falsely stated that a prominent law professor had been accused of sexual assault, citing a Washington Post article that did not exist.

“We live in a society where we are extremely concerned about fake news,” Dr. Pividori added, “and [these kinds of errors] could certainly exacerbate that in the scientific community, which is very concerning because science informs public policy.”

Another issue is the lack of transparency around how large language models like ChatGPT process and store data used to make queries.

“We have no idea how they are recording all the prompts and things that we input into ChatGPT and their systems,” Dr. Pividori said.

OpenAI recently addressed some privacy concerns by allowing users to turn off their chat history with the AI chatbot, so conversations cannot be used to train or improve the company’s models. But Dr. Greene noted that the terms of service “still remain pretty nebulous.”

Dr. Solomon is also concerned with researchers using these AI tools in authoring without knowing how they work. “The thing we are really concerned about is that fact that [LLMs] are a bit of a black box – people don’t really understand the methodologies,” he said.
 

A positive tool?

But despite these concerns, many think that these types of AI-assisted tools could have a positive impact on medical publishing, particularly for researchers for whom English is not their first language, noted Catherine Gao, MD, a pulmonary and critical care instructor at Northwestern University, Chicago. She recently led research comparing scientific abstracts written by ChatGPT and real abstracts and discovered that reviewers found it “surprisingly difficult” to differentiate the two.

“The majority of research is published in English,” she said in an email. “Responsible use of LLMs can potentially reduce the burden of writing for busy scientists and improve equity for those who are not native English speakers.”

Dr. Pividori agreed, adding that as a non-native English speaker, he spends much more time working on the structure and grammar of sentences when authoring a manuscript, compared with people who speak English as a first language. He noted that these tools can also be used to automate some of the more monotonous tasks that come along with writing manuscripts and allow researchers to focus on the more creative aspects.

In the future, “I want to focus more on the things that only a human can do and let these tools do all the rest of it,” he said.
 

New rules

But despite how individual researchers feel about LLMs, they agree that these AI tools are here to stay.

“I think that we should anticipate that they will become part of the medical research establishment over time, when we figure out how to use them appropriately,” Dr. Solomon said.

While the debate of how to best use AI in medical publications will continue, journal editors agree that all authors of a manuscript are solely responsible for content in articles that used AI-assisted technology.

“Authors should carefully review and edit the result because AI can generate authoritative-sounding output that can be incorrect, incomplete, or biased,” the ICMJE guidelines state. “Authors should be able to assert that there is no plagiarism in their paper, including in text and images produced by the AI.” This includes appropriate attribution of all cited materials.

The committee also recommends that authors write in both the cover letter and submitted work how AI was used in the manuscript writing process. Recently updated guidelines from the World Association of Medical Editors recommend that all prompts used to generate new text or analytical work should be provided in submitted work. Dr. Greene also noted that if authors used an AI tool to revise their work, they can include a version of the manuscript untouched by LLMs.

It is similar to a preprint, he said, but rather than publishing a version of a paper prior to peer review, someone is showing a version of a manuscript before it was reviewed and revised by AI. “This type of practice could be a path that lets us benefit from these models,” he said, “without having the drawbacks that many are concerned about.”

Dr. Solomon has financial relationships with AbbVie, Amgen, Janssen, CorEvitas, and Moderna. Both Dr. Greene and Dr. Pividori are inventors in the U.S. Provisional Patent Application No. 63/486,706 that the University of Colorado has filed for the “Publishing Infrastructure For AI-Assisted Academic Authoring” invention with the U.S. Patent and Trademark Office. Dr. Greene and Dr. Pividori also received a grant from the Alfred P. Sloan Foundation to improve their AI-based manuscript revision tool. Dr. Gao reported no relevant financial relationships.

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

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and much more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora. It is also not totally clear how information is stored and processed in these kinds of tools, and who has access to that information, he noted.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said. “I don’t think there’s a way out of that at this point.”
 

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

“We think that’s not appropriate, because coauthorship means that you are taking responsibility for the analysis and the generation of data that are included in a manuscript. A machine that is dictated by AI can’t take responsibility,” said Daniel Solomon, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, and the editor in chief of the ACR journal Arthritis & Rheumatology.
 

Issues with AI

One of the big concerns around using AI in writing is that it can generate text that seems plausible but is untrue or not supported by data. For example, Dr. Greene and colleague Milton Pividori, PhD, also of the University of Colorado, were writing a journal article about new software they developed that uses a large language model to revise scientific manuscripts.

“We used the same software to revise that article and at one point, it added a line that noted that the large language model had been fine-tuned on a data set of manuscripts from within the same field. This makes a lot of sense, and is absolutely something you could do, but was not something that we did,” Dr. Greene said. “Without a really careful review of the content, it becomes possible to invent things that were not actually done.”

In another case, ChatGPT falsely stated that a prominent law professor had been accused of sexual assault, citing a Washington Post article that did not exist.

“We live in a society where we are extremely concerned about fake news,” Dr. Pividori added, “and [these kinds of errors] could certainly exacerbate that in the scientific community, which is very concerning because science informs public policy.”

Another issue is the lack of transparency around how large language models like ChatGPT process and store data used to make queries.

“We have no idea how they are recording all the prompts and things that we input into ChatGPT and their systems,” Dr. Pividori said.

OpenAI recently addressed some privacy concerns by allowing users to turn off their chat history with the AI chatbot, so conversations cannot be used to train or improve the company’s models. But Dr. Greene noted that the terms of service “still remain pretty nebulous.”

Dr. Solomon is also concerned with researchers using these AI tools in authoring without knowing how they work. “The thing we are really concerned about is that fact that [LLMs] are a bit of a black box – people don’t really understand the methodologies,” he said.
 

A positive tool?

But despite these concerns, many think that these types of AI-assisted tools could have a positive impact on medical publishing, particularly for researchers for whom English is not their first language, noted Catherine Gao, MD, a pulmonary and critical care instructor at Northwestern University, Chicago. She recently led research comparing scientific abstracts written by ChatGPT and real abstracts and discovered that reviewers found it “surprisingly difficult” to differentiate the two.

“The majority of research is published in English,” she said in an email. “Responsible use of LLMs can potentially reduce the burden of writing for busy scientists and improve equity for those who are not native English speakers.”

Dr. Pividori agreed, adding that as a non-native English speaker, he spends much more time working on the structure and grammar of sentences when authoring a manuscript, compared with people who speak English as a first language. He noted that these tools can also be used to automate some of the more monotonous tasks that come along with writing manuscripts and allow researchers to focus on the more creative aspects.

In the future, “I want to focus more on the things that only a human can do and let these tools do all the rest of it,” he said.
 

New rules

But despite how individual researchers feel about LLMs, they agree that these AI tools are here to stay.

“I think that we should anticipate that they will become part of the medical research establishment over time, when we figure out how to use them appropriately,” Dr. Solomon said.

While the debate of how to best use AI in medical publications will continue, journal editors agree that all authors of a manuscript are solely responsible for content in articles that used AI-assisted technology.

“Authors should carefully review and edit the result because AI can generate authoritative-sounding output that can be incorrect, incomplete, or biased,” the ICMJE guidelines state. “Authors should be able to assert that there is no plagiarism in their paper, including in text and images produced by the AI.” This includes appropriate attribution of all cited materials.

The committee also recommends that authors write in both the cover letter and submitted work how AI was used in the manuscript writing process. Recently updated guidelines from the World Association of Medical Editors recommend that all prompts used to generate new text or analytical work should be provided in submitted work. Dr. Greene also noted that if authors used an AI tool to revise their work, they can include a version of the manuscript untouched by LLMs.

It is similar to a preprint, he said, but rather than publishing a version of a paper prior to peer review, someone is showing a version of a manuscript before it was reviewed and revised by AI. “This type of practice could be a path that lets us benefit from these models,” he said, “without having the drawbacks that many are concerned about.”

Dr. Solomon has financial relationships with AbbVie, Amgen, Janssen, CorEvitas, and Moderna. Both Dr. Greene and Dr. Pividori are inventors in the U.S. Provisional Patent Application No. 63/486,706 that the University of Colorado has filed for the “Publishing Infrastructure For AI-Assisted Academic Authoring” invention with the U.S. Patent and Trademark Office. Dr. Greene and Dr. Pividori also received a grant from the Alfred P. Sloan Foundation to improve their AI-based manuscript revision tool. Dr. Gao reported no relevant financial relationships.

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

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and much more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora. It is also not totally clear how information is stored and processed in these kinds of tools, and who has access to that information, he noted.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said. “I don’t think there’s a way out of that at this point.”
 

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

“We think that’s not appropriate, because coauthorship means that you are taking responsibility for the analysis and the generation of data that are included in a manuscript. A machine that is dictated by AI can’t take responsibility,” said Daniel Solomon, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, and the editor in chief of the ACR journal Arthritis & Rheumatology.
 

Issues with AI

One of the big concerns around using AI in writing is that it can generate text that seems plausible but is untrue or not supported by data. For example, Dr. Greene and colleague Milton Pividori, PhD, also of the University of Colorado, were writing a journal article about new software they developed that uses a large language model to revise scientific manuscripts.

“We used the same software to revise that article and at one point, it added a line that noted that the large language model had been fine-tuned on a data set of manuscripts from within the same field. This makes a lot of sense, and is absolutely something you could do, but was not something that we did,” Dr. Greene said. “Without a really careful review of the content, it becomes possible to invent things that were not actually done.”

In another case, ChatGPT falsely stated that a prominent law professor had been accused of sexual assault, citing a Washington Post article that did not exist.

“We live in a society where we are extremely concerned about fake news,” Dr. Pividori added, “and [these kinds of errors] could certainly exacerbate that in the scientific community, which is very concerning because science informs public policy.”

Another issue is the lack of transparency around how large language models like ChatGPT process and store data used to make queries.

“We have no idea how they are recording all the prompts and things that we input into ChatGPT and their systems,” Dr. Pividori said.

OpenAI recently addressed some privacy concerns by allowing users to turn off their chat history with the AI chatbot, so conversations cannot be used to train or improve the company’s models. But Dr. Greene noted that the terms of service “still remain pretty nebulous.”

Dr. Solomon is also concerned with researchers using these AI tools in authoring without knowing how they work. “The thing we are really concerned about is that fact that [LLMs] are a bit of a black box – people don’t really understand the methodologies,” he said.
 

A positive tool?

But despite these concerns, many think that these types of AI-assisted tools could have a positive impact on medical publishing, particularly for researchers for whom English is not their first language, noted Catherine Gao, MD, a pulmonary and critical care instructor at Northwestern University, Chicago. She recently led research comparing scientific abstracts written by ChatGPT and real abstracts and discovered that reviewers found it “surprisingly difficult” to differentiate the two.

“The majority of research is published in English,” she said in an email. “Responsible use of LLMs can potentially reduce the burden of writing for busy scientists and improve equity for those who are not native English speakers.”

Dr. Pividori agreed, adding that as a non-native English speaker, he spends much more time working on the structure and grammar of sentences when authoring a manuscript, compared with people who speak English as a first language. He noted that these tools can also be used to automate some of the more monotonous tasks that come along with writing manuscripts and allow researchers to focus on the more creative aspects.

In the future, “I want to focus more on the things that only a human can do and let these tools do all the rest of it,” he said.
 

New rules

But despite how individual researchers feel about LLMs, they agree that these AI tools are here to stay.

“I think that we should anticipate that they will become part of the medical research establishment over time, when we figure out how to use them appropriately,” Dr. Solomon said.

While the debate of how to best use AI in medical publications will continue, journal editors agree that all authors of a manuscript are solely responsible for content in articles that used AI-assisted technology.

“Authors should carefully review and edit the result because AI can generate authoritative-sounding output that can be incorrect, incomplete, or biased,” the ICMJE guidelines state. “Authors should be able to assert that there is no plagiarism in their paper, including in text and images produced by the AI.” This includes appropriate attribution of all cited materials.

The committee also recommends that authors write in both the cover letter and submitted work how AI was used in the manuscript writing process. Recently updated guidelines from the World Association of Medical Editors recommend that all prompts used to generate new text or analytical work should be provided in submitted work. Dr. Greene also noted that if authors used an AI tool to revise their work, they can include a version of the manuscript untouched by LLMs.

It is similar to a preprint, he said, but rather than publishing a version of a paper prior to peer review, someone is showing a version of a manuscript before it was reviewed and revised by AI. “This type of practice could be a path that lets us benefit from these models,” he said, “without having the drawbacks that many are concerned about.”

Dr. Solomon has financial relationships with AbbVie, Amgen, Janssen, CorEvitas, and Moderna. Both Dr. Greene and Dr. Pividori are inventors in the U.S. Provisional Patent Application No. 63/486,706 that the University of Colorado has filed for the “Publishing Infrastructure For AI-Assisted Academic Authoring” invention with the U.S. Patent and Trademark Office. Dr. Greene and Dr. Pividori also received a grant from the Alfred P. Sloan Foundation to improve their AI-based manuscript revision tool. Dr. Gao reported no relevant financial relationships.

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

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

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

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

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

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

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